KKH Baby Bear Book 3rd Edition

Th
i rd
Ed
the
iti
on
BABY
BEAR
BOOK
A Practical Guide on
Paediatrics
Editors
Shui Yen SOH
Saumya JAMUAR
Janil PUTHUCHEARY
Published by Red Cells Series
An imprint under SingHealth Academy, Singapore Health Services Pte Ltd
31 Third Hospital Avenue, #03-03 Bowyer Block C, Singapore 168753
SingHealth Academy Publishing Team:

Benny Chung, Sukhvinder Kaur, Jean Thee
3rd Edition, Copyright © 2015 Singapore Health Services Pte Ltd and KK
Women’s and Children’s Hospital
All rights reserved. No part of this publication may be reproduced, stored in

a retrieval system or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording or otherwise, without the prior
permission of the copyright owner. Request for permission should be
addressed to The Publisher, c/o The Editorial Office, SingHealth Academy,
31 Third Hospital Avenue, #03-03 Bowyer Block C, Singapore 168753.
Tel: (65) 6377-8649, fax: (65) 6377-4262.
Email: publications@singhealthacademy.edu.sg.
The publisher makes no representation or warranties with respect to the

contents of this book, and specifically disclaims any implied warranties or
merchantability or fitness for any particular purpose, and shall in no event
be liable for any loss of profit or any other commercial damage, including
but not limited to special, incidental, consequential, or other damages.
National Library Board Singapore Cataloguing in Publication Data

The baby bear book : a practical guide on paediatrics /
editors, Shui Yen Soh ... [et al.].—3rd ed.—
Singapore : Red Cells Series, c2015.
p. cm.
Includes bibliographical references.
ISBN-13 : 978-981-09-7864-8 (pbk.)
1. LCSH: Pediatrics—Handbooks, manuals, etc. I. Soh, Shui Yen.
RJ48
618.92—dc23 OCN930320976
3
CONTENTS
CONTENTS 3
FOREWORD 10
PREFACE 11
CARDIOLOGY 13
Cardiac Arrhythmias 13
Tan Teng Hong
Cardiomyopathy and Heart Failure in Children 26
Chen Ching Kit
Syncope — Diagnostic Approach 40
Kotecha Monika Kantilal
Infective Endocarditis in Children 46
Chen Ching Kit, Tan Teng Hong
Kawasaki Disease 55
Jonathan Choo, Tan Teng Hong
Chest Pain in Children 63
Jonathan Choo
Hypercyanotic Spells 69
Tan Teng Hong
CRITICAL CARE 72
Children’s Intensive Care Unit (CICU) 72
Mok Yee Hui, Loh Lik Eng, Chan Yoke Hwee, Janil Puthucheary, Loh Tsee Foong
Recognition of the Critically Ill Child 73
Paediatric Cardiopulmonary Resuscitation 80
ENDOCRINOLOGY 85
Adrenal Insufficiency in Children 85
Endocrinology Service, KKH
Hyperglycaemia 88
Diabetic Ketoacidosis 93
Normal Puberty and Disorders of Puberty 97
Obesity in Childhood and Adolescence 101
4
GASTROENTEROLOGY 105
Recurrent Abdominal Pain 105
Veena Logarajah
Constipation 111
Veena Logarajah
Acute Gastroenteritis 116
Christina Ong
Chronic Diarrhoea 122
Christina Ong
Milk Formula Guide 126
Chiou Fang Kuan
Failure to Thrive 128
Ajmal Kader
Prolonged Jaundice 134
Chiou Fang Kuan
Gastrointestinal Haemorrhage 138
Ajmal Kader
GENERAL AND AMBULATORY PAEDIATRICS 148

Child Development 148
Vinay Sahu, Barathi Rajendra, Mae Wong
Adolescent Health — HEADSS Assessment 162
Elaine Chew, Kumu Rajasegaran
Eating Disorders 164
Elaine Chew, Oh Jean Yin
Child Abuse and Neglect 168
Peter Wong, Kumu Rajasegaran
Drug Overdose and Poisoning 174
Gene Ong
Management of Agitated and Violent Patients 200
Radha Srikanth, Ong Say How
Management of Self-harm and Suicidal Behaviour
in Adolescents 203
Ong Say How
GENETICS 208
The Dysmorphic Child 208
Saumya Jamuar, Angeline Lai
Some Common Dysmorphic Conditions 214
Angeline Lai
Inborn Errors of Metabolism (IEM) 223
Tan Ee Shien, Teo Siak Hong
HAEMATOLOGY AND ONCOLOGY 226

Anemia 226
Joyce Lam, Angeline Lai, Rajat Bhattacharyya
Bleeding Disorders 241
Joyce Lam
5
Thrombosis and Thrombophilia in Paediatric Patients 263

Joyce Lam
Transfusion of Blood Components in Paediatrics 267
Joyce Lam
Acute Leukaemia, Tumour Lysis and Hyperleucocytosis 277
Soh Shui Yen
Central Venous Access Devices in Oncology Patients 281
Soh Shui Yen, Amos Loh, Luke Toh, Pham Thi Ngoc Anh, Chong Chia Yin
Antiemetics 287
Soh Shui Yen, Foo Koon Mian
Fever in the Immunocompromised Child 291
Soh Shui Yen, Natalie Tan Woon Hui
Infection Prophylaxis in Paediatric Haematology/Oncology 297
Soh Shui Yen, Natalie Tan, Tan Ah Moy
Lymphadenopathy 305
Prasad Ramanakrishnan Iyer, Chan Mei Yoke
Paediatric Palliative Care (PPC) 309
Chan Mei Yoke
IMMUNOLOGY & ALLERGY 311

Primary Immunodeficiency (PID) 311
Liew Woei Kang
Anaphylaxis in Children 314
Veena Rajkumar
Drug Allergy 318
Loh Wenyin
Food Allergy 321
Rajeshwar Rao
Urticaria 323
Ong Lin Xin
INFECTIOUS DISEASES 326

Chickenpox (Varicella) 326
Natalie Tan, Chong Chia Yin, Thoon Koh Cheng
Dengue Fever 329
Hand-Foot-and-Mouth Disease (HFMD), and Herpangina 333
Bacterial Meningitis 335
Meningococcal Infections 338
Needlestick Injuries 339
Ophthalmia Neonatorum 342
Tuberculosis (TB) 343
Incubation and Isolation Periods for Infectious Diseases 350
6
NEONATOLOGY 352
Classification of Newborn Babies 352
Tan Pih Lin, Khoo Poh Choo
At-risk Newborns at Delivery 356
Quek Bin Huey
Guidelines for Discharge of At-risk Babies 360
Abdul Alim
Newborn Resuscitation Guidelines 361
Quek Bin Huey
Breastfeeding 368
Chua Mei Chien
Infant Formulae 373
Tan Pih Lin
Common Skin Conditions 374
Geetha Odattil, Mark Koh
Birth Trauma 377
Tan Pih Lin
Neonatal Jaundice (NNJ) 379
Joyce Tan Ziwei, Abdul Alim
Respiratory Distress 384
Kong Juin Yee
Neonatal Sepsis 391
Lynette Tan Liling, Bhavani Sriram
Patent Ductus Arteriosus (PDA) 393
Thowfique Ibrahim
Necrotising Enterocolitis (NEC) 394
Leela Devi Mariappen, Joseph Manuel Gomez
Polycythaemia 397
Shrenik Vora
Hyperinsulinaemic Hypoglycaemia (HH) 399
Suresh Chandran, Victor Samuel Rajadurai
Neonatal Seizures 402
Nirmal Visrusthan Kavalloor
NEPHROLOGY 405
Approach to Haematuria 405
Ng Yong Hong, Allyson Tan
Acute Nephritic Syndrome 408
Ng Yong Hong, Allyson Tan
Nephrotic Syndrome (NS) 411
Chao Sing Ming
Hypertension 418
Ng Yong Hong
Urinary Tract Infection (UTI) and Vesicoureteric Reflux (VUR) 426
Chao Sing Ming
Acute Kidney Injury (Aki) 437
Indra Ganesan, Allyson Tan
Enuresis and Voiding Problems 444
Chao Sing Ming
7
Protocol for Renal Biopsy 448

Chong Siew Le, Chao Sing Ming
Renal Reference Limits 450
Chong Siew Le
NEUROLOGY 451
Abnormal Head Size in Children 451
Cristelle Chow, Derrick Chan
Headache In Children 455
Terrence Thomas
Cerebral Palsy 459
Cristelle Chow, Choong Chew Thye, Derrick Chan
Management Of Status Epilepticus 464
Derrick Chan
Seizures and Epilepsy 464
Derrick Chan
Encephalopathy 472
Wendy Liew, Derrick Chan
Strokes In Children 477
Derrick Chan
Bell’s Palsy In Children 479
Ting Teck Wah, Derrick Chan
PAEDIATRIC SURGERY 481

Common Neurosurgical Problems 481
David Low Chyi Yeu, Seow Wan Tew
The Acute Abdomen 487
Caroline Ong Choo Phaik
RESPIRATORY 496
Asthma 496
Teoh Oon Hoe, Chay Oh Moh
Lower Respiratory Tract Infections 506
Teoh Oon Hoe
Parapneumonic Effusion and Empyema 511
Anne Goh, Teoh Oon Hoe
Obstructive Sleep Apnea 515
Petrina Wong, Teoh Oon Hoe
RHEUMATOLOGY 520
Approach to Limb/Joint Pain and Limping 520
Thaschawee Arkachaisri, Justin Tan
Selected Rheumatological Investigations 523
Thaschawee Arkachaisri, Yvonne See
Juvenile Idiopathic Arthritis (JIA) 530
Systemic Lupus Erythematosus (SLE) 537
8
Juvenile Dermatomyositis (JDM) 544

Systemic Vasculitides 547
Justin Tan, Thaschawee Arkachaisri
Henoch-Schonlein Purpura (HSP) 549
Kawasaki Disease 551
Takayasu Arteritis 557
Drugs in Rheumatology 559
APPENDIX I: GROWTH CHARTS 566

Provided by Health Promotion Board, Singapore
APPENDIX II: DRUGS 590

Infections (Antibiotics, Antifungals, Antivirals) 590
Rina Ong Yue Ling, Chen Qi, Go Hui Jia
Infections (Antihelminthics, Antimalarials) 604
Jamie Stephanie
Respiratory System (Anti-asthmatics, Cough and Cold Mixtures) 612
Jamie Stephanie, Tan Wei Wei
Neurological System (Anticonvulsants) 617
Hie Szu Liang
Neurological System (Analgesics and Sedatives) 620
Praveena Kandasamy, Chee Wei Yen
Neurological System (Muscle Relaxants) 621
Lee Ting Yee
Endocrine System 623
Christine Choo Chui Yee, Selina Lim Wan Xuan
Gastrointestinal System 627
Neo Swee Lan
General Paediatrics (Antipyretics and Analgesics) 629
Praveena Kandasamy, Chee Wei Yen
General Paediatrics (Vitamins and Iron Supplements) 630
Lim Kae Shin
Cardiovascular System (Pressors, Diuretics, Antiarrhythmics,
Antihypertensives) 633
Josephine Tan Gek Foon, Geoffrey Chai, Poh Bao Hui
Cardiovascular System (Infective Endocarditis,
Antibiotic Prophylaxis) 638
Chen Ching Kit, Tan Teng Hong, Thoon Koh Cheng
APPENDIX III: USEFUL FORMULAE 642

Mok Yee Hui, Buang Siti Nur Hanim, Janil Puthucheary
9
APPENDIX IV: RESUSCITATION ALGORITHM 644

Mok Yee Hui, Buang Siti Nur Hanim, Janil Puthucheary
APPENDIX V: FLUIDS & ELECTROLYTES 647

Joel Chan, Mok Yee Hui, Christina Ong, Ng Yong Hong, Janil Puthucheary
Management of Fluids 647
Management of Electrolytes 649
Sodium Abnormalities (Hypernatraemia) 650
Sodium Abnormalities (Hyponatraemia) 651
Potassium Abnormalities (Hyperkalaemia) 652
Potassium Abnormalities (Hypokalaemia) 655
Acid-base Disorders (Acidaemia) 657
10
FOREWORD
It has been many years now that the KK Women’s and Children’s Hospital
brought the Paediatric Departments of Alexandra Hospital, Singapore
General Hospital (SGH) and Tan Tock Seng Hospital together as one
consolidated national Children’s Hospital. Together with the Department
of Paediatric Surgery from SGH and the sizable Neonatology Department
from Kandang Kerbau Hospital, the hospital now provides the full range
of specialty services for children. Over the years, these specialties have
expanded and further refined their care. As a leader in the field of the
healthcare of children, it is indeed timely that this book is published.
Children are our future and they deserve the best care when they fall
ill. This practical guide on Paediatrics will certainly help facilitate this.
Critical information that needs to be readily available when treating
a child is now encapsulated in this handy book. It is written in a clear
and concise way that makes for easy reference and understanding. The
step-by-step protocols with systematic checklists, technique descriptions
and common complications, will make it an indispensable tool for those
practising in the field.
This book should find its place in the consultation room of every doctor
providing care for children. I am sure the pages will oft be opened and will
provide the necessary guidance. I would like to warmly congratulate all
the contributors and especially the editorial team for the tireless efforts
and perseverance to bring us this practical guide.
Professor Ivy Ng
CEO
Singapore Health Services Pte Ltd
11
PREFACE
The best paediatric practices supported by research and evidence,
presented by experienced clinicians. The key messages from the relevant
literature and the practical solutions to real problems faced by those
who work with sick children. This text has for many years been the ready
reference for Paediatricians at every stage of their training, and long after.
It marks the consensus of clinical excellence at KK Women’s and Children’s
Hospital.
It has been my pleasure and privilege to be associated with this book,

which brings together the best ideas of my many colleagues, and we are
all grateful to have had the opportunity to serve the children and families
that have been our patients. My thanks to all contributors and especially
my colleagues on the editorial team.
Whether you are a medical student encountering your first sick child,
a resident in training with a challenging neonate or a practiced senior
clinician looking for reassurance you can provide to a family, I hope this
book will help you and more importantly help our patients.
Dr Janil Puthucheary
Head, Department of Paedriatric Subspecialties
KK Women’s and Children’s Hospital
12
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13
CARDIOLOGY
CARDIAC ARRHYTHMIAS
GENERAL PRINCIPLES
 Symptoms may vary depending on the age of the patient. A young
child may complain of stomach or chest pain. Older children will be
able to give a history of palpitations
 Urgency of the work-up depends on symptom severity. Children with a
history of congenital heart disease or syncope need prompt investigation
 A 12-lead electrocardiogram (ECG) with a long rhythm strip should
be obtained for any suspected arrhythmia before making a diagnosis
or instituting management
 In an acute arrhythmia with haemodynamic compromise, a good
rule of thumb is to cardiovert for a tachyarrhythmia and resuscitate if
the patient has a bradyarrhythmia
 Although certain groups of children may be at increased risk
of primary arrhythmias, in the general paediatric population,
rhythm disturbances are usually the result rather than the cause
of emergencies. Children at risk of primary cardiac arrhythmias
are those with myocarditis, cardiomyopathy, post-cardiac surgery,
congenital heart disease and drug ingestion
 Urgently treat unstable rhythms:
 Unstable rhythms that require treatment are those which
compromise cardiac output and those which have the potential
to deteriorate into a lethal rhythm
 If the arrhythmia is stable, there is time to call the cardiologist to
assess the patient and advise on treatment
 Treating a stable patient with an arrhythmia might not only be
unnecessary, but may actually worsen the situation
BENIGN ARRHYTHMIAS
Sinus Arrhythmia (See Figure 1.1)
 Irregular rhythm with gradual variation in PP intervals
 Sinus P wave precedes each QRS complex
 No change in P wave axis
 Very common — All children and young adults have evidence of
sinus arrhythmia on Holter
 Not associated with symptoms
14 The Baby Bear Book
Figure 1.1: Sinus arrhythmia.
Figure 1.2: Wandering atrial rhythm. Arrowheads indicate position of P waves. Note varying P
wave morphology and PP intervals
 Related to changes in vagal tone during respiratory phases — Heart

rate increases towards end of inspiration and decreases towards end
of expiration
 More evident during periods of low heart rate
 Further evaluation not needed unless associated with other arrhythmias
Wandering Atrial Rhythm (Wandering Atrial Pacemaker)

(See Figure 1.2)
 Irregular rhythm with ongoing changes in P wave morphology
 Associated with changes in PP interval during >2 beats
 Noted during periods of low heart rate
 Common — Seen in 25–35% of children on Holter monitoring
 Differentiate from non-benign atrial tachycardia — Rate, settings and
activities during which it is detected
 Evaluation is not necessary unless the rate is faster than expected for
escape rate or vagotonic conditions
Premature Atrial Contractions (PACs) (See Figure 1.3)

 Premature P waves differing in axis and morphology from normal
sinus P waves
 PR interval may be prolonged
 Atrioventricular (AV) conduction may be normal, aberrant or blocked
 PACs are generally benign and frequently seen in normal,
asymptomatic children. PACs may be seen in patients who have:
 Myocarditis
 Tumours
 Electrolyte abnormalities
Cardiology 15
 Indwelling central venous lines with tip/line in the right atrium

 Further evaluation is not needed unless the PACs are associated
with some other condition that warrants investigation or
treatment
Junctional Rhythm (See Figure 1.4)

 No P waves seen prior to QRS complex; atrioventricular dissociation
can be seen, with QRS rate > atrial (P) rate
 Usually a regular rhythm with narrow QRS complexes
 Rate between 40–100bpm (varies with age)
 Detected during times of vagotonia
 When rate is too fast for an escape rhythm, then further investigation
is indicated
 Not to be mistaken for Junctional Ectopic Tachycardia (JET) or
complete heart block
Premature Ventricular Contractions (PVCs) (See Figure 1.5)

 Premature QRS complex without preceding conducted P wave
 Wide QRS complex whose morphology differs from a sinus
conducted beat
 Look for symptoms of dizziness or syncope
Figure 1.3: Premature atrial contractions. Arrowheads indicate the premature P waves. The AV
conduction of the premature beats here is normal
Figure 1.4: Junctional rhythm in an asymptomatic boy. Note the absence of P wave preceding each
QRS complex. The rate here is about 60 per minute.
Figure 1.5: Two ventricular premature complexes (arrowheads) are seen in this rhythm
 Causes:
 Benign ventricular ectopics
 Structural heart disease
 Myocarditis
 Cardiomyopathy
 Electrolyte imbalance
 Benign PVCs are found in patients without underlying cardiac pathology
 Further evaluation may include the following:
 Echocardiogram
 Holter
 Treadmill to determine if suppression occurs at higher heart rates,
which usually suggests that the PVCs are benign
BRADYCARDIA AND CONDUCTION DISORDERS

Sinus Bradycardia (See Figure 1.6)
 Rhythm whose origin is the SA node (P wave is upright in leads I and aVF)
 Rate is less than normal for age:
 Neonates/infants <100bpm when awake
 1 year to 3 years <100bpm
 3 years to 9 years <60bpm
 Above 9 years <50bpm
 Causes of sinus bradycardia:
 Hypoxia
 Intubation
 Hypothyroidism
 Raised Intracranial Pressure (ICP)
 Meningitis
 Drugs (digoxin, beta-blockers, amiodarone, etc.)
 Anorexia
 Cardiac surgery (especially Fontan, Mustard, Senning procedures)
 Long QT syndrome
 Hypothermia
 Treatment generally not necessary unless patient is symptomatic
from severe bradycardia. Determine and treat underlying cause
 Treatment indicated when patients have:
 Syncope or dizziness
 Easy fatigability
 Exercise intolerance
 Congestive cardiac failure (CCF)
 Treatment strategies:
 Pharmacological Treatment
 Adrenaline 0.01mg/kg (0.1ml/kg of 1:10,000) intravenous (IV) bolus
Cardiology 17
Figure 1.6: Sinus bradycardia in a 5-year-old, heart rate of 54bpm. Note that each QRS complex is
preceded by a P wave and tha there is no AV dissociation
Figure 1.7: Sinus arrest of 4.4-sec duration seen in this Holter recording strip. The vertical
arrowheads indicate the position of the sinus P waves
Figure 1.8: First-degree atrioventricular block with a PR interval of 0.4 sec
 Adrenaline infusion 0.1–1.0mcg/kg/min

 Atropine 0.02mg/kg (min 0.1mg) IV, may be repeated once
 Isoprenaline infusion 0.01–2.0mcg/kg/min
 Pacing, temporary or permanent
Sinus Arrest (See Figure 1.7)

 Sudden absence of atrial activity
 The longest PP interval is not a multiple of the shortest PP interval
 Escape rhythms of atrial, junctional or ventricular origin are sometimes seen
 Presents with syncope
 Indications for therapy are the same as in sinus bradycardia
First Degree Atrioventricular (AV) Block (See Figure 1.8)

 Prolongation of the PR interval beyond the normal for age
 Normal values:
 Newborn to 2 months: 0.06–0.14 sec
 3 months to 2 years: 0.07–0.15 sec
 3–11 years: 0.09–0.17 sec
 12–15 years: 0.09–0.20 sec
 Causes:
 Normal variant
 Increased vagal tone, e.g. athletes
 Congenital heart defects (CHDs) with atrial enlargement, e.g.
Ebstein’s anomaly, atrial septal defect
 Rheumatic fever, myocarditis, mumps, diphtheria
 Duchenne muscular dystrophy, myotonic dystrophy
 Drugs, e.g. digoxin, beta-blockers, calcium channel blockers
 Electrolyte abnormalities, hypoglycaemia
 Generally a benign condition
 No specific treatment
Mobitz Type I Second-degree AV Block (Wenckebach)

(See Figure 1.9)
 Progressive lengthening of the PR interval with an eventual dropped
QRS complex (failure to conduct a P wave after the longest PR
interval)
 Suspect if: group beating, difference in PR interval >0.02 sec between
the beats preceding and following the dropped beat
Mobitz Type II Second-degree AV Block (See Figure 1.10)

 Relatively constant PP interval
 No progressive lengthening of the PR interval prior to an atrial event
that suddenly fails to conduct
 Considered to indicate a block in the His bundle or below
 Warrants close scrutiny as this can progress to higher-degree AV block
 If symptoms of syncope or near-syncope occur, then pacemaker
placement might be indicated
Third-degree (Complete) AV Block (See Figure 1.11)

 Complete dissociation of P wave and QRS complex
 Atrial rate higher than ventricular rate
 QRS morphology and heart rate vary according to the location of the
escape pacemaker. The higher the pacemaker, the faster the rate and
the narrower the QRS complex
 May be acquired or congenital:
 Acquired Complete AV Block:
 Most commonly associated with surgery for repair of
congenital heart disease
 If complete AV block persists >2 weeks after surgery, then
permanent pacemaker placement is indicated
Cardiology 19
Figure 1.9: Mobitz type I second-degree atrioventricular block. The arrowheads indicate the P
waves that were not conducted. Note progressive lengthening of the PR interval prior to the
dropped beats
Figure 1.10: Mobitz type II second-degree atrioventricular block. The arrowheads indicate the P
waves that were not conducted. Note constant PR interval
Figure 1.11: Complete heart block. Note atrioventricular dissociation
 Myocarditis and rheumatic fever can also cause complete AV

block but in most cases, this is temporary and resolves in <1
week — Temporary transvenous pacing may be indicated
 Congenital Complete AV Block:
 Causes:
 Congenital heart disease (congenitally corrected
transposition of the great arteries)
 Infants born to mothers with collagen vascular disease
 Long QT Syndrome
 Diagnosis is now often made by fetal echocardiography
 Patient can be asymptomatic or present later in life
 Symptoms:
 Congestive heart failure, hydrops fetalis
 Syncope
 Exercise intolerance
 Easy fatigability
 Evaluation:
 Electrocardiography with rhythm strip or long lead II
 Echocardiogram to assess for congenital heart disease, LV
size and function
 Holter monitoring
 Treadmill or exercise test to assess work capacity and heart
rate response
 Sudden death has been associated with the following:
 Severe bradycardia
 Ventricular ectopy, especially with exercise
 Prolonged pauses
 Increased QRS width
 Prolongation of QTc interval
 Permanent pacemaker placement is indicated for the
following conditions:
 Documented symptomatic bradycardia
 Wide QRS escape rhythm
 Ventricular dysfunction
 Infants with a ventricular rate of 50bpm to 55bpm or an
infant with congenital heart disease and a ventricular rate
of <70bpm
 An average heart rate <50bpm beyond the first year of life
TACHYARRHYTHMIAS
Paroxysmal Supraventricular Tachycardia (SVT) (See Figure
1.12)
 Most common significant arrhythmia in childhood
 Tachycardia from an accessory pathway is the most common type of
SVT (AV re-entrant SVT) seen in infancy and early childhood. AV nodal re-
entrant SVT becomes more common in later childhood and adolescence.
 Wolff-Parkinson-White (WPW) syndrome is diagnosed when the
accessory pathway is evident on ECG during sinus rhythm as a shortened
PR interval and a slurred upstroke of the QRS complex (delta wave)
 The majority of SVT in childhood is narrow complex tachycardia
 Signs and symptoms:
 In infants, up to half can present in heart failure
 Symptoms can be non-specific, e.g. irritability, incessant crying,
poor feeding
Figure 1.12: Supraventricular tachycardia in an infant. Note monotony of the rhythm. P waves not
evident; they are actually in the terminal part of the QRS complexes (the pseudo-Q waves)
Cardiology 21
Table 1-1: General guidelines that distinguish sinus tachycardia from supraventricular tachycardia
(SVT)
Sinus Tachycardia Supraventricular Tachycardia
Rate <180bpm >220bpm
Consistent with volume loss, fever, Non-specific — Irritability, poor
History
infection feeding, tachypnoea, sweating, pallor
Consistent with dehydration, fever, Poor perfusion
Physical sepsis, blood loss Signs of heart failure
Examination Clear lungs (creps in chest infection) Fine crepitations in lungs
No hepatomegaly Hepatomegaly
Non-specific, no cardiomegaly,
Cardiomegaly, pulmonary congestion
CXR normal, or, e.g. pneumonia as source
or oedema
of fever/sepsis
Monotonous rhythm — Fairly fixed
rate despite changes in activity.
ECG Rarely helpful, usually normal
Sudden termination/initiation.
Terminate with heart block
 Older children can complain of chest pain, palpitations or

abdominal pain
 Supraventricular tachycardia might be difficult to differentiate from
sinus tachycardia. See Table 1-1 for general guidelines that may help to
distinguish between them
 Acute Management of SVT (see summary in Figure 1.13, overleaf ):
 Haemodynamically Stable Patient:
 Consider vagal manoeuvres
 Adenosine:
 First dose: 0.1mg/kg (max 6mg)
 Rapid IV bolus via a large proximal vein, followed by
5–10mls of normal saline rapid bolus
 Second and subsequent doses: 0.2mg/kg (max 12mg/dose)
 Run the ECG on continuous manual mode (leads I, aVF, V2)
as adenosine is being given. This will give diagnostic
information on the mechanism of the SVT
 If SVT persists, the options are:
 Intravenous propranolol — 0.1mg/kg/dose over 10 mINs
(repeat 3 times PRN) then 0.1–0.3mg/kg/dose IV 3–8
hourly
 Per os flecainide — 2–3mg/kg/dose (max 100mg) STAT
and 12 hourly
 Intravenous verapamil — 0.1–0.2mg/kg/dose (max

5–10mg) over 10 mins, then 5mcg/kg/min. Do NOT give
verapamil in patients younger than 1 year.
 Intravenous/IO amiodarone — 5mg/kg/dose IV/IO. Repeat
dose of 5mg/kg/dose up to a total of 15mg/kg/day
 Intravenous digoxin loading — 0.01mg/kg, 0.005mg/kg and
0.005mg/kg at time 0, 8 and 16 hours, respectively. Check
potassium. Avoid digoxin in wide complex tachycardia and
when WPW with atrial fibrillation (AF) is being considered
 Do 12-lead ECG post-conversion to sinus rhythm
 Haemodynamically Unstable Patient:
 Immediate synchronised Direct Current (DC) Cardioversion:
0.5J/kg, 1J/kg, 2J/kg
 Intravenous adenosine can be considered while preparing for
cardioversion and if IV access is readily available
SVT
Consider Vagal Clear ABC Consider IV Adenosine

Manoeuvres (carotid (while preparing for
massage, ice pack, cardioversion and IV
valsalva) access readily available)
Haemodynamically Stable?
Yes No
IV Adenosine 0.1mg/kg (max 6mg) Sync DC Cardioversion 0.5J/kg
IV Adenosine 0.2mg/kg (max 12mg) Sync DC Cardioversion 1.0J/kg

May be repeated
Sync DC Cardioversion 2.0J/kg

Consider Sync DC Cardioversion
Digoxin
Propranolol
Consider Anti-arrhythmics
Flecainide
Amiodarone
Figure 1.13: Management protocol for supraventricular tachycardia

Cardiology 23
Ventricular Tachycardia (VT)

 Characterised by a wide QRS tachycardia and AV dissociation
 Rates vary from 120–300bpm
 In children, a wide complex tachycardia should be treated as VT until
proven otherwise
 Other causes of wide complex tachycardia:
 Antidromic SVT
 Atrial flutter or fibrillation with aberrancy
 Orthodromic SVT with aberrancy
 SVT with pre-existing bundle branch block
 Signs and symptoms:
 Symptoms are rate-related and are usually seen with rates
>150bpm
 Infants — Heart failure, poor feeding and irritability
 Older children — Chest pain, palpitations, syncope or sudden
death
 Causes of VT:
 Myocarditis, cardiomyopathy
 Structural heart disease, post-operative congenital heart disease
 Long QT syndrome, arrhythmogenic right ventricle dysplasia
 Metabolic (hypocalcaemia, hypokalaemia, hypoglycaemia,
hypothermia)
 Drug overdose, e.g. tricyclic antidepressants
 Investigations:
 Electrolytes
 Toxicology screen
 ECG with rhythm strip
 Echocardiogram
 Treatment:
 Ventricular tachycardia should be treated as an emergency unless
the patient is haemodynamically stable
 In the acute situation, synchronised cardioversion at 0.5–1.0J/kg,
then 2J/kg should be the first response. Do not delay
 For pulseless VT, first and all shocks are at 4 Joules/kg
 Intravenous amiodarone is an alternative:
 Slow bolus 5mg/kg
 May repeat 5mg/kg/dose up to a total of 3 times (15mg/kg)
 Watch for hypotension. Have CaCl2 ready
 Intravenous lignocaine:
 Loading: 1mg/kg. May repeat in 10–15 mins for 2 doses
 Infusion: 20–50mcg/kg/min
 Maintenance level: 1.5–5.0mg/L
POST-OPERATIVE ARRHYTHMIA
 Common arrhythmias seen in the post-cardiac surgery patients
include AV block, SVT and junctional ectopic tachycardia
 In post-operative patients, a key investigation is an ECG with one of
the leads attached to the atrial pacing wire:
 Connect the limb leads as usual
 Connect the V2 lead (or any chest lead that is printed in the
rhythm strip) to one of the atrial pacing wire
 Switch to ‘Manual’ or ‘Rhythm’ mode on the ECG machine
 Select the leads to record I, aVF and V2 (or the chest lead that is
attached to the atrial pacing wire)
 Start recording
 The P waves are recorded as sharp, tall spikes on the V2 tracing
JUNCTIONAL ECTOPIC TACHYCARDIA (JET)

 This is a transient arrhythmia and usually resolves within 24–72
hours. However, it may compromise cardiac output in acutely ill
patients
 The mechanism appears to be enhanced automaticity of tissues in
the His bundle
 Electrocardiogram characteristics:
 QRS morphology the same as in sinus rhythm
 Atrioventricular dissociation with ventricular rate greater than the
atrial rate or VA association with retrograde atrial activation via
the AV node
 Investigations:
 ECG, ideally with atrial wires hooked to a chest lead (“wire study”)
in order to determine the relationship of atrial and ventricular
depolarisation
 Electrolytes
 Echocardiogram to assess cardiac function
 Treatment:
 Aim is to reduce the ventricular rate to <180bpm
 Withdraw or reduce inotropic agents if possible since the
arrhythmia is catecholamine-sensitive
 Correct metabolic abnormalities, hypovolaemia and anemia
 Sedation and neuromuscular blockade
 Hypothermia 33–35°C
 Intravenous amiodarone:
 Loading dose: IV 5mg/kg over 10 mins (repeat once if
needed), followed by maintenance infusion: 5–15mcg/kg/min
for 48–72 hours; alternatively,
Cardiology 25
 Intravenous boluses of 1mg/kg over 10 mins (max 5mg/kg

over 60 mins), then maintenance infusion 5–15mcg/kg/min;
alternatively,
 Intravenous infusion 25mcg/kg/min (= loading over 4 hours),
then maintenance infusion 5–15mcg/kg/min; alternatively,
 Watch out for hypotension and bradycardia. Ensure that
calcium chloride is available by the bedside
 Intravenous dexmedetomidine:
 Loading dose: IV 1mcg/kg over 15 mins, then 0.2–0.7mcg/kg/
hr. Higher infusion rate of 3mcg/kg/hr reported to be useful
for conversion of JET to sinus rhythm
 Main side effects are hypotension and bradycardia (including
complete heart block)
 Intravenous procainamide:
 Loading dose: 10mg/kg over 20 mins
 Maintenance infusion: Start at 20mcg/kg/min, increase by
10mcg/kg/min every 15 mins till heart rate <180bpm
 Atrial or AV sequential pacing may be started to restore
synchrony once the JET rate is reduced. This modality cannot be
used if JET rates are ≥170–180 since pacing at higher rates will
compromise diastolic filling.
Bibliography
1. Vetter V. Arrhythmias. In Moller JH, Hoffman JIE, editors. Pediatric cardiovascular medicine.
Philadelphia: Churchill Livingstone; 2000, p. 844–69.
2. Case CL. Diagnosis and treatment of pediatric arrhythmias. Pediatr Clin North Am. 1999;
46(2):347–354.
3. Khan IA. Long QT Syndrome: Diagnosis and management. Am Heart J. 2002; 143(1):7–14.
4. Laird WP, Snyder CS, Kertesz NJ, Friedman RA, Miller D, Fenrich AL. Use of intravenous
amiodarone for post-operative junctional ectopic tachycardia in children. Pediatr Cardio.
2003; 24(2):133–7.
5. Plumpton K, Justo R, Haas N. Amiodarone for post-operative junctional ectopic
tachycardia. Cardiol Young. 2005 Feb;15(1):13–8.
6. Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell VO, Munoz R. Dexmedetomidine:
a novel drug for the treatment of atrial and junctional tachyarrhythmias during the
perioperative period for congenital cardiac surgery: a preliminary study. Anesth Analg.
2008 Nov;107(5):1514–22.
7. LeRiger M, Naguib A, Gallantowicz M, Tobias JD. Dexmedetomidine controls junctional
ectopic tachycardia during Tetralogy of Fallot repair in an infant. Ann Card Anaesth. 2012
Jul-Sep;15(3):224–8.
CARDIOMYOPATHY AND HEART FAILURE

IN CHILDREN
INTRODUCTION
Heart failure in children (aged 0–18 years) can be defined broadly as
the failure of the heart to supply blood to either systemic or pulmonary
circulation at an appropriate rate of flow, or to receive venous return
at an appropriate filling pressure, resulting in adverse effects on the
heart, the circulation, and the patient. As paediatric heart failure is a
relatively uncommon condition, most practitioners in primary care
or emergency departments have little practical experience with its
presentation or management in children. The clinical manifestations
might be dissimilar to those of adults, and quite variable. Because 87%
of cases of new-onset heart failure only reach a diagnosis when the
patient is in a state of severe decompensation, and <50% of children
who present with symptomatic heart failure survive for 5 years without
heart transplantation, early diagnosis and effective treatment remain
significant challenges which should be addressed.
AETIOLOGY
Heart failure has multiple causes, and can occur in children as a
consequence of congenital or acquired disorders, either systemic or
involving only the cardiovascular system.
 Heart failure due to congenital heart disease typically presents
early in life, resulting from abnormal chamber morphology, valvular
function, or circulatory connections.
 Disorders affecting the myocardium, the cardiomyopathies, may
occasionally be apparent at birth but usually manifest later in
infancy, childhood, or during adult life.
 In cardiomyopathy, the basis for heart failure is usually reduced
systolic function of the left ventricle, although associated diastolic
dysfunction is increasingly recognised as an important contributing
factor in the pathophysiology of heart failure in children.
 The cardiomyopathies (see Table 1-2) are diverse and may arise
from genetic abnormalities often involving sarcomeric and
structural proteins or can be secondary to an acquired disease
(e.g. myocarditis) or toxic exposure (e.g. anthracycline toxicity).
It is important to note that all know diagnoses account for only
approximately 35% of patients with the remainder being idiopathic.
Cardiology 27
Table 1-2. Cardiomyopathies in children
Characteristics Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Restrictive

(DCM) (HCM) Cardiomyopathy (RCM)
Epidemiology 60% idiopathic, 30% Autosomal dominant Rare in children;

familial; secondary (30–60%); mutations in can be idiopathic
to myocarditis, sarcomeric or structural or secondary to
toxins, myopathies, proteins; can be due systemic disease
arrhythmia, inborn to malformation (e.g. scleroderma,
errors of metabolism, syndromes or metabolic metabolic disease,
autoimmune diseases disorders irradiation)
Structural Dilated, poorly Hypertrophied Dilated atrium

abnormalities contractile ventricle ventricular wall —
asymmetric or concentric
Pathophysiology Dilated poorly Stiff hypertrophied Non-compliant

contractile ventricle ventricle with poor filling; (restrictive) ventricle
leads to congestion LVOTO due to ventricular results in poor
and poor systemic septal thickening or filling (i.e. diastolic
perfusion systolic anterior motion dysfunction)
of anterior mitral leaflet;
subendocardial ischaemia
due to severe hypertrophy
Associated lesions Mitral regurgitation LVOTO
Clinical features Dyspnoea, Sudden death can be Dyspnoea,

orthopnoea, poor initial presentation; orthopnoea, poor
exercise tolerance, exercise intolerance, exercise tolerance,
90% present syncope, chest pain, chest pain, CHF,
with CHF, gallop, ejection systolic murmur gallop, hepatomegaly,
hepatomegaly at left sternal border arrhythmia
Chest X-ray Cardiomegaly, Usually minimal Dilated atria,

(CXR) findings pulmonary plethora, increased pulmonary
pulmonary oedema vascular markings
ECG findings Sinus tachycardia, LVH, ST-T changes, Right atrial enlarge-
non-specific ST-T abnormal Q waves ment, left atrial
changes, low enlargement, ST
voltage, LVH changes, arrhythmia
Treatment Management of Activity restriction, Management of

CHF (diuretics, β-blockers, myectomy CHF, arrhythmia;
ACE inhibitors, for severe LVOTO, ± implantable
β-blockers), heart implantable cardioverter cardioverter
transplantation if defibrillator defibrillator; ±
end-stage anticoagulation;
heart transplantation
Long-term Progressive heart Arrhythmia, worsening Arrhythmia, sudden

complications failure, sudden death LVOTO, sudden death death
ACE — angiotensin converting enzyme; CHF — congestive heart failure; LVH — left ventricular
hypertrophy; LVOTO — left ventricular outflow tract obstruction
Clinical Features
 Symptoms of heart failure in children are superficially similar

regardless of the underlying aetiology, but physical signs might be
more specific. Systemic manifestations are mediated by sympathetic
and central neurological pathways, activated in response to
pulmonary congestion and/or decreased systemic perfusion. Clinical
features of heart failure unique to children are:
 Possible coexistence of structural congenital heart lesions,
with simultaneous pulmonary overcirculation and systemic
underperfusion (when two circulations are linked in parallel by an
intracardiac shunt or a patent ductus arteriosus).
 A change in symptom complexes over time from infancy through
adolescence. In infants and young children, these are primarily
respiratory and feeding difficulties (which are similar to the
metabolic demands of physical exertion seen in older children).
Symptoms
 See Table 1-4 for the typical features of heart failure in children,
categorised as common and less common. The New York Heart
Association (NYHA) classification of functional class is best suited to
quantify changes in functional capacity in patients with established
chronic heart failure. The Ross classification (see Table 1-5), has been
applied to younger children for the same purpose.
Physical signs
The cardinal signs of cardiac failure are cardiomegaly, tachycardia,

tachypnoea and hepatomegaly. Poor feeding and chest retractions also
feature prominently in the younger infants. The signs and symptoms of
heart failure are related to three factors: Impaired myocardial function
with decreased systemic perfusion, pulmonary congestion and systemic
venous congestion.
 Signs of impaired myocardial function

 Cardiomegaly
 A fairly consistent sign of impaired cardiac function,
secondary to ventricular dilatation and/or hypertrophy.
 May be absent in early stages, especially with myocarditis,
arrhythmias, restrictive disorders and pulmonary venous
obstruction.
Cardiology 29
Table 1-3: A simplified functional classification based on the principle fundamental disturbance in
myocardial function
 Pre-load:
 Volume overload:
 Left-to-right shunts: Ventricular Septal Defect (VSD), Atrial Septal Defect (ASD),
Atrioventricular Septal Defect (AVSD), Patent Ductus Arteriosus (PDA), Arterio-
Venous (AV) fistula, etc.
 Valvular regurgitation
 Complex heart defects with unrestricted pulmonary flow, e.g. Transposition of
the Great Arteries (TGA), Total Anomalous Pulmonary Venous Drainage (TAPVD)
 Anemia
 Iatrogenic
 Diastolic under-filling:
 Pericardial effusion
 Restrictive cardiomyopathy
 Constrictive pericarditis
 Afterload (Pressure overload):
 Congenital: Coarctation of aorta, aortic stenosis, LV or RV outflow obstruction
 Systemic hypertension
 Cor pulmonale
 Intrinsic contractility dysfunction:
 Myocarditis
 Cardiomyopathies:
 Idiopathic
 Post-chemotherapy
 Inborn Errors of Metabolism (IEM), e.g. Pompe’s disease
 Metabolic, e.g. hypothyroidism
 Coronary abnormalities:
 Anomalous origin of coronary artery (e.g. anomalous left coronary artery from
the pulmonary artery)
 Kawasaki Disease (KD)
 Post-cardiac surgery
 Myocardial contusion
 Neoplasia: Myxoma, leukaemic infiltration
 Arrhythmias:
 Bradyarrhythmia: Complete heart block
 Tachyarrhythmia: SVT, Permanent Junctional Reciprocating Tachycardia (PJRT), JET
 Conduction abnormalities: electromechanical dyssynchrony
ASD — atrial septal defect; AVSD — atrioventricular septal defect; JET — junctional ectopic tachycardia; LV — left ventricle;
PDA — patent ductus arteriosus; PJRT — permanent junctional reciprocating tachycardia; RV — right ventricle; SVT —
supraventricular tachycardia; TAPVD — total anomalous pulmonary venous drainage; TGA — transposition of great arteries
Box 1-1 Age-related time of presentation

The age of onset of cardiac failure can serve as a guide to the
differential diagnosis of the underlying aetiology:
 Foetus
 Arrhythmias — SVT, heart block
 Severe anemia
 Large arteriovenous malformation
 Premature neonates
 PDA
 Fluid overload
 Infants
 Congenital heart defects are the most common. Usual age
at presentation of failure:
 First week — HLHS, critical aortic stenosis, large AV fistula,
TAPVD
 Second week — Coarctation of aorta, other duct
dependent lesions
 Fourth to eighth week — Large left-to-right shunts
 Coronary abnormalities: anomalous left coronary artery
from pulmonary artery
 Cardiomyopathies
 Myocarditis
 Older children
 Congenital heart defects — First presentation of CHF after
1 year of age uncommon
 Myocarditis
 Cardiomyopathies
 Tachycardia
 Persistently raised heart rate >160bpm in infants and
>100bpm in older children.
 Consider SVT if heart rate >220bpm in infants and >180bpm
in older children.
 S3 and/or S4 (gallop rhythm).
 Poor peripheral perfusion — Cool extremities, pallor.
 Changes in arterial pulse
 Weak peripheral pulses.
 Bounding pulses in PDA, large AV fistula, high output failure.
 Pulsus paradoxus — Accentuation of the normal fall in blood
pressure on inspiration. Seen in cardiac tamponade. Can be
Cardiology 31
Table 1-4: Symptoms characteristic of heart failure in children
Symptoms characteristic of heart failure in children

Commonly encountered Less commonly encountered
Infants and young • Tachypnoea • Cyanosis
children • Feeding difficulty • Palpitations
(reflux, vomiting, • Syncope
feeding refusal) • Facial oedema
• Diaphoresis • Dependent oedema
• Pallor • Ascites
Older children and • Fatigue • Palpitations
adolescents • Effort intolerance • Chest pain
• Dyspnoea • Dependent oedema
• Orthopnoea • Ascites
• Abdominal pain
• Nausea
• Vomiting
Infants refers to age 0–1 year; older children refers to age 1–10 years.
Table 1-5: The Ross classification

Classification of symptomatic severity in paediatric heart failure
Class of symptoms Symptoms noted on history

I Asymptomatic
II Infants: mild tachypnoea or diaphoresis with feeding; no
growth failure
Older children: dyspnoea on moderate exertion
III Infants: marked tachypnoea or diaphoresis with feeding;
growth failure
Older children: dyspnoea on mild or minimal exertion
IV Tachypnoea, diaphoresis or respiratory distress at rest
detected by palpation of the peripheral pulses, or by looking

at the waveform on the pulse oximeter or invasive blood
pressure monitor.
 Pulsus alternans — Alternating strong and weak beats with a
constant beat-to-beat interval.
 Failure to thrive
 Signs of sympathetic overdrive, e.g. diaphoresis, peripheral
vasoconstriction, irritability.
Signs of pulmonary congestion


 Dyspnoea, tachypnoea and chest retractions
 Major presenting manifestations of cardiac failure in infants.
Fairly early signs.
 Result in poor feeding — Inability to finish the feed, taking
longer to finish each feed (>30 mins), increasing symptoms
during and after feedings.
 Cough — A chronic, hacking cough may be present secondary to
congestion of the lungs.
 Crepitations
 Rhonchi
 May be present in left ventricular failure.
 This, together with cough and crepitations, may make
differentiation from bronchiolitis, pneumonia or asthma
difficult. Superimposed pulmonary infections can and do
occur in patients with congenital heart defects.
 Factors that should bring up the possibility of heart failure:
prior history of significant cardiac defect or heart failure,
chronicity of symptoms, absence of fever, failure to respond to
treatment, cardiomegaly, hepatomegaly.
Signs of systemic venous congestion


 Hepatomegaly
 Most consistent sign of systemic venous congestion.
 Can be tender especially if congestion is severe or acute, and
older children can present with vomiting and abdominal pain
mimicking gastritis or an acute abdomen.
 Increased neck vein distension and pulsation
 Difficult to observe in infants.
 Peripheral oedema — An infrequent finding in children.
Diagnostic evaluation and investigations

Diagnostic testing is always indicated in children with suspected heart failure.
The child presenting with symptoms and signs of heart failure requires urgent
assessment to establish the diagnosis, rapidly determine their haemodynamic
Cardiology 33
status, and identify any reversible causes of heart failure. See Figure 1.14 for a
simplified diagnostic approach to cardiomyopathy.
Chest radiography

 Chest radiography is indicated as the first-line investigation in
children with suspected heart failure.
 Findings: cardiomegaly, pulmonary plethora, pulmonary oedema
Electrocardiography

 All patients should have 12-lead ECG performed at the time of
presentation with heart failure, to exclude features of congenital
or ischaemic heart disease, arrhythmia and pre-excitation
 Findings: sinus tachycardia, non-specific T-wave and ST segment
changes, LV hypertrophy, first degree heart block
 Specific ECG features for the underlying cardiac defect might
be present; a specific arrhythmic cause of heart failure might be
identified, such as incessant tachycardia (usually ectopic atrial
tachycardia), atrioventricular block, or ventricular pre-excitation
Figure 1.14. Simplified diagnostic approach to cardiomyopathy
Echocardiogram and elctrocardiogram on all patients
Primary cardiac Metabolic Neuromuscular

• Family history Urine • Physical
• Creatine • Organic acids examination
phosphokinase • Oligosaccharides • Conduction studies
• Troponin • Glucose and ketones • MRI/MRS
• Microarray screen Serum • Opthalmologic
• Holter • Amino acids examination
• Lactate
• Carnitine (total/free)
• Acylcarnitines
• Ammonia
Consider cardiac MRI Consider skin biopsy Consider muscle

biopsy
MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy

Echocardiography

 Delineate underlying structural defect(s)
 Assess cardiac chamber dilatation and hypertrophy
 Demonstrate decreased myocardial contractility and cardiac
function
 Determine response to therapy
Biochemical and routine laboratory testing


 Blood gas:
 Acidosis (usually metabolic, mixed metabolic and respiratory
in severe pulmonary oedema).
 Slight decrease in PaO2 in patients with left-to-right shunt
lesions (due to pulmonary congestion, intrapulmonary right-
to-left shunting and ventilation-perfusion mismatch); marked
hypoxaemia in patients with underlying cyanotic heart
defects
 Infants with mild and moderate heart failure tend to have a
respiratory alkalosis (lower than normal PaCO2. However in
severe heart failure or if there is a co-existing lung disorder
(e.g. pneumonia), the PaCO2 may be increased
 Useful to guide need for further respiratory support (e.g. CPAP
or intubation and ventilation)
 Urea, electrolytes and creatinine
 Hyponatraemia reflects increased water retention;
hypochloraemia and increase in bicarbonate occurs
secondary to diuretic use; potassium levels may be elevated
due to cation shift from the intracellular stores; hypokalaemia
from the use of loop diuretics
 As a baseline prior to commencing treatment, and a measure
of renal perfusion
 Liver function test (LFT)
 An evaluation of liver end-organ perfusion/injury owing to
low cardiac output
 Full blood count
 Findings: anemia, abnormal RBC indices may indicate
haemoglobinopathies, cyclic neutropenia occurs in males
with Barth syndrome
 Erythrocyte sedimentation rate (ESR)
 Indicates inflammatory disorder/infection
Cardiology 35
Biomarkers

 Natriuretic peptide biomarkers
 Brain natriuretic peptide (BNP) or amino terminal (NT-proBNP)
are established as a valuable aid to the identification of
cardiac disease in children presenting with non-specific
respiratory symptoms, and to evaluate the degree of heart
failure severity
 Serial BNP or NT-proBNP measurements can be used in
children to guide therapeutic intervention or to monitor heart
failure status
 Cardiac troponins
 Cardiac troponins is likely to be more elevated in heart failure
resulting from acute myocarditis
 Troponins can be elevated in cardiomyopathy with increasing
levels correlating with severity
Metabolic and genetic testing


 Early and accurate identification of a metabolic or genetic
aetiology for heart failure might allow for life-saving disease-
specific management, might identify family members at risk, and
might provide guidance for reproductive counseling
 Primary screening investigations for metabolic disorders
include plasma lactate, pyruvate, ammonia, plasma amino acids,
acylcarnitine profile, urine amino acids, urine organic acids, urine
mucopolysaccharide screen (glycosaminoglycans)
 Subspecialty consultation with genetic and/or metabolic services
is recommended to guide further testing such as muscle biopsy
or specific gene testing, molecular, or cytogenetic testing
Infection markers in suspected myocarditis


 Blood for PCR (parvovirus, adenovirus, EBV, CMV, HSV, HHV 6–8,
influenza A& B, mycoplasma
 Nasopharyngeal/tracheal aspirate/swab for parvovirus,
respiratory viruses
 Stool/rectal swab for viral PCR (coxsackievirus, echovirus)
Family assessment

 A detailed family history with pedigree (3 generations) is
important in establishing familial cardiomyopathy. Excluding
familial cardiomyopathy is crucial, especially when the
presentation is in the foetus or newborn
 Perform ECG and echocardiography in all first degree relatives
1. Is there congestion?
NO YES
Warm and Dry Warm and Wet

NO
A B
1. Is there low perfusion?

Signs of low perfusion
• Narrow pulse pressure
D C • Cool extremeties
YES • May be sleepy, obtunded
Cold and Dry Cold and Wet • Suspect from ACEi hypotension
• Suspect from declining serum NA+
• One cause of worsening renal function
Signs of congestion
• Orthopnoea
• High JVP
• Ascites
• Lung crepitations
• Hepatojugular reflex
• Oedema
Redrawn and modified from Stevenson LW et al. Treatment of congestive heart failure. JAMA 2002; 287:2209–10
Figure 1.15. Patterns of presentation recognised in acute decompensated heart failure
Management
In the acute management of heart failure, the patients can be thought of
as having symptoms related to fluid overload, underperfusion, or both
(see Figure 1.15). The early management of children with heart failure
should address these problems. It is important to note that indiscriminate
administration of intravenous fluid resuscitation is contraindicated, and
will worsen the condition of children with heart failure symptoms.
See Figure 1.16 for an approach to the management of acute

decompensated heart failure (ADHF), and Figure 1.17 for guidance to
the introduction of oral maintenance therapy in chronic heart failure.
Treat the underlying cause of the heart failure, if possible


 Surgery or transcatheter therapy for structural heart defect, after
stabilisation.
 Pericardiocentesis for pericardial effusion.
 Adenosine, other anti-arrhythmic agents or cardioversion for
arrhythmias causing heart failure.
 General measures
 Bed rest, limit activities.
 Nurse propped up or sitting up.
 Thermo-neutral environment; control fever.
 Tube feeding in small infants.
Cardiology 37
IS THERE?
• Hypotension
• Tachycardia
• Respiratory distress
• Gastrointestinal distress
NO SOMEWHAT YES
CLASS A CLASS B CLASS C

Is there? Admit patient Start IV diuretic therapy,
• EF >40% but <50% Start loop diuretic ± inotropic vasodilator,
• No or mild LV dilatation consider NPPV
• Good RV function
YES NO
Are symptoms improved in Is patient warm
Start ACEi Start ACEi then 48–72 hours? and diuressing? NO
(Reassess β blocker YES YES
1–2 monthly) (Reassess
NO
1–2 weekly) CLASS D
(BNP ) (BNP )
• Epinephrine
With normal Na+  Wean in • Ventilatory support
Na+, Urea and  Urea or 72 hours • Circatory support
Creatinine Creatinine
To CLASS A To CLASS C To CLASS B If no improvement

in 72 hours, consider
transplant evaluation
ACEi — angiotensin-converting enzyme inhibitor; BNP — brain natriuretic peptide; EF — ejection fraction; IV — intravenous;
LV — left ventricular; NPPV — non-invasive positive pressure ventilation; RV — right ventricular
Redrawn and modified from Kantor PF et al. Presentation, diagnosis, and medical management of heart failure in children: Canadian
Cardiovascular Society Guidelines. Can J Cardiology 2013; 29:1535–52.
Figure 1.16. Simplified algorithm for heart failure management
Echocardiographic Signs, Mild symptoms Moderate symptoms Severe symptoms Intractable symptoms
No symptoms (NYHA/Ross class II) (NYHA/Ross class III) (NYHA/Ross class IV)
(NYHA/Ross class I)
Step 4 Aldosterone antagonist
Step 3 β Blocker
Step 2 ACE Inhibitor
Step 1 Pulsed Duiretic
Consider IV inotropic Inotropic and

Indicates declining range of candidates for introduction
inpatient vasodilator mechanical
Indicates requirement for reduced or slowed up-titration therapy support device
Redrawn and modified from Kantor PF et al. Presentation, diagnosis, and medical management of heart failure in children: Canadian
Cardiovascular Society Guidelines. Can J Cardiology 2013; 29:1535–52.
Figure 1.17. Stepwise introduction of medical therapy in heart failure

 Fluid restriction necessary in admitted patients, especially if dilutional

hyponatraemia is present or in overtly fluid-overloaded patients.
 Sedation: oral chloral hydrate 10–20mg/kg/dose, 6–8 hourly/PRN.
In older patients, IV morphine infusion 10–20mcg/kg/hr can be
considered. Beware of respiratory depression.
 Correct any negative inotropic factors, e.g. acidosis,
hypoglycaemia, hypocalcaemia and anemia.
 Oxygen — Caution in patients with left-to-right shunt (e.g. VSD);
oxygen causes pulmonary vasodilatation and thus increases the
shunt, aggravating the pulmonary congestion and oedema.
 CPAP or mechanical ventilation, if necessary.
 Diuretics
 Frusemide IV/PO 1mg/kg/dose, 6–12 hourly (max dose 20–40mg/
dose in patient with normal renal function). In selected patients,
it can be used as continuous IV infusion at 0.1–1.0mg/kg/hr.
 Spironolactone as an adjunct (mineralocorticoid receptor
antagonist), and a potassium-sparing diuretic PO 1mg/kg/dose
(max 25mg) 6–12 hourly.
 Monitor urine output and serum electrolytes.
Inotropic agents

 Milrinone
 A phosphodiesterase III inhibitor that is both a vasodilator and
an inotropic agent. Useful in situations in which both these
effects are desirable, e.g. post-cardiac surgery, myocarditis.
 IV infusion 0.25–0.75mcg/kg/min.
 Should be the first choice agent for ADHF requiring moderate
inotropic support
 Dobutamine
 A β-adrenergic receptor agonist.
 Lower doses promote renal vasodilation.
 Higher doses discouraged, as they promote tachycardia.
Angiotensin-converting enzyme inhibitors (ACEi)


 Contraindicated in patients with left-to-right shunts.
 The use of ACEi therapy is indicated in children with heart failure
because of primary heart muscle disease of the systemic left ventricle.
 In advanced heart failure, ACEi therapy introduction should occur
after stabilisation of heart failure symptoms with diuretic and
simultaneous to inotropic support withdrawal.
Cardiology 39
 Captopril is the typical first choice for most infants and with
enalapril being an appropriate choice for those older than 2
years.
 Up-titration can proceed safely over 3–10 days in most inpatients,
and can be more gradual in outpatients. Target dose of captopril
is 3mg/kg/day, and enalapril 0.5mg/kg/day.
Beta-adrenergic receptor antagonist


 Benefits of beta blockers in the treatment of adults with heart
failure demonstrated in >20 randomised controlled trials. Only
few uncontrolled studies indicating benefits in children.
 Contraindication: decompensated heart failure, heart block,
bradycardia, asthma.
 Caution: reduced heart function during initial stages of therapy,
hypotension, bradycardia.
 Carvedilol is the first choice for most children with normal systolic
blood pressure; start at 0.1mg/kg/dose (max 3.125mg) 12 hourly
PO. If tolerated, double the dose every 1–2 weeks to max of
0.4–0.6mg/kg/dose (adult 12.5–25mg) 12 hourly.
 Metoprolol is the usual choice for children with reduced systolic
blood pressure; for patients <50kg, start at 0.5mg/kg/day 12
hourly PO, doubling 2-weekly to max of 4mg/kg/day; for patients
>50kg, start at 12.5mg/dose 12 hourly, doubling 2-weekly to max
of 100mg Q12H.
Options for intractable heart failure


 Options available in selected patients include intra-aortic balloon
pump (IAPB), extracorporeal membrane oxygenation (ECMO),
ventricular assist devices (VAD), and referral for heart transplant
assessment.
Bibliography
1. Chang AC, Towbin JA. Heart Failure in Children and Young Adults: From Molecular
Mechanisms to Medical and Surgical Strategies. Sanders Elsevier, 2006.
2. Kantor PF, Lougheed J, Dancea A, et al. Presentation, diagnosis, and medical management
of heart failure in children: Canadian Cardiovascular Society Guidelines. Can J Cardiol
2013;29:1535–52.
3. Kantor PF, Mertens LL. Heart failure in children. Part I: clinical evaluation, diagnostic
testing, and initial medical management. Eur J Pediatr 2010;169:269–79.
4. Maron BJ, Towbin JA, Thiene G et al. Contemporary definitions and classification of the
cardiomyopathies: an American Heart Association Scientific Statement from the Council
on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and
Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary
Working Groups; and Council on Epidemiology and Prevention. Circulation
2006;113:1807–1816.
5. Talner NS. Heart Failure. In: Heart Disease in Infants, Children, and Adolescents, 5th ed.
Emmanouilides et al Ed. Williams & Wilkins 1995:1746–1773.
6. Lonn E, McKelvie R. Drug treatment in heart failure. 2000;320:1188–1192.
7. Bruns LA et al. Carvedilol as therapy in pediatric heart failure: An initial multicenter
experience. J Pediatr 2001;138:505–511.
8. Shaddy RE, Boucek MM, Hsu DT, et al. Carvedilol for children and adolescents with heart
failure: a randomized controlled trial. JAMA 2007;298:1
SYNCOPE — DIAGNOSTIC APPROACH

Syncope is defined as a transient loss of consciousness due to transient
global cerebral hypoperfusion characterised by rapid onset, short
duration, and spontaneous complete recovery. It does not include
seizures, shock, coma or other states of altered consciousness which
may be prolonged in duration or due to a mechanism other than
cerebral hypoperfusion. It is a very common presentation in the
emergency department and the outpatient clinics. It can also be a major
cause for concern for the family.
Thorough evaluation of syncope is warranted to establish the aetiology

of syncope with enough confidence to provide a reliable assessment
of prognosis, recurrence risk, and treatment options. The workup of
syncope includes a meticulous history, a detailed physical examination,
an electrocardiogram, risk stratification and appropriately directed
investigations.
CAUSES OF SYNCOPE
 Reflex syncope: Abnormal circulatory control — Abnormal peripheral

vascular resistance or low cardiac output
 Vasovagal syncope (neurocardiogenic syncope)
 The most common cause of syncope in children.
 Mechanism — On standing, about 10% of blood volume
moves into the veins of the legs and another 5% moves into
the buttocks and pelvic area. The decrease in the venous
return causes the stroke volume to fall by about 20%. The
subsequent vasoconstriction of the peripheral vessels results
in cerebral blood flow falling by about 6%. The decreased
venous return to the heart results in vigorous cardiac
contraction. This stimulates the brain stem to decrease blood
Cardiology 41
pressure and heart rate. This decrease in heart rate and blood
pressure may cause dizziness and/or syncope. The decrease
in the venous return stimulates vagal afferent fibers which in
turn lead to massive vagal discharge in the brainstem thus
causing the bradycardia or hypotension or both.
 Situational syncope — Cough, sneeze, gastrointestinal
stimulation (swallow, defecation, visceral pain), micturition, post
exercise, post prandial, weight lifting or brass instrument playing.
 Cardiac abnormalities
 Rhythm disturbances
 Tachyarrhythmia — Wolff-Parkinson-White (WPW), RVOT
tachycardia, idiopathic VT/VF, right ventricular dysplasia.
 Ion channel abnormalities — Long QT syndrome (congenital
or drug induced), Brugada syndrome.
 Bradyarrhythmias — Heart blocks, sinus arrest, sick sinus
syndrome
 Structural heart disease:
 Coronary artery disease
 Outflow obstruction
 Left atrial myxoma
 Aortic stenosis
 Severe pulmonary stenosis
 Severe pulmonary hypertension
 Acute aortic dissection
 Prosthetic valve dysfunction
 Functional heart disease:
 Hypertrophic obstructive cardiomyopathy
 Dilated cardiomyopathy
 Myocarditis
Orthostatic hypotension:

 Volume depletion
 Drug induced
 Autonomic failure

Other differential diagnoses and mimics for syncope:
 Breath holding spells
 Near syncope
 Aborted cardiac arrest
 Neurologic: seizure, migraine
 Psychiatric: conversion disorder, hyperventilation, malingering
 Metabolic — Hypoglycaemia, hypocalcaemia, hypomagnesaemia,

hypoxia, imbalances in the sodium, potassium or chloride levels.
 Psychological
 Drugs
HISTORY TAKING:
It is the most important tool for diagnosis and risk stratification in
the evaluation of syncope. The initial evaluation should answer the
following questions:
 Is it a syncope or not?
 Was loss of consciousness (LOC) complete?
 Was LOC transient with rapid onset and short duration?
 Did the patient recover spontaneously, completely and
without sequelae?
 Did the patient lose postural tone?
If the answer to one or more of these questions is negative, exclude

other forms of LOC before proceeding with syncope evaluation.
 Has the aetiological diagnosis been determined?
 Are there data suggestive of a high risk of cardiovascular
events or death?
Age of patient
 Gives clues to the most common aetiologies.
 Infant — Should always be aggressively investigated. Myocardial
tumours, outflow obstructions, myocarditis, cardiomyopathies,
long QT syndrome and seizures are possible.
 Adolescents — The most common cause of syncope is vasovagal
syncope or orthostatic hypotension. Other causes include
arrhythmias, mitral valve prolapse, coronary artery abnormalities,
pulmonary hypertension, anemia, pregnancy, psychological
problems or drug abuse.
 Patients at any age can suffer from dysrhythmias, sick sinus
syndrome, atrioventricular block, seizures, electrolyte imbalances,
volume depletion, hypoxia or hypoglycaemia.
Description of the syncope:

Circumstances just prior to the attack.
 Position (supine, sitting or standing).
 Activity (rest/exercise/change in posture, immediately after
urination, defaecation, cough or swallowing)
Cardiology 43
 Predisposing factor (crowded or warm places, post prandial)

 Onset of attack like dizziness, palpitations, abdominal discomfort,
blurred vision.
Vasovagal syncope is often associated with prodromal symptoms such

as pallor, clammy skin, sweating, nausea, lightheadedness, dizziness,
weakness, blurred vision or visual grayout.
Syncope

 Way of falling
 Duration of loss of consciousness
 Movements
 Duration and onset in relation to falls
 Skin colour
 Tongue biting
Post syncope: Nausea, vomiting, seating, muscle aches, injury, urinary or

fecal incontinence
A history from a first-hand witness is useful as more details can be

obtained such as any seizure activity, duration of loss of consciousness,
incontinence, and post-recovery mental status of the patient.
Background medical history

 Any heart defects or previous cardiac surgery. Postoperative cardiac
children can develop arrhythmias.
 Past history of syncope. History of near drowning.
 Metabolic disorder
 Medications /drugs
Family history
 Important to elicit any family history of sudden death, arrhythmias,
congenital deafness, pacemakers or implantable cardioverter-
defibrillators.
 Need to consider conditions such as hypertrophic cardiomyopathies,
prolonged QT syndrome, Marfan syndrome, mitral valve prolapse,
right ventricular dysplasia etc.
Physical Examination
 Vital signs — The pulse rate and blood pressure, significant postural
hypotension. Syncope and tachycardia on standing up is an indicator
of orthostasis and volume depletion.
 Cardiovascular evaluation — Structural cardiac lesions or rhythm

abnormalities. Note any clubbing or cyanosis.
 Complete neurological evaluation.
Investigations
 Full blood count — Anemia.
 Urea, electrolytes and creatinine; serum calcium, magnesium and
phosphate.
 Urine pregnancy test in female adolescents
 Arterial blood gases indicated if hypoxia suspected.
 ECG — Mandatory, e.g. WPW, hypertrophic cardiomyopathy, long QT
syndrome, right ventricular dysplasia.
If a cardiac cause is suspected — Holter monitoring, echocardiography,

transtelephonic ECG, cardiac catheterisation and electrophysiological
studies might be indicated.
Exercise induced syncope is not normal and warrants evaluation
with exercise testing to exclude provokable ischaemia, heart block or
ventricular tachycardia.
If a neurological cause is suspected, investigate further with EEG, CT or

MRI scans as indicated.
Psychiatric evaluation may be necessary for conversion disorder or
hyperventilation.
For neurocardiogenic syncope (vasovagal syncope), the diagnosis can be

reasonably made in as many as half of the patients simply based on history
alone: while standing with presence of clear precipitants such as noxious
stimuli, anticipated pain, unpleasant sights or smells, heat, dehydration,
physical exercise or coincident medical illness. The presence of nausea,
sweating and/or feeling warm also suggests neurocardiogenic syncope. In
these cases, the diagnosis may be confirmed with a positive Tilt Table Test.
MANAGEMENT
At the emergency department:
 Airways, Breathing, Circulation.
 Intravenous access, oxygen administration, cardiac monitoring.
 Basic investigations as indicated above. Hypocount.
Thorough history-taking and physical examination should be performed

after patient is stabilised. It is important to determine whether the
Cardiology 45
syncope is benign such that patient is safe to go home, or if the child

need admission. Indications for admission:
 Exercise induced syncope
 Syncope when supine
 Syncope accompanied by chest pain, palpitations
 Recurrent episodes
 Family history of sudden deaths
 Congenital cardiac defects or previous cardiac surgery
 Toxic, unwell or abnormal vital signs
 Abnormal cardiac or neurological findings on clinical examination
 ECG features:
 Non sustained VT
 Inadequate sinus bradycardia in absence of negative
chronotropic medications or physical training
 Pre- excited QRS complex
 RBBB pattern with ST elevation in leads V1-3 (Brugada pattern)
 Negative T waves in right precordial leads, epsilon waves and
ventricular late potentials suggestive of ARVC
 Co-morbidities like severe anemia, electrolyte disturbances.
If the clinical diagnosis is that of a benign cause, e.g. vasovagal or

postural, and the patient looks clinically well with normal physical
findings and a normal ECG, the child can be sent home after a period
of observation in the emergency department with advice to family to
observe the child at home. Outpatient follow-up is necessary.
Management of neurocardiogenic syncope:

 Non pharmacological measures:
 Initial treatment includes education regarding awareness and
possible prevention of triggers (e.g. hot crowded environments,
volume depletion), early identification of prodromal symptoms,
and performing movements to abort the attack (e.g. supine
posture), support stockings, handgrip and arm tensing, tensing
of crossed legs, abdominal binders, sleeping with the bed tilted
up ~10°, and possibly tilt training. Tilt training is somewhat
controversial, and studies have shown mixed results.
 Adequate hydration and salt intake.
 Drug therapy (seldom required)
 Midodrine and etilefrine are alpha agonists which are studied
in randomised control trials in adults and used when lifestyle
modifications fail.
 Beta blockade has been presumed to lessen the degree of

ventricular mechanoreceptor activation owing to their negative
inotropic effect in reflex syncope. β-Blockers have failed to be
effective in five of six long-term follow-up studies.
 Fludrocortisone is shown to be ineffective in small randomised
controlled trials in children.
 Other drugs such as Disopyramide, Theophylline, and serotonin
reuptake inhibitors have been tried.
 Cardiac pacing
 Employed in patients with malignant neurocardiogenic syncope
(recurrent syncope with significant injury or drug refractory
syncope) and documented spontaneous cardio inhibitory
response during monitoring
Bibliography
1. McConnell M, Syncope in children and Adolescents, Cardio Update — Cardio Update
Newsletter, Sibley Heart Centre
2. (http://www.choa.org/cardiology/cardio-update/home.shtml)
3. Tadros GM et al. Syncope in Young Patients I: An Approach to the Patient with Syncope,
Hospital Physician, April 2002;47–54.
4. Tadros GM et al. Syncope in Young Patients II: Presentation and Management of Specific
causes of Syncope, Hospital Physician, May 2002;6–67.
5. Soteriade ES et al. Incidence and Prognosis of Syncope, The New England Journal of
Medicine, Sept 19 2002: Vol 347, No. 72, 878–885.
6. Heaven DJ, Sutton R. Syncope — A Scientific Review, Critical Care Medicine 2000: Vol 28,
No 10 (N116–N120)
7. Morag R. Syncope, eMedicine Journal, Aug 23 2001: Vol 12, No.8, Dept of Emergency
Medicine, Brooklyn Hospital Centre, http://www.emedicine.com/emerg/topic 876.htm
8. Black KD, Seslar SP, & Woodward GA (2011). Cardiogenic Causes of Pediatric Syncope.
Clinical Pediatric Emergency Medicine 12(4):266–277.
9. DiMario FJ, Jr. & Wheeler Castillo CS (2011). Clinical categorisation of childhood syncope.
Journal of child neurology 26(5):548–551.
10. Fisher J (2011). Advances in syncope. J Interv Card Electrophysiol 32(3):187–193.
11. Moodley M (2013) Clinical Approach to Syncope in Children. Seminars in Pediatric
Neurology 20(1):12–17.
12. Moya A, et al (2009). Guidelines for the diagnosis and management of syncope (version
2009). European heart journal 30(21):2631–2671.
INFECTIVE ENDOCARDITIS IN CHILDREN
DEFINITIONS
Infective endocarditis (IE) — inflammation of the valvular or mural
endocardium caused by microorganisms (bacteria or fungi) involving
Cardiology 47
either the heart or the great vessels (i.e. endarteritis — infection of

the lining of blood vessels); the pathology also may include abscess
formation.
AT RISK PATIENTS
 Congenital heart disease (CHD)
 90% of IE cases occur in individuals who have heart disease,
usually congenital
 Post-operative cardiac surgery
 Cardiac surgery itself is an important risk factor for infective
endocarditis (IE)
 Highest risk in children who had repair or palliation of
cyanotic CHD
 Incidence of IE in the first postoperative month is low for most
defects and increases with time after surgery
 When prosthetic valves or conduits are used in surgical
repairs, the risk for IE is high even in the immediate (first 2
weeks) post-operative period
 Corrective surgery for isolated VSD, secundum ASD or PDA
with documentation of no residual leak, risk for IE is the same
as for general population, 6 months after surgery
 Degenerative or rheumatic heart disease
 Normal hearts with
 Central indwelling venous catheters
 Staphylococcus aureus bacteraemia
 Intravenous drug abuse
Patients with congenital or acquired immunodeficiencies are not at
higher risk for IE
CAUSATIVE ORGANISMS
 Most common organisms are gram-positive cocci — viridans group
streptococci, staphylococci and enterococci
 Less commonly, gram-negative bacilli — HACEK group (Haemophilus
species, Actinobacillus actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, and Kingella species)
 IE associated with indwelling central catheters, prosthetic valves or
materials — Staphylococcus aureus, coagulase-negative staphylococci
 Newborn infants — Staphylococcus aureus, coagulase-negative
staphylococci, Candida species, group B streptococcus and
Streptococcus pneumoniae
 Fungi — The most common fungus is Candida, followed by Aspergillus
Clinical Features
Due to 4 underlying phenomena:
 Bacteraemia (or fungaemia) — Fever, myalgia, arthralgia, malaise
 Valvulitis — New heart murmur or change in murmur, congestive
heart failure (CHF)
 Embolic phenomenon
 petechiae, hepatosplenomegaly, splinter haemorrhages, Janeway
lesions (painless haemorrhagic lesions on palms and soles),
Osler nodes (painful lesions at fingertips), pulmonary emboli,
mycotic aneurysm, intracranial haemorrhage, and conjunctival
haemorrhages
 Immunologic responses
 glomerulonephritis, Osler nodes, Roth’s spots
Presentation:
 Indolent (subacute bacterial endocarditis)
 Prolonged low-grade fever
 Variety of somatic complaints, including fatigue, weakness,
arthralgias, myalgias, weight loss, rigors, and diaphoresis
 Fulminant (acute bacterial endocarditis)
 High, spiking fever
 Rapidly changing symptoms
 Acutely ill
 Cardiac signs are variable (see Table 1-6)1:
 Valvular destruction  regurgitant murmurs
 Cyanotic CHD in a child who has undergone a systemic-pulmonary
shunt procedure may present with declining systemic oxygen
saturation, reflecting graft infection with obstruction of flow.
 Patients with right-sided, catheter-related infection may have few
or no specific cardiovascular signs but may present with primarily
pulmonary symptoms and signs related to septic pulmonary
embolisation
Investigations
 Blood Cultures
 The likelihood of culturing the causative organism is directly
related to the volume of blood obtained (1–3ml in infants; 5–7ml
in older children).
 It is not necessary to time blood sampling with fever because
bacteraemia in IE is usually continuous.
Cardiology 49
Table 1-6: Presenting signs in children with IE

Sign %
Fever 99
Petechiae 21
Changing murmur 21
Dental caries 14
Hepatosplenomegaly 14
Congestive heart failure 9
Splenomegaly 7
Splinter haemorrhages 5
Retinal haemorrhages (Roth spots) 5
Osler nodes 4
Arthritis 3
 Three blood cultures are obtained by separate venepunctures

on the first day, and if there is no growth by the second day of
incubation, 2 more should be obtained.
 In patients who are not acutely ill and whose blood cultures are
still negative, draw 3 aerobic blood cultures over the first day and
hold antibiotics; if cultures are negative after 24 hours draw 2
cultures and incubate for 2 weeks.
 For patients with acute IE, 3 separate venepunctures for
blood cultures, with 1 hour separating first and last, before
administering empiric antibiotics.
 Request forms for the blood cultures should indicate that IE is
suspected to ensure that the laboratory will incubate the cultures
for at least 2 weeks.
 If fastidious or unusual organisms are suspected, the
microbiology laboratory should be consulted.
 Culture of arterial blood is not more useful than venipuncture.
 In stable patient suspected to have IE and has been treated with
antibiotics for <4 days but have not have a prior blood culture, stopping
the antibiotic before taking blood cultures can be considered.
Miscellaneous Laboratory Tests

 Anemia — Can be due to haemolysis or anemia of chronic disease
 Leukocytosis — Not a consistent feature of IE
 Elevated acute-phase reactants, e.g. ESR, CRP
 Renal/urine: haematuria, red blood cell casts, proteinuria, and
renal insufficiencyimmune complex glomerulonephritis
Echocardiography
 Transthoracic Echocardiography (TTE)
 Findings:
 identify vegetations (hallmark)
 determine the site and extent of infection
 baseline evaluation of ventricular performance and cardiac
chamber dimension
 monitor serial cardiac function
 pericardial effusion or myocardial abscess
 Inadequate in some circumstances:
 Obese or very muscular adolescent
 Post-cardiac surgery patients- presence of compromised
respiratory function or pulmonary hyperinflation
 Patients with poor echogenicity
 Complex cardiac anatomy
 Absence of vegetations on echocardiography does not rule out IE.
 Conversely, an echogenic mass can represent a sterile
thrombus, sterile prosthetic material, or normal anatomic
variation rather than an infected vegetation.
 Transoesophageal Echocardiography (TEE)
 TTE is usually adequate in children and may not need
transoesophageal echocardiogram
 TEE should be reserved for those who have poor echo windows,
in whom prosthetic valves cause “shadowing”, and in whom the
TTE view appears normal despite a high index of suspicion for IE
Diagnosis
The utility of the Modified Duke Criteria2 (Box 1-2) in diagnosing IE in
paediatric patients has been established3.
Management
Acute management: antibiotics4, 5 (see Antibiotic Guidelines for Paediatrics),
treatment of CHF, cardiac surgery if severe valvular regurgitation, aortic root
abscess, large vegetation, or embolic phenomena.
Long-term management: management of residual lesions or sequelae
Cardiology 51
General principles

 Prolonged course of intravenous therapy for at least 4 weeks
duration or 3 weeks afebrile
 Consider 6 weeks antibiotics if:
 Prosthetic valve IE
 Highly virulent organisms (e.g. Staphylococcus aureus)
 Relative antibiotic resistance of organism
 Dual or more antibiotics for synergistic effect
 Outpatient antibiotic therapy can be considered in
uncomplicated cases on a case-by-case basis, after the initial
hospital treatment
Surgery

 Decisions regarding surgery in patients with IE should be individualised,
with input from both the cardiologist and the cardiothoracic surgeon.
 There is limited information concerning the effects of surgical
timing on the outcomes in children, but some authors have
suggested excellent results with surgical intervention during the
active phase of infection5.
 If a patient with IE is receiving long-term oral anticoagulation,
warfarin therapy should be discontinued and replaced by heparin
immediately after the diagnosis of IE has been established in the
event that surgical intervention is required6.
Indications for surgical intervention6


 Most common indication — Severe valvular insufficiency
 Progressive cardiac failure (usually due to valvular regurgitation)
 Persistent bacteraemia after 1–2 weeks of appropriate antibiotic
therapy
 Perivalvular extension of infection/abscess formation
 Valve dehiscence, perforation, rupture, or fistula
 Fungal endocarditis
 Prosthetic valve IE (particularly early prosthetic valve IE, i.e. <12
months after valve replacement)
 Ruptured sinus of Valsalva or ventricular septum
 Significant embolic events
 Especially when the aortic or mitral valve is involved, i.e. left-sided
vegetations
 Soft indications — Anterior mitral valve vegetation (particularly
with size >10mm), or persistent vegetation after systemic
embolisation, or an increase in vegetation size despite
appropriate antimicrobial therapy
Box 1-2 Modified Duke Criteria for the Diagnosis

of Infective Endocarditis
Major Criteria
• Blood culture positive for IE
Typical microorganisms consistent with IE from 2 separate blood cultures:
Viridans streptococci, Streptococcus bovis, HACEK group; OR
Community-acquired Staphylococcus aureus or enterococci, in the absence of a
primary focus; OR
Microorganisms consistent with IE from persistently positive blood cultures,
defined as follows:
 At least 2 positive cultures of blood samples drawn >12 hours apart; OR
 All of 3 or a majority of ≥4 separate cultures of blood (with first and last
sample drawn ≥1 hour apart)
Single culture positive for Coxiella burnetti, or antiphase I IgG antibody titer
>1:800
• Evidence of endocardial involvement on echocardiogram
• Echocardiogram positive for IE (TEE recommended in patients with prosthetic
valves, rated at least “possible IE” by clinical criteria, or complicated IE
[paravalvular abscess]; TTE as first test in other patients), defined as follows:
 Oscillating intracardiac mass on valve or supporting structures, in the path
of regurgitant jets, or on implanted material in the absence of an alternative
anatomic explanation; OR
 Abscess; OR
 New partial dehiscence of prosthetic valve
• New valvular regurgitation (worsening or changing of pre-existing murmur not
sufficient)
Minor Criteria
• Predisposition, predisposing heart condition or IV drug use
• Fever, temperature ≥38ºC
• Vascular phenomenon: major arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial haemorrhage, conjunctival haemorrhage, Janeway lesion
• Immunologic phenomenon: glomerulonephritis, Osler nodes, Roth spots,
rheumatoid factor
• Microbiological evidence: positive blood culture that does not meet major criteria
or serologic evidence of active infection with organism consistent with IE
• Echocardiographic minor criteria eliminated
Definite IE
Pathological Criteria
• Microorganisms demonstrated by culture or histologic examination of
vegetation, vegetation that has embolised, or intracardiac abscess; OR
Cardiology 53
• Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic

examination showing active IE
Clinical Criteria
• 2 major criteria; OR
• 1 major and 3 minor criteria; OR
• 5 minor criteria
Possible IE
• 1 major and 1 minor criterion; OR
• 3 minor criteria
Rejected
• Firm alternative diagnosis; OR
• Resolution of symptoms with antibiotic therapy for ≤4 days; OR
• No pathologic evidence of IE at surgery or autopsy, with antibiotic therapy for ≤4
days; OR
• Does not meet criteria for possible IE, as above
IE, infective endocarditis; TEE, transoesophageal echocardiogram; TTE, transthoracic
echocardiogram
 Patients may eventually require surgical intervention for chronic

valvular stenosis or regurgitation caused by previous IE
 IE related to a haemodynamically trivial VSD should potentially be
considered for surgical repair following successful treatment of
the infection
Prognosis
Mortality
Estimated ~ 11–17%
Complications of IE

 Congestive heart failure (~7%,secondary to severe valvular
regurgitation)
 Embolic events: e.g. cerebral (stroke ~8%), pulmonary (~10%),
renal, coronary, GIT
 Periannular extension of abscess
 Arrhythmias (~8%), heart block
 Prosthetic device dysfunction
 Valvular dehiscence
 Graft or shunt occlusion
 Persistent bacteraemia or fungaemia
 Metastatic infection, e.g. renal abscess (~3%), osteomyelitis (1%)
 Mycotic aneurysms
 Glomerulonephritis or renal failure
Prophylaxis
The most recent revision of the American Heart Association (AHA)
guidelines on infective endocarditis prophylaxis occurred in 20157. The
new guidelines suggested to shift the disproportionately large focus
on antibiotic prophylaxis to an emphasis on oral hygiene, and that
prophylaxis should be targeted at conditions that are associated with
the highest probability of adverse outcomes from infective endocarditis.
For antibiotic prophylaxis guidelines for bacterial endocarditis, refer
to guideline on antibiotic prophylaxis for prevention of infective
endocarditis (see page 640).
Conclusions
Even though IE is a rare diagnosis in childhood, a high index of suspicion
in persistently febrile patients is necessary, especially in the context of
congenital heart disease.
Bibliography
1. Martin JM, Neches WH, Wald ER. Infective endocarditis: 35 years of experience at a
children’s hospital. Clin Infect Dis 1997;24:669–75.
2. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the
diagnosis of infective endocarditis. Clin Infect Dis 2000; 30:633–8.
3. Tissieres P, Gervaix A, Beghetti M, Jaeggi ET. Value and limitations of the von Reyn, Duke
and Modified Duke Criteria for the diagnosis of infective endocarditis in children. Pediatr
2003;112:e467–71.
4. Ferrieri P, Gewitz MH, Gerber MA, et al. Unique features of infective endocarditis in
childhood. Circulation 2002;105:2115–26.
5. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial
therapy, and management of complications: A statement for healthcare professionals
from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council
on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke,
and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the
Infectious Diseases Society of America. Circulation 2005; 111:e394–434.
6. Shamszad P, Khan MS, Rossano JW, et al. Early surgical therapy of infective endocarditis in
children: a 15-year experience. J Thorac Cardiovasc Surg 2013;146:506–11.
7. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: Guidelines
from the American Heart Association: A guideline from the American Heart Association
Rheumatic Fever, Endocarditis, and Kawasaki disease Committee, Council on
Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on
Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research
Interdisciplinary Working Group. Circulation 2007;116:1736–54.
Cardiology 55
KAWASAKI DISEASE
INTRODUCTION
Kawasaki disease is an acute systemic inflammatory/vasculitic disease

of unknown origin, affecting predominantly children younger than 5
years. It was first described by Dr Tomisaku Kawasaki in 1967, and is now
considered to be the main form of acquired heart disease in developed
countries.
In Singapore, the incidence is estimated at 51.4 per 100,000 children

younger than 5 years old per year (KKH and NUH databases, 2012). This
incidence is one of the highest outside Japan, and very similar to that
of Hong Kong and Taiwan. At KK Women’s and Children’s Hospital (KKH),
we see an average of about 100–120 new cases a year. The incidence of
Kawasaki Disease in Singapore appears to be increasing.
DIAGNOSIS
There is no specific diagnostic or confirmatory test for KD. KD is
diagnosed clinically using the criteria originally set forth by Dr Kawasaki
and adopted and modified by the AHA Committee on Rheumatic Fever,
Endocarditis, and Kawasaki Disease. Laboratory tests may be used to
support a diagnosis of KD.
Diagnostic Criteria:
Fever persisting for at least 5 days† and presence of at least four of the
following‡:
 Rash — Polymorphous exanthem, never vesicular or bullous; can be
accentuated in the perineum where it may be associated with local
desquamation.
 Bilateral conjunctivitis — Painless hyperaemia, non-suppurative,
usually spares the limbus. Anterior uveitis can be present if examined
by slit lamp in the first week of illness. Presence of anterior uveitis
strongly supports the diagnosis of KD.
 Changes in lips and oral mucosa — Erythema and cracking of lips,
strawberry tongue, diffuse injection of oral and pharyngeal mucosa. Lack
of discrete lesion or ulceration in the oropharyngeal/lingual mucosa.
 Cervical lymphadenopathy (≥1.5cm in diameter) — Unilateral or
bilateral, usually the former.
 Changes in extremities — Acute: erythema and oedema of hands
and feet. Convalescent: skin desquamation of the tips of the fingers
and toes (late sign).
†
In the presence of classic features, the diagnosis of KD can be
made by an experienced physician before 5 days of fever.
‡
Patients with fever and less than four other principle signs can
be diagnosed as KD (atypical KD) when coronary artery disease is
detected by echocardiography or coronary angiography.
Other Significant Clinical and Laboratory Findings:
 Cardiovascular and Respiratory:

 Cough, rhinorrhoea
 Angina pectoris or signs of cardiac failure
 Tachycardia, S3, gallop rhythm, murmur of mitral and/or aortic
regurgitation, or soft heart sounds.
 Aneurysms of peripheral arteries, e.g. axillary or femoral — Rare
 Echocardiogram changes — Arrhythmias, prolonged PR interval,
abnormal ST segment changes, abnormal T wave changes,
abnormal Q waves, or low voltages
 Chest radiograph — Cardiomegaly, pulmonary infiltrates,
pulmonary oedema
 Echocardiogram — Pericardial effusion, decreased contractility,
myocarditis, valvular regurgitations, coronary dilatation and
aneurysms
 Skin and Joints

 Perineal rash, excoriation and desquamation
 Induration and redness of the BCG scar or site
 Beau’s line in the nails during convalescence
 Arthralgia and arthritis
 Neurological
 Striking irritability, inconsolable crying
 Facial palsy or other mononeuritis (rare)
 Mononuclear pleocytosis in the CSF
Gastrointestinal
 Diarrhoea, vomiting, abdominal pain
 Mild jaundice, hydrops of the gallbladder, paralytic ileus
 Mild, transient increase in transaminase levels
Renal
 Sterile pyuria is common — Urethral origin
 Occasional proteinuria
Cardiology 57
Haematological
 Raised ESR and CRP
 Mild anemia in the acute phase
 Thrombocytosis in subacute phase
 Leucocytosis with left shift in acute phase
 Hypoalbuminaemia
Differential diagnosis
The differential diagnosis in a child with possible KD, presenting with
conjunctivitis and rash together with prolonged fever include:
 Streptococcal and staphylococcal toxin-mediated diseases (scarlet
fever, toxic shock syndrome)
 Measles, adenovirus infection and other viral infections
 Drug reactions, Stevens-Johnson syndrome
 Macrophage activating syndrome
 Leptospirosis
 Yersinia pseudotuberculosis infection (rare)
 Rickettsial infection (rare in Singapore)
 Autoimmune or immune complex diseases — SLE, JRA, polyarteritis
nodosa, Reiter’s syndrome, Behçet’s disease, inflammatory bowel
disease, postinfectious
 Sarcoidosis (rare)
 Mercury poisoning (rare)
Clinical Course
The course of KD can be described in three clinical phases:
 Acute phase — Lasting 7–14 days, characterised by fever and
inflammatory changes.
 Subacute phase — Typically lasts from approximately day 10–day 25
after onset of illness. Fever, rash and lymphadenopathy resolve, but
irritability, anorexia and conjunctival injection persist. Desquamation
of fingers and toes appears; may have arthritis and arthralgia or
myocardial dysfunction. Thrombocytosis is common.
 Convalescent phase — Begins when all clinical signs disappear and
continues until acute phase reactants return to normal, usually 6–10
weeks after onset.
A small subgroup of patients with KD (10–15%) have persistent or
recrudescent disease after the initial treatment.
Up to 1–3% of patients may have relapses or recurrences of KD after

recovering from the first episode.
Investigations
 Full blood count, erythrocyte sedimentation rate, C-reactive
protein
 Urea/electrolytes/creatinine, LFT
 Blood culture
 Urine microscopy, biochemistry, and culture
 Cardiac enzymes and troponin (if myocardial involvement/
myocarditis suspected)
 Electrocardiogram
 Chest radiograph
 Echocardiogram — Performed at day 14, and 3 months,
after onset of KD. Subsequent echocardiograms arranged by
cardiologist if the first 2 are abnormal. Earlier echocardiography
can be arranged for the patient with diagnostic issues or a patient
who is suspected of having cardiovascular complications. Early
2D Echocardiograms may also show mitral regurgitation and
pericardial effusions in patients with KD.
Management
 Intravenous immunoglobulin (IVIG)
 Intravenous immunoglobulin is the primary treatment for
patients with KD.
 Giving IVIG in the acute phase reduces the risk of coronary
aneurysm by at least 3–5 fold. Note: Reduces the risk, NOT
preventing development of coronary abnormalities.
 IVIG should be administered once KD is diagnosed, and ideally
within the first 10 days of illness. It should be given even after
the tenth day of illness if the fever persists or in patients with
coronary aneurysms and ongoing signs of inflammation.
 However, in general, IVIG is not prescribed for the patient with a
history consistent with KD but in whom the fever has subsided
for many days, as IVIG is unlikely to prevent coronary disease after
the acute inflammatory response is over.
 Dose: 2g/kg as a single infusion.
 Infuse over 8–12 hours; start at a very low infusion rate and
increase gradually. The infusion rate can be ordered as:
0.5ml/kg/hr x 15 mins, then
4.0ml/kg/hr till completion.
Cardiology 59
 Monitoring during infusion

Temperature, pulse and respiration (TPR), BP q 5 mins x 3, then
TPR, BP q 10 mins x 3, then
TPR, BP hourly till completion
The infusion site should also be monitored for extravasation
during treatment.
 Complications and side effects include:
 Chills and rigors
 Hypotension
 Drug reactions, including anaphylaxis
 Infections (blood product from pooled donors)
 A second dose can be considered for persistent or recrudescent
fever 48–72 hours after initial therapy.
 Aspirin
 Aspirin is used for its anti-inflammatory and anti-pyretic effects;
and in the subacute and convalescent phases for its anti-platelet
effect.
 Meta-analysis had demonstrated the lack of additional benefit
of adding aspirin to IVIG therapy in the prevention of coronary
complications.
 Low dose aspirin after the acute phase is probably more
important when the risk of coronary artery thrombosis is higher;
established coronary vasculitis occurs concomitantly with marked
thrombocytosis and a hypercoagulable state.
 Dose:
Acute phase — 80–100mg/kg/day (anti-inflammatory dose) in
divided doses, usually TDS to coincide with meals.
Subacute/convalescent phase — 3–5mg/kg/day (anti-platelet
dose) as a single dose with meal.
 High dose aspirin should be started in the acute phase once KD
is diagnosed. Convert to low dose aspirin once inflammatory
signs (fever and mucocutaneous changes) have subsided. Some
physicians maintain high dose aspirin for 2 weeks from the onset
of KD.
 Should a patient present late when acute inflammation has
subsided, low dose aspirin can be started.
 Aspirin therapy can be stopped after 6–8 weeks if the latest

echocardiogram is normal. Continue aspirin in patients with
persistent coronary abnormalities.
 Complications of aspirin therapy — Allergy, gastritis,
gastrointestinal bleeding, chronic salicylism and Reye’s syndrome.
 Patients allergic to aspirin, or who have contracted varicella
while on aspirin or intending to have varicella vaccination — Use
dipyridamole 1–2mg/kg/dose (adult 50–100mg) TDS. In the last 2
categories, dipyridamole can be converted back to aspirin after
4–6 weeks.
 Steroids
 Controversial, as initial reports from Japan indicated increased
risk of coronary aneurysm in KD treated with steroids, but there
have been recent reports of successful treatment with steroids
of patients with IVIG-resistant KD. There is also a concern that
steroids might aggravate any underlying infectious process.
 Currently, there is insufficient evidence to recommend steroids as
first-line for the treatment of refractory or recrudescent KD. The
Cardiology Service recommends a second course of IVIG 2g/kg as
treatment for patients with refractory or recrudescent KD.
 Pulsed methylprednisolone (30mg/kg/day as a single infusion
over 2 hours, for 1–3 days) or oral prednisolone (2mg/kg/day for
2 weeks then wean down slowly) can be considered for patients
with refractory or recrudescent KD having failed 2 courses of IVIG.
 More studies are required to establish the role of steroids as an
adjunct in primary treatment or as rescue for KD patients with
refractory of recrudescent fever.
 Other Therapeutic Agents:

Studies are underway to investigate the efficacy of Infliximab and
Etanercept for the treatment of KD.
Cardiology 61
Table 1-7: Follow-up recommendations

Risk Drug Therapy Physical activity Follow-up and Investigations
I Aspirin x 6–8 No restriction beyond 6–8 By general physician, not

weeks weeks. necessary beyond first year
post onset.
II Aspirin x 6–8 No restriction beyond 6–8 By general physician, not
weeks, or until weeks. necessary beyond first year once
ectasia resolves ectasia resolved.
III Aspirin till <10 years old: no restriction Follow-up by general physician
abnormalities beyond 6–8 weeks. or cardiologist.
resolve. ≥10 years old: activity level Annual echo ± ECG.
guided by stress testing. Angiography if stenosis
Competitive, contact sports suspected.
and endurance training
discouraged.
IV Long-term <10 years old: no restriction Follow-up by cardiologist.
Aspirin beyond 6–8 weeks. Annual echo ± 6-monthly ECG.
± Warfarin. ≥10 years old: activity Angiography if stenosis
Clopidogrel may level guided by annual suspected, or electively in
be considered for stress testing. Competitive, certain cases.
patients unable contact sports, endurance
to tolerate training and strenuous
warfarin exercise strongly
discouraged.
V Long-term Competitive, contact sports, Echo + ECG 6-monthly. Annual
Aspirin isometrics and weight Holter + Stress test.
+ Warfarin or training to be avoided. Other Angiography and repeat with
low molecular activity recommendations new-onset or worsening
weight heparin. guided by stress testing or ischaemia.
Consider perfusion scan.
ß-blocker
to reduce
myocardial
oxygen
consumption
 Supportive measures
 Non-pharmacological management of fever.
 Intravenous drip if not feeding well.
 Explanation to parents.
Follow-up of Patients with Kawasaki Disease

Long-term management and follow-up of patients with KD depends on
the degree of coronary artery involvement. Risk stratification by AHA:
Risk Level Patient Profile

I No coronary artery changes on echocardiography
at any stage
II Transient coronary ectasia which resolves on
follow-up
III Small to medium solitary coronary artery
aneurysm on echocardiogram
IV Giant coronary aneurysm or multiple small to
medium aneurysms, without obstruction
V Coronary artery obstruction confirmed by
angiography
In KKH, echocardiograms are done at the following times after

onset: 2 weeks, 3 months, 6 months, 12 months, 18 months and 2
years. Thereafter, echocardiograms at 6- or 12-monthly interval as
indicated. No further echocardiography required once two consecutive
echocardiograms document normal coronary arteries.
Bibliography
1. TH Tan, KY Wong, JT Heng. Kawasaki Disease in Singapore: Incidence and Coronary
Complications. Cardio Young, 2001;11 (Suppl 1):13.
2. AHA Scientific Statement: Diagnostic Guidelines for Kawasaki Disease. Circulation.
2001;103:335–336.
3. Dajani AS et al. Diagnosis and therapy of Kawasaki in Children. Circulation 1993;87:1776–
80.
4. Dajani AS et al. Guidelines for Long-term Management of Patients with Kawasaki Disease.
Circulation 1994; 89:916–922.
5. Durongpisitkul et al. The prevention of Coronary Artery Aneurysm in Kawasaki Disease:
A Meta-analysis on the efficacy of Aspirin and Immunoglobulin Treatment. Pediatrics
1995;96:1057–61.
6. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. AHA Scientific
Statement: Diagnosis, treatment, and long-term management of Kawasaki Disease.
Circulation. 2004;110:2747–2771.
7. Yim D, Curtis N, Cheung M, Burgner D. An Update on Kawasaki Disease II: Clinical features,
diagnosis, treatment and outcomes. Journal of Paediatrics and Child Health 2013
Aug;49(8):614–23.
Cardiology 63
CHEST PAIN IN CHILDREN

Chest pain in children is least likely to be cardiac in origin, and often
idiopathic (23–45%). It is also rarely associated with life-threatening
disease in the paediatric population.
Patients younger than 12 years are more likely to have a

cardiorespiratory aetiology of their chest pain compared with older
children, who are more likely to have a psychogenic cause. Female
patients are more likely to be diagnosed with psychogenic chest pain or
costochondritis. Recurrent symptoms occur in 45–69% of patients; up to
19% may have symptoms lasting for >3 years.
HISTORY
 Nature of chest pain:
 Time of onset and events leading to onset of pain
 Duration
 Frequency
 Nature
 Intensity
 Location
 Radiation
 Precipitating and relieving factors (including relationship to
meals and posture)
 Impact of pain on child’s lifestyle and activity level
 History of trauma
 Systems assessment:
 Elicit symptoms of chronic disease, e.g. fever, malaise, fatigue,
weight loss, night sweats
 Past medical and surgical history (in particular any cardiac surgery or
disease)
 Previous evaluation, treatment and diagnoses in patients with
recurrent chest pain
 Medication
 Family history (in particular of syncope, sudden death or
cardiovascular disease)
 Social history:
 Smoking, alcohol or illicit drugs
 Recent family or peer problems
 School performance including sports and physical fitness, etc.
PHYSICAL EXAMINATION
A thorough and complete physical examination is fundamental to an
accurate diagnosis of chest pain. In particular:
 Vital signs (including BP)
 General appearance, i.e. cyanotic, distressed, anxious, sweaty, poor
perfusion
 Evidence of trauma (e.g. bruising)
 Rash or joint swelling (collagen vascular disease)
 Abnormal breast enlargement, gynaecomastia in males
 Localised chest swelling or tenderness
 Cardiac findings (abnormal heart sounds, arrhythmias, murmurs,
muffled heart sounds, pericardial rub)
 Respiratory findings (depth and rate of breathing, retractions,
rhonchi, crepitations, decreased breath sounds, bronchial breathing
or pleural rub)
 Abdominal examination (hepatomegaly, tenderness)
 Femoral pulses
 Extremities (Temperature, cyanosis, clubbing, oedema)
 Psychological state
RED FLAGS — SIGNS AND SYMPTOMS

 Cardiac:
 Underlying congenital or acquired heart disease
 Arrhythmias
 Crushing sternal chest pain with or without radiation to left arm
or neck
 Exercise-induced chest pain
 Persistent tachycardia
 Persistent hypertension
 Hypotension
 Gallop rhythm
 Syncope
 Respiratory:
 Haemoptysis
 Dyspnoea
 Rales
 Cyanosis
 Gastrointestinal:
 Haematemesis
 Haematochezia
 Melaena
Cardiology 65
 Others:
 Febrile
 Life-threatening psychiatric illness, e.g. psychosis or suicidal ideation
DIFFERENTIAL DIAGNOSES
 Musculoskeletal (very common in pediatric patients; pain is sharp,
nagging and localised but may radiate)
 Costochondritis (mild to severe, localised, reproducible on
palpation and coughing; may have a history of recent Upper
Respiratory Track Infection (URTI))
 Muscle strain
 Trauma
 Child abuse (especially in younger children)
 Fibromyalgia (pain is continuous and lasts longer than 3 months;
tenderness may be elicited over multiple points)
 Precordial Catch or Texidor’s Twinge (sharp pain occurring at rest
usually over the cardiac apex or left lower sternal edge; short
duration; frequency varies; worsens on deep inspiration)
 Tietze’s Syndrome (observed after minor trauma; localised,
moderate and associated with visible swelling; swelling may
remit and recur; associated with an elevated Erythrocyte
Sedimentation Rate (ESR)
 Slipping Rib Syndrome (occurs when the eighth, ninth or tenth
rib overrides the rib above; onset sudden, may radiate to chest or
abdomen)
 Xiphoid-Cartilage Syndrome (occurs after vigorous running; pain
or ‘stitch’ at insertion of xiphoid into the abdominal musculature;
pressure on xiphoid may reproduce the pain)
 Others: Tumours, connective tissue disorders, acute chest
syndrome in sickle cell anemia
 Cardiac:
 Congenital heart disease, in particular:
 Conditions with left ventricular outflow tract obstruction, e.g.
aortic stenosis, hypertrophic cardiomyopathy (HCM)
 Mitral valve prolapse (chest pain probably results from
papillary muscle dysfunction and subendocardial ischaemia)
 Coronary artery anomalies
 Acquired lesions (cardiomyopathy, endocarditis, myocarditis,
AMI, rheumatic fever, accelerated atherosclerotic coronary artery
disease, dissecting aneurysm, pericarditis, Kawasaki Disease)
 Arrhythmias: Atrial fibrillation (AF), atrial flutter, supraventricular

tachycardia (SVT), ventricular tachycardia (VT)
 Respiratory:
 Pneumothorax
 Pneumonia
 Pleural effusion
 Pulmonary embolism (especially in adolescent females on oral
contraceptives)
 Foreign body inhalation
 Chronic cough
 Chronic pulmonary diseases, e.g. cystic fibrosis, chronic asthma
(with exercise-induced symptoms)
 Oesophagitis
 Mallory-Weiss tear
 Gastroesophageal reflux
 Hiatus hernia
 Referred pain from gastritis, peptic ulcer disease, cholecystitis,
pancreatitis
 Foreign body ingestion
 Psychogenic:
 Hyperventilation syndrome
 Somatoform disorder
 Stress
 Depression
 Panic attacks
 Munchausen syndrome
 Others:
 Breast disease (puberty, menstruation, pregnancy, mastitis may
cause pain in females)
 Mediastinal tumours
 Sickle cell disease with vaso-occlusive crisis
 Herpes zoster (intercostal neuralgia pain may occur days before
appearance of vesicles)
 Cigarette-smoking (with or without chronic cough), cocaine use
(palpitations, coronary vasospasm, acute myocardial infarction
(AMI), caffeine overdose, accidental ingestion or inhaled mercury
vapour and trichloroethane aerosol)
Cardiology 67
MAJOR THREATS TO LIFE

 Myocardial ischaemia or infarction
 Pericarditis with tamponade
 Aortic dissection or rupture
 Pneumothorax, pneumomediastinum or pneumopericardium
 Pulmonary embolus
 Perforated or haemorrhaging peptic ulcer
INITIAL INVESTIGATIONS
 Electrocardiogram (ECG)
 Arrhythmias: SVTs, AF, atrial flutter, VTs
 Acute ischaemic changes: ST segment depression or elevation,
symmetrical T wave inversion or tall, pointed, upright T waves;
rarely Q waves
 HCM: Left or biventricular hypertrophy
 Pericarditis: Decreased QRS voltages, generalised ST segment
elevation
 Chest radiograph (CXR)
 To exclude pulmonary causes of chest pain, e.g. pneumothorax,
pneumonia, pleural effusion
 If pulmonary congestion or cardiomegaly present, a thorough
cardiac workup is required
 Others: Rib abnormalities, fractures, markedly dilated aorta (aortic
dissection in patient with Marfan syndrome)
SPECIFIC INVESTIGATIONS, IF INDICATED

 Cardiac:
 Echocardiogram, Holter monitor, exercise stress test, cardiac
enzymes (CK, CKMB, Troponin)
 Pulmonary:
 CT chest, MRI chest, VQ scan, lung function test with and without
methacholine challenge, bronchoscopy
 Endoscopy, pH probe, abdominal ultrasound, serum amylase, LFT,
upper gastrointestinal series
 Musculoskeletal:
 Skeletal radiographs, CT spine, MRI spine, nuclear bone scan
INDICATIONS FOR ADMISSION

 Suspected coronary artery disease, pleural effusion, myocarditis,
pericarditis or aortic dissection
 Severe chest pain of unknown aetiology
INDICATIONS FOR REFERRAL TO PAEDIATRIC

CARDIOLOGIST
 Severe recurrent chest pain
 Associated with sinister symptoms, e.g. syncope, abnormal heart
rhythm (with or without exercise)
 Suspicious of congenital or acquired heart disease
Bibliography
1. Kocis KC. Chest pain in pediatrics. Pediatr Clin North Am. 1999;16(2):189–203.
2. Strafford M. Chest pain. In: Schechter NL, Berde CB, Yaster M, editors. Pain in infants,
children and adolescents. Baltimore: Williams & Wilkins; 1993. p. 571–586.
3. Pearson GD, Ingall CG, Dorosz JJ, Martin GR. Chest pain in an urban pediatric cardiology
practice. Am Pediatr Society and Soc Pediatr Res. 1998;43(4):25.
4. Coleman W. Recurrent chest pain in children. Pediatr Clin North Am. 1984;31(5):1007–1026.
5. Gutgesell HP, Barst RJ, Humes RA, Franklin WH, Shaddy RE. Common cardiovascular
problems in the young: Part 1. Murmurs, chest pain, syncope and irregular rhythms. Am
Fam Physician. 1997;56(7):1825–1830.
6. Selbst SM, Ruddy RM, Clark BJ. Chest pain in children. Clin Pediatr. 1990;29(7):374–377.
7. Swenson JM, Fischer DR, Miller SA, Boyle GJ, Ettedgui JA, Beerman LB. Are chest
radiographs and ECGs still valuable in evaluating new pediatric patients with heart
murmurs or chest pain? Pediatrics. 1997;99(1):1–3.
8. Bass C. Unexplained chest pain and and breathlessness. Med Clin North Am.
1991;755:1157–1173.
9. Clinical Manual of Emergency Pediatrics, Chp 2: Cardiac Emergencies
10. Leung AKC, Robson WLM, Cho H. Chest pain in children. Canadian Family Physician.
1996;42:1156–1164.
11. Selbst SM. Consultation with the specialist: Chest pain in children. Pediatr Rev.
1997;18(5):169–173.
12. Brenner JI, Ringel RE, Berman MA. Cardiologic perspectives of chest pain in childhood: A
referral problem? To whom? Pediatr Clin North Am. 1984;31(6):1241–1258
HYPERCYANOTIC SPELLS
Also known as hypercyanotic attacks or ‘tet spells’. These paroxysmal
attacks require immediate recognition and treatment as severe spells
may lead to seizures, cerebrovascular accidents and other complications
including death.
Cardiology 69
DEFINITION
Episodes of hyperpnoea (i.e. rapid and deep respiration), worsening
cyanosis, and disappearance or attenuation of cardiac murmur in a child
with tetralogy of Fallot. It usually occurs in patients younger than 2 years.
ACUTE MANAGEMENT
A hypercyanotic attack is a medical emergency and requires prompt
management to break the hypoxic cycle. Call for help early and inform
the cardiologist in charge.
Depending on the severity of attack, institute one or more of the

following:
 Try to calm the infant
 Have the parent hold the infant over the parent’s shoulder, or place
the child in a knee-chest position
 Administration of oxygen (although this will not reverse cyanosis due to
intracardiac shunting). Avoid if such attempts further aggravate the child
 Drugs (in order or preference, unless contraindicated):
 IV sodium bicarbonate is necessary to correct metabolic
acidosis. The dosage is 1–2 meq/kg as 1–2ml/kg of 8.4% NaHCO3
slow IV bolus. For infants younger than 3 months, administer
as 4.2% NaHCO3 (dilute the 8.4% NaHCO3 1:1 with normal
saline). Ensure the IV access is secure before administration as
extravasation can lead to severe tissue injury
 Beta-adrenergic blockade with IV propranolol (0.15–0.25mg/
kg given slowly over 5–10 mins; dose can be repeated once). In
the acute attack, propranolol slows the heart rate and reduces
the right ventricular outflow obstruction; it also has a sedative
effect. Esmolol (0.5mg/kg over 1 min; can be given as an infusion
at 50mcg/kg/min) is an alternative8
 Alpha agonists: Phenylephrine (0.1mg/kg SC or IM, 0.01mg/
kg IV, or as an infusion 0.1–0.5mcg/kg/min) or metaraminol
(Aramine®)(0.01mg/kg IV and repeated PRN, can be given as
an infusion 0.1–1.0mcg/kg/min), increases systemic vascular
resistance and reduces right-to-left shunting
 Ketamine (1–2mg/kg IV or 5–10mg/kg IM) is a drug which
simultaneously increases the systemic vascular resistance and
sedates the patient. Both effects are known to terminate the spell
 Morphine (0.1mg/kg IV or SC). Mechanism of action is via

suppression of the respiratory centre and abolishing hyperpnoea.
However, its disadvantages include slow onset and respiratory
depression. Be ready to intubate
 Ventilatory support if necessary
 General anaesthesia or emergency Blalock-Taussig shunt in
intractable cases.
MAINTENANCE THERAPY
 Propranolol and sedation as required.
 Propranolol acts by its peripheral actions of stabilising the reactivity
of the systemic arteries, thereby preventing a sudden decrease in the
systemic vascular resistance. Oral dose is 0.2–0.5mg/kg/dose 6–12
hourly, and can be slowly increased to max of 1mg/kg/dose 6 hourly
as needed
 Sedation may be with chloral hydrate or diazepam. However, avoid
midazolam which reduces systemic vascular resistance further.
Ketamine can also be used for sedation
 Treat fever aggressively and ensure adequate hydration
 Avoid epinephrine, dopamine, dobutamine which have positive
chronotropic and inotropic effects and may therefore, worsen ‘tet
spells’
 Advice to parents of a patient with Fallot’s tetralogy:
 Recognition of hypercyanotic spells: Parents should know that
such spells can be serious and potentially life threatening
 Minimise triggers which can agitate the child and calm the child
down as soon as possible
 Fever is a common trigger, so give antipyretics round the clock
when the child has fever
 Always keep the child well hydrated. See a doctor early if the child
is not feeding well
 If the child has a spell, attempt to calm the child and put in the
knee chest position
 If above measures are unable to terminate spell after 5 mins,
bring to the nearest emergency department urgently
Cardiology 71
Bibliography
1. Park MK. Paediatric cardiology for practitioners. 3rd ed. St. Louis: Mosby; 1996. chp 11 p.
123–124.
2. Sun LS, Du F, Quaegebeur JM. Right ventricular infundibular beta-adrenoceptor complex
in tetralogy of Fallot patients. Pediatr Res. 1997;42(1):12–16.
3. Southall D, Coulter B, Ronald C, Nicholson S, Parke S, editors. International child health
care: A practical manual for hospitals worldwide. London: BMJ Books; 2001. p. 179–180. By
child advocacy international.
4. Van Roekens CN, Zuckerberg AL. Emergency management of hypercyanotic crises in
tetralogy of Fallot. Ann Emerg Med. 1995;25(2):256–8.
5. Behrman RE, Kliegman RM, Jenson HB, editors. Nelson’s textbook of paediatrics. 16th ed.
Philadephia: WB Saunders Company; 2000. p. 1385–1386.
6. DeBoer S. The case of the blue baby: ED Management of tetralogy of fallot. J Emerg
Nursing. 1996;22(1):73–76.
7. Dhir AK, Dhir S. Esmolol in infundibular spasm. Anaesthesia. 1991;46(11):998.
72
CRITICAL CARE
CHILDREN’S INTENSIVE CARE UNIT (CICU)
The CICU is a specialised area with personnel, facilities and resources to
care for critically ill patients who have major organ dysfunction or who
require intensive monitoring. Patients requiring admission to the CICU
are those who require:
 Intensive care treatment with specialised equipment for major organ
failure, e.g. mechanical ventilation and/or extracorporeal life support
(e.g. ECMO, continuous haemodialysis).
 Continuous nursing care and skills that do not exist in other areas to
initiate therapy or provide sophisticated monitoring.
 Intensive care skills at very short notice, e.g. airway control and
intubation.
ADMISSION CRITERIA
All new admissions to CICU should be discussed with ICU consultant.
Mandatory Admission
 All intubated patients requiring mechanical ventilation
 Multi-organ failure
 Ongoing cardiopulmonary resuscitation or post-resuscitation
 Traumatic head injury with intracranial haemorrhage
 Newly created tracheostomy
 Severe metabolic or electrolyte abnormalities requiring therapy
exceeding general paediatric care unit guidelines such as
hyperkalaemia requiring cardiac monitoring and acute therapeutic
intervention or severe hypo- or hypernatraemia
Relative indications (including but not limited to):

 Potential airway compromise from any cause
 Shock
 Acute organ failure, e.g. Renal, liver, cardiac or respiratory failure
 Significant trauma
 Deteriorating level of consciousness
 Severe metabolic derangements
 Unstable or life threatening haematological or oncological
conditions
Critical Care 73
 Following high-risk surgery (e.g. cardiac, cardiothoracic,

neurosurgical, ENT, respiratory) or surgery in a high risk patient (e.g.
neuromuscular disease, pre-existing airway obstruction)
 Need for monitoring that cannot be supported in other areas
(e.g. ICP monitoring, arterial, central venous or pulmonary artery
monitoring). Conditions that necessitate the application of special
technological monitoring, complex intervention, or treatment
including medications that exceed individual patient care unit
policies.
DISCHARGE/TRANSFER CRITERIA
Patients in the CICU will be evaluated and considered for discharge if
there is reversal of the disease process or resolution of the unstable
physiologic condition that prompted admission to the CICU, and if there
is no longer a need for complex intervention exceeding general ward
patient care unit capabilities.
Bibliography
1. American Academy of Pediatrics, Committee on Hospital Care, and Society of Critical Care
Medicine, Pediatric Section. Guidelines and levels of care of pediatric intensive care units.
Crit Care Med. 1993;21:931–937; and Pediatrics. 1993; 92(1):166–175.
2. Ethics Committee, Society of Critical Care Medicine. Consensus statement of the SCCM
Ethics Committee regarding futile and other possibly inadvisable treatments. Crit Care
Med. 1997;25:887–891.
3. American Academy of Pediatrics, Committee on Hospital Care and the Pediatric Section
of the Society of Critical Care Medicine. Guidelines for pediatric intensive care units.
Pediatrics. 1983;72(3):364–371; and Crit Care Med. 1983;11:753.
RECOGNITION OF THE
CRITICALLY ILL CHILD
INTRODUCTION
Children are often unable or unwilling to verbalise complaints.
In addition, symptoms and signs of sepsis or cardio-respiratory
compromise are often vague and subtle in children.
The ability to assess and recognise an ill child early allows for
simple interventions and therapy such as ventilatory support, fluid
resuscitation or early antibiotics to reverse potentially life-threatening
cardiopulmonary instability.
ANATOMIC AND PHYSIOLOGICAL CONSIDERATIONS

Respiratory arrest is the most common cause of cardio-pulmonary
collapse in children. This is largely because the paediatric respiratory
system is ill-designed to cope with an increased work of breathing.
The reasons are multi-factorial and include a relatively large tongue
and floppy epiglottis, small airways with increased airway resistance,
and increased chest wall compliance due to a cartilaginous chest wall.
Respiratory failure is characterised by inadequate ventilation, insufficient
oxygenation or both.
Cardiac output is a product of stroke volume and heart rate, and blood
pressure is a function of cardiac output and systemic vascular resistance.
Circulatory shock is defined as the failure of the circulatory system to

provide oxygen and nutrients to meet tissue metabolic demands. Shock
can be classified into compensated, uncompensated or irreversible.
Compensatory mechanisms include tachycardia and increased systemic
vascular resistance in an effort to maintain cardiac output and perfusion
pressure (blood pressure) respectively. Decompensation occurs when
these mechanisms fail and result in end-organ hypoperfusion and
hypotension. Untreated, shock states can rapidly deteriorate into failure
of multiple organ systems and lead to irreversible shock and death.
The pathophysiology of shock can be divided into distributive,

hypovolaemic/haemorrhagic, cardiogenic or obstructive. It
is not unusual for one patient to have a number of different
pathophysiological patterns of shock depending on the time-course of
their disease.
Recognition of pre-shock states is important so that early goal-directed

therapy can be instituted. The regimen of resuscitation includes fluid
boluses, airway intervention and inotropic support. The key is early
shock recognition and prompt action.
HISTORY
Functionality of the child is a simple but effective measure of how ill the
child is. Questions to ask include:
 Level of activity/play
 Conscious level/irritability
 Feeding/fluid intake
 Urine output
Critical Care 75
Red flags in the history include:

 High-pitched cry/inconsolable crying
 Grunting
 Cyanosis
 Apnoeic episodes
 Pallor, cool and clammy peripheries
 Shortness of breath or dyspnoea
 Acute change in mentation
 Focal seizures
 Bloody stool in a neonate
There should be a low index of suspicion in the very young, or if there is

a significant medical history such as:
 Maternal history of GBS (in a neonate)
 Congenital cardiac defects
 Primary immunodeficiency syndromes
 Chronic steroid usage
 Haematological-oncological disorders on active chemotherapy
 History of adreno-cortical deficiency, e.g. hypopituitarism, congenital
adrenal hyperplasia, hypothalamic or pituitary lesions
VITAL PARAMETERS
Hypotension is defined as systolic BP:
<60mmHg in a neonate
<70mmHg in infants (1–12 months)
<70mmHg + [2 x (Age in Years)] in children 1–10 years
<90mmHg in children older than 10 years
Mean arterial pressure can be calculated as {50 + [2 x (Age in Years)}

mmHg.
Table 2-1: Table of normal heart rate, respiratory rate and systolic blood pressure by age
Heart Rate Respiratory Rate Systolic blood
Age
(bpm) (min) (pressure/mmHg)
Neonate 120–180 40–60 60–80
Infant (1 month to 1 year) 110–160 30–40 70–90
Toddler (1–2 years) 100–150 25–35 80–95
Young child (2–7 years) 95–140 25–30 90–110
Older child (7–12 years) 80–120 20–25 100–120
Pulse pressure (systolic minus diastolic BP) is usually >20mmHg. A

widened pulse pressure is present in distributive shock. A narrow pulse
pressure may suggest hypovolaemic or cardiogenic shock.
Unexplained tachycardia may be one of the first signs of compensated shock.
Clinical states which can rapidly progress and are life-threatening include:
Severe respiratory distress
Cardiovascular instability/cardiogenic shock
Sepsis/septic shock
Severe dehydration
Seizures/altered mental state
Trauma
Red flags in the physical examination which may indicate an unwell

child include:
 General appearance:
 Mottling of the skin
 Pallor
 Cool peripheries
 Lethargy/irritability
 Bulging tense fontanelles
 Purpuric rash
 Bruising/petechial rash
 Hyper-pyrexia (>40°C)
 Respiratory system:
 Cyanosis
 Tachypnoea/bradypnoea for age
 Kussmaul’s respirations
 Grunting
 Nasal flaring/retractions/use of accessory muscles
 Audible stridor with drooling
 Cardiovascular:
 Delayed capillary refill time (>2 secs)
 Weak/thready pulses
 Tachycardia/bradycardia/hypotension for age
 Cardiac arrhythmias
 New onset murmur
 Gallop rhythm
 Absent femoral pulses (neonate)
Critical Care 77
 Neurological:
 Focal neurological signs
 Rapidly decreasing conscious level or Glasgow Coma Score (GCS) <13
 Altered mental state
 Asymmetrical pupillary reflex
 Trauma:
 Penetrating injury of chest or abdomen
 Suspected spinal cord injury
 Flail chest
 Skull fracture
 Facial burns or burns involving >10% Body Surface Area (BSA)
Learn to integrate the signs of an unwell child as no single sign

is definitive. If a red flag is present in the history and/or physical
examination, consider the following:
 Admit for observation
 Call for senior help if there is evidence of severe respiratory distress,
poor perfusion and/or hypotension, obtundation/change in
mentation, prolonged seizure or cardiac arrhythmias
 Activate the paediatric Code Team if there is imminent cardiopulmonary
arrest, severe respiratory compromise needing intubation, or there is
difficulty stabilising the patient, e.g. difficult venous access, no response
to therapeutic interventions, potential difficult airway.
INVESTIGATIONS
 Hypocount: Exclude hypoglycaemia or DKA as a cause for obtundation
 Blood gas analysis: Evaluate for metabolic or respiratory acidosis,
sodium/potassium/calcium derangements
 FBC, U/E/Cr and group and match
 Imaging: CXR to exclude pulmonary pathology, cardiomegaly. CT
head if there are concerns regarding intracranial pathology
 Septic screen including blood and urine cultures if sepsis is suspected.
Consider CSF cultures if an intra-cranial infection is suspected
 Liver function test/coagulation profile if suspected liver dysfunction/
bleeding diathesis
 Serum lactate if available. This reflects tissue hypoperfusion and can
be used as a marker of response to therapy
 Metabolic screen if there is unexplained severe metabolic acidosis/
hypoglycaemia
 Drug toxicology screen if suspected
ACUTE TREATMENT
Regardless of cause, assess Airway, Breathing and Circulation first.
 Airway/breathing:
 Ensure patent airway. Allow position of comfort as far as possible.
 Provide humidified oxygen to all patients with respiratory distress
 Administer 100% oxygen non-rebreather facemask if hypoxia or
shock is present
 Consider intubation and assisted ventilation if there are concerns
about impending respiratory arrest, severe respiratory distress/
respiratory failure, shock or inability to maintain airway reflexes.
Assisted ventilation will reduce work of breathing and cardiac
metabolic demands especially in cardiogenic and septic shock states.
 Non invasive assisted ventilation may be considered in less emergent
circumstances.
 Consider salbutamol if there is evidence of bronchoconstriction or
nebulised epinephrine for subglottic oedema
 Institute specific therapy for underlying aetiology of respiratory failure, e.g.
antibiotics in pneumonia, anti failure therapy in heart disease, salbutamol
for asthmatic attacks, steroids for acute laryngotracheobronchitis
 Circulation:
 Access: Secure IV access early; insert 2 large bore IV cannulae if in
shock. Consider intra-osseous access if venous access is difficult.
 Fluids: Administer fluid resuscitation if there are signs of shock,
e.g. tachycardia, prolonged capillary refill time, cool peripheries.
Give IV isotonic crystalloids in aliquots of 10–20ml/kg boluses and
watch for response. If there is suspicion of cardiogenic shock, give
fluids cautiously and consider early inotropic support. (See later
chapter on “Paediatric Cardiopulmonary Resuscitation”)
The rate of infusion should be dependent on the clinical state. In acute
resuscitation, volume should be given as IV rapid boluses. In less acute
situations, the volume can be given over 15 mins to 1 hour.
Blood products should be considered in hypovolaemic shock secondary
to blood loss, severe anemia or coagulopathic states.
Consider inotropic/vasopressor support if shock is fluid-resistant or cardiogenic
in origin. Vasopressors should ideally be run via a central venous access.
 Administer EARLY antibiotic therapy (within 1 hour) if there is
suspected sepsis/septic shock
 Correct rapidly reversible, potentially life-threatening derangements.
This includes:
 Hypoglycaemia: IV dextrose 10% 4–5ml/kg or dextrose 25%
1–2ml/kg
Critical Care 79
 Symptomatic hyponatraemia: IV 3% NaCl 2ml/kg over 30 mins

 See full management of hyperkalaemia under “emergency
management of hyperkalaemia in children-algorithm” (see page
653)
 Hypocalcaemia: IV 10% calcium chloride 0.2ml/kg over 10 mins or
10% calcium gluconate 0.5ml/kg slow bolus
 Transfer patient to an appropriate care facility after initial
stabilisation
MONITORING
 Continuous pulse oximetry, heart rate and respiratory rate
monitoring
 Close BP monitoring: Consider invasive BP/CVP monitoring if there
are concerns about haemodynamic status
 Continuous cardiac monitoring if there is concerns about rhythm
disturbances or myocardial dysfunction
 Conscious level monitoring
 Urine output as a marker of perfusion and end-organ function
Bibliography
1. 2005 American Heart Association (AHA) Guidelines for cardiopulmonary resuscitation
CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients:
Pediatric advanced life support. Pediatrics. 2006;117(5):1005–1028.
2. Advanced Life Support Group. Advanced paediatric life support: The practical approach.
4th ed. London: Blackwell Publishing; 2005.
3. Mejia R, Serrao K. Assessment of critically ill children. In: Mejia R, editor. Pediatric
fundamental critical care support. Mount Prospect, Ilinois: Society of Critical Care
Medicine; 2008. p. 1.1–121.
4. Shann F. Drug Doses. 13th ed. Melbourne: Collective Pty Ltd; 2005.
5. Kleinman ME, Chaemeides L, Schexnayder SM et al. Part 14: Pediatric Advanced Life
Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care. Circulation 2010; 122(suppl 3): S876–908
6. Carcillo JA, Fields AI, American College of Critical Care Medicine Task Force Committee
Members. Clinical practice parameters for hemodynamic support of paediatric and
neonatal patients in septic shock. Crit Care Med. 2002;30(6):1365–1378.
PAEDIATRIC CARDIOPULMONARY
RESUSCITATION
In children, cardiopulmonary arrests are usually as a result of progressive
respiratory failure or shock. While the survival of children with in-
hospital cardiac arrests have increased over the last 20 years (from 9%
to 27%), survival of children from out of hospital cardiac arrests remain
unchanged and poor (6%). Despite the improved outcome of in-
hospital CPR, the majority of children surviving from cardiac arrest have
significant neurological deficits.
The provision of paediatric advanced life support usually takes place

in a hospital environment where multiple responders can be rapidly
mobilised and are capable of simultaneous actions. Important aspects to
a successful resuscitation from cardiac arrest include early high quality
chest compressions and early assisted ventilation.
ASSESSMENT
 Recognition of cardiac arrest should take no more than 10 secs.
 The absence or presence of a pulse is not a reliable determinant
of cardiac arrest; other determinants include unresponsiveness,
gasping breaths and no spontaneous respirations.
 If cardiac arrest has occurred, activate the Code/Medical Emergency
Team.
MANAGEMENT
 Airway/breathing
 Open airway by appropriate positioning of head
 Infant: Neutral head position
 Child: Head tilt-chin lift
 Jaw thrust for suspected cervical injury
 Clear the airway by brief suctioning of mouth and pharynx if
secretions are present
 Apply bag-mask ventilation with 100% oxygen (at least 15L/min
oxygen flow)
 Use an oropharyngeal airway only in the unconscious child. Measure
appropriate sized oropharyngeal airway (from incisors to angle of
mandible).
 Ensure correct mask size, tight seal between mask and face, and
assess for effectiveness of ventilation (saturations, chest rise).
 Deliver each breath with an inspiratory time of about 1 sec.
Critical Care 81
 Ventilation should occur at 10 breaths per minute (30 compressions

followed by 2 ventilations in un-intubated patients in cardiac arrest).
In intubated patients, ventilate at 10 breaths per minute without
interrupting chest compressions.
In a patient with a perfusing rhythm but absent or inadequate

respiratory effort, give 1 breath every 3–5 secs (12–20 breaths per
minute).
Circulation
 Place on cardiac monitor/defibrillator monitoring
 Place the patient on a firm board and commence External Cardiac
Massage if pulseless, heart rate <80/min in neonates or <60/min in
child with evidence of shock (see algorithm on “pulseless arrest/PEA”)
 High quality CPR requires chest compressions to be of appropriate
depth and rate, with complete chest recoil after each compression,
minimal interruptions to the chest compressions and avoidance of
excessive ventilation
 Use “two fingers” (lone rescuer) or “thumb encircling” technique for
an infant, placed just below the intermammary line
 Use the heel of 1–2 hands for an older child placed at the lower half
of the sterum in the midline.
 Push Hard: Depress at least a third of the Anterior-Posterior (AP)
diameter of the chest.
 Push Fast: Chest compressions of at least 100–120/min.
Endotracheal Intubation
Endotracheal intubation should be performed by an experienced
doctor. (See appendix “Useful formulae” for ETT size formula and lengths
and RSI agents on page 642).
Use of Rapid Sequence Induction (RSI) drugs facilitates emergency

intubation and reduces the risk of complications associated with
intubation. RSI should be used only by trained, experienced providers.
Patients in cardiopulmonary arrest and/or deep coma do not need
RSI; otherwise intubation should be preceded by oxygenation and RSI
agents.
RSI agents typically consist of an anaesthetic induction agent and a

muscle relaxant. Maintenance of oxygenation and ventilation by bag-
valve-mask ventilation should be effective before paralysis is instituted.
Avoid paralytic and sedative agents in a patient with a difficult airway.
Both cuffed and uncuffed endotracheal tubes (ETT) may be used in

infants and children. If cuffed tubes are used, cuff inflating pressures
should be monitored and limited according to manufacturer’s
guidelines. Uncuffed ETTs are recommended for neonates.
Indications for cuffed ETTs include large ETT leak, poor lung compliance
and high airway resistance.
Use both clinical assessment and confirmatory devices (where available)

to verify correct ETT placement.
Indications for intubation:

 Severe airway obstruction
 Airway protection in the presence of poor/absent airway reflexes, e.g.
decreased conscious level, prolonged seizures, abnormal brainstem
function, bulbar/pseudobulbar palsy
 Apnea or ineffective respiratory drive
 Respiratory failure not responding to or not suitable for non-invasive
ventilation
 To assist with airway toileting
Vascular access
Set 2 large bore intravenous access for resuscitation. This attempt should
take no longer than 60–90 secs.
Intraosseous (IO) access into the anterior tibial bone marrow (about
1–3cm below and medial to the tibial tuberosity) can be used if venous
access is difficult. All intravenous medications/blood products can be
given intra-osseously.
The endotracheal route can be used to give lipid-soluble emergency

drugs (LEAN- lignocaine, epinephrine/adrenaline, atropine, naloxone)
followed by a flush of 5mls normal saline and five manual ventilations.
Optimal ET drug doses are unknown, the general consensus is double or
triple the dose of lignocaine, atropine or naloxone. For adrenaline, an ET
dose ten times the intravenous dose (0.1ml/kg of 1:1000 concentration)
is recommended.
Central venous cannulation or a venous cutdown may be performed if

expertise is available.
Critical Care 83
Drugs and fluids (See appendix on “paediatric emergency drug doses”)

Use isotonic crystalloids as initial fluid for shock/fluid resuscitation. Give
aliquots of 20ml/kg boluses and assess for response.
There is no added benefit to using colloids during early resuscitative
efforts, and there is an associated risk of mortality with the use of
colloids for resuscitation in children with trauma, burns or traumatic
brain injury.
Routine use of sodium bicarbonate is not recommended in cardiac

arrest. It may be administered for treatment of tricyclic antidepressant
overdose or hyperkalaemia.
Routine use of calcium is not recommended for paediatric

cardiopulmonary arrest in the absence of documented hypocalaemia,
calcium channel blocker overdose, hypermagnesaemia or hyperkalaemia.
Gastric Insufflation
Insert a nasogastric tube if abdominal distension is marked and/or
oxygenation and ventilation are compromised.
Pass the tube after intubation as it may interfere with gastroesophageal
sphincter function, increasing risk of aspiration during intubation.
Termination of resuscitative efforts

Details of events and treatment must be recorded. Where there is no
response after 20 mins of adequate resuscitation, the senior doctor
should decide how long efforts should be continued.
SPECIAL RESUSCITATION CONDITIONS
Ventilation with a tracheostomy

Use the tracheostomy tube for assisted ventilation and watch for
adequate chest rise
If the tracheostomy tube does not allow effective ventilation even after
suctioning, change it.
If still unable to maintain effective ventilation, attempt alternative

ventilation methods such as bag-mask ventilation through the nose and
mouth while occluding the tracheal stoma.
RESUSCITATION ALGORITHM
(Please see Appendix Section page 644)
Bibliography
1. Fuhrman BP, Zimmerman JJ, editors. Pediatric Critical Care. 2nd ed. St Louis: Mosby; 1998. p.
115–116.
2. Biarent D, Bingham R, Eich C. et al. European Resuscitation Council Guidelines for
Resuscitation 2010 Section 6. Paediatric life support. Resuscitation 2010; 81:1364–1388
3. Berg MD, Schexnayder SM, Chameides L et al. Part 13: Pediatric Basic Life Support:
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care. Circulation 2010; 122 (suppl 3): S862–875
4. Kleinman ME, Chaemeides L, Schexnayder SM et al. Part 14: Pediatric Advanced Life
Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care. Circulation 2010; 122 (suppl 3): S876–908
5. Newborn and paediatric resuscitation 2011 guidelines. The Singapore National
Resuscitation Council’s Neonatal and Paediatric Resuscitation Workgroup 2010–2011.
Singapore Med J 2011; 52: 560–572
6. Choi PT, Yip G, Quinonez LG, Cook DJ. Crystalloids vs. colloids in fluid resuscitation: a
systematic review. Crit Care Med. 1999;27: 200–210.
85
ENDOCRINOLOGY
ADRENAL INSUFFICIENCY IN CHILDREN
Adrenal insufficiency when acute (adrenal crisis), is a medical
emergency. Glucocorticoid replacement is required in all forms of
adrenal insufficiency, while mineralocorticoids are required in only
primary adrenal insufficiency.
Suspect acute adrenal insufficiency in any unwell child known to

have adrenal insufficiency who has an intercurrent illness and in
any child withdrawing from steroid therapy.
Clinical and biochemical features

Acute manifestations include:
 Hypotension and shock (from loss of vasomotor tone)
 Hypoglycaemia (from low liver glucose output)
Subacute manifestations include:

 Hyperpigmentation (from chronic ACTH exposure)
 Lethargy, weakness and tiredness (from electrolyte changes)
 Loss of appetite and weight loss (from anorexia and volume
depletion)
Biochemical features
 Hyponatraemia +/- hyperkalaemia (from aldosterone deficiency)
 Hypoglycaemia (from cortisol deficiency)
 Raised urea +/- creatinine (from dehydration)
 Raised plasma renin activity (from volume depletion) and serum
ACTH (in primary adrenal insufficiency)
 Inadequate cortisol response to Synacthen stimulation
** In any severely ill child who may be presenting with adrenal

insufficiency for the first time
 Take samples for: serum electrolytes, glucose, cortisol, 17-OH
progesterone, ACTH, plasma renin and aldosterone before
administering glucocorticoids.
Table 3-1: Management of adrenal crisis
Administer IV or IM hydrocortisone (100mg/m2 body surface area) URGENTLY:

• BSA guide: 3-year-old 0.5m2 (50mg), 8-year-old 1m2 (100mg), adult 1.7m2
(150–200mg)
• Manage severe hyperkalaemia urgently if needed.
Resuscitate with normal saline 10–20ml/kg if hypotensive, in shock or poorly

perfused.
• Repeat IV normal saline 10ml/kg if needed.
• Repeat the hydrocortisone dose if poor response to intravenous hydration.
Administer 10% dextrose 2ml/kg as a slow bolus if blood glucose is low.

• Subsequently, provide adequate dextrose (5%) in the maintenance drip
(0.9% N/S), withholding potassium until the serum potassium is normal.
Continue stress doses of IV hydrocortisone 100mg/m2/day in 4–6 divided doses

until the clinical condition stabilises
• Subsequently, reduce hydrocortisone doses after consultation.
Causes of adrenal insufficiency

Primary adrenal insufficiency (serum ACTH is elevated):
 congenital adrenal hyperplasia
 adrenal hypoplasia congenita
 adrenoleukodystrophy
 Addison’s disease
 adrenal damage or removal
 autoimmune adrenalitis
Secondary adrenal insufficiency (serum ACTH is insufficient):

 hypothalamic damage or tumours
 pituitary damage or tumours
 cranial irradiation
 chronic steroid therapy causing ACTH suppression
 withdrawal from steroid therapy
Endocrinology 87
Table 3-2: Replacement therapy for adrenal insufficiency
Hydrocortisone:
• The replacement hydrocortisone dose in primary adrenal insufficiency is
12–15mg/m2/day. Requirements are higher (2–4 times) during stress to the
body (febrile illness, injury, surgery, anaesthesia).
• The replacement hydrocortisone dose in secondary adrenal insufficiency due to
ACTH deficiency is usually less than the above doses, at about 8–10mg/m2/day.
Long acting glucocorticoid:

• Prednisolone (2–4mg/m2/day) and dexamethasone (0.25–0.375mg/m2/day), as
once daily doses, are glucocorticoid options after final height has been achieved.
Mineralocorticoid:
• The replacement fludrocortisone dose in primary adrenal disease is 0.05–0.2mg/
day (NOTE: absolute dose and not per body weight or surface area). Dose
adjustments are based on serum electrolytes, BP and plasma renin activity.
Table 3-3: Peri-operative glucocorticoid cover
Major surgery:
• At induction of anaesthaesia give IV hydrocortisone 100mg/m2.
• Then give IV hydrocortisone 100mg/m2/day in 4–6 divided doses until the major
stress period is resolved.
Minor surgery:
• At induction of anaesthaesia give IV hydrocortisone 100mg/m2.
• Then give 3–4 times the usual dose of oral hydrocortisone for 24 hours.
Glucocorticoid cover for intercurrent illness

Children with, or who are at risk of, adrenal insufficiency must be given
increased doses of replacement doses of hydrocortisone for stress
according to the following guidelines:
 Moderately unwell and/or temperature 38–39ºC: give 3 times the

usual doses of hydrocortisone.
 More unwell and/or temperature >39ºC: give 4 times the usual dose
of hydrocortisone.
 If the dose is vomited within 1⁄2 hour of ingestion, repeat the dose.
 If the dose is vomited again, bring the child to Children’s Emergency.
 For gastroenteritis or diarrhea: give 4 times the usual dose of
hydrocortisone.
 For those at risk of adrenal insufficiency but not requiring everyday
replacement hydrocortisone: give hydrocortisone 60–100mg/m2/day
in 3 divided doses during the period of stress.
 When the stress is over, return to previous dosing regimen without
tapering.
Bibliography
1. Speiser PW, Wilson TA. Pediatric Adrenal Insufficiency. MedGenMed 2011. Available at:
www.emedicine.medscape.com/article/919077. Accessed October 31, 2011.
2. Jung C, Inder WJ. Management of adrenal insufficiency during the stress of medical illness
and surgery. MJA 2008; 188(7):409–413.
HYPERGLYCAEMIA
Hyperglycaemia refers to high blood glucose (BG).
The human body maintains BG levels between 4–7mmol/L in people
without diabetes, therefore a person whose BG is consistently above
7mmol/L has hyperglycaemia.
Symptoms of hyperglycaemia (increased passage of urine and thirst)
may not be noticeable until BG levels remain consistently above
15mmol/L.
Hyperglycaemia may be transient or persistent, asymptomatic
or symptomatic. It may or may not indicate that the person has
diabetes (DM).
Table 3-4: Causes of hyperglycaemia

• Diabetes mellitus (DM) • Medication induced, e.g. steroids
• Stress hyperglycaemia • Other endocrine causes
 Febrile child  Thyrotoxicosis
 Critically ill child  Cushing syndrome/disease
 Dehydrated child  Phaeochromocytoma
Endocrinology 89
Table 3-5: Practical issues and responses

Issue Question/action Practice points
Diagnosis Does the Existing diagnostic criteria for DM are based on
hyperglycaemic child BG measurements and the presence or absence of
have DM? symptoms.
Test • Symptoms of diabetes and random plasma
• Fasting BG glucose ≥11.1mmol/L or
• OGTT • Fasting (no caloric intake for at least 8 hours)
plasma glucose ≥7.0mmol/L or
• 2-hour post glucose load BG ≥11.1mmol/L
during an OGTT (glucose 1.75g/kg body weight,
max 75g).
Asymptomatic or mildly symptomatic children with
equivocal hyperglycaemia may have “pre-diabetes”
and need retesting on another day.
Classification Does the Type 1 diabetes Type 2 diabetes:
of diabetes hyperglycaemic (T1DM): • DKA at presentation is
child have insulin • DKA at uncommon
deficiency or presentation is • FH of obesity,
resistance? common T2DM, raised TG and
Test • FH of hypertension
• Fasting BG autoimmune • Acanthosis nigricans
• Fasting insulin conditions • Autoantibody negative
and c-peptide including T1DM,
• Blood/urine thyroid disease,
ketones vitiligo and celiac
• GAD antibody disease
• Islet cell antibody • Immune-
(ICA) mediated
(autoantibody
positive)
Classification may not be obvious. Early diagnosis
of T1DM is mandatory as it may be life saving. Refer
suspected diabetes early, where possible on the
same day.
Therapy How severe is the See Table 3-6 for management of hyperglycaemia in
insulin deficiency? children and adolescents.
Table 3-6: Management of hyperglycaemia in children and adolescents
MANAGEMENT OF HYPERGLYCAEMIA
Assess symptoms Assess biochemistry
Look/ask specifically for each of these symptoms Test BK, UECr and ABG in all
children with high BG
INSULIN DEFICIENCY PYRAMID

Increased passing of urine
Raised blood ketones

Kussmal’s breathing
Reduced sensorium
Low bicarbonate
abdominal pain
Increased thirst
Blood glucose
SCORE (IDPS)
Dehydration
Weight loss
Description
Nausea,
S KB D NAP Wt Th PU Score BG BK BC
10 bg
pu 9 BG
HIGH BG
th PU 8 BG
wt TH PU 7 BG
6
WT TH PU BG bk
KETOSIS
nap WT TH PU 5 BG BK
d NAP WT TH PU 4 BG BK bc
D NAP WT TH PU 3 BG BK BC

ACIDOSIS
kb D NAP WT TH PU 2 BG BK BC
s KB D NAP WT TH PU 1 BG BK BC
S KB D NAP WT TH PU 0 BG BK BC

Endocrinology 91
IN CHILDREN AND ADOLESCENTS
Assess biochemistry Establish the clinical context Decide appropriate action
Test BK, UECr and ABG in all children with Determine the IDPS Integrate context, implication and action
high BG needed
Low partial pressure CO2
Raised urea creatinine
Low corrected sodium
pH <7
UCr Na PaCO2 pH Implication What’s needed Action

May/may not be Diagnostic
Asymptomatic high BG OGTT
diabetes testing
Meets criteria
for diagnosis of
Classification
diabetes: type is
Symptomatic high BG unclear Early referral
Appropriate
Low risk of DKA,
therapy
therefore insulin
therapy not urgent
High risk of
progression to DKA Consult
Early decompensation Insulin
Urgent insulin Rx endocrinology
needed
Early DKA
ucr
Metabolic
UCr na Moderate DKA Fluids Insulin DKA workflow
emergency!
UCr Na PaCo2
Severe DKA
UCr Na PaCo2 pH<7
2012 KKH Endocrinology

Reproduced with permission only
Management of hyperglycaemia in children and adolescents:

The clinical presentation of a child with newly diagnosed or known
to have diabetes depends on the degree of insulin deficiency and
metabolic compensation.
Varying degrees of insulin deficiency are reflected by the insulin

deficiency pyramid score (IDPS, 0 being the most severe) and
corresponding symptoms and biochemical markers are mapped into the
insulin deficiency pyramid (see Table 3-6). These indicators help define
the clinical context and appropriate management.
Table 3-7: In all children with hyperglycaemia

 Determine the clinical context to identify if immediate action is needed.
 Take a complete history focusing on the following and the timing of the events:
• Polyuria and thirst
• Weight loss and appetite
• Energy levels
• Nausea, vomiting and abdominal pain.
 Examine for Kussmaul breathing (for clinical acidosis) and quantify the degree of dehydration
 Determine the neurological state (which will be affected in more acidotic states).
 Check blood or urine for ketones.
 Check blood for urea, creatinine, glucose and electrolytes.
 Check the capillary blood gas.
 Assess and investigate to classify the aetiology of diabetes.
 Take a full family history:
• Autoimmune disorders
• Metabolic conditions
 Examine for signs of insulin resistance
• Acanthosis nigricans (hyperinsulinism)
• Skin tags (hyperinsulinism)
 Examine for autoimmune conditions
• Goitre
• Vitiligo
• Mucocutaneous candidiasis
 Examine for features of the metabolic syndrome
• High BMI
• Hypertension
• Hirsutism in females
 Determine the pubertal stage
 Obtain blood samples for:
• GAD/ICA antibodies
• Fasting lipids, blood glucose, insulin and c-peptide
Endocrinology 93
DIABETIC KETOACIDOSIS
Diabetic ketoacidosis (DKA) is the leading cause of morbidity and
mortality in children and adolescents with type 1 diabetes. DKA may
also occur in patients with type 2 diabetes. Cerebral oedema secondary
to overzealous fluid management in DKA can be fatal.
 The criteria for DKA are:

 Hyperglycaemia (BG >11mmol/L)
 Metabolic acidosis (pH <7.3, HCO3 <15mmol/L)
 Blood ketones >1.5mmol/L or urine ketones 2+ and higher
Upon diagnosis, note the goals, principles and complications of DKA

treatment.
Then refer to the workflow for the management of DKA.
 The goals of treatment are:

 Correction of acidosis and reversal of ketosis
 Gradual, smooth correction of dehydration
 Restoration of blood glucose to near normal
 Avoid complications of therapy (cerebral oedema and
hypokalaemia)
 Identify and treat any precipitating illness
 The key principles of management are:

 To recognise differences in the severity of DKA
 To avoid fluid boluses unless in shock (to prevent cerebral oedema)
 To correct dehydration over 48–72 hours (to prevent cerebral
oedema)
 To maintain sufficient insulin dose (adding dextrose if needed)
until acidosis (HCO3 >15mmol/L) is reversed
 To assess neurological & biochemical status frequently during
insulin infusion
 The complications of therapy are:

 Cerebral oedema
 Hypokalaemia
 Hypoglycaemia
 Inadequate rehydration
 Hyperchloraemic acidosis
Table 3-8: Important formulae

Formula/Fluid Additional Instructions
Maintenance fluid First 10kg: 100ml/kg; next Males: max 2,500ml/day
10–20kg: add 50mg/kg; Females: max 2,000ml/day
above 20kg: add 20ml/kg
Fluid requirement (48 hours maintenance fluids Give over 48 hours
+ volume deficit) — Fluid Give over 72 hours if corr. Na
used in resuscitation >150mmol/L
Fluid deficit (ml) % dehydration x body weight 3% if mild, 5% if moderate,

(kg) x 1,000 8% if severe
Initial fluid choice 0.9% NaCl with 20mmol KCl Given for at least 12 hours
to each bag of 500ml
Subsequent fluid 0.45% NaCl with 20mmol KCl

to each bag of 500ml
Corrected Na (mmol/L) Measured Na + 0.4 (blood Estimate: add 0.3mmol/L Na

glucose — 5.5mmol/L) for every 1mmol/L glucose
>5.5mmol/L
Practice points
**Inform the Endocrine Team of all patients with DKA.
 Resuscitation:
 Bolus fluid only if in shock
 All moderate to severe DKA patients should be kept “nil by mouth”
 Fluid therapy:
 Hydrate intravenously over 48 hours
 Correct for 3–8% dehydration (dehydration is rarely above 10%)
 Use 0.9% NaCl as the initial fluid for the first 12 hours
 Add 20mmol KCL to every 500ml of fluid, unless in renal failure
 Replace ongoing fluid losses, such as vomiting or excess diuresis
only if significant
 Ongoing fluid prescription:

 There is deficit in body sodium and potassium at DKA presentation
 Always determine corrected Na levels, as high glucose causes
pseudohyponatraemia
Endocrinology 95
Figure 3.1: Workflow to manage DKA
WORKFLOW FOR THE MANAGEMENT OF DKA
ASSESS TO CONFIRM DKA

Clinical history Clinical signs Biochemical features
Polyuria, polydipsia Assess degree of dehydration Check bedside blood glucose (BG), blood
Weight loss Smell of ketones ketones (BK) and capillary blood gas.
Nausea, abdominal pain Kussmaul’s breathing • BG >11mmol/L
Tiredness, confusion Lethargy, drowsiness • HCO3 <15mmol/L, pH <7.3
• BK >1.5mmol/L
  
DIAGNOSIS OF DKA CONFIRMED
IV access
Send off blood for BG, VBC, U/E/Cr
Take 1 extra EDTA and 2 plain tubes (for
serum insulin,C-peptide, HbA1c). Send these
with the patient to CICU/HD/ward.

 CATAGORISE TO MANAGE DKA 
Severe DKA Moderate DKA Mild DKA
Shock (tachycardia, reduced pulses) Dehydration 5–8% but not in shock Minimal dehydration
Reduces conscious level/coma Hyperventilating (clinical acidosis), vomiting Tolerates fluids orally
pH <7.1, HCO3: <5mmol/L pH 7.1–7.2, HCO3: 5–10mmol/L pH >7.2, HCO3: 10–15mmol/L
  
Resuscitate Intravenous therapy Subcutaneous insulin therapy
Airway ± NG tube Nil by mouth Start wit a STAT dose of Actrapid
Breathing (100% oxygen) Calculate fluid needs and correct over 48 hours • Use 0.1 units/kg if <5 years
Circ. (0.9% NaCl 10ml/kg); assess and repeat Use 0.9% NaCl as the initial fluid • Use 0.2 units/kg if >5 years
until ciruclation is restored; max 30ml/kg Add KCl 20mmol per 500ml of fluid Continue oral hydration
 
Continuous insulin infusion General ward care
(50 units Actrapid in 50ml N/S) 7-point BG monitoring
• At 0.1 units/kg/hr, or Monitor fluid balance
• Consider 0.05 units/kg/hr if younger than Consult endorcrinology for SC insulin plan
5 years

CICU or HD care
Hourly BG, HR, BP, RR
Hourly precise input and output
At least hourly consious level checks
i-stat and BG 2 hours after start of IV
therapy, then 4 hourly; U/E/Cr 6 hourly
Cardiac monitoring for T-wave changes

 ASSESS THERAPEUTIC EFFICACY 
Acidosis not improving BG <14mmol/L Neurological deterioration
Exclude hypoglycaemia STAT
  
Reevaluate IV fluid adjustments needed Is it cerebral oedema?
IV fluid calculations Add 5% glucose to 0.9% NaCl WARNING SIGNS: Headached, slowing HR,
Insulin delivery systems and dose Switch to 0.45% NaCl + 5% glucose afer 12 irritability,  conscious level, incontinence,
Need for additional resuscitation hours of IV fluids specific signs
Consider sepsis/other causes of acidosis
 
Improvement Management of cerebral oedema
Clinically well Mannitol 0.5g/kg rapid infusion
Tolerates oral fluids Reduce IV fluids to 1/3 of original
HCO3: >15mmol/L Inform senior staff and transfer to CICI
Cranial imaging afer stabilisation

Transition to SC insulin and oral fluids
Consult Endocrinology
 Falling corrected serum Na during DKA therapy may indicate

excessive rehydration
 Rehydrate over 72 hours if corrected sodium >150mmol/L
 After 12 hours, consider switching to 0.45% NaCl if plasma
sodium level is stable or increasing
 Add 5% glucose once glucose level falls below 14mmol/L
 If necessary, use 10% dextrose to maintain glucose between
5–11mmol/L
 Acidosis and bicarbonate therapy:

 Adequate hydration and insulin therapy will reverse even severe
acidosis.
 Bicarbonate therapy is rarely required and may increase risk of
cerebral odema.
 Bicarbonate therapy should only be considered to improve
cardiac contractility in patients who are severely acidotic (arterial
pH<6.9) with circulatory failure despite fluid replacement.
 Bicarbonate should never be given without prior discussion
with a senior doctor.
 Insulin therapy:
 Start insulin therapy 1 hour after initiating fluid therapy.
 Prepare insulin infusion by adding 50 units (0.5ml) of soluble
insulin (Actrapid) to 49.5ml of 0.9% saline in a 50ml syringe pump
to produce an insulin concentration of 1U/ml.
 Commence insulin infusion at 0.1 unit/kg/hr; consider using
0.05unit/kg/hr for children <5 years.
 Consider reducing to 0.05 units/kg/hr if the rate of fall of blood
glucose exceeds 5mmol/L per hour or when the acidosis is
corrected (pH>7.3, HCO3>15mmol/L).
 Mild DKA may be managed with subcutaneous (SC) insulin.
 Transition to SC insulin and oral fluids:

 Children with pH>7.3, HCO3 >15mmol/L and blood ketones
<1mmol/L) can be transitioned to SC insulin.
 A possible regimen includes 2 basal doses of insulin (Insulatard at
pre-breakfast and pre-dinner) and 3 bolus doses of rapid acting
insulin before each main meal.
 30 mins after SC insulin is administered, stop the insulin and
glucose infusion.
Endocrinology 97
Bibliography:
1. ISPAD Clinical Practice Consensus Guidelines 2009 Compendium. Diabetic ketoacidosis in
children and adolescents with diabetes. Pediatric Diabetes 2009; 10(Suppl.):118–133.
2. Diabetes UK Position Statements and Care Recommendations. Joint British Societies Guideline
for the management of diabetic ketoacidosis. Diabetic Medicine 2011; 28:508–515.
NORMAL PUBERTY AND

DISORDERS OF PUBERTY
INTRODUCTION
Puberty is a process of physical transformation of the child into a
sexually functional adult.
 Puberty is a process, meaning a series of related events and not a
single event
 The process is sequential, meaning there is an order to the process
of normal puberty
 There is substantial variation in the onset, tempo and hence
duration of normal puberty
 The outcomes of normal puberty are:
 Normal adult height and reproductive competence
 Two distinct yet overlapping components of puberty are:
 Adrenarche and gonadarche
 Disorders of puberty can therefore be categorised into:
 Disorders of timing — Precocious or delayed onset of puberty
 Disorders of tempo and duration — Ultra-rapid or poor
progress/arrest of puberty
 Disorders of sequence — Also known as pseudo-puberty
Normal female puberty

The physical changes of normal female puberty are primarily the result
of rising levels of ovarian estrogen.
 Breast development is typically the first sign and may begin as early
as 7–8 years old or as late as 13 years old.
 Breast development is followed by height acceleration, body fat
distribution and vaginal discharge.
 Vaginal discharge is initially random, then cyclical and precedes
menstruation.
 Sexual hair development typically occurs 1–1.5 years following onset
of breast development.
 Menarche typically occurs 2–3 years after the onset of breast

development.
 Menarche is the penultimate event of normal puberty.
 The final event of normal female puberty is epiphyseal fusion and
occurs 1–2 years after menarche.
The appearance of pubic and/or axillary hair is mediated by adrenal and
ovarian androgens and dependent on genetic factors, race, ethnicity as
well as body fat mass.
Normal male puberty

The physical changes of normal male puberty are primarily the result
of rising levels of testicular androgens.
 Testicular enlargement (≥4ml) represents the onset of normal male
puberty and may occur as early as 9y or as late as 14y.
 As the testicular volume increases, the scrotal skin becomes
progressively thinner, the penile length and girth increase, the glans
penis becomes obvious and pubic hair growth begins.
 Muscle mass acquisition is followed by height acceleration.
 Voice changes occur late as a result of chronic androgen stimulated
changes to the voice box structure.
Like females, the appearance of pubic/axillary hair is variably influenced

by genetic, race and ethnicity factors.
Hirsutism, hypertrichosis and precocious sexual hair development

Hirsutism is the excessive growth of thick or dark hair in sex-hormone
dependent areas while hypertrichosis is the increase in hair growth
anywhere on the body in males and females.
Precocious sexual hair development occurs when axillary/pubic hair

develops before breast development in females and before a testicular
volume of 4mls in males. Although physiologically normal in some, such
children must be referred for evaluation.
Determining the pubertal stage

Pubertal stage is determined by a combination of visual inspection and
palpation.
Endocrinology 99
Figure 3.2: Pubertal development

Table 3-9: Guidelines for referral to a paediatric endocrinologist
Refer disorders of TIMING:

 Girls with breast development before the age of 7 years.
 Girls with both breast development and pubic/axillary hair development before
the age of 8 years.
 Girls with no evidence of breast development by the age of 13 years.
 Boys with testicular volumes of ≥4ml before the age of 9 years.
 Boys with testicular volumes of ≤4ml by the age of 14 years.
Note: Early normal puberty is not precocious puberty and care should be taken not
to “medicalise” an otherwise normal condition
Refer disorders of SEQUENCE:
 Girls with pubic/axillary hair development and no evidence of breast
development.
 Girls with vaginal discharge or menstruation and no evidence of breast
development.
 Boys with pubic/axillary hair development and testicular volumes of ≤4ml.
Note: Pseudo-precocious puberty may not be physiologically normal and needs to

be evaluated.
Refer disorders of TEMPO:
 Girls with breast development who fail to menstruate by the age of 15 years.
 Girls who start breast development when they are ≤120cm tall.
Note: The typical duration from onset of breast development to menstruation is

2½ years (average range 2–3 years). Rapid progression of puberty (which is
a difficult diagnosis to make) increases the likelihood of early growth plate
fusion; while poor progress of puberty may indicate underlying disease.
Bibliography
1. Bordini B, Rosenfield RL. Normal pubertal development: Part 1: The endocrine basis of
puberty. Pediatrics in Review 2011; 32(6):223–229.
2. Bordini B, Rosenfield RL. Normal pubertal development: Part 2: Clinical aspects of puberty.
Pediatrics in Review 2011; 32(7):281–292.
3. Dorn LD, Biro FM. Puberty and it’s measurement: A decade in review. Journal of Research
on Adolescence 2011; 21(1):180–195.
Endocrinology 101
OBESITY IN CHILDHOOD
AND ADOLESCENCE
INTRODUCTION
Obesity has become a worldwide epidemic. The consequences and costs
of obesity have escalated rapidly in the last few decades. Understanding
obesity and how to manage it is therefore vital for the individual as well
as our society.
Definition
Obesity, defined as excess body fat, occurs when energy intake exceeds
energy expenditure. It is commonly measured using Body Mass Index
(BMI, weight in kilograms divided by height in meters squared, kg/m2)
>95th percentile for age. Children with BMIs from the 85th–95th percentile
are considered “at risk”.
Pathogenesis and Aetiology

The pathogenesis of obesity is multi-factorial, involving a combination of
genetic, environmental and behavioural factors. Predictors include early
childhood obesity, elevated parental BMI, increased fasting blood insulin
(and associated decreased insulin sensitivity) and blood leptin levels.
Very rarely,genetic mutations in leptin, leptin receptor, neuropeptide

Y, pro-opiomelanocortin, prohormone convertase 1, and melanocortin
receptor MC4R and MC3R cause early-onset obesity.
See Table 3-10 for some causes of obesity.
Clinical Evaluation
History
 Previous growth/weights (at what age did the child start to put on
excessive weight?)
 Nutritional assessment
 Physical activity
 Symptoms suggestive of secondary causes of obesity (see Table 3-10)
 Symptoms suggestive of co-morbidities (see Table 3-11)
 Birth and antenatal history, including birth weight, presence of
maternal gestational diabetes
 Drug history (e.g. steroids, herbal supplements, traditional cures)
 Parents’ BMIs
Table 3-10: Causes of childhood obesity
Primary Obesity Central Nervous System Disorders

• Exogenous Obesity • Hypothalamic tumours
• Infection, inflammation, ischaemia
• Previous CNS surgery
Endocrine Disorders Miscellaneous
• Cushing Syndrome • Binge eating disorders, Bulimia
• Hypothyroidism • Drugs (e.g. Risperidone, tricyclic
• Growth Hormone deficiency antidepressants)
• Hyperinsulinaemia
Genetic Syndromes
• Prader-Willi Syndrome (PWS)
• Bardet-Biedl Syndrome
• Down Syndrome
• Pseudohypoparathyroidism
• Klinefelter Syndrome
• Alstrom Syndrome
Table 3-11: Co-morbidities and complications of obesity
Cardiovascular Neurological
• Dyslipidaemia • Pseudotumour cerebri
• Hypertension
• Arteriosclerosis
Endocrine Orthopedic
• Insulin resistance, hyperinsulinism • Blount disease
• Impaired glucose tolerance • Slipped upper femoral epiphysis (SUFE)
• Type 2 Diabetes Mellitus
• PCOS, absent/irregular menses
Respiratory Gastrointestinal
• Obstructive sleep apnea • Gallbladder disease
• Pickwickian syndrome • Steatohepatitis/non-alcoholic fatty liver
• Restrictive lung disease • Gastroesophageal reflux
Psychological
• Depression
• Eating disorders
• Social isolation
Endocrinology 103
v
Family history of obesity ± co-morbidities
v
Social history including assessment of caregivers’ involvement in
daily routine (i.e. meals, physical activity)
 Psychosocial history including issues of self-esteem, depression, risk
for eating disorders
In addition to a full physical examination, specifically look for:
 Height
 Children with exogenous obesity from over-nutrition are usually
tall for age with good growth velocity
 Children with underlying pathology tend to be short for age with
poor growth velocity
 Dysmorphic features
 Cushingoid features (i.e. moon face, acne, hirsutism, truncal obesity,
violaceous striae, hypertension)
 Signs of hypothyroidism
 Acanthosis nigricans, skin tags which suggest hyperinsulinism and
insulin resistance
 Pubertal assessment
 Hypogonadism may suggest a syndromic cause, e.g. Prader-Willi,
Bardet-Biedl, Alstrom
 Assessment of affect, mood & signs suggestive of depression/
bulimia, e.g. dental erosions, digital calluses
 Signs suggestive of co-morbidities
Investigations
Investigations are dictated by features suggestive of an underlying
pathology or presence of complication or co-morbidity. A strong
positive family history may prompt earlier screening for complications.
Management
Treatment of obesity must be viewed as dealing with a chronic
disease. Children with mild obesity ought to be managed in a primary
care setting. Emphasis is placed on targeted gradual weight loss and
then weight maintenance.
 Management of children with exogenous obesity includes:

 Obtaining a full dietary history followed by dietary counseling
 Obtaining a full activity history followed by exercise planning
 Involving the whole family in the change process to provide
psychological support
 Assessment for complications and co-morbidities

 Regular follow up.
Table 3-12: Referral guidelines
Guidelines for Referral to the Weight Management Clinic

Patients older than 6 years (i.e. primary school age and above) who are:
 >160% ideal body weight for height (% IBW)
 >140% ideal body weight for height AND have the following conditions: Obstructive Sleep
Apnea & Hypopnoea Syndrome (OSAHS), Type 2 Diabetes Mellitus, Essential hypertension,
Hypercholesterolaemia
Guidelines for Referral to a Paediatric Endocrinologist
 Obesity with any endocrine pathology, whether as a cause or as a complication
 Obesity with specific clinical associations (e.g. SUFE, PWS, Klinefelter Syndrome etc)
 Obesity with short stature (height <3rd percentile for age)
 Obesity in those younger than 4 years, especially where BMI >4 SDS (BMI SDS can be
calculated online)
Bibliography
1. Marcie B. Schneider and Susan R. Brill. Obesity in Children and Adolescents. Pediatrics in
Review 2005; 26;155
2. Ellen S. Rome. Obesity Prevention and Treatment. Pediatrics in Review 2011;32;363
105
GASTROENTEROLOGY
RECURRENT ABDOMINAL PAIN
INTRODUCTION
Approximately 10–45% of school-aged children experience frequent
abdominal pain severe enough to affect their daily activities. A complete
history and examination are the most important components in
evaluating the cause of the abdominal pain. A detailed pain history, its
effect on the daily activities of the child and family, psychosocial factors,
and examination including growth and pubertal status are of particular
importance. Broadly speaking causes of recurrent abdominal pain are
organic or functional (absence of organic pathology).
ALARM FEATURES SUGGESTIVE OF ORGANIC CAUSE:

 Young age
 Persistent right upper or lower quadrant pain
 Dysphagia
 Persistent vomiting
 Gastrointestinal blood loss
 Nocturnal diarrhea or pain
 Family history of gastrointestinal disease
 Constitutional symptoms: arthritis ,fever, oral ulcers
 Perirectal disease
 Involuntary weight loss
 Deceleration of linear growth
 Delayed puberty
Abdominal pain-related functional gastrointestinal disorders (FGID)
is the term used when there is no organic cause to explain their
symptoms, which occurs in most cases of recurrent abdominal pain.
Abdominal pain-related FGID can be further classified according to the

Rome III criteria as:
 Functional dyspepsia
 Irritable Bowel Syndrome (IBS)
 Abdominal migraine
 Childhood functional abdominal pain
 Childhood functional abdominal pain syndrome
Table 4-1: Organic causes of abdominal pain
Gastrointestinal disorders Non-gastrointestinal disorders

• Acid peptic disease • Recurrent urinary tract infection
• Infection • Pelvi-ureteric junction obstruction
• Inflammatory bowel disease • Nephrolithiasis
• Gallbladder disease • Ovarian or uterine disorders
• Pancreatic disease • Diabetes mellitus
• Hepatitis • Respiratory disorders
• Carbohydrate malabsorption
• Surgical disorders
• Foreign body
• Tumor
• Coeliac disease
• Eosinophilic gastrointestinal disease
Functional Dyspepsia
Dyspepsia refers to pain or discomfort centered in the upper abdomen.
Discomfort may be characterised by fullness, early satiety, bloating,
belching, nausea, retching or vomiting.
Diagnostic Criteria
 Symptoms affecting children age 4–18 years at least once a week for
at least 2 months
 Persistent or recurrent pain or discomfort centered in the upper
abdomen (above the umbilicus); and
 No evidence of an inflammatory, anatomic, metabolic, or neoplastic
process that is likely to explain the symptoms; and
 Symptoms not relieved by defecation or associated with the onset of
a change in stool frequency or stool form
Gastroenterology 107
Assessment
 Obtain a detailed pain history as well as a dietary, psychological and
social history to determine whether symptoms are likely to represent
organic disease
Physical examination and growth parameters should be normal

Upper GI endoscopy useful if symptoms persistent despite acid

suppressants, symptoms recur after stopping acid suppressants, or if
Helicobacter pylori related disease is suspected
Management
 Avoidance of triggers (caffeine, spicy or fatty foods)
 Acid suppressive therapy (proton-pump inhibitors, H2 receptor
blockers, sucralfate, antacids)
 Prokinetic agents (domperidone, erythromycin, metoclopramide) if
indicated
IRRITABLE BOWEL SYNDROME (IBS)

In IBS, an altered bowel habit is associated with abdominal pain which is
usually relieved with defecation.
Diagnostic Criteria
 Symptoms affecting children age 4–18 years at least once a week for
at least 2 months
 Discomfort or pain associated with 2 or more of the following at least
25% of the time
 Relief with defecation
 Onset associated with a change in stool frequency
 Onset associated with a change in stool consistency
process that is likely to explain the symptoms
 The following symptoms cumulatively support diagnosis of IBS:

 Abnormal stool frequency (>3 bowel movements per day or
<3 bowel movements per week)
 Abnormal stool form (lumpy/hard or loose/watery stool)
 Abnormal stool passage (straining, urgency or feeling of
incomplete evacuation)
 Passage of mucus
 Bloating or feeling of abdominal distension
Assessment
 History fulfilling diagnostic criteria with normal examination and
normal growth pattern is consistent with IBS
 Detailed history to ensure absence of red flags which may suggest
organic pathology
 Explore for any triggering events and psychosocial factors
Management
 Patient eduation of IBS and reassurance
 Psychotherapy — Coping with stress and dealing with symptoms
 Symptomatic relief (anti-spasmodics, laxatives)
 Probiotics
 Dietary modifications (high-fibre, low-fat, avoid caffeine)
ABDOMINAL MIGRAINE
Abdominal migraine is characterised by acute, intense, non-colicky,
midline abdominal pain that lasts for hours. It occurs intermittently with
long symptom-free periods.
Diagnostic Criteria
 2 or more episodes in the preceding 12 months affecting children
age 4–18 years
 Must include all features below:
 Paroxysmal episodes of intense, acute periumbilical pain that
lasts for 1 hour or more
 Intervening periods of usual health lasting weeks to months
 The pain interferes with normal activities
 The pain is associated with 2 or more of the following:
 Anorexia
 Nausea
 Vomiting
 Headache
 Photophobia
 Pallor
process that explains the subject’s symptoms
 Supportive criteria includes a history of motion sickness and family
history of migraine
Assessment
Targeted investigations only if relevant for e.g.
 Abdominal ultrasonography: to evaluate for abdominal masses,
cholelithiasis or renal abnormalities
 Upper gastrointestinal study: to rule out malrotation
 Cranial imaging (indicated in those with recurrent headache and
vomiting): to rule out space-occupying lesions and raised ICP
Management
 Avoidance of potential triggers
 Diet containing caffeine, amine and nitrite
 Prolonged fasting
 Altered sleep pattern
 Exposure to flickering/glaring lights
 Prophylactic pharmacotherapy
 Propranolol
 Cyproheptadine
 Sumatriptan
 Pizotifen
CHILDHOOD FUNCTIONAL ABDOMINAL PAIN (FAP)
Diagnostic Criteria
Symptoms affecting children age 4–18 years at least once a week for at
least 2 months.
Must include all of the following:
 Episodic or continuous abdominal pain
 Insufficient criteria for other FGIDs
process that explains the subject’s symptoms
CHILDHOOD FUNCTIONAL ABDOMINAL PAIN SYNDROME
Diagnostic Criteria
Must include childhood FAP at least 25% of the time and 1 or more of
the following at least once per week for at least 2 months:
 Some loss of daily functioning
 Additional somatic symptoms such as headache, limb pain, or
difficulty sleeping
Assessment
 Reasonable baseline screening
 Full blood count
 Inflammatory markers (ESR,CRP)
 Urinalysis
 Where relevant, second-line investigations
 Evaluation for Helicobacter pylori (urea breath test, stool for H.
pylori antigen)
 Renal function tests
 Stool for occult blood
 Ultrasound abdomen/pelvis
Management
 Reassurance and explanation about pain due to visceral
hypersensitivity
 Recording symptoms with pain diary
 Looking at possible psychosocial triggering factors
 Symptomatic relief (e.g. rubbing tummy with oil, analgesia if more
severe pain)
 Cognitive behavior therapy for pain management
Bibliography:
1. Plunkett A, Beattie RM. Recurrent abdominal pain in childhood. J R Soc Med 2005;
98:101–6.
2. McFerron BA, Waseem S. Chronic recurrent abdominal pain. Pediatr Rev 2012; 33:509–17.
3. Rasquin A, Lorenzo C, Forbes D, et al. Childhood Functional Gastrointestinal Disorders:
Child/Adolescent. Gastroenterology. 2006;130:1527–1537.
CONSTIPATION
INTRODUCTION
Constipation is a common pediatric complaint presenting as a delay
or difficulty in passing motion. It accounts for 3% of general pediatric
outpatient consults and 25% of pediatric gastroenterology visits.
The commonest cause beyond the neonatal period is functional
constipation, which is constipation in the absence of any organic
pathology.
Table 4-2: Normal frequency of bowel movements in infants and children
Age Mean number of Mean number of

bowel movements bowel movements
per week per day
0–3 months: breastfed 5–40 2.9
0–3 months: formula-fed 5–28 2.0
6–12 months 5–28 1.8
1–3 years 4–21 1.4
>3 years 3–14 1.0
DIAGNOSTIC CRITERIA OF FUNCTIONAL CONSTIPATION

Functional constipation is defined according to the Rome III criteria as
follows:
Two or more of the following in a child with a developmental age of at
least 4 years at least once a week for 2 months:
 ≤2 defecations in the toilet per week
 At least 1 episode of fecal incontinence per week
 History of retentive posturing or excessive volitional stool retention
 History of painful or hard bowel movements
 Presence of a large fecal mass in the rectum
 History of large diameter stools that may obstruct the toilet
Table 4-3: Differential diagnosis of constipation according to age
Infants Children>1 year

Hirschsprung’s disease Functional constipation (>95%)
Congenital anorectal malformation
Neurologic disorders Organic causes
 Encephalopathy  Hirschsprung’s disease
 Spinal cord abnormalities  Metabolic conditions
 Meningomyelocoele  Hypothyroidism
 Spina bifida  Hypercalcaemia
 Tethered cord  Hypokalaemia
Cystic fibrosis  Diabetes insipidus
Metabolic causes  Diabetes mellitus
 Hypothyroidism  Cystic fibrosis
 Hypercalcaemia  Gluten enteropathy
 Hypokalaemia  Spinal cord trauma or abnormalities
 Diabetes insipidus  Neurofibromatosis
Heavy metal poisoning  Heavy-metal poisoning
Medication side effects  Medication side effects
Cow’s milk protein intolerance
 Developmental delays
 Sexual abuse
Pathophysiology
 Passage of hard and painful stool triggers an unpleasant experience
and the child becomes fearful.
 Suppression of subsequent urge to defecate by contracting anal
sphincter and gluteal muscle.
 Withholding behavior (rising on toes, fidgeting, stiffening back
and legs) in order to avoid defecation may be seen which is often
mistaken for straining.
 Rectal mucosa absorbs water making retained stools hard and more
difficult to evacuate.
 Gradual increase in rectum size resulting in impaction of hard stools,
overflow incontinence, loss of rectal sensation and eventually loss of
urge to defecate.
Evaluation
In most cases, a thorough history and examination is adequate in
establishing whether constipation is functional or related to an organic
cause requiring further investigations.
History:
 Details of bowel history including frequency and consistency of
stools (see Bristol stool chart)
 Age of onset of constipation and potential trigger factors
 Associated symptoms, e.g. pain, bleeding, soiling, weight loss
 Age of onset
 Toilet training/toilet habits
 Withholding behavior
 Dietary history
 Family history
 Previous/current therapy
 Estimate of parent/patient adherence
 Development and school performance
 Psychosocial history
 Psychosocial disruption of child or family
Examination:
 Growth parameters
 Abdomen signs, e.g. distension, fecal masses, organomegaly
 Anal inspection, e.g. position, skin tags, fissures, soiling, perianal
erythema
 Rectal examination: not needed to be done routinely
 Back and spine examination
 Neurological examination
Investigations:
No routine investigations generally required to diagnose constipation.
Targeted investigations if unremitting severe constipation or red flags
identified.
Management
Principles of treatment are education, disimpaction, maintenance and
prevention of re-accumulation, and behavior modification.
Education
 Explanation of pathogenesis of constipation.
 Managing anxiety of parent and child.
 A sympathetic and non-accusatory approach is important.
 Explain time frame of management plan and need for long-term
therapy.
 Encourage parents to be supportive, positive and patient.
BRISTOL STOOL CHART
Separate hard lumps, like nuts

Type 1
(hard to pass)
Type 2 Sausage-shaped but lumpy
Type 3 Like a sausage but cracks on its surface
Type 4 Like a sausage or snake, smooth and soft
Soft blobs with clear-cut edges

Type 5
(passed easily)
Type 6 Fluffy pieces with ragged edges, a mushy stool
Watery, no solid pieces

Type 7
Entirely Liquid
Disimpaction
 Fecal impaction is present if the following features are identified.
 Hard mass palpable in lower abdomen.
 Dilated rectum filled with large amount of stool.
 Excessive stool in colon identified on X-ray.
Oral versus rectal route of disimpaction

 Rectal route faster but INVASIVE.
 Oral route may have issues with non-compliance.
Maintenance
 Prevention of recurrence of fecal impaction.
 Well-balanced diet, adequate fluid intake.
 Use of medications to achieve regular bowel movements.
Behaviour Modification
 Encourage child to sit on toilet for 5–10 mins after meals.
 Advice on proper positioning and foot support.
 Stool diary.
 Rewards system.
Table 4-4: Medications

Oral laxatives
Osmotic laxatives Stimulant laxatives
Lactulose 1–2ml/kg, 1−2 times x daily Bisacodyl 3–10 years: 5mg/day
>10 years: 5–10mg/day
Macrogol 1–1.5g/kg/day for disimpaction Senna 2–6 years: 2.5–5mg once to twice daily
0.4–0.8g/kg/day for maintenance 6–12 years: 7.5–10mg/day
>12 years: 15–20mg /day
Indication to Refer to Specialist Care

 Children in whom aggressive bowel clearance needs to be considered
 Presence of significant behavioral/psychosocial problems impacting
on the management
 Failure to respond to high dose of laxatives
 Persistent soiling despite laxatives
 Structural/physical causes are suspected
 Poor growth/nutritional status
 Presence of anal fissure/rectal prolapse if there is failure to be cured
by a reasonable course of laxatives (~3 months)
Bibliography:
1. Plunkett A, Beattie RM. Recurrent abdominal pain in childhood. J R Soc Med 2005; 98:101–6.
2. Rasquin A, Lorenzo C, Forbes D et. al. Childhood Functional Gastrointestinal Disorders:
Child/Adolescent. Gastroenterology. 2006;130:1527–1537
3. Tabbers M, Dilorenzo C et. al. Evaluation and treatment of functional constipation in
children and infants. Evidence-based recommendations from ESPGHAN and NASPGHAN: J
Pediatr Gastroenterol Nutr 2014;58:258–274
4. Heaton, K W, Lewis, S J . Stool form scale as a useful guide to intestinal transit time.
Scandinavian Journal of Gastroenterology,1997; 32(9): 920–924.
ACUTE GASTROENTERITIS
DEFINITION
Acute gastroenteritis is defined as diarrheal disease of rapid onset, of
<10 days duration, with or without accompanying symptoms and signs
such as nausea, vomiting, fever or abdominal pain. Transmission is
usually via faecal-oral route.
Most patients will have viral or self-limiting bacterial diarrhoea

recovering within 7–10 days. In Singapore, rotavirus is the most
common pathogen causing gastroenteritis in children. Occasionally,
children may have bacteria dysentery or, rarely, protozoal disease which
may need specific antimicrobial therapy (see Table 4-5).
It is important to establish if there were any foreign travel or contact

history. Recent antibiotic ingestion in an unwell child may suggest
Clostridium difficile infection. Immunocompromised children are at risk
of infection with more unusual organism.
Table 4-5: Infective causes of acute gastroenteritis

Viral Bacterial Intestinal Parasites
Rotavirus Salmonella species Giardia lamblia
Calicivirus, e.g. Norovirus Campylobacter jejuni Entamoeba histolytica
Astrovirus Shigella species Cryptosporidium
Yersinia enterocolitica
Escherichia coli
Clostridium difficile
Clinical Presentation
 Watery diarrhoea
 Dysentery (more likely in bacteria infection)
 Vomiting
 Fever
 Abdominal cramps
 Dehydration
 Electrolyte imbalance
 Upper respiratory tract signs may be present
Differential Diagnosis
There are many possible differential diagnoses which include other non-
enteric infections, non-infective pathology of the gut or other systemic
illnesses.
Important differential diagnoses:

 Surgical causes: pyloric stenosis, intussusception, appendicitis,
intestinal obstruction
 Other infections: urinary tract infection, upper respiratory tract
infection, meningitis, etc.
 Food intolerance
 Diabetes mellitus, Inborn errors of metabolism
 Haemolytic uraemic syndrome
 Drugs
Management of Acute Gastroenteritis

A careful history and thorough physical examination is important for
diagnosis (see Figure 4.1).
Child presenting with diarrhoea and/or vomiting

 Patient younger than 3 months
 Adominal distension, guarding or rebound tenderness
 Severe or localised abdominal pain
 Toxic looking child
 Diarrhoea >7 days
 Vomiting with no accompanying diarrhoea
 Bilious vomiting
 Failure to thrive
 Presence of major co-morbidities
Any of the above features present?
Suspected Gastroenteritis: Consider another diagnosis

Assess severity of dehydration (see Treat according to patient-specific
Table 4-6) condition
Figure 4.1: Suggested pathway on the management of acute gastroenterology

 The key issues to address are:

 Evaluation of dehydration
 Rehydration strategies
 Oral refeeding
 Medications
Evaluation of Dehydration
Dehydration can be indicated by various clinical parameters (see Table
4-6).
Table 4-6: Assessment of hydration status

Mild dehydration Moderate dehydration Severe dehydration
(3–5%) (6–9%) (>10%)
General  Alert, thirsty  Thirsty, restless or  Drowsy, floppy,
Condition lethargy/irritable unconscious
Eye  Normal  Sunken  Very sunken and dry
Tears  Present  Absent  Absent
Mouth/  Moist  Dry  Very dry
Tongue
Capillary  Normal  Prolonged >2 secs  Prolonged >2 secs
Refill
Skin Turgor  Instant recoil  Recoil in >2 secs  Recoil in >2 secs
Skin  Normal  Normal  Cold and clammy,
mottled
Fontanelle  Normal  Sunken  Very sunken
Urine  Normal  Reduced amount  Anuria/severe oliguia
Pulse rate  Normal rate  Rapid and weak  Rapid and feeble
and volume
Blood  Normal  Normal/low  Low/unrecordable
Pressure
Respiration  Normal  Deep/maybe rapid  Deep and rapid
Weight loss  3–5%  6–9%  ≥10%
 Prolonged capillary refill time >2 secs, tachycardia, absence of tears

and abnormal respiratory pattern are reliable signs of dehydration
 An active child with normal capillary refill time and moist mucous
membrane is unlikely to have severe dehydration
 If unsure which category of dehydration patient falls under, therapy
for the more severe category should be used.
Rehydration Strategies
Enteral rehydration using oral rehydration therapy (ORT) is the preferred
in children with mild to moderate dehydration. A glucose-electrolyte
solution with sodium concentration of 45–50mmol/L and osmolarity
<250mmol/L is recommended.
Table 4- 7: Composition of available ORS
Per Litre Pedialyte

Sodium (mmol) 45
Potassium (mmol) 20
Chloride (mmol) 35
Citrate (mmol) 30
Dextrose (g) 25
Osmolarity 250
 Practical tips:
 Offer ORS in small aliquots initially to allow the child to get
accustomed to the taste
 Flavours can be added to make the solution more palatable
 ORS can be frozen to make it more palatable to the child.
 ORS can be given via nasogastric route if oral fluids are not
tolerated.
Intravenous (IV) Therapy is indicated if a child has severe dehydration

(10%) or in shock. Intravenous bolus of crystalloid 20ml/kg (normal
saline) should be given. If the patient does not respond to rapid bolus
rehydration, consider the possibility of an underlying disorder such as
septic shock, toxic shock syndrome, myocarditis, cardiomyopathy or
pericarditis. Use of colloids and inotropes should be considered.
In children with moderate dehydration, intravenous fluids are indicated

if the child cannot retain oral liquids due to persistent vomiting. It is also
important to correct for fluid deficit (see Table 4-8).
Table 4-8: Intravenous fluid calculation
Calculating maintenance fluids in patients

<10kg 100ml/kg/day
or 4ml/kg/hr
10–20kg 1000ml +50ml/kg/day for each kg over 10kg
or 40ml/hr + 2ml/kg/hr for each kg over 10kg
>20kg 1500ml + 20ml/kg/day for each kg over 20kg
or 60ml/hr + 1ml/kg/hr for each kg over 20kg
Calculating Fluid Deficit

Body weight x % dehydration = Deficit in Litres
- e.g. 10kg child, 3% dehydration  10 x0.03 = 0.3L = 300ml deficit
Fluid used for rehydration is the same as maintenance fluids. Rehydration should be carried out
evenly over at least 24–48 hours
- e.g. 20kg child, 5% rehydration
Maintenance: 1,500ml/day, Deficit: 1,000ml
Therefore prescribe 2,500ml/day for first 24 hours, 1,500ml/day thereafter
Investigations
There is usually no need for any investigation including routine stool
culture if child is clinically well with normal hydration status.
For patients with moderate or severe dehydration, perform the

following investigations:
 Electrolytes, urea, creatinine, acid/base status
 Stool culture, stool virology particularly rotavirus as indicated
 Septic workup if patient in septic shock
Diet
Allow usual age-appropriate diet/feeds in child with no or mild dehydration.
 For infants and toddlers, may supplement with ORS (Pedialyte) for
rehydration.
 If child is not vomiting, give usual milk formula, breast milk or solid
foods.
 Avoid fatty or fried foods.
 Limit use of simple sugars (especially fruit juices, lucozade,
carbonated drinks).
Figure 4.2: Rehydration strategy
Assessment of Dehydration Status
No Dehydration Mild/moderate Severe

Encourage more fluid Dehydration Dehydration
intake, if possible with ORS Commence fluid challenge Treat as emergency
Give trial of oral fluid with 25ml/kg with ORS over Bolus IV Fluids 20ml/
Oral rehydration Solution 2 hours. kg normal saline.
(ORS) 25ml/kg over 2 hours Consider supplementing If child remains
Allow usual age- with usual oral fluids if shocked repeat bolus
appropriate diet/feeds. child refuses sufficient fluids 20ml/kg and
Continue breast/formula ORS. consider other causes
feeding Monitor response to ORS. of shock.
If child remains
shocked after a second
bolus, consider colloids
and inotropes.
Reassess after 4 hours Consider Nasogastric tube if Reassess: If signs of

oral fluids not tolerated shock resolved, give
intravenous fluids
If child tolerates fluid Failed trials of ORS

challenge and remains well
with no other risk factor,
consider discharge with
appropriate advice given.
Intravenous Therapy for Dehydration

 Give 0.45% sodium Chloride with 5% Dextrose for fluid deficit replacement and
maintenance (see Table 4-8) and include fluids used for resuscitation. If child >30kg, use
DSA (0.9% Saline/5% Dextrose)
 Measure plasma sodium, potassium, urea, creatinine and glucose at the start.
 Consider intravenous potassium supplementation when serum potassium level is normal
or low and child has passed urine.
 During intravenous replacement attempt to introduce ORS early and gradually, if
tolerated stop IV and continue with ORS.
Medications
Most bacterial gastroenteritis do not need antibiotics except for
bacterial dysentery or protozoal disease. Antibiotics may be indicated
for in very young, immunocompromised or septic patients.
Probiotics such as Lactobacillus acidophilus-containing products may

reduce duration of symptoms and reduce risk of Clostridium difficile
colitis
Antimotility agents such as Lomotil (Diphenoxlylate) or Imodium

(loperamide) are potentially harmful and should be avoided.
Bibliography:
1. Sandhu BK Practical guidelines for the management of gastroenteritis in children. J
Pediatr Gastroenterol Nutr. 2001 Oct;33 Suppl 2:S36–9
2. Elliot EJ. Acute Gastroenteritis in children. BMJ 2007;334:35–40
CHRONIC DIARRHOEA
DEFINITION
Diarrhoea refers to the passage of excessively liquid or frequent stools
with increased water content. This would result in stool output of >10g/
kg/day or >200g/24 hours. Chronic diarrhoea refers to diarrhoea that has
persisted for >2 weeks.
PATHOPHYSIOLOGY
 Osmotic diarrhoea occurs secondary to the presence of non-
absorbable solutes in the gastrointestinal tract usually mal-
absorption of carbohydrates. This will generate an osmotic load
causing water to be secreted into the lumen. Diarrhoea usually
settles within 24–48 hours of fasting. Stool osmotic gap is
>100mmol/L
 (Formula: 290 − 2 x [(Na+) + (K+)])
 Secretory diarrhoea occurs when there is excess of secretion over
absorption. It is caused by the activation of intracellular mediators
such as Cyclic Adenosine Monophosphate (cAMP) which stimulate
chloride secretion and inhibit neutral coupled sodium chloride
absorption. Examples include cholera, enterotoxigenic Escherichia
coli (E. coli), Clostridium difficile and rarely vasoactive peptide
secreting tumours. Secretory diarrhoea tends to be watery and

of high volume. Stool sodium content is >70mmol/L. Diarrhoea
continues despite fasting.
 Loss of absorptive surface, e.g. coeliac disease, short gut syndrome
 Inflammation of the GI tract, e.g. bacterial infection, inflammatory
bowel disease or allergic enterocolitis
CAUSES OF CHRONIC DIARRHOEA

 Enteric Infections
 Bacterial infections: Shigella, Campylobacter, Salmonella etc
 Parasitic- Giardia, Cryptosporidium, amoeba
 Viruses — Adenovirus, rotavirus
 Post enteritis Syndrome

 Common cause of persistent diarrhoea in childhood.
 Diagnosis is established on the following grounds:
 History of an acute gastroenteritis
 If possible identification of a specific pathogen.
 History of diarrhoea persisting after 2 weeks
Following gastroenteritis, carbohydrate intolerance may occur for

example lactose intolerance. This may lead to osmotic diarrhoea which
usually responds well to removal of the offending carbohydrate. Stool
reducing substance is likely to be positive.
 Chronic nonspecific diarrhoea (toddler’s diarrhoea)

 Usually associated with passing large amount of loose, often
explosive stools with undigested food particles seen in the stools.
 Growth parameters usually normal and child is well otherwise
 May be associated with high intake of fruit juice or low dietary fat
 Enteropathies:
 Cow’s Milk or Soy Protein Allergy
 Common cause of chronic diarrhea
 Symptoms usually occur before 6 months of age
 Associated manifestations
 Bloody diarrhea
 Anemia
 Protein-losing enteropathy
 Extraintestinal manifestations of atopy
 Inflammatory Bowel Disease

 Immunodeficiency
 Coeliac disease
 Eosinophilic Enteritis
 Intraluminal causes
 Bacteria overgrowth
 Bile salt deficiency or malabsorption
 Liver cirrhosis, cholestais, Terminal Ileum disease
 Pancreatic insufficiency
 Cystic Fibrosis, Schwachman-Diamond syndrome
 Congenital disorders
 Glucose-galactose malabsorption
 Tufting enteropathy
 Congenital Microvillous syndrome
 Deficiency of dissacharridases
 Congenital chloride- losing diarrhoea
 Surgical causes
 Short gut syndrome
 Intestinal blind loop- bacterial overgrowth
 Hyperthyroidism
 Acrodermatitis enteropathica
 Intestinal lymphangiectasia
 Abetalipoproteinaemia
 Vasoactive Intestinal Peptide producing tumour
 Lymphoma
 Vasculitis
 SLE
 Henoch Schonlein Purpura
 Drug-induced
 Antibiotics, laxatives, etc.
CLINICAL EVALUATION
A thorough history and complete physical examination are essential in
the evaluation of chronic diarrhoea
Careful History
 Characteristics of stools
 Watery- osmotic or secretory diarrhoea
 Greasy- pancreatic insufficiency, cystic fibrosis
 Blood, mucus- inflammatory bowel disease, allergic colitis,
infectious
 Nocturnal- likely organic disease
 Stool frequency
 Age of onset- if neonatal period to assess for congenital cause of
chronic diarrhoea
 Presence of associated symptoms
 Abdominal Pain, urgency, weight loss, vomiting
 Dietary history
 Past history of bowel surgery
 Family history of bowel disease
 Recurrent Infections
 Systemic illness
 Hyperthyroidism, vasculitis etc
Detailed Physical Examination

This would include anthropometric measurement taking into context
family growth data. Puberty should be assessed in older children.
A complete physical examination is essential including nutritional
assessment checking subcutaneous fat mass and muscle bulk. Perianal
examination should be performed to exclude perianal excoriation, rectal
prolapse or perianal signs of Crohn’s disease.
Investigations
 Stool:
 pH and reducing substances
 Microscopy for fat globules
 Stool culture for bacteria and parasites
 Blood tests:
 FBC and ESR
 Serum U/E/Cr and glucose
 Serum albumin and total protein
Endoscopy
Gastroscopy with duodenal mucosa biopsies is indicated if an
enteropathy is suspected, e.g. celiac disease, cow’s milk enteropathy.
Gastroscopy and colonoscopy with small bowel imaging are indicated if
inflammatory bowel disease is suspected
Other Investigations to detect specific disease:

 Immune status to assess for immunedeficiency
 Stool electrolytes and osmolarity
 Evaluate for secretory tumour with urine Vanillylmandelic Acid (VMA)
and serum Vasoactive Intestinal Polypeptide (VIP)
 Stool alpha-1-antitrypsin clearance to estimate stool protein loss
 Hydrogen breath test or duodenal fluid to check for bacteria
overgrowth
 Anti-tissue transglutaminase and antiendomysial antibodies to
screen for coeliac disease
 Sweat test for cystic fibrosis
 Serum zinc level
Bibliography
1. Thomas PD Guidelines for the investigation of chronic diarrhoea. 2nd ed. Gut 2003:52
(suppl V): v1–15
2. Binder HJ Causes of chronic diarrhea N Engl J Med. 2006;355(3):236.
MILK FORMULA GUIDE
COW’S MILK PROTEIN-BASED INFANT FORMULA

There are two main types of infant milk formula: whey-dominant
formula (60% whey, 40% casein) and casein-dominant formula (20%
whey, 80% casein). Whey-based milk empties more quickly from the
stomach while casein-based milk forms curds which are more slowly
digested. Although casein-based milk formulas are promoted for
feeding in ‘hungrier’ babies, there is no clear evidence to support this.
Follow-on milk formula can only be used after 6 months old and is
marketed to have higher iron content than infant first milk.
Table 4-9: Summary table of specialised milk formulas
Categories of Milk Formulas Some Examples

Elemental formula Neocate, Comidagen, Neocate Advanced,
Comidagen Plus, Elemental 028 Extra,
L-Emental
Extensively hydrolysed formula Alfare, Pregestimil, Nutramigen, Similac
Alimentum
Partially hydrolysed formula NanHA, Enfalac HA, Mamil Gold HA, Similac
Total Comfort
High calorie formula Similac Special Care®, Neosure, Pediasure,
Progress Gold, Promise, Nutren Junior, Nutren
Optimum, Ensure, Enercal Plus
Nutritionally complete formula Pediasure, Resource Just for Kids, Sustagen
Junior, Ensure, Isocal, Resource Standard,
Resource Plus, Nutren Optimum, Enercal Plus,
Ensure Plus
MCT enriched formula Monogen, Portagen
Anti-regurgitation formula Enfalac AR, Frisocomfort, Similac RS
Branched chain amino acid enriched Generaid Plus, Hepatic-Aid II
formula
Fibre-enriched formula Nutricomp Fibre, Jevity
Protein-restricted formula Suplena, Nepro, Nutricomp Renal
Specific amino acid restricted formula Camino pro® Better Milk TM with Glytactin,
Camino PRO® Amino acid, MSUD diet powder
Carbohydrate restricted formula Glucerna, Glucerna SR, Nutren Diabetes,
Nutrocomp Diabetes, Resources Diabetes
Carbohydrate minimal formula 3232A protein hydrosylate formula base, RCF
Immune modulating formula Impact, Immune-Aid, Immunex Plus
Adapted from Choosing the Right Milk Formula for Your Paediatric Patient.3
SOY FORMULA
Soy protein-based formula is indicated in infants with galactosaemia,
congenital lactase deficiency (rare) and in situations in which a vegetarian
diet is preferred. It may also be given to previously well infants with
transient secondary lactose intolerance following acute gastroenteritis.

Soy formula is not indicated in infants with cow’s milk protein allergy as
10–14% of these infants will also be allergic to soy protein.
SPECIALISED MILK FORMULA

Hydrolysed and Elemental Formulas: Indicated for patients with cow’s
milk protein allergy or severe intestinal malabsorption.
High-calorie formula: Energy-dense formulas designed for preterm
neonates and fussy-eating children to optimise caloric intake
Nutritionally-complete formula: For patients who depend primarily on
milk for their complete nutritional requirements.
MCT-enriched formula: For use in patients with impaired fat absorption.
Anti-regurgitation formula: May help to alleviate symptoms of gastro-
oesophageal reflux.
Disease-specific milk formula: Modulen IBD is used in inflammatory

bowel disease for its anti-inflammatory and mucosal-healing properties.
Bibliography
1. Puntis JWL, Beattie M, Dhawan A. Formula and complementary feeding. Oxford Specialist
Handbook of Paediatric Gastroenterology, Hepatology and Nutrition. Chapter 3, p31–35.
2. Bhatia J, Greer F. Use of Soy Protein-Based Formulas in Infant Feeding. Pediatrics
2008;121;1062–1068.
3. HP Chu. Choosing the Right Milk Formula for Your Paediatric Patient. Ann Acad Med
Singapore. 2013;42(6):311–2
FAILURE TO THRIVE
Failure to thrive in childhood is a state of under nutrition due to
inadequate caloric intake, inadequate caloric absorption/retention,
or excessive caloric expenditure. In the developed world, it is seen
in 5–10% of children. A careful history and physical examination can
identify most causes of FTT, thereby avoiding protracted or costly
evaluations.
DEFINITION:
A child is said to have FTT in the presence of one of the following:
Weight for age that falls below the 5th percentile on multiple occasions
Weight deceleration that crosses two major percentile lines on a growth
chart.
Use of any single indicator has a low positive predictive value, hence the
below anthropometric criteria are also helpful to diagnose FTT
Length <5th percentile
Weight <75% of median weight for length
Weight velocity <5th percentile
BMI <5th percentile
NOTE: Criteria should be met on multiple occasions
CAUSES:
Most cases of FTT involve inadequate caloric intake caused by behavioural
or psychosocial issues. Routine laboratory testing identifies a cause of FTT
in <1% of children and is not generally recommended. Child neglect or
abuse must be considered in all age groups, because children with FTT are
four times more likely to be abused than children without FTT.
 A practical way to categorise FTT is according to calories (see Table

4-10),
 Inadequate caloric intake,
 Inadequate caloric absorption/retention,
 Excessive caloric expenditure.
 Unclassified (unrelated to calories)
DIAGNOSTIC EVALUATION:
History
The most important part of the outpatient evaluation of FTT is obtaining
an accurate account of:
 Age of onset and growth pattern
 Child’s caloric intake
 Eating habits
 Parent-child interactions
 Review of systems to elicit symptoms of organic causes
In exclusively breast fed infants, help of lactation specialist nurse should

be sought to ensure proper technique, latch-on, and swallow. In rare
cases when intake is uncertain asking breastfeeding mothers to pump
and measurement of consumed breast milk can be helpful. Alternatively,
obtaining the weight of an undressed breastfed infant before and after
feeding may be considered.
For formula-fed infants, apart from the volume of feeds consumed, the
correct feed preparation technique should also be checked.
Table 4-10: Differential diagnosis of FTT
INADEQUATE INADEQUATE EXCESSIVE CALORIC UNCLASSIFIED

CALORIC INTAKE CALORIC EXPENDITURE
ABSORPTION/
RETENTION
Infant or toddler
Feeding difficulties Food allergy Thyroid disease SGA
Improper food/formula GER Chronic infections Neglect/abuse

preparation
Caregiver depression Pyloric stenosis Immunodeficiency Skeletal dysplasia
Behavioural/neurological Malabsorption, e.g. Coeliac, CF Chronic pulmonary disease Hypopituituarism

issues
Poverty/lack of food Inborn error of metabolism Congenital heart disease Genetic- Russell-Silver,
availability/cleft lip or Turner synd
palate/airway issues
Chronic liver disease
Malignancy
Child or adolescent
Mood disorder Food allergy Thyroid disease Constitutional
Eating disorder Inflammatory bowel disease Chronic infection or Delayed puberty

immunodeficiency
Drug abuse Malabsorption, e.g. Coeliac, CF Chronic pulmonary disease
Inborn error of metabolism Heart disease or failure
Malignancy
Renal failure, renal tubular

acidosis
Note: In certain conditions there may be an overlap between the categories.

CF and coeliac disease is extremely rare in Chinese race.
Observing a toddler’s eating habits can be helpful in evaluating for picky

eating or food refusal. Asking older children and adolescents, together
with their parents, to maintain a food journal for 3 days can give the
physician a way to measure caloric intake. Particular attention should
also be given to chart “loss of calories” via regurgitation and vomiting.
Taking a psychosocial history is essential for detecting parental or

patient depression, or identifying concerns about the caregiver’s
intellectual abilities or social circumstances.
Some children who falter in growth parameters actually demonstrate a normal
variant of growth, such as children of small parents who are growing to their
full genetic potential, large-for-gestational-age infants who regress toward the
mean, children with constitutional delay in growth, or premature infants whose
growth parameters are normal when corrected for gestational age.
A review of systems that elicits recurrent infections, respiratory symptoms,

developmental delay, vomiting or diarrhoea may point to an organic cause.
In a study, children without obvious organic symptoms elicited on

history, 92% were ultimately diagnosed with a behavioural cause of FTT.
The first consideration in examining a child with FTT is ensuring accurate
measurements. Height (or length), weight, and head circumference
should be plotted on an appropriate growth chart over time.
Although most children with FTT will have a normal examination,

physicians should be alert for signs of physical abuse or neglect.
Physicians should also seek red flag signs or symptoms of medical
conditions that might be causing FTT.
Further Evaluation
Routine laboratory testing rarely identifies a cause of FTT and is not
generally recommended. However, history or physical examination
findings sometimes suggest the need for further testing.
Table 4-11: Red flag signs and symptoms suggesting medical causes of failure to thrive
 Cardiac findings suggesting congenital heart disease (e.g.clubbing, cyanosis, murmur)
 Developmental delay
 Dysmorphic features
 Recurrent or severe respiratory, mucocutaneous, or urinary infection
 Failure to gain weight despite adequate caloric intake
 Organomegaly or lymphadenopathy
 Recurrent vomiting, diarrhoea, or dehydration
Baseline tests — Consider full blood count, renal functions, LFT, thyroid
function, C-reactive protein, erythrocyte sedimentation rate, urinalysis,
urine culture.
If indicated by history, physical examination, or initial laboratory testing,

considers the following:
 Respiratory — CXR, sweat test
 Cardiovascular — Echocardiography
 GIT — Stool for culture, ova, parasites, analysis for fat globules,
elastase and reducing substances. Coeliac screen
 Endocrine — Bone age, Synacthen test and Growth hormone testing
(under specialist supervision)
 Infection & immunology — Tests for HIV, TORCHES, TB, complements,
immunoglobulins & allergy
 Genetic and chromosomal — Turner, etc.
In rare cases, hospitalisation for observed feeding and further

investigation may be helpful. Hospitalisation should be considered if
the child does not improve with outpatient management, suspicion
of abuse or neglect exists, signs of traumatic injury are present, severe
psychosocial impairment of the caregiver is evident, or there are signs of
serious malnutrition.
Treatment:
If a disease or medical condition is identified on history, physical
examination, or additional testing, the correct approach will vary
depending on the condition.
If a diagnosis of FTT is made and no medical conditions are suggested

on examination, appropriate guidance for catch-up growth should be
made and age-appropriate nutritional counselling should be provided
to parents.
 For breastfed infants, recommend feeding more often, ensuring
lactation support, or discussing formula supplementation until
catch-up growth is achieved may be helpful.
 For formula-fed infants, instruction on how to make energy-dense
formula by concentrating the ratio of formula to water may be
helpful.
 Toddlers should avoid excessive juice or milk consumption as this

interferes with nutrition.
 Nutritional supplements may be given until catch-up growth is
achieved.
 Parents may also be instructed to provide calorie-dense foods by
adding rice cereal to foods for toddlers, cream sauces, or butter to
foods for older children or adolescents.
Close follow-up should be performed in the physician’s office,

including evaluation of height (or length) and weight. Multidisciplinary
interventions, including home medical social worker visits, dietetic
advice and psychology inputs should be considered to optimise weight
gain, parent-child relationships, and cognitive development. Finally,
although medications such as cyproheptadine have been shown to help
promote weight gain in children with cancer-related cachexia, they have
not been studied in other causes of FTT.
Prognosis and Outcomes:

There is consensus that severe, prolonged malnutrition, which is
common in developing countries, can negatively affect a child’s future
growth and cognitive development. Low-birth-weight infants who
develop FTT have also demonstrated long-term developmental effects.
However, it is unclear from current studies if normal-birth-weight
infants who develop FTT and then recover have similar long-term
consequences. A systematic review showed that FTT during the first
2 years of life was not associated with a significant reduction in IQ,
although some long-term reductions in weight and height were present.
Bibliography
1. Levy Y, Levy A, Zangen T, et al. Diagnostic clues for identification of nonorganic vs organic
causes of food refusal and poor feeding. J Pediatr Gastroenterol Nutr. 2009;48(3):355–362.
2. Cole SZ, Lanham JS. Failure to Thrive: An Update. Am Fam Physician. 2011;83(7):829–834.
3. Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE. Nelson Textbook of
Pediatrics, 19th ed. Chapter 38,147–149.e1
4. Panetta F, Magazzù D, Sferlazzas C, Lombardo M, Magazzù G, Lucanto MC. Diagnosis on a
positive fashion of nonorganic failure to thrive. Acta Paediatr. 2008;97(9):1281–1284.
5. Black MM, Dubowitz H, Krishnakumar A, Starr RH Jr. Early intervention and recovery
among children with failure to thrive: follow-up at age 8. Pediatrics. 2007;120(1):59–69.
PROLONGED JAUNDICE
Prolonged jaundice is defined by hyperbilirubinaemia that persists
beyond 14 days of life in a term infant, or beyond 21 days of life in a
preterm infant.
The following should be performed:

 Inspect stools — Look for pale chalky stools and/or dark urine that
stains the nappy
 Investigations — Direct bilirubin (or LFT), thyroid function test (TFT),
full blood count, urine culture
 Check blood group and previous routine metabolic screen
If the patient has pale stools and/or conjugated hyperbilirubinaemia

(conjugated fraction >15% or direct bilirubin >20μmol/L), the patient
needs to be referred to the Gastroenterology service as soon as possible.
Prolonged unconjugated hyperbilirubinaemia

The most common cause of prolonged unconjugated jaundice is
breast milk jaundice. It peaks around the second week and may persist
for up to 3 months. Current guidelines advocate the continuation of
breastfeeding. Although cessation of breastfeeding for 1–2 days may be
useful in confirming the diagnosis, nursing should be resumed as soon
as possible.
Pathological causes of unconjugated hyperbilirubinaemia include

hypothyroidism, haemolytic disease (e.g. G6PD deficiency, hereditary
spherocytosis) and inherited syndromes such as Crigler-Najjaar
syndrome and Gilbert Syndrome.
Conjugated hyperbilirubinaemia
Conjugated hyperbilirubinaemia is always pathological. It is defined
by conjugated bilirubin fraction >15% or direct bilirubin >20μmol/L.
All infants who present with prolonged jaundice must have their direct
bilirubin levels checked and stools inspected.
Important causes of conjugated hyperbilirubinaemia to consider:

 Structural: Biliary atresia, Choledochal cyst
 Infections: Intra-uterine infections (TORCH), Urinary tract infection,
Neonatal sepsis
Figure 4.3: Suggested approach to prolonged neonatal jaundice
Prolonged neonatal jaundice (>14 days in term

infant, >21 days in preterm infant)
Stool inspection
Direct bilirubin measurement
FBC, TFT, Urine culture
Unconjugated Conjugated
hyperbilirubinaemia hyperbilirubinaemia
Normal FBC, TFT, Abnormal FBC, TFT

Urine culture or urine culture First-line investigations: LFT,
PTPTT, Blood sugar, FBC, Urea/
electrolytes, TORCH, Urine
reducing substance
Breast milk Investigate and Early referral to gastroenterologist

Jaundice manage accordingly  Ultrasound hepatobiliary system
 Hepatobiliary scintigraphy
(HIDA scan)
 Further metabolic, genetic and
infective work-up if indicated
 Liver biopsy if indicated
 Metabolic: Inborn errors of metabolism (e.g. Galactosaemia, Urea

cycle defects, Tyrosinaemia), Neonatal haemochromatosis, Alpha-1
antitrypsin deficiency
 Endocrinopathy: Hypothyroidism, Hypopituitarism
 Toxic: Drugs, Parenteral nutrition
 Haematologic: Haemophagocytic lymphohistiocytosis (HLH)
Table 4-12: Investigations to determine cause of prolonged jaundice
First-line investigations Specific conditions

LFT Conjugated hyperbilirubinaemia (raised direct
bilirubin)
Elevated liver enzymes
PT/PTT Coagulopathy from liver impairment or Vitamin K
deficiency
Blood sugar Hypoglycaemia
FBC +/- CRP +/- Blood cultures Infection/sepsis
TFT Hypothyroidism
Urea/electrolytes/creatinine Dehydration, renal impairment
TORCH serology Intra-uterine infections
Urine culture UTI
Urine reducing substance + Check Galactosaemia, IEM
previous IEM screen
Specific investigations
Ultrasound of Hepatobiliary System Biliary atresia
Choledochal cyst
Hepatobiliary Scintigraphy (HIDA scan) Evaluate biliary excretion (Presence of biliary
excretion rules out BA)
Intraoperative cholangiography Confirms diagnosis of Biliary atresia
Percutaneous Liver Biopsy Distinguishes between neonatal hepatitis and
extrahepatic biliary obstruction
Other tests to consider
Metabolic screen: serum ammonia, Inborn errors of metabolism
lactate, amino acids, Gal-1-PUT, ferritin,
urine organic acids
Hepatitis B and C serologies, Viral hepatitis
Enterovirus, Parvovirus, HHV-6
Serum alpha-1 antitrypsin and Alpha-1 antitrypsin deficiency
phenotype
Serum triglyceride, fibrinogen, ferritin Neonatal HLH
 Familial: Alagille syndrome, Progressive familial intrahepatic

cholestatic (PFIC) syndromes
 Idiopathic neonatal hepatitis
If conjugated hyperbilirubinaemia is confirmed, the infant should be

referred to the Gastroenterology service for further evaluation. It is
important to rule out biliary atresia (BA) as early surgical intervention
(before 60 days of life) is associated with better outcome.
Biliary Atresia
Biliary atresia is a rare condition characterised by progressive fibrosis
and obliteration of the extra- and intra-hepatic biliary system. The
pathogenesis is unknown. Anatomically, biliary atresia can be classified
into the following types:
 Type 1: Atresia of the common bile duct
 Type 2: Atresia of the common hepatic duct, common bile duct and
gall bladder
 Type 3 (commonest): Atresia of right, left and common hepatic ducts,
with dysplastic gall bladder
The child with biliary atresia presents with prolonged jaundice,

acholic stools and dark urine. Hepatomegaly is usually present, while
splenomegaly is a late sign. Occasionally, infants may present with
bleeding due to vitamin K deficiency. LFT will show conjugated
hyperbilirubinaemia, associated with raised gamma glutamyl transferase
(GGT) and alkaline phosphatase (ALP). Hepato-biliary ultrasonography
may demonstrate enlarged liver and absent or irregularly-shaped gall
bladder. Hepato-biliary (HIDA) scan following phenobarbitone priming
for 3–5 days shows good hepatic uptake but absent excretion into the
intestine.
The diagnosis is confirmed at surgery with or without cholangiography

when the atretic biliary tree is evident. Kasai portoenterostomy is the
surgical procedure that aims to re-establish bile drainage into the
intestines. Early surgery within 60 days of life is associated with a better
outcome in terms of jaundice clearance and native liver survival. Medical
management after surgery is focused on prevention and treatment of
ascending cholangitis, optimising nutrition and provision of fat-soluble
vitamin supplementation. Ursodeoxycholic acid may be effective in
encouraging bile drainage. The role of corticosteroids in biliary atresia
remains controversial as current evidence has been inconclusive.
Biliary atresia patients will require long-term follow-up to monitor for

complications of liver cirrhosis and portal hypertension.
Bibliography
1. NICE (National Institute for Health and Care Excellence) Clinical Guidance 98. Neonatal
Jaundice. May 2010.
2. Lauer BJ, Spector ND. Hyperbilirubinemia in the Newborn. Pediatrics in Review
2011;32:341–349.
3. Venigalla S, Gourley GR. Neonatal Cholestasis. Semin Perinatol 2004;28:348–355.
4. Kelly DA, Davenport M. Current management of biliary atresia. Arch Dis Child
2007;92:1132–1135.
GASTROINTESTINAL HAEMORRHAGE
Gastrointestinal (GI) bleeding in paediatrics is a common problem that
occurs due to various causes at different ages. The initial approach to
all patients with significant GI bleeding is to ensure patient stability,
to establish adequate oxygen delivery, to place intravenous access, to
initiate fluid and blood resuscitation, and to correct any underlying
coagulopathies. However, in most cases bleeding is limited in volume,
allowing time for diagnosis and treatment.
GI bleeds are classified into:

 Upper GI bleeding — Blood loss proximal to the ligament of Treitz
in the distal duodenum.
 Lower GI bleeding is defined bleeding distal to the ligament of
Treitz.
AETIOLOGY
A. COMMON CAUSES OF GI BLEEDING IN NEONATES:
Upper GI tract bleeding:

 Maternal blood ingestion — Apt tests differentiates between maternal
& fetal haemoglobin.
 Stress gastritis is seen mainly in neonates in NICU, drugs like steroids
and NSAIDS’s used in their care is often the offending agent. They are
rarely of large volume.
Table 4-13: Common causes of gastrointestinal bleeding based on age and location
Age Group Upper Gastrointestinal Lower Gastrointestinal

Bleeding Bleeding
Neonates Swallowed maternal blood Swallowed maternal blood
Gastroesophageal reflux Anal fissures
Stress Gastritis Necrotising enterocolitis
Medication induced Haemorrhagic disease of the newborn
Malrotation with volvulus
Hirschsprung’s disease
1 month to Esophagitis- Due to GERD Anal fissures
2 years Gastritis and Gastroduodenal ulcer Allergic colitis (cow’s milk)
NSAID-induced ulcer Bacterial enteritis
Foreign body ingestion Mallory Weiss Intussusception
tears Meckel’s diverticulum
Esophageal varices Polyps
Gastritis and Gastroduodenal ulcer Ischaemic bowel
Dieulafoy’s lesions (gastric vascular
anomaly)
2 years and older Mallory Weiss tears Anal Fissures

Esophageal varices Bacterial enteritis
Gastritis and Gastroduodenal ulcer Inflammatory bowel disease
Dieulafoy’s lesions (gastric vascular Juvenile Polyps and Vascular lesions
anomaly) Henoch Schlonlein Purpura (HSP)
(Adapted from Arensman and Abramson 2006)
Lower GI tract bleeding:

 Anorectal Fissures — Produce bright red blood that streaks the stool
and is caused by a tear at the mucocutaneous lining. It is often
associated with constipation and is one of the commonest causes of
rectal bleeding in all age groups.
 Necrotising enterocolitis (NEC) usually develops within 10–16 days
after birth most commonly in premature infants, though can present
in 13% of term infants. Early symptoms can be non-specific before
frank bloody stools appear. Diagnosis is confirmed by the classic
finding of pneumatosis intestinalis on abdominal X-ray.
 Haemorrhagic disease of the newborn is caused by a deficiency in
vitamin K. If there is no improvement within 2 hours of IV vitamin K,
work up for coagulopathy and liver disease should be considered. It
is also an important cause of upper GI bleeding.
B. COMMON CAUSES OF GI BLEEDING IN CHILDREN (1

MONTH TO 2 YEARS):

 Esophagitis is secondary to gastroesophageal reflux and is more
common in infants with neurodisability.
 Gastritis causes small and rarely large bleeds, it is usually related
systemic infections or non steroidal anti-inflammatory drug use.

 Milk protein allergy causes allergic colitis by an adverse immune
reaction to cow’s milk and has additional symptoms including
diarrhoea, weight loss, vomiting and irritability.
 Bacterial enteritis is suspected when lower GI bleeding occurs in
association with profuse diarrhoea. Recent antibiotic use raises
suspicion for antibiotic associated colitis and Clostridium difficile
colitis.
 Intussusception is most common in infants ranging from 6–18
months of age. Symptoms include cramping, abdominal pain,
vomiting, a palpable sausage shaped mass, and diarrhoea followed
by red currant jelly stools.
 Meckel diverticulum occurs in 2% of the population, it presents as
sudden onset of painless bleeding PR consisting of large volumes of
altered blood. The bleeding is due to ileal ulceration caused by acid
secretion from the ectopic gastric mucosa.
C. COMMON CAUSES OF GI BLEEDING IN CHILDREN

(2 YEARS AND ABOVE):

 Mallory Weiss tears presents as small streaks of coffee ground contents
in the vomitus. It is due to tears in the gasto-oesophageal mucosa
secondary to retching or violent vomiting episode. Majority are self-
limiting.
 Gastroduodenal ulcers due to Helicobacter pylori can present as
haematemesis with altered blood or coffee ground appearance. It
should be suspected if there is another affected family member.
 Esophageal and gastric varices are caused by portal hypertension which
occurs when there is increased resistance to blood flow through the portal
system. The most common causes of portal hypertension in children are
portal vein thrombosis and chronic liver disease due to bilary atresia.

 Inflammatory bowel disease refers to ulcerative colitis and Crohn’s
disease, which are chronic diseases that result in inflammation of
the intestines. It is the commonest cause of persistent bleeding per
rectum in this age group. Majority of them have systemic symptoms,
raised inflammatory markers and anemia. Refractory anal fissures
especially when associated with skin tags should alert the physician
about the possibility of IBD.
 Polyps are mainly located in the rectum but can also be seen
throughout the colon. These are benign hamartomas and sometimes
autoamputate. Children present with painless bleeding per rectum,
which often streaks normal stools with fresh blood.
Questions to Ask
 First make sure it is indeed blood!
Elicit a history of foods consumed or drugs used that may give
a stool bloody appearance. This list includes certain antibiotics,
iron supplements, red liquorice, coloured vegetables, chocolate,
flavoured gelatine etc. If in doubt test for occult blood can be done,
however be aware or false positives.
 Ask about acuteness or chronicity of bleeding, colour and quantity of
the blood in stools or emesis.
Melena, rather than bright red blood per rectum, is usually a sign of
bleeding that comes from a source proximal to the ligament of Treitz.
Blood mixed in stool or dark red blood implies a proximal source
with some degree of digestion of the blood. However, massive upper
GI bleeding can produce bright red blood per rectum if GI transit
time is rapid.
 Antecedent symptoms like consistency of stool, history of straining,
abdominal pain, generalised lethargy, allergies and trauma.
 A history of vomiting, diarrhoea, fever, ill contacts, or travel suggests
an infectious aetiology.
 Recurrent or forceful vomiting is associated with Mallory-Weiss tears.
 Familial history of Helicobacter pylori or NSAID/medication use may
suggest peptic ulcer disease.
 Ask questions that may reveal underlying, but as yet undiagnosed,
organ dysfunction. E.g. recent jaundice, easy bruising, and changes
in stool colour may signal liver disease.
Physical Exam
 Look for signs of shock such as pallor, heart rate, blood pressure,
capillary refill and alertness.
 In the head and neck, look for causes such as epistaxis, nasal polyps,
and oropharyngeal erosions.
 Examine abdominal for surgical scars and elicit the reason for the surgery.
 Abdominal tenderness, with or without a mass, raises the suspicion
of intussusception or ischaemia.
 Hepatomegaly, splenomegaly, jaundice, or caput medusa suggests
liver disease and portal hypertension.
 Inspection of the perianal area may reveal fissures, fistulas, skin breakdown,
or evidence of trauma. Gentle digital rectal examination may reveal polyps.
 Looking for evidence of child abuse, such as perianal tearing, tags, or
irregularities in anal tone and contour, is also important.
 Examination of the skin may reveal evidence of systemic disorders,
such as Henoch-Schönlein purpura, and Peutz-Jeghers polyposis.
MANAGEMENT OF LARGE UPPER GI BLEED

Initial assessment
Primary goal is to determine whether the patient requires urgent
intervention (eg, endoscopic, surgical, transfusion) or can undergo delayed
endoscopy or even be discharged to outpatient management. Majority
of UGIB will stop spontaneously, however, if fresh or active bleeding is
confirmed, OGD is used to determine the source of upper GI bleeding.
In general, trace or small amounts of blood that is a first-time occurrence

are not of emergent concern. Children rarely require an extensive
laboratory workup or invasive procedures, and parents can be advised
to observe the child at home to see if these situations arise again.
Although numerous factors from the patient history, physical
examination, and initial tests have been examined for an association with
a need for intervention, no single factor is sufficiently predictive of UGIB
severity to be used for triage. The most predictive individual factors are:
 Presentation with haematemesis, with signs of hypovolaemia and a

haemoglobin <8g/dL.
 Co-morbidities, e.g. liver disease, cardiac disease, immunodeficiency,
malignancy
 History of aspirin or NSAID use.
Patients who have significant co-morbidities may require admission

regardless of the severity of the UGIB.
Quick History
 Diet and medication use
 Co-morbidities- especially liver disease.
 Symptoms of acute infection
 History of Helicobacter pylori infection in the family
 Assessment of amount of blood loss.
Management
 Check ABC, Vital parameters- perfusion, HR, BP, Saturations
 Examine for signs of surgical abdomen and portal hypertension.
 IV access (x2 large bore if significantly unwell)
 FBC- (beware initial Hb may be spuriously normal or elevated due to
haemoconcentration)
 UE- (raised urea indicates significant bleed)
 Clotting profile
 GXM (in case of significant bleed)
 Stool for Helicobacter pylori antigen test.
Resuscitation (if needed)

Initially, crystalloid fluids should be infused to maintain adequate blood
pressure.
Blood products, such as packed red blood cells may be needed. Patients
with evidence of severe hypovolaemia, shock, or evidence of ongoing
blood loss should be admitted to an intensive care setting. Close
monitoring of clinical as well as laboratory parameters are needed till
the child is stable.
Nasogastric tube
The placement of a nasogastric tube should be considered in select
patients who have suspected active UGIB. It should be noted that the
absence of blood in a gastric aspirate does not exclude the presence
of active UGIB, because approximately 15% of patients with active
bleeding can have a negative result for nasogastric lavage. Because
of these limitations, and the potential patient discomfort, use of a
nasogastric tube remains controversial.
Variceal bleeds
Gastrointestinal consultants should be involved in the management
as patient may require endoscopy to control active haemorrhage with
sclerotherapy or elastic band ligature or (in rare cases) a transjugular
intrahepatic portosystemic shunt (TIPS).
 Resuscitate with fluids or blood products if hypovolaemic. The

patient should not be over transfused. The target level of
haemoglobin should be 10g/L in order to avoid rebound rise in the
portal pressures.
 Correct coagulopathy with IV vitamin K, FFP and platelet transfusion
(if platelets <60)
 Placement of a large bore naso-gastric tube should be
considered. This will help identify ongoing bleed and decompress
the stomach.
 Most bleeding episodes stop spontaneously and respond to blood
products and careful monitoring. Patients who have bled may
require secondary prophylaxis with propranolol 0.5–1mg/kg/dose
twice a day.
 Failure to control bleeding may require the placement of a
Sengstaken-Blakemore balloon for temporary tamponade if
endoscopic treatment fails or is not possible at the time due to
the massive bleeding. In the approximately 20% of cases in which
conservative management fails (defined by multiple transfusion
requirements or an inability to maintain haemodynamic stability)
with combined pharmacotherapy and endoscopic treatments, shunt
and non-shunt surgeries are the definitive treatment.
Pharmacotherapy
 Omeprazole: Studies have shown that before-procedure PPI
therapy resulted in significantly reduced rates of high-risk stigmata
identified on endoscopy and need for endoscopic therapy. Therefore,
intravenous PPI therapy is recommended for patients who are
suspected of having acute UGIB.
Dose — Omeprazole 0.25–1mg/kg/dose TDS, evidence for higher
doses and infusion in pediatric population are limited.
 Sucralfate: can be used especially if an ulcer is suspected. Sucralfate

should be given 1 hour before meals and can be taken for 4–6 weeks
if needed.
Dose:
1 month–2 years 250mg 4–6 times daily
2–12 years 500mg 4–6 times daily
12–15 years 1g 4–6 times daily
15–18 years 2g twice daily (on rising and at bedtime) or 1g 4
times daily (1 hour before meals and at bedtime)
 Octreotide infusion: Not recommended in non-variceal UGIB. For

variceal bleed Octreotide reduces portal flow by an immediate
direct splanchic vasoconstrictive effect and by inhibiting release of
vasodilator peptides such as glucogon. It can either be given as an
intravenous bolus or by continuous infusion. Keep the child nil-by-
mouth (NBM) (except for certain oral medicines) whilst on Octreotide.
Dose: 1–2mcg/kg bolus followed by 2–5mcg/kg/hr.
 Antibiotics, antivirals and antifungal therapy should be considered in

sick children.
Endoscopy
After the initial stabilisation of patients with upper GI bleeding, upper
endoscopy is the preferred diagnostic and therapeutic tool. All patients
with significant UGIB should be referred to specialist GI team for
endoscopy. The site of upper GI bleeding can be identified in 90% of
cases when endoscopy is performed within 24 hours. This modality is
also beneficial in predicting the likelihood of continued bleeding.
Significant upper GI bleeding caused by peptic ulcers is evaluated and
treated with immediate endoscopy. Cautery, epinephrine therapy, fibrin
sealants, and endoclips are treatment options for ulcers, and biopsy
samples are taken, if warranted.
Surgery
Surgery should be considered in patients with UGIB in the following
scenarios:
 Severe, life-threatening haemorrhage not responsive to resuscitative
efforts
 Failure of medical therapy and endoscopic haemostasis with
persistent recurrent bleeding
 A coexisting reason for surgery (eg, perforation, obstruction,
malignancy)
 Prolonged bleeding, with loss of 50% or more of the patient’s blood
volume
Management of lower GI bleed

 General principles of initial assessment and management of patients
with substantial lower GI bleeding are similar to Upper GI bleed
(given above). However, urgent colonoscopy is rarely required.
Colonoscopy identifies the cause of bleeding in 80% of children.
 It is very crucial to rule out a surgical cause as in most of the cases

like intussusception, malrotation, ischaemic gut and volvulus
children may look surprising well initially. High index of suspicion is
required for early detection and this may influence outcome.
 History and examination may point towards a particular diagnosis
and they are managed accordingly (given below).
 FBC, UE, LFT, Clotting profile, CRP, ESR, GXM, Stool for Helicobacter
pylori antigen test.
 Imaging studies like barium series, US abdomen, Meckel’s scan,
CT scan or MRI may be needed before more invasive tests like
colonoscopy can be considered.
 In many cases, wireless video capsule endoscopy reveals the cause
noninvasively, but its main disadvantage is the inability to collect
tissue samples for biopsy examination.
 Colonoscopy can detect several lesions including IBD and polyps.
Vascular lesions include a wide variety of malformations, including
haemangiomas, arteriovenous malformations, and vasculitis. If these
lesions are located in the colon, colonoscopy may be diagnostic and
therapeutic. However, brisk bleeding may obscure the visual field,
making localisation the bleeding impossible.
 Rarely, radionuclear imaging with technetium-labeled red blood cells
can be used to detect bleeding at a rate as low as 0.1ml per minute.
This technique is somewhat imprecise; however, it may direct
localisation for either selective angiography, suggest a need for
video capsule endoscopy, or provide some direction for laparotomy
search and resection.
 Arteriography can be used to detect bleeding at a rate of 0.5ml
per minute and offers the advantage of providing treatment and
diagnosis. The treatment consists of embolisation and intra-arterial
administration of vasoconstrictors.
 When arteriography and nuclear scanning fail to diagnose or localise
the cause of bleeding, further options remain, including repeat
endoscopy and push enteroscopy (often also referred to as double
balloon endoscopy or enteroscopy).
 If all fails, diagnostic laparoscopy and intraoperative endoscopy can
be performed.
Management of specific conditions causing lower GI bleeding.

 For neonates with NEC, the standard treatment is aggressive medical
resuscitation with bowel rest, antibiotics, total parenteral nutritional,
and nasogastric decompression. Non-operative management of
NEC yields a 70–80% recovery rate, but urgent laparotomy or drain
placement is required in neonates in whom conservative therapy
is unsuccessful owing to progressive sepsis, bowel perforation, or
persistent bleeding.
 The history should also be used as a guide with regard to when
faecal parasites, or cultures should be ordered. Systemic antibiotics
are sometimes needed in an unwell child.
 Treatment for anal fissures consists of administration of stool
softeners and topical agents.
 The symptoms of milk protein allergy generally resolve in 48 hours
to 2 weeks after withdrawal of the offending milk product or starting
hypoallergenic formula.
 If HSP is suspected and intussusception has been ruled out, a trial of
intravenous steroids can be considered.
 Management of IBD requires referral to gastroenterology team
and involves combination of immunosuppression as well as anti-
inflammatory medications.
Bibliography
1. Arensman, and R. Abramson, L. 2006. Gastrointestinal Bleeding: Surgical Perspective.
2. Gigante, J. First Exposure Pediatrics. Mcgraw-Hill Professional Inc. 2006.
3. Hsia, R. Halpern, and J. Mola, O. 2008. Gastrointestinal Bleeding — Pediatrics.
4. Up-to-date.com
148
GENERAL AND AMBULATORY PAEDIATRICS

CHILD DEVELOPMENT
NORMAL DEVELOPMENT
Children usually attain developmental skills in a similar sequence. See
Table 5-1 for the normal developmental milestones. Developmental
screening should be performed at each patient contact, using the
checklists provided in the Child Health Booklet. Those identified to
have abnormal development should be referred to a Developmental
Paediatrician for further evaluation. For preschoolers, the two main child
development units (CDUs) in Singapore are the Department of Child
Development in KKH, and the Child Development Unit at NUH. Children
who are already in primary school should be referred to the Child and
Adolescent Mental Wellness Service in KKH or the Child Guidance Clinic
run by the Institute of Mental Health.
PATTERNS OF ABNORMAL DEVELOPMENT

 Developmental Delay:
 Development follows the normal sequence but is delayed
 May be a specific or global developmental delay
 Developmental Disorder:
 Development does not follow the normal pattern and is
aberrant or bizarre, e.g. persistence of primitive reflexes, atypical
developmental profiles
 Developmental Arrest or Regression:
 A period of normal development is followed by a failure to
acquire new skills or loss of previously established skills
 This may signify a serious underlying condition, e.g.
neurodegenerative/metabolic disorder, Landau-Kleffner
Syndrome, Rett Syndrome
AN APPROACH TO DEVELOPMENTAL AND BEHAVIOURAL

DISORDERS
A detailed history and physical examination are invaluable; specialised
investigations play only a minor role in the evaluation process.
General and Ambulatory Paediatrics 149
 Developmental history
 Gross motor
 Fine motor
 Speech/language, e.g. non-verbal language use, receptive vs.
expressive language
 Social-emotional awareness, e.g. eye contact, joint attention,
communicative intent, social appropriateness, response to family
vs. strangers
 Play (Parten’s social play stage, pretend play abilities)
 Activities of daily living
 Ask about milestones achieved, as well as current level of
functioning within each domain
 Atypical development, e.g. perseverations/obsessions/
compulsions, rigidity and poor task transitioning, motor
mannerisms, sensory issues, idiosyncratic language — Echolalia,
odd prosody, self-commentary, neologisms
 Behavior in different settings, e.g. home vs. school
 School performance, e.g. academics, behavior, socialisation skills
with peers, reports from teachers
 Reports from professionals working with the child, e.g. external
therapists
 Early temperament in infancy, e.g. social responsiveness, feeding,
sleeping, crying
 Developmental regression
 Co-morbid conditions, e.g. anxiety, depression, low self-esteem,
self-harm, aggression
 Dietary and sleep habits, e.g. nutritional deficiencies, growth
problems, fussy eaters, obstructive sleep apnea, poor sleep
 Antenatal and neonatal history:
 Cord thyroid-stimulating hormone level, APGAR Score,
prematurity, perinatal events, intrauterine infection
 Medical history:
 Chronic medical illness, seizures including absence seizures
(staring spells), otitis media, significant head injury, unexplained
febrile illnesses, hearing or visual impairment
 Drug history:
 Various drugs (e.g. steroids, beta-adrenergic receptor agonists,
methylxanthines, anticonvulsants) can affect behaviour
 Social history:
 Recent stressors, family dynamics, main caregiver(s), spoken
language at home, environmental deprivation, domestic
violence, child abuse, financial difficulty
 Family history:
 Consanguinity, any developmental disorders, hearing
impairment, seizures, neurological disorders, genetic/metabolic
disorders, psychiatric illness
Clinical examination
 Growth parameters (weight, height, occipito-frontal circumference (OFC))
 Dysmorphism
 Neurocutaneous stigmata
 Systems examination
 Full neurological examination (tone, reflexes, gait, cranial nerves,
cerebellar)
 Spine, hips
 Behavioural observations during consult
Investigations
Investigations should only be done when clinically indicated. Some
investigations that could be considered include:
 Hearing assessment (probably the most useful, and essential in any
child with language delay)
 Visual assessment
 TFTs (especially in global developmental delay with growth
problems)
 Muscle enzymes, urea/electrolytes/glucose, calcium/magnesium.
 IEM study or metabolic screen
 Karyotyping, chromosomal microarray analysis, Fragile X analysis
 TORCH screen (in children under 2 years)
 Neuroimaging (Ultrasound/CT/MRI head)
 EEG
Some Specific Conditions

Speech and Language Delay
Speech and language are components of communication. All children
presenting with a language delay should be screened for autistic
features, and have a hearing test
 Language is a system of symbolic representation that is used to
communicate meanings, feelings, ideas and intentions
 Receptive language (language processing): auditory processing,
comprehension of language
 Expressive language (language production): facial expression,
non-verbal gestures, vocabulary, phrase length, semantics,
syntax, pragmatics
 Speech is the expression of language in the verbal mode

 Speech disorders include phonological and articulation
difficulties and dysfluency (stuttering)
 Children frequently present with one of the following:
 Expressive language delay
 Mixed receptive-expressive language delay
 Phonological delay/dysfluency
 Prognosis for speech and language delay
 Most children with isolated expressive language delay do well
with Speech and Language Therapy (SLT) and show normal
language abilities subsequently
 Children with mixed language delays show slower response to
SLT, especially if there is an underlying cause such as autism.
These children may need ongoing SLT support during primary
school years
 Children with phonological delay or dysfluency tend to also
improve with SLT. Although a child may have a tongue-tie
(ankyloglossia), a frenotomy may not be indicated unless there is
limited improvement with SLT input
Autistic Spectrum Disorder (ASD)

The core clinical features of ASD comprise impairments in social
interaction, social communication and imagination, often associated
with a restricted range of interests and repetitive stereotypical
behaviors. Other associated features include sensory issues and splinter
skills. Autistic spectrum disorder has an incidence of approximately 1 in
150–400 children and is four times more common in boys.
Characteristics
 Impaired social interaction, e.g. impaired non-verbal behaviour (poor
eye contact, poor use of gestures and facial expressions), impaired
ability to make peer relationships, lack of spontaneous seeking
to share enjoyment, interests or achievements, lack of social or
emotional reciprocity
 Impaired communication/imagination, e.g. language delay, abnormal
or inappropriate language content or production, inability to initiate
or sustain a conversation with others, idiosyncratic language, lack of or
delay in imaginative or pretend play, inappropriate play
 Restricted, repetitive and stereotypical behaviour, e.g. repetitive
body movements or activities, preoccupation with objects or
subjects, restricted interests, rigid
 Sensory issues, e.g. visual stimming, under- or over-reaction to

certain sensory stimuli such as noise, textures, tastes
 Splinter skills, e.g. isolated advanced skills such as hyperplexia
M-CHAT
The Modified Checklist for Autism in Toddlers (M-CHAT) is a validated
screening tool to identify toddlers at risk for ASD who may warrant an
early developmental assessment (https://m-chat.org/). It should only be
used for children age 16–30 months. If the child’s score is 3 or more, the
child should be referred to a CDU for further investigation.
Diagnosis and management

The Ministry of Health, Singapore, has published clinical practice
guidelines for the management of ASD in preschool children in 2010.
All preschool children with suspected ASD should be referred to a CDU
for review and diagnostic assessment, according to the current DSM
criteria. School-aged children should be referred to the Child Guidance
Clinic, or be evaluated by MOE psychologists. Research has shown that
early intensive behavioral intervention is beneficial for children with
ASD. Medication may be helpful for certain children with ASD who have
concurrent ADHD or severe behavioral difficulties, but otherwise has
no place in the regular management of ASD. Various diets (gluten-free
casein-free), biomedical therapies and nutritional supplements have not
been found to make a difference in properly-conducted randomised
controlled trials. Singapore has two voluntary welfare organisations
dedicated to helping individuals with ASD: the Autism Resource Centre
(ARC) and the Autism Association of Singapore (AAS).
Attention Deficit Hyperactivity Disorder (ADHD)

The diagnosis of ADHD is based primarily on reports of characteristic
behaviors from various observers, occurring in different settings, over
an extended period of time (at least 6 months). The symptoms should
result in impairment in social and academic functioning in two or
more settings (e.g. at home and at school). These symptoms should
also be present before the age of 7 years. However, when considering
a diagnosis of ADHD, it is important to remember that inattention,
hyperactivity and impulsivity are common till 4 years old. ADHD has
an estimated incidence of 1 in 10–20 children, but there is a concern
of over-diagnosis. Often, other factors may result in a young child
behaving as though they have ADHD, but once these are addressed, the
child’s behavior may return to normal. Examples of these factors include
poor parenting strategies (e.g. caning/shouting/hitting a child), sleep
deprivation, language delay, learning disability, hearing impairment, a

major life event (parents divorcing, family bereavement), thyroid disease
or subclinical seizures.
Features of this disorder include:

 Inattention, e.g. easily distracted, careless, fails to complete tasks,
does not follow through on instructions, forgetful, difficulty
organising tasks, loses things necessary for activities, not listening
when spoken to directly
 Hyperactivity, e.g. fidgets, will not sit still, runs or climbs excessively
in inappropriate situations, difficulty engaging in leisure activities
quietly, often ‘on the go’, talks excessively
 Impulsivity, e.g. blurts out answers before questions have been
completed, difficulty waiting turn, often interrupts or intrudes others
ADHD has three sub-classifications:

 Combined type (inattentive/hyperactive/impulsive) — Children
with this type of ADHD show all three symptoms. This is the most
common form of ADHD
 Hyperactive/impulsive type — Children show both hyperactive and
impulsive behavior, but for the most part, they are able to pay attention
 Inattentive type — Formerly known as attention-deficit disorder
(ADD), these children are not overly active. They do not disrupt
the classroom or other activities, so their symptoms might not be
noticed. This subtype often affects girls rather than boys
Diagnosis and management:

The American Academy of Paediatrics updated their clinical practice
guidelines for the diagnosis and management of ADHD in children in
2012. A child should meet the DSM criteria for ADHD before being given
the diagnosis.
 In preschool children, behavioral therapy is the first-line treatment.
Methylphenidate may only be considered if a child shows limited
response to behavioral therapy with ongoing impairment in the
child’s function
 In primary school children, medications (both stimulant and non-
stimulant) can be prescribed but it is still highly-recommended
that they be used concurrently with behavioral therapy. The school
environment should also be involved in the treatment plan
 In secondary school children, treatment would be the same as for
primary school children, but should be undertaken with the assent
of the adolescent
 Doses of any medication used should be titrated to the minimum

required dose. Stimulants include methylphenidate and non-
stimulants include atomoxetine
Learning Disability
A specific learning disability refers to an underachievement in academic
skills (reading, mathematics or written expression) that is out of keeping
with a child’s age, level of intellect, education and culture. Types of
learning disabilities include reading disability (dyslexia), mathematics
disability (dyscalculia) and writing disability (dysgraphia). The term
specific learning disability does not include learning problems that are
primarily the result of visual, hearing, or motor disabilities, of intellectual
disability, of emotional disturbance, or of environmental, cultural, or
economic disadvantage.

The diagnosis of a specific learning disability can usually only be made after a
child has received regular and sufficient support in that particular area and is
still encountering difficulties. The Dyslexia Association of Singapore (DAS) also
offers good support in the form of a preschool program, school-age program,
and diagnostic services. Children with a specific learning disability will usually
benefit from regular educational support during their schooling years.
Global Developmental Delay (GDD)

Global developmental delay is defined as significant delay in two or more
major domains of development (gross motor, fine motor, speech and
language, cognition, personal and social, activities of daily living) in a child
younger than 6 years. Intellectual disability (also known as cognitive disability
or mental retardation) often causes GDD, but young children can also present
with GDD due to a lack of environmental stimulation, child abuse, neglect or
malnutrition. Children with environmental GDD usually improve with correct
support as well as with exposure to regular preschool education. Other
underlying treatable causes should also be considered and investigated early.
After the age of 6 years, if a child still has delay in more than one domain of
development, then cognitive or other assessments may need to be done to
ascertain school readiness or appropriate school placement.
Causes of GDD
In up to half of cases, the cause is not known. The commonest non-
environmental causes of GDD are:
 Genetic conditions, e.g. Down syndrome, Fragile X syndrome,
Di George syndrome, Klinefelter’s syndrome, neurofibromatosis,
Williams syndrome, Angelman syndrome and Prader-Willi syndrome.

Congenital hypothyroidism, phenylketonuria (PKU), and other inborn
errors of metabolism should also be considered
 Antenatal or perinatal complications, e.g. fetal alcohol syndrome,
congenital infections, neonatal encephalopathy
 Prematurity
 Severe refractory epilepsy
 Acquired brain injury, e.g. from trauma, meningitis, encephalitis,
heavy metal poisoning
 Visual or hearing loss
Children with autism spectrum disorder often have co-existing GDD, but
their primary diagnosis would still be ASD. Conversely, some children
with severe GDD or intellectual delay may behave as though they have
ASD (with stereotypical or repetitive behaviors), and careful delineation
of the correct diagnosis must be made.

Children with GDD need to be referred for the appropriate therapies for
help in the delayed domains of development (e.g. SLT, physiotherapy,
occupational therapy (OT), psychological support). As they often need
help from more than one allied health professional, most children with
GDD benefit from referral to the Early Intervention Program for Infants and
Children (EIPIC) centers in Singapore. The developmental paediatrician
would also screen the child for any underlying cause, perform the relevant
investigations, and treat the cause, if found. Some children with GDD will
require cognitive testing (IQ testing) at about 6 years of age to determine
the level of intellectual disability to guide appropriate school placement.
Developmental Coordination Disorder (DCD)

Children with developmental coordination disorder have difficulties
with motor coordination and may present with:
 Clumsiness
 Delays in sitting up, crawling, and walking
 Problems with sucking and swallowing during first year of life
 Problems with gross motor coordination (e.g. jumping, hopping, or
standing on one foot)
 Problems with fine motor coordination (e.g. writing, using scissors,
tying shoelaces, or tapping one finger to another)
However, DCD rarely occurs alone — it often co-exists with dyslexia,

ADHD, and language impairment.

For a child to be diagnosed with DCD there must be significant negative
consequences for the child’s clumsiness. The negative effects may be
seen in the child’s performance in school, activities at play, or other
activities that are necessary on a day-to-day basis. Also, the child’s
problems with motor coordination cannot result from such general
medical conditions as muscular dystrophy, and cannot result directly
from having intellectual disability.
An OT assessment is usually required to confirm the diagnosis of DCD.

Physical education and perceptual motor training are the best ways to
treat DCD. Using a computer to take notes may help children who have
trouble writing. Children with DCD are also at risk of low self-esteem.
In addition to the physical impairments, DCD is often associated with
problems with memory and task-sequencing. This typically results in
difficulty remembering instructions, difficulty organizing one’s time
and remembering deadlines, increased propensity to lose things or
problems carrying out tasks which require remembering several steps
in sequence (such as cooking). Hence, a more structured learning or
working environment would benefit a person with DCD.
MANAGEMENT OF DEVELOPMENTAL DELAYS AND

DISORDERS
Apart from the management strategies already highlighted in the
various sections above, many other therapy options are available. The
early detection of abnormal development and behavioral problems
facilitates the institution of early intervention such as speech and
language therapy, occupational therapy, physiotherapy and behavior
management. Some preschoolers will require placement in EIPIC
programs, and some school-age children will require placement in
Special Education Schools (http://www.moe.gov.sg/education/special-
education/schoollist/). Referrals should be made to the relevant medical
specialists.
Common concomitant problems in children with special

needs:
 Visual and hearing impairment — Minimise any impairment to
optimise child’s learning
 Epilepsy
 Orthopaedic problems — Physiotherapy, aids to optimise posture
and mobility, prevention or reduction of skeletal deformity
 Chest infections
GUIDELINE FOR REFFERAL TO CHILD DEVELOPMENT UNIT (CDU)/

OTHER AGENCIES
Preschool child
Suspected diagnosis
 Speech or language delay  Refer to Child Development Unit
 Autism (CDU)
 ADHD  Request hearing test if child has any
 Literacy delay, dyslexia or other language delay
learning disability  Refer to therapists if parents are keen
 Global developmental delay to start therapy
 Developmental coordination disorder  Refer to Genetics if dysmorphic or
 Fine motor delay strong family history
 Other behavioural problems
 Gross motor delay

 Refer to Neurology
 Suspected cerebral palsy or
neuromuscular condition
School-aged child
Suspected diagnosis
 Speech or language delay  Request hearing test and refer to
speech-language therapy
 Autism  Refer to Child Guidance Clinic
 ADHD or other behavioural  Refer to child psychiatry in KKH/NUH

problems or Child Guidance Clinic
 Dyslexia  Refer to Dyslexia Association of

Singapore (DAS)
 Intellectual disability or cognitive  Refer to hospital psychology services

delay or counsel parents to seek cognitive
assessment for alternative school
placements via school principal or
Ministry of Education (MOE)
KKH, KKWomen’s and Children’s Hospital; NUH, National University Hospital
 Feeding problems — Oromotor incoordination, gastroesophageal

reflux, tube feeding
 Bladder and bowel problems, e.g. enuresis, encopresis, constipation
 Behavioral and psychiatric concerns
 Social issues
Bibliography
1. Sharma A. Developmental examination: Birth to 5 years. Arch Dis Child Educ Pract Ed 2011,
96:162.
2. Horridge KA. Assessment and investigation of the child with disordered development.
Arch Dis Child Educ Pract Ed 2011, 96:9.
3. McDonald LAB, Rennie AC. Investigating developmental delay/impairment. Paediatrics
and Child Health 2011, 21:443.
4. AMS-MOH Clinical Practice Guidelines 1/2010. Autism Spectrum Disorders in Pre-School
Children. (http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/
guidelines/cpg_medical/2010/cpgmed_autism_spectrum_disorders_preschool_children.
html)
5. Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on
Quality Improvement and Management. ADHD: Clinical Practice Guideline for the
Diagnosis, Evaluation and Treatment of Attention-Deficit/Hyperactivity Disorder in
Children and Adolescents. Pediatrics 2011, 128:1007.
6. Robert M. Kliegman, Bonita F. Stanton, Richard E. Behrman: Nelson textbook of Pediatrics
(19th ed).
7. Ronald S. Illingworth: The Development of the Infant and Young Child (Normal and
Abnormal).
8. Lim HC, Chan T, Yoong T. Standardisation and adaptation of the Denver Developmental
Screening Test (DDST) and Denver II for use in Singapore children. Singapore Med J. 1994;
35(2):156–60.
9. American Psychiatric Association (APA). Quick reference to the diagnostic criteria from
DSM-IV-TRTM. Washington D.C: American Psychiatric Press; 2000.
10. Aylward GP. Practitioner’s guide to developmental and psychological testing. New York:
Plenum Publishing Corporation; 1994.
11. Parker S, Zuckerman B. A Handbook for Primary Care: Behavioral and Developmental
Pediatrics. Boston: Little, Brown and Company; 1995.
Table 5-1 Normal developmental milestones (Birth- 6 years)
Note: For children born premature (<37 weeks gestation), the corrected age should be used (up till 2 years
old) to assess developmental milestones
Age Gross Motor Fine Motor — Speech — Personal —
Visual Language — Social —
Hearing Behavioural
Birth Marked head lag Barely fixates/follows Alerts to sounds Visual preference for
Moro response activeGrasp reflex Cries when hungry or human face
Stepping and placing“Dolls eye” uncomfortable Sleeps and feeds
reflexes movement of eyes Opens and closes
on turning of the mouth
body
4–6 weeks Moderate head lag Fixates on objects Turns eyes to sounds Regards face
Prone — Head up and follows moving Vocalises Beginning to have
Briefly turns head persons social smile
Makes alternating In supine, follows
cycling movements object as it moves
from side to midline
3 months Mild head lag Follows from side to Turns head to sounds Initiates social smile
(by 4 months: No side (180°) at ear level Excites at toy or
head lag) Hands loosely open Vocalises/laughs/ familiar pleasant
Prone — Head up No grasp reflex squeals with situations, e.g.
45–90°, props up on Hand regard pleasure feeding, bathing
forearms (Watches
movements of own
hands)
Holds object placed
in hand
Reaches toward and
misses objects
6 months Prone — Head up Fixes on small object Imitates speech Plays peek-a-boo and
90°, props up on Follows falling sounds imitative games
hands with arms objects Polysyllabic babbling Smiles and vocalises
extended Reaches out to grasp Turns to sounds at mirror image
Rolls over prone to (palmar grasp) Stretches arms out to
supine (Supine to Transfers objects, one be lifted
prone =7months) hand to another Excited by approach
Sits with support, Mouths of familiar people
head steady Grasps own feet and Displeasure at
Bears weight on gets feet to mouth removal of toy
legs when held in
standing position
Hearing Behavioural
10 months Sits up alone and Looks for hidden toy Locates sounds well Claps hands
without support and uncovers it Babbles Waves bye-bye
Creeps or crawls Goes for objects with Says “papa”, “mama” wary of strangers
Cruises (walks index finger. indiscriminately Responds to sound of
holding on to Bangs two cubes name
furniture) held in hand Starts to explore
Looks for fallen environment
object Repeats performance
Finger thumb laughed at
apposition Holds own bottle
Finger feeds
1 year Stands alone Casting (beginning Responds well to Stranger anxiety,
Walks with one hand to throw objects name closely attached to
held to floor) Single-finger familiar adult
May shuffle on Fine pincer grasp pointing Shows affection
buttock and hand Releases object to Pushes things away Joint attention
other person on he/she does not Imitates actions
request or gesture want Enjoys putting
Mouthing virtually Calls “papa”, “mama” objects in and out
stopped specifically of boxes
Two to three words Co-operates with
with meaning dressing
Understands simple
phrases
Obeys one-step
command with
gesture
18 months Gets up and down Spontaneous scribble Mature jargoning Domestic mimicry
stairs, holding rail Builds tower of three (includes intelligible (copies mother in
without help to four cubes words) dusting, washing,
Walks up stairs, one Turns 2–3 pages at Points to 2–3 body cleaning)
hand held a time parts, Meaningful play
Walks pulling toy or Points to indicate with toys
carrying doll needs Plays alone but near
Climbs onto chair Obeys simple familiar people
Explores drawers and instructions Shows sustained
wastebaskets interest in books
No casting Drinks from cup
Takes off socks
Begins to tell mother
about wetting
Assists dressing
Hearing Behavioural
2 years Up/down steps, two Holds pencil in fist Two- to three-word Parallel play (enjoys
feet per step Copies lines phrases solitary play,
Jumps Builds tower of 6 Knows 50 words alongside peers)
Propels tricycle by cubes Understands two- Pretend play
pushing with feet Turns pages one at part instructions Not sharing
on floor a time Listens to simple Possessive
Kicks and throws ball stories Tantrums when
Enjoys nursery not understood or
rhymes and jingles demands not met
Helps with dressing/
undressing
Washes hands
Indicates toilet needs
Mainly dry by day
Helps put things
away
Uses spoon
3 years Up/down steps, Handedness (noted More-than-three- Group play
alternate feet by 2 years but firmly word phrases Cooperative play
Broad jump established by 3–4 Holds conversation (shares toys, takes
Walk on tip-toe years) Gives name/age/sex turns)
Stands on one foot Awkward tripod Asks questions — Constructive play
for seconds grasp of pencil what, who, where Brushes teeth with
Pedals tricycle Copies circle Recites some nursery help
Imitates cross rhymes Dresses/undresses
Builds tower of nine Names two colours except buttons
cubes Know front from back
Immitates Toilet-trained
construction of
“bridge” of three
cubes.
Threads beads
4 years Hops on one foot Dynamic tripod grasp Speaks Imaginative play
Balances on either of pencil grammatically and alone and with
foot for 5 secs Copies cross and clearly other children
Climbs well square Uses pronouns, Dresses with
Colours picture plurals, minimum help
Uses scissors to cut prepositions. Brushes teeth with
out pictures Gives address no help
Identifies longer of Ask questions-why, Buttons clothes
two lines how Names friends
Draws a man with Tells a story
2–4 parts besides Rote count to 10
head
Hearing Behavioural
5 years Skips on both feet Copies triangle Speaks fluently Comforts siblings/
Heel-to-toe walk Draws person with Long descriptions friends in distress
Enjoys climbing, 2−4 parts besides and explanations Protective of younger
swings and slides head Understands complex sibling
Catches bounced ball Names heavier of instructions Makes and chooses
Plays ball games two weights Enjoys riddles, jokes own friends
Knows time of day Carries out simple
Recognises numbers, domestic tasks
letters Runs errands
Names four colours Ties shoe laces
6 years Backward heel-to- Copies a diamond Adds single numbers Play with particular
toe walk Writes name, simple Spells and reads themes
words Knows days of week
Knows number of
fingers
Bibliography
1. Nelson textbook of Pediatrics (19th ed): Robert M. Kliegman, Bonita F. Stanton, Richard E.
Behrman.
2. The Development of the Infant and Young Child (Normal and Abnormal): Ronald S.
Illingworth.
3. Standardisation and Adaptation of the Denver Developmental Screening Test (DDST) and
Denver II for use in Singapore Children: HC Lim,T Chan,T Yoong: Singapore Med J 1994;
Vol 35: 156–160.
ADOLESCENT HEALTH —
HEADSS ASSESSMENT
INTRODUCTION
Adolescence is generally a healthy period of life in comparison to early
childhood and old age. As healthcare professionals in contact with
this group of individuals, it is important to understand adolescent
development and to have effective communication and consultative
skills to better guide treatment and management.
The Home, Education/Employment, Activities, Drugs, Sexuality, Suicide/

Depression (HEADSS) assessment is an excellent guide to obtain a
bio-psycho-social biopsy and an opportunity to build rapport with the
adolescent. It aids in risk assessment as well as helps guide intervention.
HEADSS COMPREHENSIVE ADOLESCENT PSYCHO-SOCIAL

SCREENING INTERVIEW
Home
 Who lives with the patient? Where? Own room?
 What are the relationships like at home?
 What do parents and relatives do for a living?
 Ever institutionalised? Incarcerated?
 Recent moves — Run-away episodes?
Education (and/or Employment)

 School/grade performance — Any recent changes? Any dramatic
past changes?
 Favourite/worst subjects
 Any years repeated/classes failed?
 Suspensions or termination, dropping out history
 Future education/employment plans/goals
 Any current employment?
 Relations with teachers, school attendance
 Bullied/bullies
Activities
 With peers (What do you do for fun? Where and when?)
 With family
 Club/school functions
 Sports, regular exercise
 Church attendance and club projects
 Hobbies — Other home activities
 Reading for fun — What?
 TV — How much weekly? Favourite shows?
 Favorite music
 Does patient have car, use seatbelts?
 History of arrests — Acting out, crime
Drugs
 Used by peers
 Used by patient; include alcohol and cigarettes
 Used by family members
 Amounts, frequency, patterns of use/abuse and car use,
while intoxicated
 Source — How is it paid for?
Sexuality
 Orientation
 Degree and types of sexual experience and acts
 Number of partners
 History of pregnancy/abortion
 Sexually transmitted diseases — Knowledge and prevention
 Contraception
Suicide/Depression
 Sleep disorders (usually induction problems, also early/frequent
waking or greatly increased sleep and complaints of increasing
fatigue)
 Appetite/eating behaviour changes
 Feeling bored?
 Emotional outbursts and highly impulsive behaviour
 History of withdrawal/isolation
 Hopeless/helpless feelings
 History of past suicide attempts, depression, psychological
counselling
 History in family or peers
 History of drug/alcohol abuse, acting out/crime, recent change in
school performance
 History of recurrent serious ‘accidents’
 Psychosomatic symptomatology
 Suicidal ideation (including significant current and past losses)
 Decreased affect on interview, avoidance of eye contact
EATING DISORDERS
Adolescents are at risk of developing an eating disorder with a lifetime
prevalence reported between 6–12%. There are several types of eating
disorders with anorexia nervosa being the most common that presents
to the family physician or paediatrician. Other clinical variants have now
been described including binge eating disorder, feeding and eating
concerns — not elsewhere classified (FEC-NEC) and avoidant/restrictive
food intake disorder (ARFID). These conditions will usually present with
physical manifestation of malnutrition, growth and pubertal concerns.
Bulimia nervosa tends to present in older adolescents with little or
minimal physical symptoms.
ANOREXIA NERVOSA (AN)

 Restriction of energy intake leading to a significantly low body
weight in the context of age, sex, developmental trajectory, and
physical health.
 Intense fear of gaining weight, or persistent behavior that interferes
with weight gain.
 Body image disturbance or persistent lack of recognition of the
seriousness of the current low body weight.
Sub types
 Restricting: only restriction of intake last 3 months
 Binge/purge: engages in binge eating or purge behaviors
(vomiting, laxatives, diuretics) last 3 months
CLINICAL MANIFESTATION
Most adolescents presenting with eating disorders will have the
following issues:-
 Characteristic cognitive and behavioral signs
 Intentional caloric restriction
 Preoccupation with weight, food, calories, fat, and dieting
 Thoughts of “feeling fat” when weight is normal or low
 Fear of gaining weight
 Feelings of guilt and shame about eating
 Frequent weighing
 Weight determines self-esteem
 Binge-eating
 Inappropriate compensatory behaviours (purging) — Including
self-induced vomiting, use of laxatives, diet pills, excessive
exercise
 Growth and developmental abnormalities
 Precipitous weight loss or gain or frequent weight fluctuations
 Failure to gain expected weight or height
 Delayed or interrupted pubertal development
 Medical consequences of the eating disorder
 Nutritional deficiencies: acute malnutrition can be a medical
emergency
 Medical instability (see criteria for admission)
 Physical signs that may be seen in anorexia nervosa are listed below.
 Hypothermia
 Bradycardia
 Orthostatic pulse and blood pressure
 Dull, thinning scalp hair
 Lanugo hair
 Emaciated, wears oversized clothes
 Flat affect
 Cold extremities, acrocyanosis
 Primary or secondary amenorrhea
If an eating disorder is suspected, the first priority is to determine

medical stability and to evaluate for complications of the disordered
eating pattern. Remember that patients do not have to be at a
significantly low BMI. If the patient’s weight is dropping rapidly, medical
instability can occur at the next visit — close follow-up appointments, e.g.
2 weeks until involvement of treatment team is recommended. The most
common medical criteria used for risk management is bradycardia
Suggested investigations
 Electrocardiography (ECG)
 Full blood count, renal panel, serum calcium, serum magnesium,
serum phophate, random blood sugar level or hypocount, LFT, TFT
and in females, serum luteinising hormone (LH), follicle stimulating
hormone (FSH), oestradiol
Medical instability and criteria for acute admission

 Resting heart rate <50bpm
 Electrocardiogram abnormalities, e.g. prolonged QTc
 Significant postural and/or haemodynamic changes
 Hypotension
 Systolic BP drop >20mmHg from lying to standing position
 Diastolic BP drop >10mmHg from lying to standing position
 Heart rate increase of >30bpm from lying to standing position
 Dehydration
 Temperature <35.5°
 Electrolyte abnormalities
On admission to the general paediatric ward

 Keep CRIB (complete rest in best)
 Monitor vital parameters 4–6 hourly depending on medical status
 Cardiac monitoring
 Postural blood pressure and heart rate BD
 Blood investigation and/or ECG as above if not already done
 Refer to the Adolescent Medicine team — Inform the Adolescent
Medicine doctor, Adolescent Resource Nurse and Dietician
 Suicidal precautions if high risk
If medically stable and not high risk for suicide, all new patients with an eating
disorder can be referred to the Adolescent Medicine service as an outpatient.
Please call the adolescent medicine physician to discuss these cases.
Refeeding Syndrome
The clinical manifestations of refeeding syndrome can potentially cause fatal
shifts in fluids and electrolytes into the cells with rapid refeeding of starved
patients. The increased glucose load can cause a surge of insulin secretion
which stimulates glycogen, fat and protein synthesis. There is activation of the
ATPase symporter which transports glucose into the cells. Magnesium and
phosphate are also taken up into the cells and water follows by osmosis. These
processes, coupled with a total body depletion of these electrolytes result
in a decrease in the serum levels of phosphate, potassium, and magnesium.
Hypophosphataemia is classical with a nadir presenting at Day 5–7 of refeeding.
Patients who are admitted for medical instability are at risk for refeeding
syndrome. Their nutritional intake and meal plans should be medically
supervised and ordered by the dietician. Frequent monitoring of serum
electrolytes in particular serum phosphate, potassium, magnesium and
blood sugar (hypocount) is recommended daily especially for the first 5
days of refeeding.
Goals of treatment
 Treatment goals for medical admission
 Nutritional rehabilitation
 Medical stabilisation and prevention of serious medical
complications (average length of hospital stay is 10–14 days)
 Reinforce to the family the seriousness of the condition —
Mortality rate 1.8%–5.9% described
 Psychoeducation for patient and family
 Introduction to Family Based Treatment (FBT)
Family based treatment (FBT) or Maudsley approach now considered

first-line treatment
 Effective, protective against relapse
 Family (parental) involvement vital using strategies to empowers
caregivers to refeed their adolescent
 Non-blaming approach that focuses on moving forward from the
disease
 Best prognosis if treated rapidly and aggressively (achieving 2kg
weight gain in first 4 weeks of treatment with weight restoration
within 6 months of presentation)
 Optimal care from multidisciplinary team approach

 Emphasises weight and growth restoration and resumption of
menses or puberty
 Emphasises cessation of disordered eating pattern and body
image distortion with restoration of normal meal patterns that
promote health and social norms
Bibliography
1. H Y Lee, Z Hoodbhoy. You Are Worth More Than What You Weigh: Preventing Eating
Disorders. Annals Academy of Medicine 2013 Feb;42(2):64–5.
2. Lee HY, Lee EL, Pathy P, Chan YH. Anorexia nervosa in Singapore: an eight-year
retrospective study. Singapore Med J. 2005 Jun;46(6):254–6.
3. DSM criteria (Diagnostic and statistical manual of mental disorders, 5th ed: DSM-IV.
Washington, D.C. American Psychiatric Association Press).
4. Katzman, D. et al. Medical Complications in Adolescents with Anorexia Nervosa: A Review
of the Literature; Int J Eat Disord 2005;37:S52–S59.
5. Critical Points for Early Recognition and Medical Risk Management in the Care of
Individuals with Eating Disorders. 2nd ed. AED report 2012.
6. Rosen, D. Identification and Management of Eating Disorders in Children and Adolescents;
Pediatrics 2010;126;1240–1253.
7. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ 2008; 336;1495–
1498.
8. Couturier J, Kimber M, Szatmari P. Efficacy of family-based treatment for adolescents with
eating disorders: A systematic review and meta-analysis. Int J Eat Disord 2013;46:3e11.
9. Katzman D., et al. The role of the pediatrician in Family-Based treatment for Adolesent
Eating Disorders: opportunities and Challenges.
CHILD ABUSE AND NEGLECT
DEFINITIONS
In 1999, the World Health Organisation (WHO) provided the following
refinement of the definition and classifications of Child Abuse and Neglect:
“Child abuse or maltreatment constitutes all forms of physical and/or

emotional ill treatment, sexual abuse, neglect or negligent treatment or
commercial or other exploitation, resulting in actual or potential harm
to the child’s health, survival, development or dignity in the context of a
relationship of responsibility, trust or power.”
The preamble to the definition is the emphasis that to fully understand

child abuse and neglect as it presents itself in any particular culture,
there is a need to consider the attitudes, values and philosophy that are
prevalent in the society in which it occurs and at a given time.
Physical Abuse
The physical abuse of a child covers any actual or potential physical
harm resulting from an interaction or lack of an interaction, which is
reasonably within the control of a parent or person in a position of
responsibility, power or trust. This may be single or repeated incidents.
The perpetrators or the instruments used to inflict physical harm may be
single or multiple.
Emotional Abuse
Emotional abuse includes the failure to provide a developmentally
appropriate, supportive environment, including the availability of a
primary attachment figure, so that the child can develop a stable and
full range of emotional and social competencies commensurate with
his or her personal potentials and in the context of the society in which
the child dwells. There may also be acts towards the child that cause or
have a high probability of causing harm to the child’s health or physical,
mental, spiritual, moral or social development. These acts must be
reasonably within the control of the parent or person in a relationship
of responsibility, trust or power. Acts include restriction of movement,
patterns of belittling, denigrating, scapegoating, threatening, scaring,
discriminating, ridiculing or other non-physical forms of hostile or
rejecting treatment.
Neglect and Negligent Treatment

Neglect is the failure to provide for the development of the child in all
spheres: Health, education, emotional development, nutrition, shelter,
and safe living conditions, in the context of resources reasonably
available to the family or caretakers. It causes or has a high probability of
causing harm to the child’s health or physical, mental, spiritual, moral or
social development. This includes the failure to properly supervise and
protect children from harm as much as is feasible.
Sexual Abuse
Child sexual abuse is the involvement of a child in sexual activity that he
or she does not fully comprehend, is unable to give informed consent to,
or for which the child is not developmentally prepared and cannot give
consent, or that violate the laws or social taboos of society.
Child sexual abuse is evidenced by this activity between a child and an

adult or another child who by age or development is in a relationship
of responsibility, trust or power, the activity being intended to gratify or
satisfy the needs of the other person. This may include but is not limited to:
 The inducement or coercion of a child to engage in any unlawful
sexual activity
 The exploitative use of a child in prostitution or other unlawful sexual
practices
 The exploitative use of a child in pornographic performances and materials
Exploitation
Commercial or other exploitation of a child refers to use of the child in
work or other activities for the benefit of others. This includes, but is not
limited to, child labour and child prostitution. These activities are to the
detriment of the child’s physical or mental health, education or spiritual,
moral or social-emotional development.
RECOGNITION OF CHILD ABUSE AND NEGLECT

The diagnosis of child abuse is not easy. A high index of suspicion by the
professional who sees the child is required. It is based on a combination
of medical findings that are unexplained, implausible and inconsistent
with the history obtained, patterns of injury that suggest they have been
caused by abuse rather than by accident, and certain characteristics
and behaviour of the child and family. Appropriate medical and social
investigations are required to confirm or elaborate on the diagnosis, and
a period of observation of the child’s response may be necessary.
Non-accidental Physical Injuries

When to Suspect Abuse
 Injuries are seen repeatedly and not adequately explained by normal
childhood activities
 The parent’s or caretaker’s story of the child’s injury is vague,
inadequate or implausible, e.g. a 5-month-old infant cannot climb
into a tub of hot water
 Delay in seeking medical attention for the injury
 The story may be inconsistent or contradictory, and the parent’s
reaction to the seriousness of the injury is inappropriate
 Injuries such as abrasions and bruises of varying age
 Injuries with patterns (circular, square, tramline, herringbone)
 Circular marks around the wrists, ankles or penis
 Clustered or grouped injuries (e.g. 3–4 oval bruises suggestive of a
slap on the face, or a grasp around a limb)
 Injuries over body parts that are usually clothed

 Injuries to genitalia, with vague history
 Injuries to eyes, ears and internal organs
 Head injuries with vague history
 Broken bones and ribs of varying ages; swollen, painful and
dislocated joints
 Burns and scalds, especially over the buttocks or soles of the feet
Behavioural Symptoms of Physical Abuse

 Fear of parents/caretaker
 Overly compliant, withdrawn, unusual fear of authority
 Wariness of physical contact
 Unusual hunger for affection
 Fear of going home after school or child care
 Sudden change in behaviour, e.g. from noisy to shy and passive, or
becoming aggressive
 Wetting/soiling pants inappropriate for age group
 Sleep problems including nightmares
 Constantly watching for possible danger, apprehensive when other
children cry
Neglect
Some Physical Signs
 Consistent and regular hunger
 Malnutrition
 Low weight for age
 Gaining weight when hospitalised or placed in alternative care
 Poor language skills and coordination
 Poor hygiene (child constantly unwashed)
 Poor teeth, gum disease, untreated sores, not immunised against illness
 Consistent lack of supervision
Some Behavioural Symptoms

 Poor bonding with parents
 Clings to any adults, goes too easily with strangers
 Unusually tired, listless or motionless
 Feeds hungrily or hardly at all
 Hungry for adult affection and attention
 Habitual school truant or late-comer
 Poor school performance, learning difficulties
 Reluctance to go home
 Rocking, sucking, head-banging
Emotional or Psychological Abuse

Emotional abuse can harm children just as much as other forms of abuse. It
can be difficult to identify because it does not leave any physical injuries and it
often goes unrecognised until a child shows signs of emotional problems.
Some Key Features

 Stunted growth: Non-organic FTT
 Accelerated growth away from family
 Feeding behaviour grossly disturbed
 Delayed mental and emotional development
 Unusual patterns of urination and defecation
 Poor social adjustment, anti-social behaviour, unhappy, irritable
and defiant

 Changes in behaviour
 Lying and stealing
 Destructive or violent behaviour
 Child rocks, sucks or bites self
 Being very shy, passive, compliant
 Being aggressive and constantly seeking attention
 Low self-esteem, negative statements about self
 Inability to mix with other children
Sexual Abuse
Some Physical Signs
 Pain, itching, discharge or bleeding in genital area
 Bruises to breasts, buttock, lower abdomen or thighs
 Vaginal infections with or without associated UTIs
 Abdominal pain suggestive of pelvic inflammatory disease
 Recurrent headaches which are not neurological in origin
 Sexually-transmitted diseases
 Painful urination, bedwetting inappropriate for age
 Pregnancy, especially teenage pregnancy
 Torn, stained, bloody underclothes
 Symmetrical bruises over the medial aspects of both thighs which suggest
that the child’s hips were forcibly abducted during the act of sexual assault

 Fear of being hurt during dressing/nappy change
 Inappropriate sexual activity
 Fear of being alone with a particular adult
 Extreme reactions, e.g. phobia to the opposite sex

 Depression or low self-esteem
 Distorted self-perception, e.g. being dirty or unclean
 Uncontrollable crying and screaming
 Sexual themes/fears in artwork, stories or play
 Strong fear/anxiety (especially about going home)
 Child reports having dreams or fears that seem to have sexual overtones
 Exhibit self-destructive behaviour such as self-mutilation, alcohol/substance
abuse, excessive risk-taking that may endanger life, and suicidal attempts
 Eating disorders including anorexia nervosa
 Child demonstrates sexual behaviour beyond his/her years and
supposed knowledge, e.g. hyper-sexualised behaviour
 Delinquent, aggressive or truant behaviour at school not explained
by other causes in a previously well-behaved child
 Regressive behaviour, e.g. sudden return to wetting or soiling
 Unwilling to participate in normal physical or social activities
 Poor relationship with other children
 Promiscuity, prostitution, homosexuality
Munchausen Syndrome by Proxy (MSP)

MSP was first described in 1977 in children whose parents (usually
mothers and rarely fathers) invented stories of illness about their child
and then substantiated the stories by fabricating false physical signs.
Warning Signs
 The illness is unexplained, prolonged or extremely rare
 The symptoms and signs have a temporal association with the
mother’s presence
 The symptoms may also be incongruous, e.g. blood-stained vomit in
a child who is pink and laughing and has good pulse
 The mother is a hospital addict and is more anxious to impress the
doctor than worried about her child’s illness
 The treatment prescribed is ineffective and not tolerated
 There are multiple illnesses and similar symptoms in other members
of the family
 Other siblings may be similarly affected, and there has been non-
accidental injury or unexplained death of other children
DRUG OVERDOSE AND POISONING
GENERAL PRINCIPLES OF POISONS MANAGEMENT

Presentation of poisoned paediatric patients to the Emergency
Department demands prompt action to prevent poisoning by using
decontamination, to enhance elimination or to treat poisoning with
supportive care and, for a few poisons, antidotes. The cornerstone in the
management of the poisoned child remains supportive.
Figure 5.1 (overleaf ) outlines the management of acute ingestions.

Remember to treat the patient and not the poison.
Child with an Acute Movement Disorder
 Dyskinesia: Amphetamines, anticholinergics, antihistamines, cocaine,
gamma-hydroxybutyrate
 Dystonia: Antipsychotics and metoclopramide, selective serotonin
reuptake inhibitors and tricyclic antidepressants
 Rigidity: Malignant hyperthermia, neuroleptic malignant syndrome
and phencyclidine
Sympathomimetic Syndrome
 Clinical presentation: CNS excitation, seizures, tremors, hyperreflexia,
hyper/hypotension, tachycardia
 Biochemical: Low potassium, raised blood glucose, acidosis
 Management: Supportive, prevent hyperthermia
 Toxic agents: Amphetamines, theophylline, salbutamol, cocaine
Serotoninergic Syndrome
 Clinical presentation: A primary neuroexcitation spectrum of toxicity
involving predominantly 5-HT2 receptors with abnormalities of:
 Mental status: Agitation/restlessness/confusion/hypomania
 Motor system: Clonus/myoclonus inducible/spontaneous/
ocular tremour/shivering, hyperreflexia/hypertonia/rigidity
 Autonomic nervous system: Diaphoresis/tachycardia/
flushing/mydriasis
 Course: Up to several days to weeks after discontinuing treatment
 Differential diagnosis: May resemble anticholinergic and neuroleptic
malignant syndromes
 Management: Supportive
Acute Ingestion
Maintain Vital Signs

Airway
Breathing
Circulation (monitor electrolytes/ECG)
Conscious, Conscious, Unconscious

Non-toxic Definite Toxicity
 Recovery position.
 Reassure parents  Activated charcoal 1g/kg  Oral airway/intubate.
 Educate parents on ‘child- for absorbable poisons  I/V line, KIV fluid
safe’ environment  Milk for household resuscitation. Take blood
 Discharge after review detergent ingestions. for sugar & toxicology (Li
 Substances which do not Hep tube) KIV do ABG.
bind to charcoal include Consider immediate
strong acids, alkalis, Fe, antidote therapy:
Conscious,
Li, cyanide, KI, small ionic  10% Dext.(2ml/kg)
Intermediate Toxicity
molecules.
 Naloxone (0.1mg/kg,
 e.g. Paracetamol  Admit all cases to general max 2mg)
ingestions still within ward or High Dependency
therapeutic range, and  Atropine (0.02mg/kg)
as indicated for
serum levels at least 20  4.2% NaHCO3 (1–2ml/
monitoring, KIV antidote
units below toxic range in kg)
therapy.
the normogram.  Flumazenil (5mcg/kg
 Observe for 4–6 hours stat I/V, repeat every
post-ingestion 60secs to max 40mcg/
 Discharge after review kg (max 2mg))
 Educate parents on  Digibind
safety precautions and to  Gastric lavage with wide
return to clinic/hospital if bore N/G tube after
symptomatic airway control
 May need clinic review  Contraindications:
Corrosives, Caustics, Acids,
Petroleum distillates
 CXR if aspiration/
Note: chemical pneumonitis/
 Look out for various toxidromes mediastinitis suspected
 If ingestion was ≤1 hour, activated charcoal or gastric lavage for  Admit to ICU with
gastrointestinal decontamination may be considered if indicated transport monitor
 If child’s GCS is ≤8, secure airway and resuscitate before
performing gastrointestinal decontamination
Figure 5.1: Management of acute ingestions

 Agents involved: Monoamine Oxidase Inhibitors (MAOIs),

clomipramine, SSRIs, tryptophan (particularly in combination)
 Remarks: This clinical picture may resemble an acute infection and,
therefore, may be easily overlooked
Neuroleptic Malignant Syndrome

 Clinical presentation: Hyperthermia, muscle rigidity, metabolic
acidosis and confusion
 Toxic causes: Use of antipsychotic agents
 Management: Supportive, body cooling
 Specific antidote — Bromocriptine
 Remarks: Bear in mind that this presentation may resemble the
serotoninergic syndrome
Anticholinergic Toxidrome
 Clinical presentation: Dry flushed skin, dry mouth, mydriasis,
delirium, hallucinations, tachycardia, ileus, urinary retention,
hyperthermia, coma and respiratory arrest
 Specific antidote: Physiostigmine (contraindicated if ECG abnormal
or has underlying heart disease)
 Remarks: The syndrome may be overlooked due its resemblance to
fever and infection. It may also resemble sympathomimetic overdose
Cholinergic Toxidrome
 Clinical presentation:
 Muscarinic effects: Incontinence (diarrhoea/urinary), abdominal
cramps, miosis, bradycardia, emesis, lacrimation, salivation
respiratory hypersecretion, diaphoresis
 Nicotinic effects: Tachycardia, hypertension, muscle fasciculation,
paralysis, tremor, muscle weakness, agitation, seizures and coma
 Specific antidotes: Atropine and pralidoxime
 Toxic agents: Organophosphates and carbamates
 Clinical tip: The syndrome may be diagnosed by the specific response
to antidotes, and by lower levels of the cholinesterase enzyme
Opioid Toxidrome
 Clinical presentation: Miosis, CNS depression, (sedation and lethargy
to coma), respiratory depression, hypoxia, pulmonary oedema
 Differential diagnosis: Other sedative hypnotics typically do not
cause miosis
 Specific antidote: Naloxone
 Remarks: Lomotil (diphenoxylate poisoning) and codeine in cough
mixtures
Biochemical Presentation
Child with Increased Osmolar Gap
 Osmolar gap = (Measured osmolality) − (Calculated osmolality)
(normal 0mOsm/L ± 5mOsm/L)
 Calculated osmolality: 2 × (Na+ in mEq/L) + (Glucose in mg/dL) / 18 +
(BUN in mg/dL) / 2.8 = ± 290mOsm/L
 Toxic agents: Acetone, ethanol, ethyl ether, ethylene glycol, isopropyl
alcohol, mannitol, methanol, renal failure and ketoacidosis (diabetic
and alcoholic)
Child with an Increased Anion Gap Acidosis

 Anion gap = (Na+) − [(Cl–) + (HCO3–)] (Normal: 8–12mEq/L)
 Toxic causes: Severe paracetamol poisoning, beta-adrenergic agents,
carbon monoxide, cyanine, iron, isoniazid, salicylates, theophylline,
toxic alcohols and valproic acid
The following criteria must be satisfied before the child is discharged

from the clinic/hospital:
 Asymptomatic
 No biochemical abnormalities, for example, hypoglycaemia,
metabolic acidosis
 No signs to suggest non-accidental injury or neglect
 No signs to suggest willful ingestion/suicidal intent (in teenagers)
 Where ‘time bomb’ ingestions are ruled out, e.g. lithium, iron, MAOIs,
phenytoin, carbamazepine, slow-release medications
Gastrointestinal Decontamination
 Ipecac and other pro-emetic agents: Not recommended for routine
use in paediatric poisonings
 Carthartics are currently not recommended in paediatric poisoning
 Poisons with delayed gastric emptying:
 Aspirin
 Digoxin
 Tricyclic antidepressants
 Phenobarbitone
 Delayed-release preparations
Table 5-2: Gastrointestinal decontamination — Methods, doses, indications, contraindications

and complications
Method Dose Indications Contraindications Complications
Activated 1g/kg  ≤1 hour of ingestion  Unprotected airway  Aspiration
Charcoal (AC) (serve with syrup to of significantly toxic  Poor absorped  Peritonitis from
increase palatability) substance substances perforated intestines
 ≥1 hour if delayed  Hydrocarbons, e.g.  Pseudo-intestinal
gastric emptying or kerosene, camphor obstruction (especially
sustained release  Alcohols, e.g. with repeated charcoal
preparations methanol, ethylene doses and dehydration)
glycol, ethanol, etc.
 Metals and
Inorganic salts,
e.g. fluoride, iron,
lithium, potassium
 Alkali and mineral
acids
Gastric Lavage  ≤1 hour of significant  Combative alert  Perforation of
amounts of substances patients oesophagus or
of intermediate  Unprotected airway stomach
toxicity and even small  Sustained release  Nasopharyngeal
amounts of substances products or enteric trauma
of high toxicity coated tablets (whole  Intratracheal
 After ≥1 hour, can bowel irrigation placement
still consider gastric preferable)  Vomiting and
lavage for poisons with  Corrosive substances, a aspiration
delayed absorption hydrocarbon with high
aspiration potential,
rapidly absorbed
substances (e.g.
alcohols, imidazoline
products used in
over-the-counter
preparations for
nasal and ocular
decongestion, such
as oxymetazoline,
naphazoline,
tetrahydrozoline)
 high risk of
haemorrhage or
gastrointestinal
perforation due to
pathology, recent
surgery or other
medical complications
Method Dose Indications Contraindications Complications

Whole bowel  Osmotically-  Sustained released  Unprotected airway
irrigation balanced agents: preparations or altered conscious
(WBI) GoLytely,  Enteric-coated status
Polyethylene medicines ingested  Intestinal obstruction
glycol (PEG) to
be given
 35ml/kg/hr (max
500ml/hr)
Antidotes
 Specific toxins may need specific antidotes
 From N-acetyl-cysteine (NAC) for paracetamol poisoning to digibind
for digitalis toxicity and desferoxamine for iron poisoning, the only
difference with regards to paediatric poisoning is in the dosage that
has to be tailored to the individual paediatric-sized patient
 However, some antidotes though available may not be required.
Instances of seizures have occurred in benzodiazepine overdose
when supportive measures were sufficient till effects resolve
Enhanced Elimination
 Enhance and promote the clearance of the toxin from the system
 Their roles depend on the substance concerned and the respective
pharmacokinetics with their respective volumes of distribution
 Multiple-dose Activated Charcoal (MDAC):
 Acts as a ‘gastric dialysis’ and has a role in specific agents
 MDAC is administered as 0.5–1g/kg 2–4 hourly, which has
been shown to be useful for theophylline, phenobarbitone and
carbamazepine poisonings, and also, theoretically, drugs with small
volumes of distribution and that are not strongly protein–bound
 The loading dose is 10:1 (Activated charcoal-to-drug ratio), or
1–2g/kg if drug unknown
 Doses vary from 0.25–0.5g/kg every 1–6 hours (adults 20–60g)
every 1, 2, 4 and 6 hours
QUANTITATIVE TOXICOLOGY TESTS
PARACETAMOL POISONING
Paracetamol poisoning is the most common form of pharmaceutical
poisoning. It is usually accidental in young children and non-accidental
in the adolescents.
Table 5-3: The more common medications and the optimal time for screening their serum toxic
levels
Drug/Toxin Optimal Time after Ingestion
Paracetamol * 4 hours
Carbamazepine 2–4 hours
Carboxyhaemoglobin Immediate
Digoxin 4–6 hours
Ethanol 1/2–1 hour
Ethylene glycol 1/2–1 hour
Iron 4 hours
Lithium 2–4 hours (repeat 6–12 hours later for sustained released preparations)
Methanol 1/2–1 hour
Methaemoglobin Immediate
Phenobarbitone 1–2 hours
Phenytoin 1–2 hours
Salicylates* 2–6 hours (repeat 6–12 hours later for sustained released preparations)
Theophylline 1–2 hours (repeat 6–12 hours later for sustained released preparations)
* Follow normograms if it is an acute ingestion
Table 5-4: Household products and plants that are ‘toxic’ for children
Acid/alkali: Boric acid, bowl Alcohols: Ethanol, ethylene Antiseptics: Camphor, hydrogen
cleaners, clinitest tablet, disc glycol, methanol, isopropyl peroxide, phenol, pine oil
battery alcohol
Cyanide Hydrocarbons: Aliphatics, Industrial chemicals:
aromatics Burtyrolactone (solvent
foracrylate), methylene chloride,
selenious acid (gun blueing), zinc
chloride
Mothballs: Napthalene Nail products: Acetone (polish Pesticides: Organophosphates,
remover), acetonitrile (sculptured carbamate
nailremovers), methacrylic
acid (artificial nailprimer),
nitromethane (artificial nail-
remover)
Plants: Aconite, cantharidin, Rodenticides: Arsenic, Weed/bug killers: Lindane,
castor bean, clove oil, comfrey, hydroxycoumarin, indanediones, nicotine, paraquat
fox glove, na hwang, specific strychnine
mushrooms, nutmeg, oleander,
pennyroyal oil
Table 5-5: Commonly ingested non-toxic substances

Air fresheners, aluminium foil, antiperspirants, baby lotions, baby Wipes, ball-point pen ink, calamine lotion,
candles, chalk, charcoal, cigarette ashes, clay, crayons, cyanocrylate glues, deodorants, dessicants, disposable
diapers, erasers, superglue, gum, incense, ink (without aniline dyes), lip balm, lipstick, magic markers,
matches (<3 paper books), newspaper, paraffin, pencils (contain graphite), plaster, plastics, silica gel, stamp
pad link, sunscreen products, thermometers (<0.5ml elemental mercury), water colour paints
Table 5-6: Substances of which one teaspoon or one tablet that can kill a 10kg child
Minimum Potential Dose No of Tablets/Spoonfuls that
Drug
(mg/kg) can Potentially Cause Fatality
Tricyclic antidepressants
 Amitriptyline 15 1–2
 Imipramine 15 1
 Desipramine 15 1–2
Antipsychotics
 loxapine 30–70 1–2
 Thioridazine 15 1
 Chlorpromazine 25 1–2
Antimalarials
 Chloroquine 20 1
 Hydroxychloroquine 20 1
 Quinine 80 1–2
Anti-arrythymics
 Quinidine 15 1
 Disopyrimide 15 1
 Procainamide 70 1
Calcium channel blockers
 Nifidepine 15 1–2
 Verapamil 15 1
 Diltiazem 15 1
Camphor 100 1 teaspoon
Methylsalicylate 200 <1 teaspoon
Theophylline 8.4 1
Narcotics
 Codeine 7–14 1–2
 Hydrocodone 1.5 <1 teaspoon
 Methadone 1–2 1
Oral hypoglycaemics
 Chlorpropamide 5 1
 Glibenclamide 0.1 1
 Glipizide 0.1 1
Podophyllin 25% 15–20 1ml
Pharmacokinetics
Absorption: Paracetamol is rapidly absorbed and peak concentrations
occur within 1–2 hours for standard tablet or capsules and even quicker
(<1⁄2 hour) in liquid preparations. Sustained-release preparations may
continue up to 12 hours and toxicity cannot be assessed using the
normogram.
Distribution: After absorption, paracetamol distributes rapidly with

a volume of distribution of 0.9L/kg. Absorption and distribution are
completed by 4 hours post-overdose with standard-release preparations
and within 2 hours in liquid preparations.
Metabolism and elimination: The half-life of paracetamol in therapeutic

use is 11/2–3 hours. In overdose, the clearance of paracetamol becomes
saturated and the half-life may be >4 hours.
In overdoses, production of a toxic metabolite, N-acetyl-p-

benzoquinonimine (NAPQI), occurs and when conugated with
glutathione, is excreted as a non-toxic conjugate in the urine. As
glutathione is depleted, this reactive metabolite binds covalently to
hepatic macromolecules and leads to cell death.
Determination of severity of paracetamol overdose:

 Dose ingested and assessment of risk
 Paracetamol concentration
 Clinical presentation
Toxic Ingestion
Toxic ingestion is defined as follows:
 Acute single-dose poisoning:
 ≥200mg/kg or 10g (whichever is less) (both paediatric
and adults)
 Repeated supratherapeutic ingestion:
 >24 hours staggered dose:
 In children younger than 6 years or high-risk group: ≥4g or
100mg/kg/day (whichever is less)
 Older than 6 years: 6g or 150mg/kg/day (whichever is less)
 Symptomatic patients:
 This includes patients following ingestion of paracetamol that
presents with repeated vomiting, abdominal tenderness in the
right upper quadrant, or mental status changes
 If an unknown dose has been ingested, one should always err

on the assumption that a potentially toxic amount has been
ingested
 Early toxic ingestion of paracetamol is usually largely
asymotomatic, apart from vomiting and nausea
 Where there are other signs and symptoms early on following
paracetamol ingestion, one should always rule out co-ingestants
associated with the paracetamol (e.g. Panadol Cold®/Panadol
Extra®, etc) or other causes for the signs and symptoms
Factors in Paracetamol Poisoning and Management

The time of acute ingestion is important (i.e. acute, single-ingestion).
This is where serum paracetamol can be done and correlated with the
normogram (see Figure 5.3).
Note that Repeated Supratherapeutic Ingestions of Paracetamol (RSTI)

do not correlate with the normogram.
In estimating the amount ingested, one should always overestimate

rather than underestimate the amount ingested, e.g. after the child has
vomited out or has spilled the paracetamol syrup.
Sustained Released Preparations

There is a potential for delayed absorption in sustained-release
paracetamol formulations. In a single acute ingestion, if more than
200mg/kg or 10g (whichever is less) has been ingested, NAC treatment
should be started immediately. In all cases, serum paracetamol levels
should be taken at 4 hours or more post-ingestion (as with standard
preparations) and repeated 4 hours later. If either level is above the
normogram line, NAC should be commenced or continued. NAC may be
discontinued if both levels fall below the nomogram line.
Co-relating Serum Paracetamol Levels

The normogram is used to risk stratify a patient who has acutely
ingested paracetamol. It is based on the serum paracetamol level taken
at least 4 hours after ingestion. The normogram applies only to once-
off acute oral paracetamol ingestions and is not for cases where there
are repeated ingestions of paracetamol (see Figure 5.4 for repeated
supratherapeutic toxic ingestion management flow chart). Treatment
should start if above the ‘150-line’.
Indications for Admission

 Patient is symptomatic (irrespective of dose)
 If toxic dose is consumed
v Unknown dose taken
 Suspected non-accidental ingestion (irrespective of dose)
v Poor home support (lives alone, inability of caregivers to monitor)
Clinical Symptoms and Signs of Paracetamol Poisoning

 Post-acute ingestion (<24 hours): Asymptomatic to non-specific
gastrointestinal irritation (e.g. nausea, vomiting abdominal pain)
 24–48 hours: Tender hepatomegaly with jaundice
 Day 4–5 post-poisoning: Acute liver and renal failure
Other features: Erythema, urticaria, haemolytic anemia, pancreatitis,
haemorrhage
Investigations in Suspected Paracetamol Poisoning

Serum paracetamol level: Taken 4 hours post-ingestion
PT: Abnormal by 24–36 hours
LFTs: Alanine Aminotransferase (ALT)/Aspartate Transaminase (AST)
begin to rise by 12 hours, peaks at 72–96 hours
Management
 Resuscitation:
 Immediate threats to the Airway, Breathing and Circulation are
extremely rare in isolated paracetamol overdose
 In exceptional cases, massive ingestion causing extremely high
serum paracetamol levels (i.e. >800mg/L) may be associated
with an early decrease in level of consciousness and with lactic
acidosis
 Supportive management is appropriate in such cases, with NAC
administered in routine doses, although prolonged infusions may
be required
 Recovery is usual with supportive care
 Any alteration of conscious state should prompt bedside
testing of the patient’s serum glucose level and correction of
hypoglycaemia
 Presence of hypoglycaemia may be secondary to hepatic failure
and intensive care monitoring is required
Aysmptomatic
Symptomatic (irrespective
of time of ingestion)
Repeated vomiting,
<2 hours 2–8 hours >8 hours right-upper quadrant
post-toxic post-toxic post-toxic abdominal tenderness,
ingestion ingestion ingestion or mental status changes
Activated Measure serum Commence IV NAC

charcoal paracetamol investigations:
1g/kg level within Serum paracetamol levels
4–8 hours post- Glucose
ingestion ALT/AST
INR/PT
Urea/Creatinine
Plot serum Blood gas
paracetamol
level on
normogram
UNDER normogram OVER normogram

(line of probable (line of probable
hepatic toxicity — hepatic toxicity — Admit
150mg/L at 4 hours) 150mg/L at 4 hours)
Continue IV NAC
If symptomatic:
Commence IV NAC and Measure ALT at end
Consider co-
perform investigations if of NAC infusion
ingestions, admit
not done prior:
and investigate
Glucose
ALT/AST
INR/PT ALT ↑
If asymptomatic: Urea/Creatinine
No further medical Blood gas
treatment required
Continue IV NAC
and monitor
ALT Normal
Figure 5.2: Acute accidental paracetamol poisoning management flow chart
500
450 If acetaminophen concentration falls above
400 solid line, hapatotoxicity is PROBABLE
350
300
250
200
Plasma or Serum Acetaminophen Concentration (mcg/ml)
150 (4 hours. 200mcg/ml)

100
90
80
70 If acetaminophen concentration falls between dashed
60 and solid lines, hapatotoxicity is POSSIBLE
50
40
30 (12 hours. 50mcg/ml)
20
10
9
8
7
6
5
4
Continue acetylcysteine therapy when acetaminophen
concentration is on or above dashed line
3
4 8 12 16 20 24
Hours since ingestion
Figure 5.3: Normogram relating plasma or serum acetaminophen concentration and probability
of hepatotoxicity at varying intervals following ingestion of a single toxic dose of acetaminophen.
(Adapted from Clinical Practice Guidelines; Management of Drug Overdose and Poisoning; MOH
Clinical Practice Guidelines 2/2000)
 Decontamination:
 Activated charcoal:
 Activated charcoal (1g/kg or up to 50g) can be given if <2 hours
 May have a role in sustained-release preparations even after 2
hours of ingestion
 Haemoperfusion:
 Limited studies available but charcoal haemoperfusion
may be considered in severe paracetamol poisoning in the
intensive care setting after consultation with the relevant
specialists
 Antidote:
 NAC:
 NAC is the recommended antidote of choice for paracetamol
poisoning and should be administered to all patients judged
to be at risk of developing hepatotoxicity after paracetamol
overdose
 When risk assessment indicates that NAC is required, it is
administered as a three-stage infusion, totaling 300mg/kg
over 20 hours
 IV NAC is supplied as a 20% solution (200mg/ml) in 30ml vials.
It is diluted with dextrose 5% (not in normal saline)
 Note that excessive diluent volume may cause
hyponatraemia and secondary seizures in children while
too highly concentrated a solution may increase the risk of
anaphylactoid reactions
 A concentration of 40mg/ml of NAC in D5% is generally
safe. For older children requiring large loading doses, higher
concentrations up to 55mg/ml may be used
 A loading dose of 150mg/kg over 15 mins followed by 50mg/kg
over the next 4 hours, then 100mg/kg over the next 16 hours
 If hepatic injury is suspected after the 3 infusion stages, NAC
is continued at the rate of the last infusion stage (100mg/kg
each 16 hours or 150mg/kg/24 hours) until there is clinical
and biochemical evidence of improvement
 NAC reduces mortality if commenced late in patients with
established paracetamol-induced fulminant hepatic failure.
In this setting, NAC reduces inotrope requirements, decreases
cerebral oedema and increases the rate of survival by about
30% (Grade C, Level 4)
 Anaphylactoid reactions manifested by rash, wheeze or mild

hypotension occur in 5–30% of patients during the first two
NAC infusions. Management is supportive, with temporary
halting or slowing of the infusion, and administration of
antihistamines (IV promethazine 0.2mg/kg, up to 10mg)
 The occurrence of an anaphylactoid reaction does not
preclude the use of NAC on another occasion if indicated
 Severe life-threatening reactions are very rare, but may occur
in predisposed individuals, such as patients with asthma and
in those who ingested smaller amounts of paracetamol
 Methionine:
 Methionine can considered as an alternative antidote for
paracetamol poisoning especially in the setting of known
allergy to NAC
 It is given orally 50mg/kg/dose (max 2.5g) 4H for 4 doses. It is
associated with more adverse reactions than NAC
 Management of non-accidental toxic ingestions:
 Admission irrespective of levels for non-accidental ingestion
 Serum levels mandatory
 Management of toxicity poisoning accordingly
 Consider multi-drug poisoning:
 4–8 hours: Measure paracetamol levels (at or after 4 hours
post-ingestion)
 Plot paracetamol level on normogram
 Start IV NAC if over normogram at 150mg/L (1,000µmol/L)
at 4 hours (line of possible hepatotoxicity)
Table 5-7: Dosage for children in different weight ranges

Dosage for children weighing <30kg:
 IV NAC 150mg/kg diluted with 3ml/kg of D5% over 15–30 mins, then
 IV NAC 50mg/kg diluted with 7ml/kg of D5% over 4 hours, then
 IV NAC 100mg/kg diluted with 14ml/kg of D5% over 16 hours
Dosage for children weighing 30–50kg:
 IV NAC 150mg/kg diluted with 100ml of D5% over 15–30 mins, then
 IV NAC 50mg/kg diluted with 250ml of D5% over 4 hours, then
 IV NAC 100mg/kg diluted with 500ml of D5% over 16 hours
Dosage for children weighing >50kg:
 IV NAC 150mg/kg diluted with 200ml of D5% over 15–30 mins, then
 IV NAC 50mg/kg diluted with 500ml of D5% over 4 hours, then
 IV NAC 100mg/kg diluted with 1,000ml of D5% over 16 hours
 >8 hours: Commence IV NAC (do not wait for levels)

 Obtain paracetamol levels as possible
 Obtain ALT stat and repeat at the end of IV NAC infusion or
12 hourly, whichever comes first
 If the serum paracetamol level is subsequently found to be
below the normogram line, NAC may be ceased; if above
the line, it should be continued till below and ALT static or
normal
 Obtain FBC (platelet), International Normalised Ratio (INR)
or Prothrombin Time (PT), U/E/Cr, glucose and ABG (if
venous bicarbonate is low) and repeat as indicated
A baseline serum ALT level, international normalised ratio and platelet
count provide useful baseline data for later risk assessments.
 Symptomatic patients (clinical or biochemical):
 Start IV NAC without waiting for levels (even <8 hours) if
symptomatic or has biochemical abnormalities
 Obtain paracetamol levels, ALT/AST, FBC (platelet), INR or PT, U/E/
Cr, glucose and ABG stat
 If symptomatic and paracetamol levels are below the
normogram, consider toxic co-ingestions
 Repeated supratherapeutic toxic ingestion:
 Commence IV NAC (do not wait for levels)
 Obtain paracetamol and ALT/AST levels as soon as possible
 If paracetamol <10mg/L and ALT/AST normal, nil further
treatment, stop infusion
 Obtain INR or PT, U/E/Cr, glucose and ABG (if bicarbonate
abnormal) at admission
 Repeat ALT/AST and serum paracetamol levels at 8–12 hours
 If ALT/AST normal or static and paracetamol <10mg/L, stop
infusion
 If abnormal, continue IV NAC infusion and repeat ALT/AST 12
hourly and investigations as indicated (Grade D, Level 5)
 Unknown time of ingestion:
 Start IV NAC
 Investigations and management are similar to supratherapeutic
repeated dose ingestion
 Severe paracetamol poisoning:
 Hepatocellular necrosis is the major toxic effect of paracetamol
poisoning
 Biochemical evidence of maximal damage may not be attained
until 72–96 hours after ingestion of the overdose
Adults and Children >6 years High Risk Factors* and/or

with no risk factors Children <6 years
Ingested >6g/day or >150mg/kg/day Ingested >4g/day or >100mg/kg/day

(whichever is less) (whichever is less)
Commence IV NAC
INVESTIGATIONS:
 Serum paracetamol levels
 ALT/AST
 Other investigations: Glucose, INR/PT, Urea/Creatinine, Blood gas
ALT Normal Any other results

AND
Serum Paracetamol
<10–20mg/L Admit and Continue IV NAC infusion
Repeat serum paracetamol level

Stop IV NAC infusion and ALT at 8–12 hours
If asymptomatic:
No further medical ALT Normal or Any other results
treatment required decreasing
 Continue IV NAC infusion

No further
If symptomatic:  Monitor ALT 12 hourly
treatment required
Consider co-ingestions, intervals
admit and investigate  Other monitoring and
investigations as indicated
 Refer to specialist
High-risk Groups*
 Regular ethanol consumption >21 units/week in males, 14 units/week in females
 Conditions causing gluthathione depletion — Malnutrition, HIV, eating disorders, cystic fibrosis
 Regular use of enzyme-inducing drugs:
 Anti-epileptics — Carbamazepine, phenytoin, phenobarbitone
 Anti-TB drugs — Isoniazid, rifampicin
 Other drugs — St John’s Wort
Figure 5.4: Repeated supratherapeutic ingestion management flow chart

 Severe liver damage in the context of paracetamol poisoning has

been defined as a peak plasma ALT activity exceeding 1,000IU/L.
For those institutions who do not have ready access to ALTs, AST
may be used instead
 An AST exceeding 1,000IU/L indicates severe liver damage. A more
accurate test for assessing prognosis is the INR or PT test. Acute renal
tubular damage and necrosis may occur, usually in association with
hepatocellular necrosis, but rarely in the absence of major liver damage
 Resuscitation and intensive care monitoring is required
 One should consider need for transfer post-stabilisation to a liver
transplant unit
Indicators of Severe Paracetamol Poisoning

 Metabolic:
 Metabolic acidosis (pH <7.3 or bicarbonate <18) despite
rehydration
 Hypotension despite adequate fluid resuscitation
 Hypoglycaemia
 CNS:
 Encephalopathy or signs of rasised ICP
 Liver function/coagulopathy:
 INR >2.0 at or before 48 hours or >3.5 at or before 72 hours
 Consider measuring INR every 12 hours
 Peak elevation occurs around 72–96 hours
 LFTs are not good markers of hepatocyte death
 Renal:
 Renal impairment (creatinine >200mcg/mol/L)
 Monitor urine output
 Serial U/E/Cr
 Consider haemodialysis if >400mcg/mol/L
SALICYLATE POISONING
Epidemiology
Salicylate poisoning is relatively uncommon in Singapore. Accidental
ingestion in children can occur. This usually involves adult medication.
Besides aspirin tablets, there are less obvious forms of salicylates such
as bismuth salicylate which is a common ingredient in over-the-counter
anti-diarrhoeal agents (e.g. Pepto-Bismol®, Kaopectate®). Methyl
salicylate (oil of wintergreen) is a common ingredient of Chinese herbal
medications, as well as liniments and ointments used in the management
of musculoskeletal pain. Chronic dermal application of some salicylate-
containing products can produce systemic salicylate toxicity.
Pharmacokinetics
 The type of formulation (e.g. liquid, effervescent, extended-release,
enteric-coated) affects the degree of absorption
 With therapeutic dosing of regular aspirin tablets, peak plasma
concentrations are usually achieved 15–60 mins after ingestion. Peak
concentrations following ingestion of extended-release or enteric-
coated preparations typically occur between 4–14 hours after ingestion
 Peak concentrations in overdose may be delayed as a result of
pylorospasm or bezoar formation
 Exhibits saturation kinetics in overdose in high doses; half-life of
salicylate is greatly increased (may be up to 30 hours)
 For children on chronic salicylate therapy, even a slight change in
dose may result in a great increase in plasma concentration
Table 5-8: Types of salicylate poisoning

Salicylate Conversion Type of Use Remarks
Factor
Aspirin 1.00 Oral, suppositories
Bismuth 0.50 Oral Pepto-Bismol®, Maalox Total
subsalicylate Stomach Relief®, Kaopectate®
contain 262mg (regular
strength) or 525mg (extra-
strength) of bismuth salicylate
per 15ml; which yield 8.7 or
17.5mg/ml of aspirin equivalent
Choline magnesium 1.30 Oral
salicylate
Choline salicylate 0.75 Oral
Magnesium 1.21 Oral
salicylate
Methyl salicylate 1.18 Dermal, flavouring
agent
Oil of wintergreen 1.40 Dermal, flavouring Contains methyl salicylate 98%
agent w/w, 1ml = 1.4g aspirin
Salicylic acid 1.30 Dermal >6% may cause tissue
destruction on contact or
ingestion
Salsalate 1.40 Oral
Sodium salicylate 1.13 Oral
Trolamine salicylate 0.63 Dermal
 Salicylic acid (HS) is a weak acid that exists in a charged

(deprotonated) and uncharged (protonated) form: H+ + sal- <—> HS
 Treatment of salicylate intoxication is directed toward increasing
systemic and urine pH and driving the above reaction to the left,
‘trapping’ the salicylate anions in the blood and urine (by preventing
back-diffusion across the renal epithelium into the systemic circulation)
Admission for Further Evaluation and Management

 All symptomatic patients should be admitted irregardless of dose
ingested, e.g. haematemesis, tachypnoea, hyperpnoea, dyspnoea,
tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion
 All patients with known or suspected suicidal intent or non-accidental
ingestion (e.g. child abuse) irrespective of amount ingested
 Poor home support (lives alone, inability of caregivers to monitor)
 If asymptomatic and had suspected toxic ingestion
 Acute ingestion of aspirin or aspirin equivalent of an amount that
exceeds 150mg/kg or 6.5g, whichever is less
 Ingestion of oil of wintergreen (98% methyl salicylate) if:
 Patients younger than 6 years, and greater than a lick or taste
 Patients 6 years and older, >4ml
Determination of Severity
In the initial assessment of the severity of toxicity the four following
areas should be considered:
 Dose ingested
 Salicylate concentration
 Clinical grading of toxicity
 Acid-base grading of severity
Toxic Ingestion
Chronic toxicity can develop from doses of 100mg/kg/day. Patients with
cirrhosis, low protein states or renal impairment develop toxicity with
lower doses.
Table 5-9: Assessment of acute salicylate intoxication based on dose ingestion (Temple, 1981)
Ingested Dose (mg/kg) Estimated Severity
<150 No toxic reaction expected
150–300 Mild to moderate toxic reaction
300–500 Serious toxic reaction
>500 Potentially Lethal
 The triad of salicylate poisoning consists of hyperventilation, tinnitus,
and gastrointestinal irritation (classic salicylism)
 Paediatric patients may not manifest respiratory alkalosis
 In children: Hyperventilation, dehydration and neurological
dysfunction are greater in chronic overdoses compared with single
acute ingestions
 Pyrexia: Mild pyrexia is common and is due to increased metabolic
activity
 Gastrointestinal effects: Nausea and vomiting are common.
Less common are epigastric pain and haematemesis. Vomiting
contributes significantly to electrolyte imbalance and dehydration.
Aspirin, especially enteric-coated formulations, are known to develop
concretions and bezoars in the stomach and act as a direct GI irritant
leading to nausea, vomiting, and abdominal pain

CNS effects: CNS symptoms can occur with declining salicylate
concentrations because of CNS trapping of ionised salicylate.

 Others: Non-cardiogenic pulmonary oedema and renal failure occur
occasionally and always in association with other signs of significant
poisoning
Biochemical Presentation
In children with salicylate poisoning, plasma concentrations 6 hours
after an acute overdose very roughly correlate with toxicity as follows:
Severity of Acute Toxicity Serum Concentration (Post-6 hours)

Mild Toxicity 30–50mg/dL
Moderate Toxicity 50–70mg/dL
Severe Toxicity >75mg/dL
Table 5-10: Clinical grading of salicylate toxicity

Severity Clinical features
Mild Nausea, vomiting, tinnitus
Moderate Confusion, hyperventilation
Severe CNS: Hallucinations, seizures, coma, cerebral oedema
Respiratory: Pulmonary oedema
Salicylate Concentration Conversion Factor:

mg/dL x 0.0072 = mmol/dL
mmol/dL ÷ 0.0072 = mg/dL
Metabolic acidosis: Major feature of salicylate poisoning as a result of

‘uncoupling of oxidative phosphorylation’ which leads to:
 Increase in metabolic rate
 Increased oxygen consumption
 Increased CO2 formation
 Increased heat production
 Increased glucose utilisation
This may be exacerbated by:

 Accumulation of organic acid metabolites
 Starvation and dehydration induced ketosis
 Lactic acidosis
Glucose Metabolism
Hypoglycaemia: Intracellular > extracellular
May occur due to:
 Increased peripheral glucose demand
 Increased rate of tissue glycolysis
 Impaired rate of glucose synthesis
Note that tissue may be lower than plasma glucose.
Hyperglycaemia: May occur due to increased glycogenolysis.

Hypokalaemic patients or patients with total body potassium depletion
are unable to produce an alkaline urine.
Coagulation effects: Salicylates competitively inhibit Vitamin

K-dependent synthesis of factors II, VII, IX and X, reflected in an increased
INR. A prolonged PT, usually more than twice normal, occurs predictably
in significant overdoses. Vitamin K will correct the PT rapidly. As in
therapeutic use, aspirin, but not other salicylates, impairs platelet
aggregation.
Hepatic effects: Rises in transaminases occur not uncommonly, are

usually not clinically significant, and resolve over several days.
Differential Diagnosis
 DKA (glucose high but in salicylate poisoning tends to be low)
 Severe dehydration/gastroenteritis with metabolic acidosis
 Sepsis syndrome
 IEM
 Other forms of poisoning such as ethylene glycol or ethanol intoxication
Management of Salicylate Poisoning

 The goals of treatment of salicylate intoxication are to correct fluid
and electrolyte imbalance and to enhance excretion
Table 5-11: Biochemical investigations

Biochemical Investigations Timing Comments
Full blood count Baseline
Coagulation profile Baseline Any coagulopathy should be
corrected with IV Vitamin K
Urea, calcium, creatinine, Baseline and repeat as Keep K in the optimal range of
glucose necessary in moderate to 4–4.5mmol/L
severe salicylate poisoning
Arterial blood gas Baseline and repeat as
necessary in moderate to
severe salicylate poisoning
Urinalysis and urine pH Baseline and repeat as Keep urine pH between 7.5–8
necessary in moderate to Titrate bicarbonate infusion as
severe salicylate poisoning necessary
Plasma salicylate 6 hours post-ingestion Repeat salicylate level every
concentration 2 hours until levels declining
then as necessary
Table 5-12: Acid-based grading of severity of salicylate toxicity

Stage Blood pH Urine pH Comment
I >7.4 >6 Respiratory alkalosis
Increased urinary excretion of NaHCO3, K+
& Ca2+
II >7.4 <6 Metabolic acidosis with compensating
respiratory alkalosis
Intracellular K+ depletion, urine H+
excretion
III <7.4 <6 Severe hypokalaemia and metabolic
acidosis
 Treatment of salicylate intoxication is directed toward increasing

systemic and urine pH by the administration of sodium bicarbonate
Salicylate excretion depends on the following factors:

 Dose of salicylates
 Blood and urine pH: An alkaline urine (pH >7.5) dramatically
increases salicylate clearance by ion-trapping
 Potassium concentration: In the presence of hypokalaemia, urine
alkalinisation is impossible
 Hypokalaemia may be noted only when the serum pH is corrected
as the acidosis may mask severe potassium depletion (particular
common in chronic poisoning)
 Pre-existing liver or renal failure
Resuscitation
 Airway:
 Intubation of the salicylate-poisoned patient can be detrimental
and should be avoided unless necessary
 If intubation is necessary for severe obtundation, hypotension,
hypoventilation, or severe metabolic acidosis, ensure
appropriately high minute ventilation and maintain alkalaemia
(via serial blood gas analysis)
 Consider haemodialysis for patients who require intubation
 Breathing:
 Supplemental oxygen should be administered as needed.
Pulmonary oedema and acute lung injury may occur and should
be treated with oxygen and if available non-invasive ventilation.
Intubation with positive end-expiratory pressure (PEEP) may be
necessary, but should be avoided if possible (Grade D, Level 5)
 Circulation:
 IV fluids should be administered as necessary to replace
insensible fluid losses (11/2–2 times maintenance) from
hyperpyrexia, vomiting, diaphoresis, and elevated metabolic rate
 There should be judicious administration of fluids in presence of
suspected pulmonary oedema or cerebral oedema
 Supportive treatment:
 Supplemental glucose:
 Salicylate intoxication may decrease CNS glucose levels
despite a normal peripheral glucose level
 Supplemental glucose should be given to patients with altered
mental status regardless of serum glucose concentration
 Potassium repletion:
 Hypokalaemia, if present, must be treated aggressively as it
results in ineffective urine alkalinisation
 Supplemental potassium should be given to maintain serum
4–4.5 unless renal failure is present
GI Decontamination
 Patients with known or suspected acute salicylate overdose should
receive gastrointestinal decontamination with activated charcoal
irrespective of the suspected time of ingestion
 MDAC should be administered every 4 hours for 24 hours in a dose of
1g/kg (max 50g) until symptoms have resolved and plasma salicylate
concentration is <30–40mg/dL
 However, note that gastric irritation, nausea and altered mental
status all combine to put the salicylate-poisoned patient at
substantial risk for aspiration
Enhanced Elimination
 Alkalinisation:
 Alkalinisation with sodium bicarbonate (i.e. urinary and serum
alkalinisation) is an essential component of management of the
salicylate-poisoned patient
 Alkalaemia from respiratory alkalosis is not a contraindication to
sodium bicarbonate therapy
 In severe salicylate poisoning with systemic pH <7.4, give a
slow bolus of 1–2mEq/kg/hr of NaHCO3. Bicarbonate should be
added to the main drip with IV infusion rates of starting at a rate
of at least 11/2–2 times the maintenance fluids and adjusted to
maintain a urine output of 1.5–2ml/kg/hr with urine pH 7.5–8
Haemodialysis
 Haemodialysis is the definitive treatment to prevent and treat
salicylate induced end-organ injury
 The indications for haemodialysis are primarily clinical and include:
 Severe acidosis or hypotension refractory to optimal supportive
care (regardless of absolute serum aspirin concentration)
 Evidence of end-organ injury i.e. seizures, rhabdomyolysis,
pulmonary oedema
 Renal failure
 Plasma salicylate concentration >100mg/dL (7.2mmol/L) in the
setting of acute ingestion or plasma salicylate concentration
>60mg/dL (4.3mmol/L) in the setting of chronic salicylate use
 Consider for patients who require endotracheal intubation
unless that indication for mechanical ventilation is respiratory
depression secondary to a co-ingestant
Post-stabilisation Monitoring
 Salicylate-poisoned patients require frequent laboratory monitoring
to assess both clinical status and response to therapy. A salicylate
level and blood gas should be drawn 2–3 hourly until both the
plasma salicylate level is falling and the acid-base status is stable or
improving for 2 consecutive readings
 Aim to achieve a urine pH of 7.5–8.0:
 Adjust the rate of sodium bicarbonate infusion if the urine pH
remains <7.5
 Check urea and electrolytes every 3–4 hours, the serum potassium
should be kept in the range 4.0–4.5
 Total/ionic calcium should be checked and managed as it may be
low due to bicarbonate therapy/respiratory alkalosis
Late Complications, Prognosis — Follow-up

 Long-term sequelae (neuropsychiatric) are a significant risk in
severe poisonings due to the potential for damage from acidosis,
hypoglycaemia and hypoxia
 Risk factors for neuropsychiatric sequelae or death:
Patient epidemiology: Extremes of age, chronic toxicity
Clinical: Seizures, coma on admission
Biochemical: Low pH, low pO2, low K
Bibliography
1. Ministry of Health. Clinical Practice Guidelines: Management of Drug Overdose and
Poisoning; MOH Clinical Practice Guidelines 2/2000. Singapore: Ministry of Health; 2000.
MANAGEMENT OF AGITATED AND

VIOLENT PATIENTS
INTRODUCTION
Violent and agitated behaviour can be the manifestation of many
psychiatric as well as medical conditions. It is often not essential and in
fact not possible to establish and manage the cause of the agitation and
aggression before managing the behaviour.
Risk factors for violence and aggression

 Patients with Psychosis or bipolar affective disorder
 Children with NAI or have reason to fear for their own safety due to
their own trauma
 Patients with disruptive behaviour disorders like conduct disorder,
ADHD, impulsivity etc
 Patients who have misused substances/acute intoxication.
 Children with high levels of anxiety can also present with agitation
and violent behaviour
Issues should be taken into consideration when managing

behavioural disturbance in children and adolescents:
 All aggressive and violent children and adolescent should have a
comprehensive diagnostic evaluation.
 Physical restraint can be emotionally traumatic for children, hence
behavioural strategies or seclusion should be preferred.
 First-line management — De-escalation
 Second-line management — Seclusion and restraint
 Third-line management — Use of oral medications such as
benzodiazepines and antihistamines. If there is a history of psychotic
illness, intramuscular injection of haloperidol can be used.
 The lowest possible dose of medications should be used.
 A senior medical staff should be involved in decision-making for
using medications.
If the child or adolescent continues to be unmanageable, the child

psychiatrist on call must be consulted and if safety is a concern,
admission to psychiatric inpatient unit (IMH) should be considered.
Verbal de-escalation techniques when a child is restrained

 Talk to the child
 Use a calm space
 Listen to the child
 Acknowledge his feelings of anger.

 Set time limits
 Motivate him — “ I want you to calm down”, “I want you to help me to
calm you down”.
 Use relaxation techniques- ask the child to take deep breaths and
relax his muscles. Demonstrate this to the child.
 Distract the child by changing the focus to positive
Rapid tranquillisation is defined as ‘the use of psychotropic medication

to control agitation, threatening or destructive psychotic behaviour’
Aims and objectives of rapid tranquilisation

 reduce the risk of physical harm to other patients, staff and the
patient
 reduce the distress to the patient caused by acute agitation
 The primary objective of rapid tranquilisation is to calm the patient
and not sedate them. However, sometimes sedation is unavoidable.
What to watch and monitor?

 Paradoxical reactions, including hyperactive/aggressive behaviour
have been occasionally reported with benzodiazepine use. This may
be more likely to occur in children/adolescents and patients with
developmental delay or organic brain syndromes.
 The most serious acute complication of benzodiazepines remains
respiratory depression.
 Children and adolescents are more likely to be antipsychotic-naïve and
there is a greater risk of dystonic reaction and other acute side effects.
 The most commonly encountered problems (can happen even after
a single dose) after administration of Haloperidol are:
1) acute dystonia,
2) oculogyric crisis (type of acute dystonia which includes
blepharospasm, periorbital twitches, and protracted staring
episodes), and
3) akathisia.
The parameters to be monitored when medications are given to manage

agitated and violent behaviour are
 blood pressure
 pulse
 respiratory rate
 temperature
 oxygen saturation
Table 5-13: Medications

Suggested ORAL medications: Suggested intramuscular injections
Children 6–12 years old: CONSULT CHILD PSYCHIATRIST
Oral Promethazine 0.5–1mg/kg stat (max BEFORE GIVING ANY I.M.
50mg) INJECTIONS
Oral Hydroxyzine 0.6mg/kg stat Children 6–12 years old:
Oral Diazepam 0.2–0.3mg/kg stat (max IM Promethazine 0.5–1mg/kg/dose stat
10mg)* (max 50mg)
IM Lorazepam 0.02mg/kg/dose-0.06mg/kg/
Above 12 years old: dose (max 1–2mg)
Oral Promethazine 12.5–25mg stat If psychotic/history of psychosis:
Oral Hydroxyzine 12.5–25mg stat IM Haloperidol 1–3mg stat (max 0.15mg/
Oral Lorazepam 1–2mg stat* kg/day)
Above 12 years old:
IM Promethazine 12.5–25mg stat
IM Lorazepam 0.5–1mg stat
If psychotic/history of psychosis:
IM Haloperidol 2.5–5mg stat
Conclusion
 Always give the child an opportunity after the incident to address
any concerns due to the whole incident.
 Remember to talk to parents to explain the management.
 A root cause analysis of how the violence started in the first place
would produce valuable information.
 Concerns raised must be followed up and the child may need referral
to specialists who deal with the issues in detail.
Bibliography
1. KKH Drug formulary
2. Ellison JM, Blum NR, Barsky AJ (1989) Frequent repeaters in a psychiatric emergency
service. Hospital & Community Psychiatry; 40: 958–960.{(in Pereira.S, Gard.D and
Brandford. D , Rapid Tranquilisation of acutely disturbed patient, Royal college of
Psychiatrists, CPD online, May 2009.(www.rcpsych.ac.uk)}
3. Pereira.S, Gard.D and Brandford. D , Rapid Tranquilisation of acutely disturbed patient,
Royal college of Psychiatrists, CPD online, May 2009.(www.rcpsych.ac.uk)
MANAGEMENT OF SELF-HARM AND

SUICIDAL BEHAVIOUR IN ADOLESCENTS
It is not uncommon for troubled adolescents to be referred to KKH for

self-harm and suicidal behaviour. Deliberate self-harm (DSH) is also
known as non-suicidal self-injury (NSSI). The motivations for carrying
out self-harm are often multiple and certainly multi-factorial, with
interpersonal conflicts and disputes being frequent precipitating factors.
Individuals who have impulsive traits, poor frustration tolerance, anxiety,
depression, conduct disorders and borderline personality traits are more
predisposed to engaging in self-harm behaviour.
Self-harm is a set of maladaptive behaviour used to cope with intense

and negative feelings, and could range from cutting, overdosing,
peeling/scratching of skin, hitting and biting of self etc. Individuals
with self-harm behaviour are not suicidal in intent per se but the risk of
suicide is elevated in this group of patients: 60 to100 times higher than
in the general population. As the frequency of self-harm increases, so
do the risk of suicidal thoughts and plans. The recurrence of self-harm
behaviour also increases with a past history of self-harm.
Self-harm typically happens when other means to self-soothe failed or

the individual does not know how to do so. A common misconception is
that self-harming adolescents are seeking attention. They are not.
Observe the following when attending to individuals who self-harm:

 Attend to the injury, and assess whether surgical intervention
or superficial first-aid is required. Be mindful to check for cuts in
obscure locations on the body such as thighs. Self-cutting in the
inner thighs could be a sign of prior or existing sexual abuse.
 Even if surgical intervention is not needed, decide whether admission

is required especially those individuals coming from complex family
and social backgrounds, when there is concomitant high suicide risk or
when the adolescent is visibly distressed over an ongoing stressor that
would not go away any time soon. Do admit the adolescent if you are
uncertain as it is better to err on the side of caution.
 If admission is not required, consider referring the patient to the
Psychology Service outpatient clinics. Many individuals with self-
harm behaviour benefit from Cognitive Behavioural Therapy (CBT)
and SSRI antidepressants.
 Stay calm as the attending doctor. Do not judge or criticise the

behaviour of the adolescent. Let them know that even though you
cannot help solve their problems, you or someone in the hospital/
clinic could lend a listening ear.
 If there is a chance you are able to engage the adolescent in greater
depth, do use the HEADSS assessment to assess in greater details
presence of adverse psychosocial factors. This screen can be used to
guide further management like referrals to other services.
Adolescents who self-harm do not stop the behaviour overnight. Many

continue to do so for years before they either reduce the frequency
of self-harm or stop completely. Improvements in self-harm is likely
attributed to their developing maturity and self-esteem with time.
Fortunately, suicide rate for the youth in Singapore remains low at about
1.3 per 100,000 (2011) compared to other countries. Reasons behind
the low rate include availability of youth outreach, effective healthcare
and emergency response systems, low poverty rate and high education
attainment, firearms ban and strict anti-drug policies. However, there are
still individuals who choose suicide to resolve their problems. Up to 70%
of suicide completers had a mental disorder prior to suicide.
About 30% of completed suicides have a past history of suicide

attempts. Repeat suicide attempt rates are high: 16% at 1 year and 23%
at over 4 years.
Suicide rate from 2006 to 2011

No. of suicides per 100,000
12 2.50
Age 10–19
Age 10–19 suicides
10 2.00 Suicides (Male)

8
1.50 Age 10–19
6
1.00 Suicides (Female)
4
0.50 No. of Suicides
2 Per 100,000
0 0.00
2006 2007 2008 2009 2010 2011
Year
Source: IMH, 2012.

Suicide risk assessment

The major risk factors for suicide among adolescents (adapted from
Cash and Bridge (2009)) are as follows:
 Previous suicide attempt
 Psychopathology
 Especially major depressive disorder, bipolar disorder, conduct
disorder, and substance use disorders
 Psychiatric co-morbidity, especially the combination of mood,
disruptive, and substance use disorders
 Dysfunctional personality traits (especially antisocial, borderline,
histrionic, and narcissistic traits)
 Feelings of hopelessness and worthlessness
 Impulsive aggression: the tendency to react to frustration or
provocation with hostility or aggression
 Family factors
 A family history of depression or suicide
 Loss of a parent through death or divorce
 Family discord
 Physical and sexual abuse
 Lack of a support network, poor relationships with peers and
feelings of social isolation
 Suicidal intention (in terms of motivation and planning such as
writing suicide note, last acts, attempts to conceal suicide)
 Availability of lethal means and lethality of method used
 Lack of relief after being saved
 Having been exposed to suicide (e.g., suicide or suicide attempt in
family members or friends; media reporting)
 Gender (Males age 15–19 years) and ethnicity (Indians and Chinese)
It has been shown that psychiatrists were not better than general
physicians in predicting suicide. Hence possessing the necessary
knowledge and skills in performing an adequate suicide risk assessment
is extremely helpful in guiding your management of the suicidal patient.
Management of suicidal patients in the ward

 Commence on Monitoring/Observation Record Chart
 Hourly observation on: — whereabouts of patient
— what is patient doing
 Referral to Child Psychiatrist on duty
 Nurse in a bed visible to nurses and nearest to nurses’ station
 Curtains open at all times
Table 5-14: Management of suicidal patients at KKH Children’s Emergency

PATIENT’S CONDITION OFFICE HOURS AFTER OFFICE HOURS
 Suicidal patients  Call our KKH CAMWS Child  Low suicide risk referral to KKH CAMWS
 who are cleared of Psychiatrist on-call and discuss can be done using the referral form
medical concerns, e.g. management plan. provided. Referral to MSW to follow-up on
non-toxic overdoses, minor  Low suicide riskchild case as well. Parents must still ensure close
lacerations (not requiring psychiatrist may recommend: supervision, accept responsibility for safety
T&S or post T&S), • An early follow up appointment and for bringing the child for follow up.
OR at SOC: Child Guidance Clinics  High suicide risk or risk assessment is
 who have only psychiatric (CGC) or at CAMWS, depending uncertainpatient should be referred
symptoms without medical on whether child has previous to IMH A&E for suicide assessment. The
issues. contact with either service. need for admission is dependent on IMH
• Parents must be willing to assessment and not by KKH.
ensure close supervision, accept  If highly suicidal, the patient should be
responsibility for safety and for sent in an ambulance (some parents may
bringing the child for follow up. not be able to bring patient to IMH or are
• Referral to MSW to follow-up on ambivalent about IMH referral, both of
case as well which may cause unnecessary delay).
 High suicide risk child • Inform IMH Registrar on-call about transfer
psychiatrist may recommend to the A&E for assessment.
referral to IMH A&E (via  If parents refuse to go IMH A&E, consult
ambulance). IMH Registrar/Child Psychiatrist on-call
• Inform IMH A&E who would then be able to advice on
patient’s management.
• The case manager of CAMWS should be
informed by CE the next working day at
8am so that he/she can follow-up with
clinic appointment booking and other
necessary arrangements if any.
 Suicidal patients  Resuscitate and stablise as

 with medical/surgical necessary.
concerns, e.g. toxic  Admit to KKH with suicide
ingestions, surgical precautions (see below)
wounds requiring operative Please highlight this in
exploration/repair the admission notes and
OR inform the admission and
 unable to rule out organic nursing staff to allow the
pathlogies, i.e. requiring necessary bed and staffing
inpatient monitoring and requirments to be prepared.
management.
Useful Numbers:
IMH operator: 6389 2000 (24 hours)
IMH/CGC Clinic Appointment Call Centre: 6389 2200 (8am–6pm)
KKH CAMWS Case Manager/Admin: 6394 8599 (8am–5.30pm)
 Remove hand-rub from the foot of bed

 Accompany to toilet/bathroom by nurses/parents/caregivers
 Not allowed out of the ward unless accompanied by the parents/
caregivers
 Upon consulting the Child Psychiatrist on duty and if the decision
is to transfer to IMH (adolescent still at high risk for suicide but
otherwise medically stable), ward team to initiate referral to IMH
 Remove suicide precaution if the adolescent is no longer at high
suicide risk and upon instruction by the reviewing child psychiatrist
Bibliography
1. Chia BH, Too Young to Die: An Asian Perspective on Youth Suicide, Jan 1999.
2. Spirito A, Esposito-Smythers C (2006). Attempted and completed suicide in adolescence.
Annual Review of Clinical Psychology, 2:237–266.
3. Owens D (2002). Fatal and non-fatal repetition of self-harm: Systematic review. British
Journal of Psychiatry, 181:193–199.
4. Cash S, Bridge J (2009). Epidemiology of youth suicide and suicidal behaviour. Current
Opinion in Pediatrics, 21:613–619.
208
GENETICS
THE DYSMORPHIC CHILD

The word ‘dysmorphic’ refers to an unusual appearance, usually of the
face. A dysmorphic child may present with the following problems:
 One or more birth defects or malformations, e.g. cleft lip/palate
or CHD
 Developmental delay or intellectual disability
 FTT or obesity
 Short or tall stature
 Behavioural problems, e.g. ADHD
WHY IS IT IMPORTANT TO MAKE A DIAGNOSIS FOR A

DYSMORPHIC CHILD?
In most situations, having a diagnosis for a dysmorphic child does
not mean that there is a specific intervention or treatment. Why, then,
should we try to come to a diagnosis? Having a specific diagnosis:
 Makes available to the parents and doctors all the accumulated
knowledge about the condition
 Gives information about the possible complications, allowing early
detection, treatment and possibly prevention of complications
 Gives information about prognosis and risk of recurrence
 Gives families the option to access relevant support groups
 Facilitates participation in research into identification of causative
genes and therapeutic options
HISTORY
 Pregnancy:
 Previous pregnancy losses
 Maternal illnesses during the pregnancy, e.g. fever or rash
 Exposure to medications, alcohol, cigarette-smoking, or
recreational drugs
 Results of prenatal tests, e.g. ultrasound scans, amniocentesis
 Perinatal:
 Details of the birth, including evidence of polyhydramnios,
oligohydramnios or fetal distress, gestation at birth, mode of
delivery
Genetics 209
 Birth-weight, length and head circumference of the baby at birth

 Condition of the baby soon after birth, including evidence of
respiratory distress, feeding problems and neonatal hypoglycaemia
 Developmental:
 Early developmental milestones
 Developmental regression
 Formal developmental, hearing or vision assessments
 Behaviour
 Sleep patterns, e.g. frequent nocturnal awakening and
fragmented sleep in children with Smith-Magenis syndrome
 Personality, e.g. gregarious personality in Williams syndrome
 Medical:
 Thorough list of malformations present
 Medical problems, e.g. seizures
 Family:
 A three-generation pedigree, noting consanguinity, miscarriages,
stillbirths and deaths of siblings
CLINICAL EXAMINATION
 Overall appearance (gestalt)
 Facial appearance:
 Shape of head and face
 Spacing of eyes (hyper- or hypotelorism), length of palpebral
fissures, upslanting or downslanting palpebral fissures
 Size and shape of nose and mouth
 Shape and position of ears
 Proportion of limbs, joint contractures, joint hypermobility
 Hands and feet: Size, shape, number of digits, nails
 External genitalia
 Skin changes, e.g. hyperpigmented or depigmented lesions
 Birth defects, e.g. cleft lip
 Cardiovascular examination
 Abdominal palpation for organomegaly
Minor Anomalies
 These are defined as physical features present in <5% of the general
population, which are of no clinical significance in themselves
 They may be clues to the underlying diagnosis, especially if >3 are
present together
 They are most common in the face, external ears, hands and feet
 They may be present as a familial trait. Parents and siblings should be
examined before ascribing significance to a particular anomaly
Objective Measurements
 Height, weight and head circumference
 Other measurements that should be taken depend on the diagnosis
being considered, e.g. measuring arm span, upper-to-lower-segment
ratios when considering Marfan syndrome
 There are standard charts for the normal measurements at different ages
Photographs are Useful in a Number of Ways

 If the child is seen for the first time in late childhood or adolescence,
reviewing baby and early childhood photographs may help in
making the diagnosis, especially with syndromes in which the
dysmorphic features become less apparent with age,
e.g. Beckwith-Wiedemann syndrome
 Photography at the time of clinical assessment, with parental
consent, serves as an important part of the medical record. If the
child is undiagnosed, the photographs can be shown to fellow
geneticists for their opinion
MAKING A CLINICAL DIAGNOSIS

Gestalt — Some diagnoses are made based on the overall appearance
of the patient, e.g. the way that most people can recognise a child with
Down syndrome.
Pattern recognition — An uncommon malformation or combination
of anomalies may point to a particular diagnosis or group of conditions.
The next step is to compare the clinical findings and history with
those expected in the syndrome being considered. Several textbooks
describe many of the syndromes and include photographs that can be
used for comparison.
Computerised database search — Which then suggests possible
diagnoses, from the over 3,000 identifiable syndromes which have
been reported. Photographs are usually available for comparison with
the patient. An example of such a computerised database is POSSUM
(Pictures Of Standard Syndromes and Undiagnosed Malformations).
Training and experience are needed to use these databases effectively.
Defer assigning a specific diagnosis rather than assigning an incorrect

diagnosis because labels, once applied, are hard to remove. An incorrect
diagnosis also leads to inappropriate counselling and stigmatisation.
Using such terms as ‘funny-looking kid (FLK)’, ‘elfin facies’ or ‘happy

puppet’ is not acceptable today, as they have taken on unfavourable
connotations.
Genetics 211
LABORATORY INVESTIGATIONS
Generally, ‘genetic’ investigations are labour-intensive and expensive.
Thus, they should be ordered judiciously.
Cytogenetics/Chromosome studies
 Standard banded karyotype:
 To be visible on a standard karyotype, a chromosome deletion or
duplication probably involves more than five million bases of DNA
 A high proportion of genes are involved in the development and
functioning of the brain, thus a child with a cytogenetically visible
chromosome abnormality is likely to have developmental delay
in association with other malformations, rather than an isolated
congenital malformation, e.g. an isolated CHD
 FISH:
 This technique is most commonly applied in the diagnosis of
microdeletion syndromes, e.g. Prader-Willi/Angelman syndromes,
deletion 22q11 syndromes, Miller-Dieker syndrome, and Williams
syndrome where the chromosome deletion is generally too small
to be seen on a standard karyotype
 Chromosomal microarray analysis (CMA):
 This is a DNA-based method of measuring gains and losses of
DNA throughout the human genome and is able to identify
chromosomal abnormalities, inclduding submicroscopic
abnormalities that are too small to be detected by conventional
karyotyping. It is recommended as the first tier test in the genetic
evaluation of infants and children with unexplained intellectual
disability, multiple congenital anomalies or autism spectrum
disorder and has a diagnostic yield of 10–15%.
 Practical points:
 For standard karyotype and/or FISH studies on peripheral blood,
send 3–5mls blood in a sodium heparin tube (green-topped
Vacuette) to the cytogenetics laboratory.
 For chromosomal microarray analysis, send 3–5mls of blood in an
EDTA tube (purple-topped Vacuette) to the DNA laboratory
 Blood for cytogenetics investigations should be drawn using
sterile technique
Molecular/DNA Studies
 Molecular studies are not necessary if the diagnosis is clinically
unambiguous, e.g. in Marfan syndrome, diagnosis is based on clinical
criteria (Modified Ghent diagnostic nosology)
 Indications for undertaking molecular studies include:

 When the diagnosis is not clear clinically
 When the parents are at risk of a second affected child and would
like prenatal diagnosis
 Potential limitations of molecular studies:
 Genetic heterogeneity of a syndrome, i.e. more than one
gene involved, e.g. in tuberous sclerosis, where mutations in
at least two genes TSC1 (chromosome locus 9q34) and TSC2
(chromosome locus 16p13.3) have been identified
 Inability to identify all mutations in a gene, e.g. in Marfan
syndrome, in which there are many mutations possible in the
FBN1 gene, some unique to only a few families
 Practical points:
 For molecular/DNA studies, send 3–5mls of blood in an EDTA
tube (purple-topped Vacuette) to the DNA laboratory
 A completed consent form must accompany requests for
molecular/DNA studies
Biochemical/Metabolic Laboratory Testing

 Storage disorders, e.g. the mucopolysaccharidoses: Urine
glycosaminoglycans (GAGs)
 Peroxisomal disorders, e.g. Zellweger syndrome: Plasma very long
chain fatty acids (VLCFAs)
AFTER THE DIAGNOSIS IS MADE

When informing parents about the diagnosis, special points to note
include:
 Enough time set aside by the clinical staff
 Meeting in a quiet and private place
 Both parents should be present
Often, it is a time of ambivalence for the parents. While they may be

relieved that there is finally an explanation for all the problems their
child has had, there is also understandably a sense of loss and grief, as
they may feel that they have ‘lost’ a normal child. Referral to a social
worker or even a psychologist may be necessary.
A multi-disciplinary approach is often required to address the individual

medical problems the child may have. Besides the medical aspects,
attention must also be paid to the social and psychological problems
the child and his family may face. If there are relevant support groups,
Genetics 213
e.g. Down Syndrome Association of Singapore, contact details should be

made available.
WHAT IF NO DIAGNOSIS IS IDENTIFIABLE?

In such situations, although no underlying cause is identified, the
individual medical and developmental problems should receive
appropriate attention and management.
Further diagnostic options available to the clinician are:

 Showing photographs of undiagnosed patients to fellow geneticists.
Advances in information technology have made international
expertise more readily available
 Following the patients over time. In some syndromes, the physical
features become more apparent with age. Furthermore, new
syndromes may be described and new diagnostic tools become
available. With the passing of time, a previously undiagnosed
syndrome may become clear
CONCLUSION
The approach to the diagnosis of a dysmorphic child is based on a
systematic approach of history-taking and clinical examination, followed
by ordering the relevant laboratory investigations. Checking textbooks
of syndromes and computerised databases, as well as discussing
with fellow geneticists and with our colleagues in the laboratories,
is often helpful in coming to an overall diagnosis. Finally, effective
communication with the child’s parents is very important, during the
diagnostic process, when a syndrome diagnosis is made and also when
no syndrome can be identified.
Bibliography
1. Jones KL, editor. Smith’s recognizable patterns of human malformation. 5th ed.
Philadelphia: WB Saunders; 1997.
2. Cassidy SB, Allanson JE, editors. Management of genetic syndromes. New York: John Wiley
& Sons; 2001.
3. Gorlin RJ, Cohen MM Jr, Hennekam RCM, editors. Syndromes of the head and neck. 4th ed.
New York: Oxford University Press; 2001.
4. POSSUM (Pictures Of Standard Syndromes and Undiagnosed Malformations). Version 5.6.
The Murdoch Children’s Research Institute, Melbourne, Australia.
5. Hunter AGW. Medical genetics: 2. The diagnostic approach to the child with dysmorphic
signs. CMAJ. 2002;167(4):367–372.
SOME COMMON
DYSMORPHIC CONDITIONS
DEFINITIONS
Syndrome
 Derived from Greek, meaning ‘running together’
 Refers to a group of features that occur together consistently, and
implies a common specific cause, though the cause may not be
known at present
Sequence
 Refers to a group of features, resulting from a cascade of events
initiated by a single primary factor
 For example, in the Potter Sequence, the cascade of events is: renal
agenesis, lack of fetal urine, severe oligohydramnios. pulmonary
hypoplasia and restricted intrauterine space, compressed facial
appearance and limb deformities like talipes
Association
 Refers to a group of features that occur together commonly, but not
as consistently as in a syndrome, e.g. the VATER association
CHROMOSOME DISORDERS
Down Syndrome
 Incidence:
 1-in-650 live births, can vary between 1-in-600 to 1-in-2,000
among different populations
 Overall incidence rises after maternal age of 35 years
 Features:
 Diagnostic features in the neonate: Hypotonia, poor Moro reflex,
hyperextensibility of joints, excess skin on back of neck, flat facial
profile, slanted palpebral fissures, anomalous auricles, dysplasia of
pelvis, dysplasia of middle phalanx of fifth finger, single palmar crease.
100% have at least four features, and 89% have six or more features
 Dysmorphic features: Brachycephaly, late closure of fontanelles,
third fontanelle, hypertelorism, up-slanting palpebral fissures,
epicanthic folds, Brushfield spots (rarely seen in Asians), small
nose, low nasal bridge, open mouth with protruding tongue,
short neck, short broad hands, single palmar crease, hypoplasia
of the middle phalanx of the fifth finger with clinodactyly, wide
gap between first and second toes
Genetics 215
 Short stature
 Developmental delay, intellectual disability. Intelligence Quotient
(IQ) is typically between 25 and 50
 CHDs in about 40% of cases. The common defects are: VSD, AVSD,
ASD, FT and PDA
 Gastrointestinal malformations in about 15% of cases, including
tracheooesophageal fistula (TOF), pyloric stenosis, duodenal
atresia, annular pancreas, Hirschsprung’s Disease and imperforate
anus
 Haematologic disorders: Neonatal polycythaemia, leukaemoid
reaction and acute leukaemia (characteristically AML-M7). The
incidence of leukaemia in Down syndrome is about 1%.
 Thyroid disorders are common, thus annual TFTs are
recommended
 Cause:
 95% have trisomy for chromosome 21, due to non-disjunction
 4–5% have an unbalanced translocation, in which a chromosome
21 is attached to another chromosome, most commonly
chromosome 14, either arising de novo or being transmitted from
one of the parents
 <1% have mosaic trisomy 21
 Diagnosis:
 Karyotype
 In the case of an unbalanced translocation, parental karyotyping
is indicated
 Recurrence risks:
 For trisomy 21, the recurrence risk after one affected child is
generally accepted to be 1% for women younger than 37 years
and twice age-appropriate risk for women 37 years and older.
 For Down syndrome due to unbalanced translocations, the
recurrence risk is affected by which other chromosome is
involved in the translocation, whether the translocation is
de novo or inherited, and if inherited, whether the origin is
paternal or maternal
 For D-G translocations, i.e. involving one of the group D
chromosomes (13, 14 or 15), 50% arise de novo and 50% are
inherited. If the father is the balanced translocation carrier,
the recurrence risk is 2–5%. If the mother is the balanced
translocation carrier, the recurrence risk is 10%. These actual
recurrence risks are much lower than the theoretical risk, which is
1-in-3 or 33%
 For G-G translocations, i.e. involving one of the group G

chromosomes (21 or 22), 90% arise de novo and 10% are
inherited. For inherited 21/22 translocations, the recurrence risk is
4%. For inherited 21/21 translocations, all viable zygotes will have
translocation Down syndrome i.e. the recurrence risk is 100%
Trisomy 18 (Edward Syndrome)

 Birth incidence:
 About 1-in-8,000 live births
 Features:
 Pre- and postnatal growth restriction
 Polyhydramnios and decreased fetal activity
 Dysmorphic features: Prominent occiput, micrognathia, low-set
malformed ears, overlapping flexed fingers, prominent calcaneus,
short sternum, undescended testes
 Severe intellectual disability
 Neonatal hypotonia, followed by development of hypertonia
 CHD in about 85% of cases, including valvular heart disease,
VSD, PDA, etc.
 Urogenital and gastrointestinal anomalies
 Shortened life expectancy: Only 5% survive to 12 months of age.
70% of deaths are due to cardiopulmonary arrest, with central
apnea being a major factor in the neonatal period and infancy
 Cause:
 Majority have trisomy for chromosome 18, which is associated
with advanced maternal age
 A few have translocations
 Diagnosis by karyotype
 Recurrence risk:
 0.5% for trisomy 18 after one affected child
Trisomy 13 (Patau Syndrome)

 About 1-in-30,000 live births
 Features:
 Mean birth-weight is 2,600g. Postnatally, they characteristically
have feeding difficulties and FTT
 Dysmorphic features: Microcephaly, scalp defects (commonly
at the vertex), sloping forehead, microphthalmia, hypotelorism,
cleft lip (lateral or median), micrognathia, malformed ears, short
neck, redundant nuchal skin, postaxial polydactyly, flexed fingers,
undescended testes
Genetics 217
 Severe developmental retardation. Holoprosencephaly is

common
 CHDs and structural renal anomalies are common
 An interesting haematologic finding is that of nuclear projections
in polymorphonuclear leukocytes, which has been reported in
25–80% of cases
 Shortened life expectancy: Only 5–10% survive to >12 months of
age. Cardiopulmonary arrest is the most common cause of death;
central apnea may be an important factor.
 Cause:
 Majority have trisomy for chromosome 13, which is associated
with advanced maternal age
 Recurrence risk low (∼ 0.5%) for trisomy 13
Turner Syndrome
 About 1-in-3,000 liveborn girls
 This is one of the most common chromosome disorders at
conception, but the majority (about 98–99%) miscarry, usually in
the early stages of pregnancy
 Features:
 In neonates, lymphoedema of hands and feet and excess
nuchal skin
 Short stature. Mean untreated adult height is about 145cm
 Pubertal failure, infertility due to streak gonads
 Dysmorphic features: Webbed neck, increased carrying angle
of elbows, broad (shield) chest, widely spaced nipples, narrow
hyperconvex nails, multiple-pigmented naevi
 CHDs in 23%, most commonly bicuspid aortic valve, coarctation
of the aorta and aortic valve disease
 Structural renal anomalies
 Majority have normal intelligence, but may have specific
learning difficulties
 Hypothyroidism, DM and inflammatory bowel disease occur more
frequently in girls and women with Turner syndrome, than in the
general population
 Patients with a 45,X/46,XY karyotype have an increased risk of
gonadoblastoma
 Cause:
 50% have 45,X karyotype
 About 20% have isochromosome X
 About 30% have mosaicism (45,X/46,XX or 45,X/46,XY)

 A small proportion have other rarer karyotypes
 Management:
 Growth hormone treatment
 Oestrogen replacement therapy, at puberty
 Surveillance for associated complications
Fragile X Syndrome
 Incidence:
 1-in-4,000 males
 This is the most common form of inherited intellectual disability
 Features:
 Intellectual disability of variable severity
 Dysmorphic features: Macrocephaly, long face, prominent jaw
(which develops during adolescence), big ears, post-pubertal
macro-orchidism
 Delayed developmental milestones
 Shy personality
 Behavioural problems: Autism, ADHD and hyperactivity
 Cause:
 Most commonly due to a mutation in the FMR1 gene on the
long arm of the X chromosome (locus Xq27.3). This locus is
designated FRAXA
 The FMR1 gene consists of a sequence of CGG triplet repeats.
Normally, there are 5–55 CGG triplet repeats
 In a full mutation, there are >200 CGG triplet repeats. All males
and about 35% of females with a full mutation will have features
of the syndrome
 FMR1 alleles with 55–200 CGG triplet repeats are pre-mutation
alleles. When female pre-mutation carriers pass the pre-mutation
alleles to their offspring, the allele is unstable and the number
of CGG triplet repeats may increase. If the number of CGG
triplet repeats increases to >200, their offspring will have the
full mutation. When male pre-mutation carriers transmit the
pre-mutation allele to their children, the allele remains stable and
does not expand
 About 20% of female premutation carriers have premature
ovarian failure (cessation of menses below 40 years of age). This
information would be helpful for reproductive planning.
Genetics 219
 Adult male premutation carriers (and some females) develop a

late-onset progressive neurological syndrome, fragile X tremor
ataxia syndrome (FXTAS), with cerebellar tremor/ataxia, cognitive
decline, and brain atrophy.
 A few other fragile sites on the long arm of the X chromosome
have been described, but only FRAXE (chromosome locus Xq28)
has been shown to have phenotypic effects
 Diagnosis:
 DNA analysis: This is the method of choice for the diagnosis of
Fragile X syndrome. It identifies not only affected males, but also
differentiates pre-mutation alleles from normal alleles. In a child
with intellectual disability, chromosome analysis by karyotyping
or chromosome microarray analysis should also be done to
exclude other chromosomal abnormalities
 The inheritance of Fragile X syndrome is X-linked. There are
implications for the extended family of the affected person, thus
carrier testing should be offered to relevant members of the
extended family
CONTIGUOUS GENE DELETION SYNDROMES

Deletion 22q11 Syndrome/Velocardiofacial Syndrome
(VCFS)
 Incidence 1-in-4,000
 Features:
 Dysmorphic features: Long face, flat malar region, prominent
nose with squared nasal root, hypoplastic alae nasi, narrow
nasal passages, long philtrum, thin upper lip, slender and
tapering fingers
 Cleft palate, submucous cleft palate, velopharyngeal
incoordination or incompetence (resulting in nasal regurgitation,
hypernasal voice and recurrent serous otitis media)
 CHDs, including VSD, right-sided aortic arch, FT, pulmonary
atresia with VSD, interrupted aortic arch. Conotruncal defects are
the most characteristic
 Learning difficulty and mild intellectual disability
 Structural renal anomalies in about 35% of cases
 T-lymphocyte dysfunction and hypocalcaemia in infancy may
occur, which are features of DiGeorge syndrome
 Psychiatric illness in up to 20% of affected adults, in particular
schizophrenia
 Cause:
 Submicroscopic deletion of chromosome 22q11
 Inheritance is autosomal dominant, with variable expressivity
 Majority of cases represent new mutations; about 15% have
inherited the microdeletion
 Diagnosis:
 Fluorescent in-situ hybridisation (FISH)
 Parents of affected children should be tested, as clinical features
may be very mild. If one parent also has a 22q11 deletion, the risk
of recurrence for future children is 1-in-2 or 50%
 The acronym ‘CATCH 22’, which was coined for the phenotypic
features found in this condition, is regarded as derogatory and
should not be used
Williams Syndrome
 Incidence 1-in-10,000 to 1-in-20,000 births
 Features:
 Dysmorphic features: Epicanthic folds, periorbital fullness, stellate
iris pattern, flat midface, depressed nasal bridge, anteverted
nostrils, long philtrum, thick lips
 Growth deficiency
 Infantile hypercalcaemia
 CHDs, most commonly supravalvular aortic stenosis and
pulmonary artery stenosis
 Intellectual disability
 Characteristic personality: Unreserved, gregarious pattern of
speech
 Cause:
 Submicroscopic deletion of chromosome 7q11.23 that includes
the elastin (ELN) gene in 95% of patients
 Inheritance appears to be autosomal dominant, but almost all
cases represent new mutations and are sporadic. Parent-to-child
transmission is rare because affected adults rarely reproduce
 Diagnosis by FISH
OTHER DISORDERS
Noonan Syndrome
 Incidence 1-in-2,500 live births
 Features:
 Short stature
 Dysmorphic features: Hair may be wispy in infancy and become
curly and woolly in childhood. The facial features change with age
Genetics 221
 Facial features in the neonate: Tall forehead, hypertelorism,

downslanting palpebral fissures, epicanthic folds, depressed nasal
root, upturned nasal tip, low-set and posteriorly angulated ears,
excessive nuchal skin
 Features in infancy and childhood: Relatively large head,
hypertelorism, downslanting palpebral fissures, ptosis, hooded
eyelids, low-set and posteriorly rotated ears, broad or webbed
neck, characteristic chest deformity (pectus carinatum superiorly
and pectus excavatum inferiorly), undescended testes
 CHDs in about 65%, most commonly dysplastic pulmonary valve
and/or pulmonary valve stenosis. Hypertrophic cardiomyopathy
(HCM), obstructive or non-obstructive, occurs in 20–30%
 Feeding difficulties in early infancy are common, occurring in
77% of cases. These range from mild difficulties with poor suck to
severe difficulties requiring prolonged tube feeding
 Mild intellectual disability in 35%. Mean IQ ranges from 64–127.
There may be specific learning problems, especially with speech
and articulation
 Structural renal anomalies
 Lymphatic abnormalities, including lymphoedema
 Bleeding abnormalities in 50–65%, including factor XI, XII or VIII
deficiency, von Willebrand Disease (vWD) and Platelet Dysfunction
 Cause:
 Most of the early cases appeared to be sporadic, but recent
reports indicate parent-to-child transmission in 30–75%, with
autosomal dominant inheritance and highly variable expressivity
 Mutations in PTPN11 (ch12q24.1), SOS1 (ch2p22.1), KRAS (ch12p12.1),
BRAF (ch7q34), RAF1 (ch3p25.2) and NRAS (1p13.2) have been
identified in about 80% of people with Noonan Syndrome
 If diagnosis is suspected clinically, genetic testing can be
considered for confirmation of diagnosis.
Marfan Syndrome
 Incidence 1-in-5,000 to 1-in-10,000
 Features:
 Tall stature and disproportionately long limbs, resulting in a
decreased upper-to-lower-segment ratio and an increased arm-
span-to-height ratio
 Other musculoskeletal features: Arachnodactyly, reduced elbow
extension, pectus excavatum or carinatum, flat feet, scoliosis
 Facial features: Dolichocephaly, down-slanting palpebral fissures,
enophthalmos, malar hypoplasia, retrognathia
 Cardiovascular abnormalities: Mitral valve prolapse is common.

Progressive aortic root dilatation is the most severe abnormality,
and may result in increasing aortic regurgitation and heart failure
or aortic dissection and rupture. These are the leading causes of
death in people with Marfan syndrome
 Ocular abnormalities: Lens dislocation in 50–80% of cases
(usually upward), flat cornea, increased axial length of the globe,
hypoplastic iris or ciliary muscle
 Pulmonary apical bullae, spontaneous pneumothorax (frequency
is low: 4.4%)
 Cause:
 Autosomal dominant inheritance, with very high penetrance.
About 25% of patients represent new mutations
 Mutations in the fibrillin 1 (FBN1) gene (chromosome locus
15q21.1). Multiple mutations of all sorts have been found, the
majority identified in not more than one unrelated individual.
FBN1 mutations are also found in other conditions, e.g. familial
aortic aneurysm and familial ectopia lentis. Thus, finding a
mutation in FBN1 does not necessarily confirm the presence of
Marfan syndrome. Mutation analysis is usually embarked on,
if there are considerations about prenatal diagnosis or pre-
implantation genetic diagnosis
 Diagnosis:
 Modified Ghent diagnostic nosology
 In general, besides clinical examination, at least two specific
studies are necessary for diagnosis: cardiac evaluation, including
echocardiography, and slit-lamp eye examination
BIBLIOGRAPHY
1. Gorlin RJ, Cohen MM Jr, Hennekam RCM, editors. Syndromes of the head and neck. 4th ed.
New York: Oxford University Press; 2001.
2. Jones KL, editor. Smith’s recognizable patterns of human malformation. 5th ed.
Philadelphia: WB Saunders; 1997.
3. Cassidy SB, Allanson JE, editors. Management of genetic syndromes. New York: John Wiley
& Sons; 2001.
4. POSSUM (Pictures Of Standard Syndromes and Undiagnosed Malformations). Version 5.6.
The Murdoch Children’s Research Institute, Melbourne, Australia.
5. Hall B. Mongolism in newborns: A clinical and cytogenetic study. Acta Paediatr Scand.
1964;154(Suppl):1–95.
6. Firth HV, Hurst JA, Hall JG. Oxford Desk Reference Clinical Genetics.Oxford University Press;
2005
7. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-
Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth
P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med
Genet.2010;47:476–85
Genetics 223
INBORN ERRORS OF METABOLISM (IEM)

INTRODUCTION
Although individually rare, Inborn Errors of Metabolism (IEM) collectively
have an incidence of about 1:3000 in Singapore. The National Expanded
Newborn Screening (NENS) laboratory at KKH has been screening
samples of Singaporean children since 2006.
The most opportune time to diagnose an inborn error of metabolism

is soon after birth when the baby is asymptomatic. Often, metabolic
decompensation can occur within the first week of life resulting in
critical illness. Severe morbidity and mortality can result from the first
presentation alone.
Which conditions do we screen for?

Expanded newborn screening allows us to screen for several inborn
errors of metabolism, including amino acid disorders, organic acidurias
and fatty acid oxidation defects (see Table 6-1).
Normal screening results indicate that the individual has a very low risk
of having one of the listed disorders but does not completely rule out
the possibility. Where there is clinical concern a metabolic physician
should be consulted even in the face of normal screening result. Please
also note that there are many inborn errors of metabolism that cannot
be detected by this extended newborn screen. Where there is clinical
concern, a metabolic physician should be consulted.
Practical aspects
When to do the test?
The ideal window for testing is between 24–72 hours of life although
samples are still acceptable up to 7 days of life. Since some of these
conditions present in the first few days of life, early sampling is
preferred. The levels of these metabolites vary in the first few weeks of
life and so samples taken after 7 days of life give difficulties in reliable
interpretation. In particular, fatty acid oxidation defects metabolites may
have normalised.
Preterm babies should also have their samples taken at 24–72 hours
of age with further samples as required based on the preterm baby
protocol.
Table 6-1: Conditions that are screened
Primary Targets Secondary Conditions

Those conditions the programme is aiming Conditions that may well be identified
to detect while investigating abnormal results for
the primary targets.
 Amino Acid Disorders:  Amino Acid Disorders:
 Phenylketonuria including biopterin  Hyperphenylalanine
defects  Arginase deficiency
 Maple Syrup Urine Disease  Citrin deficiency
 Citrullinaemia type 1  Hypermethioninaemia
 Argininosuccinic Aciduria  Tyrosinaemia Types 2 and 3
 Tyrosinaemia type 1
 Homocystinuria (pyridoxine
unresponsive)
 Organic Acid Disorders:  Organic Acid Disorders:
 Propionic acidaemia  3-Methylcrotonyl-CoA carboxylase
 Methylmalonic acidaemia (MUT) deficiency
 Cobalamin A/B  2-Methyl-3-hydroxybutyric aciduria
 Isovaleric acidaemia  3-Methylglutaconyl-CoA dehydratase
 ß-ketothiolase deficiency deficiency
 Glutaric acidaemia type 1  Isobutyryl-CoA dehydrogenase
 Malonic aciduria deficiency
 3-Hydroxy-3-methylglutaryl-CoA lyase  2-Methylbutyryl-CoA dehydrogenase
deficiency deficiency/short branch chain acyl-CoA
 Multiple carboxylase deficiency  Ethylmalonic encephalopathy
 Cobalamin C/D defect
 Fatty Acid Oxidation Disorders:  Fatty Acid Oxidation Disorders:
 Primary carnitine deficiency/carnitine  Carnitine palmitoyltransferase
uptake deficiency deficiency type 1
 Medium chain acyl-CoA  Carnitine palmitoyltransferase
dehydrogenase deficiency deficiency type 2
 Very long chain acyl-CoA  Carnitine-acylcarnitine translocase
dehydrogenase deficiency deficiency
 Long chain hydroxy acyl-CoA  Multiple acyl-CoA dehydrogenase
dehydrogenase deficiency deficiency/glutaric aciduria type 2
 Trifunctional protein deficiency  Short chain acyl-CoA dehydrogenase
deficiency
 Medium/short chain hydroxy acyl-CoA
dehydrogenase deficiency
 Medium chain ketoacyl-CoA thiolase
deficiency
Genetics 225
What is needed?
One drop of blood obtained via heel prick should be allowed to saturate
each circle on the newborn screening card. The cards should be allowed
to fully air dry (for 3–4 hours) and sent to the newborn screening lab
within 24 hours of collection.
226
HAEMATOLOGY AND ONCOLOGY
ANEMIA
GENERAL APPROACH TO ANEMIA

DEFINITION
True anemia occurs when there is a decrease in the circulating red cell
mass, leading to impaired ability to meet the body’s demand for oxygen.
Spurious anemia occurs when there is a dilutional effect of an increase in
plasma volume, e.g. in fluid overload and cardiac failure.
CLINICAL SYMPTOMS
Symptoms include fatigue, breathlessness, dizziness, headache and
blackouts.
Severity of clinical symptoms depends on:

 Severity of anemia
 Speed of onset — Gradual onset better tolerated
 Age and cardiovascular status of patient — Better tolerated in young
HISTORY
 Previous blood tests and transfusion history — For comparison
 Duration of symptoms — Recent or long-standing
 Family history — Consanguinity, congenital anemias, gallstones
 Dietary history — Goat’s milk ingestion, meat intake, vegans
 Drugs and exposure to toxic chemicals
 Blood loss — Including menstrual history
 Abnormal bruising
 History of other illnesses — Diarrhoea, signs of hypothyroidism,
autoimmune disorders
 Medical history — Neonatal hyperbilirubinaemia in G6PD deficiency
 Stature — Short in Fanconi anemia
 Skin and sclera — Pallor, jaundice, purpura, bruises, petechiae
 Signs of nutritional deficiencies — Iron, ascorbic acid
 Signs of chronic illness — Thyroid, renal
Haematology and Oncology 227
Table 7-1: Causes of true anemia

Decreased Production Increased Destruction/Loss
Nutritional deficit of: Blood Loss
• Iron
• Folate
• Vitamin B12
• Ascorbic acid
Reduction in precursors Haemolysis (intrinsic to RBCs)
• Aplasia • Haemoglobinopathies
• Malignancy • Enzyme deficiencies
• Myelofibrosis • Membrane defects
Ineffective erythropoiesis Haemolysis (extrinsic to RBCs)
• Anemia of chronic disease • Autoimmune or isoimmune
• Thalassaemia • Infections
• Myelodysplastic syndrome • Physical or chemical agents
Table 7-2: Possible common causes of anemia based on full blood count (FBC)
MCV/MCHC WBC Platelets
↓/↓ Fe deficiency ↓ Aplasia ↓ Aplasia
(hypochromic, Thalassaemia (leucopenia) Malignancy Malignancy
microcytic) Chronic illness SLE Blood loss
Drugs
↑/↑ Vit B12 / ↑ Blood loss ↑ Haemolysis
(macrocytic) Folate (leucocytosis) Haemolysis Fe deficiency
deficiency Infections Myeloproliferative
disorder
N/N Blood loss Primitive Malignancy
(normochromic, Haemolysis (blasts etc) Myeloproliferative
normocytic) Chronic illness disorder
Hypersegmented Vit B12/Folate
neutrophils deficiency
Table 7-3: Possible common causes of anemia based on reticulocyte count

Reticulocytes
↑ Blood loss
Haemolysis
Nutritional deficiency responding to treatment
↓ Aplasia
Malignancy
 Cardiovascular — Heart failure

 Organomegaly — Lymph nodes, liver, spleen
 Rectal examination (if necessary) — Melaena
INVESTIGATIONS
FBC, Peripheral Blood Film (PBF) and reticulocyte count can give a lot
of information and help in deciding what further investigations to do.
Blood investigations like LFT, renal panel, TFT, iron studies, Hb

electrophoresis, autoimmune markers, Vitamin B12 and folate are
ordered on the basis of the suspected diagnosis.
When to Do a Bone Marrow Aspirate (BMA)

 Malignancy suspected — Blasts, primitive white cells in the PBF,
tumour elsewhere
 Myelodysplastic change seen — Hypogranular, hypolobulated
neutrophils
 Aplasia suspected — Reticulocytopenia, pancytopenia
 Anemia of uncertain origin
Send BMA for morphology, immunophenotype and cytogenetics. If

lymphoma or metastatic solid tumour is suspected, bilateral BMA and
trephine biopsies should be performed.
TREATMENT
 Treat underlying condition. In iron deficiency, remember to continue
treating for months after Hb normalises to replenish body iron stores
 Treat symptoms of anemia, e.g. heart failure
 Transfuse when there is ongoing blood loss/haemolysis or if there is
symptomatic anemia. In longstanding anemia, there is no need to
transfuse if Hb is stable and patient is not symptomatic
 If Hb is very low, correct anemia slowly in stages, e.g. if Hb is 3g/dl,
correct to Hb of 8g/dl on first day , then to Hb of 12g/dl the next day
USEFUL FORMULAE IN ANEMIA

Volume of packed cell transfusion (ml) = (Desired Hb minus Current Hb
in g/dl) x (Body weight in kg) x 3.5
Mentzer Index = Mean corpuscular volume (MCV) / Red blood cell (RBC)
(<13 more likely thalassaemia trait, >13 more likely iron deficiency)
IRON DEFICIENCY ANEMIA (IDA)

Iron deficiency is an important cause of anemia in children, and often
presents as a mild to moderate microcytic, hypochromic anemia.
Chronic iron deficiency can result in other non-haematological
consequences including effects on neurocognition and immunity.
Causes of IDA include nutritional insufficiency, gastrointestinal blood
loss, malabsorption syndromes, menstrual losses, infants on an exclusive
fresh cow’s milk diet.
DIAGNOSTIC WORKUP
Conditions that can produce a hypochromic, microcytic anemia and be
confused with IDA include hereditary anemias (commonly thalassaemia
in Singapore) and anemia of chronic disease. The initial workup
should always include a thalassaemia screen to exclude concomitant
thalassaemia trait. However, it should be noted that co-existing iron
deficiency can artifactually result in a low HbA2 level, masking the
diagnosis of beta-thalassaemia trait. A repeat thalassaemia screen should
be performed if microcytosis persists despite correction of iron deficiency.
Common laboratory tests used to diagnose iron deficiency include:

 Serum iron — There is diurnal variation with higher serum values
late in the day. Levels also fluctuate with dietary iron intake. Serum
iron cannot be used on its own to diagnose iron deficiency
 Serum transferrin/total iron binding capacity (TIBC) — Transferrin
is the carrier protein of iron in the blood, and is assayed directly
as serum transferrin or indirectly as the total iron binding capacity
(TIBC) of the patient. This has limited utility on its own, but has some
value when used to derive the transferrin saturation.
 Transferrin saturation = Serum iron / TIBC
 Iron deficiency is more likely to be present when the transferrin
saturation is <15%
 Serum ferritin is a sensitive parameter for the assessment of iron
stores in healthy subjects. However ferritin is an acute phase reactant
and may be elevated in the presence of chronic inflammation,
infection, malignancy or liver disease. Values of <30mcg/L are
suggestive of iron deficiency in children. A serum ferritin level of
>100mcg/L suggests that iron deficiency is unlikely to be present
 Soluble transferrin receptor is upregulated when iron supply is
inadequate, and is a useful measure of iron status as it is not affected
by inflammation or infection. Serum levels are directly proportional
to degree of iron deficiency. This test is available only in some
specialised laboratories in Singapore
Figure 7.1: Approach to diagnosis, management and assessment of treatment response in iron
deficiency anemia
Transferrin saturation — serum iron/total iron binding capacity

IDA — Iron deficiency anemia
ACD — Anemia of chronic disease
Hb — Haemoglobin
Retic — Reticulocytes
 Bone marrow iron staining is considered the gold standard for the
diagnosis of iron deficiency, but is not routinely performed due to
the invasive nature of the test
MANAGEMENT OF IDA
Successful treatment of IDA in infants and children lies in appropriate
dosing and scheduling of oral iron therapy, dietary modifications and
follow-up assessment for response.
 Oral iron therapy with 3–6mg/kg/day of elemental iron. The

supplement should be given between meals, and with juice
(not milk, as iron is chelated by calcium in milk). See Table 7-4
for a summary of the elemental iron content of common iron
supplements in Singapore
 Dietary modifications — Iron-containing complementary foods
should be introduced at 4–6 months of age. Exclusive feeding with
fresh cow’s milk for infants younger than 12 months is not advised as
it is a poor source of iron. High iron-content food products include
red meats, cereals fortified with iron and dark green leafy vegetables
 Parenteral iron therapy should be reserved for patients with severe,
persistent anemia who have proven intolerance to oral supplements,
malabsorption, or poor compliance to oral therapy. Intravenous iron
sucrose (100mg of elemental iron/5ml) is available locally. Parenteral
iron should be used with caution because of the risk of anaphylaxis
 Red cell transfusions should only be reserved for patients with
severe, symptomatic anemia compromising end-organ function.
Administer with caution to avoid precipitating cardiac failure
Table 7-4: Iron supplements and their elemental iron content

Iron Supplement Elemental iron content
Iron polymaltose drops 50mg per ml
Ferrous fumarate 66mg per 200mg tablet
Ferrous gluconate (Sangobion) 30mg per 250mg capsule
Iron sulphate (Nutroplex Liquid with iron and lysine) 15mg per 5ml
• Recommended doses for treatment of IDA are 3–6mg/kg/day of elemental iron.

Assessment of response to therapy

Response to iron replacement therapy can be monitored with serial
reticulocyte counts and Hb assessments. After therapeutic doses of oral
iron, a reticulocytosis should be seen within 72 hours. Hb should rise by
at least 1g/dL within 4 weeks, and should be monitored subsequently
every 2–3 months until it reaches the age-adjusted normal range.
Iron supplements should then be continued for a minimum of 3 more
months to replace storage iron pools. Early discontinuation of iron
therapy will frequently lead to recurrence of iron deficiency.
The most common causes for non-responders to iron supplements are

compliance failures and intolerance to medication as iron formulations
do result in gastric irritation. Ongoing gastrointestinal blood loss or
other causes of anemia also have to be evaluated in non-responders.
THALASSAEMIA
Thalassaemia is the most common genetic disease in the world.
About 4–5% of population of Singapore carry the disease gene. Adult
haemoglobin comprises of 2 alpha (α) and 2 beta (β) globin chains
in a tetramer (α2β2). Defect in any of the globin chains will cause
thalassaemia — α globin chain defect causing α thalassaemia and β
globin chain defect causing β thalassaemia.
BETA (β) THALASSAEMIA

Two β-globin genes are present — one on each chromosome 11. More
than 300 mutations have been described in this gene with resultant
reduction in the production of normal β-globin chains.
ΒETA (β) THALASSAEMIA MINOR OR TRAIT

Clinically asymptomatic. Presents with microcytic anemia (Hb 9-11
gm/dl usually). PBF shows microcytosis, hypochromia, target cells.
Haemoglobin electrophoresis shows raised HbA2 which in conjunction
with microcytic anemia is diagnostic of beta thalassaemia trait. No
treatment or routine follow up is necessary. However family screening,
genetic counseling and referral to the National Thalassaemia Registry
(NTR) are important.
ΒETA (β) THALASSAEMIA MAJOR

 Clinical Presentation
 Presents at <1 year of age, usually 3–6 months
 Anemia and mild jaundice. Hepatosplenomegaly
 Diagnosis
 Severe microcytic anemia.
 PBF: microcytic hypochromic red blood cells (RBC), target cells,
polychromasia, nucleated RBCs
 Hb electrophoresis — Absent or severely reduced HbA, raised
HbF and HbA2. HbH stain negative.
 Treatment
 Blood Transfusion
 15–20ml/kg every 4–6 weeks. Keep baseline Hb 9–10g/dL and
post-transfusion Hb 13–14g/dL
 Blood is ABO and Rh matched. Preferably extended RBC
(C,c,D,E,e) and Kell Ag matched
 Leucodepletion — At donation or by bedside filter
 Monitor for Transfusion Reactions
 Febrile non-haemolytic reaction — Fever, rigors, skin rash, wheezing
 Anaphylactic reaction — Severe reaction with hypoxia, hypotension
 Haemolytic reaction: presents with haemoglobinuria, loin pain
Figure 7.2: Approach to microcytic anemia
FBC – Microcytosis, Hypochromia
Peripheral Blood Film (PBF); Serum Ferritin;

Thalassaemia screen (Hb Electrophoresis, HbH stain,
ɑ thalassaemia mutation analyses)
Ferritin – Low
No HbA. HbF only or
Thalassaemia screen HbA2 – Raised
HbF/ HbE
Normal
β Thalassaemia Major/ β Thalassaemia

Iron Deficiency Minor
HbE-β Thalassaemia
 Treatment of Transfusion Reactions

 STOP transfusion. Vital sign monitoring every 15 mins
 Allergic reaction — IV Diphenhydramine 1mg/kg and IV
Hydrocortisone 4mg/kg
 Suspected haemolytic reaction — Repeat group and cross-
match; Direct Coomb’s Test (DCT). Notify and liaise with blood
bank
 Monitor for Long Term Complications of Transfusion
 Iron overload (each bag of blood contains about 200mg of iron).
Effects of iron overload include: cardiomyopathy, liver cirrhosis,
endocrinopathy (short stature, delayed puberty, hypothyroidism,
hypoparathyroidism, diabetes mellitus), skin pigmentation
 Risk of blood borne infections- Hep B, Hep C, HIV, Syphilis,
Malaria, CMV
 Iron Chelation
 Desferrioxamine (DFO)
 Start when serum ferritin >1,000mcg/L. Usually after 10–20
transfusions and 18–24 months of age
HbH positive Ferritin – Normal

ɑ Mutation +ve HbE present Thalassaemia screen
Normal
ɑ Thalassaemia HbE Homo/ Consider rare causes e.g.

Minor heterozygous sideroblastic anaemia
 Dose 20–50mg/kg/day, 5–7 days/week. Start at lower dose

and increase slowly
 Infuse subcutaneously over 8−12 hours each night
 Side effects: Painful swelling at injection sites, visual and
auditory neurotoxicity, osteoporosis
 Increases risk of Yersinia enterocolitica infection; stop
during diarrhoea and abdominal pain
 Concomitant Vitamin C 50–100mg 1 hour after start of
injection daily helps iron excretion
 Deferiprone (Ferriprox/L1)
 First oral iron chelator licensed for use
 Particularly effective for myocardial iron removal
 Dose 75–100mg/kg/day TDS given with meals
 Risks — Agranulocytosis (<1%), weekly FBC monitoring is
recommended
 Arthralgia of large joints; transaminitis.
 Deferasirox (ExJade)
 Oral iron chelator
 Dose 20–30mg/kg/dose once daily before meals. To be
dissolved in water or apple juice
 Side effects — Skin rash, gastrointestinal disturbances,
renal toxicity (glomerulopathy/tubulopathy)
 Licensed for use in children older than 2 years
(Oral chelators can be combined with DFO in severe iron
overload conditions.)
 Splenectomy for Hypersplenism
 Can be considered when older than 5 years. Reduces
requirement for transfusion
 Mostly by laparoscopic approach with minimal morbidity
 Indications: Transfusion requirement >220ml/kg/year,
hypersplenism, mechanical discomfort
 Pneumococcal, meningococcal and Haemophilus Influenzae B
vaccinations before splenectomy
 Penicillin prophylaxis after splenectomy: 250mg BD long term
 Risks of thrombosis, pulmonary hypertension, infections by
encapsulated organisms to be considered before performing
splenectomy
 Haematopoietic Stem Cell Transplantation (HSCT)
 Only curative option in thalassaemia. However treatment
related mortality is significant
 HLA-matched sibling HSCT is the best option with >80%
thalassaemia-free survival rate
 Alternate donor transplant including matched unrelated

donor, cord, haploidentical transplants are also possible
options however with less success rates
 Supplements
 Folic acid 1–5mg once a day
 Vit C 50–100mg once a day if on DFO therapy
 Calcium supplements
ΒETA (β) THALASSAEMIA INTERMEDIA

Severity of the disease is in between thalassaemia major and
thalassaemia minor. The disease spectrum ranges from intermittent
transfusion requirement (transfusion intervals more than every 3
months) to no transfusion at all. Presents usually after 1 year of age
with variable pallor, jaundice and hepatosplenomegaly. However
extramedullary haematopoiesis, skeletal changes and iron overload can
be problematic even in those with minimal transfusion requirements
and hence need to be monitored closely.
 Causes
 HbE/beta (β) thalassaemia
 Homozygous β+ thalassaemia genes
 Concomitant α thalassaemia
 Diagnosis
 Moderate microcytic hypochromic anemia (Hb between 6–9g/dl)
 PBF shows hypochromic microcytic RBCs, target cells,
polychromasia, nucleated RBCs
 Hb Electrophoresis: No or severely reduced HbA, raised HbF and
presence of HbE (in HbE/β thalassaemia)
 Treatment
 Folic acid — 1–5mg once a day
 Transfusion as necessary, during intercurrent infections, growth
failure, skeletal changes
 Splenectomy may be considered in case of significant
enlargement of spleen
 Hydroxyurea (hydroxycarbamide) may reduce transfusion
requirement and extramedullary haematopoiesis
Table 7-5: Recommended investigations for Beta (β) thalassaemia major patients
System Investigation Age to Start Frequency of

Monitoring
Iron Load Serum ferritin • Before initiation of transfusion • Every 3 months
Liver iron content
• After 10–20 transfusions • Yearly
Liver MR (biopsy not routine)
Liver biopsy
Cardiac iron load (MR) • 10 years • Every 1–2 years
Chelation-associated Audiometry • After commencing chelation • Yearly

Eye review • Yearly
Bivalent ion levels (e.g.
• Yearly
Zinc, copper)
Chelation-specific • Every 1 week to 3 months
lab tests
Liver Function  LFT • Before initiation of transfusion • Every 3 months
Cardiac Function Physical examination • At diagnosis • Every 6 months

Echocardiogram, MUGA • 10 years • Every 1–2 years
scan, or cardiac
MRI T2*
Endocrine Height (standing and • At diagnosis • Every 6 months

Function sitting)
Puberty staging • 10 years • Yearly till puberty completes
Serum TSH • 12 years • Yearly
Serum calcium and • 12 years • Yearly
phosphate
Random blood glucose • Pre-transfusion • Every 6 months
Bone DEXA bone densitometry • 10 years • Every 1–2 years

scan
Infections Hepatitis B sAg, sAb • Before initiation of transfusion • Every 1–2 years
Hepatitis C serology
HIV screen
Adapted with permission from “Guidelines for the Clinical Care of Patients with Thalassaemia
in Canada”
ALPHA (α) THALASSAEMIA
ALPHA (α) THALASSAEMIA MINOR

(1 or 2 gene deletion or non-deletional mutation)
Clinically asymptomatic. FBC parameters may show microcytosis and
hypochromia in 2-gene deletion. However single gene deletion can
present with a completely normal FBC and are called silent carriers.
Diagnosis can be done only by genetic testing as Hb electrophoresis
and HbH stains are normal. HbH stain may be positive for HbH inclusion
bodies in two gene deletion carriers. DNA analysis shows either one
or two alpha gene deletion or rarely non-deletional changes like Hb
Constant Spring (-α/αα, -α/-α, --/αα, -α/αcs).
Treatment
No treatment or follow up is necessary. Lifespan is normal. However
family screening, genetic counseling and referral to the NTR is important.
HAEMOGLOBIN H (HBH) DISEASE

 Clinical presentation is that of thalassaemia intermedia
 Usually presents with pallor, mild jaundice and
hepatosplenomegaly
 However early presentation in infants is also possible
 Diagnosis
 PBF shows microcytosis, hypochromia and striking poikilocytosis
 HbH stain shows typical golf ball appearance (HbH Inclusion
bodies)
 DNA analysis commonly shows --/-α or --/αcs
 Treatment
 Folic acid supplementation 1–5mg/day
 Blood transfusion as necessary (infections, growth failure, skeletal
changes, etc.)
 Splenectomy if significant splenomegaly causing mechanical
discomfort and hypersplenism
FETAL HYDROPS SYNDROME/BART’S HYDROPS FETALIS

 Maternal toxaemia during pregnancy
 Hydrops fetalis
 Stillbirth or early postnatal death
 Diagnosis
 Should be suspected antenatally in case of fetal hydrops and
investigated appropriately
 FBC shows very severe anemia. HbH band in haemoglobin

electrophoresis may be seen
 DNA analysis shows --/-- (no alpha chains)
 Treatment
 Prevention is the best therapeutic strategy because of the
severity of the disease
 It may be possible to do fetal transfusions at regular intervals and
early delivery followed by transfusions after birth. There are some
reported survivors in literature
CO-INHERITENCE OF ALPHA (α) & BETA (β) THALASSAEMIA

Since the prevalence of both α and β gene defects are common in
Southeast Asia, co-inheritance of α and β thalassaemia in various
combinations are not uncommon. This actually reduces the severity of
the clinical presentation as the globin chain imbalance is less, causing
less haemolysis. DNA analysis for both α and β thalassaemia gene is
important to make the exact diagnosis. Family screening, appropriate
genetic counseling are important along with referral to the NTR.
GENETIC COUNSELLING AND PRENATAL DIAGNOSIS

In Singapore all citizens and permanent residents with confirmed
thalassaemia should be referred to the NTR. The NTR collates national
data on thalassaemia, provides free counselings on thalassaemia, and
offers thalassaemia screening to family members at subsidised rates.
Couples who are both heterozygous for the same type of thalassaemia
carry a 25% risk of having a child with thalassaemia major phenotype.
Through counseling and screening, these couples can be prospectively
identified and offered the option of prenatal diagnosis. The preferred
method for prenatal diagnosis is by chorionic villus sampling (CVS) and
this is done at around 12 weeks of gestation and the sample is then
subjected to DNA analysis. Providing a confirmed genetic diagnosis will
enable the couple to make an informed decision about the pregnancy,
especially in cases of homozygous β thalassaemia and 4-gene deletion
α thalassaemia where the clinical phenotype is predicted to be
thalassaemia major and fetal hydrops respectively.
Pre-implantation genetic diagnosis (PGD) is now possible by selecting

embryos which are not affected by thalassaemia. Theoretically, if there
is an older sibling with thalassaemia major, PGD for thalassaemia can be
combined with tissue matching with the affected sibling with a view to
providing tissue-matched stem cells for transplantation in the affected
sibling. However, this practice carries ethical concerns and may not be
widely acceptable.
Bibliography:
1. Chew EC, Lam JCM. Diagnosis and Management of Iron Deficiency Anaemia in Children
— A Clinical Update. Proceedings of Singapore Healthcare. 21(4):278–85.
2. World Health Organization. Iron Deficiency Anaemia: Assessment, Prevention, and Control
— A Guide for Program Managers. Geneva, Switzerland: World Health Organization; 2001.
WHO/NHD/01.3.
3. Weatherall DJ, Clegg JB. The Thalassaemia Syndromes. 4th ed. Blackwell Science; 2001.
4. Cao A, Rosatelli MC, Monni G, Galanello R. Screening for thalassaemia: A model of success.
Obstet Gynecol Clin North Am; 2002(29):305–28.
5. NF Olivieri. The β-Thalassaemias. N Eng J Med. 1999;341(2):99–109.
6. “Guidelines for the Clinical Management of Thalassaemia” Published by Thalassemia
International Federation 2007. No:9 ISBN:978-9963-623-59-4. www.thalassaemia.org.cy.
7. “Guidelines for the Clinical Care of Patients with Thalassemia in Canada”. www.
thalassemia.ca.
8. “Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT)”
Published by Thalassaemia International Federation 2013. No 19 ISBN 978-9963-717-03-3.
BLEEDING DISORDERS
PHYSIOLOGY OF HAEMOSTASIS
Haemostasis refers to maintenance of vascular integrity when there is
injury, at the same time limiting the clot to the site of injury without
systemic propagation. It involves interplay between the platelets,
the vascular endothelium and the coagulation factors. It consists of
a primary phase which results in production of a platelet plug and a
secondary phase with activation of procoagulant proteins resulting in
the formation of a cross-linked fibrin clot.
When uncontrolled, the haemostatic response can lead to thrombosis

and tissue damage. The patency of vessels in normal, uninjured tissues is
maintained by natural inhibitors of coagulation, consisting of:
 Tissue factor pathway inhibitor
 Antithrombins
 Protein C/Protein S pathway
 The fibrinolytic system which degrades fibrin and is necessary to
allow for complete wound healing
WORKUP OF A CHILD WITH A SUSPECTED BLEEDING

DISORDER
HISTORY
 Nature of the bleed:
 Location and type — Bleeding from skin, mucosal surfaces,
petechiae and purpura are typically seen in thrombocytopenia
whereas joint, muscle, soft tissue bleeds and palpable
ecchymoses are more likely to be seen in a coagulation defect
 Duration — Bleeding that stops and then recurs quickly is
suggestive of a true underlying bleeding disorder
 Time of onset — Acute bleeds that have occurred recently over a
period of days to weeks without a prior history is suggestive of an
acquired disorder; bleeding shortly after birth (e.g. oozing when
cord separates, post-circumcision) suggests a congenital condition
 Menorrhagia in pubertal females — Up to 20% girls with
menorrhagia at menarche have now been recognised to have a
bleeding disorder
 Any precipitating factors, e.g. trauma, dental extractions and
surgery — Bleeds precipitated by relatively minor injuries or
surgery are more likely to be due to a significant underlying
bleeding disorder
 Family history and pedigree:

 Ask about bleeding history from all members of the family,
especially in male relatives to exclude X-linked disorders
 Haemophilia can result in abnormal bleeding in a female carrier
 Menstrual history and obstetric history of female relatives
 Drug history:
 Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs)
 Anticonvulsants and antibiotics (e.g. penicillins) causing drug-
induced thrombocytopenia
 Warfarin, low molecular weight heparins
 Skin for petechiae/purpura/telangiectasia
 Bleeding from nasal and oral mucosa
 Pallor and other signs of anemia
 Joints — Swelling or chronic changes (e.g. contractures) secondary
to repeated bleeding episodes
 Deep tissue bleeds and intramuscular swelling
 Systemic illness, e.g. liver or collagen vascular disease

 Evidence of non-accidental injuries
LABORATORY STUDIES
 FBC with a peripheral blood smear — look at all three cell lines:
 Hb may be decreased if there is significant blood loss
 Bicytopenia or pancytopenia may indicate bone marrow failure
syndrome or infiltrating marrow lesion like leukaemia/lymphoma
 Platelet counts to determine severity of thrombocytopenia.
Platelet morphology to look at the size of the platelets. A
decreased count may be the result of platelet clumping from
EDTA dependent antibodies (spurious thrombocytopenia). Large
platelets are seen in Bernard-Soulier Syndrome and May-Hegglin
anomaly. Decreased platelet size may indicate Wiskott-Aldrich
Syndrome. Platelet morphology is important, as a mean platelet
volume from an automated count may not accurately reflect
platelet size
 Bleeding Time (BT):

 A screen for defects of primary haemostasis
 Increased BT with a normal platelet count may indicate a
qualitative platelet defect, von Willebrand disease or collagen
vascular disease
 The traditional test is the Ivy template bleeding time,
which is poorly standardised with questionable sensitivity,
specificity, and reliability.
 Varies with age, age-related norms available
 Currently not performed in most centres
 Platelet function screen (PFA):

 A point-of-care device which is a substitute for the bleeding time
if available
 More standardised and validated method of screening for platelet
function defects and von Willebrand disease
 Values are reported as closure times (CT) for collagen/ADP and
collagen/epinephrine cartridges
 Abnormal closure times may indicate either a primary platelet
function defect, drug effect, e.g. Aspirin or von Willebrand
disease
 Correlation with clinical features and further confirmatory tests
will be necessary
Table 7-6: Interpretation of laboratory studies used to diagnose bleeding disorders

Platelets PT APTT Differential Diagnosis Follow-up Studies
N N N • Mild vWD • vWD studies
• Platelet dysfunction • PFA/platelet aggregation tests
• Factor XIII deficiency • 5M urea clot lysis test
• Defects of fibrinolysis • Factor XIII assay
• α2 antiplasmin assay
N N ↑ • Congenital factor deficiency, • APTT mixing study
e.g. Haemophilia A/B • Factor VIII, IX, XI, XII assays
• Specific factor inhibitor/lupus • vWD studies
anticoagulant • Lupus anticoagulant
• vWD • TT/Reptilase time
• Heparin contamination
N ↑ N • Factor VII deficiency • PT mixing study
• Specific factor inhibitor • Factor II / VII / IX / X assays
• Vitamin K deficiency • LFT
• Liver disease
• Warfarin effect
N ↑ ↑ • Factor inhibitors/ • PT/APTT mixing studies
lupus anticoagulant • Factor assays
• Combined factor deficiencies/ • LFT
isolated Factor II / V / X • Fibrinogen assays
deficiency • TT/Reptilase time
• Vitamin K deficiency
• Hypofibrinogenaemia/
dysfibrinogenaemia
• High dose warfarin/heparin
↓ ↑ ↑ • Disseminated intravascular • Factor assays, D-dimer
coagulopathy (DIC) • Fibrinogen assays
• Liver dysfunction • LFT
• Kasabach-Merritt Syndrome
↓ N N • Acute/chronic • ANA/dsDNA
immune thrombocytopenia • Complement
• Autoimmune • Bone marrow studies
thrombocytopenia
• Platelet production defect/
marrow failure syndromes
• Malignancy
• Platelet consumption
• Platelet sequestration
 Prothrombin time (PT) and Activated Partial Thromboplastin Time (APTT):

 Surveys the secondary phase of haemostasis
 Normal ranges are age-dependent. In newborns, PT and APTT
may be mildly raised due to immaturity of the coagulation
system. Most revert to adult levels by 6 months of age
 The PT evaluates the extrinsic and common pathway
 The INR is commonly reported with the PT. However this should
be used only to guide warfarin therapy and not as a laboratory
test of coagulation
 The APTT evaluates the intrinsic system and common pathway
 See Table 7-6 for interpretation of abnormal platelet, PT and/or
APTT results
 Mixing studies of PT and APTT:

 Abnormal study of PT and APTT should be followed by a mixing study
 This is performed by mixing equal volumes of patient’s plasma with
pooled normal plasma containing normal levels of clotting factors
 If the PT or APTT normalises, a factor deficiency may be present.
 If the PT or APTT is persistently prolonged beyond the upper
limit of the normal range, an inhibitor may present (e.g. specific
factor inhibitor, lupus anticoagulant)
 Note that presence of a lupus anticoagulant only causes an in-
vitro prolongation of the PT or APTT and does not result in any
clinical bleeding symptoms
 Factor assays:
 When the APTT mixing study indicates a factor deficiency,
quantitate factors VIII, IX, XI and von Willebrand factor as these
deficiencies are associated with clinical bleeding
 Deficiencies in factor XII, prekallikrein and high molecular
weight kininogen can cause an increase in the APTT but are not
associated with clinical bleeding
 When the PT mixing study indicates a factor deficiency, factor VII
should be quantitated
 Thrombin time (TT):

 Laboratory test looking at the time required for a clot to form
when thrombin is added to plasma. Increased TT can be due to:
 Low fibrinogen activity
 Dysfunctional fibrinogen
 Presence of fibrin split products
 Heparin contamination
Figure 7.3: Algorithm for investigation of a bleeding child
History and physical examination suggestive of

underlying bleeding disorder
Petechiae, ecchymoses, mucosal bleeding or other Soft tissue, muscle, joint bleeding or other
symptoms suggestive of a platelet disorder symptoms suggestive of a coagulopathy
Platelet Count PT/APTT
Low Normal Normal Abnormal
• Immune • Platelet function defect Mixing Studies

thrombocytopenia • von Willebrand disease
• Marrow failure syndromes • Factor XIII deficiency
• Malignancies • Drugs
• Congenital platelet
Not corrected Corrected
disorders
• Platelet consumption/
sequestration
• DIC (PT/APTT will also be Factor inhibitor
prolonged)
↑ PT Normal PT ↑ PT
↑ APTT ↑ APTT ↑/Normal APTT
• Multiple factor • Haemophilia • Factor VII deficiency

deficiencies • Other factor deficiency • Vitamin K deficiency
• Common pathway • von Willebrand disease • Liver disease
factor deficiencies • Warfarin
• DIC
 The reptilase clotting time can be used to exclude heparin

contamination as the action of reptilase is not affected by
heparin. It will be normal if the TT is prolonged due to heparin
contamination
 Fibrinogen measurement:
 Fibrinogen can be measured quantitatively and functionally to
detect hypofibrinogaenemia and dysfibrinogenaemia
 Platelet aggregation studies:

 These measure the degree and pattern of platelet aggregation
after the addition of platelet agonists (adenosine diphosphate
(ADP), adrenaline, collagen, thrombin, arachidonic acid, and
ristocetin)
 Allows for the diagnosis of storage pool defects, Bernard-Soulier
Syndrome and Glanzmann thrombasthaenia
 Recently, flow cytometry allows for the direct detection of
platelet-surface glycoprotein expression which are absent in
Bernard-Soulier Syndrome and Glanzmann thrombasthaenia
THROMBOCYTOPENIA
This is defined as a platelet count of of <150x109/L. A low platelet count
needs to be confirmed by a review of the peripheral smear especially
in an asymptomatic child. False values (pseudothrombocytopenia)
can arise from aggregation of platelets in the syringe caused by
agglutination by EDTA antibodies, and counting of non-platelet particles
like fragmented red or white cells by automated counters.
CAUSES OF THROMBOCYTOPENIA
 Platelet destruction/consumption
 Immune-mediated:
 Immune thrombocytopenia (ITP)
 Autoimmune thrombocytopenia
 Drug-induced
 Post-transfusion purpura
 Non-immune mediated
 Haemolytic uraemic syndrome (HUS)
 Thrombotic thrombocytopaenic purpura (TTP)
 Disseminated intravascular coagulopathy (DIC)
 Giant haemangioma (Kasabach-Merritt Syndrome)
 Mechanical heart valves
 Impaired platelet production

 Congenital disorders
 Fanconi anemia
 Bernard-Soulier Syndrome
 Wiskott-Aldrich Syndrome
 Amegakaryocytic thrombocytopenia
 Chromosomal disorders
 Trisomy 13, 18
 Acquired
 Aplastic anemia
 Malignant marrow infiltration
 Myelofibrosis
 Drug-induced
 Platelet sequestration
 Hypersplenism
IMMUNE THROMBOCYTOPENIA
Immune thrombocytopenia (ITP) is an acute self-limiting condition
with a peak incidence between 1–6 years of age and usually lasting
<12 months in duration. Children younger than 1 year, or older than 10
years tend to have a more chronic course. Immune thrombocytopenia
is a diagnosis of exclusion based on a suggestive history and absence of
findings indicating an alternative cause of thrombocytopenia.
The onset is acute, usually after an antecedent viral illness 1–3 weeks
earlier. Symptoms include the sudden onset of petechiae, purpura,
epistaxis, oral mucosal bleeding and less commonly haematuria and
gastrointestinal tract bleeding.
Physical examination usually reveals a well child with no evidence

of pallor, weight loss or chronic illness. There should be no
hepatosplenomegaly, lymphadenopathy or skeletal defects.
Investigations
 Full blood count and peripheral blood film
Thrombocytopenia should be the only finding, without evidence
of involvement of other cell lines. The peripheral blood film should
be examined to exclude spurious thrombocytopenia or abnormal
platelet morphology.
 Autoimmune markers (ANA, dsDNA, complement)

This is not mandatory but can be screened if there is any suggestive
history or signs of an underlying autoimmune disorder, especially in
older children.
 Viral serologies
This is not mandatory, but can be useful to find out if an underlying
viral aetiology can be identified.
 Bone marrow studies

This is only indicated if there is any evidence of bone marrow
pathology, e.g. involvement of other cell lines, abnormal blasts,
organomegaly. A bone marrow aspirate is not routinely required
for the diagnosis of ITP. It may be performed prior to commencement
of corticosteroid therapy in some institutions to exclude an
underlying leukaemia as steroids can mask an early presentation of
haematological malignancies.
Treatment Options
The decision to offer conservative or medical treatment remains
controversial as there is no universally accepted “safe” platelet level.
However observational studies have shown a lower rate of major
9
spontaneous haemorrhages if the platelet count is ≥20x10 /L. A careful
discussion should be held with the family regarding risks and benefits of
treatment options.
 Conservative
 Most children will recover spontaneously without any medical
treatment within 12 months
 However care must be taken to avoid contact sports, rough play
and intramuscular injections
 Drugs that interfere with platelet function, e.g. aspirin, NSAIDS
should be avoided
 Intravenous immunoglobulin (IVIG)

 Blocks Fc receptors on reticuloendothelial organs, e.g. spleen
responsible for destruction of antibody-coated platelets
 Dose is between 1–2g/kg
 Response in platelet count is expected within 72 hours
 Adverse effects include fever, nausea, headache, anaphylaxis and
serum sickness
 Slowing the rate of IVIG infusion may alleviate side effects
 Corticosteroids
 Interferes with production of anti-platelet antibodies by
B-lymphocytes
 A bone marrow aspirate is not mandatory, but may be performed
according to institutional practice before commencing steroid
therapy as it can mask an early presentation of leukaemia
 Dose is between 1–2mg/kg/day for up to 6 weeks
 Repeated courses may be necessary for long-term remission
CHRONIC IMMUNE THROMBOCYTOPENIA

About 10–30% of children with acute ITP develop chronic persistent
thrombocytopenia beyond 12 months of duration. An underlying
autoimmune disorder/collagen vascular disease has to be excluded,
especially in older children. Patients with chronic ITP may not always
need treatment especially if the platelet counts remain ≥20x109/L as the
platelet count alone does not predict the risk of haemorrhage.
Spontaneous recovery can still occur a few years after the original
diagnosis. In refractory, symptomatic patients, treatment options
include azathioprine, danazol, vinca alkaloids, rituximab and
splenectomy.
NEONATAL THROMBOCYTOPENIA
The platelet count in both pre-term and term infants at birth is the same
as adult values (150–400x109/L) as platelet production is established
towards the end of the first trimester of pregnancy. The incidence of
thrombocytopenia in the neonatal intensive care setting is ~ 25%.
Causes of Neonatal Thrombocytopenia

 In a “sick” infant
 Placental insufficiency
 Perinatal asphyxia
 Congenital viral infection (TORCHES infection)
 Necrotising enterocolitis
 Neonatal sepsis
 Congenital heart disease
 In a “well-looking" infant
 Neonatal alloimmune thrombocytopenia
 Maternal autoimmune thrombocytopenia
 Wiskott-Aldrich Syndrome
 Amegakaryocytic thrombocytopenia
 Trisomy 13, 18 (there will be characteristic syndromic features)
Management
Management of neonatal thrombocytopenia is dependent on the
clinical condition of the child. There are no widely accepted guidelines
for platelet transfusions in neonates. Factors to consider include the
gestational age of the infant, the underlying condition of the child,
whether any active bleeding is present and if any invasive procedures
are being performed. As a general rule platelets should be given to
thrombocytopaenic neonates when the degree of thrombocytopenia
alone or in combination with other complications results in an
unacceptable risk of haemorrhage, and they should be given in tandem
with aggressive therapy for the underlying conditions precipitating the
thrombocytopenia. Most centres would aim to keep the platelet count
above 20–50x109/L.
NEONATAL ALLOIMMUNE THROMBOCYTOPENIA (NAIT)

This is a condition similar to rhesus haemolytic disease of the newborn
where the mother produces anti-platelet antibodies directed against
paternal platelet antigens present in fetal platelets. The incidence has
been quoted as 1 in 1000 pregnancies although it is believed to be rare
in Asian populations. Human platelet antigen 1a (HPA-1a) is the most
common antigen implicated.
Presentation
 40% can occur in the first pregnancy with no prior sensitisation
 The typical presentation is a well-looking newborn with petechiae
and purpura
 However about 20% of neonates can present with an intracranial
bleed
 The degree of thrombocytopenia can be very severe with platelet
9
counts frequently <10x10 /L
 Resolution of the thrombocytopenia occurs in 3–6 weeks after
delivery
Investigation
 There is no confirmatory test for the diagnosis of NAIT
 However the diagnosis is highly suggestive if an anti-platelet antibody
can be demonstrated in the mother with the corresponding platelet
antigen shown to be present on the father and infant
 Specific platelet antibody and antigen testing is not performed in
Singapore currently and has to be sent overseas
Management
 For the affected neonate, cranial imaging should be performed to
exclude intracranial haemorrhage
 If clinically indicated, transfusion with antigen-negative platelets
is preferable. However antigen typing of platelet units is not
routinely done in Singapore. Transfusion with maternal or
random platelets is the next best option
 Intravenous immunoglobulin at a dose of 1–2g/kg can also be
used to increase the platelet count
 The risk of NAIT and its consequences increases with each
subsequent pregnancy. Management of future pregnancies needs
to be coordinated with a specialist obstetrician as monitoring of
fetal platelet counts, maternal administration of corticosteroids/
IVIG or intrauterine platelet transfusions may be necessary
CONGENITAL BLEEDING DISORDERS
HAEMOPHILIA A AND B
Most patients with congenital bleeding disorders will be issued a
local Medik Awas (Medic Alert) card, as well as the World Federation of
Haemophilia (WFH) card, stating their diagnosis and treatment plans.
Background
Haemophilia is an X-linked bleeding disorder affecting ~1-in-7,000 males.
Haemophilia A is Factor VIII deficiency.
Haemophilia B is Factor IX deficiency.
Assessment
 Prompt bleeding or suspected bleeding in the head, neck, chest,
GIT and abdominal regions should be treated with clotting factor
immediately, even before assessment is complete.
 Clotting factor replacement should not be delayed by diagnostic
imaging.
 Assess site and extent of bleeding and the impact on function.
Table 7-7: Clinical characteristics of Haemophilia A and B

Severity Clotting factor level Bleeding Episodes
% activity (IU/ml)
Severe <1% of normal Frequent bleeding episodes common, predominantly into
(<0.01) joints and muscles. Bleeding can occur spontaneously or
after minor injury
Moderate 1–5% Can bleed after minor injury. May have joint bleeding. Severe
(0.01–0.05) bleeding with trauma, surgery, invasive procedures
Mild >5–40% Severe bleeding with major trauma, surgery, invasive
(0.01–0.40) procedures.
Management
 Most bleeds will require factor replacement except for bruises and
minor soft tissue injuries that do not impact function and mobility.
 Invasive procedures such as arterial puncture, lumbar puncture
must only be performed after clotting factor replacement.
 Prompt clotting factor replacement reduces pain and long term
consequences of bleeding.
 Do not give IM injections, aspirin or NSAIDs.
General Measures For Bleeds

R.I.C.E.S. for joint and muscle bleeds
For muscle and joint bleeds RICES will limit bleeding and reduce pain.
Initiate on arrival.
 R = Rest (in position)
 I = Ice (cold pack to reduce bleeding and pain)
 C = gentle Compression bandage
 E = Elevation
 S = Splint (severe/recurrent bleeds)
Venous access
 Venous access is often the major fear and stressor for children
with haemophilia and their parents. Use distraction and
relaxation techniques. Ask parents about their preferred method
for distracting/comforting their children.
 Treat veins with care; they are the lifeline for patients with
haemophilia. Apply pressure for 3 mins post-venepuncture.
Analgesia
 Paracetamol/codeine is sufficient in most cases; morphine or
tramadol can be used for severe pain
 Splinting/immobilisation is an effective adjunct for reducing

severe pain
 Avoid using products containing aspirin or NSAIDS (e.g.
ibuprofen, diclofenac) as these potentially interfere with
platelet function
Antifibrinolytic Therapy (Tranexamic acid)

 Often helpful for mucosal bleeding (most common form of
bleeding), e.g. mouth bleeds, epistaxis, menorrhagia
 Reduces breakdown of blood clots and is effective for treating
and preventing recurrence of mouth bleeds and epistaxis
 May be given alone or as adjunct to DDAVP/factor concentrate.
 Dose of tranexamic acid (500mg tabs) is 25mg/kg/dose (max:
1.5g/dose) TDS orally for 5–7 days
 Contraindicated in haematuria
Physiotherapy
Referral to physiotherapy for joint and muscle bleeds is essential.
Physiotherapy should commence as soon as pain has subsided and
bleed has been controlled.
SPECIFIC CLOTTING FACTOR REPLACEMENT IN HAEMOPHILIA A
Factor VIII:
Dose of Factor VIII (IU) = Body weight (kg) x 0.5 IU/kg x desired increase
in plasma Factor VIII (%). Doses should be rounded to the nearest whole
vial size to avoid wastage.
Table 7-8: Tranexamic acid dosages

Weight Tranexamic acid
<20 250mg tds
20–30 500mg tds
30–40 750mg tds
>40 1000mg tds
Table 7-9: Doses of Factor VIII for bleeds

Site of Bleed Desired Factor VIII Duration (Days) Comments
Factor VIII dose (IU)
level (% of per kg body
normal) weight
Joint 40–60 25 1–3 or longer Depends on response
Muscle (Minor) 40–60 25 1–3 or longer Depends on response
Muscle (Major) Calf and forearm
including bleeds may lead to
ileopsoas bleeds compartment
• Initial 80–100 50 1–2 syndrome
• Maintenance 30–60 25 3–5 or and be limb
longer as threatening. Consult
prophylaxis haematologist
during and orthopaedic
physiotherapy surgeon.
Involvement of
ileopsoas muscle
may be associated
with significant
blood loss.
Gastrointestinal Tranexamic acid is
tract helpful
• Initial 80–100 50 1–6
• Maintenance 50 25 7–14
Epistaxis 30–50 25 1–2 Use tranexamic acid
25mg/kg 8 hourly
Oral mucosa 30–50 25 1–2 for 5–7 days as an
Dental 50–100 25 1–2 adjunct therapy
extraction
Haematuria 30–100 50 3–5 *Tranexamic acid is
contraindicated
Central Always treat with
Nervous System factor replacement
• Initial 80–100 50 1–7 prior to CNS
• Maintenance 50 25 8–21 imaging. Urgent
consult with
haematologist and
neurosurgeon
Deep Laceration 50 25 5–7
Continued overleaf
Site of Bleed Desired Factor VIII Duration (Days) Comments

Factor VIII dose (IU)
level (% of per kg body
normal) weight
Retropharyngeal
• Initial 80–100 50 1–7
• Maintenance 50 25 8–14
Retroperitoneal 80–100 50 3–5
Surgery (major)
• Pre-Op 80–100 50 At induction and
up to POD 7
• Post-Op 30–50 20 POD 8–14
Dose of Factor VIII for surgical procedures:

Major surgical procedures require FVIII levels to be raised to 100% (i.e.
50IU/kg). Maintain circulating factor VIII activity of 80%–100% for the
first 7 postoperative days and 30–50% for up to the fourteenth post-
operative day. The duration of bleeding risk should be discussed with
the surgeon and used to guide factor replacement therapy.
Dose of Factor VIII for dental extractions:

Minor dental extractions:
 Factor VIII activity of 50% before extraction.
 To maintain levels of at least 50% for treatment of persistent
oozing.
Major dental procedures:
 Loading dose = 50 IU/kg followed by
 Maintenance dose = 15 IU/kg every 8–12 hours for the first 1–2
days, then same dose 1–2 times a day for 5 days or until wound is
adequately healed.
Tranexamic acid should be given up to the seventh post-operative day
for all dental procedures.
DDAVP (Desmopressin)
 Releases stored FVIII into the circulation
 To be used only in patients with mild haemophilia A where
there is documented evidence in the medical record of safe and
satisfactory response to a DDAVP challenge
 Not adequate for haemostasis in major bleeding
 Generally not recommended in young children (<3 years) due to

documented reports of hyponatraemia and seizures. Relatively
contraindicated in children with previous seizure disorders.
IV Desmopressin: 0.3mcg/kg infusion (to monitor BP and pulse

during infusion)
Intranasal Desmopressin: 150mcg (for patients <50kg); 300mcg (for
patients >50kg)
MANAGEMENT OPTIONS FOR PATIENTS WITH FACTOR VIII

INHIBITORS
 Swarming with Factor VIII:
 More likely to be effective if inhibitor level<5 BU
 Initial Dose: 70–140 FVIII/kg bolus
 Maintenance: 4–14 FVIII/kg/hr of continuous infusion (dose can
be increased much more and should be adjusted according to
plasma Factor VIII levels)
 APCC (Activated Prothrombin Complex Concentrate/FEIBA)

Initial Dose: 50–100 IU/kg/dose, depending on severity of haemorrhage
Dosing Interval: Up to 4 times a day
* Avoid concomitant use of tranexamic acid with APCC due to

increased risk of thrombosis
 Activated FVIIa (Novoseven)

Initial Dose: 0.9mcg/kg/dose to be repeated 2 hourly until bleeding
stops.
SPECIFIC CLOTTING FACTOR REPLACEMENT IN HAEMOPHILIA B

Factor IX:
Dose of Factor IX (IU) = Body weight (kg) x 1.0 IU/kg x Desired increase
in plasma Factor IX (%). Doses should be rounded to the nearest whole
vial size to avoid wastage.
Dose of Factor IX for surgical procedures:

Major surgical procedures require FIX levels to be raised to 100% (i.e.
100IU/kg). Maintain circulating factor IX activity of 80–100% for the first
7 postoperative days and 30–50% for up to the fourteenth postoperative
day. The duration of bleeding risk should be discussed with the surgeon
and used to guide factor replacement therapy.
Table 7-10: Doses of Factor IX for Bleeds

Desired Factor IX
Factor IX dose per Duration
Site of Bleed Comments
level, % kg body (Days)
of normal weight
Joint 40–60 50 1–3 or longer Depends on response
Muscle (Minor) 40–60 50 1–3 or longer Depends on response
Muscle (Major) Calf and forearm bleeds may lead to

including compartment syndrome and be limb
ileopsoas bleeds threatening. Consult haematologist
and orthopaedic surgeon.
• Initial 60–80 75 1–2
Involvement of ileopsoas muscle
• Maintenance 30–60 50 3–5 or longer
may be associated with significant
as prophylaxis
blood loss.
for physiotherapy
Gastrointestinal tract
• Initial 60–80 75 1–6 days
Tranexamic acid is helpful
• Maintenance 30 30 7–14 days
Epistaxis 30–50 50 1–2 days
Oral mucosa 30–50 50 1–2 days Use tranexamic acid 25mg/kg 8 hourly
Dental extraction 50–100 50 1–2 days for 5–7 days as an adjunct therapy
*Tranexamic acid is
Haematuria 30–100 75 3–5 days
contraindicated
Central Nervous
System Always treat with factor replacement
• Initial 80–100 100 1–7 days prior to CNS imaging. Urgent consult
• Maintenance 30 30 8–21 days with haematologist and neurosurgeon
Deep laceration 50 50 5–7 days
Retropharyngeal
• Initial 80–100 100 1–7 days
• Maintenance 50 50 8–14 days
Retroperitoneal 80–100 100 3–5 days
Surgery (major) At induction and

• Pre-Op 80–100 100 up to POD7
• Post-Op 30–50 50 POD 8–14
Dose of Factor IX for dental extractions:

Minor dental extractions:
Factor IX activity of 50% before extraction.
To maintain levels of at least 25% for treatment of persistent oozing.
Major dental procedures:

Loading dose = 100IU/kg followed by
Maintenance dose = 30IU/kg every 8–12 hours for the first 1–2 days, then
same dose 1–2 times a day for 5 days or until wound is adequately healed.

VON WILLEBRAND DISEASE
Background
Von Willebrand disease is the most common inherited bleeding disorder
affecting up to 1% of the population, with most cases caused by a mild
quantitative deficiency of von Willebrand factor (vWF). Quantitative or
qualitative deficiencies of vWF cause inadequate platelet adhesion and
secondary deficiency of Factor VIII. It affects males and females equally.
It is characterised by easy bruising, bleeding from mucosal membranes
(particularly epistaxis, oral mucosa, and menorrhagia) and post-op
bleeding (see Table 7-11).
MANAGEMENT OF ACUTE BLEEDS IN VON WILLEBRAND DISEASE

PATIENTS
Antifibrinolytic Therapy (Tranexamic Acid)

 Bleeds in patients with mild von Willebrand disease tend to
be minor and occur from mucosal surfaces. Treatment with
tranexamic acid is usually sufficient to control bleeding.
 May be given alone or as an adjunct therapy to DDAVP/
factor concentrate.
 Dose of tranexamic acid is 25mg/kg/dose tds orally for 5–7 days
 Referral to the ENT surgeon may be required for local control of
bleeds from epistaxis
DDAVP (Desmopressin)
 Patients with mild to moderate Type 1 vWD can be treated with
DDAVP when there is documented evidence in the medical
record of safe and satisfactory response to a DDAVP challenge
Table 7-11: Phenotypes of von Willebrand Disease

vWF Defect Typical bleeding
pattern
Type 1 Mild to moderately reduced levels of vWF Typically associated with
(common) mild bleeding
Type 2 Abnormal structure and function of vWF, several variants including: Variable bleeding
(uncommon) 2A — Decreased formation of high molecular weight vWF multimers, pattern
interfering with collagen binding
2B — Abnormal affinity of platelets, leading to significant
thrombocytopenia
2M — Decreased affinity of the vWF molecule for platelet glycoproteins
2N — Decreased affinity of the vWF molecule for Factor VIII, can
present with symptoms similar to haemophilia
Type 3 (rare) Severe quantitative defect of vWF Patients may behave like
those with moderate to
severe haemophilia
 Occasionally effective in Type 2 vWD, never effective in Type 3 vWD

 Contraindicated in Type 2B vWD as it worsens
thrombocytopenia
 Expect two- to three-fold increase in Factor VIII/vWF level.
 Generally not recommended in young children (younger than 3
years) due to documented reports of hyponatraemia and seizures.
Relatively contraindicated in children with previous seizure disorders.
IV Desmopressin: 0.3mcg/kg infusion (to monitor BP & pulse during

infusion)
Intranasal Desmopressin: 150mcg (for patients <50kg), 300mcg (for
patients >50kg)
FVIII/vWF Plasma Concentrate for von Willebrand Disease

 Human plasma-derived product containing both Factor VIII and
von Willebrand factor concentrate
 Used to treat bleeding in patients with Type 2 and Type 3 vWD
 Required in Type 1 vWD if severe bleeding or unresponsive to DDAVP
 Dose of factor concentrate to be used will depend on clinical
severity of disease and bleed
*Please round up the dose to the nearest whole vial size. Do not
waste any factor.
Table 7-12: Doses of Factor VIII/von Willebrand Factor Concentrate for bleeds in severe Type 3 vWD
Type of bleeding Dose of Factor Concentrate
Oral mucosa/epistaxis/menorrhagia 50 - 100 Factor VIII units/kg
Gastrointestinal 100 - 150 Factor VIII units/kg
Joint/muscle 100 - 150 Factor VIII units/kg
CNS bleed 100 - 250 Factor VIII units/kg
Please note that these doses are used in cases of severe vWD (e.g. Type 3).
Patients with Type 1 vWD often required lower doses of factor concentrates.
Please consult haematologist if required.
Dose of Factor VIII for surgical procedures:

Pre-operative loading dose: 150 Factor VIII units/kg
Maintenance post-operative doses: 100 - 150 Factor VIII units/kg at 8–12
hourly intervals until wound is adequately healed.
Dose of Factor VIII for dental extractions:
Minor dental extractions —
vWF activity of 50% before extraction
Dose of 100 Factor VIII unit/kg before procedure
Major dental extractions —

vWF activity of 75% before major extraction
Dose of 150 Factor VIII unit/kg before procedure
OTHER BLEEDING DISORDERS

HAEMORRHAGIC DISEASE OF NEWBORN (HDN)
Newborn infants have lower levels of Vitamin-K dependent clotting factors
(Factors II, VII, IX, X) due to poor transplacental passage of Vitamin K and low
levels stored in the neonatal liver. Endogenous production of Vitamin K in
the infant gut occurs only after a few weeks when the intestinal microflora is
established. Infants who have not been given exogenous intramuscular or
oral Vitamin K after birth are at risk of developing HDN.
Presentation
 Most common sites of bleeding are from the umbilicus,
mucous membranes, gastrointestinal tract, circumcision and
venepuncture sites. Haematomas can occur at sites of trauma,
including sites related to instrumental delivery. Intracranial
bleeding is a risk.
 Early HDN
 Presentation is within first 24 hours
 Associated with maternal medications, e.g. anticonvulsants
affecting Vitamin K metabolism
 Classic HDN
 Presents 2–7 days after birth
 Seen in infants who did not receive Vitamin K prophylaxis at
birth
 Late HDN
 Presents 2–12 weeks after birth
 Most commonly seen in breastfed infants who did not
receive Vitamin K prophylaxis at birth as human milk is low
in Vitamin K content
 Can also be seen in infants with chronic diarrhoea,
malabsorption syndromes and chronic antibiotic therapy
Management
 Severe episodes of bleeding can be treated with fresh frozen
plasma/prothrombin complex concentrate
 Vitamin K can be given subcutaneously with local pressure if
bleeding is not severe. Avoid intramuscular injections because of
the risk of haematoma
 IV Vitamin K can be given; however it must be administered as a
slow infusion due to risk of anaphylactic reactions
DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC)

Disseminated intravascular coagulation (DIC) is an acquired
clinicopathological syndrome characterised by systemic activation
of coagulation leading to generation of fibrin clots that cause
microvascular thrombosis and organ failure; as well as concomitant
consumption of platelets and coagulation factors that can result in
bleeding. Causes include sepsis, malignancies (commonly seen in acute
promyelocytic leukaemia), haemolytic transfusion reactions, toxins and
trauma.
Clinical features include signs of bleeding into skin and mucosa at

multiple sites. There is oozing from venepuncture sites, petechiae and
purpura. There can be fulminant bleeding from internal organs such
as the gastrointestinal tract, brain and lungs, leading to shock and
end-organ failure. At the same time microvascular thrombi in arterial
and venous sites also contribute to end-organ failure, especially in the
kidneys and brain.
Diagnosis
 The diagnosis of DIC is based on a combination of clinical features
supported by relevant laboratory tests
 Suggestive laboratory findings include:
 Thrombocytopenia
 Red cell fragmentation seen on the peripheral blood film
 Prolonged PT, APTT
 Low fibrinogen
 Raised markers of fibrinolysis — Raised D-dimer, fibrin
degradation products (FDP)
Management
 The underlying cause of DIC must be treated
 Management is mainly supportive, with correction of any factors
that can further precipitate or worsen DIC, including hypotension,
hypoxia and hypothermia
 Maintain platelet counts >50x109/L
 FFP/cryoprecipitate to correct coagulopathy if there is active
bleeding
 Maintain fibrinogen >1g/L.
Bibliography
1. Kasper. C. K. Diagnosis and Management of Inhibitors To Factor VIII and IX.
2. An introductory discussion for physicians. World Federation of Haemophilia. 2004:34;1–26
3. White GC et al. Definitions in Haemophilia: Recommendation of the Scientific
Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization
Committee of the International Society on Thrombosis and Haemostasis. Thromb
Haemost 2001; 85: 560
THROMBOSIS AND THROMBOPHILIA IN

PAEDIATRIC PATIENTS
Venous and arterial thrombosis are rare events in children, with an
estimated incidence of 1–6 per 100, 000. Risk factors for thrombosis
in children differ markedly from adults, as conditions such as
atherosclerosis, hypertension, smoking and diabetes mellitus are rarely
present in children. The highest rate of thrombosis in children occurs in
two age groups — infants younger than 1 year and adolescents older
than 13 years.
Predisposing Conditions
These include:
 Indwelling catheters (single most important risk factor)
 Infection/trauma/surgery/vascular malformation/cardiac disease/
prosthetic valves
 Inflammatory diseases — Systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease
 Renal diseases — Chronic renal failure, nephrotic syndrome
 Drugs — High-dose steroids, asparaginase
 Inherited thrombophilias
Signs and Symptoms

 Venous thromboembolism:
 Warmth, tenderness and swelling of a limb
 Homans sign — Calf pain on dorsiflexion of the ankle
 Inability to flush or draw blood from an indwelling catheter
 Chest pain, haemoptysis, palpitations (pulmonary embolism)
 Headache, neurological impairment (cerebral venous sinus
thrombosis)
 Arterial thrombosis:
 Neurological symptoms, e.g. hemiplegia (paediatric stroke)
 Impaired limb perfusion
Diagnostic Investigations
 Imaging
 Doppler ultrasound to diagnose upper or lower limb deep venous
thrombosis/catheter-related thrombosis
 Upper limb thrombosis may require CT venography or MR
venography as Doppler ultrasound may relatively insensitive for
the detection of intra-thoracic thrombosis
 CT pulmonary angiography (CTPA) is recommended as the
imaging modality for suspected PE
 CT or MRI brain with angiography for diagnosis of paediatric stroke
Thrombophilia Testing in Children

Thrombophilia refers to a genetic predisposition to the development
of venous and arterial thromboembolic disease. The contribution of
inherited thrombophilia in paediatric thrombosis is unknown, as the
majority of young children who develop thrombosis have multiple
risk factors. Thrombophilia testing of children with paediatric stroke is

common, with reported prevalence of inherited thrombophilias varying
from 20–50%. The utility of thrombophilia testing during an acute event
is controversial, as thrombosis itself will result in transient changes in
serum levels of antithrombotic proteins.
The identification of an inherited thrombophilia should not influence

the acute management of thrombosis in a child. There is not enough
data to determine whether the presence of thrombophilia should
influence the duration of anticoagulation. A family history may or
may not be present, but should always be asked for when considering
thrombophilia testing.
 Whom to Test
 Routine testing in unselected children with a first episode of
venous thromboembolism (VTE), especially if catheter-related, is
not recommended
 Consider testing if there are recurrent episodes of unprovoked VTE
 Consider testing adolescents with spontaneous, unprovoked VTE
 Testing of asymptomatic children with a positive family
history is controversial and should only be made after careful
discussion and counselling with the family
 What to Test
 Protein C  Fasting homocysteine
 Protein S (free and functional)  Factor VIII assay
 Antithrombin  Factor V Leiden gene**
 Lupus anticoagulant  Prothrombin G20210A gene**
 Anticardiolipin antibodies
(** Prevalence in Asians is <1%)
 When to test
 Testing for thrombophilia in the acute setting may result in an
incorrect diagnosis of inherited thrombophilia as levels of Protein
C, Protein S and antithrombin may show a transient decrease
during acute thrombosis
 Protein C, S and antithrombin are also affected by anticoagulants
including heparins and vitamin K antagonists
 Thrombophilia testing should ideally be carried out when the

acute event has resolved and anticoagulants have been taken off
for at least 6 weeks
 Genetic tests are not affected during an acute episode and can be
performed any time
Management of Venous Thromboembolism

The aims of anticoagulant therapy in children with VTE include:
 Reduce risk of thrombus extension and embolisation
 Reduce risk of recurrent thrombosis
 Reduce the incidence of post-thrombotic syndrome by limiting
vascular damage
 Anticoagulant Therapy
 Low molecular weight heparin (LMWH) — subcutaneous
 Usually used as first-line therapy for management of acute VTE
 Monitored using serum Anti-Xa levels, targeting a therapeutic
level of 0.5–1 U/ml
 Caution should be exercised in children with renal impairment
as LMWHs are renally excreted
 Anticoagulant effect not completely neutralised by protamine
 Unfractionated heparin (UFH) — intravenous

 Indicated in situations where there is significant bleeding risk
as duration of action is shorter compared to LMWH
 Anticoagulant effect can be 100% neutralised by protamine
 Disadvantages include intravenous route of administration
and need for frequent monitoring of APTT every 4–6 hours to
achieve therapeutic target of between 60–80s
 Warfarin
 Vitamin K antagonist
 Indicated where long-term anticoagulation is required beyond
6–12 months
 Multiple interactions with other medications and food
 Monitored using INR, usually targeted between 2–3 for
management of VTE
 Duration of anticoagulant therapy

 Duration of therapy is guided by site of thrombosis and
presence of ongoing risk factors
 General principles include:

 Catheter-related VTEs — Anticoagulation therapy for 6
weeks to 3 months
 Secondary VTE with risk factors — Anticoagulation
therapy for a minimum of 3 months, or until resolution of
the precipitating factor
 First unprovoked VTE — Anticoagulation therapy for 6–12
months
 Recurrent unprovoked VTEs — Consider indefinite
anticoagulation therapy
 Thrombolytic Therapy
 The use of thrombolytic therapy is usually not indicated in the
majority of children with VTE, but may be considered in the
presence of extensive thrombosis or in critical situations such as
intra-cardiac/pulmonary embolism
 Available agents include streptokinase and tissue plasminogen
activator (TPA)
Bibliography
1. Chalmers EA et. al. Guideline on the investigation, management and prevention of venous
thrombosis in children. British Committee for Standards in Haematology. http://www.
bcshguidelines.com/documents/BCSHChildhoodVTEFinalDec2010.pdf.
2. Raffini L. Thrombophilia in Children: Who to Test, How, When and Why? American Society
of Haematology Education Book 2008. http://asheducationbook.hematologylibrary.org/
content/2008/1/228.full.pdf.
3. Kenet G. et al. Impact of Thrombophilia on Risk of Arterial Ischemic Stroke or Cerenral
Sinovenous Thrombosis in Neonates and Children. Circulation 2010;121:1838–47.
4. Monagle P et al. Antithrombotic Therapy in Neonates and Children: ACCP Evidence-Based
Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e737S-801S.
5. KK Hospital Guidelines for Anticoagulation Therapy in Children.
TRANSFUSION OF BLOOD COMPONENTS IN

PAEDIATRICS
Transfusion of red cells and other blood components in paediatrics may

be required in clinical situations such as acute blood loss, bone marrow
failure and in preparation for major surgical procedures. However
transfusion of blood products is associated with a definite risk of adverse
reactions and should only be carried out when the expected benefits are
likely to outweigh the potential hazards.
SAFETY ISSUES RELATED TO TRANSFUSION OF BLOOD

PRODUCTS
There must be a clear, documented clinical indication for transfusion.
Informed consent should be obtained from parents or guardians prior
to transfusion of blood components. The person giving consent should
be informed of the benefits, risks and potential complications associated
with transfusion of blood components.
Correct patient identification is critical when taking blood samples for
group and cross matching and when transfusing blood components to
patients. Errors in mislabelling and patient identification can result
in an incompatible blood transfusion, which has potentially fatal
consequences for the patient.
DETERMINING THE CHOICE OF ABO GROUPS FOR BLOOD

COMPONENTS
 Persons who are ABO Group A have red cells expressing

A-antigens, and have circulating Anti-B antibodies in plasma
 Persons who are ABO Group B have red cells expressing
B-antigens, and have circulating Anti-A antibodies in plasma
 Persons who are ABO Group AB have red cells expressing both
A-antigens and B-antigens, and do not have any circulating
Anti-A or Anti-B antibodies in plasma
 Persons who are ABO Group O have red cells that do not express
either the A-antigen or B-antigen, and have circulating Anti-A
and Anti-B antibodies in plasma
 A pack of red cells of a particular ABO blood group is expected to
contain the corresponding red cell antigens
 Platelets, fresh frozen plasma (FFP) and cryoprecipitate contain
large amounts of plasma, and are expected to carry antibodies
associated with the corresponding ABO blood group
 The choice of ABO groups for transfusion of different blood
components can thus be summarised below:
Table 7-13: Choice of ABO groups for blood components

ABO Group of Blood Component to be Transfused
Patient’s ABO Group Red Cells Platelets FFP
A
First Choice A A A
Second Choice O B AB
B
First Choice B B B
Second Choice O A AB
AB
First Choice AB AB AB
Second Choice A/B A/B -
O
First Choice O O O
Second Choice - A/B A/B
RED CELL TRANSFUSIONS

 The aim of red cell transfusions is to increase the oxygen carrying
capacity of the blood by increasing haemoglobin concentration
in patients with anemia
 The decision to transfuse should not be merely based on a
“number” but on a clinical indication
 There are few large studies looking at the effectiveness of
haemoglobin transfusion thresholds in children
 In general, red cell transfusion may be beneficial especially in
symptomatic patients or in patients with ongoing blood loss
when Hb <7g/dL
 There is usually very little indication for red cell transfusion when
the Hb is >10g/dL
 By consensus, common transfusion triggers (see Table 7-14) based
on haemoglobin levels used in paediatrics include:
 The volume of red cells to be transfused can be calculated using
the formula
 Volume to be transfused (ml) = (Desired Hb minus Current
Hb in g/dl) x (Body weight in kg) x 3.5
 The volume of red cells to be transfused is usually between
10–15ml/kg and should not exceed 20ml/kg
Table 7-14: Common RBC transfusion triggers
Clinical Situation Hb Transfusion Trigger (g/dL)

Neonate in intensive care 12
Patients undergoing chemotherapy
Stable 8
Unstable/febrile 9
Patients with chronic anemia on regular 9
transfusion therapy
 A transfusion of 10ml/kg of red cells is expected to raise the Hb

by 2–2.5g/dL. However this is variable and dependent on the
underlying clinical condition of the child
PLATELET TRANSFUSIONS
 The degree of thrombocytopenia does not always correlate
with bleeding severity, especially in conditions such as immune
thrombocytopenia
 The decision for platelet transfusion should not be based on
platelet counts alone but on the clinical situation and other risk
factors for bleeding
 There are also few large studies looking at the effectiveness of
platelet transfusion thresholds in children
 By consensus, common transfusion triggers based on platelet
counts used in paediatrics include:
Table 7-15: Common platelet transfusion triggers

Clinical Situation Platelet Transfusion Trigger (x109/L)
Neonate 30–50
Bone marrow failure (e.g. aplastic anemia) 10–20
Patients undergoing chemotherapy
Stable 20
Unstable/febrile 30
Prior to lumbar puncture 50
Prior to surgical procedures 50–80
Prior to neurosurgical procedures 100
 The volume of platelets to be transfused is 10ml/kg or 4 units/m2

9
— this is expected to raise the platelet count by 30–50x10 /L
 In Singapore, platelets for paediatric patients can be ordered
either as single units of “apheresed platelets paediatric” (APP) or
“cell-separated platelets” (CSP)
 1 unit of CSP is equivalent to 4–6 units of APP
 In general, children weighing >40kg should be transfused with a
unit of CSP
FRESH FROZEN PLASMA (FFP) TRANSFUSIONS

 Fresh frozen plasma contains coagulation factors, fibrinogen,
albumin and immunoglobulins
 Fresh frozen plasma should not be transfused merely to correct
an “abnormal” PT or APTT without a prior assessment of the
underlying cause of coagulopathy
 The indications for FFP transfusion include:
 Reversal of warfarin overdose, in combination with
prothrombin complex concentrate (PCC) and Vitamin K
 Acute disseminated coagulopathy
 Coagulopathy associated with liver disease
 Clotting factor deficiencies for which no alternative clotting
factor concentrates are available, e.g. Factor XI deficiency
 Massive transfusion
 The recommended dose of FFP is 10–15ml/kg
CRYOPRECIPITATE
 Cryoprecipitate contains high amounts of Factor VIII, von
Willebrand factor, fibrinogen and Factor XIII
 It is not recommended for clotting factor deficiencies
where specific clotting factor concentrates are available (e.g.
Haemophilia A and B)
 Because of the higher concentration of fibrinogen in
cryoprecipitate compared to FFP, it is useful in clinical situations
where potential volume overload is an issue
 Indications for use of cryoprecipitate include:
 Hypofibrinogenaemia
 Disseminated intravascular coagulopathy
 Advanced liver disease
 Massive transfusion
 The recommended dose of cryoprecipitate is 5–10ml/kg
MODIFIED BLOOD COMPONENTS

LEUCODEPLETED/“CMV-NEGATIVE” BLOOD PRODUCTS
 White blood cells present in red cells and platelets is associated
with various adverse effects such as non-haemolytic febrile
transfusion reactions, HLA alloimmunisation and transmission of
intracellular organisms such as cytomegalovirus (CMV)
 In Singapore, due to the high CMV seropositive rate, “CMV-
negative” blood products are not obtained from CMV- seronegative
individuals, but are produced from leucoreduction of donated blood
 From 2012, a change in the production method of platelets
resulted in all platelet concentrates in Singapore being
leucodepleted. There is thus no need to specially request for
“CMV-negative”/leucodepleted platelets
 However universal leucodepletion of red cells is still not practiced
in Singapore. Hence special requests for “CMV-negative”/
leucodepleted red cells must be made when indicated
 Indications for use of leucodepleted blood components include,
but are not limited to:
 Haematopoietic stem-cell transplant recipients
 Solid organ transplant recipients
 Immunocompromised patients at risk of infection with
intracellular organisms
 Congenital immunodeficiencies
 Premature neonates
 Intrauterine transfusions
 Patients experiencing frequent non-haemolytic febrile
transfusion reactions
IRRADIATED BLOOD PRODUCTS

 Gamma irradiation of red cells and platelets renders
T-lymphocytes non-viable
 Irradiation of blood products hence prevents transfusion-
associated graft-versus-host disease (TaGVHD) mediated by
donor T-lymphocytes
 Fresh frozen plasma is an acellular blood product and does not
require irradiation
 Indications for use of irradiated blood components include, but
are not limited to:
 Intrauterine transfusions
 Congenital immunodeficiency, especially in T-cell
immunodeficiency syndromes, e.g. DiGeorge syndrome,
severe combined immunodeficiency
 Haematopoietic stem cell transplant patients

 Patients treated with purine analogues, e.g. Fludarabine
 Transfusion from first- and second-degree relatives
 All granulocyte products
WASHED RED CELLS

 Washing of red cells removes the majority of plasma and plasma
proteins from the unit
 There is a red cell loss of 10–20% associated with the procedure
 Units of washed red cells must be used within 24 hours as the
procedure is carried out in an open system
 Indications for use of washed cells include:
 Patients with IgA deficiency
 Patients with a history of severe anaphylactic transfusion
reactions or recurrent allergic transfusion reactions
 Patients with haemolytic uraemic syndrome (HUS)
ADVERSE TRANSFUSION REACTIONS

 An adverse transfusion reaction is defined as an undesirable
response in a patient temporally associated with the
administration of a blood component
 Transfusion reactions can be acute (presenting within 24 hours) or
delayed
 It is important to recognise a transfusion reaction as many of the
early signs and symptoms can be non-specific, including fever,
chills, rigors and urticarial rash
 Allergic reactions and febrile non-haemolytic transfusion
reactions are common but less serious whereas acute
haemolytic transfusion reactions, bacterial contamination of
blood products and transfusion-related acute lung injury (TRALI)
are less common but life-threatening
WHAT TO DO WHEN AN ADVERSE TRANSFUSION REACTION IS

SUSPECTED
 All suspected transfusion reactions must be reported to the
issuing Blood Bank
 Any ongoing transfusion of the suspected unit must be stopped
immediately
 Monitor the patient’s vital signs
 Do an immediate clerical check at the bedside to detect any
misidentification and major ABO mismatch. This is the most
common cause of an acute haemolytic transfusion reaction.
 Maintain intravenous access for treatment if necessary

 Coordinate with the Blood Bank regarding samples to collect for
investigation of the suspected transfusion reaction
 Do not initiate any further transfusions without consultation with
the Blood Bank/haematologist
 See Figure 7.4 for the various approaches to diagnosing the
likely type of adverse transfusion reaction depending on the
presenting symptoms
 See Table 7-16 for the features and management of the various
types of adverse transfusion reactions
Table 7-16: Features and management of adverse transfusion reactions

Transfusion Reaction Features Management
Allergic reaction Morbilliform rash Antihistamines
Urticaria Steroids
Flushing Transfusion can be restarted if signs and
Localised angioedema symptoms subside
For future transfusions — Premedicate
with antihistamines/steroids
Consider washed cells if recurrent
Febrile non-haemolytic Fever (≥38oC or a rise of ≥1oC from Antipyretics

transfusion reaction pre-transfusion value) For future transfusions — Premedicate
Chills/rigors with antipyretics
Headache Use white cell filter
Vomiting Consider leucodepleted blood products
if recurrent
Acute haemolytic reaction Fever/chills/rigors Maintain Airway, Breathing, Circulation

Back/flank pain Hydration to maintain urine output
Hypotension/shock Diuretics to maintain urine output
Severe pain at IV site Inotropic support
Haemoglobinuria/oliguria Treatment of DIC
Disseminated intravascular
coagulopathy (DIC)
Transfusion Reaction Features Management

Anaphylaxis Hypotension Rash Maintain Airway, Breathing, Circulation
Respiratory symptoms — Hydration
laryngospasm, stridor, wheezing Adrenaline , Antihistamines, Steroids
Inotropic support
Transfusion-associated Fever Maintain Airway, Breathing, Circulation

sepsis (bacterial Chills/rigors Supportive management, e.g. inotropic
contamination) Hypotension/shock support
Renal failure Appropriate systemic antibiotic therapy
Transfusion-associated Acute respiratory distress within 6 hours Maintain Airway, Breathing, Circulation
acute lung injury (TRALI) of transfusion Oxygen and ventilatory support
Bilateral pulmonary infiltrates on CXR
Hypoxaemia
No evidence of circulatory overload
Transfusion-associated Acute respiratory distress Maintain Airway, Breathing, Circulation

circulatory overload Hypertension/tachycardia Oxygen and ventilatory support
(TACO) Evidence of left heart failure Diuretics
Pulmonary oedema on CXR
Transfusion-associated Fever Immunosuppression

graft- versus-host disease Gastrointestinal symptoms Prevent by transfusing irradiated blood
(TaGVHD) Rash products for patients at risk
Hepatitis
Pancytopenia
Figure 7.4: Approach to diagnosing the type of transfusion reaction based on presenting symptom.
Source: HSA-MOH Clinical Practice Guideline on Clinical Blood Transfusion 2011, Pages 63–64
Fever/chills
Acute Haemolytic Bacterial Febrile Non- Haemolytic

Reaction Contamination Transfusion Reaction
Hives/Urticaria
With respiratory symptoms and/or
No other symptoms hypotension
Allergic Reaction Anaphylatoid or Anaphylactic

(Mind) (Severe)
Dyspnea Tachycardia
Hypertension
Hypotension
Rash/Urticaria Transfusion Associated
CXR shows infiltrates
Circulatory Overload (TACO)
Anaphylaxis
TRALI
Anaphylactoid
Hypotension
Acute Haemolytic
Bacterial Contamination
Reaction
Anaphylactoid
TRALI Anaphylaxic (Severe)
Bibliography
1. Health Sciences Authority — Ministry of Health Singapore Clinical Practice Guideline on
Clinical Blood Transfusion 2011. http://www.moh.gov.sg/content/dam/moh_web/HPP/
Doctors/cpg_medical/current/2011/Blood%20transfusion%20Final.pdf
2. British Committee for Standards in Haematology. Transfusion Guidelines for Neonates and
Older Children. British Journal of Haematology 124(4):433–453
3. The Royal Children’s Hospital Melbourne Clinical Practice Guideline for Blood Product
Transfusion. http://www.rch.org.au/clinicalguide/guideline_index/Blood_product_
transfusion/
ACUTE LEUKAEMIA, TUMOUR LYSIS

AND HYPERLEUCOCYTOSIS
Acute leukaemia is the most common malignancy in childhood. In general
there are 2 types of acute leukaemia in children — acute lymphoblastic
leukaemia (ALL) and acute myeloid leukaemia (AML). Although urgent
diagnosis and treatment are important, immediate supportive care is
also necessary to monitor, prevent and treat complications such as acute
tumour lysis syndrome and hyperleucocytosis.
INVESTIGATIONS FOR PATIENTS NEWLY DIAGNOSED WITH

ACUTE LEUKAEMIA
 Blood Tests
 Full blood count (FBC); peripheral blood film (PBF)
 Clotting profile (PT and aPTT). Serum fibrinogen and d-dimers
should be done in patients with suspected or possible
disseminated intravascular coagulation (DIC), e.g. in sepsis or
acute promyelocytic leukaemia (APL).
 Biochemistries: Renal panel and electrolytes — including serum
creatinine, potassium, calcium and phosphate; uric acid; lactate
dehydrogenase (LDH); LFT
 Serum immunoglobulins — IgG, IgA, IgM
 Viral immunity status
 Mandatory: Hepatitis B surface antigen (HBsAg), Hepatitis B
surface antibody (anti-HBs), Hepatitis B core total antibody
(anti-HBc), Varicella-zoster virus (VZV) IgG
 Others: Hepatitis C total antibody, CMV IgG, EBV VCA IgG, HSV
total antibody, HIV screen, Measles IgG, Mumps IgG, Rubella
IgG
 G6PD screen (if G6PD status unknown)
 Blood cultures (if febrile)
 Group and Cross Match
 Imaging Studies
 Chest X-ray (CXR) — Should be performed before the patient
receives any sedation (to exclude mediastinal mass)
 Echocardiogram (prior to first dose of anthracyclines)
 Bone Marrow Aspirate (BMA)

 Bone marrow aspirate examination or morphology
 Bone marrow aspirate immunophenotyping (by flow cytometry)
 Bone marrow aspirate cytogenetics

 Other investigations as required by treatment protocol, e.g.
minimal residual disease (MRD), oncogene fusion tests (OFTs).
Trephine biopsy may be required if there is a dry tap.
 Lumbar Puncture (LP)

 Cerebrospinal fluid profile
 Cerebrospinal fluid cytospin for blasts
The first LP should be done by an experienced doctor to reduce the risk
of traumatic tap. Intrathecal Methotrexate is usually given with the first
LP. Ensure adequate platelet counts (>50x109/L) before LP.
IMMEDIATE SUPPORTIVE MANAGEMENT

 Tumour Lysis Syndrome and Hyperleucocytosis
Tumour lysis syndrome (TLS) is a metabolic emergency that results from
massive tumour cell destruction, leading to biochemical derangements
that overwhelm the body’s excretory mechanisms. Laboratory TLS, as
defined by Cairo-Bishop, is 2 or more of the following within 3 days
before and 7 days after commencement of chemotherapy:
 hyperuricaemia ≥476µmol/L or 25% increase from baseline

 hyperkalaemia ≥6.0mmol/L or 25% increase from baseline
 hyperphosphataemia ≥2.1mmol/L or 25% increase from baseline
 hypocalcaemia ≤1.75mmol/L or 25% decrease from baseline.
In clinical TLS, deposition of urate and phosphate in the kidney results

in acute renal impairment. Severe electrolyte derangements such as
hyperkalaemia and hypocalcaemia can lead to cardiac arrhythmias,
tetany, and seizures and can be life- threatening. Patients with
acute leukaemia and high white cell count (>100x109/L) are at risk
of developing TLS. Other malignancies with high risk of tumour
lysis include high grade bulky lymphomas, e.g. Burkitt’s lymphoma/
leukaemia. Patients with underlying renal impairment are at higher risk
of developing TLS.
Hyperleucocytosis is defined as white blood cell (WBC) count

higher than 100x109/L. Hyperleucocytosis increases blood viscosity
(hyperviscosity) especially in the microcirculation, and leads to
leucostasis, which is the aggregation of blasts in the blood vessels.
Leucostasis is more common in AML as myeloblasts are larger in size
compared to lymphoblasts. Leucostasis symptoms most often involve

the lungs and the central nervous system. Symptoms can therefore
include respiratory distress, desaturation, headache, confusion,
drowsiness, seizure, visual disturbance, stroke, renal impairment etc. The
risk of symptomatic leucostasis is higher in ALL with WBC ≥300x109/L
and in AML with WBC ≥100x109/L (especially in M4/M5 subtypes).
 Management of TLS and Hyperleucocytosis:

 Hydrate with IV dextrose/saline at 3L/m2/day for at least 72 hours.
Patients with very low WBC may be given less fluids.
 Do not add potassium or phosphate to IV fluids.
 Start PO allopurinol 100mg/m2/dose TDS and continue till
peripheral blasts is reduced and serum uric acid level is normal.
Reduce dose in renal impairment. Consider recombinant
urate oxidase (rasburicase) if high risk of tumour lysis or renal
impairment (see Box).
 Urine alkalinisation is no longer recommended but may be
considered if there is metabolic acidosis. Alkalinisation increases
solubility of uric acid in the urine and prevents crystallisation
in the renal tubules. However, over- alkalinisation causes
crystallisation or precipitation of xanthine, hypoxanthine and
phosphate, and also worsens hypocalcaemia. To alkalinise, add
15ml 8.4% NaHCO3 to each 500ml of IV dextrose/saline and
subsequently adjust the amount of added NaHCO3 to keep the
urine pH 6.5–7.5. Urine pH should be measured at each void
when the patient is on alkalinisation. Do not alkalinise when
patient is on rasburicase.
 Specific electrolyte abnormality (hyperkalaemia,
hyperphosphataemia) should be treated accordingly (See
Nephrology chapter). Hypocalcaemia is not treated unless it is
symptomatic.
 If clinical TLS develops or fails to improve with above measures,
urgent renal dialysis will be necessary.
 Hyperleucocytosis should be managed by hydration and
other supportive care as described above, as well as prompt
initiation of chemotherapy. Leucopheresis may be considered for
patients with symptomatic leucostasis not responding to above
supportive care, if prompt chemotherapy cannot be initiated.
Leucopheresis is not recommended in asymptomatic patients,
and is contraindicated in APL.
 Clinical and laboratory monitoring — see next page.
Use of Recombinant Urate Oxidase (Rasburicase) in Tumour Lysis

Syndrome
(Decision to use rasburicase should be made by senior physician.)
Consider use of rasburicase in patients with high risk of TLS: bulky high grade

advanced stage non-Hodgkin lymphoma (e.g. Burkitt’s lymphoma, lymphoblastic
lymphoma); Burkitt’s leukaemia; ALL or AML with WBC ≥100x109/L, or LDH two
or more times more than ULN; elevated and rising uric acid especially if there is
underlying renal dysfunction.
Contraindicated in G6PD-deficiency, haemolytic anemia or hypersensitivity

Dose: IV 0.15–0.2mg/kg/dose Q24H for 1–7 days. (Senior physician to review if

more than 1 dose is needed.)
For 96 hours after the last dose of rasburicase, blood samples for uric acid

measurement should be sent to Lab immediately without delay, and preferably
transported in cool condition (e.g. with cooling packs). Uric acid results may be
falsely low post-rasburicase if there is delay in measurement, and especially if the
blood samples are at room temperature.
ULN — upper limit of normal
 Blood Products and Antibiotics

 Transfuse platelets if there is clinical bleeding or if there is
severe thrombocytopenia (<20x109/L). Keep platelets higher if
the patient is febrile (>30x109/L), bleeding (>50x109/L or even
higher if severe bleed) or if the patient is undergoing invasive
procedures (>50x109/L).
 Transfuse RBC if patient has severe anemia (Hb <6–7g/dL)
and symptomatic. In patients with newly diagnosed acute
leukaemia and high WBC, RBC transfusion may contribute to
hyperviscosity. Consider delaying RBC transfusion in these
patients until WBC is lower.
 Coagulopathy (DIC) in patients with hyperleucocytosis or APL
should be aggressively managed: Transfuse FFP/cryoprecipitate
to keep fibrinogen >1g/L and correct abnormal PT/aPTT.
 Start IV antibiotics if patient is febrile or septic (see febrile
neutropenia guidelines).
 Monitoring
 Monitoring during hyperhydration: Strict intake/output
monitoring with fluid tally every 4–6 hours during
hyperhydration. Ensure urine output >100ml/m2/hr (or >4ml/kg/
hr for infants). IV furosemide 0.5–1mg/kg/dose may be needed
if there is inadequate urine output or positive fluid balance

exceeding 600ml/m2/day. Weigh patient daily.
 Daily blood tests during first week of induction: FBC, Renal Panel,
Calcium, Phosphate, Uric Acid
 Close monitoring (every 4–6 hours, or less frequently if low risk of
ATLS) of serum potassium, phosphate and calcium until disease
load has reduced and no evidence of tumour lysis.
 Selected patients may need more frequent monitoring of FBC,
uric acid, and/or coagulation tests.
PSYCHOSOCIAL SUPPORT AND CHILD LIFE PROGRAMMES

Care of the child with cancer requires a team approach. Once the
diagnosis is established, the primary oncologist will hold a conference
with the patient’s family. The family will also be referred to medical social
workers as well as the Children Cancer Foundation for psychosocial
support and child life programmes.
Bibliography
1. Cairo, M. S. & Bishop, M. Tumour lysis syndrome: new therapeutic strategies and
classification. Br J Haematol 127, 3–11, doi:10.1111/j.1365-2141.2004.05094.x (2004).
2. Coiffier, B., Altman, A., Pui, C. H., Younes, A. & Cairo, M. S. Guidelines for the management
of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 26,
2767–2778, doi:10.1200/jco.2007.15.0177 (2008).
3. Cairo, M. S., Coiffier, B., Reiter, A., Younes, A. & on behalf of the, T. L. S. E. P.
Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome
(TLS) in adults and children with malignant diseases: an expert TLS panel consensus.
British Journal of Haematology 149, 578–586, doi:10.1111/j.1365-2141.2010.08143.x (2010).
4. Oberoi, S. et al. Leukapheresis and low-dose chemotherapy do not reduce early mortality
in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis. Leuk
Res 38, 460–468, doi:10.1016/j.leukres.2014.01.004 (2014).
5. SickKids Handbook of Supportive Care in Pediatric Oncology. 1st ed (2009).
6. Supportive Care of Children with Cancer: Current Therapy and Guidelines from the
Children’s Oncology Group (The Johns Hopkins Series in Hematology/Oncology) 3rd ed
(2004).
CENTRAL VENOUS ACCESS DEVICES IN

ONCOLOGY PATIENTS
The two most common long-term central venous access devices (CVADs)
used in oncology patients in KKH are the single-lumen Port-a-cath and
the double-lumen Hickman line. The CVADs can be kept in situ for the
entire duration of treatment, which can be as long as a few years. For
shorter-term venous access, a peripherally inserted central catheter
(PICC) may be used.
Both types of CVADs are inserted under general anaesthesia by

paediatric surgeons or intervention radiologists, using maximum sterile
barrier (MSB) precautions. Before insertion of the CVAD, ensure that:
 The coagulation profile is normal.
 The platelet count is at least 50x109/L (or higher if required by
surgeon)
 The patient is not having any active infection.
 Absolute neutrophil count is preferably at least 1x109/L. However,
this is usually not possible in children with newly diagnosed
haematologic malignancies.
Transfusion of blood products (red cells, platelets, plasma) may therefore
be needed peri-operatively, so pre-operative investigation results
should always be discussed with the surgeon and anaesthetist.
 The CVADs can be used immediately after insertion, after

checking that the line is in the correct place. The tip of the CVAD
should be at the junction of superior vena cava and right atrium.
 Sentinel blood cultures are drawn from a newly inserted CVAD
at first access to detect bacterial colonisation which may have
inadvertently occurred at insertion.
 After completion of therapy, removal of the CVAD can be done as
a day-surgery procedure.
PORT-A-CATH
The port-a-cath consists of a reservoir (or “port”) component and a
catheter component. It is an implanted subcutaneous central venous
access device, and thus should have minimal impact on body image
and requires very little care at home. Patients can shower or swim with
the device. The port-a-cath is accessed using a non-coring needle (e.g.
“Gripper needle”). Ordinary hypodermic needles should not be used as
they will damage the port septum. Topical anaesthetic can be applied
before accessing.
EXTERNAL TUNNELED CATHETERS (e.g. HICKMAN LINE)

The Hickman line is a percutaneous external catheter that can have one
or more lumens. There is a subcutaneous Dacron cuff near the exit site
that acts both as an anchor and as a barrier against infection. A double-
lumen Hickman line allows infusion of multiple drugs and is useful for
patients undergoing intensive chemotherapy or haematopoietic stem
cell transplant (HSCT). A suitable dressing (e.g. Tegaderm) is applied
over the exit site of the line at all times. The child cannot swim with
the Hickman line in situ. The child can take a shower, but with the line
covered (e.g. with a plastic bag) to prevent contact with water. The
external catheter may be more easily dislodged in very young children.
The long-term risk of infection and thrombosis is also higher than
implanted ports.
CARE OF CENTRAL VENOUS ACCESS DEVICE

 Strict hand hygiene and aseptic technique should be adhered to
for all procedures involving central lines. Only trained medical and
nursing personnel are allowed to use and maintain central lines.
 Skin preparation is done with chlorhexidine gluconate 2% with
isopropyl alcohol 70%. Catheter hubs or tubing cabs must also be
cleaned before each access with chlorhexidine gluconate 2% with
isopropyl alcohol 70% — “30s scrub and 30–60s dry."
 Tubings are changed every 3–4 days with routine use, and every 24
hours with lipids or blood product infusion.
 Port-a-cath needles are changed every 6–7 days. Dressings are
changed once a week with needle change. When de- accessing, the
port-a-cath is flushed with 10ml of normal saline and then heparin-
locked with 5–10ml of heparin-saline (100 units heparin per ml). To
make up 10mls of heparin-saline (100 units heparin per ml), add 1ml
of concentrated heparin sodium (1000u/ml) to 9ml of normal saline.
When not in use, the port-a-cath is flushed and heparin-locked once
a month.
 For Hickman lines, dressings are changed twice a week using gauze
dressing or once a week using transparent dressing. When de-
accessing, the Hickman line is flushed with 10ml of normal saline,
followed by 5ml of heparinised saline (10 units of heparin per ml).
When not in use, flushing and heparin-locking of Hickman line
should be done at least once a week.
COMPLICATIONS OF CENTRAL VENOUS ACCESS DEVICES

 Occlusion
Suspect CVAD occlusion when there is difficulty infusing fluids,
difficulty withdrawing blood (withdrawal or partial occlusion), or
both (complete occlusion). CVAD occlusion may be intraluminal (e.g.
thrombus or fibrin sheath) or extraluminal (mechanical factors such
as malpositioning of catheter tip, kink in the line, or even catheter
fracture). For newly inserted CVAD with suspected occlusion, inform
surgeon immediately and consider early linogram. Refer to algorithm
for management of suspected occlusion of CVAD with previously
normal blood backflow and smooth infusion. Thrombolytic therapy
with Urokinase may be necessary — see guidelines.
 Infection
The CVAD can be infected as a result of a catheter-related blood
stream infection or as part of a general septicaemia. When there is
a new onset of fever, blood cultures should be taken from CVAD.
Blood cultures from a peripheral vein are not necessary if the child
has a CVAD and is clinically stable. If peripheral blood cultures are to
be taken, it should not cause any delay in starting IV antibiotics. The
infection is likely to be catheter-related if:
 The skin over the port site or line track is red, inflamed or tender,
or if there is purulent discharge.
 The child develops fever and chills soon after the CVAD is flushed.
 There is no obvious source of the bloodstream infection in a
septic child with CVAD.
 Both central and peripheral blood cultures are positive, and the
differential time to positivity (DTP) is 2 or more hours. The DTP refers
to a blood culture drawn from the CVAD becoming positive before a
simultaneously drawn blood culture from a peripheral vein.
 The central cultures are positive whereas the peripheral blood
cultures (if taken) are negative
Figure 7.5: Algorithim for suspected CVAD infection

Tunnel/Exit Infection: Newly inserted Catheter-related Bloodstream Infection: Positive
Redness around CVAD site (within POD7)? blood culture from CVAD, and absence of other sources of infection.
Assess severity Inform surgeon# Appropriate IV Antibiotics via CVAD (alternating lumens);
who inserted CVAD Repeat blood cultures after 72 hours of appropriate antibiotics
Mild erythema; Induration (especially Persistent bacteraemia (after ≥72
no fever if along line tract or Refer surgeon-on-call#
hours of appropriate antibiotics)/
over port pocket)/fever/ and ID for urgent
OR Clinical deterioration
Topical care; purulent discharge removal* of CVAD
OR Septic emboli/infective
observe 24 hours within 24 hours.
endocarditis
Swab discharge (if any) OR Fungaemia
and send for culture OR Rapidly growing
mycobacteraemia
Recurrent (≥2) Refer surgeon-on-call#
Refer surgeon-on-call. bloodstream infection with and ID for removal* of
Progression
Start IV antibiotics via the same micro-organism CVAD within 7 days.
within 24 hours
peripheral cannula.
(Do not access CVAD till Newly inserted CVAD Inform surgeon#
Improvement surgical review) (within POD7) who inserted CVAD
Continue IV antimicrobial therapy for at least 10–14 days (or longer

e.g. for fungaemia, mycobacteraemia) from first negative culture.
* If CVAD is removed, the catheter tip should be sent for culture. # or intervention radiologist
Figure 7.6: Algorithim for suspected CVAD occlusion
Suspect CVAD Occlusion if: For newly • Inform surgeon or intervention

• Nil or sluggish backflow inserted CVAD radiologist who inserted the CVAD.
• And/or inability to infuse • Consider early linogram
No
Check external components (connections, Yes • CXR to check for kink/compression/
taps and tubings) for any kink/occlusion/ malposition/migration.
dislodgement. • If pain/swelling in neck/arms: doppler
ultrasound to look for thrombosis.
• Inform surgeon/intervention
Is there any leak, swelling or pain around CVAD?
radiologist.
No
• Reposition the patient, e.g. lift arm, turn head.
• Ask patient to give a few hard coughs.
• Try brisk pulses of 0.9% saline into the CVAD.
• Consider repositioning Gripper needle (port).
If CVAD is still blocked
Thrombolytic therapy with Urokinase*
If CVAD is still
If CVAD is still blocked blocked
Repeat Urokinase* • CXR to check for kink/compression/
malposition/migration.
• Linogram to assess catheter tip
migration, leakage or occlusion.
• Inform surgeon/intervention
radiologist.
* Guidelines for Use of Urokinase for Blocked CVADs

• A senior doctor (registrar and above) should be informed.
• Ensure patient is not allergic to Urokinase, and is not having any active or recent bleeding or major surgery.
• Dilute Urokinase with 0.9% saline to achieve final concentration of 5,000 units of Urokinase per ml.
- e.g. To 1 vial of 60,000 units Urokinase, add 12ml of 0.9% saline to get 5,000 units/ml.
• Instil diluted Urokinase (5,000 units/ml) slowly into blocked CVAD following usual aseptic technique:
- 2ml for blocked port-a-cath; 1ml for each blocked Hickman or PICC lumen.
• For completely blocked CVADs, the 3-way tap technique uses an empty 10ml syringe to withdraw as much as
possible from the CVAD; the resultant negative pressure allows the Urokinase in another syringe to be slowly
drawn into the catheter.
• After instilling Urokinase, leave for 1–4 hours, and then attempt to aspirate and discard at least 2–3ml. Then
flush with 10–20ml of 0.9% saline. Avoid flushing Urokinase directly into patient’s systemic circulation.
• If CVAD is still blocked, repeat the same steps but leave Urokinase for 12–24 hours before aspirating.
Figure 7.7: Algorithim for suspected drug extravation

Algorithm for Suspected Drug Extravasation
Suspected extravasation: Vesicant chemotherapeutic

Swelling / erythema / pain / leakage over catheter site during drug infusion agents commonly used in
paediatric oncology
• Cisplatin
Stop the infusion immediately. Leave needle in situ. • Dactinomycin
• Daunorubicin
• Doxorubicin
• Idarubicin
Aspirate 3 - 5 ml of fluid and blood from the needle.
• Vinblastine
• Vincristine
• Vinorelbine
Check if infused drug is a vesicant.
No Yes
Obtain urgent consult with Plastic Surgery.

Notify Oncology Pharmacy and get advice on antidote.
Instill specific antidote via the needle in-situ, as well as

subcutaneously using 25G needle into area of extravasation
(only after urgent Plastics and Pharmacy consult.)
• Remove needle and clean • Remove needle and clean area with antiseptic.
area with antiseptic. • Apply cold compress (for anthracyclines) or
• Apply cold compress. warm compress (for other vesicants).
• Elevate affected limb. • Elevate affected limb.
• Prescribe analgesics. • Prescribe analgesics.
• Document the incident. • Document the incident.
Appropriate IV antibiotics should be alternated between CVAD lumens,

and be given for at least 10–14 days from first negative blood culture
(See also section on “Febrile Neutropenia”). The Infectious Disease (ID)
physician and surgeon should be consulted regarding the need for
CVAD removal (See Algorithm for Suspected CVAD Infection). CVAD
removal may be necessary in the following situations:
 persistent positive blood cultures after 72 hours or more of
appropriate antimicrobial therapy
 clinical deterioration
 septic emboli or infective endocarditis
 fungaemia
 rapidly growing mycobacteraemia
 recurrent blood stream infection with the same organism
 catheter tunnel or port pocket infection, especially if exudate
cultures are positive for Pseudomonas.
A new CVAD should be inserted only after completion of antimicrobial
therapy and when off-therapy blood cultures are negative.
 Extravasation
Extravasation occurs when the port-a-cath needle is dislodged or IV
cannula is not in the vein and fluid/drug being infused goes into the
subcutaneous tissue. Vesicant chemotherapeutic drugs can cause

a lot of local tissue damage, resulting in ulceration, necrosis and
secondary infection if the extravasation is not recognised and treated
early. Therefore if there is extravasation of chemotherapeutic drugs,
the patient should be attended to immediately (see Figure 7.7).
Bibliography
(2004).
2. G. Gonzalez, A.M. Davidoff, S.C. Howard et al; Safety of Central Venous Catheter Placement
at Diagnosis of Acute Lymphoblastic Leukemia in Children. Pediatr Blood Cancer
2012;58:498–502.
3. Junqueira BL, Connolly B, Abla O, et al. Severe neutropenia at time of port insertion is
not a risk factor for catheter associated infections in children with acute lymphoblastic
leukemia. Cancer 2010;116:4368–4375.
4. O’Grady NP, Alexander M, Burns LA, et al; Healthcare Infection Control Practices Advisory
Committee. Guidelines for the prevention of intravascular catheter-related infections. Am
J Infect Control. 2011;39(4 suppl 1):S1–S34.
ANTIEMETICS
ANTINEOPLASTIC THERAPY-INDUCED NAUSEA AND

VOMITING IN CHILDREN
Antineoplastic therapy includes conventional chemotherapy, biologics
and targeted therapies, as well as radiotherapy (RT). These treatments
can cause nausea and vomiting. Types of antineoplastic therapy-induced
nausea and vomiting (AINV):
 Anticipatory AINV — Occurs prior to or soon after administration
of chemotherapy, usually in patients who previously experienced
poorly controlled acute or delayed AINV.
 Acute AINV — Occurs within the first 24 hours after administration of
chemotherapy.
 Delayed AINV — Occurs >24 hours after administration of chemotherapy,
and can last up to 7 days after the last dose of chemotherapy, e.g. cisplatin,
carboplatin, cyclophosphamide, doxorubicin.
 Breakthrough AINV — Occurs despite prophylactic anti-emetics.
The severity and duration of AINV vary between different

chemotherapeutic agents. The emetogenicity rating of a drug is based
Emetogenicitya Antineoplastic Agents (agents that are more commonly used in paediatric oncology are in bold) Recommended Prophylaxis Breakthrough AINV
Table 7-17: Antineoplastic agents: Acute emetogenic potential in children (when given singly) and
MINIMAL Alemtuzumab Dasatinib Hydroxyurea Nelarabine Thalidomide No routine prophylaxis

emetogenic risk Asparaginase Decitabine Imatinib (≤400mg) Panitumumab Thioguanine
(<10 %) Bevacizumab Denileukin Interferon-alpha Pentostatin Trastuzumab
Bleomycin Dexrazoxane Lapatinib Rituximab Valrubicin
Bortezumib Erlotinib Lenalidomide Sorafenib Vinblastine
Cefuximab Fludarabine (IV) Melphalan (PO) Sunitinib Vincristine
Chlorambucil (PO) Gefitinib Mercaptopurine Temsirolimus Vindesine
Cladribine (2-CDA) Gemtuzumab Methotrexate (≤50mg/m2) Vinorelbine (IV)
LOW Amifostine (<300mg/m2) Cyclophosphamide Etoposide (IV/PO) Methotrexate Teniposide Prophylaxis with single drug:
emetogenic risk Amsacrine (PO <100mg/m2/day) Fludarabine (PO) (>50 – <250mg/m2) Thiotepa (≤300mg/m2) 1. Ondansetron or Granisetron
(10 – 30 %) Bexarotene Cytarabine (≤200mg/m2) 5-Fluorouracil Mitomycin Temozolomide
Busulfan (PO <4mg/day) Docetaxel Gemcitabine Mitoxanthrone (PO≤75mg/m2, no RT)
Capecitabine Doxorubicin liposomal Imatinib (>400mg) Nilotinib Topotecan 1. Add or increase dose
Ixebepilone Paclitaxel Vorinostat of dexamethasonec.
Pemetrexed
Radiation to head/neck, cranium, craniospinal or pelvis: Ondansetron/granisetron can be given as prophylaxis or rescue. 2. Add agent of
different class
Aldesleukin, IL-2 Busulfan (PO ≥ 4mg/day) Dactinomycin Lomustine (CCNU) Prophylaxis with 2 drugs:
to regimen,
MODERATE (>12 million units/m2) Carmustine (<250mg/m2) Daunorubicin Melphalan (IV) 1. Ondansetron or Granisetron
e.g. lorazepam;
emetogenic risk Amifostine (≥300mg/m2) Clofarabine Doxorubicin Methotrexate 2. Dexamethasonec.
diphenhydramine;
(30 – 90 %) Arsenic trioxide Cyclophosphamide Epirubicin (≥250mg/m2 – <12g/m2) (If dexamethasone contraindicated:
metoclopramided.
Azacitadine (IV <1.5g/m2) (PO ≥100mg/m2/day) Idarubicin Oxaliplatin Diphenhydramine ± Metoclopramided)
Bendamustine Cytarabine (>200mg/m2 – <3g/m2) Intrathecal Therapyb Temozolomide
Busulfan (IV) Ifosfamide (PO >75mg/m2, or with RT)
recommended ant-emetic Prophylaxis
Irinotecan Vinorelbine (PO)

Radiation to upper abdomen or half body: Ondansetron/granisetron before each RT fraction, with/without dexamethasone for 5 – 7 days.
HIGH Altretamine Dacarbazine Prophylaxis with 3 drugs:
emetogenic risk Carboplatin Mechlorethamine 1. Ondansetron or Granisetron
(>90 %) Carmustine (≥250mg/m2) Methotrexate (≥12g/m2) 2. Dexamethasonec.

Cisplatin Procarbazine (If dexamethasone contraindicated:
Cyclophosphamide (≥1.5g/m2) Streptozocin Diphenhydramine ± Metoclopramided)
Cytarabine (≥3g/m2/dose) Thiotepa (≥300mg/m2) 3. Aprepitante
Total body (TBI) or total nodal irradiation (TNI): Ondansetron/granisetron before each RT fraction, PLUS dexamethasone for 5–7 days.
a
Based on frequency of emesis in absence of prophylaxis
b
For intrathecal chemotherapy, prophylaxis with ondansetron alone is usually effective
c
Dexamethasone should be given with a H2-blocker. Ensure no contraindications to dexamethasone (see next table).
d
Metoclopramide should be given with diphenhydramine to reduce/prevent extrapyramidal side effects.
e
Ensure no contraindication or drug interactions.
Drug Class Drug Name and Doses Remarks/Possible Side Effects/Cautions

5-HT3 (Serotonin) Ondansetron IV or PO Occasionally may cause headache, constipation.
Antagonists - 0.15–0.2mg/kg/dose (max. 8mg/dose) Q8–12H QT prolongation (uncommon to rare).
Granisetron IV
- 0.01–0.04mg/kg/dose (max. 3mg/dose) Q12–24H
Granisetron PO
Corticosteroids Dexamethasone IV or PO Short-term corticosteroids may cause mood swings, agitation, insomnia and dyspepsia.
- 0.1–0.2mg/kg/dose (max. 8mg/dose) Q8-12H Contraindicated with immunologic and biologic agents such as interferon and
- Reduce dose by half if given concurrently with aprepitant. interleukin-2.
- Add H2-blocker (ranitidine famotidine) to reduce dyspepsia. Avoid in patients receiving chemotherapy for brain tumours.
- Radiotherapy with moderate-to-high emetogenic potential: PO dexamethasone Avoid in patients already receiving steroids as part of their cancer treatment (e.g.
0.05–0.1mg/kg/dose (max. 4mg/dose) once daily for 5–7 days. May need tailing if longer leukaemia, lymphoma).
schedules given.
©
Neurokinin-1 (NK1) Aprepitant (Emend ) Possible clinically significant drug interactions.
Antagonist - Age ≥12 years, OR age <12 years and >30kg: PO 125mg on Day 1 May cause nausea, constipation, hiccups.
(1 hr before chemotherapy); 80mg once daily on Days 2 and 3.
- Age >6 months, <30kg: 3mg/kg (max 125mg) on Day 1 (1 hr before chemotherapy);
2mg/kg (max 80mg) once daily on Days 2 and 3.
- Reduce dexamethasone dose by half when used together.
Table 7-18: Anti-emetic agents
Benzodiazepines Lorazepam IV or PO Drowsiness; dizziness; amnesia; respiratory depression; occasionally behaviour change
(For anticipatory AINV, start the night before or on morning of treatment.)
Others (Recommend to Diphenhydramine IV or PO Diphenhydramine, metoclopramide and promethazine may cause drowsiness.
start at lower doses and - 1–2mg/kg/dose (max. 50mg/dose) Q6–8H Extrapyramidal effects of metoclopramide may be prevented by diphenhydramine.
to increase if persistent Metoclopramide IV or PO Metoclopramide is not recommended in children aged <1 year.
symptoms) - 0.1mg/kg/dose (max.0.5mg/kg/day or 30mg/day) (give with diphenhydramine) Promethazine may cause respiratory depression in very young children. Avoid
Promethazine PO promethazine in children below 2 years old.
- 0.25–1mg/kg/dose (max. 25mg/dose) Q6–8H
on the percentage of patients who will experience vomiting if not given

any prophylaxis. Multi-agent combination chemotherapy and higher
chemotherapeutic drug doses are generally associated with higher
emetogenicity. Radiotherapy can also cause nausea and vomiting. Total
body irradiation (TBI) or total nodal irradiation (TNI) is highly emetogenic.
Radiation to upper body or half body is of moderate emetogenic risk.
(Remember also to consider other causes of vomiting in cancer patients,

e.g. bowel obstruction, intra-abdominal sepsis, electrolyte imbalances,
raised intracranial pressure etc.)
General Guidelines:
 Choice of anti-emetics should be based on the chemotherapeutic
agent with the highest emetogenic potential within the combination
chemotherapy (or radiotherapy) regimen, as well as patient’s prior
experience.
 Anti-emetics should be commenced before starting chemotherapy
or radiotherapy — at least 1 hour for oral anti-emetic, and 15–30
mins for parenteral antiemetic.
 Anti-emetics should be given round the clock (not PRN) during
chemotherapy if there is at least moderate emetogenic risk.
 Anti-emetics should continue until chemotherapy has completed
and there is no vomiting or nausea for at least 24 hours.
 If there are risk factors or history of delayed AINV, continue
oral dexamethasone and 5-HT3 antagonist for further 2–3 days
(sometimes up to 7 days).
 To take note of side effects, possible drug interactions, cautions and
contraindications.
Bibliography
1. Dupuis, L. L. et al. Guideline for the prevention of acute nausea and vomiting due
to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 60,
1073–1082, doi:10.1002/pbc.24508 (2013).
2. Dupuis, L. L. et al. Guideline for the classification of the acute emetogenic potential of
antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 57, 191–198,
doi:10.1002/pbc.23114 (2011).
3. Basch, E. et al. Antiemetics: American Society of Clinical Oncology Clinical Practice
Guideline Update. Journal of Clinical Oncology 29, 4189–4198, doi:10.1200/
jco.2010.34.4614 (2011).
4. NCCN Clinical Practice Guidelines in Oncology: Antiemesis (Ver 2.2014)
5. SickKids Handbook of Supportive Care in Pediatric Oncology. 1st ed (2009)
6. Supportive Care of Children with Cancer: Current Therapy and Guidelines from the Children’s
Oncology Group (The Johns Hopkins Series in Hematology/Oncology) 3rd ed (2004)
7. Online LexiComp®, accessed on (29th May 2014)
8. Frank Shann. Drug Doses. 15th ed.
FEVER IN THE IMMUNOCOMPROMISED

CHILD
DEFINITIONS
 Fever is defined as a single temperature of ≥38.5°C or two episodes
of ≥38°C (taken 30 mins apart).
 Definition of neutropenia:
 Normal neutrophil count is >1,500/mm3 (1.5x109/L).
 Mild neutropenia refers to absolute neutrophil count (ANC) of
<1,500/mm3 (1.5x109/L)
 Significant or moderate neutropenia refers to ANC ≤500 cells/
mm3 (0.5x109/L), or one that is expected to fall below 500 cells/
mm3 (0.5x109/L) over the next 48 hours. This is the working
definition for most febrile neutropenia guidelines. However, our
management algorithm (see Figure 7.8 on page 294) will use
ANC of 1,000/mm3 (1x109/L) as cut-off.
 Severe neutropenia refers to ANC ≤200 cells/mm3 (0.2x109/L).
 The term “profound” is sometimes used to describe neutropenia
in which the ANC is ≤100 cells/mm3 (0.1x109/L).
 Febrile neutropenia in an immunocompromised patient is a medical
emergency. Prompt attention, administration of appropriate broad
spectrum antibiotics and supportive treatment is critical for a
favourable outcome.
INITIAL EVALUATION
History
 Underlying cancer diagnosis and significant past history.
 Chemotherapy schedule — What and when the last
chemotherapy was given. This will help to predict the severity
and duration of the neutropenia. Profound (ANC <0.1x109/L) and
protracted (>7 days) neutropenia are major risk factors. Certain
drugs (e.g. doxorubicin, high-dose cytarabine or methotrexate)
can cause severe mucositis.
 Associated symptoms, e.g. cough, breathing difficulties,
diarrhoea, abdominal pain
 Systemic review
 Allergy to drugs and to blood products
 History of transplant
 Current medications
 Check vital signs and perform a thorough examination, especially
to look for evidence of occult infection.
 Have a high index of suspicion as the usual signs of inflammation
(i.e. erythema, induration, tenderness and pus) are typically
attenuated when a patient is neutropaenic. The only signs of an
abscess may be minimal tenderness or swelling.
 Look out for pallor or bleeding.
 Examine the oral cavity and perineum for ulcers.
 Examine the skin especially bone marrow aspiration sites, central
line sites and around the nails
 If history is suggestive, look for respiratory distress (Pneumocystis
jirovecii, previously known as Pneumocystis carinii, pneumonitis,
“PCP”)
 Examine the abdomen for distension, tenderness and bowel
sounds. Think of typhilitis (neutropaenic colitis) or pancreatitis in
the face of abdominal pain ± diarrhoea/vomiting.
 Do not perform rectal examination or urinary catheterisation in a
neutropaenic patient.
INVESTIGATIONS
Appropriate investigations should be done immediately and include:
 Full blood count (FBC)
 Group and cross match (GXM)
 Blood cultures — Aerobic and anaerobic.
 One set from central lines — Port-a-cath; each lumen of central
venous line (e.g. Hickman, PICC). This is mandatory for all febrile
patients with central venous line.
 One set percutaneously from peripheral veins — This is
mandatory for febrile patients without central lines, but may be
omitted in stable patients with central lines. If peripheral blood
cultures are taken, they should be drawn simultaneously with
“Central” blood cultures, to enable evaluation of differential time
to positivity (DTP).
 Each specimen should be clearly and correctly labelled (e.g.
aerobic culture from small lumen).
 Fungus grows well in aerobic media and a separate fungal
blood culture is unnecessary unless rare or fastidious species
are suspected. Send fungal cultures only after discussion with
infectious diseases or microbiology service.
 Urea, electrolytes, creatinine (renal panel); Calcium/phosphate/
magnesium
 Liver function test

 Urinalysis and urine culture, urine fungal smear. Urine collection
should not delay initiation of antibiotics.
 Stool culture and stool fungal smear. Stool collection should not
delay initiation of antibiotics.
 Imaging (e.g. CXR) and other investigations (e.g. respiratory viruses)
as indicated.
 Prothrombin time and aPTT is not necessary in stable patients.
MANAGEMENT
Remember that in the face of severe neutropenia, there may be no
pyuria for a suspected UTI, a normal CXR in pulmonary infection and
no CSF pleocytosis in meningitis. A high index of suspicion is crucial.
Investigations should not delay initiation of antibiotics — there is no
need to wait for urine and stool tests to be sent off before starting
antibiotics. Rectal enemas or suppositories should not be given to
neutropaenic patients.
 General supportive and resuscitative measures as required — “ABC”.
 Monitor parameters (heart and respiratory rate, blood pressure) at
least 4 hourly. Look out for inappropriate tachycardia (impending
shock) or tachypnoea (pneumonitis/chest infections).
 Transfusions:
 Maintain Hb >8g/dL; if there is respiratory distress or bleeding,
maintain >9–10g/dL. If a packed cell transfusion is required, order
20ml/kg over 4 hours.
 Maintain platelets ≥30x109/L if febrile, or ≥20x109/L if afebrile.
If there is active surface bleeding, maintain ≥50x109/L;
gastrointestinal bleeding ≥80x109/L and intracranial bleeding
≥100x109/L.
 Correct electrolyte abnormalities.
 Stop any ongoing chemotherapy, e.g. oral 6-mercaptopurine or
6-thioguanine
 Prophylactic antimicrobials (e.g. co-trimoxazole for PCP prophylaxis,
acyclovir for HSV prophylaxis), if present, should be continued
 If the patient is on GCSF, this should be continued till neutrophil
recovery.
 Steroids should be continued. Abrupt discontinuation during sepsis
may trigger adrenal crisis.
 Initial antibiotic cover:
 Prompt empiric broad-spectrum antibiotic cover is necessary as
the progression of infection in neutropaenic patients can be very
rapid, especially with gram-negative organisms.
Figure 7.8: Immunocompromised patient with fever
Immunocompromised Patient with Fever
ANC <1x109/L ANC ≥1x109/L
IV Piperacillin-Tazobactam* Manage according to clinical condition
Blood Culture Negative @ 48 hours Positive Blood Culture Clinical Deterioration
Treat accordingly (alternating lumens) for

≥7–14 days (or longer, e.g. CVAD infection) IV Meropenem*
IV Amikacin*
IV Vancomycin*
ANC ≥0.5x109 /L ANC <0.5x109 /L
Persistent Fever Consider adding IV
No risk factors** Any risk factors** >48 hours Amikacin*
Stop antibiotics if Stop antibiotics after

5–7 days, if afebrile Persistent Fever
afebrile >24–48 hours Add IV Amphotericin*
>48 hours >96 hours
*Drug Doses: **High Risk Febrile Neutropaenic (Any of the following risk
IV Piperacillin-Tazobactam 80mg (pip)/kg/dose Q6H IV factors):
Amikacin 7.5mg/kg/dose (max 750mg) Q12H  HSCT within 6 months and/or still on immunosuppressants
IV Meropenem 20–40mg/kg/dose (max 2g) Q8H IV  Down syndrome
Vancomycin 15mg/kg/dose Q6H  Recent overwhelming sepsis
IV Amphotericin B 0.5mg/kg/dose on day 1; 0.75mg/kg/  ALL on induction or re-intensification phases
dose on day 2; 1mg/kg/dose Q24H thereafter.  AML
Pre-medications for Amphotericin B:  Lymphomas, e.g. Burkitt’s
IV Hydrocortisone 2–4mg/kg (max 100mg) IV  High risk neuroblastoma
Diphenhydramine 1–2mg/kg (max 50mg)  Relapsed/progressive malignancy on intensified treatment
 Clinically unwell — chills/rigors, excessive tachycardia,
(Above amphotericin B doses are for conventional hypotension
amphotericin B)
 In general, the first-line treatment is broad-spectrum and covers

for the pathogens unique to the particular hospital setting,
especially gram-negative organisms
 Piperacillin-Tazobactam is a recommended initial monotherapy
agent as it has broad spectrum gram- positive, gram-negative
(including Pseudomonas) and anaerobic cover. It is also well-
tolerated and has a good toxicity profile.
 If there is haemodynamic instability (hypotension, excessive
tachycardia), antibiotic cover should be escalated/broadened (see
algorithm below.)
 Adjust antimicrobial regimen based on clinical, radiological (if any)
and/or culture data. Definitive antimicrobial therapy should be given
for at least 7–14 days. Longer duration is needed for central vascular
access device (CVAD) infections or invasive fungal infections.
Risk Factors in Febrile Neutropenia

 Haematopoietic stem cell transplantation (HSCT) patient within 6
months of transplant and/or still receiving immunosuppressants
 Down syndrome
 Recent overwhelming sepsis
 Any of the following diagnoses:
 ALL on induction or re-intensification phases
 Acute myeloid leukaemia
 Lymphomas, e.g. Burkitt’s
 High risk/Stage 4 neuroblastoma
 Relapsed or progressive malignancy on intensified treatment
with/without marrow involvement
 Presentation:
 Chills and rigors/excessive tachycardia that is out of proportion to
the fever/hypotension
 Respiratory — Desaturation/respiratory distress/new infiltrates
on CXR
 GI — Vomiting, severe mucositis, perianal ulcer or abscess,
abdominal pain
 Altered mental state
 Any significant local infection
Beta-Lactam Allergy
Most penicillin-allergic patients can tolerate cephalosporins and
piperacillin-tazobactam, due to negligible cross-reactivity between
penicillins and newer generation cephalosporins . However, those with
intermediate to severe type 1 hypersensitivity reactions to penicillins
(severe urticaria, bronchospasm, hypotension) should be treated
with combinations that avoid β-lactams and carbapenems, such as
ciprofloxacin plus clindamycin. Consider Infectious Diseases and Allergy
consults in these cases.
Aminoglycosides
Caution regarding use of aminoglycosides in patients with:
 Glomerular filtration rate <60ml/min/1.73m2
 Abnormal serum creatinine
 Previous slow clearance of aminoglycoside
 Hearing impairment
 Multiple nephrotoxic medications
Follow institution guidelines on therapeutic drug monitoring of
aminoglycosides.
Empiric Antifungal Therapy

 Predisposing factors to invasive fungal diseases include: acute
myeloid leukaemia, high-risk acute lymphoblastic leukaemia,
relapsed acute leukaemia, allogeneic haematopoietic stem cell
transplant, highly myelotoxic chemotherapy regimens that cause
prolonged severe neutropenia.
 Empiric antifungal therapy with IV amphotericin B should be
considered for these patients with persistent neutropaenic fever of
unclear origin despite >96 hours of appropriate antibiotics.
 See Figure 7.8 for doses of conventional amphotericin B and pre-
medications. Pre-medications may be discontinued after several days
if there is no reaction but be prepared to reinstitute if the patient
develops fever, chills, rigors or hypotension related to amphotericin B
infusion.
 Liposomal amphotericin B (AmBisome) is less nephrotoxic and may
be preferred in selected patients.
 Monitor and replace electrolytes (K+, Mg2+, PO43−) while on
amphotericin as the drug causes tubulopathy (especially with
conventional formulation).
 If fever persists despite the addition of amphotericin, repeat blood

cultures and imaging (e.g. CT chest, CT sinuses) are required to
exclude new organisms or occult infections.
 Recrudescence of fever in the face of a rising total white cell count
is highly suggestive of a fungal infection and this should be treated
with IV amphotericin or fluconazole.
 In some patients, where prolonged profound neutropenia is
expected, the role of prophylactic empiric antifungals can be
considered, e.g. fluconazole.
Bibliography
1. Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in
neutropenic patients with cancer: 2010 update by the infectious diseases society of
america. Clin Infect Dis 52, e56–93, doi:10.1093/cid/cir073 (2011).
2. Lehrnbecher T et al. Guideline for the Management of Fever and Neutropenia in Children
With Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation. J Clin Oncol
30, 4427–4438, doi:10.1200/jco.2012.42.7161 (2012).
3. Alexander SW, Wade KC, Hibberd, PL & Parsons SK. Evaluation of risk prediction criteria for
episodes of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol 24, 38–42
(2002).
4. Pichichero ME. Use of selected cephalosporins in penicillin-allergic patients: a paradigm
shift. Diagn Microbiol Infect Dis 57, 13S-18S, doi:10.1016/j.diagmicrobio.2006.12.004
(2007).
5. Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer
patients. NICE clinical guideline 151. 2012.
INFECTION PROPHYLAXIS IN PAEDIATRIC

HAEMATOLOGY/ONCOLOGY
The following are general measures to reduce infections in
immunocompromised oncology and haematopoietic stem cell transplant
(HSCT) patients:
 All staff and visitors should wear a surgical facemask and practise
hand hygiene. Sick staff/visitors should not enter the oncology/HSCT
ward.
 Patients with active contagious diseases (e.g. respiratory illness,
chickenpox) should be nursed in single isolation rooms away from
the other immunocompromised patients.
 Patients are advised to follow food safety measures. In general, food
should be well cleaned and eaten fresh. All meat and eggs should
be thoroughly cooked. Dairy products, honey, and juices should be
pasteurised.
 Patients should practise frequent hand washing and regular baths to

maintain personal hygiene and cleanliness, with special attention to
oral cavity and perineal area.
 Plants, including fresh or dried flowers, are not allowed in the
oncology/HSCT rooms because of possible presence of fungal
moulds and spores.
 Patients at risk of invasive mould infections (e.g. allogeneic HSCT
recipients, patients with severe combined immunodeficiency) are
nursed in single rooms with double doors, HEPA (high efficiency
particulate air) filtration, positive air pressure, and with high rates of
room air exchanges (>12 exchanges per hour).
PNEUMOCYSTIS JIROVECII (PREVIOUSLY PNEUMOCYSTIS

CARINII PNEUMONIA, PCP)
Pneumocystisi jirovecii can cause severe life-threatening pneumonitis
in immunocompromised patients with severe lymphopenia and
neutropenia. Prophylaxis is indicated for patients undergoing treatment
for acute leukaemia, patients undergoing haematopoietic stem cell
transplant, patients with severe combined immunodeficiency, patients
undergoing intensive chemotherapy for certain brain and solid tumours,
and patients receiving moderate–high doses of systemic corticosteroids
for longer than 4 weeks. Prophylaxis should continue for at least
3–6 months after end of chemotherapy or immunosuppression. The
following drugs can be used for PCP prophylaxis:
 Trimethoprim/sulfamethoxazole (Co-trimoxazole) 5mg/kg/day of
trimethoprim (TMP) component, in 2 divided doses, 2 days a week.
This is the gold standard for PCP prophylaxis. Co-trimoxazole should
be discontinued 1 week before till at least 72 hours after high-dose
methotrexate. Patients with G6PD-deficiency, allergy or intolerance
(prolonged myelosuppression) may need to consider the other
prophylaxis options.
 Nebulised pentamidine 300mg for children 5 years and older, or
8mg/kg/dose for children younger than 5 years, given 4-weekly.
Inhaled (MDI) or nebulised salbutamol, given before nebulised
pentamidine, helps reduce the risk of cough and bronchospasm.
Nebulised pentamidine is not recommended in children younger
than 2 years. Postpone if patient is having respiratory infection.
 IV pentamidine 4mg/kg/dose infused over 1–2 hours, every 2–4

weeks. May cause hypotension and hypogycaemia.
 PO dapsone 2mg/kg/dose (max 100mg) once daily, or 4mg/kg/dose
(max 200mg) once weekly. Contraindicated in G6PD-deficiency. May
cause abnormal LFT, haemolysis and methaemoglobinaemia.
CHICKENPOX
A person with active chickenpox infection is contagious beginning 2
days before and until 5 days after appearance of the skin vesicles. If
an immunocompromised patient is exposed to active chickenpox, IV
Varicella Zoster Immunoglobulin (VZIG) 25 units/kg should be given
within 10 days of exposure. The incubation period is 21 days (if VZIG
is not given), or 28 days (if VZIG is given). During this period, it may
be necessary to consider withholding intensive chemotherapy. If
chickenpox should develop, IV acyclovir should be given for at least
7 days, until all lesions have crusted and with no appearance of new
lesions for 48 hours. The dose of IV acyclovir is 500mg/m2/dose 8 hourly
(or 10mg/kg/dose 8 hourly for children younger than 1 year), given with
adequate hydration.
HERPES SIMPLEX VIRUS (HSV)

Immunocompromised patients with recurrent HSV infections should be
given prophylactic acyclovir PO 40mg/kg/dose BD (max 1g/day).
MEASLES
If the exposure is within 6 days, intravenous immunoglobulin (IVIG)
0.5mg/kg should be given. The incubation period is 14 days, during
which chemotherapy should be withheld if possible.
SPLENECTOMY/ASPLENIA
Splenectomised patients are at risk of developing severe sepsis from
encapsulated bacteria. Prior to splenectomy, the patient should be
vaccinated against:
(1) Streptococcus pneumoniae
(2) Haemophilus influenza Type B
(3) Neisseria meningitidis.
No vaccines are contraindicated in patients with asplenia.
This is our recommended vaccine schedule for patients (age 2 years and
older) not previously vaccinated, and going for elective splenectomy:
0 weeks Prevenar 13®, Menactra®, Hiberix®

8 weeks Prevenar 13®, Menactra®, Hiberix® (if <5years)
16 weeks Pneumovax23®
Annual Seasonal Influenza vaccine
At 5 years Pneumovax23®, Menactra®
Every 5 years thereafter Menactra®
If a patient will be undergoing elective splenectomy, the vaccines

should be completed at least 14 days prior to surgery. If it is not possible
to administer these vaccines prior to splenectomy, they can be given
after the fourteenth post-operative day. In addition, annual influenza
vaccine is also recommended.
Post-splenectomy, the patient is advised to take penicillin prophylaxis

250mg BD daily (125mg BD if younger than 5 years). Alternative
antibiotic prophylaxes include amoxicillin (10mg/kg/dose BD) or
erythromycin. Antibiotic prophylaxis also applies to patients with
asplenia or functional asplenia (e.g. sickle cell disease, post-splenic
irradiation, or graft versus host disease). Duration of antibiotic
prophylaxis is still controversial, but should be until minimum age 5
years and at least 1–2 years post-splenectomy, or longer (until age 18
years, or even lifelong) for higher-risk patients.
CENTRAL VENOUS ACCESS DEVICES (CVAD)

Patients with CVAD should receive standard antibiotic prophylaxis
against infective endocarditis during invasive procedures such as
gastrointestinal or genitourinary operations and invasive dental
procedures. The standard prophylaxis is IV ampicillin 50mg/kg (max 2g)
30 mins before the procedure, or PO amoxicillin 50mg/kg (max 2g) 1
hour before the procedure. Alternative prophylaxis in case of penicillin
allergy include clindamycin 20mg/kg (max 600mg) given within 1 hour
(PO) or 30 mins (IV) before procedure. (Refer to infective endocarditis
prophylaxis guidelines.)
HAEMATOPOIETIC STEM CELL TRANSPLANT (HSCT)

RECIPIENTS
Table 7-19: Suggested infection prophylaxis for paediatric HSCT recipients
Infection Drug and Doses Duration
General IVIG 0.5g/kg/week • Keep serum IgG >4g/L

• Discontinue after Day+100 if serum IgG >4g/L
Herpes simplex virus IV Acyclovir • For HSV prophylaxis in HSV-seropositive allogeneic

2
(HSV); ≥40kg: 250mg/m /dose Q12H HSCT recipients, begin acyclovir at start of
2
Varicella zoster virus (VZV) <40kg: 250mg/m /dose Q8H conditioning, and continue until neutrophil
PO Acyclovir engraftment OR resolution of mucositis OR 30 days,
≥4kg: PO 800mg BD whichever is later.
<40kg: PO 40mg/kg/dose BD • For VZV prophylaxis in VZV IgG-positive allogeneic
HSCT recipients, continue for 1 year post-HSCT
OR end of immunosuppressive therapy, whichever
is later.
Fungal infections Allogeneic HSCT: Ambisome IV • Start from Day+1 of HSCT, and continue till neutrophil
1mg/kg/dose three times a week; OR engraftment and if no GVHD.
PO Posaconazole 4mg/kg/
dose (max 200mg) TDS Allogeneic HSCT recipients who are younger than 6
years OR not able to tolerate oral medications (e.g.
Autologous HSCT: Fluconazole severe vomiting, mucositis, diarrhoea) should be
IV/PO 5–6mg/kg/day (max 600mg given IV ambisome.
if younger than 13 years, or 400mg if
13 years and older).
Pneumocystis Gold standard is co-trimoxazole • Start after neutrophil engraftment

jirovecii pneumonia (See section on ‘PCP’). • Continue for 6–12 months post-allogeneic HSCT
• Continue for 3–6 months post-autologous HSCT
• Longer duration if still on immunosuppressive therapy
or chronic GVHD
Encapsulated bacteria PO Penicillin V 250mg BD For patients who have undergone splenic irradiation
(Or 125mg BD if younger than (e.g. total body irradiation or total nodal
5 years). irradiation) or with chronic graft-versus-host-
disease:
• Start after cessation of co-trimoxazole
Cytomegalovirus (CMV)
Our centre adopts a pre-emptive strategy for early CMV infection
in allogeneic HSCT recipients. Cytomegalovirus-seronegative HSCT
recipients should receive leucocyte-depleted blood products. Screening
for CMV viraemia using CMV-DNA PCR is done at least once a week
until at least 100 days post-HSCT. Intravenous ganciclovir is started
for patients who have CMV viraemia (2 or more consecutively positive
CMV-DNA PCR) at dose of 5mg/kg/dose (induction) Q12H for 7–14
days, and then continued at 5mg/kg/day (maintenance) for minimum
2 weeks total (induction and maintenance), till PCR negative and at

least day +100 post-HSCT, whichever is longer. An alternative is oral
valganciclovir, to be used when PCR negative and until at least day +100
days post-HSCT, whichever is longer.
VACCINATION
Vaccination for Close Contacts of Immunocompromised Patients
 Household contacts should not receive oral polio vaccine (OPV).
Individuals with recent OPV (within 4–6weeks) should not come
into close contact with immunocompromised patients.
 Close contacts (including staff, family members and visitors) who
are VZV-seronegative should receive varicella vaccine, but should
avoid contact with immunocompromised patient if they develop
vaccine-associated skin lesions, until the skin lesions clear.
 If an infant in the household has received rotavirus vaccine, the
highly immunocompromised patient should avoid handling the
infant’s diapers for 4 weeks after the vaccination.
Killed Vaccines
 In general, killed or inactivated vaccines (influenza, DTaP, Hib,
IPV, Hepatitis B and pneumococcal) can be safely given to
immunocompromised patients although a lower immunologic
response and reduced protective effect is expected. Killed
vaccines should be given two or more weeks prior to
immunosuppression, and should be avoided within two weeks of
initiation of immunosuppression.
 Immunisations or boosters may be resumed according to
schedule 3–6 months after completion of chemotherapy (at least
6 months if given rituximab).
 HSCT recipients may be given killed vaccines 6–12 months post-
HSCT.
Live Vaccines
 Live vaccines (MMR, varicella, OPV, BCG) should never be given to
patients on chemotherapy or immunosuppression. Live vaccines
should be given ≥4 weeks prior to immunosuppression.
 MMR and varicella may be given only if the patient is no longer
immunocompromised — at least 3–6 months post-completion of
chemotherapy, or at least 24 months post-HSCT (with no ongoing
immunosuppression for at least 6 months, no active GVHD, and
>8–11 months from last dose of IVIG).
 OPV should be replaced with IPV.
Other Vaccines to be Considered Post-HSCT:

 Meningococcal vaccine: recommended if previous splenectomy
or college student living in dormitories.
 Hepatitis A vaccine: recommended if GVHD or liver disease or
other hepatitis virus infections.
 Human papillomavirus (HPV) vaccine may also be considered.
Table 7-20: Suggested immunisation schedule post-HSCT

Suggested Re-immunisation Months Post-HSCTa
Schedule for the HSCT
Recipient ≥6 ≥12 ≥14 ≥24
Age Age Age Age Age Age
<7 ≥7 <7 ≥7 <7 ≥7
1. Inactivated influenza vaccine b X X (annual, lifelong)
2. Diphtheria, Tetanus, Pertussis – Tdap Td Td
3. Haemophilus influenzae type b (Hib) – X X X
6-in-1c
6-in-1c
6-in-1c
4. Inactivated polio vaccine (IPV) X X X

5. Hepatitis B# X X X#
Pneumococcal vaccine d – X X X
Measles, mumps, rubella (MMR)* – – – X*
Varicella * – – – X*
a. Note that this is a general guideline. The duration of immunosuppression is highly

variable and dependent on the type of HSCT (allogeneic or autologous), the source
of stem cells, presence of GVHD and/or ongoing immunosuppressive therapy.
b. Children between 6 months to 8 years of age who have not previously received
influenza vaccine should receive 2 doses 1 month apart.
c. 6-in-1 (DTaP + IPV + Hib + HepB)
d. Pneumococcal vaccine — 13-valent pneumococcal conjugate vaccine (PCV13–up
to 18 years old) can be given as early as 3 months post-HSCT, for 3 doses; 23-valent
polysaccharide vaccine (PPSV23) may be used for patients older than 18 years.
#Check anti-HBs antibody titire 1 month after the last Hepatitis B vaccination.
*Caution regarding live vaccines (see text above). The second dose of MMR should be
≥6 months from first dose. The second dose of varicella vaccine should be ≥3 months
from the first dose.
Table 7-21: Vaccination in patients with primary immunodeficiencies (PID)

Category of PID Specific examples Contraindicated
X-linked agammaglobulinaemia BCG, OPV, Yellow

Common variable immunodeficiency (CVID) fever, and live oral
B-Lymphocyte
Selective IgA deficiency typhoid vaccine are
IgG subclass deficiency contraindicated.
Severe combined immunodeficiency (SCID)

DiGeorge syndrome All live vaccines
T-Lymphocyte
Wiskott-Aldrich syndrome (WAS) contraindicated.
Hyper-IgM syndrome
Live bacterial vaccines

Chronic granulomatous disease (CGD)
contraindicated —
Phagocyte Leucocyte adhesion defect (LAD)
BCG, live oral typhoid
Myeloperoxidase deficiency
vaccine
Persistent complement, properdin and factor

Complement None contraindicated.
B deficiency
Adapted from Table 13, ACIP General Recommendations on Immunization Jan 2011
Bibliography
(2004).
2. Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell
Transplant Recipients — Recommendations of CDC, the Infectious Disease Society of
America, and the American Society of Blood and Marrow Transplantation. MMWR
Recomm Rep. 49(RR-10): 1–125, CE1–7 (2000).
3. Tomblyn, Chiller et al. Guidelines for Preventing Infectious Complications among
Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol Blood Marrow
Transplant 15: 1143–1238 (2009)
4. Science, Robinson et al. Guideline for Primary Antifungal Prophylaxis for Pediatric Patients
With Cancer or Hematopoietic Stem Cell Transplant Recipients. Pediatr Blood Cancer
61:393–400 (2014).
5. Döring, Müller et al. Analysis of posaconazole as oral antifungal prophylaxis in pediatric
patients under 12 years of age following allogeneic stem cell transplantation. BMC
Infectious Diseases 12:263 (2012).
6. Patel, Chisholm et al. Vaccinations in Children Treated with Standard-Dose Cancer Therapy
or Hematopoietic Stem Cell Transplantation. Pediatr Clin N Am 55: 169–186 (2008).
7. Rubin, Levin et al. 2013 IDSA Clinical Practice Guideline for Vaccination of the
Immunocompromised Host. Clin Infect Dis 58 (3): e44–e100 (2014).
8. General Recommendations on Immunization: Recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Vol. 60 No. 2 (2011).
LYMPHADENOPATHY
DIFFERENTIAL DIAGNOSES
 Infections:
 Bacterial: Staphylococcus aureus, Streptococcus pyogenes,
Bartonella (Cat Scratch Disease), Brucellosis, Tularaemia
 Viral: Epstein-Barr virus (EBV), Cytomegalovirus (CMV), HIV,
Measles, Rubella
 Mycobacterial: Mycobacterium tuberculosis, Mycobacterium avium-
intracellulare, Mycobacterium scrotulareum
 Protozoan: Toxoplasmosis, Malaria
 Fungal: Histoplasmosis, Coccidiomycosis, Cryptococcus,
Aspergillosis
 Autoimmune conditions:
 Juvenile chronic arthritis
 SLE
 Immnodeficiency syndromes:
 Chronic granulomatous disease
 Hyper-IgE syndrome (Job Syndrome)
 Leucocyte adhesion deficiency
 Malignant conditions:
 Leukaemia/lymphoma
 Metastatic solid tumours, e.g. neuroblastoma
 Miscellaneous:
 Kawasaki Disease
 Kikuchi Disease
 Sarcoidosis
 Histiocytosis
 Storage disease, e.g. Gaucher disease, Niemann-Pick Disease
 Medications, e.g. phenytoin
HISTORY
 Age of patient
 Duration of symptoms
 Recurrent infections, recurrent skin sepsis
 Constitutional symptoms, e.g. fever, loss of appetite, loss of
weight
Table 7-21: Investigations and management of lymphadenopathy

Signs and Symptoms Conditions Investigations Management
Suspected
Isolated cervical Viral lymphadenitis None needed Observe
lymphadenopathy, Await resolution in
Otherwise well up to 4–6 weeks.
Fever, lethargic, upper S. aureus infection FBC, Bld C/S IV Ampicillin and IV
respiratory tract infection, S. pyogenes infection Ultrasound scan if Cloxacillin.
pharyngitis, otitis media suppuration Incision and drainage
suspected if abscess formation.
Oral mucositis, dental Anaerobic oral flora FBC, Bld C/S Penicillin or
abscess Clindamycin
School-going age group, Infectious FBC, LFT, Symptomatic
fever, lethargy, white mononucleosis-like EBV IgM treatment
exudates on tonsils, syndrome CMV IgM (Avoid Ampicillin)
hepatosplenomegaly,
generalised
lymphadenopathy
Usually 1–5 years Non-tuberculous Mantoux test (50% Complete surgical
old, usually multiple mycobacterium may be positive) excision.
unilateral, firm lymph infection Excision biopsy Antibiotics
nodes. May undergo rapid (Clarithromycin
suppuration or rupture ± Rifampicin) for
and form cutaneous sinus patients:
tracts.  With established
sinus tracts
 At high risk for
facial nerve
damage if
excision is done
 With intra-
parotid adenitis
 With incomplete
LN excision
Unilateral or bilateral Tuberculous adenitis Mantoux test Treat as for PTB:
firm, discrete, non-tender CXR (normal in 70% Two months of
lymph nodes, often of cases) Rifampicin, Isoniazid
fixed to underlying FBC, ESR and Pyrazinamide
tissues, may progress Lymph node biopsy followed by 4 months
to become matted. May of Rifampicin and
be associated with low- Isoniazid
grade fever and systemic
symptoms.
Signs and Symptoms Conditions Investigations Management

Suspected
Fever, vasculitic rash, Autoimmune condition FBC, ESR Steroid therapy
arthralgia, arthritis, C3C4,
hepatosplenomegaly, ANA, anti-ds DNA
generalised
lymphadenopathy
Fever, loss of Malignant condition FBC, PBF, ESR Treat underlying
appetite, weight loss, LDH, uric acid malignancy
petechiae, pallor CXR
hepatosplenomegaly, Excision biopsy
supraclavicular lymph
node enlargement
Fever, rash, conjunctivitis, Kawasaki Disease FBC, Bld C/S IV Immunoglobulin
red lips, strawberry CRP, ESR, High dose Aspirin
tongue, unilateral cervical 2D Echocardiogram
lymph node enlargement,
swollen or erythematous
hands or feet,
BCG scar erythema
or induration
Infective Cause
Bilateral lymphadenopathy Acute bilateral lymphadenitis

Otherwise well Febrile and ill-looking
Observe for up to 4–6 weeks Admit to hospital
FBC, blood cultures

Resolve Does not resolve, or U/S if suppuration suspected
Progressive, or
New signs and symptoms
IV ampicillin and cloxacillin
Discharge FBC, PBF, ESR Incision and drainage if there

CXR is abscess formation
Mantoux test
Figure 7.9: Suggested algorithm for an infective cause

Non-infected Cause
Autoimmune condition suspected Malignant condition suspected
FBC, ESR, C3, C4 FBC, PBF, ESR, LDH, uric acid

ANA, Anti-ds DNA Excision biopsy (inform pathologist if lymphoma
suspected so that fresh specimen is obtained for
appropriate stain)
Mantoux test
Figure 7-10: Suggested algorithm for a non-infected cause
 Rash, arthralgia
 Drug history
 Travel history; Contact history; Exposure to cats; Animal scratches
 Examine enlarged lymph node for: Size, warmth, tenderness,
overlying skin erythema, fluctuancy, mobility
 Other lymph node involvement: Cervical, occipital, axillary,
epitrochlear, inguinal, popliteal
 Presence of pallor, jaundice
 Joints for swelling, tenderness, limited range of movement
 Skin for vasculitis, petechiae, purpura
 Abdomen for hepatosplenomegaly, intra-abdominal masses
 Localised infection
INVESTIGATIONS AND MANAGEMENT

Please see Table 7-21.
Features which may prompt lymph node biopsy in a child with

lymphadenopathy:
 Lymph node size >2cm or increasing in size
 Supraclavicular lymphadenopathy
 Abnormal CXR
 Presence of systemic signs and symptoms: fever, night sweats,
weight loss, hepatosplenomegaly
If lymph node biopsy is to be done, consult oncologist and ID physician

first.
The biopsy specimen is usually sent for the following:

 Histology (inform pathologist beforehand if lymphoma is
suspected as a fresh specimen is often required)
 Gram stain, culture and sensitivity
 Acid Fast Bacillus (AFB) smear/AFB culture and sensitivity, AFB
Polymerase Chain Reaction (PCR)
 Fungal smear/fungal culture
PAEDIATRIC PALLIATIVE CARE (PPC)
PAEDIATRIC PALLIATIVE CARE (PPC)

The World Health Organisation defines palliative care as “active total
care of patients whose disease is not responsive to curative treatment.
Control of pain, of other symptoms, and of psychological, social and
spiritual problems is paramount. The goal of palliative care is the
achievement of the best quality of life for patients and their families.”
Emphasis is placed on excellent communication skills both with patients

and with their families. Clinical skills in history taking and examination
are essential. Investigations are carried out only if the result will
contribute to the patients’ management. Care of palliative patients
always involves assessment and re-assessment to ensure maximal relief
of symptoms. Patients and their families are intimately involved in
decision making regarding treatment options and care.
Paediatric patients suitable for PPC

Children with these 4 categories of diseases may benefit from a referral
to PPC:
 Diseases where cure is possible but may fail, e.g. cancer
 Incurable diseases but child may live for extended period, e.g. AIDS,
muscular dystrophy
 Progressive diseases from diagnosis, e.g. neurodegenerative diseases
 Non-progressive diseases but shortened life-span, e.g. cerebral palsy
Adult versus Paediatric Palliative Care

The paediatric palliative model of care is integrated and seamless,
throughout initial diagnosis, active curative treatment and symptom
relief, sharing care with community, home and inpatient palliative
care and bereavement services. It is important to gradually move from

curative treatment to palliative care without rigid boundaries.
The adult model of 6 months prognosis as referral criteria cannot apply

in PPC. The focus of care may be more “aggressive” as well, in that there
may be more hospitalisations, and “active” treatment may be ongoing.
A parent should never have to choose between palliative care and hope
for a cure. The psychosocial needs are arguably more intense in PPC.
Families may also prefer the child to be at home rather than in a hospice.
Barriers to PPC
Children may be referred late or not at all to PPC due to barriers such as:
 Physician’s prognostic paralysis regarding child’s illness
 Stigma surrounding death and palliative care, both by physician and
parents
 Misunderstanding of purpose of PPC, e.g. abandonment or giving
up and stopping all treatment
PPC can help with the following categories of needs:

 Symptom management, e.g. pain, vomiting, excessive secretions
 Psychosocial support, e.g. identify child and family’s fears, coping
and communication styles
 Spiritual support, e.g. review child’s hopes, dreams, values, life-
meaning, role of prayer and ritual and beliefs regarding death
 Discussion of Advance Care Plan with parents and child (if child is old
enough)
Conclusion
Palliative care aims to improve quality of life for patients with life-
limiting illnesses and their families regardless of age (i.e. including
children), regardless of stage of illness (i.e. curative treatment, chronic
stage, recovery, terminal stage), and regardless of outcome (i.e. death or
survival).
311
IMMUNOLOGY & ALLERGY
PRIMARY IMMUNODEFICIENCY (PID)

Primary immunodeficiencies (PIDs) are a large and growing group of
over 300 different disorders caused by genetic defects of the immune
system.
Primary immunodeficiencies are currently classified into nine

groups, based on the main immunological defects: predominantly
antibody deficiencies; combined immunodeficiencies; combined
immunodeficiencies with associated or syndromic features; diseases
of immune regulation; congenital defects of phagocyte number or
function, or both; defects of innate immunity; auto-inflammatory
disorders; complement deficiencies; and phenocopies of PIDs.
Table 8-1: "Reg flags" for primary immunodeficiency
1 Family history Positive for early unexplained death, sepsis, recurrent

infections, or specific immunodeficiency diagnoses
2 Frequent infections Elevated frequency of documented infections including
 Four or more new ear infections within 1 year.
 Two or more serious sinus infections within 1 year.
 Two or more pneumonias within 1 year.
3 Chronic infection Persistent sinusitis and otitis media, bronchiectasis, recurrent
abscesses
4 Severe infection Sepsis, osteomyelitis or meningitis, especially if recurrent
or severe
5 Complications of infection e.g. cerebral abscess complicating sinusitis
6 Site of infection Unusual sites, e.g. liver or brain abscess
7 Infecting organism Opportunistic, recurrent, or unusual pathogens, e.g.
Aspergillus, Serratia, Nocardia, Burkholderia cepacia, post-
natal severe CMV infection, disseminated mycobacterium
infection
8 Response to therapy Poor response or recurring infection after antimicrobial
discontinuation or needing IV antibiotics to clear infection
9 Other signs Failure to thrive, severe dermatitis, recurrent diarrhoea,
autoimmunity
Whilst it is estimated that around 60% of PIDs can be easily diagnosed

with simple and inexpensive blood tests, many PIDs remain
underdiagnosed on a global scale. Hopefully, as the technical ability
to identify gene defects improves, more and more genetic causes of
PID will be identified. Screening for some of the most severe forms of
immunodeficiency will also diagnose more individuals and improve
treatment outcomes.
Table 8-2: Evaluation of suspected immunodeficiency (adapted from Rosen, Cooper & Wedgewood
1995; and Shyur & Hill 1996)
Suspected More Advanced
Clinical Findings Initial Tests
Abnormality Tests
Antibody deficiency, Sinopulmonary and Immunoglobulin levels B-cell enumeration
e.g. X-linked Agamma- systemic infections (IgG, IgM, IgA) (CD19, CD20)
globulinaemia, (pyogenic bacteria)
Common Variable Enteric infections Antibody titres to
Immunodeficiency (CVID) (enterovirus, other viruses, vaccine conjugate
Giardia sp.) protein antigens
(diphtheria, tetanus)
Autoimmune disease Antibody titres to IgG subclass levels
(ITP, haemolytic anemia, polysaccharide vaccine
Inflammatory Bowel antigens (older than
Disease (IBD)) 2 years) before and
after immunisation
(pneumococcal
polysaccharide vaccine)
Cell-mediated Pneumonia (pyogenic Total lymphocyte counts T-cell enumeration and
immunity bacteria, fungi, subsets (CD3, CD4, CD8,
e.g. DiGeorge Syndrome Pneumocystis jirovecii, CD19, CD20, CD56)
viruses)
Gastroenteritis (viruses, HIV, ELISA/Western blot In vitro T-cell
Giardia sp. Cryptosporidium proliferation to
sp.) mitogens, antigens, or
allogeneic cells
Dermatitis/mucositis
(fungi)
Immunology and Allergy 313
Suspected More Advanced

Clinical Findings Initial Tests
Abnormality Tests
Combined antibody See above See above See above
and cell-mediated
immunity, Disseminated T cell receptor profile
e.g. Severe Combined mycobacterium and/or and repertoire
Immunodeficiency, fungal infections.
ataxia telangiectasia, ADA assay
Wiskott-Aldrich Alpha-fetoprotein
syndrome, Combined Platelet count/size
immunodeficiency, CD40 Ligand
hyper-IgM syndrome
Asplenia or Bacteraemia or Peripheral blood Technetium-99 spleen
hyposplenia, haematogenous infection smear for Howell-Jolly scan
e.g. sickle cell anemia (pneumococcus, other bodies Haemoglobin
streptococci, Neisseria sp.) electrophoresis (HbSS)
Phagocytes Recurrent superficial and Absolute neutrophil Quantitative
Neutropenia, Chronic deep-seated infections count and trend phagocytosis and
granulomatous disease with Aspergillus, Nocardia chemotaxis studies
and catalase-positive Neutrophil oxidation
organisms. test by Nitroblue
Granuloma formation Tetrazolium (NBT) Test
with obstructive or Dihydrorhodamine
symptoms (DHR)
Complement, Bacterial sepsis C3, C4 Alternative pathway
e.g. C4 deficiency, (pyogenic infection, esp. assays
hereditary angiodema encapsulated bacterial CH50 (total haemolytic Individual component
infections, e.g. Neisseria sp. complement) assays
Autoimmune
disease (lupus, GN)
Recurrent angioedema
with no urticaria
Innate immunity Disseminated Immunoglobulin levels IL12-IFNg cytokine
defect, mycobacterium, fungal or (IgG, IgA, IgM, IgE) evaluation
e.g. IL12-IFNg pathway Salmonella disease
defect Absolute neutrophil and
lymphocyte counts
Bibliography
1. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies, J Clin Immunol
Sep 2015
ANAPHYLAXIS IN CHILDREN
DEFINITION
Anaphylaxis has been defined as a severe, life-threatening generalised
or systemic hypersensitivity reaction, typically involving the skin,
mucous membranes or both with at least one of the following:
 Respiratory compromise, e.g. dyspnoea, bronchospasm, stridor,
hypoxia
 Cardiovascular compromise, e.g. hypotension, collapse
The outcome of anaphylaxis is fatal in up to 2% of cases and the

estimated deaths due to anaphylaxis is 1–3 per million annually. Foods
are the most common trigger in children, teens and young adults. Insect
stings and medications are relatively uncommon triggers in children.
COMMON CAUSES OF ANAPHYLAXIS

 Food: Peanut, egg, seafood, cow’s milk, bird's nest, wheat
 Medications: Ibuprofen (NSAIDS), antibiotics, blood products,
anaesthetic agents
 Insect bites: Bees, wasps, ants
 Others: Latex, immunotherapy, idiopathic
RISK FACTORS
 History of anaphylaxis
 Multiple food and drug allergies
 Poorly controlled asthma
 Underlying lung disease
* Note: The absence of these does not exclude risk of anaphylaxis
CLINICAL MANIFESTATIONS
 Respiratory: Stridor/dyspnoea/dysphasia/persistent cough/wheeze/
tongue swelling
 Cardiovascular: Pallor/hypotension/tachycardia/altered
consciousness/cardiac arrest
 Gastrointestinal: Nausea/vomiting/diarrhoea/severe abdominal pain/
bloody stool
 Mucocutaneous: Pruritus/urticaria/erythema/conjunctival erythema/
flushing/angioedema
 Neurological: Light headedness/confusion/anxiety/altered
consciousness
DIAGNOSIS
Anaphylaxis is a clinical diagnosis. A clear, exhaustive, relevant history of
sequence of events usually helps to arrive at the diagnosis. Some centres
have used serum mast cell Tryptase to differentiate anaphylaxis from
other causes of cardiorespiratory collapse and multiorgan failure.
ACUTE MANAGEMENT
Rapid diagnosis and treatment is crucial. Establish airway, breathing and
circulation. Immediate and concurrent administration of Intramuscular
adrenaline is the treatment of choice. In severe refractory anaphylaxis
and in circulatory collapse, the intravenous route is indicated. Inhaled
route may be useful in reduction of airway swelling but is not the
treatment of choice.
Adrenaline: 0.01ml/kg adrenaline (1:1000; 1mg/ml), max single dose

0.5mg in the anterolateral thigh. To be repeated at short intervals (every
10 mins) until the child’s condition stabilises. If intravenous epinephrine
is used, a dose of 0.1 micrograms/kg/min is recommended.
Normal saline fluid boluses to treat shock and hypovolaemia.

Antihistamines, steroids and nebulised salbutamol are adjuvants in
management of anaphylaxis.
There is no evidence for use of antihistamines in the acute setting. If

needed for adjuvant symptomatic management, oral non-sedating
antihistamines should be used whenever possible. First generation
antihistamines should be reserved for use when parenteral route is
warranted.
FURTHER MANAGEMENT
All children with anaphylaxis should be admitted for at least 6 hours
observation. Late phase anaphylactic reactions are well documented for
up to 72 hours but most manifest in the first 4–6 hours.
Identifying the food allergen implicated in the anaphylactic reaction

is important in preventing inappropriate restrictions on the growing
child’s diet and lifestyle. Where a trigger for the anaphylaxis has been
identified, appropriate advice should be given to prevent exposure to
avoid recurrence.
ANAPHYLAXIS ALGORITHM
Patient with signs and symptoms of anaphylaxis
Adrenaline (1mg/ml, 1:1000) 0.01ml/kg (max 0.5ml)

lateral thigh. Repeat in 10 mins if needed
Initiate ABC management, O2, monitoring, fluids
Yes
Airway compromise/obstruction/respiratory failure? Prepare for intubation/definitive airway management
No
Cardiovascular compromise? Hypotension Shock Fluid resuscitation — 20ml/ Fluids and adjunctive
Yes kg NS, repeat if needed pharmacological therapy
No
Adjunctive pharmacological therapy-H1, H2

blockers, Steroids, Bronchodilators Adjunctive pharmacological
therapy-H1, H2 blockers, CICU Admission for further
Steroids, Bronchodilators management
Cetirizine: 1–2 years — 2.5mg, 2–6 years — 5mg; Yes

6–18 years — 10mg OR Diphenhydramine1–2mg/ Further fluids, Inotropes
Hypotension persistent?
kg, IM/IV (max dose 50mg; Use only if parenteral
administration of H1 blocker required)
Bronchodilator
>10kg: Salbutamol 10 puffs: Ipratropium 4 puffs No
<10kg: salbutamol 5 puffs: Ipratropium 2 puffs
Use nebulised if high flow O2 required
Hydrocortisone: IV 4mg/kg, repeated 6 hourly if needed,
OR MethylPrednisolone: IV 2mg/kg Bolus
OR oral prednisolone 2mg/kg od
Yes
Reassess child, symptoms and signs improved? Admit at least 6–12 hours (Can be Biphasic)
No
Yes
Consider repeat IM adrenaline, Symptoms resolved, Discharge home with
Admit to hospital. Child is well education and follow-up
No
Reinitiate medical management,

Admit to hospital
Figure 8.1: Anaphylaxis algorithm

Identification of the allergen with skin prick/serum specific IgE testing

should be carried out by referral to the Paediatric Allergy service with
appropriate and relevant information with the referral.
Self-Injectable Adrenaline
Any child considered to be at continuing risk of anaphylaxis should be
prescribed a self-injectable adrenaline device. These include:
 History of previous anaphylaxis
 Idiopathic/exercise induced anaphylaxis
 Food allergy with coexisting persistent asthma.
 Reactions to trace of allergens, repeated exposure likely and
remoteness to medical care
On prescription of an injectable adrenaline device, adequate training,

anaphylaxis education, follow up arrangements and individualised
management plans should be undertaken.
 EpiPen (adrenaline 0.3mg) if weight is >30kg
 EpiPenJr (adrenaline 0.15mg) if weight is <30kg
 Or comparable injectable adrenaline product with specific
instructions
Bibliography
1. Muraro et al, EAACI Task Force on Anaphylaxis in Children. The management of
anaphylaxis in childhood: position paper of the European academy of allergology and
clinical immunology. Allergy 2007: 62: 857–871.
2. Liew WK, Chiang WC, Goh AEN, Lim HH, Chay OM, Chang S, Tan JHY, Shih EC, Kidon M.
Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers
over time. Asia Pac Allergy. 2013 January; 3(1): 29–34.
3. Simons et al, World Allergy Organization Guidelines for the Assessmentand Management
of Anaphylaxis. WAO Journal 2011; 4:13–37.
4. Cheng A; Canadian Paediatric Society. Emergency treatment of anaphylaxis in infants and
children. Paediatr Child Health 2011;16(1):35–40
5. NICE Clinical guideline for Anaphylaxis management, Dec 2011, UK.
6. Sheikh A, Ten Broek V, Brown S,Simons F. H1-antihistamines for thetreatment of
anaphylaxis with andwithout shock. Cochrane Database SystRev 2007;CD006160.
7. Winbery SL, Lieberman PL. Histamine and antihistamines in anaphylaxis.Clin Allergy
Immunol. 2002;17:287–317.
8. Church MK, Maurer M, Simons FER, Bindslev-Jensen C, van Cauwenberge P, Bousquet J,
Holgate ST, Zuberbier T. Risk of first-generation H1-antihistamines: a GA2LEN position
paper. Allergy 2010; DOI:10.1111/j.1398-9995.2009.02325.
DRUG ALLERGY
INTRODUCTION
An adverse drug reaction (ADR) is defined as any noxious, unintended
and undesired effect of a drug that occurs at doses used for prevention,
diagnosis or treatment.
A drug allergy is defined as an immunologically mediated response to a
pharmaceutical and/or formulation agent in a sensitised patient.
Table 8-3: Clinical manifestations of immunologically mediated ADRs

Clinical Manifestations Examples of Causative Agents
IgE mediated Urticaria, Angioedema, β-Lactam antibiotics, Platinum-
Bronchospasm, Anaphylaxis based chemotherapeutics,
Perioperative agents
Cytotoxic Haemolytic anemia, Penicillin, Quinine, Sulfonamides
Thrombocytopenia,
Granulocytopenia
Immune Complex Serum sickness Penicillin, Infliximab
Delayed type hypersensitivity Contact dermatitis, Exanthems Penicillins, Sulfonamide antibiotics,
NSAIDs
DRESS* Cutaneous, Fever, Eosinophilia, Anticonvulsants, Sulfonamides,
Hepatic Dysfunction, Allopurinol
Lymphadenopathy
Blistering Conditions Erythema multiforme, SJS, TEN# Sulfonamides, Cephalosporins,
Anticonvulsants, NSAIDs
Immunologic Nephropathy Interstitial nephritis, Membranous Penicillin, Sulfonamides, Gold,
glomerulonephritis Penicillamine, Allopurinol
*DRESS: Drug rash with eosinophilia and systemic symptoms.
#SJS: Stevens-Johnson syndrome, TEN: Toxic epidermal necrolysis
EVALUATION
History Taking
A thorough history is essential in the evaluation of patients with
suspected drug allergies
The most important components of a drug allergy history are:

 Is a drug reaction plausible? What is the chronological order of events?
 What was the reaction? Was it an immediate or delayed reaction?
 Was the reaction mild or severe?

 Had the patient taken the same or a cross-reactive medication before
the reaction?
 Has the patient been exposed to the same or similar medication
since the reaction?
 Has the patient experienced similar symptoms in the absence of
drug treatment?
If a drug-induced allergic reaction is suspected, it is important to

distinguish between immediate and non-immediate reactions in order
to decide on subsequent tests and management
Diagnostic Tests
The most useful test for detecting IgE-mediated drug reactions caused
by large-molecular-weight biologicals and penicillin is the immediate
hypersensitivity skin test. However the sensitivity of allergy tests is not
100% and most are not validated
Drug provocation tests (DPTs) remain the gold standard for the
identification of an eliciting drug when test results are negative, not
validated or not available. DPTs should almost never be performed if the
reaction history is consistent with a severe non-IgE-mediated reaction
(eg. SJS/TEN, DRESS, hepatitis, haemolytic anemia)
Table 8-4: Immediate and non-immediate reactions

Drug Allergy Diagnostic Tests
Immediate (<1 Hour) • Skin prick/intradermal tests
Type-I (IgE-mediated) mechanism • Drug provocation tests
• Specific IgE assays
Delayed • Delayed-reading intradermal tests
Usually Type-IV (T cell-mediated) mechanism • Patch tests
• Drug provocation tests
MANAGEMENT
Management would depend on the severity of the reaction and the
option of safer alternatives
In cases of severe reactions and absence of confirmatory tests,

implicated drugs must be avoided
For any other reaction where there is definite medical indication for
the drug in question, either a DPT can be performed to confirm the
diagnosis or induction of drug tolerance may be considered
Indications For Referral To Allergy Service

 Investigation of a suspected drug allergy, e.g. Skin test, Drug
provocation test
 Serious reaction, e.g. Anaphylaxis, Severe cutaneous adverse reaction
(SCAR)
 Evaluation of safer alternatives in patients with multiple drug
allergies
In cases where the history is clearly consistent with a drug allergy and
the patient does not have any of the above features, a referral is not
required.
Beta-Lactam Hypersensitivity
β-Lactams are the most common causes of drug hypersensitivity
reactions. Skin prick and intradermal tests are useful for immediate
reactions but a drug provocation test is needed to confirm the diagnosis
if there is a strong suspicion of allergy and negative results.
Cross-reactivity depends on the antigenic determinant involved, i.e.

β-Lactam ring or side chain.
Up to 10% of patients with IgE-mediated penicillin allergy may be

allergic to cephalosporins; 3–5% for third generation cephalosporins
In cases of mild reactions, a β-Lactam with a different side chain can be
considered an alternative
Similar side chain/possible Similar side chain/possible Similar side chain/possible

cross-reactivity with group cross-reactivity with group cross-reactivity with group
Penicillin G Amoxicillin, Ampicillin Ceftriaxone (3rd)
Cephalothin (1st) Cephalexin (1st) Cefotaxime (3rd)
Cephaloridine (1st) Cefaclor (2nd) Cefepime (4th)
NSAID Hypersensitivity
NSAID hypersensitivity can be immune-mediated or as a result of
cyclooxygenase (COX) inhibition. A drug provocation test is needed to
confirm the diagnosis regardless of the underlying mechanism.
Seven percent of patients with NSAID hypersensitivity also react to

acetaminophen.
Patients with cross-reactive NSAID and acetaminophen hypersensitivity

would benefit from a drug provocation test to a selective COX-2
inhibitor, e.g. Celecoxib, Etoricoxib.
Bibliography
1. Drug Allergy: An updated practice parameter. Annals of Allergy, Asthma & Immunology.
2010; 105: 274.e2–78
2. Antonino Romano, Maria J. Torres. Diagnosis and management of drug hypersensitivity
reactions. J Allergy Clin Immunol. 2010; 127:S67–73
3. Michael E. Pichichero. Use of selected cephalosporins in penicillin-allergic patients.
Diagnosis Micro and Inf Dis. 2007; 57:13S-18S
4. Mario S. Borges. NSAID Hypersensitivity (Respiratory, Cutaneous and Generalised
Anaphylactic Symptoms). Med Clin N America. 2010; 94: 853–864
FOOD ALLERGY
INTRODUCTION
Most food allergies manifest early in childhood. Children grow out of
most food allergies by school age, except those to nuts and shellfish,
where tolerance is less likely.
Cow’s milk, eggs, peanuts, tree nuts, fish, shellfish, soy, and wheat account
for 90% of all food-allergic reactions. In addition, birds nest allergy has
been reported from this region. Any food can cause an allergic reaction.
Children with food allergies are best followed up by the allergy service,
with dietician support. Referral for children admitted with a suspected
allergic reaction should be prompt .
Cow’s Milk Allergy

Classically presents in infancy, either acutely or with chronic symptoms.
Acute presentations include severe atopic eczema worsened by
switching from breast to formula feeds, acute vomiting, urticarial rashes,
drowsiness or wheezing. Chronic symptoms include gastroesophageal
reflux disease, failure to thrive, chronic diarrhoea with perianal
excoriation, and paradoxically, constipation. Also be aware of the well
looking, breast-fed infant presenting with fresh blood in the stools.

Investigations may not be very helpful as more than half cases are not
IgE mediated. Treatment is by avoiding intact cow’s milk proteins and
replacing by Extensively Hydrolysed formula (eg. Alfare, Alimentum,
Nutramigen), amino acid formula (Neocate) or soya formula (Isomil).
Sometimes, maternal avoidance of dairy products might be helpful.
Egg Allergy
Usually presents acutely during the weaning period, when egg is
introduced for the first or second time. The allergen is stronger than milk
and the reaction is usually IgE mediated. Acute rashes and lip or facial
swellings are typical. Vomiting, wheezing and drowsiness are common.
It is the most likely food to cause anaphylaxis in infancy.
Antihistamines are usually required, preferably non-sedating, occasionally,

steroids are also used. Adrenaline may be required if anaphylaxis is the
presenting feature.
Investigations are useful, and can help guide when it would be safe to
reintroduce. This can take a few years. There is no contra-indication to
MMR vaccine, and of late, most Flu vaccines are also safe to administer.
Peanut Allergy
The incidence is lower here than in the West, but it is still the commonest
cause of anaphylaxis after infancy. Almost all sensitisation has occurred
by the age of 2 years. Mostly presents with acute reactions, the offending
food may not be obvious, as small quantities hidden in other products can
elicit a reaction. A positive skin prick test is not diagnostic of allergy, nor
does it correlate with severity of reactions.
Only 1 in 6 children are known to grow out of peanut allergy. Research

into desensitisation is ongoing.
Only 40% are known to also react to tree nuts, therefore avoidance of all
nuts is not mandatory, but may be appropriate till further investigations
have been performed. If the child is tolerating other nuts, they should
continue to consume these.
Shellfish Allergy
Can present at any age, usually with acute rash or angioedema. Early
presentation is associated with more severe disease. Secondary
sensitisation is common in older children with allergic rhinitis or asthma,
already sensitive to house dust mites or cockroach. These children
usually have milder symptoms. Reactions are most commonly to prawns
and shrimp. Scallops, abalone, squid can all cause reactions, but may not
cross react with prawns/shrimp.
Testing can be useful if a particular species is suspected. Fish and shellfish

do not tend to cross-react. Generally, shellfish allergy is not outgrown.
URTICARIA
INTRODUCTION
Urticaria is a heterogeneous group of diseases. All types share a
common distinctive skin reaction pattern. It is characterised by the
sudden appearance of wheals. It may be associated with angioedema.
A wheal consists of three typical features:

 A central swelling of variable size, surrounded by a reflex erythema
 An itching, or sometimes burning sensation
 A fleeting nature, with its skin returning to its normal appearance
within 1–24 hours
Angioedema is characterised by:

 A sudden swelling of the deeper layers of the dermis
 Sometimes pain rather than itching
 Frequent involvement of the mucous membranes
 Resolution taking sometimes up to 72 hours
Acute urticaria/angioedema can be caused by infection (especially viral),

drug and food or latex allergy. Other possible causes include plant or
animal contacts. When no cause is found, it is called idiopathic urticaria.
Symptoms usually last over a few days, resolving within 6-week duration.
Table 8-5: Classification of Urticaria

Types Subtypes
Spontaneous urticaria Acute urticaria
Chronic urticaria
Physical urticaria Cold contact urticaria
Delayed pressure urticaria
Heat contact urticaria
Others Aquagenic urticaria
Exercise induced urticaria
Contact urticaria
Figure 8-2: Chronic Urticaria Treatment Protocol for Paediatrics (≤16years)
Patient presents with chronic

urticaria symptoms1
Step 1 antihistamine2
Symptoms resolved?*
Yes No
Monitor Step 2 antihistamine (x2)
Symptoms resolved?*
Yes No
*(refer to
Monitor Step 3 antihistamine (x3) specialist clinic)
Symptoms resolved?*
Yes No
Monitor Step 4 antihistamine (x4)
If symptoms are still persisting*
Choice 1 Choice 2
Switch Antihistamine Add

(x2 dose) Montelukast (Singulair)
Symptoms resolved?*
Yes No
Monitor Further evaluation
Treatment Protocol for Chronic Spontaneous Urticaria

1. Chronic urticaria refers to urticaria symptoms persisting for >6 weeks.
2. Antihistamines used does not include first generation antihistamines
3. Specialist clinic refers to Dermatology or Allergy Clinic
^Time between each step is 2 weeks.
*Time between each step is 6 weeks.
Chronic urticaria is defined by the presence of hives on most days of

the week, for a period of 6 weeks or longer. In children, it tends to settle
spontaneously, but can go on for years. It is not triggered by allergens,
and a cause is rarely found.
The management of urticaria consists of two important approaches.

Firstly, the identification and elimination of the underlying cause(s) and/
or eliciting triggers if any. Secondly, treatment is aimed at providing
symptomatic relief. This is achieved with the use of anti-histamines.
In chronic urticaria, the recommended first-line treatment is with a

new generation, non-sedating H1-antihistamine. Higher doses and a
prolonged course are often required.
Investigations for urticaria (especially in chronic urticaria) are usually

unnecessary. However, if an allergic food reaction is suspected, a skin prick
test or IgE-specific blood test may be sometimes ordered. A dermatologist
or allergist should be consulted before these tests are carried out.
All cases of chronic urticaria should be followed up by a dermatologist

or allergist.
Bibliography
1. T. Zuberbier et al. EAACI/GA(2)LEN/EDF/WAO guideline: definition,classification and
diagnosis of urticaria. Allergy 2009:64:1417–1426.
2. T. Zuberbier et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy
2009:64:1427–1443.
3. Bailey et al. An update on childhood urticaria and angioedema. Current Opinion in
Pediatrics. Vol 20(4), August 2008, p425–430.
4. Martin K. Church et al. Chronic spontaneous urticaria in children: Itching for insight.
Pediatr Allergy Immunol 2011:22:1–8.
5. Steven K.W.Chow et al. Management of chronic urticarial in Asia: 2010 AADV consensus
guidelines. Asia Pac Allergy 2012. 2:149–160.
6. Anne Kobza Black. Urticaria and angioedema key facts. (updated 2000) British Association
of Dermatologists. Therapy guidelines committee.
326
INFECTIOUS DISEASES
CHICKENPOX (VARICELLA)
INCUBATION
Ten to 21 days, generally 14–16 days. Can be as long as 28 days in
patients given passive immunisation.
CLINICAL FEATURES
 Prodrome of fever, cough, malaise and pruritus
 Generalised maculopapular rash which progresses to clear vesicles
then cloudy vesicles and finally scabs
 Skin lesions start over the face or trunk, appear in crops and spread
outward to the limbs
 Oral ulcers can occur
 Fever generally lasts 3–5 days
 Suspect secondary bacterial infections if fever lasts >5 days
 Mild, atypical and inapparent infections can occur
COMPLICATIONS
 Secondary bacterial infections — Cellulitis, necrotising fasciitis
 Varicella pneumonitis
 Encephalitis, cerebellar ataxia, meningitis, transverse myelitis
 Reye’s Syndrome
 Thrombocytopenia
 Hepatitis
 Arthritis
 Glomerulonephritis
 Disseminated varicella
 Long term: Herpes zoster
CONTAGIOUS PERIOD
Two days before onset of rash until all scabs have dried up (about 1
week, longer in immunocompromised patients).
Infectious Diseases 327
TRANSMISSION
 Person-to-person direct contact
 Chickenpox and disseminated herpes zoster: Airborne and droplet
spread of respiratory secretions and vesicle fluid
 For herpes zoster: Direct contact with or droplet spread of vesicle fluid
TREATMENT
 Immunocompetent Patients
 Oral acyclovir only if:
 Secondary contact case in a family
 Older than 12 years
 Chronic skin or pulmonary conditions
 On long-term salicylate therapy
 On short- or long-term, intermittent or aerosolised steroids
 Start oral acyclovir within 72 hours (preferably within 24 hours)
of rash onset
 Intravenous acyclovir for complicated varicella, e.g. encephalitis,
disseminated varicella
 Immunocompromised Patients
 Intravenous acyclovir until all lesions have crusted, then oral
acyclovir for another 3 days
Acyclovir Dose
Oral 20mg/kg/dose 6 hourly
Intravenous Younger than 1 month: 10mg/kg/dose 8 hourly
Older than 1 month: 500mg/m2/dose 8 hourly
Isolation
 From 7 days after exposure until all lesions have scabbed
 Patient is contagious from about 2 days before onset of illness
 If given varicella immunoglobulin, isolate until 28 days after
exposure
Immunocompetent Patients Exposed to Chickenpox

 If no history of previous chickenpox, assume patient is susceptible to
varicella. Varicella vaccine can be offered. It may prevent or modify
the illness provided it is given within 72 hours of exposure i.e. index
case is at Day 1–2 of illness. May not protect against disease if the
patient was exposed at the same time as the index case
 The vaccine is given as two doses subcutaneously 3 months apart in
children 12 years or younger, or 6–10 weeks apart if older than 12 years
Immunocompromised Patients Exposed to Chickenpox

 Ask patient for previous history of chickenpox
 Check patient’s record for varicella antibody result (if previously
done)
 If varicella immunity is unknown, screen patient’s blood for varicella
zoster virus (VZV) IgG antibody (call Virology Lab for urgent testing)
 If result shows antibody positive, no action is required
 If result shows antibody negative, give varicella immunoglobulin
(VZIG) within 10 days of exposure. Please refer to KKH Varicella
Post-Exposure Prophylaxis Protocol on KKH intraweb under PAME
Clinical Guidelines.
 Dose: 25IU/kg, or 1ml/kg (vials of 125IU/5ml)
 Do NOT overdose, as this may lead to fluid overload and
hyperviscosity
 Refer to ID/Infection Control team to implement post-exposure
prophylaxis protocol
Discharge if fit, otherwise isolate from other patients for 28 days (from
date of exposure).
If patient is susceptible to chickenpox but has received IV immunoglobulin

(IVIG at 400mg/kg) in the past 3 weeks, VZIG is not required.
BONE MARROW TRANSPLANT (BMT) PATIENTS

Varicella immunoglobulin should be given within 96 hours of exposure
if significant exposure has occurred to the following group of BMT
patients regardless of previous varicella antibody result:
 Patients who are undergoing conditioning regimen
 Allogeneic patients <24 months after BMT
 <24 months after BMT and on immunosuppressive therapy
 Acute or chronic Graft-versus-host Disease (GVHD)
 Varicella antibody — Negative BMT patient undergoing
conditioning treatment, who is exposed to VZV vaccine and
having a varicella-like rash
NEONATES
Give VZIG within 96 hours of exposure if:
 Mother develops chickenpox within 5 days before delivery till
2 days after delivery
 Hospitalised, is premature >28 weeks of gestation and mother has
no history of chickenpox and is varicella antibody negative
 Hospitalised, is premature <28 weeks of gestation, or <1kg
regardless of maternal history or varicella antibody status
TYPES OF SIGNIFICANT EXPOSURE FOR SUSCEPTIBLE

PERSONS
 Household: Residing in the same household
 Playmate: Face-to-face indoor play
 Hospital:
 Varicella patient in the same 2−4 bedroom; or adjacent beds in a
large ward
 Face-to-face contact with an infectious patient or staff member,
or visit by a person deemed contagious
 Herpes zoster — Intimate contact (e.g. touching or hugging) with
a person deemed contagious
Bibliography
1. Pickering LK, editor. Red Book: Report of the Committee on Infectious Diseases. 28th ed.
Elk Grove Village, IL: American Academy of Pediatrics; 2009.
2. Centers for Disease Control and Prevention; Infectious Disease Society of America;
American Society of Blood and Marrow Transplantation. Guidelines for preventing
opportunistic infections among hematopoietic stem cell transplant recipients. MMWR
Recomm Rep. 2000;49(RR-10):1–128.
DENGUE FEVER
DENGUE INFECTION
Causative agent: Dengue virus, serotypes 1–4
Incubation period: 3–14 days, usually 5–7 days
Infectious period: 1 day before until 5 days after the onset of illness,
during the period of viraemia
Transmitted by: Aedes aegypti and Aedes albopictus mosquitoes,
which bite during the day
DENGUE FEVER
An acute febrile illness lasting 2–7 days, associated with two or more of
the following:
 Maculopapular rash, flushing or petechiae; with islands of sparing
 Headache
 Retro-orbital pain
 Myalgia
 Arthralgia
DENGUE HAEMORRHAGIC FEVER (DHF)

All the following four criteria must be fulfilled:
 Fever, or recent history of acute fever
 Haemorrhagic manifestations — Bruising and bleeding at
venepuncture sites, gums or the gastrointestinal tract. Other
examples are epistaxis, a positive tourniquet test, or petechiae
 Low platelet count (<100x109/L)
 Objective evidence of plasma leakage:
 Elevated haematocrit
 Low serum protein
 Ascites
 Pleural or pericardial effusions
The following suggest impending decompensation:

 Severe abdominal pain
 Prolonged vomiting
 Abrupt change from fever to hypothermia
 Change in level of consciousness (irritability or somnolence)
DENGUE SHOCK SYNDROME (DSS)

 The four criteria for DHF, and
 Evidence of circulatory failure:
 Rapid and weak pulse
 Narrow pulse pressure of <20mmHg
 Hypotension
 Cold, clammy skin
 Altered mental status
Usually develops 3–6 days after onset of symptoms.

Signs of possible decompensation are:
 Disappearance of fever
 Drop in platelets
 Increase in haematocrit
OTHER COMPLICATIONS
 Central nervous system: Encephalopathy, encephalitis, aseptic
meningitis, transverse myelitis, Guillain-Barre Syndrome
 Myocarditis
 Transaminitis
 Haemoglobinuria — Intravascular haemolysis
 Vertical transmission to newborn babies
2009 WHO REVISED DENGUE CASE CLASSIFICATION:
Dengue without Warning Signs

Fever and two of the following:
 Nausea, vomiting
 Rash
 Aches and pains
 Leukopenia
 Positive tourniquet test
Dengue with Warning Signs**
Dengue as defined above with any of the following:
 Abdominal pain or tenderness
 Persistent vomiting
 Clinical fluid accumulation (ascites, pleural effusion)
 Mucosal bleeding
 Lethargy, restlessness
 Liver enlargement >2cm
 Laboratory: increase in HCT concurrent with rapid decrease in platelet count
** Requires strict observation and medical intervention
Severe Dengue
Dengue with at least one of the following criteria:
 Severe Plasma Leakage leading to:
- Shock (DSS)
- Fluid accumulation with respiratory distress
 Severe Bleeding as evaluated by clinician
 Severe organ involvement
- Liver: AST or ALT ≥1,000
- CNS: impaired consciousness
- Failure of heart and other organs
INVESTIGATIONS
 FBC: Thrombocytopenia, leucopenia or lymphocytosis with atypical
}
lymphocytes, neutropenia, raised haematocrit Not routine, only if child
is unwell/has
 Renal panel: Hyponatraemia possible features
 LFT: Elevated transaminases (AST > ALT) of pre-shock/shock
 Coagulation studies: Prolonged PT and aPTT
 Group and cross-match: May need transfusion
 Dengue IgG/IgM antibody and Virus NS1 antigen
 Chest radiograph if chest signs present, or work of breathing
increased (pleural effusion)
MANAGEMENT
Routine
 Usually only supportive care is required
 Paracetamol for fever (avoid NSAIDs)
 Complete rest in bed if platelet count <50x109/L
 No intramuscular injections
 IV access
 Monitor vital signs including BP at least every 4 hours
 Strict intake/output (I/O) chart. Maintain hydration
 Daily platelet count and haematocrit from third day of illness
 Put all children admitted to KKH with dengue fever on the Clinical
Pathway for Paediatric Dengue Fever
 Dengue is a notifiable disease — Notify Ministry of Health (MOH) via
Communicable Diseases Live and Enhanced Surveillance (CDLENS)
within 24 hours
Hypovolaemia
 In patients with a rising haematocrit or falling platelet count,
administer an IV bolus of normal saline (10ml/kg to 20ml/kg)
followed by a maintenance dextrose/saline infusion
 Stop IV fluids when the haematocrit <40% and adequate
intravascular volume is present; avoid volume overload
Bleeding
 Platelet transfusion only for active bleeding
 FFP is indicated if there is a consumption coagulopathy
 Use whole blood or packed cells to replace blood loss
 Oxygen can be given for patients with respiratory symptoms
Further Management
Some indications for admission to Children’s Intensive Care Unit (CICU)
are:
 Requirement for continuous monitoring
 Requirement for inotropic support
 Significant bleeding, especially in the setting of severe
thrombocytopenia or coagulopathy
 Evidence of end-organ hypoperfusion, e.g. altered mental status,
oliguria despite fluids
 Respiratory compromise, e.g. secondary to pleural effusions
Bibliography
1. Istúriz RE, Gubler DJ, Brea del Castillo J. Dengue and dengue hemorrhagic fever in Latin
America and the Caribbean. Infect Dis Clin North Am. 2000; 14(1):121–140.
2. Radakovic-Fijan S, Graninger W, Muller C, Honigsmann H, Tanew A. Dengue hemorrhagic
fever in a British travel guide. J Am Acad Dermatol. 2002;46:430–433.
3. Mayers DL. Exotic virus infections of military significance: Haemorrhagic fever viruses and pox
virus infections: Advances in military dermatology. Dermatologic Clinics. 1999; 17:29–40.
4. Dengue fever. In: Goh KT, Paton N, Lam MS, Wong SY, editors. Physician’s guide to
communicable diseases in Singapore. Communicable Disease Centre, and Quarantine and
Epidemiology Department, Ministry of the Environment; 1998. p. 15–7.
5. Halstead SB. Dengue fever/dengue haemorrhagic fever. In: Behrman RE, Kliegman RM,
Jenson HB, editors. Nelson textbook of pediatrics. 16th ed. Philadelphia: WB Saunders;
2000. p. 1005–1007.
6. World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and
Control. Geneva, Switzerland:WHO, 2009.
HAND-FOOT-AND-MOUTH DISEASE
(HFMD), AND HERPANGINA
INTRODUCTION
 Caused by Enteroviruses (EV)
 About 25 EV have been shown to cause HFMD, especially enterovirus
71 (EV 71), Coxsackie A16, A6 and echoviruses
 A variant of HFMD is herpangina, which presents with mouth ulcers
but no rash and is due to the same group of EV
CLINICAL
 Generally a mild disease affecting young children
 Recovery in about 1 week
 Typically presents with fever for up to 5 days:
 Mouth ulcers
 Vesiculo-papular rash lasting 7–10 days over the palms, soles and
buttocks
 Sometimes there are papules over the shins
 Herpangina patients have multiple mouth ulcers over the posterior
pharynx, buccal mucosa and tongue, but no rash
 Complications are rare: myocarditis, pulmonary oedema, interstitial
pneumonitis, brainstem encephalitis, aseptic meningitis, acute
flaccid paralysis and even death
INCUBATION PERIOD
Three to five days (2 days to 2 weeks)
TRANSMISSION
 Direct contact with saliva, nasal secretions and fluid from vesicles
 Oral-faecal transmission via contaminated food, drink and fomites
CONTAGIOUS PERIOD
 Virus excretion occurs from a few days before, during the acute
stage of illness and continues for 3–4 weeks from the saliva and 6–12
weeks from the faeces
MANAGEMENT
 Isolate the patient in a single room or cohort patients with same
disease condition
 Symptomatic treatment with close attention to hydration
 Close monitoring for complications:
 Vomiting, change in sensorium, seizures, myoclonic jerks
 Hypertension/hypotension, tachycardia out of proportion to
fever (normally pulse increases by about 10bpm above baseline
for every 1°C rise in temperature)
 Raised total white cell count
 IVIG is a possible therapy for patients with complicated disease
 Medical certificate for 10 days after onset of illness
 No swimming for next 3 months in order to decrease transmission to
susceptible hosts
All HFMD patients need to have throat swab for EV 71 PCR sent to MOH
for surveillance purposes. For complicated patients, in addition to throat
swab, send stools and vesicular fluid for EV PCR +/- Enterovirus culture.
Hand-foot-and-mouth disease is legally notifiable within 24 hours of

diagnosis. One also needs to indicate the childcare centre or school that
the patient attends.
Bibliography
1. American Academy of Pediatrics. Enterovirus (Nonpolio) Infections (Group A and B
Coxsackieviruses, Echoviruses, and Enteroviruses). In: Pickering LK, editor. Red Book:
Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2009;p287–288.
2. Lee TC, Guo HR, Su HJS, Yang YC, Chang HL, Chen KT . Diseases caused by enterovirus 71
infection. Pediatr Infect Dis J 2009; 28:904–910.
BACTERIAL MENINGITIS
INTRODUCTION
The three most common organisms causing haematogenously acquired
bacterial meningitis in otherwise healthy children (beyond the neonatal
period) are Streptococcus pneumoniae, Neisseria meningitidis and
Haemophilus influenzae Type b (Hib).
SYMPTOMS AND SIGNS

 Fever
 Headache
 Photophobia
 Vomiting
 Neck stiffness
 Back pain
 Myalgia
 Rash
 Confusion and disorientation
 Lethargy
 Seizures
 Kernig’s and Brudzinski’s signs
 Sixth nerve palsy (suggesting raised ICP)
 Papilloedema (uncommon)
 Coma
Symptoms and signs are dependent on the patient’s age and the
duration of illness. Infants may not have neck stiffness but may be
irritable and have inconsolable crying. They may also feed poorly and
have vomiting and diarrhoea. A bulging fontanelle may indicate raised
ICP but is not a highly sensitive or specific sign for meningitis. Grunting
respirations indicate a critically ill infant.
INVESTIGATIONS
 Lumbar puncture (LP) — CSF for cell count, gram stain and culture:
 Cells — Predominantly polymorphs (normal CSF WBC: younger
than 1 month <20/uL, 1–2 months old <10/uL, older than 2
months <5/uL; and no polymorphs)
 Protein — Elevated (normal CSF protein in children: younger
than 1 month 0.3–1.2g/L, 1–3 months old 0.2–0.6g/L, older than 3
months 0.1–0.4g/L)
 Glucose — Reduced (normal CSF glucose concentration should

be approximately 2⁄3 of serum levels; younger than 6 months
2.0–5.6mmol/L, older than 6 months 2.4–4.3mmol/L)
 Pressure — Accepted upper limit during LP with patient in the
left lateral decubitus position is 150mm of water in older children
and 85–110mm of water in younger children. A normal range
between 0–60mm of water has been reported in neonates
 Latex agglutination tests for detection of polysaccharide antigen
is most reliable for Hib (85–95%), followed by S. pneumoniae
(50–75%) and N. meningitidis (33–50%)
 Polymerase chain reaction for detection of N. meningitidis
Contraindications to LP:
 Signs of raised ICP
 Cardiorespiratory instability
 Infection in the area through which the LP needle will pass
 Evidence of coagulopathy
Interpretation of blood-contaminated CSF (‘Traumatic Taps’):

 Traumatic LP’s occur in up to 20% of cases. Simple calculations
to correct for blood contamination are based on the assumption
that the ratio of white to red cells in the CSF attributable to blood
contamination is approximately 1:500
 Another approach would be to determine the Observed:
Predicted WBC (O:P) ratio:
CSF WBC (Predicted) = CSF RBC x Blood WBC / Blood RBC
The predicted value is subtracted from the actual or observed
CSF WBC . True CSF leucocytosis exists when the observed CSF
WBC count is greater than the predicted WBC count (although
this method appears to offer better sensitivity and specificity
than using the CSF white to red cell ratio alone, it may over-
correct the WBC count)
 It has been suggested by some authors that contamination of the
CSF by less than 10,000 red cells x106 does not influence the CSF
white cell count and many authorities still believe that it is safer
to interpret blood contaminated CSF using the same criteria as a
non-contaminated CSF
 Full blood count

 C-reactive protein — Useful in distinguishing bacterial from viral
meningitis but has the limitation of low specificity
 Blood culture — Positive in most children with bacterial meningitis

especially that caused by Hib or S. pneumoniae
 Serum glucose or hypocount at the time of LP
MANAGEMENT
 Antimicrobial therapy (see Central Nervous System: Meningitis under
Antimicrobial guidelines on KKH intraweb)
 Dexamethasone administered just before or concurrently with the first
dose of IV antibiotics significantly diminishes the incidence of neurologic
and audiologic deficits due to Hib meningitis. Early administration also
improves outcome in pneumococcal meningitis. The recommended
dose of IV dexamethasone is 0.2mg/kg/dose Q8H for 2–4 days
 Supportive care — Unless the patient is mildly affected, the initial
care should be in ICU as most life-threatening complications occur
early and require urgent intervention
PROGNOSIS AND SEQUELAE

The mortality rate is <5–10% for the three most common pathogens.
Case fatality rate and neurological sequelae are greatest with
pneumococcal meningitis.
Sensorineural hearing loss is the most common sequelae. It occurs in

20–30% of patients after S. pneumoniae meningitis and in 5–10% of
cases after meningitis due to Hib or N. meningitidis. Hearing should
be tested within 1 month of discharge to detect hearing loss as
early as possible.
PREVENTION
 Hib conjugate vaccine has had a dramatic impact on reducing the
incidence of invasive Hib disease
 Pneumococcal conjugate vaccine (Prevenar 13) is part of the
National Childhood Immunisation Programme (NCIP) in Singapore.
Children older than 2 years who are at risk of developing
invasive pneumococcal disease should also receive the 23-valent
polysaccharide vaccine in addition to the conjugate vaccine
 Quadrivalent meningococcal conjugate vaccine against A, C, Y and
W-135 strains is recommended for high-risk children (e.g. asplenia)
older than 2 years. Meningococcal serogroup C conjugate vaccine is
routinely administered in some countries
 Chemoprophylaxis
 Meningococcal disease (see “Meningococcal Infections” overleaf )
 Hib — Rifampicin prophylaxis is recommended for all household

contacts
Dose:
0–3 months: 10mg/kg once daily for 4 days
3 months to 12 years: 20mg/kg once daily for 4 days
>12 years and adults: 600mg once daily for 4 days
MENINGOCOCCAL INFECTIONS
 Caused by Neisseria meningitidis
 Can result in bacteraemia, meningitis, septic shock, DIC and focal
infections
 Usually serogroups A, B, C, W-135 and Y
 Vaccination available against A, C, W-135 and Y
 Children with terminal complement defects, properdin deficiencies,
functional or anatomic asplenia, are at high risk for meningococcal
infections
 Incubation period 1–10 days, usually <4 days
TREATMENT
 Intravenous Penicillin G (300,000units/kg/day), or
Ampicillin (200–400mg/kg/day), or
Ceftriaxone (100mg/kg/day) or Cefotaxime 300mg/kg per day Q6H
(if IV drip contains calcium)
 Treat for 5–7 days if meningitis, 10–14 days if septic shock
 Give rifampicin to eradicate nasopharyngeal carriage, unless the
primary treatment was with Ceftriaxone
TRANSMISSION AND PRECAUTIONS

 Droplet transmission of respiratory tract secretions
 Respiratory isolation for 24 hours after initiation of effective therapy
 Place the patient in a single room
 When a single room is not available and cohorting is not achievable,
maintain spatial separation of at least 3ft between the infected
patient and other patients and visitors
 Wear a mask during examination or when suctioning of patients with
suspected meningitis/meningoccocal infection within 24 hours of
initiation of therapy
HIGH-RISK CONTACTS FOR WHICH CHEMOPROPHYLAXIS

IS RECOMMENDED
 Household contact, especially children
 Childcare or nursery school contact during the previous 7 days
 Direct exposure to patient’s secretions during the 7 days before the
onset of disease, e.g. kissing, sharing toothbrushes or eating utensils
 Frequently sleeps or eats in same dwelling as index patient
 Mouth-to-mouth resuscitation
 Unprotected contact during endotracheal intubation
PROPHYLAXIS REGIME FOR MENINGOCCOCAL EXPOSURE

 Healthcare workers and adult household contacts
Rifampicin 10mg/kg/dose (max 600mg) Q12H PO x 2 days, or
Ceftriaxone 250mg IM x 1 dose (pregnancy), or
Ciprofloxacin 500mg PO x 1 dose (liver dysfunction)
 Children
Rifampicin: Older than 1 month — 10mg/kg/dose (max 600mg)
Q12H x 2 days
Younger than 1 month — 5mg/kg/dose (max 600mg) Q12H x 2 days, or
Ceftriaxone 125mg IM x 1 dose (younger than 15 years)
 Note: 1 capsule rifampicin = 150mg
 Prophylaxis for medical and nursing personnel NOT routinely
recommended. Prophylaxis is ONLY recommended for staff who have
had unprotected direct droplet exposure (such as mouth-to-mouth
resuscitation, intubation or suctioning) within 24 hours of initiation of
effective antibiotic therapy
Bibliography
1. Pickering LK, ed. Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk
Grove Village, IL: American Academy of Pediatrics; 2009.
2. Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett’s principles and
practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone; 2010.
NEEDLESTICK INJURIES
Needlestick injuries and mucous membranes exposures to blood and
body fluids are known occupational hazards for healthcare workers.
Precautions to avoid needlestick exposures include:
 Do not recap needles
 Do not overfill sharp boxes
 Ensure sharp box is within reach to enable immediate disposal

 Dispose of sharps immediately into sharp boxes yourself
 Do not leave sharps for others to clear
 Communicate with assistants during procedures to avoid crossing
paths with sharps
Blood-borne viruses that can be transmitted through needlestick and

mucous membrane exposures include: Hepatitis B (6–30% risk), C (3.5%
risk) and HIV (0.3% percutaneous, 0.09% mucous membranes).
All healthcare workers should ensure that they have immunity against
hepatitis B (see Table 9-1 next page). For hepatitis C, no vaccine, antiviral
drugs or imunoglobulin are recommended as prophylaxis. For HIV,
depending on the type of exposure and the status of the source patient,
anti-HIV drugs as prophylaxis may be recommended for 4 weeks, after
consultation with an ID physician.
After suffering a needlestick injury, staff should:

 Express blood from the puncture site
 Irrigate the wound with normal saline
 Wash with chlorhexidine detergent/soap and water
Injuries requiring suturing should be treated as usual
In mucous membrane (eyes, mouth) exposure:

 Flush the area with water or saline
 All exposures should be reported to the relevant clinic (Women’s 24-
hour Clinic in KKH)
 Report within 2 hours as this is the ideal time for starting
anti-HIV prophylaxis
Staff and the source patient should be tested for hepatitis B surface antigen,
anti-Hepatitis B surface antibody, anti-hepatitis C serology and HIV serology.
In obtaining consent for HIV testing:

 Explain need for testing in view of needlestick/mucosal exposure
 Reassure patient about confidentiality
 Assess risk factors, e.g. patients who have had unprotected sex (oral/
anal) with an infected partner of either sex, men who have sex with
men or both sexes, patients with multiple sexual partners, intravenous
drug abusers, recipients of blood products before 1985, babies born
to HIV-infected mothers, patients who have been exposed to possibly
non-invasive procedures, e.g. tattooing and scarification
Table 9-1: Recommendations for hepatitis B prophylaxis after percutaneous exposure to blood that
contains (or might contain) HBsAg*
Treatment When Source Is
Exposed Person
HBsAg-Positive HBsAg-Negative Unknown or Not Tested
Administer HBIG,# Initiate hepatitis B Initiate hepatitis B
Unimmunised 1 dose and initiate vaccine series vaccine series
hepatitis B vaccine
Previously immunised
Known responder No treatment No treatment No treatment
Known non-responder HBIG, 2 doses or HBIG No treatment If known high-risk
1 dose and initiate source, treat as if source
immunisation† were HBsAg positive
Response unknown Test exposed person for No treatment Test exposed person for
anti-HBs∆ anti-HBs∆
 If inadequate HBIG,  If inadequate, vaccine
#1 dose and vaccine booster dose‡
booster dose‡
 If adequate, no  If adequate, no
treatment treatment
* Modified from Centers for Disease Control and Prevention, 1997. HBsAg indicates hepatitis B surface antigen; HBIG, hepatitis B
immune globulin; anti-HBs, antibody to HBsAg.
#
Dose of HBIG, 0.06ml/kg, intramuscularly.
†
Persons known NOT to have responded to a three-dose vaccine series and to reimmunisation with 3 additional doses should be
given 2 doses of HBIG (0.06ml/kg), 1 dose as soon as possible after exposure and the second 1 month later.
∆
Adequate anti-HBs is >10mIU/ml.
‡
The person should be evaluated for antibody response after the vaccine booster dose. For persons who received HBIG, anti-HBs
testing should be done when passively acquired antibody from HBIG is no longer detectable (e.g. 4–6 months); if they did not
receive HBIG, anti-HBs testing should be done 1–2 months after the vaccine booster dose. If anti-HBs is inadequate (<10mIU/
ml) after the vaccine booster dose, 2 additional doses should be administered to complete a three-dose reimmunisation series.
 Provide information about HIV antibody test (PCR, Western, Blot,

Serology)
 Assess impact of result on person’s lifestyle
 Assess patient’s support system and coping mechanisms
 Perform risk reduction education
Bibliography
1. Centers for Disease Control and Prevention. Immunization of healthcare workers:
Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the
Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR. 1997; 46(RR-
18):22–23.
OPHTHALMIA NEONATORUM
GONOCOCCAL INFECTION
 Onset: Day 2–5 of life
 Profuse creamy discharge, may be bloodstained
 Swollen lids
 Periorbital oedema
Lab Investigation
 Swab for gonococcal culture
 Usual swab transport system (Copan swabs)
 No need for a Thayer Martin plate
Treatment
 Contact precautions when handling baby
 Normal saline eyedrops (antibiotic drops are not required), 2 drops
every 10 mins x 1 hour, then 2 drops every 30 mins x 2–4 hours, then
2 drops hourly x 3 days
 Ceftriaxone IM 50mg/kg x 1 dose (max 125mg)
 If ceftriaxone is contraindicated, e.g. NNJ or first week of life, give
cefotaxime IM/IV at 100mg/kg x 1 dose
 If there is any suspicion of complicated gonococcal infection, e.g.
septic arthritis, septicaemia, give ceftriaxone or cefotaxime IV for 7
days (14 days if meningitis)
 Send mother and partner/spouse to Department of Sexually
Transmitted Infections (STI) Control (DSC) clinic for screening and
treatment
CHLAMYDIA TRACHOMATIS
 Onset: Day 5–14 of life, may be up to 6 weeks
 Watery eye discharge
 Progresses to become purulent
Lab Investigation
 Swab for Chlamydia trachomatis immunofluorescence. Use
plastic dacron-tipped swab (comes with the slide for Chlamydia
immunofluorescence)
 Send during office hours or next working day
 No need to send after office hours as there is yield even after
starting treatment
Treatment
 Oral erythromycin 50mg/kg/day divided 6 hourly (2 weeks)
 Efficacy of erythromycin is about 80%, a second course may
be required
 Topical treatment alone for conjunctivitis is not advisable as
it is unable to eliminate nasopharyngeal carriage and prevent
subsequent pneumonitis
 Send mother and partner/spouse to DSC clinic for screening and
treatment
STAPHYLOCOCCUS AUREUS, STREPTOCOCCUS

PNEUMONIAE, ESCHERICHIA COLI, HAEMOPHILUS
INFLUENZAE INFECTIONS
 Framycetin or gentamicin eyedrops 2–4 hourly (7–10 days)
 Avoid chloramphenicol eyedrops
Bibliography
1. Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett’s principles
and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone; 2010. p.
2763–67.
TUBERCULOSIS (TB)
INTRODUCTION
 Caused by Mycobacterium tuberculosis
 Acid-fast bacillus
 Transmission usually air-borne
PRESENTATION
 History of contact with an adult with active TB
 Risk of disease in exposed children highest in infancy (43% vs 5–10%
in adults)
 Higher risk of extrapulmonary disease in children
 Higher mortality rates if <4 years
Latent Tuberculosis Infection (LTBI)

 Asymptomatic infection with no abnormal physical findings
 Positive or reactive mantoux test or T spot TB
 Chest x-ray may be normal or show only granulomas or calcification
in the lung, regional lymph nodes or both
 LTBI may evolve into active TB disease
Tuberculosis (TB) Disease

 Pulmonary tuberculosis (PTB):
 Most asymptomatic
 Early manifestations include fever, weight loss, cough, night
sweats and chills
 Lymphadenitis:

Most common form of extrapulmonary TB

Usually cervical, supraclavicular and submandibular nodes

Can be unilateral or bilateral

Lymph nodes generally firm and rubbery, non-tender and fixed
to underlying tissues
 Can progress to affect several nodes
 May be associated with active PTB
 Meningitis/miliary TB (rare):
 Miliary disease is a disseminated form of TB which occurs when
massive bacteraemia causes disease in two or more organs
 Clinical manifestations are protean depending on the site
of involvement
Other extrapulmonary involvement includes pericardium, pleura,

abdominal viscera, bone/joint, kidney.
DIAGNOSIS
Chest X-ray (CXR)
 Hilar adenitis
 Segmental lesions
 Collapse or consolidation
 Calcification occurs >6 months after infection
 Multiple lung foci or cavitation
 Pleural effusions (rare)
 Miliary disease
Mantoux Test (MTT)

 Site: Clean volar surface of left forearm
 0.1ml of tuberculin injected intradermally
 26G tuberculin needle angled upwards

 Tense intradermal wheal 6–10mm should be obtained immediately
during injection
 Do not cover or dress the injection site
 Read mm of induration 48–72 hours later (transverse diameter only)
 Incubation period from infection to a positive MTT is 2–12 weeks
(median 3–4 weeks)
 10% of immunocompetent children with culture-documented
disease do not have an initial reactive MTT
 Children who are immunosuppressed, or who have viral infections
(especially measles, varicella and influenza), and miliary TB are often
anergic and do not demonstrate a reactive MTT
 Positive mantoux reaction:
Induration >10mm (younger than 12 years)
>15mm (older than 12 years)
>5mm (any age) if no previous BCG and exposure
to contagious index patient or immunosuppressed
patient
Vesiculation or pustular reaction of any size
Microbiology
 Specimens collected according to site of suspected infection should
be sent for AFB smear, AFB culture, TB nucleic acid amplification tests
(PCR)
Site Specimen
Pulmonary TB (PTB) 3 specimens from gastric lavage (early
morning) or sputum or induced sputum +/-
bronchoalveolar lavage +/- pleural fluid
Lymphadenitis Biopsy and histology of the affected lymph
node(s)
Meningitis Cerebrospinal fluid
 Isolation of M. tuberculosis by culture from the above specimens

establishes the diagnosis of TB
 Organisms are isolated from fewer than 50% of children and 75% of
infants with PTB
 Culture material should be obtained from children with evidence of
TB disease especially when:
 An isolate from the source case is not available
 Immunocompromised, e.g. HIV infection
 Extrapulmonary disease
TREATMENT
Site of TB Drugs and Duration of Treatment
PTB, lymphadenitis 6 months — 2 months HRZ followed by 4 months
of HR;
or
9 months of HR; or 2 months HRE followed by 7
months of HR
Extrapulmonary 9–12 Months — 2 months HRZE followed by 7–10
months HR
(H: Isoniazid; R: Rifampicin; Z: Pyrazinamide; E: Ethambutol)
 If drug resistance is suspected, initial therapy should include a fourth

drug, either ethambutol or streptomycin, until drug susceptibility
results are available
 Pyridoxine is recommended if:
 Diet deficient in milk and meat/nutritional deficiencies
 Symptomatic HIV-infected children
 Breastfed infants and their mothers
 Pregnant adolescents and women
 Complete TB notification form on diagnosis
 Refer to TB Control Unit for Daily Observed Therapy (DOT) if
compliance is a problem or multi-drug-resistant (MDR) TB
PERSONS AT INCREASED RISK FOR DRUG-RESISTANT

TUBERCULOSIS INFECTION OR DISEASE
 History of treatment for active TB
 Source case for the contact received treatment
 Contacts of a patient with a drug-resistant contagious TB disease
 Foreign-born persons
 Residents of areas where the prevalence of drug-resistant TB is
documented to be high
 Persons whose source case has positive smears for AFB or cultures
after 2 months of appropriate anti-TB therapy
CHEMOPROPHYLAXIS
Indicated for contacts with reactive mantoux test or T spot TB but clear
CXR or MTT conversion i.e. increase in induration by 10mm (e.g. from
3mm to 13mm) when retested 12 weeks after last contact with index case.
 Isoniazid-susceptible — 9 months Isoniazid daily
 Isoniazid-resistant — 6 months Rifampicin daily
 Isoniazid- and rifampicin-resistant — Consult infectious disease
specialist
Table 9-2: Management of the newborn infant whose mother (or other household contact) has
LTBI or TB disease
Circumstances Recommendations Remarks
Mother or household No separation required The mother usually needs
contact has a normal treatment of LTBI i.e.
chest radiograph, Give BCG vaccine chemoprophylaxis. The
asymptomatic newborn infant needs no
special evaluation or therapy.
The positive MTT result could
be a marker of an unrecognised
case of contagious TB within
the household, thus other
household members should
have a MTT and further
evaluation
Mother or household Infant should be separated from Other household members
contact has an mother or contact until evaluation should have a MTT and further
abnormal chest is complete evaluation
radiograph
If TB disease is found, isolation
should continue until the mother
or contact is receiving appropriate
anti-tuberculosis therapy
Evaluate infant for TB disease. Test

mother or contact for HIV
Mother or household  The infant should be evaluated for TB in the mother or
contact has clinical congenital TB and tested for HIV contact should be reported
or radiographic infection immediately to the Department
evidence of possibly • An MTT, a CXR, a LP and of Clinical Epidemiology so that
contagious TB appropriate cultures should be investigation of all household
performed promptly members can be performed
• Placenta should be sent for promptly
histology and AFB smears and
cultures All contacts should have a MTT,
CXR and physical examination
• Regardless of the MTT
results, treatment of the
infant with congenital
TB should be initiated
promptly with isoniazid,
rifampin, pyrazinamide, and
streptomycin
Continued overleaf
Circumstances Recommendations Remarks

Mother or household  If the infant is receiving
contact has clinical treatment, separation is not
or radiographic necessary
evidence of possibly
 If congenital TB is excluded, give
contagious TB
(Continued) BCG vaccine and isoniazid until
the infant is 3–4 months of age,
at which time the MTT should be The infant should be evaluated
repeated at monthly intervals during
 If the MTT at 3 months is positive, treatment
the infant should be reassessed
for TB disease. If disease is not
present, isoniazid should be
continued for at least 9 months
 If the MTT at 3 months is negative
and the mother and other
household contacts with TB have
good adherence and response
to treatment and are no longer
contagious, isoniazid may be
discontinued
 If the mother (or household
contact) has disease due to drug-
resistant TB or has poor adherence
to treatment and DOT is not
possible, the infant should be
given BCG vaccine and separated
from the ill mother or household Note: Patients with multiple
members. The infant and mother drug-resistant TB should be
or contact should be on DOT on DOT therapy
therapy
Management of the newborn infant whose mother (or other household

contact) has LTBI or TB disease:
 Based on categorisation of the maternal or household contact
infection
 Protection of the infant from infection is of paramount importance
 Separation of the infant from the mother or household contact
should be avoided when possible
INFECTION CONTROL AND PREVENTION

 The following children are considered contagious, and standard and
airborne precautions must be observed:
 Cavitating or extensive PTB
 Positive sputum AFB smears
 Laryngeal involvement
 Open abscess
 Nurse in a negative-pressure isolation room

 Doors to the room should be kept closed at all times
 All procedures should be carried out within the room
 No cough-inducing procedures, e.g. chest physiotherapy
 High-filtration TB (N95) masks on entry into room. Use a surgical
mask on the patient, if movement out of the room is necessary
 Limit visitors
 Do not allow children or immunosuppressed visitors
 All family members who are visitors may require CXR to rule out
active PTB as well (consult infectious disease specialist)
 De-isolate if sputum or gastric lavage for AFB smear negative x 3, and
no cough
Bibliography
2. Jacobs RF, Starke JR. Mycobacterium tuberculosis. In Long SS, Pickering LK, Prober CG,
editors. Principles and Practice of Pediatric Infectious Diseases. 2nd ed. Philadelphia, PA:
Churchill Livingstone Churchill Livingston, 2003, p. 791–810.
3. Centers for Disease Control and Prevention. Guidelines for Preventing the Transmission
of Mycobacterium Tuberculosis in Health-care Settings, 2005. MMWR, 2005;
54(no. RR-17):1–121.
INCUBATION AND ISOLATION PERIODS

FOR INFECTIOUS DISEASES
Table 9-3: Incubation period for Infectious Diseases and isolation time frame
Disease Incubation Period Isolation of Patient
Chickenpox 10–21 days (up to 28 From school and non-immune friends until
days if VZIG is given) last vesicle has dried (1 week after appearance
of rash)
Diphtheria 3–6 days Droplet precautions for patients and carriers
with pharyngeal diphtheria until two cultures
from both the nose and throat are negative
Contact precautions for patients with

cutaneous diphtheria until two negative
cultures of skin lesions
Cultures should be taken at least 24 hours

apart after stopping antibiotics
Enterovirus infection 3–6 days Contact precautions for duration of
hospitalisation
Rubella 14–23 days Droplet precautions for 7 days after the onset
of rash
Measles 8–12 days Airborne precautions for 5 days after
appearance of rash
Meningococcal 1–10 days Droplet precautions until 24 hours after
infection initiation of effective therapy
Mumps 14–21 days Droplet precautions until 5 days after onset of
parotid swelling
Poliomyelitis 7–21 days Contact precautions for duration of
hospitalisation or until stool cultures are
negative
Rabies Average 4–6 weeks Standard precautions for duration of illness
Typhoid Fever Usually 1–2 weeks Enteric precautions for duration of illness
and until stool cultures are negative (three
consecutive specimens obtained at least 48
hours after stopping antibiotics)
Whooping Cough Usually a week (range Droplet precaution for 5 days after starting
6–20 days) antibiotics; if unable/unwilling to start
antibiotics, precautions for 14 days
PLEASE REFER TO “ANTIMICROBIAL GUIDELINES” ON

KKH INTRAWEB FOR FURTHER DETAILS ON
ANTIMICROBIAL THERAPY
352
NEONATOLOGY
CLASSIFICATION OF NEWBORN BABIES

Newborn babies are classified according to their gestational age, birth
weight, and other physical attributes.
GESTATIONAL AGE (GA)

Obstetric Methods
 Last Menstrual Period (LMP): GA calculated from the first day of
last menstrual period. The estimated date of delivery is calculated
by adding 7 days to the first day of last menstrual period and then
subtracting 3 months from that
 Ultrasound: Reliable method, especially if performed within the
first trimester. Various measurements may be used such as Crown-
rump Length (CR length), bi-parietal diameter, femur length, and
abdominal circumference
Neonatal Methods
 Dubowitz Score (see Figure10.1 next page): Performed 12–24 hours
after birth
 Ballard Score (see Figure10.2 p. 354): A simplified version of the
Dubowitz score. Infant does not need to be alert or vigorous.
Accuracy is ± 2 weeks
The best estimate of neonatal GA is determined from both obstetric
and neonatal methods. If the two methods differ from each other by >2
weeks, it is customary to take the neonatal estimate.
 Extreme pre-term <28 weeks
 Very pre-term 28 weeks to <32 weeks
 Moderate to late preterm 32 weeks to <37 weeks
 Post-term: GA at birth is >42 weeks
WEIGHT
 Extremely Low Birth Weight (ELBW): <1,000g
 Very Low Birth Weight (VLBW): <1,500g
 Low Birth Weight (LBW): <2,500g
Neonatology 353
Figure 10.1: Dubowitz Score

Figure 10.2: Ballard Score
RELATIVE SIZE
 Small for gestational age (SGA): Birth weight <10th percentile for
estimated GA
 Appropriate for gestational age (AGA): Birth weight between
10th–90th percentile for estimated GA
 Large for gestational age (LGA): Birth weight >90th percentile for GA
Neonatology 355
Common problems with LGA babies (especially >4kg) are:

 Birth trauma
 Perinatal asphyxia
 Hypoglycaemia
 Polycythaemia
SYMMETRICAL AND ASYMMETRICAL GROWTH

RETARDATION
In symmetrical growth retardation, the baby is small but the growth
parameters (head circumference, length, and weight) are proportionate
to each other. This pattern commonly occurs in early pregnancy and
may be related to constitutional factors such as a genetic syndrome or
an intra-uterine infection.
In asymmetrical growth retardation, head growth is relatively spared

as compared to length and weight. Babies are born appearing wasted
and malnourished. Typically, this happens in late pregnancy. Common
causes include placental insufficiency, pregnancy induced hypertension,
and multiple pregnancies.
Common problems in growth-retarded babies:

 Hypothermia
 Hypoglycaemia
 Polycythaemia
 Perinatal hypoxia
The Ponderal Index (PI) is another measurement that is helpful in

determining if growth retardation is acute or gradual in onset:
Birth weight in grammes

PI = x 100
Length in centimetres
PI >2.41 indicates chronic growth retardation

PI <2.41 indicates acute or sub-acute growth retardation
Bibliography
1. Ballard JL, Novak KK, Driver M. A simplified score for assessment of fetal maturation of
newly born infants. J Pediatr. 1979;95(5 Pt 1):769–774.
2. Dubowitz LM, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the
newborn infant. J Pediatr. 1970;77(1):1–10.
AT-RISK NEWBORNS AT DELIVERY

The following are examples of situations when the newborn baby may
become compromised and the presence of a paediatric or neonatal
doctor should be sought. This list is not exhaustive:
INDICATIONS FOR ATTENDANCE (STANDBY) BY NEONATAL

RUNNER MEDICAL OFFICER:
(Other than all code green or blue or brown or red deliveries)
 Fetal distress:
 Persistent late decelerations
 Severe variable decelerations without baseline variability
 Scalp pH ≤7.25
 Thick meconium stained liquor (TMSL) and moderate meconium
stained liquor (MMSL)
 All prolapsed cord
 Antepartum haemorrhage, e.g. placenta praevia major (PPM)
 Multiple births (exception — uncomplicated term dichorionic
diamniotic [DCDA] twins) = Department of OG to provide own standby
 Estimated weight <2,000gm
 Estimated gestation ≤34 weeks
 Severe pre-eclampsia or eclampsia
 Suspected major fetal malformations (as instructed in the Birth
Defect Counseling [BDC] form)
 All failed or difficult instrumental deliveries
For deliveries ≤28 weeks, multiple pregnancy and fetal distress, the
Neonatal Registrar will standby together with the medical officer
BABIES FOR NEONATAL REVIEW SOON AFTER BIRTH IN

OPERATING THEATRE (OT) OR DELIVERY SUITE (DS):
 All babies with respiratory distress or cyanosis

 All babies with Apgar scores <6 at 1 min or 5 mins
 All babies <2,000g (if no standby)
 All babies with major congenital malformations diagnosed
antenatally/postnatally (see instructions in BDC form)
 All neonatal pyrexia >37.5o
 AII suspected birth injuries
 AII assisted breech deliveries and instrumental deliveries (except
Wrigley’s)
Neonatology 357
 AII polyhydramnios or severe oligohydramnios (amniotic fluid index,

AFI <4.0). These babies should be seen in OT or DS to be screened for
defects before feeding or sending to PW (peripheral ward nursery).
For polyhydramnios — oesophageal patency should be verified by
passing an orogastric tube before sending to PW
 AII babies with siblings with previous invasive Group B Streptococcus
(GBS) disease
 AII babies with maternal HIV or untreated syphilis
 AII babies with recent maternal exposure to chickenpox
At standby for all babies <32 weeks, the following added items
should be available
 Ask for resuscitaire with blender oxygen
 T-piece or neopuff and SpO2 monitoring should be available
 Polyethylene wrap for temperature control
Prepare equipment prior to delivery of baby
Check equipment prior to delivery of baby, even if prepared by labour
ward or OT nurse
After resuscitation or review, and before transfer

 check temperature, airway, breathing, circulation
 investigation: hypocount if necessary
THE FOLLOWING BABIES CAN BE SENT TO THE WELL-BABY

NURSERY
Runner MO must review within 2–4 hours of birth. Peripheral ward (PW)
nurses to put these babies on respiratory distress monitoring chart on
arrival in the ward.
 Setup for sepsis but are well and afebrile at birth: Preterm prelabour
rupture of membranes (PPROM) >18 hours, foul liquor, maternal
fever not associated with epidural.
 Born to recently diagnosed GBS carriers that are not treated
adequately i.e. less than two doses of antibiotics before delivery.
 Maternal autoimmune disease with positive anti-Ro or anti-La
antibodies.
 Maternal drug or substance abuse.
 Untreated Rh negative or other isoimmunised mothers.
 Babies weighing 4,000 gm and above.
Guidelines on where to admit the babies after birth. The list is not
exhaustive and serves as a guide
 Neonatal Intensive Care Unit (NICU)
 Birth weight <1,500g
 Gestation <32 weeks
 Critically ill requiring any ventilation
 High oxygen requirement >40%
 Severe perinatal asphyxia
 Major birth defects as mentioned above
 Special Care Nursery (SCN)

 Gestation <35 weeks
 Birth weight <2,000g
 Respiratory distress requiring close review or oxygen
 TMSL
 Suspicion of infection and need for antibiotics, e.g. PPROM and
maternal GBS
 Poor respiratory effort requiring resuscitation with Positive
Pressure Ventilation (PPV) at birth
 Hypoglycaemia
 Antenatal diagnosis of cyanotic congenital heart but baby
saturating well after birth
LIST OF “P” BABIES TO BE REFERRED TO NEONATOLOGIST

FOR CARE
All newborn babies should be seen by a physician trained in
their assessment. Some babies require more attention. Careful
assessment and monitoring of these infants is essential to prevent any
complications:
 Weighing <2,270gm
 Weighing >4,000gm
 Premature babies born <37 completed weeks of gestation
 Intrauterine growth retarded babies (IUGR)
 Babies with congenital malformations and antenatally diagnosed
abnormalities
 Apgar scores of <6 at 1 min or 5 mins
 Multiple births
 Babies from mothers with gestational diabetes or insulin-dependant
diabetes mellitus
 Born after prolonged rupture of membranes (>18 hours)/infected
liquor/suspected intrauterine infection/maternal pyrexia >37.50C
 Thick meconium stained liquor
Neonatology 359
 Fetal distress
 Cord prolapse babies
 Respiratory distress
 Breech and instrumental deliveries other than outlet forceps
 Birth injuries
 Polyhydramnios or oligohydramnios
 Deliveries after 42 weeks gestation
 Maternal sedation within 4 hours delivery
 History of previous neonatal deaths
 Any other conditions which in the opinion of the obstetrician the
baby needs early attention by the neonatologist
 All meconium stained liquor
* Emergency caesarean section babies (other than standby)
* Mothers younger than 16 years, or older than 40 years
* History of previous babies with severe neonatal jaundice
* Mothers with pregnancy induced hypertension /hypertension from
other cause
* Mothers with hyperthyroidism
* Maternal drug or substance abuse
* Maternal sexually transmitted diseases
* Mothers with hepatitis, pulmonary, cardiac disease
* Rh negative or other isoimmunised mothers
* Mothers who are Thalassaemia carriers
* History of previous congenital abnormalities
* These babies if born after office hours could be seen in peripheral

wards during the next morning round
CODES RELEVANT TO NEONATAL DEPARTMENT

In some occasions, urgent standby or attendance by neonatal staff
may be needed at delivery. These are the codes in the hospital that are
relevant to the neonatal staff
 Code green: all fetal bradycardia requiring crash caesarean section.
Who responds: Active registrar, runner MO.
 Code blue for neonates: flat baby, imminent delivery of premature
baby <28 weeks, severe asphyxia. Who responds: runner MO, active
and passive registrar, code nurse, NICU team (Associate consultant
and/or Registrar) on active take (weekdays and office hours), after
office hours and weekends: everyone on call
 Code brown: shoulder dystocia. Who responds: Active registrar,

runner MO
 Code red: peri-mortem caesarean section. Who responds: Runner
MO, passive and active registrars, resuscitation nurse on call
Bibliography
1. Department of Neonatology. Department Guidelines. Singapore: KK Women’s and
Children’s Hospital; 2014.
GUIDELINES FOR DISCHARGE

OF AT-RISK BABIES
At-risk babies to be discharged after meeting all the criteria below:

 Gestation of at least 35 weeks
 Weight ≥1.9kg
 Medical problems resolved or manageable on an outpatient basis
 Able to suck, swallow and breathe in a coordinated fashion in order
to take all feeds by mouth
 Able to maintain body temperature ≥36.50C outside the incubator at
room temperature
 Apnea-free for at least 5 days off respiratory stimulants
 Gaining weight steadily while taking a standard diet of milk (breast
milk or formula)
Prior to discharge, perform:

 A complete physical examination
 Case-note review to identify any remaining problems
 Immunisation, and instruct parents on subsequent immunisations
 Parents must be ready to take baby home and anticipatory guidance
must have been provided
 CPR training to parents or caregivers as needed
 Liaise with the home care team for babies going home with special
assistance such as respiratory support, oxygen or intra-gastric tube
feeding
 Instructions regarding bathing/medications
 Prepare the home
 Cot
 Nappies
Neonatology 361
 Other children
 Other support
 Any other special equipment required
Ensure that there is appropriate medical follow-up; for example with:

 Neonatologist
 Ophthalmologist
 Physiotherapist (early intervention therapy)
 Cardiologist
 Paediatric surgeon
 Dietician
Explore enrollment in a parent support group or similar forum.
NEWBORN RESUSCITATION GUIDELINES

 Most newly born babies are vigorous and do not require intervention
from intrauterine to extra-uterine life
 However, about 10% of newborns may require some assistance to
begin breathing at birth and about 1% may need major resuscitative
measures such as intubation, chest compressions, and/or medications
Assessment at birth and simple newborn care
Initial steps: drying, warming,

positioning, suction to open the
airway, stimulation
Positive pressure ventilation
Chest compression
Medications
Figure 10.3: Inverted pyramid of newborn resuscitation

 Anticipation, adequate preparation, accurate evaluation, rapid

action and effective communication are the important factors for the
success of resuscitation of the newborn.
 The following resuscitation guidelines are based on the Neonatal
Resuscitation Program (NRP) 6th Edition of American Academy of
Pediatrics and American Heart Association
PREPARATION
 Personnel: at least 1 person who can initiate resuscitation should
be immediately available. If high risk delivery anticipated, at least 2
persons should be at standby, with 1 person able to do a complete
resuscitation including intubation and insertion of umbilical lines
 History: Check the perinatal history for high risk factors. Refer to
the previous guidelines on indications for standby. Ask about the:
gestation, number of babies, presence of meconium staining, and
bleeding. These determine the level and extent of likely resuscitation
effort needed:
 Equipment should be checked and ready for every delivery.
 Temperature control. The radiant warmer should be turned on
prior to delivery, and dry blankets and a woolen cap should be
available. If preparing for delivery of a preterm infant <32 weeks
gestation, also get ready polyethylene wraps.
 Airway. Prepare the following:
 Suction apparatus. Prepare the suction bulb or appropriate
sized suction catheter. The suction pressure should be set
between 80–100mmHg.
 Laryngoscopes with appropriate size blades. Make sure the
light is bright and extra batteries are available.
 Endotracheal tubes appropriate for gestation and size of
infant (ETT 2.5, 3.0, 3.5, and 4.0).
 Meconium aspirator if meconium stained amniotic fluid
present.
 Breathing:
 Oxygen with blender and SpO2 probe and monitor should
ideally be available for every delivery.
 Ventilation device: either a self-inflating bag or T-piece.
T-piece allows you to set the Peak Inspiratory Pressure (PIP)
and Positive End Expiratory Pressure (PEEP), and gives a more
consistent pressure during ventilation. It can also provide
CPAP (continuous positive airway pressure).
 Face masks of appropriate sizes
Neonatology 363
Figure 10.4: Resuscitation algorithm
Birth Term gestation? Yes -stay with mother Routine care

Breathing or crying? Provide warmth
Good tone? Clear airway if necessary
Liquor clear? Dry
No Ongoing evaluation
Warm, position, clear airway if necessary, dry, stimulate No

30 sec
HR below 100, No Laboured breathing

gasping, or apnea or persistent cyanosis?
Yes Yes
PPV,
SpO2 monitoring Clear airway
60 sec SpO2 monitoring
Consider CPAP
No
HR below 100?
Yes
Take ventilation
corrective steps
Postresuscitation care
No
HR below 60?
Yes
Consider intubation
Chest compressions Targeted Preductal SpO2
Coordinate with PPV After Birth
Take ventilation No 1 min 60%–65%

corrective steps 2 min 65%–70%
HR below 60?
Intubate if no chest rise! 3 min 70%–75%
4 min 75%–80%
Yes 5 min 80%–95%
Consider:
10 min 85%–95%
Hypovolaemia IV Adrenaline
Pneumothorax
Adapted from Singapore Neonatal Resuscitation Course

 Circulation
 Emergency umbilical vessel catheterisation set
 Drugs for resuscitation
WHEN THE BABY IS BORN
Assessment at Birth:
 Assess if term, breathing or crying, vigorous and if liquor is clear
If yes, the newborn can be dried and nursed skin to skin with mom,
or placed under the radiant warmer for warmth
Initial Stabilisation
 If no, perform the initial steps of stabilisation.
 Place under radiant warmer. Dry the infant, especially the head
and face, and wrap in warm towels
 Make sure the airway is opened by ensuring head is in slightly
extended position or ‘sniffing air’ position. A shoulder roll may
help
 Clear the airway of secretions by suctioning the oropharynx,
and then the nares. Avoid deep pharyngeal suction and gastric
aspiration soon after birth as this may cause bradyarrhythmias
from vagal stimulation.
 Stimulate by gentle flicking of the soles or rubbing the baby’s
back
 Check the vital signs next — heart rate and breathing
Ventilation
 If the baby is apnoeic or heart rate is <100bpm, start positive
pressure ventilation with self-inflating bag or T-piece at a rate of
40–60 breaths per minute
 Ventilation is the most important step in newborn resuscitation, and
it should not be delayed for >1 min if the initial steps do not improve
the heart rate or breathing
 Watch for chest rise and auscultate for equal air entry
 Be careful not to over inflate the lungs as it may cause air leak and
further compromise the newborn
 The best response to effective ventilation is improvement in heart
rate, color and activity
 If no improvement is seen after 5–10 breaths, readjust the mask and
position of the head, clear the airway of secretions, ensure the mouth
is open and ventilate again. You may go up on the pressure gently
Neonatology 365
 If no improvement in chest rise is seen, alternative airway such as

endotracheal intubation or laryngeal mask should be considered
 A saturation probe should be attached to the baby’s right hand or
wrist if ventilation is initiated
 Ventilation can be initiated with room air for term baby, but
subsequent oxygen concentration should be titrated according to
saturation at age in minutes of life
Intubation
Intubation is indicated when there is ineffective ventilation with a bag
and mask, prolonged positive pressure ventilation is required or tracheal
suctioning is required in baby born through meconium stained amniotic
fluid and the baby is not vigorous at birth.
See Table 10-1 for a guide to size and length of ETT.
After intubation, confirm accurate tube placement by auscultating

for equal air entry, look for equal chest rise, misting of the ET tube. A
calorimetric end-tidal carbon dioxide detector can also be used.
External Cardiac Massage (ECM)

 Indicated if heart rate falls below 60bpm despite effective ventilation
 The oxygen should be turned up to 100% if ECM is indicated
 The preferred method of chest compression is the thumb-encircling
Place both thumbs at the junction of the middle and lower third of
the sternum, with the fingers wrapped around the back
 Compress the sternum at a rate of 120/min, coordinated with
ventilation at a ratio of 1 ventilation to 3 compressions
Table 10-1: Guide to size and length of ETT

Weight Gestational age ETT Size *Depth of
(g) (weeks) (mm) insertion (marking
of ETT at upper lip)
(cm)
<1,000 <28 2.5 6
>1,001–2,000gm 28–33 3.0 7–8
>2,001–3,000gm 34–38 3.5 8–9
>3,000gm >38 3.5–4.0 9–10
* Estimated depth is (6 + weight in kg)

* Caution in the extremely low birth weight infants <750g. Depth of insertion may be <6cm
* Use the vocal cord guide on ETT — it should be placed at level of the vocal cords
 The sternum should be depressed to a depth of 1/3 the antero-

postero diameter of the chest
 Continue ECM with ventilation for 45–60 secs, and check the heart
rate again.
 Chest compression can be stopped if heart rate improves to above
60bpm and is steadily increasing
 Continue ventilation until heart rate is >100bpm and baby has
sustained regular breathing
Resuscitation Medications
 Adrenaline
 Indication: when HR <60/min despite 45–60 secs of effective
chest compression and bag-and-mask ventilation.
 Dose: intravenous route is preferred. IV 0.1–0.3ml/kg of 1:10,000
solution as a rapid bolus. ETT adrenaline can be considered at
a dose of 0.5–1ml/kg of 1:10,000 solution if no venous access
is available. However, subsequent doses should be given via
intravenous route as the absorption and effectiveness of ETT
adrenaline is not well studied in neonates
 Adrenaline works by increasing the rate and strength of heart
contractions and peripheral constriction
The fastest and most reliable method of obtaining vascular access is by

cannulating the umbilical vein. Insert the catheter about 3–4cm past the
abdominal wall. Ensure there is easy aspiration of blood. Although it is
possible to advance the catheter to a depth of 8–10cm into the inferior vena
cava, it may become wedged in an undesirable location, e.g. the hepatic or
portal vein.
 Volume expanders — normal saline or emergency blood

 Indications: evidence or suspicion of acute blood loss with signs
of hypovolaemia or shock at delivery, i.e. Pallor, tachycardia,
tachypnoea, hypotension, poor capillary filling and weak pulses
 Type: normal saline, Emergency blood
 Dose: 10ml/kg given as a slow bolus over 10–15 mins
SPECIAL CONSIDERATIONS
 Meconium Stained Liquor (TMSL)
There is a risk of meconium aspiration and subsequent asphyxia or
persistent pulmonary hypertension of the newborn
Neonatology 367
 If the baby is vigorous and crying well at birth, routine care only is
indicated and the oropharynx can be cleared with gentle suctioning
 If the baby is depressed at birth with poor cry and tone, the infant
should immediately be handed to neonatal staff. Intubation of the
trachea under direct laryngoscopy and suction via ETT attached to
meconium aspirator should occur before inspiratory efforts have
been initiated. Withdraw tube while applying continuous suction
pressure to see if meconium is obtained from the ETT
Reintubation and suctioning can be repeated as long as significant
amounts of meconium are removed and the baby is not too bradycardic
 Failure to respond to resuscitation

Consider the following problems:
 Technical errors: ETT in oesophagus or displaced into the
nasopharynx; ETT in right main bronchus; ETT blocked or kinked;
ETT size inappropriate; inflation pressure inadequate; wrong
connection of tubing
 Pneumothorax and air leaks
 Shock
 Malformations, e.g. choanal atresia, laryngeal anomalies, tracheal
 Problems, pulmonary hypoplasia and cystic malformations,
 Diaphragmatic hernia, cardiac and skeletal defects
 Drug depression
 Brain damage, trauma, asphyxia
 Severe sepsis
 Hypothermia
POST-RESUSCITATION CARE:
 Check ETT tube is secured. A CXR should be done soon after transfer
to check position
 Insert an oro-gastric tube to deflate the stomach
 Maintain the temperature of the baby
 If umbilical lines are inserted, secure the lines before transfer
 Speak to the family members and explain what has happened and
that the baby will be transferred to the neonatal intensive care unit
APGAR SCORE
 Scored in first and fifth minute of life; if the baby is still depressed and
needs resuscitation, repeat every 5 mins until the score reaches ≥7.
 Premature babies may have lower scores due to their gestational age.
 Valuable in monitoring the response of the newborn to resuscitation.
It does not drive the resuscitation steps.
 Only one of many measures of a baby’s well-being; it has to be

interpreted in the context of other findings and parameters such as
ante-partum history and monitoring, cord-gas values, and clinical status.
 Scores in later minutes are more predictive of neonatal outcome
than initial Apgar scores.
 Many babies with poor Apgar scores have normal development.
Conversely, many babies with neurological impairment had normal
Apgar scores.
Table 10-2: Apgar score chart

SCORE
SIGN
O 1 2
Heart rate (P) Absent <100/min >100/min
Respiratory effort (R) Absent Slow, irregular Regular
Muscle tone (Activity) Limp Some flexion Active moves
Reflex irritability
No response Grimace Cough,sneeze, cry
(Grimace)
Pink body, blue
Colour (Appearance) Blue all over or pale Pink all over
extremities
Bibliography
1. Neonatal Resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care. Pediatrics Vol. 126 No. 5 November 1,
2010 pp. e1400–e1413
2. Committee on fetus and newborn, American Academy of Pediatrics. Use and Abuse of
Apgar Score. Pediatrics. 1986;78:1148–1129
BREASTFEEDING
BENEFITS OF BREASTFEEDING
Breastmilk is the preferred food for babies. A rich body of scientific
evidence supports the advantages of breastfeeding for both mother
and baby. Beyond the nutritional benefits and psychological bonding,
breastfeeding protects the baby from infections, allergic disorders and
reduces the risk of metabolic diseases such as obesity, type 2 diabetes
and cardiovascular disease.
Neonatology 369
Therefore, it is the professional and moral obligation of healthcare

providers to advocate breastfeeding and support the mother and baby
in every possible way. Any period of breastfeeding is better than no
breastfeeding at all.
The following are some of the benefits of breastfeeding:
Protection against Infection

 Breast milk contains many anti-infective agents including secretory
IgA, lactoferrin, macrophages, and leukocytes and reduces:
 respiratory tract infections
 otitis media
 viral diseases
 diarrheal diseases by promoting the growth of healthy and
non-pathogenic bacteria in the intestine, preventing E.coli from
binding with the intestinal mucosa
 the risk of necrotising enterocolitis (NEC) in premature infants
Protection against Atopy and Allergy

 Breastfed babies are less likely to develop eczema, asthma and other
atopic diseases. Breastfeeding is especially beneficial for babies
who are at high risk of developing atopic diseases, e.g. strong family
history of allergy
 Breast milk contains species-specific protein. Complete breastfeeding
delays introduction of foreign proteins such as cow’s milk protein
Nutritional Benefits
 Breast milk provides adequate nutrition for term babies up to 6
months of age
 The composition of breast milk evolves to reflect the changing
nutritional needs as the baby gets older
 Breast milk contains many compounds (e.g. omega-3 fatty acids) that
are not present in infant formulae
 Although the quantitative amount of iron is less than cow’s milk, the
iron in breast milk is much more easily available to the baby
Other Benefits
 Breastfeeding does not require special preparation or a clean water
supply; it is relatively pathogen-free, economical, comes at a neutral
temperature
 Promotes mother-infant bonding
The current recommendation is exclusive breastfeeding with no

supplementary fluids until 6 months of age. Thereafter, appropriate
complementary foods are gradually introduced. Baby can be breastfed up
to 2 years of age or longer.
CHARACTERISTICS OF HUMAN MILK

Colostrum: Produced in the first few post-partum days; yellowish in
appearance; rich in immunoglobulins, especially secretory IgA and other
anti-infective components.
Transitional milk: Gradually appears several days post-partum;

increases in volume, caloric content and water-soluble vitamins.
Immunoglobulin components are less than colostrum.
Mature milk: There is a great biological variation in the characteristics

of milk between individuals and even in the same individual at different
phases of lactation. As the baby matures, human milk undergoes
considerable variation to keep up with the baby’s nutritional needs.
 Mature milk in large part is water; fat content is most variable
 Caloric density is about 67 calories/100ml
 Fore milk: Early part of the feeding; more dilute and contains less fat
 Hind milk: Later part of the feeding; more concentrated and contains
more fat. As the energy content is higher in the hind milk, it is
important to empty the breast completely during feeding
STOOL AND URINE PATTERN IN BREASTFED BABIES

Breastfed babies have characteristic stool and urine patterns. This helps
in the assessment of the adequacy of feeding.
 First 24 hours:
 Passes meconium 1–2 times
 Passes urine once or twice
 24–48 hours:
 More meconium, appearance of transitional stool
 Passes urine 2–4 times over 24 hours
 48–72 hours
 Transitional stool changing to yellowish breastmilk stool
 Urination frequency increases to 3–4 times over 24 hours
 Beyond 72 hours
 Frequent loose yellowish stool
 Passes urine 6–8 times over 24 hours
Failure to pass adequate amounts of urine and delayed appearance of
yellowish mature stools are objective indications of inadequate feeding
Neonatology 371
TEN STEPS TO SUCCESSFUL BREASTFEEDING (WHO/

UNICEF)
KKH is an accredited baby friendly hospital and full compliance to
the ten steps to successful breastfeeding ensures that exclusive
breastfeeding is promoted and protected. These include:
 A written breastfeeding policy that is routinely communicated to all
health care staff
 Training all health care staff in skills necessary to implement this policy
 Antenatal education to inform all pregnant women about the
benefits and management of breastfeeding
 Achieving skin-to-skin contact between mother and baby within 5
mins of birth for at least 1 hour for both vaginal births and caesarean
births without general anesthesia
 Showing mothers how to breastfeed and how to maintain lactation,
even if they should be separated from their infants. The correct latch-
on and positioning during breastfeeding is shown to mothers
 Giving newborn infants no food or drink other than breast milk
unless medically indicated. Supplemental feeding can be offered
through a cup or spoon to avoid nipple confusion
 Practicing rooming-in — allow mothers and infants to remain
together — 24 hours a day. A short separation may be necessary
during medical examination and procedures but this time should be
limited as much as possible
 Encouraging breastfeeding on demand with no restriction on the
frequency and duration of feeding. Early and frequent feeding helps
establish mother’s milk supply, promotes clearance of meconium,
reduces incidence of jaundice, and minimises breast engorgement
 Giving no artificial teats or pacifiers to breastfeeding infants
 Ensuring mothers have access to community breastfeeding support groups
and other breastfeeding resources on discharge from the hospital or clinic
Full compliance with the International Code of Marketing of Breast milk

Substitutes is also vital in the protection of exclusive breastfeeding.
MONITORING THE ADEQUACY OF FEEDING

The mother-and-baby dyad should be monitored closely and frequently
in the first week to assess adequacy of feeding and to allow the
identification and correction of difficulties. An adequately breastfed
baby has following characteristics:
 Good suck and swallow pattern
 Frequent feeding at least 8–12 times a day
 Normal frequency of urine and stools — See “Stool and Urine Pattern
in Breastfed Babies” in the previous page
 No excessive weight loss (>7% by Day 3 of life)
Full-term breastfed babies most often regain birth weight by 14 days;

a weight loss of >7% of the birth weight during the first week calls for
comprehensive review of the mother-and-baby dyad.
CONTRAINDICATIONS TO BREASTFEEDING
There are very few contraindications to breastfeeding:
 Galactosaemia in the baby
 Maternal psychosis
 Maternal active TB
 Maternal HIV
 Maternal herpes with active lesion on the breast
 Maternal chemotherapy or radiotherapy for cancer treatment
 Selected medication: Radioactive iodine, anti-malaria drugs; some
drugs are transmissible through breast milk; offer alternative therapy
whenever available
A positive hepatitis B serology and Venereal Disease Research

Laboratory (VDRL) test are not contraindications to breastfeeding.
INDICATIONS FOR REFERRAL TO LACTATION

CONSULTANTS
Lactation consultants are professionally qualified nurse or healthcare
professionals who are invaluable in supporting breastfeeding in both in-
hospital and community settings. In Singapore, most hospitals provide
lactation support services.
These are some general indications for referral to lactation consultants:

 Decreased milk supply
 Difficulty in latching-on
 Unable to express milk
 Breast problems: Engorgement, sore nipple, nipple confusion,
inverted nipples
 High-risk infants: Premature, very-low-birth-weight babies
 Returning to work
 Maternal anxiety
Neonatology 373
INFANT FORMULAE
Breastfeeding is best. Neonate and mother should be adequately
supported for total breastfeeding. When breastfeeding is not
available, formula feeding can be instituted with an aim of reinitiating
breastfeeding at every opportunity.
FORMULAE FOR TERM INFANTS

Cow’s-milk-based formulae: The commonly available formulae belong
to this group. Characteristics:
 Caloric density: 20 calories/oz (note: 1oz = 30mls)
 Protein: Cow’s-milk-based; whey: casein ratio 60:40 or whey
hydolysate
 Carbohydrate component: Lactose
 Available as iron-enriched and iron-poor formulations
Note: Cow’s-milk-based iron-enriched formula is the preferred formula
for babies in situations where breastfeeding is not available.
Soy-protein-based formulae: Often misused for minor ailments such

as fussy feeding, vomiting, frequent URTI, and prevention of atopy.
Characteristics:
 Caloric density — 20 calories/oz
 Protein — Soy protein
 Carbohydrate — Glucose polymer and/or sucrose
 Fat — Vegetable oil
 Vitamins and minerals — Higher than cow’s-milk-based formulae
 Indications:
 Galactosaemia
 Documented allergy to cow protein (see note on “Hypoallergenic
formulae” overleaf )
 Contra-indications and precautions:
 Pre-term babies: Higher risk of developing rickets as calcium
absorption is hampered by phytates
 There is significant cross-sensitivity between cow-protein and
soy-protein; use with caution in documented cow-protein
allergic patients
Hypoallergenic formulae: So called as the protein components

are enzymatically broken down to short chain polypeptide or free
amino acids. Major indications are documented cow-protein allergy
and prevention of allergy in babies who are at very high risk of
developing atopy.
FORMULAE FOR PRE-TERM INFANTS

 Caloric density: Higher than term formulae; usually 24 calories/oz (27
calories/oz are available if indicated by dietitian)
 Protein: Higher protein content; up to 3gm/dl
 Carbohydrate: Glucose polymers and lactose
 Fat: A large proportion of Medium Chain Tri-glycerides (MCT);
40–50% of the fat may come as MCT oil
 Minerals: Higher calcium and phosphorus
 Vitamins: Higher vitamin A and D
 Solute load and osmolar load: Lower
 Indications: Pre-term babies with higher energy requirement or
those <1.8kg at birth
TRANSITIONAL FORMULAE
Generally used for pre-term babies upon discharge from hospital.
Characteristics:
 Caloric density: 22 calories/oz
 Protein: Intermediate protein content between term and pre-term
formulae
 Carbohydrate: Glucose polymer and lactose
 Fat: 25% fat as MCT, rest as long chain fatty acids
 Vitamins: Higher than term formula
 Minerals: Higher than term formula
Note: These are general guidelines on formula characteristics and
usages. Please consult individual product information sheet.
Bibliography:
1. Appendix F: Composition of Nutritional Products. In: Siedel HM, Rosenstein BJ, Pathak A,
editors. Primary Care of the Newborn. 2nd ed. St. Louis: Mosby; 1996. p. 504–510.
2. Lee L, Alexander L. Enteral Nutrition. In: Ng SCY, editor. Neonatal Nutritional Handbook.
Singapore: Singapore Pediatric Society; 2002. p. 41–54.
COMMON SKIN CONDITIONS
ERYTHEMA TOXICUM
 Very common
 Appears within the first 48 hours of life
 Presents as scattered erythematous macules and papules,
occasionally with small pustules
Neonatology 375
 Mostly occurs on face, trunk and upper extremities

 Baby is generally well
 No specific treatment is necessary, self resolves in a few days or a
week
MILIA
 Presents as single or multiple small, white papules
 Most commonly appears on forehead and face, especially nose bridge
 Contains keratin
 Ruptures and disappears after few days or weeks
 No specific treatment is necessary apart from routine cleanliness
MOTTLING (CUTIS MARMORATA)

 Scattered areas of erythema with pale areas in-between
 Common following exposure to cold; becoming less obvious with
warming
 If baby is unwell, need to exclude pathological associations, e.g.
hypothermia, poor perfusion, shock, sepsis , CNS disturbances and
hypothyroidism
TRANSIENT NEONATAL PUSTULAR MELANOSIS

 More common in dark-skinned babies
 Maybe present at birth and last for 4–5 days
 Heterogeneous with pustules and vesicles and areas of dark macule
 Baby is clinically well
 No specific treatment is necessary
 May be confused with neonatal herpes and bacterial infection
SUCKING BLISTER
 Believed to be due to vigorous sucking of the baby either in-utero or
immediately after birth
 Presents in the accessible areas such as hand and forearm
 Baby is well
 Should not be confused with neonatal herpes and bullous impetigo
ACNE NEONATORUM
 Rarely presents at birth
 Appears in the first 2–4 weeks of life
 Appears as skin-coloured to pinkish papules, mostly on forehead,
face and body
 Most undergo resolution without treatment
 Advise against heavy application of emollients
INFANTILE HAEMANGIOMA
 Most common vascular tumours; they are proliferative lesions that
usually develop during first few weeks of life
 Most commonly appearing on the head and neck area
 They undergo a fast proliferative growth phase in the first 5–6
months of life, followed by a slow growth phase until about 1 year of
age
 Will regress or involutes thereafter but this will depend on the size of
the haemangioma
 Regression may result in telangiectasias or skin atrophy
Some haemangiomas may be associated with congenital anomalies; in

particular, larger segmental haemangiomas. These are the sites they can
occur at and their associated anomalies:
 Facial segmental haemangiomas (PHACE syndrome — Posterior
fossa abnormalities, Haemangiomas, Arterial abnormalities,
Cardiac abnormalities and Eye abnormalities)
 Perineum segmental haemangiomas (PELVIS syndrome —
Perineal haemangioma, External genital malformations,
Lipomyelomeningocele, Vesicorenal abnormalities, Imperforate
anus and Skin tag)
 Referral to dermatologists for treatment must be considered in the

following circumstances:
 Very large and unsightly lesions
 Ulcerating haemangiomas
 Life-threatening — Beard distribution
 Lesions that impair vision, hearing, breathing or feeding
 Multiple lesions with visceral involvement
CAPILLARY VASCULAR MALFORMATIONS

 These are malformed dilated blood vessels in the skin
 Appear as blotches of red or purple skin discolouration on any part
of the body
 Always present at birth, although they may become more obvious
with time
 Two common capillary vascular malformations:
 Naevus Flammeus (salmon patch, stork bites)

 Patchy light-red area
 Common on forehead, eye-brow and nape of neck
Neonatology 377
 Blanches on pressure
 More intense in colour and noticeable when baby is crying
 Most lesions will spontaneously disappear within the first year of
life
 Stork bites tend to be more persistent
 Most do not require treatment
 Port-wine Stain
 Intensely red to reddish-purplish macule
 Commonly unilateral in distribution
 Does not cross midline
 If present on forehead (distribution of ophthalmic division of
trigeminal nerve) can be associated with Sturge-Weber Syndrome
MONGOLIAN BLUE SPOT

 Extremely common (up to 75% in Asian babies)
 Large irregular areas of bluish or purplish-blue discolouration
 Mostly on buttock or on the back
 Many disappear in toddler years; some may persist
 No treatment is necessary
BIRTH TRAUMA
RISK FACTORS FOR BIRTH TRAUMA

 Maternal factors:
 Primiparous
 Older multipara
 Small malformed pelvis
 Obstetric factors:
 Breech position
 Precipitous delivery
 Abnormal presentation (transverse, face, brow)
 Instrumental delivery (Forceps or vacuum extraction)
 Shoulder dystocia
 Fetal factors:
 Macrosomia
 Prematurity
CAPUT SUCCEDANEUM
This is a diffuse swelling of the scalp, resulting from impairment of
venous return due to prolonged delivery. Underlying collection is tissue
fluid. It crosses the suture lines and is more pronounced at the time of
delivery; the swelling can be indented. This undergoes natural resolution
within 1–2 days and no active management is necessary.
CEPHALOHAEMATOMA
This results from the rupture of blood vessels from the skull to the
periosteum. The swelling does not cross the suture line as the blood
collects in the sub-periosteum. It may be less noticeable at birth and
progressively becomes enlarged as the blood continues to collect. A
linear skull fracture may be present. With time it becomes calcified and
forms a distinct bony swelling.
SUB-GALEAL BLEED
A potentially severe form of bleeding. Fortunately it is also rare. The
bleeding is diffuse over the scalp and fluctuant in nature. It tends to
move towards the dependent side. Observe and monitor in SCN.
Large cephalohaematomata or sub-galeal bleeds may lead to

haemodynamic instability. More commonly, they aggravate
hyperbilirubinaemia.
CLAVICULAR FRACTURE
More common in a macrosomic baby with shoulder dystocia.
Occasionally a ‘snap’ is heard during delivery. The features include
asymmetric Moro reflex and restricted upper extremity movement on
the affected side. The fracture may be detected on palpation.
The treatment is reassurance and a simple figure-of-eight bandage to
immobilise the arm. The prognosis for healing without deformity
is excellent.
ERB’S PALSY
Due to excessive traction of the neck during delivery. The severity varies
from mild praxia with spontaneous recovery to more severe permanent
damage. This is due to injury to the brachial plexus involving the cervical
fifth and sixth nerves. This results in an inability to abduct the extremity
at the shoulder, externally rotate the arm, and supination. The infant
holds the arm in adduction and internal rotation.
Neonatology 379
KLUMPKE’S PARALYSIS
A more severe form of brachial plexus injury. The nerves involved are
the cervical seventh and eighth and first thoracic nerves. It commonly
causes paralysis of the hand and may be associated with an ipsilateral
Horner’s Syndrome. The treatment of Erb’s and Klumpke’s Paralyses is
neuro-rehabilitation with active and passive range-of-motion exercises.
FACIAL NERVE PALSY

Usually a peripheral nerve injury due to the compression of the facial
nerve between the facial bone and mother’s pelvis or obstetric forceps
at the time of delivery. The face is asymmetrical with deviation of the
unaffected side during crying, absence of naso-labial fold on the affected
side. The infant may not be able to close the eyelid of the affected side
and proper eye care is necessary to prevent drying of conjunctiva.
NEONATAL JAUNDICE (NNJ)
The following guidelines are applicable to the inpatient management of

NNJ at the Department of Neonatology, KK Hospital.
RISK FACTORS
 Prematurity
 Low birth weight
 Perinatal hypoxia/hypoxia
 Cephalohaematoma or bruising
 Blood type incompatibility
 Polycythaemia
 Sepsis
 Inadequate feeding
 Delayed passage of meconium
 G6PD Deficiency
ROUTINE INVESTIGATIONS
The following investigations should be carried out for all babies who are
started on phototherapy:
 Full blood counts, including PBF and reticulocyte count
 Blood group, rhesus type and direct Coomb’s test of the baby (“NNJ
profile” for baby)
 Blood group, rhesus type and abnormal antibodies of the mother

(“NNJ profile” for mother)
 Serum bilirubin (SB), if >4 hours have elapsed since the last bilirubin
determination
Phototherapy involves the exposure of as much of the baby’s skin as possible

to blue fluorescent lights, which emit wavelengths in the 430–490nm range.
 Decreases the bilirubin level by enhancing the conversion of
bilirubin in the exposed skin to a more easily excretable form
 Increasing the amount of skin exposure to blue lights can enhance
bilirubin excretion
 Use eye covers to prevent damage to baby’s eyes
Single Blue Phototherapy

 The exposure of one plane of body surface (e.g. either the baby’s
front or back) to the phototherapy light
 Regularly turning the baby helps to maximise the exposure of all
surfaces
Double Blue Phototherapy

 The simultaneous exposure of two body surface planes to two
separate sets of blue lights, i.e. both front and back.
 Recommended if the SB level above double blue phototherapy
criteria or if the rate of rise of SB is >5μmol/L/hr.
Intensive Phototherapy
 Involves the use of 4 lights to achieve higher irradiance/light intensity
 Maximises exposure of all body surfaces in four planes (front, back,
right and left sides)
Criteria for Phototherapy:

There are two sets of phototherapy criteria, each tailored to a specific
group of babies:
 Babies <35 weeks and/or <2kg,
 Babies born at >35 weeks gestation and with birth weight >2kg (fall
under the NNJ Pathway; see “The NNJ Pathway” next page)
For babies born at <35 weeks or with birth weight <2kg (who do not fall
under the NNJ Pathway), see Table 10-3 for the phototherapy guidelines
to be used.
Neonatology 381
Table 10-3: Phototherapy guidelines for babies born with birth weight <2kg or at <35 weeks
Birth Weight Photo Level (mmol/L) Exchange Level (mmol/L)
(grammes) Normal Abnormal Normal Abnormal
<1,250 150 120 220 190
1,250–1,499 170 140 250 220
1,500–1,999 200 170 310 270
2,000–2,400 220 190 340 300
≥2,500 260 230 400 340
For this group, abnormal criteria are applied if:

 Jaundice is observed within 24 hours of delivery
 Blood group incompatibility with positive direct Coomb’s test, or
antibody titre >128
 G6PD deficiency
 Sepsis
 Significant cephalohaematoma or bruising
Double blue lights are used when the SB is <35μmol/L below the
exchange level or rate of rise of SB is >5μmol/L/hr.
Phototherapy could be stopped if the SB level is 35μmol/L below the
photo start level.
THE NNJ PATHWAY

 Risk- and age-stratified management scheme for NNJ
 Applies to babies born at >35 weeks gestation and with birth weight
>2kg
 High- or low-risk classification system
High Risk Factors for significant jaundice:

 Jaundice observed in first 24 hours
 Blood group incompatibility with positive direct Coomb’s test, or
antigen-specific maternal antibody titer >128
 G6PD deficiency
 Gestational age 35–36 weeks at birth
 Significant cephalohaematoma or significant bruising
 Exclusive breastfeeding, only if not nursing well, as evidenced by:
 Weight loss >10% of birth weight
 <5 wet diapers per day
 Clinical evidence of dehydration
 Age <72 hours and baby’s blood group unknown and mother’s
blood group O+
 Age <72 hours and both parents’ blood groups unknown
 Sepsis
Low-risk: All others not belonging to high-risk group
Table 10-4: High-risk phototherapy criteria
Do Double
Off Start Start
Admit for Volume
Age in Hours Phototherapy/ Single Blue Double Blue
Phototherapy Exchange
Discharge Phototherapy Phototherapy
Transfusion
Day 1
90 130 140 220 260
(<24 hours)
Day 2
(>24–48 160 180 190 250 290
hours)
Day 3
(>48–72 190 210 220 280 320
hours)
Day 4–5
(>72–120 190 220 220 300 340
hours)
>120 hours to
220 260 260 300 340
Day 14
Table 10-5: Low-risk phototherapy criteria

Do Double
Off Start Start
Admit for Volume
Age in Hours Phototherapy/ Single Blue Double Blue
Phototherapy Exchange
Discharge Phototherapy Phototherapy
Transfusion
Day 2
190 210 220 300 340
>24–48 hours
Day 3
220 250 260 320 360
>48–72 hours
Day 4–5
220 260 260 360 400
>72–120 hours
>120 hours to
260 300 300 360 400
Day 14
Neonatology 383
OTHER ISSUES
Feeding:
 Feeding can be continued; nil by mouth if the baby needs exchange
transfusion
 Increase feeds by at least 10% over the usual expected intake
 Continue breastfeeding
 If not near or at exchange transfusion level, the baby can be taken off
the lights for up to 30 mins to breastfeed
Double Volume Exchange Transfusion:

If the SB is at exchange transfusion level:
 A medical emergency: Admit the baby immediately for intensive
phototherapy
 Proceed with exchange if the SB does not fall below the desired level
within 3 hours of starting intensive phototherapy
Exchange transfusion should be done immediately:

 When the SB is >85μmol/L above the exchange level
 In any jaundiced infant with signs of kernicterus (or the intermediate
to advanced stage of acute bilirubin encephalopathy: Hypertonia,
arching, retrocollis, opisthotonos, fever, high-pitched cry) even if the
SB level is falling
Discontinuation of phototherapy:
 Once the ‘off phototherapy’ level has been reached and the baby has
completed at least 24 hours of phototherapy
 Rebound SB does not need to be sent
 The baby can be discharged immediately after discontinuation
Parental and caretaker education:

Prior to discharging the baby, emphasise the importance of early follow-
up:
 Especially important for babies discharged before age 48 hours
 Emphasise the risks and manifestations of acute bilirubin
encephalopathy and its consequences
Breastfed babies:
 Give thorough breastfeeding advice
 Teach mothers and caregivers the signs of dehydration
Borderline premature babies (35–36 weeks gestation):

A vulnerable group:
 Tend to be discharged from hospital as early as full-term well babies
because of their larger physical size and apparent maturity
 At higher risk of developing jaundice requiring phototherapy
 Advice to parents of this particular group must be particularly
instructive
Bibliography:
1. American Academy of Pediatrics. Clinical Practice Guideline: Management of
hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics.
2004;114(1):297–316.
2. Seidman DS, Ergaz Z, Paz I, Laor A, Revel-Vilk S, Stevenson DK, Gale R. Predicting the
risk of jaundice in full-term healthy newborns: A prospective population-based study. J
Perinatol.1999;19(8 Pt 1):564–567.
3. Newman TB, Liljestrand P, Escobar GJ. Jaundice noted in the fi rst 24 hours after birth in a
managed care organization. Arch Pediatr Adolesc Med. 2002;156(12):1244–1250.
4. Wong HB. Singapore Kernicterus. Singapore Med J. 1980;21(3):556–567.
5. Kaplan M, Hammerman C. Severe neonatal hyperbilirubinemia: A potential complication
of glucose-6-phosphate dehydrogenase defi ciency. Clin Perinatol. 1998;25: 575–590.
RESPIRATORY DISTRESS
Respiratory distress in babies can manifest as many signs/symptoms
including:
Nasal flaring, grunting, tachypneoa, chest wall retractions, tachycardia,
cyanosis/desaturations, stridor, CO2 retention, irritability, apnea (usually
the last sign!)
GENERAL MANAGEMENT PRINCIPLES

 Overall care: Keep baby in a thermoneutral environment (nurse in an
incubator or under a radiant warmer set to maintain skin temperature
at 36.50 C by using servo control). Minimise disturbance and handling
by grouping together blood sampling and procedures. Any disturbance
of a sick baby may cause apnea, bradycardia and desaturations. Babies
who are intubated or on CPAP might even need sedation (morphine
drip or chloral hydrate), though need to be used judiciously in the
preterm population due to side effects like hypotension.
 On-going monitoring: Continuous monitoring to record heart rate,
respirations,oxygen saturation and temperature (servo probe on
baby’s skin) would be needed. BP can be measured non-invasively
with oscillometric blood pressure cuff (may over-read) or with
intra-arterial line (more reliable and continuous). Blood gas (arterial
Neonatology 385
preferred, via peripheral arterial line or umbilical catheter) should

be monitored every 4–6 hours, or more frequently during acute
stage of respiratory illness. When ventilator parameters are changed,
follow up blood gas should be done 30–60 mins after. Calculation of
Oxygenation index and AaDO2 should be done with every blood gas
when infant’s respiratory illness is severe.
 Investigations: Investigate for cause of respiratory distress (CXR,
infection markers like FBC, CRP, Blood cultures, blood glucose, NPA
for respiratory viruses). Repeat CXR to be considered if any acute or
gradual worsening of respiratory status or escalation of ventilatory
support. Blood glucose, FBC and CRP, blood urea, creatinine and
electrolytes. If change in nature of secretions, consider sending
endotracheal aspirates for gram stain and culture.
 Treatment: Different modes of ventilatory support can be used
depending on the underlying cause for respiratory distress as well
as the degree of support needed. Oxygen should be humidified and
blended to keep target saturation ranges (term versus preterm) in
order to prevent side effects from hyperoxia or hypoxaemia. Treat
the underlying causes, for example: antibiotics (infection), caffeine
(apnea of prematurity) while supporting baby’s respiratory status.
OXYGEN DELIVERY
Oxygen is a drug! It should be given judiciously just enough maintain
targeted SpO2 (86–96% for preterm, and 93–98% for term) with PaO2
of 40–60mmHg generally (babies with PPHN might need higher).
Hence, oxygen blending should be used at all times if available to avoid
hyperoxia related complications.
Oxygen can be delivered to infants without positive pressure via:
 Hood box: Where infant’s head is placed in a hood infused with
humidified oxygen (set at desired concentrations)
 Nasal cannulae (NC): Usually used in babies with chronic lung disease
when they fail to maintain target saturations after depronging from
CPAP. Adjustment can be made with flow 0.5–2LPM (not more than
2LPM is practiced in our department), and set FiO2 0.21–1.00. Babies
with significant chronic lung disease can be discharged home on NC
oxygen under home care arrangement.
CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP)

In CPAP, a continuous flow (usually 6L per min) of heated and humidified
air (with or without oxygen) is circulated past the infant’s airway at a
set pressure (usually 5cmH20, not recommended for >7cmH20)) while
the infant breathes spontaneously. The air-oxygen mixture (FiO2) and
airway pressure (PEEP) can be adjusted. It is usually delivered by nasal

prongs either via the ventilator circuit or bubble (under water) CPAP
system. An orogastric tube should be placed as CPAP can cause gastric
distension interfere with lung inflation by pushing up the diaphragm.
Continuous positive airway pressure might be contraindicated in
babies with gastrointestinal anomalies (mostly obstruction, congenital
diaphragmatic hernia), necrotizing enterocolitis, or immediate post
GI-related surgical repair. It sometimes causes agitation/excessive crying
especially near term or term babies, hence mild sedation (eg. chloral
hydrate) can be considered.
Indications for using CPAP:

 Diseases with low functional residual capacity: Hyaline membrane
disease, transient tachypnoea of newborn, pulmonary oedema and PDA
 Recurrent apneas: CPAP may reduce or terminate attacks in pre-term
babies with apnea of prematurity
 Upper airway or airway closure disease: obstructive airway (eg. Pierre
Robin syndromes), obstructive sleep apnea, Broncho-pulmonary
dysplasia, bronchiolitis, tracheomalacia
 As a weaning mode from mechanical ventilator
 Short trial in meconium aspiration syndrome
Failure of CPAP and indications for mechanical ventilation:

 FiO2 >0.4 on PEEP 5–6cmH20
 PaCO2 >65mmHg on arterial blood gas
 Marked retractions
 Frequent apneas and bradycardias
 Intractable metabolic acidosis
 Cardiovascular collapse
 Decreased respiratory effort (Neuromuscular disease, deep sedation
and paralysis)
Trouble shooting before intubation: exclude errors in blood gas sampling,
machine malfunction, improper CPAP application (may try chin strap), and
nasal obstruction by secretions, water in the tubing, consider nasal IMV
mode (might not be appropriate depending on baby’s status).
MECHANICAL VENTILATION (MV)

When CPAP/NIMV ventilator modes are not sufficient, babies need to be
intubated and supported via invasive mechanical ventilation. The most
commonly used mode of conventional mechanical ventilation (CMV)
in the our NICU are pressure limited (+/- volume targeted), time cycled
modes, synchronisation with baby’s inspiratory breaths, if any. Volume
Neonatology 387
targeted or volume guarantee (VG) mode is the mode of preference in

our department as it is associated with less ventilator induced injury or
complications. In specific lung pathologies or failure of conventional
mechanical ventilation (CMV), a different strategy of ventilation like high
frequency oscillatory ventilation (HFOV) mode can be used.
Below are some general principles regarding CMV in babies:

 Ventilator flow rate: This should be adequate to generate required
PIP, inspiratory time, and allow wash-out of exhaled CO2 and
compensate for leaks around ETT and tubing. Generally, it is set at
6–8L per minute.
 Peak inspiratory pressure (PIP): PIP is adjusted to ensure adequate
but not excessive chest movement. It is generally set between15–
20cmH2O pressure (higher PIP may be needed if the compliance is
low). In volume-guaranteed (VG) mode, the set PIP serves as the
upper limit of pressure allowed for generating the volume prescribed
for the baby. If baby’s lungs compliance improves, the measured PIP
might very well be lower than the set, or on the other hand, the set
PIP (max PIP) might need to be increased in order to achieve the set
tidal volume if lungs are stiff.
 Positive End Expiratory Pressure (PEEP): Usually set at 5–6cmH2O.
PEEP that is inappropriately high over-distends alveoli, causes
pneumothoraces, decreases compliance, impedes venous return and
diminishes cardiac output (hypotension)
 Tidal Volume (Tv): this is set as the desired tidal volume (whatever PIP
needed to achieve volume is used, with the safety margin of the set
max PIP). Usually it’s set between 4–6ml/kg in newborn babies. This
can be difficult when there is a large leak around the ETT.
 Fraction of inspired oxygen (FiO2): This is adjusted to maintain PaO2
between 40–60mmHg (SpO2 86–96%) in premature infants and PaO2
between 50–85mmHg (SpO2 93–98%) in term infants. Avoid hyperoxia
as it is associated with increased risk of ROP in preterm babies.
 Rate: The ventilator rate greatly depends on clinical status of
the baby. Initial setting is usually 30–40 breaths per minute and
is adjusted to maintain PaCO2 of 40–50mmHg or 50–60mmHg
(permissive hypercarbia) in chronic babies if pH is maintained
between 7.25–7.35. Hypocarbia pCO2 <35mmHg should be avoided
as it will cause reduced cerebral blood flow and especially harmful in
a premature brain as well as babies suffering from hypoxic ischaemic
brain injury
 Inspiratory Time (iT) and Expiratory Time (eT): These two parameters
affect the ventilator rate. iT is generally kept between 0.35–0.4 sec,
the longer the better for oxygenation. eT should be longer than the
iT in order to effectively clear CO2 from the lungs.
Although strategies for ventilation are recommended according to the

working diagnosis of the newborn, the response of the individual infant
is variable and changes should be made quickly if there is no clinical
improvement or deterioration while on mechanical ventilation.
Clinical assessment of chest expansion, air entry, colour and peripheral
perfusion is important. Blood gas should preferably be checked 30 mins
after any change in ventilator setting.
PaO2 and PaCO2 can be altered independently of one another:

 PaO2 low: Increase FiO2, increase PIP (in steps of 1–2cmH2O), increase
I:E ratio, and increase PEEP (in steps of 1cmH2O)
 PaCO2 high: Increase rate (in steps of 5–10 breaths per minute),
increase PIP (in steps of 1–2cmH2O), increase or decrease PEEP (in
order to increase delta P, defined by PIP-PEEP)
Consult senior doctors for the use of surfactant and other

pharmacological adjuncts such as inotropes, sedative and analgesics
(choral hydrate, phenobarbitone, morphine sulfate), volume expanders
(normal saline, plasma). Senior doctors should be consulted to explore
possible use of other modalities of ventilation (e.g. high frequency
ventilation) or other adjuncts (pulmonary vasolidators, e.g. inhaled nitric
oxide, sildenafil, or MgSO4).
DETERIORATION DURING VENTILATION

Sudden clinical deterioration: Usually manifests in the form of
hypoxia (a fall in oxygen saturation, clinically cyanosed), hypercapnea,
bradycardia or a blocked ETT
 Observe for air entry and chest expansion; consider ETT suction
and direct laryngoscopy to ensure the tube is in the right position.
A disposable ETCO2 detector can be a great tool to reconfirm that
endotracheal tube is still in place, as a colour change will indicate
correct placement (expired CO2 changes color). An obstructed tube
by secretions or pulmonary haemorrhage (especially considered
when a baby has a large PDA) can be the reason for this.
 Exclude pneumothorax by auscultation or by transillumination. In an
emergency situation, a tension pneumothorax can be drained by needle
aspiration of the pleural space. Otherwise wait for CXR for confirmation
especially in the extremely low birth weight infants who usually gives a
false positive transillumination tests given their thin chest wall.
Neonatology 389
 Consider re-intubation in cases of suspected blocked or dislodged tube

 T-piece resuscitator (Neopuff) should be readily available for trial of manual
PPV or mask PPV in between extubation and reintubation episodes.
Gradual deterioration: This is usually accompanied by a slow fall in

PaO2 and/or increased desaturation episodes. As this may be due to a
displaced or blocked ETT or air leak as well, these should be excluded
first. Other possible causes:
 Inappropriate and inadequate ventilator settings: Due to progressive
deterioration of underlying disease state. Consider increase in PIP,
rate, and/or FiO2
 Baby fighting against ventilator: Blocked or mal-positioned ETT and
inadequate ventilation should be excluded first. Sedation should be
given after exclusion of other causes. Synchronisation of ventilation
usually avoids this problem
 Need for redosing of surfactant: Babies with severe hyaline
membrane disease may need repeated dose of surfactant (can be
done 6–12 hours after last dose depending of type of surfactant
used)
 Intraventricular haemorrhage: Pallor, bulging fontanelle, seizures, fall
in Hb, sudden desaturation, hypotension and acidosis may indicate
intraventricular haemorrhage. This can be confirmed by bedside
cranial ultrasound
 Infection: Nosocomial infections are common. Maintain vigilance and
test appropriately. Consider changing the antibiotic therapy
 Hypotension: Check BP. Review fluid volume given to the patient.
Consider administration of normal saline or plasma or vasopressors
such as dopamine
 Anemia: Frequently due to iatrogenic causes such as blood sampling
(in the tiny baby) or congenital
 Metabolic imbalance: Check electrolytes, urea, creatinine
 Poor environmental support: Avoid excessive handling, group and
plan procedures, and ensure a thermo-neutral environment
Refractory hypoxia: If the PaO2 remains below 40mmHg despite

apparent adequate ventilation and FiO2 ≥50%, consider the following:
 The baby is fighting or breathing out of synchrony with the ventilator
 Increased intra-pulmonary shunting caused by progressive
atelectasis or lobar lung collapse
 Pulmonary hypertension with shunting through the foramen ovale
and/or PDA
 Fixed cyanotic heart disease
WEANING OFF THE VENTILATOR

When the baby’s condition has improved, ventilator settings should be
weaned whenever possible to prevent lung injury. Set PIP (If on SIPPV
mode) can be reduced by 1–2cmH2O to 16–18cmH20; set tidal volume
(if on VG mode) to 4–4.5ml/kg — monitoring PIP needed to achieve
volume set rate can be reduced (to be lower than baby’s spontaneous
breath but not lower than 25). When achieved weaning to minimal
settings as above, extubation should be considered.
In order to maximise success of weaning and extubation:

Sedation and muscle relaxant, if used, should be discontinued or at least
reduced to minimal dose. Administration of a loading dose of caffeine
citrate should be considered in preterm infants of ≤34 weeks gestation.
Adjuctive therapy like inhaled nitric oxide is generally weaned to off
before planning for extubation.
Consider CPAP or hood box O2 after extubation if anticipating baby to

not tolerate room air (based on the severity of lung disease and pre-
intubation need of support). After extubation, monitor the baby closely
for worsening respiratory distress. Blood gas should be followed (30–60
mins after extubation) and consider performing CXR to evaluate for any
atelectasis (not mandatory).
Failure to Wean
 Immaturity: Maturation of control of breathing may be delayed in
premature baby
 Chronic lung disease
 Laryngeal oedema, sub-glottic stenosis, lower tract obstruction.
Nebulised adrenaline can be used, or pre-extubation
dexamethasone can be considered.
 Pulmonary oedema: PDA, fluid over-load
 Central nervous system: Severe brain injury from severe IVH and HIE,
or congenital malformations
 Infection, aspiration of milk, atelectasis
 Metabolic and electrolyte imbalance
 Inadequate nutritional status, anemia
Neonatology 391
NEONATAL SEPSIS
DEFINITION
Neonatal sepsis is a syndrome characterised by the combination of
bacteraemia (or fungaemia) and systemic signs of infection presenting
in the first 30 days of life.
Early onset sepsis (first 3 days of life) results from perinatal infection.
Late onset sepsis (between 4 and 30 days of life) results from perinatal or
postnatal infection.
CAUSES
The most common organisms responsible for early onset sepsis
(EOS) are GBS and Escherichia coli. Less common organisms are
Streptococcus viridans, Enterococcus, gram negative bacteria and Listeria
monocytogenes.
The common organisms responsible for late onset sepsis (LOS) are
coagulase negative staphylococcus, Staphylococcus aureus, Enterococcus,
GBS, gram negative bacteria (such as E. coli, Klebsiella, Pseudomonas,
Enterobacter, Serratia, Acinetobacter, and Candida spp.)
RISK FACTORS
Maternal risk factors:

 Preterm delivery
 GBS colonisation
 Prolonged rupture of membranes >18 hours
 Chorioamnionitis (maternal fever, uterine tenderness, purulent or
foul smelling liquor, maternal tachycardia >100/min, fetal tachycardia
>160/min, maternal leucocytosis)
 Urinary tract infection
Infant risk factors:

 Prematurity
 Low birth weight
 Male gender
 Black race
 Need for mechanical ventilation
 Presence of intravascular devices
 Skin or mucosal breakdown
 Necrotizing enterocolitis
 Use of H2 blockers
 Use of third generation cephalosporin (fungal infection)
CLINICAL PRESENTATION
Clinical presentation is often subtle and not specific.
Signs include:
 Temperature instability (hypothermia or hyperthermia)
 Cardiovascular: tachycardia, hypotension
 Respiratory: apnea, tachypnoea, nasal flaring, retractions, grunting
 Gastrointestinal: poor feeding, poor suck, feeding intolerance, jaundice
 Neurological: lethargy, irritability, seizures
INVESTIGATIONS
 Full blood count: very high or low white cell count, neutropenia,
increased immature to total neutrophil ratio >0.20, white
cell abnormalities such as vacuolation or toxic granulation,
thrombocytopenia
 C reactive protein
 Blood culture
 Urine microscopy and culture
 Lumbar puncture is indicated in infants with a positive blood culture,
in infants whose clinical course or laboratory data are suggestive
of bacteraemia, and in infants who do not respond to antimicrobial
therapy in the expected manner
 Maternal high vaginal swab, placental histology
PREVENTION
Intrapartum antibiotics prophylaxis for the prevention of GBS infection
has decreased the incidence of early onset sepsis.
Indications for intrapartum antibiotics include:

 Positive antenatal cultures for GBS (except for women who have a
caesarean delivery without labour or membrane rupture)
 Unknown maternal colonisation status with gestation <37 weeks,
rupture of membranes >18 hours or maternal pyrexia
 Group B streptococcal bacteriuria
 Previous infant with invasive GBS disease
Adequate prophylaxis is defined as penicillin, ampicillin, cefazolin or

clindamycin given 4 hours or more before delivery.
Neonatology 393
Management
In early-onset infection, the first-line antibiotics are penicillin G/
ampicillin and gentamicin. They have synergistic activity against GBS
and Listeria monocytogenes.
In late onset infection, the choice of antibiotics depends on known

prevalence and sensitivity of organisms in the unit.
 To commence cloxacillin and an aminoglycoside.
 To consider cefotaxime /meropenem if clinical condition
deteriorates. To continue with the appropriate antibiotics once the
results of the culture are available.
PATENT DUCTUS ARTERIOSUS (PDA)

The ductus arteriosus is present in all newborn babies. It closes
spontaneously in healthy term infants soon after birth in response to an
elevated PaO2. However, in pre-term babies, it may persist giving rise to
a variety of problems.
CLINICAL MANIFESTATIONS
 Usually apparent between second and fourth day of life
 May not be accompanied by a murmur, especially in very small
premature babies
 Symptoms are often non-specific and a high degree of vigilance is
necessary
 Clinical features include unexplained apneas, increased oxygen
requirements, respiratory distress, bounding pulses, hyperactive
precordium, widened pulse pressure, a systolic or continuous
systolic-diastolic murmur, metabolic acidosis and worsening
ventilatory status
 An untreated PDA may lead to progressive heart failure, pulmonary
oedema, and pulmonary haemorrhage
DIAGNOSIS
 Chest x-ray shows cardiomegaly and pulmonary congestion
 The diagnosis is confirmed with an echocardiogram, which also
helps to exclude ductus dependent cardiac lesions where
indomethacin is contraindicated
MANAGEMENT
 Restriction of fluid by 10–20ml/kg/day less than the daily requirement
 Pharmacological closure with indomethacin is the mainstay of
treatment in premature babies. Indomethacin inhibits prostaglandin,
which is essential for maintaining ductal patency
 The usual dose of indomethacin is 0.2mg/kg/dose 12 hourly (3
doses). It is infused slowly over 1⁄2 hour. Various modifications of the
dosage regimen are practiced as well
 The course can be repeated 48 hours after the last dose
 Relative contraindications to indomethacin therapy (use with caution
when the following conditions are present): Significant intraventricular
haemorrhage, NEC, significant renal impairment, thrombocytopenia
 Monitor for diminishing urine output, gastrointestinal bleeding, and
hyponatraemia
 Caution when using with nephrotoxic medications such as gentamicin and
other aminoglycosides (monitor for nephrotoxicity and renal insufficiency)
 Surgery is indicated if indomethacin is contraindicated, or if medical
treatment fails (usually after 2 courses fail to close the PDA).
NECROTISING ENTEROCOLITIS (NEC)

Necrotising enterocolitis (NEC) is a condition characterised by varying
degrees of mucosal necrosis and is predominantly seen in premature
infants. Age of onset depends on gestation:
 Preterm infants: 2 weeks to 3 months of life
 Term infants: First week of life
Incidence of NEC in the very low birth weight (VLBW) infants is about 5–7%.
RISK FACTORS
Prematurity Treatment of PDA with ibuprofen or indomethacin
Feeding — formula feeding and rapid advancement of feeds Hypotension requiring inotropes
Perinatal asphyxia Severe chorioamnionitis
Polycythaemia Use of H2 blockers
Umbilical catheters Maternal cocaine abuse
Sepsis Congenital gastrointestinal abnormalities
Patent Ductus Arteriosus (PDA) Congenital heart disease

Neonatology 395
CLINICAL FEATURES
Non-specific signs and symptoms: Abdominal signs and symptoms

 Lethargy  Feeding intolerance
 Tachycardia >160/min  Vomiting
 Temperature instability  Increased pre-feed residuals >30%
 Apnea and bradycardia with desaturations  Abdominal distension with tenderness and
discoloration
 Systemic hypotension  Bloody or bilious gastric aspirates
 Ileus
 Bloody stool
INVESTIGATION
 Full blood count (12–24 hourly until stabilisation of neutrophils and
platelets), CRP, blood culture, electrolytes, arterial blood gas, blood
sugar monitoring, coagulation profile (12–24 hourly until normal).
 Serial AXR (AP and decubitus) 6–8 hourly.
 Stool for rotavirus, enterovirus and bacterial culture (if no stool, send
rectal swab).
 Group and cross match blood.
Non-specific laboratory findings: neutropenia, leukocytosis,

hyponatraemia, metabolic acidosis, hyperglycaemia, DIC picture (in
severe NEC).
Radiological findings: Fixed dilated bowel loops or ‘sentinel loop sign’,

pneumoperitoneum, portal venous gas, pneumatosis intestinalis (latter
two pathognomonic for NEC).
MANAGEMENT
 Manage Airway, Breathing and Circulation (consider ventilatory
support in Stage 2 NEC and above).
 Continuous BP monitoring (via intra-arterial insertion)
 Nil orally. Initiate total parenteral nutrition.
 Nasogastric decompression
 Fluid resuscitation: Normal saline bolus 10–20ml/kg (as required).
Consider FFP for volume expansion if there is associated
coagulopathy.
 Lumbar puncture (only if stable and clinically indicated)
 Intravenous antibiotics for 7–14 days for definite NEC
 Cloxacillin, gentamicin/amikacin and metronidazole

 Escalate to cefotaxime/meropenem if there is worsening clinical
status
 Fluconazole prophylaxis in Stage 2 NEC and above
 Early referral to paediatric surgeon. Absolute indication for urgent
laparotomy is presence of pneumoperitoneum.
Table 10-6: Modified Bell Staging Criteria for NEC

Stage Systemic signs Abdominal Radiographic Treatment
signs signs
1A: Temperature Gastric retention, Normal or mild Nil orally,
Suspected NEC instability, abdominal ileus antibiotics for
apneoa, bradycardia, distension, 3 days
lethargy emesis, occult blood
in stools
IB: Same as IA Same as IA and Same as IA Same as IA

Suspected NEC grossly bloody stool
IIA: Same as IA Same as IA plus Intestinal dilatation, Nil orally,
Confirmed NEC absent bowel ileus, pneumatosis antibiotics for
(mild disease) sounds with or intestinalis 7–10 days
without abdominal
tenderness
IIB: Same as IA, plus Same IA plus Same as IIA with Nil orally,
Confirmed NEC mild metabolic abdominal portal vein gas antibiotics for
(moderate acidosis, mild tenderness 14 days
disease) thrombocytopenia abdominal wall
cellulitis and
palpable abdominal
mass
IIIA: Same as IIB, plus Same as I and Same as IIB, plus Nil orally,
Advanced hypotension, II, plus signs definite ascites antibiotics for
NEC (severe bradycardia, of generalised 14 days, fluid
disease, bowel respiratory acidosis, peritonitis, marked resuscitation,
intact) metabolic acidosis, tenderness and inotropic
disseminated distension of support,
intravascular abdomen. ventilator
coagulation, therapy,
neutropenia paracentesis
IIIB: Same as IIIA Same as IIIA Same as IIB, plus Same as IIIA
Advanced pneumoperitoneum plus surgery
NEC (severe
disease, bowel
perforated)
Neonatology 397
PROGNOSIS
 Mortality rate between 20–40%.
 Late complications include cholestasis, stenosis, strictures, short-
bowel syndrome, and malabsorption.
 Affected infants have about 25% risk of developing
neurodevelopmental delay.
Bibliography:
1. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic
decisions based upon clinical staging. Ann Surg 1978; 187:1–7.
2. Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria.
Pediatr Clin North Am 1986; 33:179–201.
POLYCYTHAEMIA
DEFINITION
A haematocrit value >65% when obtained from a large, freely flowing
peripheral vein
PATHOPHYSIOLOGY:
Incidence — 1.5–4% of all live births.
Haematocrit value peaks at 2–4 hours of life due to transudation of fluid

out of the intravascular space.
The relationship between haematocrit and viscosity is almost linear till

65% and exponential after that. As the viscosity increases, there is an
impairment of tissue oxygenation and perfusion and a tendency to form
microthrombi, which may cause severe damage to gut, cerebral cortex,
kidneys and adrenal glands.
AETIOLOGY:
Polycythaemia in neonates can be due to compensatory mechanism
for intra-uterine hypoxia, secondary to fetal transfusions or due to some
other fetal causes.
 Secondary to Intrauterine hypoxia: due to increased red blood

cells (RBC) production as compensation; as suggested by increased
number of nucleated RBCs
 Intra uterine growth retardation (IUGR)

 Maternal pregnancy-induced hypertension (PIH)
 Maternal gestational diabetes mellitus (GDM) (due to intrauterine
hypoxia)
 Maternal smoking
 Maternal cyanotic heart disease
 Post term
 Secondary to transfusions:
 Delayed cord clamping (>3 mins)
 Holding baby below the level of introitus
 Twin to twin transfusion
 Maternal — fetal transfusion
 Perinatal asphyxia
 Iatrogenic — blood transfusion
 Other causes:
 Dehydration
 Trisomy 13, 18, 21
 Hypothyroidism, thyrotoxicosis
 Congenital adrenal hyperplasia
 Beckwith-Weidemann syndrome
CLINICAL FEATURES/SYMPTOMS:
Most of the symptoms are non-specific and related to underlying cause.
Neurological: Hypotonia, irritability, jitteriness, seizures
Cardiovascular: Tachycardia, cyanosis
Respiratory: Respiratory Distress
Gastrointestinal: Poor suck, vomiting, feeding difficulties
Metabolic: Hypoglycaemia, pathological jaundice
Haematologic: Thrombocytopenia
MANAGEMENT:
 Ensure adequate hydration.
 Correct underlying cause and treat complications.
 Definite treatment is partial exchange transfusion (PET) where blood
is taken out slowly and replaced with normal saline (preferred) or
plasma.
Neonatology 399
Partial Exchange Transfusion (PET):
Indications:
 Symptomatic polycythaemia
 Haematocrit >70% in asymptomatic infant
Target: To attain haematocrit of 55%
Route of PET: Intra-arterial line (IAL) and IV line or umbilical venous

cannulation (UVC)
Volume of blood exchanged:

Volume to be exchanged = Blood volume x (Observed haematocrit − desired haematocrit)
Observed Haematocrit
Blood Volume = 80mls/kg in term babies and 90mls/kg in preterm

babies.
COMPLICATIONS OF POLYCYTHAEMIA:
Neurologic: Seizures, strokes, motor deficits, low IQ scores
Cardiovascular: Cardiomegaly, increased pulmonary resistance,
decreased cardiac output, congestive cardiac failure (CCF)
Gastrointestinal: Necrotizing enterocolitis (NEC), ileus
Renal: Renal vein thrombosis, renal failure, oliguria
Others: Priapism, testicular infarct, peripheral gangrene
Bibliography
1. Department of Neonatology: Protocol for management of Polycythemia in neonates.
K.K. Women’s and Children’s Hospital, Singapore 2012.
(Dr. Shrenik Vora and Dr. Bhavani Sriram)
HYPERINSULINAEMIC
HYPOGLYCAEMIA (HH)
Hyperinsulinism should be suspected in an infant having hypoglycaemia

while on a glucose infusion rate of >8mg/kg/min. While increasing
glucose infusion rate by 2mg/kg/min at every step, send the infants’
blood for plasma sugar, insulin, C-peptide, cortisol, ketone bodies and
non-esterified fatty acids (NEFA) during an episode of hypoglycaemia.
Look for evidence of sepsis. If the blood results showed detectable

insulin levels with hypoglycaemia, hypoketonaemia, hypofattyacidaemia
(NEFA) and a response to glucagon IM/IV (rise in glucose concentration
of >1.5mmol/L within 30 mins), diagnosis of HH can be made.
Attempt to raise glucose levels in these infants primarily by increasing

glucose concentrations. A central line should be secured for dextrose
concentrations above 12.5%. The goal is to maintain plasma glucose
levels above 3.5mmol/L in order to prevent hypoglycaemic brain injury
(Discuss the case with senior physician from neonatology/paediatric
endocrinology). Look for inborn errors of metabolism screening results
done at birth. Serum ammonia levels are elevated in infants with
Hyperammonaemia-hyperinsulinism (HI/HA) syndrome, second most
common cause of congenital hyperinsulinism.
Hyperinsulinaemic hypoglycaemia can be transient or persistent

(genetic or congenital). Recessive mutations in the KATP channel of the
β-cells of pancreas, encoded by ABCC8 and KCNJ11 genes, are the most
common causes of congenital HH. Transient forms are often seen in
infants of diabetic mothers, IUGR infants, following perinatal asphyxia
and in dysmorphic infants like Beckwith-Weidemann syndrome. Most of
them resolve spontaneously in days or rarely in weeks. A prolonged form
of HH is seen in some IUGR infants, lasting for 4–6 months and almost all
of them respond well to diazoxide.
Oral diazoxide is the drug of choice (5–20mg/kg/day in 3 divided doses)

in the treatment of HH. It is a KATP channel agonist and is effective in
most forms of HH, except in diffuse disease due to AR inherited ABCC8/
KCNJ11 mutations. Oral chlorothiazide (7–10mg/kg/day in 2 divided
doses) should be combined with diazoxide to combat the fluid retention
side effects of diazoxide. Diazoxide, being protein-bound, toxicity could
be severe in infants with hypoalbuminaemia. In diazoxide-responsive
infants, on successful weaning of intravenous dextrose, fasting tolerance
can be done (6 hours of fasting with hourly HC, only water can be fed)
to confirm the infant’s ability to fast 6 hours without hypoglycaemia. If
the infant can fast without hypoglycaemia, discharge home and plan
for follow up in 4–6 week interval. In diazoxide unresponsive infants
(inadequate glycaemic response in 3–5 days of diazoxide treatment),
genetic studies should be requested.
Neonatology 401
Confirm Diagnosis:
Glucose infusion rate (GIR) >8mg/kg/min
Laboratory blood glucose <3mmol/L
Detectable insulin/C peptide
Hypoketotic
Low free fattyacids (NEFA)
Serum ammonia may be raised (HI/HA syndrome)
Glycaemic response to glucagon
Commence: + Response
Diazoxide/chlorothiazide Assess fasting tolerance
Titrate GIR and discharge
No Response
Glucagon
Octreotide
Genetic studies (Blood to Exeter, UK)
Differentiate Focal from Diffuse forms

18F- DOPA PET/CT scan
Focal Diffuse
Lesionectomy High calorie diet/frequent feeds

Glucagon infusion
Octreotide
Follow up:
Unresponsive
MRI Brain Day 6–7
Growth
Subtotal pancreatectomy (95%)
Development
Diabetes Mellitus
Pancreatic exocrine supplements
Genetic counseling
NB: In HH infants target plasma glucose between 3.5–8mmol/L to prevent injury
Figure 10.5: Algorithm for management of hyperinsulinaemic hypoglycaemia

While results of genetic studies are awaited, glucagon infusion (SC/IV

1–20mcg/kg/hr) and octreotide (SC/IV 5–35mcg/kg/day; continuous
infusion or 6–8 hourly SC injections) can be tried while on increasing
glucose infusion rate. Octreotide in higher doses has the risk of
necrotizing enterocolitis. If genetic studies suggest focal disease, DOPA-
PET imaging can localise the lesion and the infant can be cured by
lesionectomy. If diffuse disease is confirmed, subtotal pancreatectomy
(95% pancreas) is the treatment of choice.
NEONATAL SEIZURES
SEIZURE PATTERN
Subtle seizures constitute 50% of the seizures in the newborns. They
may be in the form of tonic horizontal deviation and jerking of the
eyes, repetitive blinking or fluttering of the eyelids, oral and buccal
movements (drooling, sucking, yawning), tonic limb posturing,
complex purposeless movement (‘swimming’, ‘bicycling’), apneas and
rhythmic fluctuations of vital signs. Seizures may also present as focal or
multifocal clonic seizures, tonic seizures, and myoclonic seizures.
JITTERINESS VERSUS SEIZURE

A number of ‘seizure-like’ behavioral states may be confused with
seizures. These include jitteriness, movement during rapid eye
movement (REM) sleep, decorticate and decerebrate posturing, and
autonomic dysfunction.
Clinical Features Jitteriness Seizure

Abnormality of gaze or eye movements Absent Present
Autonomic changes Absent Present
Response to stimulation Yes No
Movement ease with passive flexion Yes No
Predominant movement Tremor Jerking
COMMON CAUSES OF NEONATAL SEIZURES

 Hypoxic ischaemic encephalopathy
 Metabolic (hypoglycaemia, hypocalcaemia, hypo/hypernatraemia)
 Infections (meningitis)
Neonatology 403
 Intracranial bleeds
 Inborn errors of metabolism
 Neonatal abstinence syndrome
 Congenital malformations
 Benign idiopathic neonatal seizures: “fifth day fits”, benign
examination and clinical course.
 Benign familial neonatal convulsions: family history of neonatal
seizures and spontaneously resolves in few days to weeks.
WORKUP FOR NEWBORN WITH SEIZURE

 Perinatal history including family history, risks for sepsis, drug usage,
diabetes, and perinatal hypoxia
 Physical examination
 Basic laboratory tests:
 Full blood count and CRP
 Electrolytes
 Calcium, magnesium and phosphate
 Blood glucose
 Additional tests:
 Lumbar puncture
 Plasma ammonia and lactate
 Plasma and CSF amino acids, urine organic acids
 Toxicological screen
 Electroencephalography or amplitude integrated EEG (aEEG)
 Neuroimaging: Ultrasound, CT scan, or MRI
ACUTE MANAGEMENT
 Maintain airway and breathing
 Correct hypoglycaemia and electrolyte disturbances
 Intravenous phenobarbitone 10–20mg/kg over 30 mins; a dose of
5mg/kg
can be repeated after an hour up to max cumulative dose of 40mg/
kg. Take precautions against apnea, hypotension and desaturation
 If the seizure is persistent, consider IV phenytoin 10–20mg/kg at a
rate not more than 1mg/kg/min, with cardiac monitoring
 If the seizure persists, consider additional drugs such as
benzodiazepines. The usual dose of diazepam is 0.1–0.3mg/kg/dose.
Infuse slowly under cardio-respiratory monitoring. Or, midazolam
may be given 0.1mg/kg/dose slow IV push over 5 mins
 Additional drugs:
 Intravenous antibiotics till infection can be ruled out
 Calcium gluconate (if hypocalcaemic)
 IV pyridoxine
 Consult neurologist
Bibliography:
1. Olson DM. Neonatal Seizures. NeoReviews. 2012 Apr 1;13(4):e213–e223.
405
NEPHROLOGY
APPROACH TO HAEMATURIA
DEFINITION
 Microscopic haematuria is defined by the presence of >5 red blood
cells per high-power field. The diagnosis of gross haematuria is made
when blood is present in the urine that is visible to the naked eye.
A positive urine dipstix is not good enough for diagnosis. A false-positive
result may be caused by haemoglobinuria, myoglobinuria, drugs such as
rifampicin, food such as beetroot or improper use of strips. Urate crystals
in the urine of infants may cause a pink discolouration to the nappy.
Microscopic examination is essential to confirm haematuria.
LOCALISING THE ORIGIN OF HAEMATURIA (GLOMERULAR

VS NON-GLOMERULAR)
 Glomerular bleeding is suggested by the presence of Red Blood Cell
(RBC) casts or granular casts
 Phase contrast microscopy is performed on a fresh urine specimen.
RBC from glomeruli shows distortion and variation in shape and size
(dysmorphic). Lower tract bleeding gives RBC uniform in shape and
size (isomorphic). Sensitivity and specificity is >90% in detecting
glomerular haematuria
 Presence of WBC casts suggests renal inflammation
Table 11-1: Categories of haematuria

Symptomatic Asymptomatic
Gross haematuria Symptomatic gross haematuria Asymptomatic gross haematuria
Microscopic Symptomatic microscopic Asymptomatic microscopic
haematuria haematuria haematuria
 Intermittent
 Persistent
 With proteinuria
CAUSES
 Infection:
 Bacterial:
 Upper tract: Pyelonephritis (usually microscopic haematuria)
 Lower tract: Cystitis, urethritis, vulvitis, balanitis (gross
haematuria is usually seen in cystitis)
 Viruses: Adenovirus, cytomegalovirus (CMV)
 Tuberculosis (TB) [this is rare]
 Glomerulopathy — Thin glomerular basement membrane disease,
IgA nephritis, Alport’s Syndrome
 Hypercalciuria with/without stones
 Renal calculi
 Trauma
 Other rare causes: Bleeding disorders, tumours, chemical cystitis
HISTORY
 Associated symptoms:
 Infection: Fever, dysuria, frequency, loin pain
 Stone disease: Pain, passage of ‘sand’/stones
 Acute glomerulonephritis (AGN): Preceding upper respiratory
tract infection (URTI), oedema
 Secondary cause: Fever, rashes, arthralgia/arthritis
 Nature of haematuria: Terminal haematuria often suggests local
causes such as urethritis/vulvitis
 Previous episodes of gross haematuria
 History of trauma
 Family history of haematuria, proteinuria, renal disease, deafness or
stone disease
CLINICAL EXAMINATION
 Local examination
 Evidence of glomerulonephritis: Hypertension, oedema
GROSS HAEMATURIA
Investigations (Symptom-directed)
 Urine culture
 Urine calcium/creatinine ratio
 Full blood count (FBC)
 Renal panel
 Clotting study where appropriate
Nephrology 407
 Complement level (C3)

 Kidney-Ureter-Bladder (KUB) X-ray for radio-opaque calculi
 Renal ultrasound
 Other imaging studies/biochemical tests where appropriate
Treatment
 Treat underlying cause
 Follow-up till resolution
When to Refer?
 Persistent beyond 1 week
 Recurrent
 Hypertension, abnormal renal function, presence of proteinuria or
structural anomaly on renal ultrasound
MICROSCOPIC HAEMATURIA
Asymptomatic microscopic haematuria is common. It is found in up to
4% of school-going children on urine screening. With repeated testing
on three consecutive samples, <0.5% remain positive.
What Do I Do in a Child with Microscopic Haematuria?

In the absence of proteinuria and symptoms, repeat urine microscopy. If
persistent in at least 3 samples over 1 month, then proceed to investigate.
Investigations (Symptom-directed)
 Urine protein/creatinine ratio
 Urine culture
 Urine calcium/creatinine ratio
 Urine phase contrast microscopy
 Renal ultrasound
 Others as indicated
How Often Do I Follow Up if the Above Investigations are

Normal?
Three monthly for a year, examining the urine for proteinuria (urine
protein/creatinine ratio [uPCR] >0.2 (mg/mg) or 20 (mg protein/mmol
creatinine) denotes the presence of proteinuria) at every visit. Thereafter,
if negative for protein, may be followed up yearly with urine microscopy,
looking in particular for proteinuria.
What if Protein is Detected?

 Proceed to quantitate protein by doing timed urine collection
 If >4mg/m2/hr, refer to a nephrologist
 If <4mg/m2/hr, follow-up closely for worsening proteinuria. If proteinuria
resolves, manage as for isolated microscopic haematuria
Indications for Renal Biopsy

 Associated significant proteinuria (40mg/m2/hr on timed urine
collection)
 Azotaemia
 Hypertension
 Recurrent gross haematuria
 Family history of glomerulonephritis
Bibliography
1. Milford DV, Robson AM. The Child with Abnormal Urinalysis, Haematuria and/or
Proteinuria. Clinical Paediatric Nephrology 3rd ed. Oxford University Press; 2003.
2. Diven SC, Travis LB. A practical primary care approach to haematuria in children. Pediatr
Nephrol. 2000; 14(1):65–72.
3. Ahmad G, Segasothy M, Morad Z. Urinary erythrocyte morphology as a diagnostic aid in
haematuria. Singapore Med J. 1993; 34(6):486–488.
ACUTE NEPHRITIC SYNDROME
DEFINITION
Sudden onset of symptoms of glomerular injury (haematuria, hypertension),
and varying degrees of renal insufficiency.
DIFFERENTIAL DIAGNOSIS
 Post-infectious:
 Bacterial:
 Group A β-haemolytic Streptococcus (most common)
 Pneumococcus sp.
 Staphylococcus sp.
 Klebsiella sp.
 Meningococcus sp.
 Salmonella typhi
 Mycoplasma pneumoniae
Nephrology 409
 Viral:
 HIV
 Coxsackie
 Ebstein-Barr
 Hepatitis B
 Influenza
 Mumps
 Henoch–Schönlein purpura (HSP) with nephritis
 Systemic lupus erythematosus (SLE)
 IgA nephropathy
 Membranoproliferative glomerulonephritis
 Hereditary nephritis (Alport’s syndrome)
 Infective endocarditis (IE)-related
 Shunt nephritis
HISTORY
 History of upper respiratory tract infection 1–2 weeks prior to onset
of acute nephritis. Latent period between pyoderma and onset of
acute glomerulonephritis (AGN) is variable
 Facial swelling/oedema
 Gross haematuria
 Oliguria
 May have systemic symptoms — Fever, malaise, anorexia, headaches
 Extra renal symptoms like arthritis, rash (systemic and extra renal
symptoms are often seen in SLE nephritis)
Table 11-2: Investigations
Investigations
Urine microscopy Dysmorphic RBC, RBC casts
Proteinuria (proportional to RBC)
Renal panel Elevated blood urea and creatinine
Full blood count Anemia (as in SLE) ± leucocytosis
Leucopenia, especially lymphopenia is seen in SLE
Bacteriological and serological studies Throat swab (may be negative if treated)
Elevated Anti-streptolysin O titre (ASOT), Antihyaluronidase and
Antideoxyribonuclease
Immunological markers Hypocomplementaemia (CH50, C3, C4)
Autoimmune markers — elevated double stranded DNA, Anti-
Nuclear Antibody titres in SLE
Radiology CXR: Cardiomegaly, pulmonary congestion/oedema
Renal ultrasound: Non-specific echogenic kidneys
 Hypertension
 Oedema
 Ascites
 Circulatory congestion — Tachypnoea, tachycardia, cardiomegaly,
hepatomegaly
MANAGEMENT
 Supportive/symptomatic:
 Bed rest
 Salt and water restriction to insensible water loss (400ml/m2/day)
plus half urine output
 Treatment of hypertension
 Drugs that can be used include: Loop diuretics (frusemide)
calcium channel blocker or hydralazine
 If severe, refer to section on hypertension
 Antibiotics indicated in patients with positive cultures. Penicillin is
drug of choice (erythromycin in allergic individuals)
NATURAL HISTORY
Resolution of:
Gross haematuria 2 weeks
Oliguria 2 weeks
Azotaemia 2 weeks
Hypertension 4 weeks
Decreased C3 6 weeks
Proteinuria 6 months
Microscopic haematuria 12 months
INDICATIONS FOR RENAL BIOPSY

 Severe renal failure of unknown/uncertain aetiology
 Atypical features such as co-existent Nephrotic Syndrome (NS)
 Delayed resolution
PROGNOSIS
 Excellent in post-streptococcal AGN, with restoration of renal
function in >90%
 Rapidly progressing glomerulonephritis (RPGN) in 1%
Nephrology 411
Bibliography
1. Smith JM, Faizan MK, Eddy AA. The Child with Acute Nephritic Syndrome. Clinical
Paediatric Nephrology 3rd ed. Oxford University Press; 2003.
2. Barratt M, Avner E, Harmon B (editors). Pediatric Nephrology. 4th ed. Baltimore: Lippincott
Williams & Wilkins; 1999.
NEPHROTIC SYNDROME (NS)
INTRODUCTION
Nephrotic Syndrome (NS) is a syndrome characterised by:
 Heavy proteinuria:
 ≥40mg/m2/hr (timed urine collection), or
 Protein/Creatinine ratio (uPCR) ≥2 (mg/mg) or random Urine Total
Protein (UTP) ≥3g/L
 Hypoalbuminaemia (<25g/L)
 Generalised oedema
 Hyperlipidaemia
It is the most common cause of generalised oedema in children and a

major clinical presentation of childhood glomerulonephritis.
It is presumably an immune-mediated disorder of glomerular podocyte

dysfunction resulting in increased protein permeability and massive
urinary protein loss. It is either a primary glomerular disease — most
common being Idiopathic Nephrotic Syndrome (INS) or secondary to a
systemic disease (most common being SLE, HSP).
Other isolated NS can be due to rare genetic diseases, infections, drugs
or neoplasia.
Table 11-3: Glomerular histology and steroid response in Primary INS*

Glomerular Histology Steroid Response (%)
Minimal-change Disease (MCD) 93.1
Diffuse mesangial hypercellularity (DMH) 55.6
Focal segmental glomerulosclerosis (FSGS) 29.7
Membranoproliferative glomerulonephritis (MPGN) 6.9
Membranous nephropathy 0
* Histologic appearance and steroid response in 471 children with primary nephrotic syndrome.
Table 11-4: Definitions

Complete remission UTP <0.2g/L or uPCR<0.2 (mg/mg) or dipstick protein <1+ for
3 consecutive days
Partial remission Decrease in proteinuria of ≥50% over presenting value or uPCR
between 0.2–2 (mg/mg) or dipstick protein 1+ to 3+
Steroid responsive/sensitive Remission achieved with steroid therapy alone
Initial response Complete remission within initial 4 weeks of steroid therapy
Relapse UTP >3g/L or protein:creatinine ratio ≥2 (mg/mg) or Albustix
≥3+ for 3 consecutive days or oedema with proteinuria
Frequent relapses Two or more relapses within 6 months of initial response, or four
or more relapses within any 12-month period
Steroid dependence Two consecutive relapses occurring during corticosteroid
treatment or within 14 days of its cessation
Steroid resistance Failure to achieve remission after 8 weeks of steroid therapy
Late steroid resistance Steroid resistance develops after being steroid sensitive
previously, e.g. in FSGS
CLASSIFICATION AND DEFINITIONS
 Steroid responsiveness is of greater prognostic value than histology.

Therefore most children with INS do not need a renal biopsy.
 Clinical response to steroid therapy and the clinical course
determines the management and prognosis of patients. Thus the
broad clinical classification of Steroid-sensitive Nephrotic Syndrome
(SSNS) and Steroid-resistant Nephrotic Syndrome (SRNS).
 The clinical course further divides SSNS to Steroid Dependency and
frequent relapsing NS.
 The clinical response and clinical course should be accurately
determined as they form the basis and rationale for treatment (see
Table 11-4).
There are several distinct major histological types in Primary INS:

 Minimal Change Disease (MCD) as the majority and largely SSNS
 Focal segmental glomerulonephritis (FSGS) — increasingly seen with
high incidence of steroid resistance and may progress to renal failure
 Membranous and membrano-proliferative nephropathy which are
rare but being SRNS, has guarded prognosis.
Nephrology 413
MANAGEMENT
Investigations
 Confirm diagnosis — Urinalysis, UTP, serum protein and albumin,
blood lipids
 FBC — Look for haemoconcentration due to intravascular
contraction which may increase risk of thrombosis
 Renal panel — Look for hyponatraemia due to rapid over-hydration;
azotaemia due to prerenal cause
 Other investigations (e.g. CXR, urine/blood culture) are guided by
clinical picture
 Diagnosis is straight forward and does not require 24-hour urine
protein measurement
 Screening for systemic disease (e.g. SLE) only if there are clinical indications
Principles of Treatment and Management

 To induce remission and treat complications:
 Prednisolone is the mainstay of treatment (Refer to treatment
regimens). Important to monitor side effects and explain to parents
 Common complications are:
 Shock/hypotension: NS patients are particularly at risk of
hypotension. Needs albumin ± furosemide
 Infections: cellulitis, primary peritonitis (usually Streptococcus
pneumoniae), UTI, chest infections. Treat with Ceftriaxone
(50mg/kg/dose, max 2g/dose)
 Thromboembolism (renal vein, cerebral vein, pulmonary
embolism): rare. Needs anticoagulation
 Symptomatic hyponatraemia (may be due to IV over-
hydration). Needs albumin+ furosemide
 Symptom relief of severe oedema while awaiting response to steroids
 Using IV albumin with furosemide infusions. Such infusions are
expensive and can cause transfusion related complications
 Indications for IV albumin ± furosemide are:
 Shock/pre-shock — Hypovolaemia, oliguria with raised
haematocrit and low urinary sodium
 Severe anasarca, e.g. severe periorbital oedema, severe
ascites, scrotal oedema
 Symptomatic hyponatraemia (with CNS symptoms)
 Intavenous albumin is given as 1–1.5g/kg/dose of 20%
albumin (in 10g/50ml per bottle, avoid wastage) over 4 hours
with a bolus of IV furosemide1–2mg/kg/dose midway and at
the end of the infusion
 Early detection and treatment of relapse

 Home monitoring and parent/caretaker education is important
 In the longer term, monitor and avoid or minimise untoward side-effects
of therapy while awaiting complete resolution in the majority of children
POINTS TO REMEMBER
 Indications of hospitalisation include:
 severe oedema or intractable oedema in SRNS that require IV
albumin/furosemide
 complications (see above)
 secondary NS that may need workup and specific treatment
 Most patients do not require Albumin+ Furosemide infusions. They
should be given only if there are indications
 First clinical response to steroid treatment will be an increase in urine
output and weight loss (often before resolution of proteinuria) and
occurs after 7–10 days of prednisolone
 Patient can be safely discharged once clinical response is evident
Complete remission occurs in 2–4 weeks.(80% by 2 weeks, >90% by 4
weeks. Possible SRNS if >4 weeks)
 Explanation to parents is important for long term management:
Home log using Albustix to detect early relapse. Intercurrent
infection may induce un-sustained proteinuria (<5 days). If there
is no oedema and an improving trend in Albustix after 3 days, no
treatment of relapse is needed
 Relapsing course is expected in >70% patients and parents need to be
fore warned and that follow up will be required for at least 1–2 years
 It is important to exclude noncompliance in treatment failure (as in
most chronic illnesses) and address this problem before considering
steroid resistance
 Complete resolution of NS is considered if patient remains well
for 4–5 consecutive years. A small % of patients may relapse into
adulthood with less favourable prognosis
Clinical features for non-MCNS that may necessitate renal biopsy include:
 Steroid resistance
 Prominent/gross haematuria
 Positive family history
 Hypertension
 Non-prerenal azotaemia
 Evidence of systemic disease
Nephrology 415
Nephrotic Syndrome
Prednisolone 60mg/m2/day (max 60mg/day) x 4 weeks
Steroid-sensitive Steroid-resistant
Prednisolone 40mg/m2/EOD x 4 weeks, then taper over 4 weeks Refer to Nephrologist
Cyclosporine
No relapse consecutively Relapse Treat hyperlipidaemia
for 4–5 years Treat oedema with albumin +
Prednisolone 60mg/m2/day x 2 diuretics Consider ACEI /ARB
weeks or longer until remission, Mycophenolate, Rituximab
Cured
then EOD dosing, taper over
6–8 weeks
Infrequent relapses Frequent relapses Steroid-dependent
Prednisolone 0.1–0.5mg/kg/EOD
Prednisolone 60mg/m2/day for (school age) or 0.1–1.0mg/kg/EOD
2 weeks or longer till remission, (pre-school age) x 6–12 months
then taper over 6–8 weeks at
EOD dose Unsuccessful
Refer for evaluation. Longer
term EOD Prednisolone Lowest alternate-day steroid with
depending on steroid threshold Cyclophosphamide 2–2.5mg/kg/
when relapses occur day x 12 weeks
or
Cyclosporin 5–6mg/kg/day
x 1–2 years
or
MMF 1000–1200mg/m²/day
x 1–2 years
Threshold <0.5mg/kg/EOD Threshold >0.5mg/kg/EOD
or steroid toxicity
Prednisolone 0.1–0.5mg/kg/EOD
for 6–12 months Treat as for steroid dependency
Figure 11.1: Algorithm for the management of childhood nephrotic syndrome

 Age of onset <1 year or >12 years (onset <3 months is congenital
NS, 3–12 months genetic NS and congenital infections should be
considered, >12 years behave like adult NS)
TREATMENT REGIMENS
General considerations:
General considerations:
 Treatment for initial presentation is usually prolonged and intensive
to ensure prolonged remission.
 Treatments of relapses are less intensive as they are usually detected
early. Treatment does not require hospitalisation if relapse is
uncomplicated.
 Up to 80% of childhood NS has MCNS with the majority (93%) being
SSNS and thus an excellent prognosis with no long term renal morbidity.
 Morbidity is mainly due to complications of the nephrotic state and
steroid side-effects (especially retarded growth, serious infections,
cataract) which necessitates the use of steroid sparing drugs (e.g.
cyclophosphamide, cyclosporine, mycophenolate). Rituximab is
reserved for refractory NS or SRNS.
 All immunosuppressive drugs have significant side-effects and their use
requires clear indications and parental consent with careful monitoring.
Table 11-5: Prednisolone regimen for initial presentation of nephrotic syndrome
Duration (Total Dosage (single dose; can be in divided dose if necessary)

3 months)
4 weeks 60mg/m2/day (max 60mg)
4 weeks 40mg/m2/alt. days (max 40mg)
Tapering alternate day doses till 5mg/m2/alternate days of steroid over last 4 weeks
Alternatively there are regimens that suggest longer remission can be

achieved by using 6 weeks of 60mg/m²/day and 6 weeks of 40mg/m²/
EOD.
Calculation of prednisolone dose:
Weight (kg) x Height (cm)

Body Surface Area (m2) =
3,600
Nephrology 417
Table 11-6: Prednisolone regimen for relapse of nephrotic syndrome

Duration Dosage (single dose)
At least 2 weeks or until remission 60mg/m2/day (max 60mg)
Thereafter Prednisolone at EOD doses starting at 60mg/

m², reducing stepwise by 10mg/m² every 8 days till
5–10mg/m² over 6–8 weeks
Documentation of hypoalbuminaemia is usually not necessary for the
diagnosis of relapse.
TREATMENT OF RELAPSED NS AS OUTPATIENT

 Non-oedematous patient
 Treat after ascertaining sustained proteinuria, i.e. UTP ≥3g/L or
Albustix ≥3+ for >3 days
 Unsustained proteinuria may occur with intercurrent infection,
e.g. URTI, but proteinuria should improve after 3–5 days.Up
to 25% of the relapses remit spontaneously and therapy is
unnecessary
 Oedematous patient (swelling, sudden weight gain + significant
proteinuria of >2+) should be treated as full relapse irrespective of
duration of proteinuria
Immunisations
Immunisations can be given when patient is in remission and on low
dose alternate day Prednisolone. Live attenuated vaccination should be
deferred until patient is off steroids for at least 3 months.
Bibliography
1. Steroid Responsive Nephrotic Syndrome. A. Godfrey Clark, T. Martin Baratt. In Pediatric
nephrology 4th ed (1999) 731–748.
2. The primary nephrotic syndrome in children. Identification of patients with minimal
change nephrotic syndrome from initial response to prednisone. A report of the
International Study of Kidney Disease in Children. J Pediatr 1981;98(4):561–4.
3. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy in nephrotic syndrome: a
meta-analysis of randomised controlled trials. Arch Dis Child. 2000;83(1):45–51
4. Ekka BK, Bagga A, Srivastava RN. Single versus divided-dose prednisolone therapy for
relapses of nephrotic syndrome. Pediatr Nephrol. 1997;11(5):597–9.
5. MOH clinical practice guideline: Glomerulonephritis 6/2001
6. Steroid sensitive nephrotic syndrome in Avner et al, Pediatric Nephrology 5th ed 2004
7. Eddy AA Nephrotic syndrome in children. Lancet 2003; 362:629–639
8. Esfahani ST et al. Clinical course and outcome of children with steroid sensitive nephritic
syndrome. Pediatr Nephrol (2011) 26:1089–1093
9. LA Greenbaum et al. Childhood nephritic syndrome- current and future therapies. Review
Nephrology (2012): 445–458
10. Lombel RM et al. Treatment of steroid sensitive nephrotic syndrome: new guidelines from
KDIGO Pediatr 2013; 28:415–426
HYPERTENSION
DEFINITION
Defined as average systolic blood pressure (SBP) and/or diastolic blood
pressure (DBP) that is ≥95th percentile for gender, age and height on
three or more occasions*. Refer to blood pressure (BP) level charts listed
for both genders based on age and height centiles.
* Except children with Stage 2 hypertension or a child with
symptomatic hypertension.
Table 11-7: Blood pressure levels for boys by age and height percentile
Age BP Systolic BP (mmHg) Diastolic BP (mmHg)

(Year) Percentile  Percentile of Height   Percentile of Height 
 5th
10 25th 50th 75th 90th 95th
th
5th
10 25th 50th 75th 90th 95th
th
1 50th 80 81 83 85 87 88 89 34 35 36 37 38 39 39
90th 94 95 97 99 100 102 103 49 50 51 52 53 53 54
95th 98 99 101 103 104 106 106 54 54 55 56 57 58 58
99th 105 106 108 110 112 113 114 61 62 63 64 65 66 66
2 50th 84 85 87 88 90 92 92 39 40 41 42 43 44 44
90th 97 99 100 102 104 105 106 54 55 56 57 58 58 59
95th 101 102 104 106 108 109 110 59 59 60 61 62 63 63
99th 109 110 111 113 115 117 117 66 67 68 69 70 71 71
3 50th 86 87 89 91 93 94 95 44 44 45 46 47 48 48
90th 100 101 103 105 107 108 109 59 59 60 61 62 63 63
95th 104 105 107 109 110 112 113 63 63 64 65 66 67 67
99th 111 112 114 116 118 119 120 71 71 72 73 74 75 75
4 50th 88 89 91 93 95 96 97 47 48 49 50 51 51 52
90th 102 103 105 107 109 110 111 62 63 64 65 66 66 67
95th 106 107 109 111 112 114 115 66 67 68 69 70 71 71
99th 113 114 116 118 120 121 122 74 75 76 77 78 78 79
5 50th 90 91 93 95 96 98 98 50 51 52 53 54 55 55
90th 104 105 106 108 110 111 112 65 66 67 68 69 69 70
95th 108 109 110 112 114 115 116 69 70 71 72 73 74 74
99th 115 116 118 120 121 123 123 77 78 79 80 81 81 82
6 50th 91 92 94 96 98 99 100 53 53 54 55 56 57 57
90th 105 106 108 110 111 113 113 68 68 69 70 71 72 72
95th 109 110 112 114 115 117 117 72 72 73 74 75 76 76
99th 116 117 119 121 123 124 125 80 80 81 82 83 84 84
7 50th 92 94 95 97 99 100 101 55 55 56 57 58 59 59
90th 106 107 109 111 113 114 115 70 70 71 72 73 74 74
95th 110 111 113 115 117 118 119 74 74 75 76 77 78 78
99th 117 118 120 122 124 125 126 82 82 83 84 85 86 86
8 50th 94 95 97 99 100 102 102 56 57 58 59 60 60 61
90th 107 109 110 112 114 115 116 71 72 72 73 74 75 76
95th 111 112 114 116 118 119 120 75 76 77 78 79 79 80
99th 119 120 122 123 125 127 127 83 84 85 86 87 87 88
Nephrology 419

 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
9 50th 95 96 98 100 102 103 104 57 58 59 60 61 61 62
90th 109 110 112 114 115 117 118 72 73 74 75 76 76 77
95th 113 114 116 118 119 121 121 76 77 78 79 80 81 81
99th 120 121 123 125 127 128 129 84 85 86 87 88 88 89
10 50th 97 98 100 102 103 103 106 58 59 60 61 61 62 63
90th 111 112 114 115 117 117 119 73 73 74 75 76 77 78
95th 115 116 117 119 121 121 123 77 78 79 80 81 81 82
99th 122 123 125 127 128 128 130 85 86 86 88 88 89 90
11 50th 99 100 102 104 105 107 107 59 59 60 61 62 63 63
90th 113 114 115 117 119 120 121 74 74 75 76 77 78 78
95th 117 118 119 121 123 124 125 78 78 79 80 81 82 82
99th 124 125 127 129 130 132 132 86 86 87 88 89 90 90
12 50th 101 102 104 106 108 109 110 59 60 61 62 63 63 64
90th 115 116 118 120 121 123 123 74 75 75 76 77 78 79
95th 119 120 122 123 125 127 127 78 79 80 81 82 82 83
99th 126 127 129 131 133 134 135 86 87 88 89 90 90 91
13 50th 104 105 106 108 110 111 112 60 60 61 62 63 64 64
90th 117 118 120 122 124 125 126 75 75 76 77 78 79 79
95th 121 122 124 126 128 129 130 79 79 80 81 82 83 83
99th 128 130 131 133 135 136 137 87 87 88 89 90 91 91
14 50th 106 107 109 111 113 114 115 60 61 62 63 64 65 65
90th 120 121 123 125 126 128 128 75 76 77 78 79 79 80
95th 124 125 127 128 130 132 132 80 80 81 82 83 84 84
99th 131 132 134 136 138 139 140 87 88 89 90 91 92 92
15 50th 109 110 112 113 115 117 117 61 62 63 64 65 66 66
90th 122 124 125 127 129 130 131 76 77 78 79 80 80 81
95th 126 127 129 131 133 134 135 81 81 82 83 84 85 85
99th 134 135 136 138 140 142 142 88 89 90 91 92 93 93
16 50th 111 112 114 116 118 119 120 63 63 64 65 66 67 67
90th 125 126 128 130 131 133 134 78 78 79 80 81 82 82
95th 129 130 132 134 135 137 137 82 83 83 84 85 86 87
99th 136 137 139 141 143 144 145 90 90 91 92 93 94 94
17 50th 114 115 116 118 120 121 122 65 66 66 67 68 69 70
90th 127 128 130 132 134 135 136 80 80 81 82 83 84 84
95th 131 132 134 136 138 139 140 84 85 86 87 87 88 89
99th 139 140 141 143 145 146 147 92 93 93 94 95 96 97
BP: Blood Pressure

* The 90th percentile is 1.28 SD, 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over
the mean.
Table 11-8: Blood pressure levels for girls by age and height percentile

 5th
10 25th 50th 75th 90th 95th
th
5 th
10 25th 50th 75th 90th 95th
th
1 50th 83 84 85 86 88 89 90 38 39 39 40 41 41 42
90th 97 97 98 100 101 102 103 52 53 53 54 55 55 56
95th 100 101 102 104 105 106 107 56 57 57 58 59 59 60
99th 108 108 109 111 112 113 114 64 64 65 65 66 67 67
2 50th 85 85 87 88 89 91 91 43 44 44 45 46 46 47
90th 98 99 100 101 103 104 105 57 58 58 59 60 61 61
95th 102 103 104 105 107 108 109 61 62 62 63 64 65 65
99th 109 110 111 112 114 115 116 69 69 70 70 71 72 72
3 50th 86 87 88 89 91 92 93 47 48 48 49 50 50 51
90th 100 100 102 103 104 106 106 61 62 62 63 64 64 65
95th 104 104 105 107 108 109 110 65 66 66 67 68 68 69
99th 111 111 113 114 115 116 117 73 73 74 74 75 76 76
4 50th 88 88 90 91 92 94 94 50 50 51 52 52 53 54
90th 101 102 103 104 106 107 108 64 64 65 66 67 67 68
95th 105 106 107 108 110 111 112 68 68 69 70 71 71 72
99th 112 113 114 115 117 118 119 76 76 76 77 78 79 79
5 50th 89 90 91 93 94 95 96 52 53 53 54 55 55 56
90th 103 103 105 106 107 109 109 66 67 67 68 69 69 70
95th 107 107 108 110 111 112 113 70 71 71 72 73 73 74
99th 114 114 116 117 118 120 120 78 78 79 79 80 81 81
6 50th 91 92 93 94 96 97 98 54 54 55 56 56 57 58
90th 104 105 106 108 109 110 111 68 68 69 70 70 71 72
95th 108 109 110 111 113 114 115 72 72 73 74 74 75 76
99th 115 116 117 119 120 121 122 80 80 80 81 82 83 83
7 50th 93 93 95 96 97 99 99 55 56 56 57 58 58 59
90th 106 107 108 109 111 112 113 69 70 70 71 72 72 73
95th 110 111 112 113 115 116 116 73 74 74 75 76 76 77
99th 117 118 119 120 122 123 124 81 81 82 82 83 84 84
8 50th 95 95 96 98 99 100 101 57 57 57 58 59 60 60
90th 108 109 110 111 113 114 114 71 71 71 72 73 74 74
95th 112 112 114 115 116 118 118 75 75 75 76 77 78 78
99th 119 120 121 122 123 125 125 82 82 83 83 84 85 86
9 50th 96 97 98 100 101 102 103 58 58 58 59 60 61 61
90th 110 110 112 113 114 116 116 72 72 72 73 74 75 75
95th 114 114 115 117 118 119 120 76 76 76 77 78 79 79
99th 121 121 123 124 125 127 127 83 83 84 84 85 86 87
10 50th 98 99 100 102 103 104 105 59 59 59 60 61 62 62
90th 112 112 114 115 116 118 118 73 73 73 74 75 76 76
95th 116 116 117 119 120 121 122 77 77 77 78 79 80 80
99th 123 123 125 126 127 129 129 84 84 85 86 86 87 88
11 50th 100 101 102 103 105 106 107 60 60 60 61 62 63 63
90th 114 114 116 117 118 119 120 74 74 74 75 76 77 77
95th 118 118 119 121 122 123 124 78 78 78 79 80 81 81
99th 125 125 126 128 129 130 131 85 85 86 87 87 88 89
Nephrology 421

 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th
12 50th 102 103 104 105 107 108 109 61 61 61 62 63 64 64
90th 116 116 117 119 120 121 122 75 75 75 76 77 78 78
95th 119 120 121 123 124 125 126 79 79 79 80 81 82 82
99th 127 127 128 130 131 132 133 86 86 87 88 88 89 90
13 50th 104 105 106 107 109 110 110 62 62 62 63 64 65 65
90th 117 118 119 121 122 123 124 76 76 76 77 78 79 79
95th 121 122 123 124 126 127 128 80 80 80 81 82 83 83
99th 128 129 130 132 133 134 135 87 87 88 89 89 90 91
14 50th 106 106 107 109 110 111 112 63 63 63 64 65 66 66
90th 119 120 121 122 124 125 125 77 77 77 78 79 80 80
95th 123 123 125 126 127 129 129 81 81 81 82 83 84 84
99th 130 131 132 133 135 136 136 88 88 89 90 90 91 92
15 50th 107 108 109 110 111 113 113 64 64 64 65 66 67 67
90th 120 121 122 123 125 126 127 78 78 78 79 80 81 81
95th 124 125 126 127 129 130 131 82 82 82 83 84 85 85
99th 131 132 133 134 136 137 138 89 89 90 91 91 92 93
16 50th 108 108 110 111 112 114 114 64 64 65 66 66 67 68
90th 121 122 123 124 126 127 128 78 78 79 80 81 81 82
95th 125 126 127 128 130 131 132 82 82 83 84 85 85 86
99th 132 133 134 135 137 138 139 90 90 90 91 92 93 93
17 50th 108 109 110 111 113 114 115 64 65 65 66 67 67 68
90th 122 122 123 125 126 127 128 78 79 79 80 81 81 82
95th 125 126 127 129 130 131 132 82 83 83 84 85 85 86
99th 133 133 134 136 137 138 139 90 90 91 91 92 93 93
BP: Blood Pressure

* The 90th percentile is 1.28 SD, 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over
the mean.
Classification of hypertension in children and adolescents 17 years and younger

Normal <90th percentile
≥90th and <95th percentiles or ≥120/80mmHg in
Pre-hypertensive
adolescents
Hypertensive ≥95th percentile
Stage 1 hypertension 95th–99th percentile + 5mmHg
Stage 2 hypertension ≥99th percentile + 5mmHg
BP levels >9th percentile in a clinic but normotensive outside
White Coat Hypertension a clinical setting. Ambulatory BP monitoring (ABPM) usually
required to make diagnosis
WHEN SHOULD BLOOD PRESSURE BE MEASURED?

 Children older than 3 years who are seen in medical care settings
should have their BP measured at least once during every clinic visit
 Children younger than 3 years should have their BP measured in
special circumstances:
 History of prematurity, very low birth weight, or other neonatal
complication requiring intensive care
 Congenital heart disease (repaired or un-repaired)
 Recurrent urinary tract infections, haematuria, or proteinuria
 Known renal disease or urologic malformations
 Family history of congenital renal disease
 Solid-organ transplant
 Malignancy or bone marrow transplant
 Treatment with drugs known to raise BP
 Other systemic illnesses associated with hypertension
(neurofibromatosis, tuberous sclerosis)
 Evidence of elevated intracranial pressure
SEVERE HYPERTENSION
 Not rigorously defined thus leading to confusion at times
 Useful definition:
 Blood pressure elevation that fulfils (and usually exceeds) the
definition of Stage 2 hypertension and that is accompanied by
severe symptoms; physical exam and/or laboratory findings of
accelerated hypertension are frequently also present
 20mmHg above the 95th percentile
 Adult definition:
 Blood pressures which are 50% above normal blood pressure or
>180/120mmHg
 Children presenting with severe symptoms need to be treated more
rapidly:
 It is risky to lower the BP too rapidly, especially in those whose
hypertension has been long-standing
 In such patients, a shift in cerebral autoregulation occurs which
in the hypertensive state protects the brain from excessive
perfusion
 Too rapid lowering of the BP in patients with such alterations
of cerebral flow might lead to ischaemic stroke from under
perfusion of the brain
 Can be subdivided into hypertensive emergency or hypertensive
urgency
Nephrology 423
HYPERTENSIVE EMERGENCY
 Presence of severe hypertension (as defined above) and
 The presence of end organ injury such as: cardiac failure (left
ventricular hypertrophy, pulmonary oedema), hypertensive
retinopathy (papilloedema, exudates and fundal haemorrhages),
hypertensive encephalopathy (altered mental state, convulsions),
cerebral haemorrhage, cerebral infarction
Treatment
 All cases of hypertensive emergency should be admitted to the ICU
for continuous BP monitoring
 Aim of treatment is to lower the BP to the desired range gradually so
as to minimise hypertensive sequelae, yet not compromise perfusion
to vital organs due to a sudden decrease in BP
 BP should be reduced by 25–30% of the original value over first 6–8
hours, followed by gradual reduction over next 24–48 hours
 Pay attention to pupillary reactions, consciousness level and
neurological examination
 Saline for volume expansion should be available on standby in case
of sudden hypotension
 Choice of antihypertensive agent:
 Depends on aetiology of hypertension
 Antihypertensive with rapid onset of action, short half-life, safe
and efficacious is preferred
 Intravenous route of administration preferred in hypertensive
emergency (see Table 11-9 for drugs that can be used in a
hypertensive emergency)
 Long acting oral medications can be introduced after reasonable
BP control within 24–48 hours of initiation of IV antihypertensive
infusion
HYPERTENSIVE URGENCY
 Presence of severe hypertension with no evidence of acute end
organ damage/compromise
 Patients may have symptoms of nausea, headache or blurred vision
Treatment
 Goal of therapy is reduction of BP over a 24-hour period
 Choice of either IV or oral antihypertensive. Oral agents can be used
to gradually lower BP in such patients who are asymptomatic and
does not have evidence of immediate end organ injury
 See Table 11-10 for oral drugs that can be used in hypertensive urgency.
Table 11-9: Drugs used for hypertensive emergency

Drug/Route Dose Onset of Action Duration Precautions
IV labetolol IV bolus 0.2–1mg/ 5–10 mins 3–6 hours Heart block,
(25mg/ml 5ml kg/dose (max orthostatic
vial) 40mg/dose) then hypotension, avoid
IV continuous in heart failure and
0.25–3mg/kg/hr asthma
(max 120mg/hr)
IV sodium IV continuous Instantaneous 1–2 mins Nausea and
nitroprusside 0.5–10mcg/kg/ vomiting, cyanide
(50mg/2ml vial) min accumulation with
prolonged use.
Protect from light
and monitor blood
cyanide level when
infusing for >72
hours or in patients
with renal failure.
IV hydralazine IV bolus 5–15 mins 3–8 hours Not preferred
(20mg/ampoule) 0.1–0.5mg/kg/ in SLE
dose 4–6 hourly
(max 20mg/dose,
3.5mg/kg/day)
IV furosemide IV bolus 1–6mg/ 5 mins 2 hours Hypokalaemia.
(20mg/2ml kg/dose 6–12 Rapid infusion
ampoule) hourly increases risk
of ototoxicity.
May exacerbate
hypercalcaemia or
hyperuricaemia
IV esmolol IV bolus 0.5mg/ 1–2 mins 10–20 mins Hypotension, avoid
(100mg/10ml kg/dose then in heart failure and
vial) IV continuous asthma, very short
infusion acting, profound
0.05–0.15mg/ bradycardia
kg/min
max 0.3mg/kg/
min
IV bumetanide IV bolus 2–3 mins 4–6 hours More costly than
(2mg/4ml 0.015–0.1mg/kg/ furosemide. Rapid
ampoule) dose 6–24 hourly infusion increases
(max 10mg/day) risk of ototoxicity.
May exacerbate
hypercalcaemia or
hyperuricaemia
Nephrology 425
Table 11-10: Oral drugs used for hypertensive urgency, in order of preference
Drug/Route Initial dose Maximum dose Precautions
PO nifedipine 0.25–0.5mg/kg/dose 3mg/kg/day, 90mg/ Rapid onset
(immediate release 6–8 hourly (5mg / day hypotension,
5mg/liquid dose) tachycardia, headache
capsule, 10mg/
liquid capsule)
PO hydralazine 0.25–0.5mg/kg/dose Max 7.5mg/kg/day, Not preferred in SLE,
(10mg/tablet) 8–12 hourly (25mg/ 200mg/day tachycardia
dose)
PO propranolol 0.25–1mg/kg/dose Max 5mg/kg/day, Avoid in asthma and
(10mg/tablet, 8–12 hourly (80mg/ 320mg/day cardiac failure. Monitor
40mg/tablet, dose) heart rate
1mg/ml
suspension)
PO captopril 0.1–0.3mg/kg/dose 6mg/kg/day, Hypotension in
(12.5mg/ 8–12 hourly (6.25mg/ 150mg/day high renin states,
tablet, 1mg/ml dose) renal failure and
suspension) hyperkalaemia. Very
young neonates are
dosed differently
PO clonidine 0.5–1mcg/kg/dose Max 25mcg/kg/day, Sedation, bradycardia
(25mcg/tablet) (100mcg/dose) TDS 1,200mcg/day and xerostomia
Bibliography
1. Hypertension. Barratt M, Avner E, Harmon B (eds). Pediatric Nephrology. 4th ed. Baltimore:
Lippincott Williams & Wilkins; 1999;959–1050.
2. National High Blood Pressure Education Program Working Group on High Blood Pressure
in Children and Adolescents (2005). The fourth report on the diagnosis, evaluation, and
treatment of high blood pressure in children and adolescents. National heart, lung, and
blood institute, Bethesda, Maryland. National institute of health, NIH publication 05:5267.
3. Adelman RD, Coppo R, Dillon MJ. The emergency management of severe hypertension.
Pediatr Nephrol. 2000;14(5):422–427.
4. Yap HK. Acute renal failure. Yip WCL, Tay JSH, editors. A practical manual on acute
paediatrics. Singapore: P.G. Publishing; 1989;273–288
5. Flynn JT, Tullus K. Severe hypertension in children and ad.olescents: pathophysiology and
treatment. Pediatr Nephrol. 2009;24(6):1101–12 .
6. Gilmore RM, Miller SJ, Stead LG. Severe hypertension in the emergency department
patient. Emerg Med Clin North Am. 2005;23(4):1141–58.
7. Lande MB, Flynn JT. Treatment of hypertension in children and adolescents. Pediatr
Nephrol. 2009;24(10):1939–49.
8. LexiComp online.
9. Joint Formulary Committee. British National Formulary for Children. 2010–2011 ed.
London: BMJ Group and Pharmaceutical Press; 2010.
10. Chandar J, Zilleruelo G. Hypertensive crisis in children. Pediatr Nephrol. 2012;27:741–751.
URINARY TRACT INFECTION (UTI)

AND VESICOURETERIC REFLUX (VUR)
INTRODUCTION
Urinary tract infection (UTI) is one of the most common bacterial
infections seen in children and a leading cause of acute sepsis in infants
requiring hospitalisation. Incidence of renal involvement or acute
pyelonephritis is high, especially during infancy (up to 80%).
Although the majority of children with UTI have an excellent

prognosis, there is a definite risk of renal damage or scarring following
pyelonephritis especially in those with vesicoureteric reflux (VUR) or
obstructive uropathy.
CLINICAL CLASSIFICATION
The epidemiology, pathophysiology and prognosis of UTI are
interrelated and differ according to age, sex and in particular the site of
infection. A useful classification is according to the site of infection (see
Table 11-11).
While >80% of patients with upper UTI have typical clinical features of
unexplained fever with or without urinary symptoms, it is important
to look at clinical features of atypical or complicated UTI which may
suggest underlying renal/renal tract abnormalities that warrant
attention and further investigations including MCU.
Table 11-11: Clinical classification of childhood UTI

Clinical Features Upper Tract Infection Lower Tract Infection
Age Generally <2 years Generally >2 years
Renal involvement Neonates and young infants are No risk
at high risk
Sex Female = Male in infancy Female > Male
Female > Male past infancy
Fever + —
(All febrile UTI have presumed
pyelonephritis)
Voiding Problem — +
Dysuria — +
Frequency — +
Suprapubic pain — +
Loin pain (older children) + —
Nephrology 427
Clinical Features of Atypical (complicated) UTI

 Past history UTI /renal or renal tract abnormality/bladder dysfunction
 Septicaemia/seriously ill
 Poor urine output, raised serum creatinine
 Palpable abdominal mass /bladder
 Treatment failure within 48 hours
 Uncommon uropathogen, e.g. Pseudomonas
DIAGNOSIS AND MANAGEMENT

(Also refer to KKH clinical pathway on uncomplicated UTI)
Upper Urinary Tract Infection

 The cardinal symptom of pyelonephritis is unexplained high fever,
often with chills and rigors. UTI should be suspected in such instances,
especially in infants. Cloudy urine is a more specific symptom than
smelly urine.
 A pre-treatment, properly collected mid-steam urine culture is
mandatory to establish a firm diagnosis of UTI.
 Up to 9% of patients with pyelonephritis may have equivocal or
negative urine cultures. If urine culture is equivocal and suspicion of
pyelonephritis is high, a Dimercaptosuccinic Acid (DMSA) scan may
be indicated to establish diagnosis.
 When early initiation of antibiotic treatment is necessary, an invasive
method of urine collection (suprapubic tap, catheterisation) is justified.
 E. coli is the most common uropathogen (>80%). Gentamicin is
recommended as the first-line antibiotic (93% sensitivity) and
ceftriaxone (almost 100%) as an alternative.
 Although ceftriaxone has almost 100% sensitivity, it is used as
second-line treatment for fear of emergence of resistant bacterial
strains. However, in patients with compromised renal function,
ceftriaxone is the antibiotic of choice.
 Ampicillin is added in infants for treatment of enterococci, which is
not uncommon in this age group.
Urine culture — points to remember:

 Bagged urine specimen is often contaminated and should not be
used for the urine culture.
 Label clearly the method used for urine collection as diagnostic
criteria vary (see below).
 Always obtain fresh urine. Direct plating of urine onto dipslides can
be done outside office hours.
 Always interpret culture results with clinical correlations
Lower Urinary Tract Infection

 Common in young girls
 Presents with voiding problems — Dysuria, frequency and
suprapubic pain
 Fever is not a feature
 Though troublesome and often recurrent, no cause for alarm
because there is no associated renal involvement and therefore
imaging studies is unnecessay.
APPROACH TO INVESTIGATIONS FOLLOWING UTI
Principle
 Most of the experimental and clinical evidence strongly supports the
concept that both VUR and UTI are responsible for acquired renal
scarring and that this damage takes up to 6 months to establish and
to become evident on the DMSA scan.
 Once formed, scarring is irreversible and when extensive, it can
significantly reduce the function of the affected kidney (<45%
differential function on DMSA scan).
 An acute inflammatory response associated with renal parenchymal
infection is the pre-requisite for acquired renal scarring.
 Dilating VUR (grade III-V) remains an important risk factor for Acute
Pyelonephritis (APN) and renal scarring.
Table 11-12: Urine culture and sensitivity results and interpretations

Method of Collection Colony Forming Units/ml (Pure Growth) Probability of Infection (%)
Suprapubic tap Gram-negative bacilli: Any count >99%
Gram-positive cocci >1,000 >99%
Transurethral catheterisation >100,000 95%
10,000–100,000 Infection likely
= 1,000 Doubtful, repeat if indicated
<1,000 Infection unlikely
Clean catch mid-stream 2 specimens >100,000 90%
1 specimen>100,000 80%
= 50,000–100,000 Doubtful; repeat if indicated
<50,000 Infection unlikely
Mixed growth Contamination

Nephrology 429
Clinical Diagnosis of Urinary Tract Infection
Fever
No Yes
Lower Tract Infection Upper Tract Infection
Urine Culture Urine Culture
Age Age
<12 years ≥12 years <28 days ≥28 days
7–10 day Consider 3-day

Full septic
course course Toxic Non-toxic
work-up
co-trimoxazole
 Co-trimoxazole* or IV Ampicillin and

 Nitrofurantoin* or Gentamicin pending Admit ± Admit†
 Cephalexin or culture results until
 Trimethoprim afebrile for 48 hours, then
Revise antibiotics once culture oral antibiotics for total
results are available of 14 days
 Gentamicin ± Ampicillin or
 Ceftriaxone or Cefotaxime ±
* Contraindicated in children with G6PD deficiency
†
Consider Outpatient treatment oral antibiotics in older children
Ampicillin until afebrile for 24
who are non-toxic and feeding well, with the following: hours then to oral antibiotic
 Send properly collected urine for culture according to antibiogram for
 Treat with oral cephalosporin (cephalexin or cefuroxime) or co- total of 14 days
amoxiclav
 Review in 2–3 days and revise treatment accordingly to culture
and sensitivity result
Figure 11.2: Algorithm for the management of uncomplicated febrile UTI in children
Table 11-13: Antibiotic treatment of upper urinary tract infection
Choice of Antibiotics Duration of Treatment

Intravenous Antibiotics: Total duration: 14 days
First-line  IV therapy until no fever for 24 hours,
 Gentamicin 5–6mg/kg/day Q24 hourly
then switch to oral therapy according to
 Infant younger than 3 months, add Ampicillin
antibiogram
100–200mg/kg/day Q6 hourly  For those with bacteraemia, parenteral
Precautions for gentamicin therapy: therapy should be continued for
If serum creatinine abnormal for age range,
7–10 days
ensure adequate hydration and consider
second-line antibiotics for fear of gentamicin
Infants older than 28 days:
nephrotoxicity.
 Parenteral therapy until afebrile for
If continued >48 hours, check gentamicin trough
levels. 24 hours, then oral therapy
Second-line
 Ceftriaxone 50mg/kg/dose Q24 hourly
 Cefotaxime 50mg/kg/dose Q8 hourly
Cefotaxime is preferred in neonates.
Oral antibiotics:
 First generation cephalosporins, e.g.
Cephalexin (50mg/kg/day Q8 hourly)
 Co-amoxiclav (Amoxicillin 50mg/kg/day Q12
hourly)
Table 11-14: Antibiotic treatment of lower urinary tract infection

Choice of Antibiotics Duration of Treatment
 Co-trimoxazole (TMP/SMZ)*: 7 days of antibiotics
TMP 8mg/kg/day Q12 hourly
Older than 12 years: 3 days TMP/SMZ can be
 Nitrofurantoin*: 5–7mg/kg/day Q6 hourly
considered instead of standard 7 days
treatment
 Cephalexin: 50mg/kg/day Q8 hourly
 Trimethoprim: 8mg/kg/day Q12 hourly (useful

for G6PD deficient patients)
(* Screen for G6PD deficiency)

Nephrology 431
Risk of scarring correlates to:

 Age (inversely) — <2 years are at high risk
 Severity of VUR: Dilating VUR (Grade III-V) being at higher risk
 Recurrence of UTI
While somewhat controversial, investigations following uncomplicated
febrile UTI are basically aimed at discovering any underlying renal and
renal tract abnormality that may predispose patient to repeat infections.
Parents need to be informed that recurrent UTI is likely to occur in the
initial 6 months and that they should be vigilant of possible recurrent
UTI when their child has fever of unknown source.
Imaging Studies
Investigations should include renal ultrasound, DMSA scans and
Micturating Cystourethrogram (MCU) each with its own purpose and
merits.
 Renal ultrasound:
 To be done as soon as possible. A good screen for major
abnormalities including:
 Hydronephrosis, hydroureter
 Abnormal renal size and/or position
 Cysts/calculi
 It is not sensitive in detecting VUR, pyelonephritis and renal
scarring
 Dimercaptosuccinic acid (DMSA) scans:
 Gold standard for the diagnosis of APN but may be difficult to
differentiate inflammatory changes from scarring
 Gold standard for the diagnosis of renal scars when done 6
months post infection and is able to assess differential function of
the kidneys
 It greatly helps in making clinical decisions and is recommended
for all patients
 Micturating cystourethrogram (MCU):
 Radiographic MCU is the gold standard for the diagnosis of VUR
 It also detects abnormalities of lower urinary tract: Bladder,
urethra
 Most centers do not recommend routine MCU after first febrile
UTI, as it is invasive with inherent radiation risk, and should be
done in selected patients
 Indications generally include:
 Atypical/complicated UTI
 Abnormal renal US or DMSA scans
 Recurrent UTI
Establish a firm diagnosis

Yes No
US Observe and education
Abnormal Normal
DMSA at 6 months Normal Education

If recurrent UTI
Scars
MCU± Urodynamic study in toilet trained child
Treat only dilated VUR ± urotherapy
Figure 11.3: Approach to investigations following UTI
 Direct radioisotopic MCU (with catheterisation) has the advantage

of having significantly lower radiation than radiographic method
but it is not as accurate in assessing severity of VUR or the diagnosis
of posterior urethral valve. It should only be used as follow up
study of primary VUR.
 Indirect diethylene triamine pentacetic acid (DTPA) cystography is
sometimes done as it has the advantage of avoiding catheterisation
but again, it is less accurate and unable to detect lower-grade VUR.
It is generally used for children older than 6 years, who can void on
command, or patients who refuse catheterisation
GUIDELINES FOR MICTURATING CYSTOURETHROGRAPHY

(MCUG)
Background
Micturating cystourethrography is a fluoroscopically monitored definitive
imaging study of the:
 Lower urinary tract:
 Bladder, urethra, vesico-ureteric junction
 Upper urinary tract:
 Only if VUR is present
Nephrology 433
Indications for doing MCUG must be clear and the disadvantages

include:
 Invasive procedure requiring bladder catheterisation
 Radiation risk to gonads, especially in females
INDICATIONS
 Gold standard for the diagnosis of VUR
 Definitive diagnosis of PUV in boys especially if bilateral dilated
upper tract is present on ultrasound
 Diagnosis of neuropathic bladder where bladder hypertrophy and
trabeculation can be seen on MCUG due to back pressure changes
POINTS TO REMEMBER
 Micturating cystourethrography is not an urgent procedure, it should
only be done when the UTI is adequately treated, usually 2–4 weeks
after an infection.
 After a UTI, antibiotic prophylaxis (usually co-trimoxazole 2–3mg/
kg ON) should be started, especially in infants and those with
ultrasound abnormalities, until MCU result is known.
 In doubtful cases of pelviectasis, follow up renal ultrasound and
MAG3 scan to exclude pelvic ureteric junction obstruction are
preferred before considering MCUG.
 Neonates present a technically more challenging group (especially
female) with increased failure rate and trauma. Thus indications for
early MCUG in neonates must be clear.
PRECAUTIONS
 Indications must be present. If doubtful, consult senior doctor or
renal physician
 Adequate explanation must be given to parents regarding
indications, procedure and possible problems. Risks of procedure are
acceptable if indications are present
 Complications of MCU include:
 Infection:
 Minimise risk through proper aseptic technique
 Co-trimoxazole cover in patients <2 years
• Co-trimoxazole (trimethoprim 8mg/kg/day in BD dose) for
3 days starting the day before MCU
• Use Trimethoprim alone in patients with G6PD deficiency
 Trauma — minimise by:
 Adequate lubrication/local anaesthesia with sterile 1%
lignocaine gel
 Correct-sized catheter; 5F to 8F feeding tube, depending on

patient size
 Advance catheter until urine flows out freely, then advance
by about 2cm before securing with tapes. Catheter length
introduced should not exceed 4–5cm in neonates and
7–10cm in older children
 Avoid using force when resistance is met
 Aftercare:
 Ensure antibiotic cover and prophylaxis
 Advise on possible dysuria (rarely leading to retention of urine)
VESICOURETERIC REFLUX (VUR)

Vesicoureteric reflux is a heterogeneous group of disorders. It is either
a primary developmental disorder with or without renal dysplasia or is
secondary to obstruction at the bladder or urethra. In its uncomplicated
primary form, only dilating VUR (Grade III-V) needs treatment. The first
line of treatment is medical
Indications for surgical treatment are:
 Failed medical treatment
 Associated urological abnormalities, e.g. urethrocele, duplex systems,
obstructive uropathy
Medical Treatment:
 Daily low-dose antibiotics, minimal dose to prevent urosepsis. Check
G6PD status.
 Co-trimoxazole and Nitrofurantoin should not to be used in
infants <3 months.
 Choice of antibiotic:
 Co-trimoxazole/Trimethoprim (2–3mg/kg ON)
 Cephalexin (15–20mg/kg ON)
 Nitrofurantoin (2mg/kg ON)
 Regular follow-up:
 Until resolution of VUR or till patient is 6 years old
 Beyond 6 years old and if there is no recurrent UTI, focus
should be on renal involvement with long term follow up for
hypertension and proteinuria if there is significant scarring
 If VUR still causes UTI past 6 years old, treatment is surgical as
there is little chance of spontaneous resolution beyond this age
 Urodynamic study is sometimes indicated if bladder dysfunction
is suspected in children older than 6 years with persistent VUR
 Repeat MCU is not mandatory especially if DMSA scan is normal
Nephrology 435
Vesicoureteric Reflux (VUR)
Low Grade (I & II) High Grade (III & IV)
No treatment Medical Treatment Surgical Treatment

 Antibiotic Indications:
prophylaxis and  Failed medical
follow-up until VUR treatment:
resolves or until 6  Breakthrough UTI
years of age  DMSA
 MCU and repeat deterioration
DMSA if recurrent  Non-compliance
Follow up x 1 year no UTI  Co-existent
recurrent UTI  Ultrasound for renal uropathy
growth  Single normal
kidney
Consider discharge  Grade V VUR
Persistent VUR beyond 6 years old

No scar Stop antibiotic and observe
Repeat DMSA Recurrent UTI
Scar No Yes
Long-term follow-up if Urodynamic studies and surgery

significant scarring or reduced
differential function is present
Figure 11.4: Clinical Approach to VUR

 High grade VUR (Grade III and above) needs:

 Antibiotic prophylaxis
 May need follow-up MCU
 Follow-up DMSA scan if there is recurrent UTI with possibility of
new scar formation
 If child is older than 5 years with febrile UTI for the first time,
antibiotic prophylaxis is recommended for 1–2 years from time of
infection if VUR is present
When to Refer to the Nephrologist

 If VUR is high-grade
 If VUR is secondary to obstructive uropathy
 If significant renal scarring is present, especially with differential
function (<45%)
 If there is a positive family history
 If there are complicated pathologies, e.g. duplex, urethrocele,
trabeculated bladder
Bibliography
1. Brandström P, Esbjörner E, Herthelius M et al. The Swedish reflux trial in children: J Urol
(2010);184:274–297.
2. American Academy of Pediatrics Steering committee on quality improvement,
subcommittee on urinary tract infection: urinary tract infection: clinical practice guideline
for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24
months. Pediatrics (2011);128:595–610.
3. Routh JC, Bogaert GA, Kaefer M et al. Vesicoureteral reflux: current trends in diagnosis,
screening and treatment. Eur Urol (2012);61:773–782.
4. Coulthard MG. Is reflux nephropathy preventable and will the NICE childhood UTI
guidelines help? Arch Dis Child (2008);93:196–199.
5. Shaikh N, Ewing AL, Bhatnagar S et al. Risk of renal scarring in children with a first urinary
tract infection: a systematic review. Pediatrics (2010);126:1084–91.
6. Ording Müller LS. Imaging in urinary tract infection: top-down or down-up? Pediatr Radiol
(2011);41 (Suppl 1):S96–S98.
7. National Institute of Clinical Excellence. Urinary Tract Infection in Children, London: NICE,
2007; available at: http://guidance.nice.org.uk/CG54.
8. Saadeh SA, Mattoo TK. Managing urinary tract infections. Pediatr Nephrol (2011);26:1967–
76.
9. Peters CA, Skoog SJ, Arant BS Jr, Copp HL, Elder SJ, Hudson RG et al. Summary of the
AUA guideline on management of primary vesicoureteral reflux in children. J Urol
(2010);184:1134–44.
10. Jodal U, Smellie J,Lax H, Hoyer PF. Ten year results of randomized treatment of children
with severe vesicoureteric reflux. Final report of the International Reflux Study in Children.
Pediatr Nephrology (2006);21:785–792.
Nephrology 437
ACUTE KIDNEY INJURY (AKI)

DEFINITION
Abrupt decrease in glomerular filtration rate, resulting in the inability
of the kidneys to maintain water and electrolyte homeostasis and acid-
base balance, with an ensuing rise in the serum creatinine.
Classified into
 Oliguric renal failure — Urine output is <300ml/m2/day or <1ml/kg/hr
 Non-oliguric renal failure — Urine output is maintained
APPROACH
Distinguishing Between Acute and Chronic Renal Failure
Features of chronicity include:
 Growth failure
 Past or family history of renal disease
 Chronic hypertensive retinopathy
 Renal osteodystrophy or rickets
 Small kidneys on renal ultrasound
Features such as anemia, hyperphosphataemia, and hypocalcaemia are

not distinguishing features as they may occur in ARF.
Differentiate Between Pre-renal, Renal and Post-renal

Causes
Urine for Microscopic Examination
Cells Dysmorphic red cells Glomerulonephritis
White cells Pyelonephritis
Eosinophils Acute interstitial nephritis
Casts Red cell Glomerulonephritis
Tubular cells/epithelial cells
Crystals Uric acid Tumour lysis
Urinary Indices
 Children
Urine osmolality Urine sodium FENa (%) Renal failure index
(mOsm/kg) (mmol/L)
Pre-renal >500 <10 <1 <1
Renal <350 >60 >1 >2
 Neonates
Urine osmolality Urine sodium FENa (%) Renal failure index
(mOsm/kg) (mmol/L)
Pre-renal >400 <30 <2.5 <2.5
Renal <400 >60 >2.5 >2.5
Fractional excretion of sodium Urine/plasma Na

(FENa) = Urine/plasma Cr
Renal failure index Urine Na
(RFI) = Urine/plasma Cr
Ultrasound of urinary tract
Large,echogenic Small echogenic ± Dilated ureters, pelvis

kidney kidney cysts
AKI Chronic kidney failure Post renal obstruction
Figure 11.5: Differentiating cause of acute renal failure on ultrasound
Table 11-15: Paediatric RIFLE to stage AKI

Estimated GFR Urine Output
Risk eGFR decrease by 25% <0.5ml/kg/h for 8 hours
Injury eGFR decrease by 50% <0.5ml/kg/h for 16 hours
Failure eGFR decrease by 75% <0.5ml/kg/h for 24 hours

or <35ml/min/1.73m2
Loss Persistent failure >4 weeks
End Stage Renal Failure Persistent failure >3 months
Height (cm) x 36.2

eGFR =
serum Creatinine (μmol/L)
If previous baseline serum creatinine unavailable, then estimate eGFR as
100ml/min/1.73m2
Nephrology 439
Causes of Acute Renal Failure

Pre-renal Volume depletion Haemorrhage
Gastrointestinal losses: Vomiting, diarrhoea
Renal losses: Tubulopathies
Third space loss Hypoalbuminaemic states: Nephrotic

syndrome, liver disease
Burns, crush injury
Capillary leak syndrome, septicaemia
Circulatory failure Cardiac tamponade, Congestive cardiac failure,

Pericarditis
Renal Glomerulonephritis Acute nephritic syndrome
Post-infectious glomerulonephritis
Henoch Schonlein purpura
Lupus nephritis
Rapidly progressive glomerulonephritis
Vascular Haemolytic-uraemic syndrome

Renal artery and vein thrombosis
Tubulointerstitium Interstitial nephritis Allergic

Post-infectious
Tubular necrosis Progress from pre-renal conditions

Nephrotoxins — Drugs (aminoglycosides,
amphotericin, ifosphamide, cisplatin)
Radiocontrast dye
Intratubular Pigment injury — Haemoglobinuria,

obstruction myoglobinuria
Uric acid nephropathy (tumour lysis syndrome)
Crystalluria — Acyclovir
Post-renal Obstructive uropathy Posterior urethral valve
Obstruction of single kidney or bladder
Bilateral ureteric obstruction
Management of Acute Renal Failure

Reverse reversible factors:
 Correct Dehydration
 Hypotension
 Infection
 Nephrotoxicity
 Obstruction
Child with intravascular depletion, oliguria and

azotaemia
Normal saline or FFP

20ml/kg over 1 hour
Persistent oliguria
IV frusemide 2–4mg/kg Good urine output
Persistent oliguria Pre-renal renal failure
Established renal failure
Figure 11.6: Initial approach to patient with oliguric renal failure
In most cases, management is conservative while awaiting recovery of

renal function. The aim of management is to:
 Correct fluid/electrolyte abnormalities
 Provide adequate nutrition
Investigation
 Full blood count, film, reticulocyte count.
 Renal panel, serum calcium, serum phosphate, acid base assessment
 Serum and urine osmolality, urine sodium, urine creatinine (to
differentiate between pre-renal and renal cause)
 Urinalysis, urine protein/creatinine ratio (uPCR), urine culture
 Serum C3,C4, ANA, dsDNA, ANCA, ASOT (if clinical picture suggestive
of glomerulonephritis)
 Chest x-ray (if cardiac or respiratory signs present)
 Renal ultrasound with Doppler studies of renal vessels
 Renal biopsy if indicated
Fluid Management
Principle:
 If euvolaemic, replace Insensible Water Loss (IWL = 400ml/m2/day)
plus urine output
 If fluid overloaded, replace Insensible Water Loss plus half of urine output
 Weight gain or hyponatraemia during this phase indicative of fluid overload
 Intravenous furosemide (1mg/kg/dose) promotes renal blood flow
during the early stage
Nephrology 441
 Larger doses of IV 2–4mg/kg/dose over 15 mins may be required

 Doses exceeding 100mg/day may not have additional benefit
Electrolyte Management
Hyperkalaemia
 Prompt treatment if T wave changes on ECG or K+ >6.0mmol/L
 Monitor ECG
 Drugs
Table 11-16: Drugs for managing hyperkalaemia

Treatment Administration Remarks
IV 4.2% sodium bicarbonate 1–2mmol/kg/dose over May cause sodium overload/
15 mins hypertension in patient with
renal problem
IV 10% calcium gluconate 0.5–1ml/kg over 5–10 mins May cause hypocalcaemia,
and repeat after 5 mins if tissue necrosis or heart block
ECG changes persist (bradycardia)
PO sodium polystyrene sulfonate Oral 1g/kg/dose (max 30g) Contraindicated in obstructive
(Resonium) 6 hourly bowel disease and neonates
with reduced gut motility (risk
of intestinal necrosis). May cause
nausea, constipation, paralytic
ileus or diarrhea.
PR sodium polystyrene sulfonate 1g/kg/dose (max 30g) Should be retained for at least
(Resonium) 30–60 mins. Work faster than
oral but effects may be lower.
May cause cecal perforation plus
the side effect as above
IV 50% dextrose + 1ml/kg/dose + 0.1unit/kg of May cause hypoglycaemia, need
IV soluble insulin insulin (max 10 unita) to recheck hypocount
Nebulised salbutamol 2.5mg if <25kg May cause tachycardia

5.0mg if >25kg
(max 20mg/dose in 4ml NS)
“See full management of hyperkalaemia under “Emergency management of hyperkalaemia in children- algorithm on page 653
Hyponatraemia
 Results from fluid overload
 If Na ≥120mmol/L, correct by restriction of free water
 If Na <120mmol/L or symptomatic, correct to 125mmol/L
 Na+ deficit = 0.6 x body weight (kg) x [(desired Na+) − (actual Na+)]
 Correct slowly, raising serum Na+ by not more than 1mmol/hr to a
max rate of 12mmol/L per day
Metabolic acidosis
 Judicious use of sodium bicarbonate
 Aim for half correction. Formula for calculating bicarbonate
replacement = 1/3 x body weight (kg) x base excess.
 Be mindful that bicarbonate replacement will increase CO2 tension
and an intact respiratory system is needed to eliminate CO2
produced
 Be aware of Ca++ levels as correction of acidosis will cause shift from
ionised to non-ionised form
Hyperphosphataemia and hypocalcaemia

 Hyperphosphataemia is managed by dietary phosphate restriction
and phosphate binders (calcium carbonate or calcium acetate).
 Calcium replacement may be initiated when phosphate levels
are lowered when calcium phosphate product <4.5 (mmol/L)2
 Calcium-based Phosphate binder doses:
Age group Frequency Calcium acetate Calcium carbonate

66mg/Tab equivalent 625mg/Tab equivalent
<1 year 3–4 times a day with ¼ Tab
meals
1–6 years ½ Tab
6–12 years 1 Tab
12–18 years 2 Tab
 Doses are titrated based on meal frequency and serum phosphate

levels.
 Calcium acetate is preferred where there is hypochlorhydria due
to either gut immaturity or due to use of medications such as
omeprazole and ranitidine.
Nutritional Management
 Minimum of 25% of the daily caloric requirement is necessary to
reduce ongoing catabolism
 May require up to 25% dextrose, infused via central line
 Protein is restricted to 1g/kg/day
Hypertension
See “Hypertension” on page 418
Nephrology 443
Drugs
 Minimise use of nephrotoxic drugs. If necessary, monitor drug levels
and side-effects
 Doses may have to be adjusted in renal impairment
DIALYSIS
Aim
Maintain fluid, electrolyte and acid-base balance; remove endogenous
and exogenous toxins until renal function recovers.
Indications
The indications are not specific and should be individualised. In children,
the dialysis is usually initiated for indication of fluid overload.
Indications for initiating dialysis include:
 Oliguria/anuria
 Plasma urea >35mmol/L
 Hyperkalaemia >6.5mmol/L unresponsive to conservative treatment
 Intractable metabolic acidosis (serum bicarbonate <10mmol/L)
 Pulmonary oedema unresponsive to conservative therapy
 Symptomatic uraemia — Encephalopathy, pericarditis (generally
when urea >50mmol/L)
 Toxins
Modes of Dialysis in ARF

 Peritoneal dialysis
 Haemodialysis
 Continuous venovenous haemodialysis
OUTCOME
Three phases:
 Oliguric phase — Lasts few days to 6 weeks
 Diuretic phase
 Recovery phase — May last for months
Mortality
Dependent on cause. Overall about 30%, usually if coincident with
multi-organ failure.
Bibliography
1. Ministry of Health. A Guide to Paediatrics. Singapore: Ministry of Health; 1997.
2. Lesley Rees, Nicholas Webb, Paul Brogan, editors. Paediatric Nephrology. Oxford
Handbooks in Paediatrics. 2007
3. Adelman RD, Coppo R, Dillon MJ. The emergency management of severe hypertension.
Pediatr Nephrol. 2000;14(5):422–427.
4. Barratt M, Avner E, Harmon B, editors. Pediatric Nephrology. 5th ed. Baltimore: Lippincott
Williams & Wilkins; 2004.
5. Chan JC, Williams DM, Roth KS. Kidney failure in infants and children. Pediatr Rev.
2002;23(2):47–60.
6. Akcan-Arikan A, Zappitelli L, Loftis LL et al. Modified RIFLE criteria in critically ill children
with acute kidney injury. Kidney International 2007;71:1028–1035.
ENURESIS AND VOIDING PROBLEMS
Enuresis is a common, socially disruptive and stressful condition affecting

10% of school-going children with 1% continuing into adulthood.
DEFINITIONS
Nocturnal enuresis (NE)/bedwetting:
Wetting while asleep beyond 5 years of age and frequently enough to
be disturbing. Usually twice or more in a week
Primary nocturnal enuresis:

Never been dry for an extended period of >6 months
Primary monosymptomatic nocturnal enuresis (PMNE):

Primary nocturnal enuresis that occurs as the only problem, i.e. the
patient is otherwise well with voiding
Secondary nocturnal enuresis:

Was consistently dry for at least 6 months and then bedwetting recurred
Unstable bladder:
Frequent micturition, urgency and wetting. Holding manoeuvres like
squatting, crossing legs to stop the urge
Incontinence:
No control over voiding or involuntary wetting. Constant wetting may
be associated with UTI and clinical signs of neuropathic bladder
CLINICAL ASSESSMENT
A good history and careful examination, followed by a simple urinalysis
as a screen for urinary abnormalities are all that is needed. Imaging
Nephrology 445
studies and urodynamic studies should be reserved for those with a

complicated history or abnormal clinical findings.
Up to 30% of so-called ‘monosymptomatic’ enuretics are found to have

bladder instability. Identification of this group of patients is important
for successful treatment. Bladder instability may present with urgency,
holding episodes and urge incontinence.
Physical examination in an enuretic is usually normal. However, it is

important not to miss a usual case of neuropathic bladder or polyuria.
THERAPY IN PMNE
General Measures
Good ‘doctoring’ is essential — explanation of ‘benign’ nature and not a
psychopathological condition.
Active intervention or therapy can achieve dryness in 30–70% within
1–3 months.
Indications for treatment:

 6 years and older
 Bed-wetting is frequent (more than twice a week)
Treatment modalities
Two established treatment modalities are the use of desmopressin
(DDAVP) and the enuresis alarm.
Tricyclic antidepressants (imipramine) cannot be recommended as first-line
therapy because of its potential fatal side effect in overdose. Anticholinergics
like oxybutnin can act as adjunctive therapy when nocturnal enuresis is
associated with detrusor overactivity as one of the aetiologic factors.
Desmopressin treatment
Desmopressin is a synthetic analogue of the natural-occurring anti-
diuretic hormone or vasopressin (AVP) but is more potent in its anti-
diuretic affect and thus it will always improve incontinence.
Desmopressin treatment in NE is rarely associated with water
intoxication. Nonetheless patients and their families need to be warned
of potential adverse effects and avoid overdrinking before bedtime.
Minor side effects reported include headache, abdominal pain and
aggressiveness.
Figure 11.7: Initial clinical assessment of nocturnal enuresis
Establish Pattern of Wetting

History
History
 Questionnaire for voiding and wetting
- Day-time or night-time wetting
- Urge to void
- Holding manoeuvres
 Questionnaire for constipation or soiling
 Urinary diary (frequency /volume chart)
 Behavioural profile/family history
Clinical
Assessment  Inspection of genital area
 Lumbosacral signs of spinal
dysmorphism
 Neurological defects in lower limbs —
pes cavus, hyper-reflexia
 Lumbosacral reflex activity when
indicated
Negative Positive
Primary Onset
Often positive family history
Normal voiding
Voiding problems — Dysuria, urgency,
incontinence
Encopresis
Evidence of UTI/pelvic surgery
Urinalysis ± Urine C/S Secondary onset
Positive clinical findings
Negative
Primary Monosymptomatic
Nocturnal Enuresis (PMNE) Specialist Referral
No further investigations,
offer treatment
Nephrology 447
Figure 11.8: Treatment guidelines for primary monosymptomatic nocturnal enuresis

Age >5 years No Reassurance
Frequency >2 times a week
Yes
Discuss treatment options
DDAVP Enuresis alarm
Oral 0.2–0.4mg or
Intranasal 20–40mcg
for at least 1 month
Good
Poor response
response after 3
months
Partial/good Poor response
response (wet nights
(wet nights reduced by Reassess Off alarm
reduced by <50%)
50%)
Good Poor
compliance compliance Wet Dry
Continue Treatment
 3 months or more
 May reduce dose by half DDAVP ± Counselling Discharge
 Reassess alarm
Dry/acceptable Enuresis alarm ± DDAVP Retry enuresis alarm
Discharge/treat on
special occasions Good response No response
Refer to specialist
Enuresis alarm
The enuresis alarm is effective with a reported success rate around 60–
80%. Alarm training has a reported relapse rate of 15–40%. Retreatment
is often effective.
When compared with pharmacotherapy, alarm treatment appears to

have more sustained effect when off-treatment.
Bibliography
1. Moffatt MEK, Kato C, Pless IB. Improvements in self-concept after treatment of nocturnal
enuresis: Randomised controlled trail. J Pediatr. 1987;110(4): 647–652.
2. Chao SM, Yap HK, Tan A, Ong EK, Murugasu B, Low EH, Tan SP. Primary monosymptomatic
nocturnal enuresis in Singapore — Parental perspective in an Asian community. Ann Acad
Med Singapore. 1997;26(2):179–183.
3. Von Gontard A, Eiberg H, Hollmann E, Ritting S, Lehmkuhl G. Molecular genetics of
nocturnal enuresis: Clinical and genetic heterogeneity. Acta Paediatr. 1998;87(5):571–578.
4. Yap HK, Chao SM, Murugasu B, Ong EK, Low EH, Tan A. Efficacy and safety of DDAVP in
the treatment of nocturnal enuresis in an Asian community. J Paediatr and Child Health.
1998;35:151–153.
5. Hjälmås K. Desmopressin treatment: Current status. Scand J Urol Nephrol.
1999;33(202):70–72.
PROTOCOL FOR RENAL BIOPSY
PREPARATION
On the day of admission:

 Ensure patient is well and blood pressure (BP) is normal
 Obtain consent
 Take blood for full blood count (FBC), coagulation profile (PT/PTT),
group and match (GXM) for 1 unit of packed red blood cells (and
others as indicated by nephrologist)
 Set intravenous (IV) cannula
 Inform nephrologist on admission
 Confirm the timing of ultrasound-guided biopsy with Diagnostic
Imaging Department and inform histopathology laboratory
technician for preparation and microscopy on the biopsy day
 Fast patient 6 hours before procedure
 Consider IV maintenance drip for young patients (please check with
nephrologist in-charge)
Nephrology 449
On the biopsy day:

 Send patient to ultrasound room 15 mins before procedure,
accompanied by a doctor (who is certified in administering moderate
sedation) and a nurse
 Things to prepare and to bring along:
 Oxygen saturation monitor
 Properly filled histology form
 Consent form for procedure
 Sedation to be given upon instruction by nephrologist and these will
usually include Ketamine ± Midazolam
POST-BIOPSY CARE
 Monitor pulse/respiration/BP: Q15 mins x 4, Q30 mins x 2, hourly x 4,
then 4 hourly thereafter if stable
 Inform senior doctor if patient’s heart rate or blood pressure is not
within normal range for the age
 Patient to lie flat in bed overnight
 To inform senior doctor if there is:
 Abdominal pain
 Fever
 Persistent gross haematuria x 2
 Vomiting
ON DISCHARGE
 To change to lighter dressing upon discharge
 To issue excuse chit from physical activities (PE)/sports for 6 months.
RENAL REFERENCE LIMITS
Table 11-17: Urinary Reference Limits (95th percentile) by age on spot urine sample for calcium,
urate and oxalate
Age (year) Urinary Calcium/ Urinary Urate/ Urinary Oxalate/

Creatinine Creatinine Creatinine
(mmol/mmol) (mmol/mmol) (mmol/mmol)
/12–6/12
1
2.2 1.6 0.22
/12–1
6
2.2 1.5 0.17
1–2 1.5 1.4 0.13
2–3 1.4 1.3 0.10
3–5 1.1 1.1 0.08
5–7 0.8 0.8 0.07
7–10 0.7 0.56 0.06
10–14 0.7 0.44 0.06
14–17 0.7 0.40 0.06
Bibliography
1. Vera Matos, Guy van Melle, Oliver Boulat, Michele Markert, Claude Bachmann, Jean-Pierre
Guignard. Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine
ratios in a healthy pediatric population. J Pediatr 1997;131:252–7
2. Vera Matos, Guy Van Melle, Dominique Werner, Daniel Bardy and Jean-Pierre Guignard.
Urinary Oxalate and Urate to Creatinine Ratios in a Healthy Pediatric population. AKJD
1999;34:E6
Acknowledgements
Dr Kelvin Xu for proofreadiing and checking of drug dosages.
451
NEUROLOGY
ABNORMAL HEAD SIZE IN CHILDREN
All children should have their occipito-frontal circumference (OFC)

measured at birth and as part of routine child health surveillance.
OFC is measured with a non-stretchable measuring tape extended
laterally around the head from the occiput to the glabella over the
eyebrows.
Common aspects in evaluation of an abnormal OFC:

 Obtain previous measurements
of OFC, height and weight
 Measure parent’s OFC
 Obtain a comprehensive
antenatal history and family
history
 Obtain a developmental
history and note for milestone
regression
 Check if visual and hearing
assessments have previously
been performed and their
results
 Clinical examination should
include: Figure 12.1: Measuring OFC in children
 Screening for dysmorphism
 Full neurological examination including gait and visual fields
 Developmental assessment
 Follow-up and monitoring development and other growth
parameters is important in determining the appropriate time for
investigations
Approach to Macrocephaly
Macrocephaly is defined as a child’s OFC being more than the 97th
percentile for the child’s age and gender.
Causes of Macrocephaly (See Figure12.2)

Macrocephaly
Hydrocephalus
Non-communicating Communicating
Anatomic
- Arnold-Chiari malformation - Post-meningitis

- Dandy-Walker malformation - Subdural fluid collections - Familial
- Aqueductal stenosis - Intra-cranial haemorrhage - Overgrowth
- Congenital toxoplasmosis - Benign enlargement of syndromes
sub-arachnoid spaces (e.g. Soto’s)
- Neurocutaneous syndromes
(e.g. neurofibromatosis,
tuberous sclerosis)
- Hydraencephaly
Figure 12.2. Macrocephaly
Microcephaly
Primary
1. Autosomal recessive primary

microcephaly
2. Chromosomal abnormalities
(e.g. Trisomy 21,13,18; ring Antenatal/Perinatal
chromosomes)
3. Genetic disorders (e.g. Rubin-
stein-Taybi Rett syndrome) 1. Disruptive Injuries: neonatal stroke
4. Brain malformations (e.g. micro- 2. Infections: TORCH
cephaly vera, lissencephaly, 3. Teratogens: Maternal alcohol, an-
holoprosencephaly) ti-cancer or anti-epileptic therapy
5. Metabolic disorders (e.g. 4. Deprivation: Maternal hypothy-
Batten’s disease, amino and roidism, placental insufficiency
organic aciduras)
6. Familial
Figure 12.3 Microcephaly

Neurology 453
Megaencephaly Thick skull/scalp
- Craniosketal dysplasias
Metabolic Chronic cerebral (e.g. rickets, cleidocranial
edema dysostosis
- Hyperphosphatemia
- Alexander’s disease - Toxins (e.g. lead,

- Canavan’s disease vitamin A)
- Lysosomal storage - Endocrine (e.g. hy-
disorders poparathyroidism)
Secondary
Postnatal
1. Disruptive injuries: head trauma, neonatal

encephalopathy
2. Infections: meningoencephalitis
3. Toxins: lead poisoning
4. Deprivation: malnutrition, hypothyroidism
Important aspects in evaluation of macrocephaly:

 Obtain a history of any symptoms of increased intra-cranial pressure
such as headache, vomiting, poor feeding and irritability
 Look for signs of increased intra-cranial pressure such as dilated scalp
veins or sun-setting eyes
 Look for impaired ocular movements, ataxia, and perform a visual
field assessment in co-operative children
 Blood investigations should be directed to the suspected cause;
useful tests include full blood count, renal panel, bone panel and
TFT (a metabolic screen is useful in the presence of dysmorphism or
other systems involvement)
 Perform neuroimaging only if indicated — OFC crossing centiles,
focal neurological deficits, possible raised intracranial pressure,
developmental delay or regression
 Imaging of choice is MRI, but CT head will suffice in emergency
situations to look for gross pathology
Evaluation of Microcephaly
Does child have clinical features, other organ involvement, vision/hearing

impairments, or family history to suggest a specific disease or syndrome?
YES NO
YES Proportionate microcephaly

Do specific testing Is microcephaly proportionate
Does child have neurologic signs
for that condition to height and weight?
or symptoms or a family history of
neurologic disease?
NO
Is microcephaly severe (<-3SD) or are there neurologic NO

signs or symptoms?
NO
YES
YES
Obtain MRI for further evaluation
Observe and consider

MRI suggests a specif- MRI is normal or non-specific
MRI and blood investi-
ic condition or injury Consider blood investigations
gations (see text) if child
pattern. (see text)
develops neurologic
Do specific testing for Consider Rett syndrome in girls
signs or symptoms or
that condition
worsening microcephaly
Figure 12.4 Evaluation of Microcephaly

Neurology 455
Approach to Microcephaly
Microcephaly is defined as a child’s OFC being less than the 3rd percentile
for the child’s age and gender. Primary microcephaly is a result of
abnormal brain formation in-utero, and secondary microcephaly is a
result of a disease process impairing growth of a normally formed brain.
Causes of Microcephaly (See Figure 12.3)
Important aspects in evaluation of microcephaly (See Figure 12.4):

 History should include details from the antenatal period and any
significant perinatal events, including maternal illness and lifestyle
 Examination of the head to note the shape, suture lines
and fontanelle is important to determine the possibility of
craniosynostosis which is an important differential of microcephaly
(look for ridging of suture lines and fusion, proptosis, syndactyly or
polydactyly)
 Useful investigations in neonates include TORCH screen, cranial
ultrasound and a karyotype
 Additional useful investigations in the older child include a
metabolic screen if there is multi-system involvement or significant
family history, and TFT
HEADACHE IN CHILDREN
INTRODUCTION
Headaches are common in children, and may result in missed school
and reduce participation.
Acute headaches and rapidly progressive symptoms raise the suspicion
of intracranial pathology.
Primary vs Secondary headache

Primary headaches are typically migraine and tension-type headaches.
Secondary headaches are caused by head and neck or systemic
conditions (see Table 12-1).
Table 12-1: Secondary headache in children
Common causes of secondary headache in children

Head and neck conditions Systemic disorders
sinusitis, allergic rhinitis fever
otitis media viral infections
temporomandibular joint pain hypertension
dental disorders medication side effect
head injury dehydration
meningitis hypercapnia
epileptic seizure or following a seizure hypoglycaemia
intracranial bleeding hypercalcaemia
brain tumour dialysis
idiopathic intracranial hypertension
History
Document frequency, time of day, nature of pain, site, duration and pain
score; Ask about triggers, aura, associated symptoms, relieving factors.
Migraine headaches
Aura, if present, may be visual (fortification, blurring, scotomas) or focal
dysesthesia (sensory).
Pain is typically throbbing, uni- or bilateral. Often there is also light and
sound avoidance (photo- and phono-phobia) or nausea and vomiting.
Rarely visual perceptual disorder, cutaneous sensory symptomatology
occurs.
Tension-type headaches
Bilateral location over frontal, temporal regions; pressing/squeezing
quality. No associated symptoms
Neurology 457
Some children have both migraine and tension-type headaches.

Headaches can be classified according to frequency into:
 Episodic Headache: Headaches <15 days/month for 3 months (≥10
episodes).
Or
 Chronic headache: Headaches ≥15 days/month for 3 months.
Some children have fleeting episodes, others describe constant 24/7
headache.
Physical examination
 Note head circumference, vital signs
 Complete neurological evaluation and general systemic examination
 Look for neck stiffness, neurocutaneous stigmata, focal neurological
deficits
 ** always examine for papilloedema (avoid using mydriatics for
fundoscopy)
WARNING SIGNS
Neuroimaging may be indicated if there is/are:
 signs and symptoms of raised intracranial pressure
 change in behaviour or deteriorating school performance
 early morning vomiting
 headache waking up patient from sleep
 abnormal neurological findings or papilloedema
Management goals
 Explain to patient and parents that response to treatments takes
time
 Use a ‘compressed’ pain score: 0 — none, 1 — mild headache, 2 —
severe needing pain relief so that patients/parents can focus on
triggers/lifestyle change rather than pain itself
Eliminate secondary causes that may contribute to chronic

headache
Treat allergic rhinitis, sinusitis or dental disorders; prescription lenses for
myopia.
Non-pharmacological interventions
 education, attention to routine
 physical conditioning: incorporating regular, enjoyable sport or
physical exercises are important
 sleep hygiene: keep bedtime constant, even during school holidays
and weekends; sleep deprivation is a trigger
 cognitive behavioural therapy, relaxation techniques
Pharmacological treatments
Acute symptom relief

 Only when unbearable, restriction of daily activities. Avoid overuse.
 Consider paracetamol, ibuprofen, triptans (age>12 years)
 Avoid medication overuse: limit pain relievers to ≤2 times a week, ≤8
times a month
Prophylactic medication
 For chronic migraine, consider amitriptyline (check ECG), topiramate,
valproate or beta blockers
 Amitriptyline may also be useful in chronic tension type headaches
Bibliography
1. Antilla P. Tension-type headache in childhood and adolescence. Lancet Neurol.
2006;5:268−274.
2. Bigal ME, Lipton BE. The differential diagnosis of chronic daily headaches: an algorithm-
based approach. J Headache Pain. 2007;8:263–272.
3. Damen L, Bruijn JK, Verhagen AP, Berger MY, Passchier J, Koes BW. Symptomatic
treatment of migraine in children: a systematic review of medication trials. Pediatrics.
2005;116:e295–302.
4. Eiland LS, Jenkins LS, Durham SH. Pediatric migraine: pharmacologic agents for
prophylaxis. Ann Pharmacother. 2007;41:1181–90
5. Gladstein J, Rothner D. Chronic daily headache in children and adolescents. Sem Ped
Neurol. 2010;17:88−92.
6. Mack KJ. Management of chronic daily headache in children. Exp Rev Therap. 2010
7. Rosenblum R, Fisher P. A guide to children with acute and chronic headaches. J Pediatr
Healthcare. 2001;15: 229–235.
8. Winner P. Pediatric headache. Curr Opin Neurol. 2008;21:316–322.
Neurology 459
CEREBRAL PALSY
INTRODUCTION
 Cerebral Palsy (CP) is a non-progressive disorder of motor function
and movement appearing early in life secondary to damage/lesion
of the developing brain. Cerebral palsy remains a clinical diagnosis.
Evidence of motor dysfunction must be present; clinical findings &
symptoms may evolve over time. Most patients exhibit symptoms as
infants or toddlers.
Prevalence: estimated 2–2.5 per 1000 live births

CAUSES AND RISK FACTORS

Most cases are believed to be due to prenatal factors. Perinatal asphyxia
plays a role in some while prematurity is a common association in
5–15% of surviving very low birth weight infants. More than one
aetiologic factor is often identified.
 Prenatal
 Infections
 Vascular pathology
 Placental insufficiency
 Genetic factors
 Maternal metabolic disturbances
 Intrauterine exposure to toxins
 Developmental brain lesions
 Perinatal
 Prematurity
 Infections
 Fetal/neonatal stroke
 Hypoxia-ischaemia
 Postnatal
 Brain Infections
 Hypoxia-ischaemia
 Toxic or metabolic encephalopathy, e.g. kernicterus, heavy metals
 Traumatic brain injury- accidental or non-accidental
 Seizures
 Stroke
CLASSIFICATION
Different classification systems for CP serve different functions.
Classification based on clinical findings is most widely used. It may be
classified according to the extremities involved and/or characteristics of
neurologic dysfunction.
 Spastic CP (70%). At least two of:
- Abnormal pattern of posture and/or movement
- Increased tone (not necessarily constantly)
- Pathological reflexes (hyperreflexia or abnormal Babinski
response
 Quadriplegia: all four extremities equally involved
 Diplegia: legs more affected than arms
 Hemiplegia: one-sided, arm more affected than leg
 Monoplegia
 Dyskinetic CP (10%)
- Involvement of basal ganglia and extra-pyramidal tracts.
characterised by abnormal pattern of posture and/or
movement
- Involuntary, uncontrolled, recurring, occasionally
stereotyped movements of affected body parts
 Choreo-athetoid: dominated by both chorea and athetosis
 Dystonic: dominated by involuntary movements and sustained
abnormal posture
 Ataxic CP (10%)
 Mixed CP (10%)
ASSOCIATED PROBLEMS
Intellectual disability
Language & speech impairments
Psychosocial behavioral problems
Epilepsy
Feeding and swallowing difficulties
Hearing impairment
Visual disorders, strabismus, refractive errors
Scoliosis
Pulmonary disease
Poor growth and nutrition,
Orthopedic problems (e.g., joint subluxations and dislocations and hip
dysplasia),
Urinary disorders, e.g. voiding dysfunction
Neurology 461
EVALUATION
Detailed history
 Antenatal, perinatal, postnatal history
 Developmental history
 Exclude familial or neurodegenerative disorder masquerading
as CP. Ask about consanguinity, regression of milestones, family
history of similar affected siblings/relatives, consanguinity, episodic
exacerbation of symptoms
 Social history, effect on family
 Others: education, special aids
 Medications
Physical and neurological examination

 Define the type of CP
 Assess mental and physical functional status
 Assess associated problems
 Growth, development and head circumference
 Dysmorphism
 Neurologic deficits, abnormalities of muscle tone, power and gait,
brisk tendon reflexes, clonus, presence of involuntary movements,
persistence of primitive reflexes, contractures
Laboratory studies
 No specific tests to confirm the diagnosis of CP
 Neuroimaging should be performed to establish an aetiology and for
prognostic purposes. Magnetic resonance imaging is preferred to CT scan.
 Children with atypical features in the history or neurologic examination
should be thoroughly evaluated to exclude other conditions including
metabolic and genetic disorders. Useful investigations include
karyotype, metabolic testing, TORCH screen in neonates
 Children with hemiplegia or imaging evidence of cerebral infarction
may have a prothrombotic coagulation disorder and may benefit
from screening.
MANAGEMENT
Treatment goals are directed at reducing disability and maximising
potential in all areas of development including activities of daily living.
Goals should be functional and realistic with periodic re-evaluation.
Optimal management of the child with cerebral palsy requires a
collaborative goal-oriented approach in which a multidisciplinary
team works with the family to address the child’s medical, social,
psychological, educational and therapeutic needs.
Treatment modalities
 Rehabilitation therapy
 Physiotherapy
 Occupational therapy
 Speech therapy
 Behavioral therapy
 Mechanical devices to assist patients in sitting, walking, or
communicating , to prevent and correct deformities, to control
involuntary movements
 Orthoses, serial casting, braces, special chairs
Suspected CP: child with disorder

of movement and posture
Detailed History, Physical and

Neurological Examination
Exclude Establish a definitive diagnosis

progressive of Cerebral Palsy
degenerative
disorders
Determine type of CP
• Spastic Hemiplegia
Identifying Possible Causes Diplegia
Quaddriplegia
• Dyskinetic
• Ataxic
• Mixed
Obtain neuroimaging study
MRI preferred to CT
Other tests as needed, e.g. metabolic,
coagulopathy, genetic evaluation • Assess Functional Status
(mental, physical,emotional,educational)
• Assess growth & development
• Assess neurological deficits
• Screen for associated medical & social problems
(eg. seizures, vision, hearing, feeding, impact on child & family
Develop management plans

- Collaborative, functional, realistic, goal-oriented approach with periodic
re-evaluation
- Multidisciplinary team working with family,
- Neuro-rehabilitation/early intervention programme
Figure 12.5: Evaluation and Management of the child with Cerebral Palsy (CP)
Neurology 463
 Pharmacotherapy
 Anti-spasticity medications
i. Oral agents (baclofen, diazepam)
ii. Botulinum toxin A injections for focal spasticity
 Medications for seizures, involuntary movements
 Surgery
 Orthopedic tendon lengthening, tendon transfer, bony fusion
 Neurosurgery, e.g. selective dorsal rhizotomy
 Gastrointestinal
 Special education may assist children with special needs
 Pyschosocial therapy
Common presentations to the ED/reasons for admission

 Respiratory problems especially pneumonia
 Status epilepticus/uncontrolled seizures
 Unexplained irritability — Consider acute infections, pain from
fractures/subluxation, intestinal obstruction, brain trauma and
possibility of non-accidental injury
Bibliography
1. Yeargin-Allsopp M, Van Naarden Braun K, Doernberg NS, et al. Prevalence of cerebral palsy
in 8-year-old children in three areas of the United States in 2002: a multisite collaboration.
Pediatrics 2008; 121:547.
2. Bjornson K, Hays R, Graubert C, et al. Botulinum toxin for spasticity in children with
cerebral palsy: a comprehensive evaluation. Pediatrics 2007; 120:49.
3. Platt MJ, Cans C, Johnson A, et al. Trends in cerebral palsy among infants of very low
birthweight (<1,500g) or born prematurely (<32 weeks) in 16 European centres: a
database study. Lancet 2007; 369:43.
4. Ashwal S, Russman BS, Blasco PA, et al. Practice parameter: diagnostic assessment of the
child with cerebral palsy: report of the Quality Standards Subcommittee of the American
Academy of Neurology and the Practice Committee of the Child Neurology Society.
Neurology 2004; 62:851.
5. Delgado MR, Hirtz D, et al. Quality Standards Subcommittee of the American Academy
of Neurology and the Practice Committee of the Child Neurology Society, Practice
parameter: pharmacologic treatment of spasticity in children and adolescents with
cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee
of the American Academy of Neurology and the Practice Committee of the Child
Neurology Society. Neurology 2010; 74:336.
6. CE Buckon, SS Thomas, and JH Piatt. Selective dorsal rhizotomy versus orthopedic
surgery: a multidimensional assessment of outcome efficacy. Arch Phys Med Rehabil 85
(2004);457–465.
7. Simchen MJ, Goldstein G, Lubetsky A, et al. Factor v Leiden and antiphospholipid
antibodies in either mothers or infants increase the risk for perinatal arterial ischemic
stroke. Stroke 2009; 40:65.
MANAGEMENT OF STATUS EPILEPTICUS

Status epilepticus is a neurological emergency. It is defined as a
continuous seizure lasting >30 mins, or acute repetitive seizures without
return of consciousness inter-ictally for >30 mins. Recent studies show
that most unprovoked seizures abort spontaneously within the first
5–10 mins, after which the risk of a prolonged seizure will be high.
See Figure 12.6 for the clinical pathway for the management of status
epilepticus.
SEIZURES AND EPILEPSY
SEIZURES
Definition
Seizures are a transient occurrence of signs and/or symptoms due
to abnormal excessive or synchronous neuronal activity in the brain.
Seizures are a symptom, not a diagnosis. Acute causes of seizures
include:
 Head trauma
 Hypoglycaemia
 Hyponatraemia
 Hypocalcaemia
 Meningitis/encephalitis
 Intracranial haemorrhage, etc.
In children with no acute cause, a first afebrile seizure is said to have

occurred. Recurrent seizures may result in a diagnosis of epilepsy.
Status epilepticus (SE): >30 mins of a continuous seizure activity or

multiple seizures without intervening recovery of consciousness. A
functional definition of status epilepticus is a seizure persisting beyond
5–10 mins.
Acute symptomatic seizures: seizures which have an obvious and

immediate preceding cause (e.g. an acute systemic, metabolic or toxic
intake) or an acute cerebral event. These seizures are often isolated
events and do not recur when the cause is removed.
Neurology 465
Ensure ABCs
Check glucose, U&E, Ca, Mg
If glucose <3mmol/L, give 5ml/kg 10% dextrose IV
IV access No IV access
Diazepam 0.25mg/kg IV
Max dose 10mg/dose Diazepam 0.4mg/kg PR
or Max dose 10mg/dose
Lorazepam 0.1mg/kg IV
Max dose 4mg/dose
5 mins
5 mins
IV access No IV access
Repeat dose x 1
Diazepam 0.4mg/kg PR
Max dose 10mg/dose
Phenytoin† 20mg/kg IV over 20 mins

• Give neat
• Infusion rate: Max 1mg/kg/min
• Max dose 1500mg
• Monitor ECG and BP
• Avoid in patients already on phenytoin
Phenobarbitone 20mg/kg IV over 20–30 mins

• Dilute with normal saline
• Infusion rate: Max 1mg/kg/min
• Monitor BP
Transfer to CICU for anaesthesia under EEG monitoring
†
<1 year of age, use phenobarbitone first rather than phenytoin.
Figure 12.6: Clinical pathway for the management of status epilepticus

Classification of Seizures
The International League Against Epilepsy (ILAE) Seizure Classification
(1981) divides seizures into generalised and partial seizures:
 Generalised seizures — Seizures which rapidly spread throughout

bilateral networks
 Tonic — Stiffening of the limbs/body
 Clonic — Rhythmic regular jerking of the limbs, body.
 Tonic-clonic — Tonic stage followed by clonic stage
 Absence — Staring with brief loss of awareness, accompanied
by eyelid fluttering, lip-smacking or chewing movements but
NOT loss of posture, i.e. do not fall over. Lasts <1 min, many
times a day. Commonly mistaken for ‘daydreaming’. Triggered by
hyperventilation
 Myoclonic — Irregular jerking typically of arms or legs but can
occur in eyelids, body
 Atonic — Crumpling up to ground
A ‘drop attack’ is a descriptive term but not a specific seizure type. Patients
typically have sudden stiffening or jerking of the body resulting in a forceful
fall to the ground. This can be a spasm or a tonic or myoclonic seizure.
 Partial seizures — Originate in networks in one hemisphere of the

brain
The 1981 classification divides seizures based on consciousness

involvement:
 Simple partial seizure — Patient is conscious during the seizure.
Can be:
 Motor — stiffening/jerking of a limb
 Sensory — pain/numbness in a limb (somatosensory),
transient homonymous haemianopia
 Complex partial seizure — Impaired conscious level: may appear
dreamy or confused.
 Accompanied by automatisms — meaningless complicated
actions, e.g. plucking at clothes. Commonly lasts several
minutes. Typically arise from temporal or frontal lobe.
 May be preceded by auras — fear, unpleasant smell
 Not to be confused with absence seizures (shorter, more
frequent) or complex (complicated) febrile seizures
Neurology 467
The current 2010 classification adds subgroups to generalised seizures

and recommends more comprehensive description of focal seizures.
Febrile seizures
Seizures occurring in:
 Children aged 6 months to 6 years with
 Temperature >38°C, and
 Absence of CNS infection.
Can be simple: OR
complicated (complex):
<15 mins long >15 mins long

single in 24 hours and generalised multiple in 24 hours and focal

Approach:
Check diagnostic criteria above and in Febrile Seizure pathway
Establish fever present: >38°C. (Child may be afebrile before seizure and
febrile immediately after seizure.)
Identify source of infection and fever
Exclude central nervous system infection as a cause
Give antipyretics for comfort care. This does not prevent/reduce febrile
seizure occurrence.
Supply Febrile Seizure patient information leaflet
Provoked seizures
Seizures in context of intercurrent illness and absence of fever in 24 hours
Majority do not require treatment. Acute treatment with
benzodiazepines +/- phenytoin/phenobarbital occasionally required if
recurrent within 24 hours or prolonged.
Epilepsy
Epilepsy: a disorder of the brain characterised by an enduring
predisposition to generate epileptic seizures and by the neurobiologic,
cognitive, psychological and social consequences of this condition
Epilepsy syndrome: a complex of signs and symptoms, investigation
findings (EEG, MRI), treatment response and prognosis that define a
unique epileptic condition, e.g. benign rolandic epilepsy
Epileptic disease: A pathologic condition with a single specific well-
defined aetiology, e.g. Dravet syndrome.
Important paediatric epilepsy syndromes

Infantile spasms (West syndrome)
 Epileptic encephalopathy of infancy (seizures are so severe the brain
function and development are affected)
 Incidence: 1-in-4,000 to 1-in-6,000 live births
 Peak frequency: 4–6 months of age
 Triad of epileptic spasms (flexor, extensor, mixed), hypsarrhythmia on
EEG and cognitive/developmental deterioration
Aetiology:
 Idiopathic (<5%)
 Symptomatic
 Disorders of cerebral development
 Neuronal migrational/developmental, e.g. heterotopia, dysplasia,
hemimegalencephaly
 Neurocutaneous syndromes, e.g. tuberous sclerosis, Sturge-
Weber, neurofibromatosis
 Metabolic and degenerative disorders
 Metabolic disorders, e.g. phenylketonuria, non-ketotic
hyperglycinaemia, pyridoxine def.
 Degenerative disorders of uncertain aetiology, e.g.
leucodystrophies, Alpers’ disease
 Perinatal or postnatal chronic acquired cerebral lesions
 Hypoxic-ischaemic encephalopathy and cerebral infarction
 Cerebral trauma
 Cerebral tumour
 Maternal toxaemia
 Metabolic and endocrine disorders
 Infantile spasms evolving from neonatal seizure syndromes, e.g.
Ohtahara’s syndrome
 Prognosis: Guarded. 75–90% have developmental delay. Risk of
developing Lennox Gastaut syndrome. Prognosis better with
idiopathic West syndrome.
 Treatment:
 Oral corticosteroids (prednisolone) or adrenocorticotropic
hormone (ACTH)
 Vigabatrin
 Ketogenic diet
 Other medication, e.g. Topiramate, Pyridoxine
 Surgical treatment for underlying focal cortical dysplasias
Neurology 469
Lennox-Gastaut syndrome
 Age of onset 1–14 years
 Severe epileptic disorder with triad of:
 Multiple seizure types, typically tonic, atypical absence, tonic,
myoclonic and tonic-clonic seizures
 Elecroencephalogram — diffuse, slow spike-and-wave 1–2.5 Hz
complexes, slow background
 Diffuse and severe cognitive impairments, learning disability
 Status epilepticus common, especially non-convulsive forms
 Aetiology: many causes, about 25% are cryptogenic
 Prognosis for seizure control and mental development poor
 Treatment: Medication: sodium valproate, benzodiazepines, e.g.
clobazam/nitrazepam
 Commonly refractory to medication
 Surgery: Corpus callosotomy for drop attacks, Vagus Nerve
Stimulator
Benign rolandic epilepsy

 Estimated 15% of all childhood epilepsy; age of onset 5–10 years
 Typically infrequent seizures in sleep, sometimes awake/asleep,
rarely only when awake
 Simple partial seizures of the face, oropharynx and upper limb, at
times with secondary generalisation
 Normal neurological examination, normal intelligence
 Elecroencephalogram — Centrotemporal spikes
 Treatment: e.g. sodium valproate indicated if frequent seizures or
cognitive impairments
 Excellent prognosis with remission by mid-teenage years
Childhood absence epilepsy

 School-age children with a peak age of 6–7 years, 2–8% of all cases of
epilepsy
 Normal neurologic examination
 Absence seizures: brief (5–10 secs) staring and unresponsive,
behavioural arrest, sometimes with eyelid fluttering, automatisms,
mild clonic movement of upper limbs
 Induced by hyperventilation (3–5 mins)
 Treatment with sodium valproate, ethosuximide. Made worse by
carbamazepine
Juvenile myoclonic epilepsy (JME)

 Generalised epilepsy with multifactorial inheritance
 Early morning sudden myoclonic jerks, generalised tonic-clonic
seizures. 33% have absence seizures
 Onset in adolescence (range 12–18 years)
 Interictal EEG — Generalised polyspike and spike-and-wave
discharges at 4–6Hz
 Valproate usually controls seizures, treatment may be life-long
Evaluation
 Determine whether patient does or does not have seizures (seizures
vs non-seizures)
 Determine the seizure type or syndrome
 Determine aetiology where possible
 Assess co-morbidity
 Formulate a management plan
Diagnosis is based almost exclusively on a clinical history of two or more

unprovoked seizures.
 Careful and detailed history
 Seizure or non-seizure
 Clear description of seizure episode, circumstances, precipitants,
frequency of attacks, symptoms before and during the
attacks (including physical symptoms, psychic symptoms and
impairment of consciousness), duration of symptoms, symptoms
after the attack, incontinence
 Past medical history, including head injury, medications
 Developmental history
 Social history
 Family history
 Neurological and physical examination
 Diagnostic Studies
 Electroencephalography (EEG)
 Value — Confirming abnormal electrical activity and
syndromic classification
 Limitations:
 Non-specific
 Interpretation requires special knowledge and experience
 Easily affected by drugs, toxic or metabolic changes
 Does not elucidate cause
Neurology 471
 Elecroencephalography cannot be used to make the diagnosis

of epilepsy unless an actual seizure is recorded
 First EEG can be normal in 50% of persons with epilepsy
 A small percentage of normal children have epileptiform
activity on EEG but never have a seizure
 Brain imaging — CT if emergency, MRI preferred
 Indicated in focal epilepsies, neurological deficits, young age,
difficult-to-control seizures
 Not required in Benign Rolandic Epilepsy, Childhood Absence
Epilepsy
 Laboratory tests, lumbar puncture as indicated
Aetiology
 Idiopathic
 Symptomatic — Underlying brain pathology
 Hypoxia/trauma
 Malformations
 Meningitis/encephalitis
 Tumours
 Stroke
 Cerebral degeneration
 Toxins/metabolic dysfunction/inborn errors of metabolism
 Cryptogenic — Symptomatic with lack of clear aetiology
Treatment
 Aim: Stop or reduce seizures,maintain quality of life
 Establish firm diagnosis of epilepsy before starting treatment
 Consider seizure type, severity, recurrence risk, epilepsy
syndrome, aetiology, co-morbidity, precipitants
 Mainstay of treatment — Anti-epileptic drugs (AEDs).
 Indications to treat:
 Recurrent seizures, severity, epilepsy syndrome
 Presence of risk factors
 Accompanying neurological, psychosocial problems
 Initiate monotherapy using appropriate medication, titrating up to a
maintenance dose
 Balance between drug efficacy and tolerability
 Holistic approach — Psychosocial management and epilepsy
support important
 Duration of therapy
 Usually 2 years but syndrome diagnosis and treatment response
important
 70% will respond to first or second medication; 30% do not respond.
 Children seizure-free for 2 years will have seizure recurrence in
30% on stopping medication
 Other treatment modalities

 Epilepsy Surgery
 Special diets, e.g. ketogenic diet
Bibliography
1. Update of Epilepsy in Paediatric Patients. Mayo Clinic Proceedings Vol 71 (9) Sept 1996.
2. Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes.
Epilepsia 1989; 30:389–399.
ENCEPHALOPATHY
DEFINITION
Any diffuse disease of the brain that alters brain function or structure.
Hallmark of presentation is with altered mental state, and not easily
recognised in newborns, infants or children. Though uncommon in
children, prompt recognition and initiation of treatment is important as
it can be associated with significant mortality and long-term morbidity.
Clinical presentation:
Subtle — Behavioural or personality changes
loss of memory and cognitive ability
Obvious — Lethargy, progressive loss of consciousness.
There may be specific localising features such as seizures, ataxia or other

focal motor signs. Systemic features such as fever, vomiting, lethargy,
loss of appetite and headache may also be present.
Neurology 473
Differential diagnosis:
The following list includes the common causes but is not exhaustive.
 Infections and parainfections (bacterial, virus, fungal)
 Autoimmune causes (e.g. CNS vasculitis, Hashimoto’s
encephalopathy, N-methyl-D aspartate receptor antibody
encephalitis, voltage gated potassium antibody encephalitis)
 Space occupying lesions (haemorrhage, malignancy)
 Seizure related (Non-convulsive status, post ictal, epileptic
encephalopathy)
 Toxins (e.g. drugs, radiation, certain metals)
 Metabolic (uraemia, hyperammonaemia, hyper/hypoglycaemia,
lactic acidosis, liver failure, mitochondrial disorders)
 Hypertensive encephalopathy
 Hypoxic/ischaemic causes (Hypoxic ischaemic encephalopathy, near
drowning, stroke, venous thrombosis)
A detailed history can help to establish a possible aetiology. History

should include:
 Timing and nature of deterioration
 Recent febrile illnesses
 Presence of any systemic symptoms such as rash
 History of travel or contact with animals
 Likelihood of toxin exposure
 History of trauma
 Significant past medical history including pre-existing neurological
status, development, birth history, detailed vaccination history
 Family history of neurological, metabolic, vascular, haematological
disease. History of parental consanguinity.
Clinical assessment
Initial assessment should be ABC (Airway, Breathing and Circulation).
 Assessment of the child with altered consciousness should include
the following:
 Depth of altered consciousness using the Glasgow coma scale
(GCS) or modified GCS for children younger than 5 years (see
Table 12-2). Consider ICU admission if GCS is <9.
 In a child with mild encephalopathy, clinical presentations may
be subtle. Assess orientation and memory with the mini mental
state exam (see Table 12-3).
Table 12-2: GCS and MGCS

Glasgow Coma Scale Modified Coma Scale for Infants
Eye opening Eye opening
Spontaneous 4 Spontaneous 4
To speech 3 To speech 3
To pain 2 To pain 2
None 1 None 1
Verbal Verbal
Oriented 5 Coo/babbles 5
Confused 4 Irritable 4
Inappropriate words 3 Cries to pain 3
Non specific sounds 2 Moans to pain 2
None 1 None 1
Motor Motor
Follows commands 6 Normal spontaneous movements 6
Localises pain 5 Withdraws to touch 5
Withdraws to pain 4 Withdraws to pain 4
Abnormal flexion 3 Abnormal flexion 3
Abnormal extension 2 Abnormal extension 2
None 1 None 1
Table 12-3: Mini mental state exam

Orientation:
Date and place of birth
Registration:
‘I shall say 3 words for you to remember. Repeat them after I have said them.’
Mental Reversal:
Spelling ‘WORLD’ backwards; 5 serial subtractions of 7
First Recall:
Recalling the 3 words the patient is asked to remember
Temporal orientation
Year; Month; Day of month; Day of week
Spatial orientation
Country; place
Naming
Objects; body parts
Three-stage Command
E.g. ‘take this paper with your left hand, fold it in half, and hand it back to me’
Neurology 475
 Brain stem examination for possibility of herniation: posture,

tone, peripheral and plantar reflexes, oculocephalic reflexes, pupil
size and pupillary response to light, respiratory pattern. Note that
drugs, toxins, and metabolic abnormalities may mimic signs of
herniation.
 Signs of meningism: bulging fontanelle in an infant, nuchal
rigidity or positive Kernig’s sign in older children.
 Signs of raised intracranial pressure: falling coma score,
Cushing’s reflex with hypertension and bradycardia, abnormal
pupil responses, decerebrate and decorticate position, altered
breathing patterns and papilloedema.
 Seizures are important to recognise. These may be subtle and
include tonic eye deviation, tonic or clonic movements of the face
of limbs.
Investigations
Investigations should be tailored to each individual child in discussion
with neurologists, based on history and examination findings and may
include:
 Full blood count, electrolytes, Ca, Mg, PO4, ESR, CRP, LFT, plasma
glucose, TFT, ammonia.
 Serology and virology studies: blood cultures, nasopharyngeal
aspirate, and mycoplasma throat swab/serology.
 Lumbar puncture for cerebrospinal fluid analysis unless
contraindicated: Opening pressure, microscopy, culture, latex
agglutination if there has been prior antibiotics treatment, Viral PCR
(enterovirus, herpes simplex virus, mycoplasma)
 Consider the following second-line investigations if clinically
indicated and previous investigations have been unremarkable.
Screen for autoimmune causes: ANA, dsDNA, anti-thyroglobulin, anti-

thyroperoxidase antibodies (TFT can be normal)
Screen for metabolic causes: Lactate, serum amino acids, urine organic
acids
 Neuroimaging: MRI is the preferred imaging modality. CT brain may
be ordered to exclude neurosurgical emergencies such as a space
occupying lesion or an intracranial bleed. Magnetic resonance
angiography/spectroscopy can be helpful but may not be indicated
in all cases.
 Electroencephalogram (EEG): May be considered if there is any
concern regarding subclinical seizures.
Management
The need for supportive management such as ICU care, management of
raised intracranial pressure with initiation of neuroprotective measures,
should be considered in any child presenting with altered mental status.
Specific treatment should be guided according to the likely aetiology.
In many circumstances, it is appropriate to initiate broad-spectrum

antimicrobials and antiviral treatment pending the results of diagnostic
studies. The first-line treatment regimen is ceftriaxone 100mg/kg/day,
acyclovir 10mg/kg/dose 8 hourly, and depending on clinical suspicion,
ciprofloxacin to cover for mycoplasma or rickettsial infections.Treatment
of acutely reversible causes such as hypoglycaemia and electrolyte
abnormalities should be promptly recognised and treated. Anticonvulsant
medications may be required to control and/or prevent seizures, if present.
Bibliography
1. Thompson C, Kneen R, Riordan A, Kelly D, Pollard A. Encephalitis in children. Arch Dis Child
2012;97:150–161.
2. Davies E, Connolly DJ, Mordekar SR. Encephalopathy in children: an approach to
assessment and management. Arch Dis Child 2011.
3. Kirkham FJ. Non-traumatic coma in children. Arch Dis Child 2001 85:303–312.
Neurology 477
STROKES IN CHILDREN
Pediatric stroke is more common that perceived, with an incidence of
13/100,000 person-years. Up to 45% are haemorrhagic, unlike adults (20%).
Presentation can be subtle, is commonly missed and often results in
presentation >48–72 hours after onset. These include:
Children Neonates
Weakness/numbness of face/arm/leg Seizures
Difficulty walking due to focal weakness/ Severe sleepiness
incoordination
Slurred speech/aphasia/difficulty Paucity of movement on one side
comprehending
Severe headache/dizziness
Visual abnormalities
Focal seizures followed by weakness

Aetiology
Risk factors differ at different ages in the paediatric population and can
be ischaemic or haemorrhagic.
Children aged 1 month to 18 years

Ischaemic Haemorrhagic
Intracranial infections Arterial dissection Vascular abnormalities
Trauma Vasculitides Bleeding diatheses
Congenital/acquired heart Extracorporeal Malignancy
disease membrane oxygenation
(ECMO)
Blood disorders Idiopathic
Moyamoya disease
Children aged birth to 28 days

Cardiac disease Placental issues Dehydration
Blood disorders Vascular abnormalities Extracorporeal membrane
oxygenation
Infections Trauma/catheterisation Idiopathic
Maternal factors Birth asphyxia
Cerebral sinus venous thrombosis (CSVT)

This can result in venous infarcts or haemorrhage. It may present as
strokes above or have a more protean manifestation. Risk factors include
dehydration, sinus/ear infections, head/neck trauma, blood disorders,
cancer, immunological diseases and head/neck surgery.
Suspicion should prompt addition of MR venogram to MRI brain

imaging and other investigations.
ACUTE MANAGEMENT PROTOCOL FOR PAEDIATRIC STROKES

(1 month-18 years)
Acute presentation with clinical symptoms and signs of stroke:
 Evaluate Airway, Breathing, Circulation
 Intravenous hydration full maintenance (do not fluid restrict)
 High flow oxygen (5L/min) regardless of oxygen saturation to reduce
ischaemic penumbra
Neuroimaging:
 Computed tomography brain useful for diagnosing space occupying
lesions and haemorrhagic stroke
 Magnetic resonance imaging (with diffusion-weighted imaging and
MR angiogram) superior for ischaemic stroke, vasculitides
Evaluate for aetiology based on history, examination findings and
neuroimaging
Other investigations, anti-platelet and anticoagulation therapy

should be tailored to individual patients based on the above and in
consultation with the attending Paediatric Neurologist.
Neurology 479
BELL’S PALSY IN CHILDREN
 Bell’s palsy (BP) is an acute, peripheral facial nerve paralysis of

unknown cause. It is possibly due to inflammation and oedema of
the peripheral facial nerve.
 Incidence in children is lower (6.1 per 100,000 person years)
compared to adult (20 per 100,000 person-years). Recovery in
children is better (up to 90%) compared to adult (up to 70%).
 The key to diagnosis lies in good clinical history and thorough clinical
examination. It is crucial to exclude other conditions with similar
presentations.
 Differential diagnoses of facial nerve paralysis include:
 Upper motor neuron causes: Stroke, malignancy
 Lower motor neuron causes: Herpes zoster (Ramsay Hunt
Syndrome), otitis media, parotid gland lesion, trauma, leukaemia,
hypertension, systemic neuromuscular diseases (e.g. myasthaenia
gravis)
 Suggested clinical approach
 History:
 Important to establish that symptoms of facial nerve palsy is
acute and isolated. Child should be otherwise well.
 Physical examination
 Complete thorough neurological examination:
 Forehead muscles should be involved.
 Other cranial nerves should be normal.
 Peripheral neurological examination should be normal.
 Otherwise, neurology consult and neuroimaging (where
appropriate) should be considered.
 Ear examination:
 It should normal with no vesicles or sign of inflammation.
 Otherwise, ENT consult should be considered.
 Parotid gland: It should be normal.

 Blood pressure: To exclude hypertension.
 Systemic examination: Child should be well. To look out for signs
of easy bruising, pallor, organomegaly etc
 Management
 To improve facial function recovery in adult with BP, steroid
treatment is recommended while antiviral treatment (e.g.
acyclovir) has a probable modest benefit.
 There is a lack of evidence that either steroid treatment or

antiviral treatment will be beneficial for children with BP.
 Supportive measures like eye patching and eye drops should be
instituted when BP is diagnosed.
 Child should be followed up regularly to monitor for
complications (e.g. exposure keratitis) and to watch for gradual
recovery of facial function.
 Key points
 Children with BP mostly recover well without any specific
treatment.
 It is important to exclude other conditions that mimic
presentation similar to BP. This can be achieved with thorough
history taking and competent clinical examination.
Bibliography
1. Lunan R, Nagarajan L. Bell’s palsy: a guideline proposal following review of practice.
Journal of Paediatrics and Child Health 44(2008):219–220
2. Gronseth GS, Paduga R. Evidence-based guideline update: Steroids and antivirals for Bell
palsy: Report of the Guideline Development Subcommittee of the American Academy of
Neurology. Neurology (2012) Nov 27;79(22):2209–13
3. Pitaro J, Waissbluth S, Daniel S.J. Do children with Bell’s palsy benefit from steroid
treatment? A systematic review. International Journal of Pediatric Otorhinolaryngology 76
(2012):921–926
4. Űnűvar E, Oğuz F, Műjgan S, Kılıc A. Corticosteroid treatment of childhood bell’s palsy.
Pediatric Neurology Vol.21 No.5 (1999):814–816
481
PAEDIATRIC SURGERY
COMMON NEUROSURGICAL PROBLEMS
HEAD INJURY
Head injury is the most common neurosurgical problem encountered
in children. The majority will have minor head injury (defined by a GCS
of 14–15) and will recover fully, but a small number will deteriorate
and develop severe neurological sequelae, usually from secondary
brain injury or the presence of an intracranial haematoma. The aim is to
identify this group of children.
The history and clinical findings may provide an indication of the

severity of the injury.
 A history of a fall from a height of >1m or involvement in
a road traffic accident is significant
 The conscious state of the child is an important indicator of the
presence of an intracranial lesion
 Clinical examination in children younger than 2 years may be difficult
and unreliable
Skull X-rays are not useful predictors of the presence of an intracranial

haematoma, although they are useful for detecting a skull fracture.
Suggested indications for skull X-rays are:
 Suspected penetrating injury
 Suspected depressed fracture
 Compound skull fracture
 Child younger than 2 years with ‘boggy’ scalp haematoma
 Suspected child abuse
Computed tomography (CT) head is the procedure of choice for

assessment of acute head injury in children. Although there are recent
concerns about the relatively high dose of radiation associated with a
CT scan in a small child compared to an adult, a CT head is indicated
whenever the presence of an intracranial lesion is suspected, based on
history or clinical examination.
Initial Management
 Assess the ABCs
 Prompt ventilatory support and treatment of shock are mandatory to
prevent secondary brain injury
Management of Minor Head injury (GCS 14–15)

 Two hourly neurological observations for 6 hours, then reduce
frequency if stable
 Intravenous drip if child is dehydrated as a result of vomiting.
Analgesic (paracetamol), anti-emetics (domperidone, ondansetron) if
indicated
 CT head if child deteriorates clinically (drop in GCS >2 points is significant)
Management of Moderate Head Injury (GCS 9–13)

 Resuscitate if necessary
 Urgent CT head, urgent pre-operative blood tests including GXM and
coagulation profile.
 Admit to Children’s Intensive Care Unit (CICU) or High Dependency
(HD), depending on clinical status. Hourly neurological observations
 Nil orally, IV drip, IV Ondansetron for vomiting and wretching
 Neurosurgical operation where indicated
Management of Severe Head Injury (GCS 8 and below)

 Resuscitate — Intubation and ventilation mandatory. * It is important
to avoid excessive hyperventilation PCO2 <30mmHg
 To ensure patient is fully sedated and paralysed if necessary (patient
should not be gagging or moving while intubated)
 Urgent CT head, urgent pre-operative blood tests including GXM and
coagulation profile
 To OT directly for neurosurgical operation if indicated, or to CICU
(ICP monitoring indicated)
 Manage according to severe head injury protocol with aggressive
neuro-protective measures
 Non-accidental injury should be suspected when the history given
and/or the clinical findings are suspicious. The presence of a
sub-dural haemorrhage in an infant is highly suspicious
Post-traumatic Epilepsy
 Immediate seizure: Seizure occurring at moment of impact; usually
does not have any long term sequelae, no need for CT or anti-
convulsants if child is well
Paediatric Surgery 483
 Early or late seizures: Need further investigations and assessment by

paediatric neurologist
NEUROSURGICAL EMERGENCIES
Neurosurgical emergencies are the result of one or more of the
following:
 Rapid disruptive or compressive forces distorting or disrupting part
of the nervous system, e.g. intracranial haemorrhage, direct trauma
 The blood supply to a portion of the brain is interrupted by a
thrombus in or an occlusion of a vessel, e.g. ischaemic stroke,
traumatic carotid artery dissection
 Loss of perfusion pressure of the entire cerebral hemisphere from
decrease in systemic BP or increased ICP
BRAIN HERNIATION SYNDROMES

An expanding mass lesion in or outside the brain will soon exhaust the
capability of the brain and CSF to tolerate the added volume within the
closed calvaria. The ICP rises and this causes movement or herniation of
brain tissue across the natural boundaries of dura and bone, leading to
clinically and anatomically characteristic brain herniation syndromes.
These have a profound effect on neurological function, resulting in high
morbidity and mortality.
Herniation usually results from:

 Intracranial haemorrhage — Spontaneous or traumatic
 Progressive regional or diffuse brain oedema (cerebral ischaemia,
infarction, hypoxia, encephalopathy)
 Disturbance of CSF equilibrium in the setting of raised ICP, e.g. after
LP in patient with supratentorial mass lesion
Types of Brain Herniation

 Transtentorial herniation (uncal herniation):
 Classical triad of loss of consciousness, unilateral pupillary
inequality (anisocoria) and contra-lateral hemiparesis
 Seen for example, in extradural haematoma involving temporal
region
 Cerebellotonsillar herniation:
 Seen in rapidly expanding cerebellar mass lesion, e.g.
spontaneous cerebellar haemorrhage, or haemorrhage into a
medulloblastoma
 Increasing drowsiness and sudden respiratory arrest are
presenting symptoms
Management of Brain Herniation Syndromes

 Resuscitate ABCs — Intubation and ventilation if GCS ≤8
 Hyperventilation, *It is important to avoid excessive hyperventilation
PCO2 <30mmHg
 Intravenous mannitol
 Urgent CT head to determine cause
 Surgical management of cause
 Monitoring in CICU
ACUTE HYDROCEPHALUS
Hydrocephalus is the result of an imbalance in CSF production and
resorption. The time course of ventricular enlargement is usually
hours although this can occur over days. There must be clinical
signs or evidence of raised ICP. In most instances, the cause of acute
hydrocephalus is obstructive in nature can lead to sudden neurological
deterioration. The diagnosis must be suspected early and confirmed by
clinical and radiological exams, either CT or MRI.
Aetiology of Acute Hydrocephalus in Children.

 Shunt obstruction in a shunted child
 Brain tumour — Posterior fossa (e.g. medulloblastoma), suprasellar
(e.g. craniopharyngioma)
 Acute exudative meningitis
 Head trauma, e.g. epidural haematoma in posterior cranial fossa
 Intraventricular haemorrhage, e.g. ruptured AVM
Medical Treatment
 Head position raised to 30˚
 Respiratory management — Intubate and ventilate (if GCS <9.
Restrict fluids, osmotic agents, diuretics)
 BP control, * It is important to note the presence of Cushings
Response to a rising ICP and not give anti-hypertensives.
Surgical treatment
 Ventriculostomy (EVD)
 Shunt
 Endoscopic third ventriculostomy (ETV — In cases of obstructive
hydrocephalus)
 Revise shunt (in shunted child with blocked shunt)
 Mass lesion causing hydrocephalus — EVD/remove mass lesion
ACUTE SHUNT MALFUNCTION

Symptoms
Symptoms consistent with increased ICP (e.g. headaches, nausea and
vomiting), which progresses to lethargy, stupor and coma. These are
signs of brainstem compression and if untreated, will lead to respiratory
failure and death. Symptoms can occur rapidly, within a few hours in
those who are shunt-dependent. It is important to speak to parents to
determine if the child’s behaviour is abnormal.
Clinical Findings
 Irritability, progressing to decerebrate posturing
 Gaze impairment or abnormal pupillary responses
 Focal neurological signs
Investigations
 Computed tomography scan or MRI (old films may be required for
comparison)
 Shunt X-ray series — Skull X-ray AP/Lateral, Chest and Abdomen
X-ray AP
 Shunt tapping (only if ordered by neurosurgeon, and to be done by
neurosurgical team)
Treatment
 Intravenous mannitol (to consult neurosurgeon before giving)
 Shunt tapping to release CSF (possible only if blockage is in distal
end of shunt)
 Urgent revision of shunt
Child with Ventriculoperitoneal (VP) Shunt and Acute

Abdomen
 Inform neurosurgeon
 The shunt may need to be externalised even if no surgery is
indicated for the acute abdomen
 If laparotomy is required, externalisation of shunt can be done at the
same setting
SPONTANEOUS INTRACEREBRAL HAEMATOMA IN

CHILDREN
Causes
 Arteriovenous malformation rupture
 Haemorrhage into tumour
 Coagulopathy, e.g. haemophilia, leukemias
 Vasculopathy — Moya-moya Disease, vasculitis

 Post-operative haemorrhage
 Aneurysmal subarachnoid haemorrhage
Management
 Resuscitate as for mass lesion (see “Brain Herniation Syndromes”)
 Urgent CT scan to determine cause
 Do PT, aPTT and treat coagulopathy if present, aggressively with
transfusion FFP.
 Cerebral angiogram and/or MRI/Magnetic Resonance Angiogram
(MRA)/CT angiogram if indicated
 Neurosurgical treatment where and when appropriate
INTRACRANIAL INFECTIONS
 Epidural empyema, e.g. Pott’s puffy tumour
 Subdural empyema, e.g. secondary to sinusitis or HIB meningitis
 Intracerebral abscess
Management
 Diagnosis confirmed on CT scan or MRI (+/- contrast enhancement)
 Drainage by craniotomy or burrhole; aspiration or excision of
intracranial abscess
 Appropriate IV antibiotics for 4–6 weeks
SPINAL INJURIES
 Traumatic spinal injury
 Spinal Cord Injury Without Radiologic Abnormality (SCIWORA)
 Spinal cord compression from epidural (extradural) masses
 Intraspinal haemorrhage (tumour, AVM, AV fistula)
 Spinal infections
Management
 Spinal nursing if instability suspected
 Intravenous dexamethasone or methylprednisolone where indicated
 Urgent MRI
 Surgical decompression where indicated
 Surgical stabilisation where indicated
THE ACUTE ABDOMEN
INTRODUCTION
The baby or child presenting with acute abdominal pain represents
a common undifferentiated problem that may be medical or surgical
in nature. The possible underlying causes range from simple mild
gastroenteritis to rare but life-threatening conditions like malrotation
with volvulus. It is important to recognise surgical diagnoses early
because generally investigations and treatment need to be performed
much more urgently compared to medical causes. This chapter outlines
an approach to the paediatric acute abdomen and describes some
common surgical conditions and less common but important surgical
emergencies.
CLINICAL PICTURE
The likely diagnoses are guided by both the age and the symptom
complex. Certain diagnoses are more common according to the age of
presentation (see Table 13-1).
In terms of the symptoms, the patient may present predominantly with

pain or with vomiting or both. If the predominant symptom is:
 Pain
 Constant pain aggravated by movement — The main surgical
conditions to exclude will be those causing peritonitis or
ischaemia.
 Colicky pain — Consider obstruction
 Vomiting — Then the main surgical conditions to exclude will be
those causing intestinal obstruction
Symptom complex Examples of “ medical” conditions Examples of “surgical” conditions
Pain or peritonitis + pancreatitis, gastroenteritis, appendicitis, Meckel’s diverticulitis,

ischaemia constipation, urinary tract infection perforated ulcer, torsion ovary, bowel
ischaemia from incarcerated hernia
Vomiting or intestinal Overfeeding, gastroenteritis, pyloric stenosis, malrotation with
obstruction constipation, gastroesophageal volvulus, intussusception, adhesive
reflux disease, meningitis obstruction
Table 13-1: Age-related differential diagnoses of patients presenting with abdominal pain and/or
vomiting. Only the more common and a few urgent uncommon causes are listed
Diagnoses/Age Group Baby Toddler Child Adolescent
Abdominal “Surgical” Causes
Intussusception
Incarcerated hernia
Malrotation with volvulus
Appendicitis
Meckel’s diverticulum obstruction/infection
Testicular torsion/ovarian torsion
Ectopic pregnancy
Hirchsprung’s disease
Pyloric stenosis
Trauma (including possible child abuse)
Choledochal cyst
Solid tumour with bleed
Abdominal “ medical “ causes
Acute gastroenteritis
Mesenteric adenitis (associated with viral illness)
Gastroesophageal reflux disease
Urinary tract infection
Constipation colic
Functional abdominal pain
Inflammatory bowel disease
Peptic ulcer disease
Hepatitis, pancreatitis
Pneumonia
Diabetic ketoacidosis
Pelvic inflammatory disease, dysmenorrhea
Henoch Schonlein Purpura
Dengue
Higher possibility Moderate possibility Low possibility

HISTORY AND PHYSICAL EXAMINATION

Key points in the history include:
 Feeding — Current feeding regimen, appetite, feeding problems,
last meal or feed, and most importantly if the child potentially needs
surgery, instruct NIL BY MOUTH until further review
 Vomiting — Colour of vomitus, volume, duration and frequency
 Urine output — As indicator of hydration status
 Bowel output — Constipation, diarrhoea, presence of blood or
mucus in stools
 Abdominal pain — Intensity, site, type (constant or intermittent),
change in pain type or site. Associated features, e.g. not moving
(peritonitis) vs. colicky (‘rolling around’, drawn-up legs with pallor).
Associated abdominal distension.
 Relevant prior history — Solitary or repeated events, previous
surgery, travel history
 Medication and allergies — Antispasmodic medication, antibiotics,
analgesia
The sequence of symptoms, e.g. pain and change in bowel habits and /
or timing of medication is important to differentiate between some of
the common differential diagnoses like appendicitis and gastroenteritis.
The physical examination is directed toward assessment of general

status (especially hydration and sepsis) and establishing a working
diagnosis. In an uncooperative child, abdominal examination may be
difficult and requires patience. Giving sedation for examination may
mask important signs and should not be done without consulting a
senior doctor. A full abdominal examination includes checking the
inguinal hernia orifices, external genitalia and perineum. Gentle per
rectal examination is necessary in some situations. If inexperienced,
this can be deferred until a senior doctor is available, to reduce need for
repeat examination.
INVESTIGATIONS
Please use good clinical judgment when ordering investigations so as to
reduce patient distress, radiation risk and cost.
Common screening tests

 Full blood count — Anemia, blood loss, bacterial vs viral infections,
platelet count
 C-reative protein — Occasionally useful as infective marker
 Urea, electrolytes and creatinine — Hydration status, electrolyte

derangements, pre-operative assessment
 Prothrombin time/aPTT and group and cross match — For major
surgery or if there are other conditions such as liver impairment
 Urinalysis +/- Urine culture — Pyuria, nitrites, ketones, crystals,
stones, haematuria
 Abdominal x-ray — Supine AXR is preferred. If suspecting intestinal
obstruction, an additional erect or lateral decubitus view is useful.
Look for soft tissue masses, calcifications (faecolith, stones), bowel
distension, bowel gas distribution and bowel wall thickness.
Other tests (as indicated in specific situations)

 Liver function tests, amylase — When liver or pancreatic disease is
suspected
 Chest x-ray — To look for lower lobe pneumonia, effusion,
concomitant lung pathology, aspiration pneumonia
Specialised imaging
 Abdominal ultrasound — Commonly ordered for suspected
appendicitis, pyloric stenosis and intussusception. Useful as screen
for solid organ masses and occasionally for abscess collections.
However, note that there is limited accuracy in obese patients,
patients with gaseous bowel distension and abdominal trauma
injuries
 Computed tomography scan — Associated with radiation risk.
Requested only where the abdominal ultrasound is unable to
accurately visualise the necessary information.
 Contrast study — Upper GI study is procedure of choice to rule out
malrotation with volvulus
 Air enema — Therapeutic procedure in intussusception performed
by the radiologist under fluoroscopy guidance, without sedation.
More details under section on intussusception.
 Meckel’s scan — Radioisotope scan; done electively and patient
requires 24 hours pre-scan H2 antagonists. Diagnostic accuracy is
about 80–85%.
MANAGEMENT
 Fluid resuscitation — Children with surgical acute abdomen are
often dehydrated, with hidden third space loss, particularly with
intestinal obstruction. Consider intravenous saline 10ml/kg boluses
in addition to maintenance fluids. Replace specific losses, and correct
electrolyte imbalance. Monitor heart rate and urine output to assess

response.
 Intestinal decompression — Nil by mouth, insert a good size
nasogastric tube for hourly aspiration and passive drainage in-
between, until intestinal function is ascertained or re-established.
Replace nasogastric losses using ml for ml saline mix (500ml NS with
10ml of 7.45%KCL)
 Surgery — The surgeon will discuss surgical options with the
parents/caregiver. Once confirmed, institution practice requires
the following: obtain written informed consent from parent/
legal guardian, fill in and fax OT chit to OT reception and inform
anaesthetist on-call. Trace all pending investigations; ensure blood or
blood products are available if required.
 Pain management — While under observation, limit strong
sedation and opioid analgesia until the diagnosis has been
established and definitive management decided. It is important to
treat the cause of pain, rather than just the symptom.
COMMON AND IMPORTANT SURGICAL CONDITIONS
Incarcerated Inguinal Hernia

 Clinical examination should make the diagnosis immediately evident
 Differential, may include an encysted hydrocoele of the cord and
torsion of an undescended testis.
 Try to reduce the hernia by gentle traction and pressure. Sedation
and analgesia may be helpful, but ensure adequate hydration and
monitoring of the child
 An easily-reduced hernia can be reviewed in clinic and scheduled on
next elective list. Difficult reductions and other cases like neonates
who are at high risk of re-incarceration should be discussed with the
surgeon. Admission and immediate surgery is required if irreducible.
Infants have higher risk of contralateral hernia, so bilateral
herniotomy is usually advised.
Malrotation and Volvulus

 Typically occurs about Day 3 to Day 5 in an otherwise well baby.
Majority present in infancy. In older children, the presentation is that
of recurrent abdominal pain and failure to thrive.
 Bilious (green) or yellow vomiting may be the only presenting
complaint so high index of suspicion is needed.
 Failure to recognise volulus is catastrophic as it results in gangrene of
the entire small bowel, resulting in life-threatening sepsis and short

gut syndrome
 Abdominal signs are often absent. A red and shiny abdomen
indicates imminent gangrene and urgent surgery is required without
waiting for contrast study
 Abdominal x-ray may be normal or may show an abnormal gas
distribution pattern
 Contrast upper GI study is diagnostic with abnormal duodenojejunal
position showing malrotation and/or cork-screw appearance
signifying volvulus
 Operative repair includes detorsion of the bowel and a Ladd’s
Procedure which includes an appendicectomy, widening of the small
bowel mesentery with reorganisation of position of small bowel to
the right side of the abdomen and the large bowel on the left.
Intussusception
 Most commonly occurs between 5–9 months and up to 3 years old
 Typically idiopathic and preceded by URTI or a febrile episode. In
recurrent cases and older children, need to consider a pathological
lead point like Meckel’s diverticulum or polyp.
 Classic history of intermittent severe abdominal colic with drawing
up of legs, pallor and vomiting of undigested food. Red-currant-jelly
stools are less common and represent late presentation.
 Physical examination — Abdominal distension, occasionally palpable
mass in the right hypochondrium (RHC).
 Abdominal x-ray — May show RHC soft tissue mass or dilated bowel
loops. However, frequently non-diagnostic and is mainly indicated if
perforation is suspected.
 Ultrasound — Accuracy is operator-dependent, hence in centres that
lack this expertise, a diagnostic air enema may be recommended
instead. Confirmatory if target lesion or pseudokidney sign is seen.
 Management — Arrange with the radiologist for air enema reduction.
Secure venous access and ensure adequate fluid resuscitation before
procedure. Air enema is contraindicated if there is clinical suspicion
of peritonitis. There is rare risk of bowel perforation. In KKH, air enema
success rate is >85%. Institution protocol requires that the baby
receives prophylactic antibiotics during the procedure and pre-
operative blood investigations are available.
 Surgery is required as first-line treatment in a child presenting in
shock or with peritonitis or after failed air enema reduction. Surgery
may entail laparoscopic or open reduction and/or resection of
gangrenous bowel.
 Recurrent intussusception is reported in up to 15% of children, with

highest risk occurring within the first 24 hours.
Paralytic Ileus
 Common between 2–5 years of age
 Often preceded by gastroenteritis, and several visits to different
doctors. Antispasmodics are often prescribed to treat abdominal colic
from gastroenteritis. In young children, these ingested medications
exacerbate paralytic ileus secondary to the gastroenteritis.
 On clinical examination, the abdomen is generally distended, but
soft. There may be generalised tenderness. Abdominal x-ray may
show generalised small and large bowel distension with some air/
fluid levels.
 Differential diagnoses include intestinal obstruction from other
causes, e.g. perforated appendicitis with pelvic abscess
 Treatment is by a period of gut rest. A flatus tube for colonic
decompression sometimes brings rapid and significant relief of
abdominal distension.
Appendicitis
 Most common surgical emergency in children
 Classic presentation of peri-umbilical pain radiating to the right
iliac fossa, worse on jumping or walking, with associated anorexia
and fever. Physical examination reveals tenderness with rebound
tenderness and guarding at the RIF.
 Younger children often have atypical presentation, with nonspecific
central abdominal pain and vomiting of undigested food.
 Occasionally, complicated appendicitis may present late with signs
of peritonitis, sepsis or intestinal obstruction (dehydration, delirium,
generalised tenderness, abdominal distension and bilious vomiting)
 Other atypical presentations will be in obese patients, cases of
retro-caecal/pelvic appendicitis or patients with prior oral antibiotic
ingestion where the signs and symptoms will be masked.
 Appendicitis is often misdiagnosed as other common paediatric
conditions. Some clues include the following:
 Complicated appendicitis vs. gastroenteritis — Perforated
appendicitis with a pelvic abscess may present with fever and
diarrhoea. However, typically the abdominal pain and fever start
first, followed by diarrhoea after a couple of days, unlike the
concurrence of symptoms in gastroenteritis.
 Appendicitis vs. urinary tract infection — Occasionally the urine
microscopy in appendicitis may show some haematuria/pyuria,
which represent irritation or urine stasis if the inflamed appendix

is situated near the bladder. A pelvic abscess may also cause
some suprapubic tenderness. This should be differentiated from
burning sensation of dysuria related to cystitis.
 Many other differentials are possible. If unsure of the diagnosis,
observation and frequent review is necessary. Raised total white
count and CRP are suggestive but non-specific. Abdominal
Ultrasound has reported sensitivity and specificity in the range of
86–95%, but is very operator dependent. Ultrasound is useful if the
clinical diagnosis is uncertain, and to exclude ovarian torsion in girls.
CT abdomen has slightly higher accuracy rate but is not routinely
performed because of the radiation risk, and has not been shown to
decrease the negative appendicectomy rate in children.
 Recommended treatment is appendicectomy and most cases in KKH
are done via laparoscopy. Possible post-operative complications include
intra-abdominal abscess, wound infection and intestinal adhesions. For
complex appendicitis presenting late with phlegmon, an alternative
option to emergency surgery is for prolonged intravenous antibiotics
followed by interval appendicectomy. This option should be decided by
the surgeon after weighing risks/benefits.
 Clinical pathways for simple and complicated appendicitis are available
in KKH. The average length of stay is 2.4 days and 6.3 days respectively.
Haematemesis
 Newborn — Swallowed blood
 Neonate and infant — Gastritis, reflux oesophagitis
 Older kids — Gastritis, Mallory-Weiss tear, duodenal ulceration
 Resuscitate, evaluate losses (Hb and haematocrit). If minor and
with normal Hb, it may not be necessary to cross match. Any major
bleed with a significant drop in Hb will need full work-up and blood
products for resuscitation and stand-by in case of further bleeding.
Bleeding Per Rectum

 Most common — Fissure-in-ano, enterocolitis, bloody diarrhaea,
colonic polyp. Haemorrhoids are unusual in younger children.
 Blood loss is typically minimal to moderate. Clinical examination
includes assessment of general status and abdominal examination with
per rectal examination (may be deferred till later if there is an obvious
painful anal fissure) with proctoscopy reserved for adolescents.
 Investigations: Stool culture. Colonoscopy if history is suggestive of
colonic lesion or inflammatory bowel disease.
 In contrast to bright red blood from the anus/colon, bleeding from

a Meckel’s diverticulum is typically large amount and looks like fresh
malaena. Bleeding occurs when ectopic gastric mucosa causes an
ulcer in adjacent small bowel mucosa. Surgical resection is done
laparoscopically assisted in KKH, or may be open.
Bibliography:
1. Marin JR1, Alpern ER. Abdominal pain in children. Emerg Med Clin North Am. 2011
May;29(2):401–28, ix-x. doi: 10.1016/j.emc.2011.01.001.
2. Ross A and LeLeiko N. S. Acute Abdominal Pain. Pediatr. Rev. 2010;31;135–144. DOI:
10.1542/pir.31-4-135.
496
RESPIRATORY
ASTHMA
DEFINITION
Asthma is a heterogeneous disease, characterised by chronic airway
inflammation. It affects between 1–18% of the population worldwide,
and is estimated to affect 1-in-5 children in Singapore. It is characterised
by a history of respiratory symptoms of wheeze, shortness of breath,
chest tightness and cough that vary over time and in intensity,
associated with variable expiratory flow limitation.
DIAGNOSIS
Diagnosis is often based on good history and physical examination,
especially in children. The response to treatment and presence of
bronchodilator response on spirometry in older children may further
help to establish the diagnosis. Asthma should be considered in
individuals with the following typical features, especially if there is
positive family history of asthma or personal history of atopy:
 More than one symptom of wheeze, shortness of breath, cough or
chest tightness
 Symptoms worse at night or in the morning
 Symptoms vary over time and in intensity
 Symptoms triggered by viral infections, exercise, allergens, weather
changes, laughter, smoke or pollution
For children younger than 5 years, a probability based approach to

diagnosis and therapeutic decision is suggested by the 2014 Global
Initiative for Asthma (GINA) guidelines, as episodic wheezing and cough
are also common in young children without asthma, especially those
younger than 2 years. The more of the following features a child has, the
higher the probability of asthma and/or response to asthma treatment:
 Personal history of atopy, or family history of asthma
 More than three episodes of viral-induced wheeze per year, or severe
episodes and/or night worsening
 Between episodes has cough, wheeze or heavy breathing during
play or when laughing
Respiratory 497
 Symptoms (cough, wheeze, heavy breathing) for >10 days during

upper respiratory tract infections
In children older than 6 years, spirometry may further aid diagnosis and
assessment of asthma control.
Children who have atypical symptoms/signs, children who do not

respond as expected to therapy, and in children younger than 1 year
especially, differential diagnoses need to be considered and excluded
with appropriate investigations.
DIFFERENTIAL DIAGNOSIS
 Recurrent viral wheeze
 Pulmonary tuberculosis
 Recurrent aspiration (e.g. gastroesophageal reflux, swallowing
dysfunction)
 Chronic rhinitis/sinusitis
 Foreign body inhalation
 Chronic lung disease (e.g. bronchiectasis, interstitial lung disease,
bronchopulmonary dysplasia)
 Airway structural abnormalities (e.g. tracheobronchomalacia,
tracheobronchial stenosis)
 Airway compression/obstruction (e.g. mediastinal mass, vascular
rings, bronchial tumours)
 Genetic disorders (e.g. cystic fibrosis, primary ciliary dyskinesia)
 Congenital or acquired immunodeficiency
 Cardiac conditions (e.g. heart failure, congenital heart disease)
 Vocal cord dysfunction, hyperventilation, dysfunctional breathing
HISTORY
 Personal history of atopy — Allergic rhinitis, eczema, allergic
conjunctivitis
 Family history of atopy — Asthma, allergic rhinitis, eczema, allergic
conjunctivitis
 Triggers, e.g. viral infections, house dust mites, animal dander,
tobacco smoke, pollution, physical activity, stress
 Exposure to environmental tobacco smoke, and smoking history in
adolescents
 Assessment of asthma control/severity
 Frequency and severity of exacerbations, including use of written
asthma action plan (WAAP) and level of medical care attended
 Daytime and nocturnal asthma symptoms
 Physical activity related asthma symptoms, activity limitation due

to asthma
 Reliever medication use
 Asthma Control Test (ACT) score
 Medications
 Understanding of asthma action plan, controller and reliever
medications prescribed
 Adherence to controller medications
 Reasons for non-adherence, e.g. steroid phobia, child/parental
over-estimation of asthma control, inconvenient medication
regimen
 Inhaler technique assessment
 Assess co-morbid conditions, e.g. allergic rhinitis, eczema, allergic
conjunctivitis, obesity
 “Red flag” symptoms, e.g chronic moist/productive cough, symptoms
onset after choking episode, noisy inspiration, persistent tachypnoea
even at rest, syncopal episodes
 Growth parameters — Obesity, failure to thrive (“red flag” sign)
 Signs of co-morbid atopic conditions, e.g. dry eczematous skin, pale
and oedematous nasal turbinates, infraorbital shiners, enlarged
tonsils
 Signs of chronicity — Harrison’s sulci, barrel chest
 Air entry, wheeze and bronchodilator response, signs of respiratory
distress if symptomatic at time of consult/examination
 Signs of complications of treatment — Oral thrush, reduction in
linear growth, cushingoid features (long-term systemic or high-dose
inhaled corticosteroids)
 “Red flag” signs, e.g. clubbing, coarse crepitations, cardiac murmur,
loud second heart sound, stridor, biphasic wheeze
INVESTIGATIONS
Investigations are not mandatory for the diagnosis of asthma, as a
detailed history and careful physical examination are often sufficient.
They may be important for the diagnosis and exclusion of differential
diagnoses, especially in young children, or in presence of “red flag”
symptoms and signs. In children older than 5–6 years, peak expiratory
flow assessment and spirometry can be helpful for diagnosis at
presentation, and assessment of asthma control on follow up.
Respiratory 499
 Chest x-ray — Useful for the exclusion of differential diagnoses,e.g.

foreign body, pneumothorax, bronchiectasis, persistent lobar
collapse, lymphadenopathy.
 Peak expiratory flow (PEF) assessment — Performed with a
simple peak flow meter. A PEF >80% of predicted PEF for height is
considered “normal”, but it is important to take into consideration
personal best PEF/percentage predicted PEF in a growing child, and
the trend of the PEF on serial measurements. Serial measurements
may help to provide better objective assessment of response to
treatment.
 Spirometry — Bronchodilator response with increase of forced
expiratory volume in 1 sec (FEV1) of >12% suggests a diagnosis of
asthma, or partly controlled/uncontrolled asthma in a child with
a clinical presentation consistent with asthma. FEV1 has greater
sensitivity than PEF. Advise to avoid the use of bronchodilators
before performing spirometry (6 hours for short acting beta-
agonists, and 12 hours for long acting beta-agonists).
 Bronchial provocation tests — Mannitol/exercise challenge tests
are not routine investigations. They are useful in the clinical setting
when spirometry is inconclusive for asthma, or in the evaluation of
asthma as the cause of exercise induced symptoms when spirometry
is normal. Refer to a paediatric pulmonologist for bronchial
provocation tests.
 Fractional concentration of exhaled nitric oxide (FeNO) — FeNO
is elevated in eosinophilic asthma, but also in non-asthma
conditions (e.g. allergic rhinitis). This test may help guide diagnosis
and management of asthma in certain situations, but there is no
established guideline available at this point to recommend routine
use.
 Skin prick tests — Assess for sensitisation to allergens, e.g. house
dust mites, cat dander, dog dander, mould. May be useful for
advising trigger avoidance/interventions. Advise to stop the use of
antihistamines 7 days before a skin prick test.
Assessment of asthma severity, control and risk factors

The classification and terminology used to guide asthma clinical
assessment and management has evolved with recent guidelines, but
despite some revised definitions and changes, the basic principles of
management remain largely the same.
The 2014 GINA asthma control assessment includes asthma symptom

control assessment, and assessment of future risk of adverse outcomes.
Asthma symptom control assessment is based on daytime and

nocturnal asthma symptoms, reliever medication use, and activity
limitation, and classified as “well controlled”, “partly controlled” or
“uncontrolled”. Some important risk factors for poor asthma outcomes
in children include low FEV1 (especially if <60% predicted), smoking or
exposure to tobacco smoke, poor treatment adherence, history of severe
exacerbation, intensive care unit admission or intubation. Having one or
more risk factors increases the risk of exacerbations even if symptoms
are well-controlled. In the 2014 GINA guidelines, asthma severity is now
assessed retrospectively from the level of treatment required to control
symptoms and exacerbations.
See Table 14-1 for the KKH approach to assessment of asthma control,
adapted from earlier GINA guidelines. Our asthma control assessment
includes abnormal lung function, Emergency Department attendances
and admissions for asthma into consideration. The table serves only as
Table 14-1: KKH approach to asthma control assessment

Level of asthma control Controlled Partly controlled Uncontrolled
In the past 4 weeks, has the All measures below 1 or 2 measures below
child had present present in any week
Daytime asthma None/twice or less More than twice a week
symptoms (wheezing, per week
cough, difficulty 3 or more features
breathing) of partly controlled
asthma on the left
Activity limitations due None Any present in any week
to asthma
Nocturnal symptoms/ None Any
awakening due to
asthma
Reliever medication use None/twice or less More than twice a week
per week
Lung function test (PEF Normal Less than 80% predicted
or FEV1) or personal best (if
known) and/or
Bronchodilator response
present (large and/or
small airways)
Asthma exacerbations None Once or more per year Once in any week
requiring hospitalisation
or Emergency
Department attendance
Respiratory 501
a guide — any other significant considerations and future risk factors

relevant to the child should be taken into account to form a global
assessment to guide management — refer to “Review of controller
therapy” below for explanation. Please refer to the GINA guidelines for
their latest tables on asthma clinical assessment.
ASTHMA MEDICATIONS AND MANAGEMENT

All children diagnosed with asthma should be prescribed reliever
medications, e.g. salbutamol metered dose inhalers (MDI) for use when
having asthma symptoms/exacerbations.
Children whose asthma symptom control is assessed as “partly

controlled” or “uncontrolled” should be considered for treatment with
controller medications, e.g. inhaled corticosteroids (ICS), leukotriene
receptor antagonists (LTRA), or ICS and long acting beta-agonist (LABA)
combination therapy. The recommended initial therapy is low dose ICS
(e.g. fluticasone proprionate 100–200mcg daily or budesonide 200mcg
daily) for children older than 6 years, but higher step controller therapies
(e.g. budesonide 400mcg daily or ICS/LABA combination therapy)
may be initiated for children with uncontrolled asthma, significant risk
factors, or presenting with severe exacerbation.
In children 5 years or younger, controller therapy should be considered

if the asthma symptoms are not controlled, if wheezing episodes are
frequent (e.g. three or more episodes within 3–6 months), or if wheezing
episodes are severe (e.g. two episodes requiring hospitalisation within
a few months). The recommended initial therapy for children 5 years
or younger is low-dose ICS (fluticasone 100mcg daily), but higher step
controller therapies may be considered if there are significant risk factors
or poor asthma control.
The controller medications commonly used are inhaled fluticasone

proprionate and budesonide, ICS/LABA combination therapy
(salmeterol/fluticasone or formoterol/budesonide combination), and
oral LTRA (montelukast). The inhaled controller medications can be in
form of MDIs or dry power inhalers (DPI), e.g. accuhaler or turbuhaler.
Children younger than 6 years should always use their MDI together
with spacers, while children older than 6 years have the additional
option of DPIs to choose from if they are able to use the DPIs correctly. In
children younger than 3–4 years, the spacer should be used with a face
mask. See Table 14-2 for the KKH controller steps based on controller
medications available in the hospital formulary, adapted from GINA
guidelines. Refer to the GINA guidelines for their tables on estimated

clinical comparability of different inhaled corticosteroids and stepwise
controller therapy for asthma for different paediatric age groups.
Asthma education is an integral part of asthma management. The child
and the caregiver must be educated on the disease, triggers, trigger
avoidance, and the functions of controller and reliever medications
prescribed. The safety and importance of adherence to controller therapy
need to be emphasised. Correct inhaler technique and the maintenance
of spacer devices should also be taught to the child and caregiver. Please
refer to the GINA website: http://www.ginasthma.org and the KKH WAAP/
Asthma Patient Information Leaflet for more information.
Table 14-2: KKH stepwise approach to controller therapy

Step 1 Step 2 Step 3 Step 4 Step 5
Reliever medication when needed
Children Preferred Low dose ICS Double low Refer Paediatric
≤5 Fluticasone dose ICS Respiratory
years 100mcg Fluticasone Specialist
daily 200mcg
daily
Double low dose
Alternative LTRA Low dose ICS ICS + LTRA
Montelukast + LTRA
Children Preferred Low dose ICS Medium Consider referral
≥6 Fluticasone dose ICS to Respiratory
years 100mcg Fluticasone Specialist
daily 200mcg
Budesonide daily Medium/high
No 200mcg Budesonide dose ICS +
controller daily 400mcg LABA Refer
therapy daily Seretide (25/50) Paediatric
MDI 2 puffs BD Respiratory
Seretide Specialist
(25/125) MDI 2
puffs BD Medium/
Symbicort high dose
(4.5/160) 1–2 ICS + LABA
puffs BD + LTRA
Alternative LTRA Low dose ICS Consider referral

Montelukast + LTRA to Respiratory
Specialist
Medium/high
dose ICS + LTRA
Respiratory 503
An individualised WAAP should be given and explained to each child

and caregiver, to empower them to manage mild exacerbations at
home, and provide instructions on when they should seek medical
attention. The importance of a smoke free environment should be
emphasised to the caregivers if the child is exposed to environmental
tobacco smoke. Smoking cessation advice should be provided if an
adolescent patient or the caregivers smoke. Smokers who are keen to
quit smoking can be referred to trained smoking cessation counselors
or QuitLine (free smoking cessation counseling service by the Health
Promotion Board).
REVIEW OF CONTROLLER THERAPY

A child should be reviewed 1–3 months after initiating controller
therapy to review response. Subsequent reviews can be scheduled at
3–6 monthly intervals if there is good response. Young children, children
with uncontrolled asthma, or children requiring high step controller
therapy should be reviewed at closer intervals.
If there is poor or no response to treatment, review the child’s adherence

to controller therapy, inhaler device technique, environmental triggers,
co-morbid conditions, before considering stepping up controller
therapy. In general, if the asthma is partly controlled or uncontrolled,
consider stepping up controller therapy. The step of controller therapy
the child is at, the duration the child has been on the controller therapy,
and the general trend of asthma control should be considered before
stepping up controller therapy. For example, a 7-year-old child with a
history of monthly hospitalisation for asthma started on and adherent
with Step 4 controller therapy for 2 months may not need a further
step up in controller therapy even though his asthma is still classified as
“uncontrolled” because of an attendance to the Children’s Emergency for
mild exacerbation 1 week before the clinic review. Review and consider
an alternative diagnosis other than asthma if treatment response is poor,
or if there are any atypical features.
If good asthma control is achieved and maintained for at least 3–6

months, controller therapy may be reduced stepwise to the lowest step
required to maintain control. A child may lose asthma control when
controller therapy is stepped down or ceased, so advice needs to be
given to the child and caregivers to recognise recurrence of symptoms.
A follow up review should be scheduled, so that controller therapy can
be restarted or stepped up if there is worsening of asthma control.
HIGH RISK ASTHMA

A small group of children may have asthma with high disease burden.
They have frequent acute care attendances or admissions, and are at
increased risk of asthma morbidity and mortality. These children should
be managed under the close supervision of paediatric respiratory
specialists. Following the 2008 MOH Management of Asthma Clinical
Practice Guidelines, children with asthma who meet the following
criteria should be referred to the Respiratory Medicine Service:
 Poor asthma control
 Two or more exacerbations per month needing acute care
 Two or more hospitalisations for asthma within 3 months
 Requires reliever medication three or more times per week
 Severe exacerbation needing HD/ICU care
 Other risk factors, e.g. poor socioeconomic background,
persistent non-adherence to controller therapy
 <3 years and requires medium to high doses of ICS and not
responding as expected
 Requires high dose ICS
 On prolonged low to moderate ICS for >6 months and remains
symptomatic
MANAGEMENT OF ACUTE EXACERBATION

Refer to the KKH Asthma Clinical Pathway for management of acute
exacerbations at the Children’s Emergency (CE) and in the ward. The
general principles of management in the outpatient setting are as
follow:
 Assess severity of the exacerbation — See Table 14-3 for a guide on
assessing severity of asthma exacerbation.
 Consider and exclude alternative diagnoses, associated
complications especially if “red flag” history, symptoms or signs are
present, e.g. foreign body aspiration, pneumonia, pneumothorax
 Maintain oxygenation, maintain SaO2 ≥95% with oxygen
supplementation
 Relieve bronchospasm with intensive bronchodilator therapy
 Salbutamol MDI 10 puffs (5 puffs if child <10kg) with ipratropium
bromide MDI 4 puffs (2 puffs if child <10kg) every 20 mins up to 3
cycles for mild to moderate exacerbation (KKH CE Asthma Clinical
Pathway)
 Nebulised 0.5% salbutamol: 0.025% ipratropium bromide: normal
saline (1ml: 1ml: 2ml if child ≥10kg; 0.5ml: 0.5ml: 1ml if child
<10kg) with at least 6L/min oxygen if severe exacerbation with
Respiratory 505
Table 14-3: Assessing severity of asthma exacerbation

Severe or Life-
Mild Moderate
threatening
Breathless On exertion On talking At rest
Speaks in Sentences Phrases Words
Conscious level Normal May be agitated Agitated, confused,
drowsy
Accessory muscle use Nil + ++/paradoxical, thoracic-
abdominal movement
Wheeze/rhonchi Variable Loud Loud/silent
Pulse rate/minute <100 100–200 >200
Pulsus paradoxus Nil May be palpable, Palpable, >25mmHg,
10–25mmHg Nil if exhausted
Physical exhaustion Nil No Yes (cyanosed)
SaO2 in room air ≥95% 92–95% <92%
PEF (predicted/ ≥80% 60–80% <60%
personal best)
Respiratory rate ↑ ↑↑ ↑↑↑/↓ (exhaustion)
SaO2 <90% on oxygen supplementation (KKH CE Asthma Clinical

Pathway)
 If good response to treatment and meet discharge criteria (SaO2
≥95%, mild end expiratory or no wheeze, mild or no retractions,
not tachypnoeic, adequate hydration and nutrition), discharge
with salbutamol MDI 4 hourly (0.3 puffs/kg, min 2 puffs, max
8 puffs), to taper over a few days to as needed basis. A WAAP
should be provided.
 Arrange for admission, or refer/transfer to an Emergency
Department if severe exacerbation on presentation, deterioration
despite treatment, or does not respond well enough to meet
discharge criteria.
 For severe exacerbation presenting at a hospital setting, may
consider additional treatments — IV magnesium sulphate, IV
aminophylline or IV salbutamol — refer to the KKH Asthma
Clinical Pathway.
 Relieve underlying inflammation
 Prednisolone (1–2mg/kg/day, max 60mg/day) for moderate
to severe exacerbations, for 3–5 days. Refer to the KKH CE
Asthma Clinical Pathway for other indications for initiating oral

corticosteroids.
 IV hydrocortisone (4–5mg/kg, max 100mg/dose) for moderate to
severe exacerbations and unable to retain oral corticosteroids.
 Review controller therapy, step up until follow up review if
needed.
 Advise on symptoms and signs of recurrence and worsening of
exacerbation, trigger avoidance.
 Review inhaler technique and provide WAAP.
 Arrange appropriate follow up review.
Bibliography
1. Ministry of Health. Management of Asthma. MOH Clinical Practice Guidelines 1/2008.
Singapore: Ministry of Health; 2008. Available from: http://www.moh.gov.sg/mohcorp/
uploadedFiles/Publications/Guidelines/Clinica Practice Guidelines/Asthma%20CPG%20
booklet.pdf
2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention
2014. Available from: www.ginasthma.org
LOWER RESPIRATORY TRACT INFECTIONS
CROUP (ACUTE LARYNGOTRACHEOBRONCHITIS)

 Acute laryngotracheitis/acute laryngotracheobronchitis
 Affects children 6 months to 5 years old, peak age between 6 months
to 2 years old
 Most commonly caused by parainfluenza virus, other viruses include
respiratory syncytial virus, adenovirus
 Usually begins with symptoms of upper respiratory tract infection
and fever, followed by gradual onset of hoarseness, harsh “barking”
cough and stridor over 1–2 days. Croup symptoms usually worsen at
night. The stridor usually worsens with crying or agitation. Symptoms
resolve usually over a few days to a week.
 “Red flag” symptoms and signs — sudden onset, toxic looking,
drooling or dysphagia — consider alternative diagnosis e.g. acute
epiglottitis, retropharyngeal abscess, bacterial tracheitis, foreign
body aspiration.
 Management
 Minimal agitation.
 Humidified oxygen to keep SaO2 ≥95.
Respiratory 507
 Oral dexamethasone (0.6mg/kg, max 10mg) in single dose, or in

2–3 divided doses 12 hourly. Consider IV or IM administration if
unable to retain orally. May consider dexamethasone 0.15mg/kg
single dose if mild croup. Observe for at least 2 hours as the effect
of dexamethasone may not be apparent until a few hours.
 If moderate to severe croup (respiratory distress, stridor at
rest, SaO2 <95%, dehydrated), administer nebulised adrenaline
(1:1000) 0.5ml/kg, max 5ml/dose (standard dose 2mls at KKH
CE). Children who have received nebulised adrenaline with good
response should be closely monitored for at least 3–4 hours for
recurrence of symptoms.
 Admission for monitoring and further treatment may be
necessary for moderate to severe croup. Nebulised adrenaline
may be administered as needed, but if multiple frequent doses
are required, transfer to Intensive Care Unit.
 Consider discharge if not toxic, adequate hydration and good oral
intake, no stridor at rest (or minimal stridor only when agitated),
not in respiratory distress and SaO2 ≥95%. Advice caregivers to
monitor closely and return if worsening of symptoms occurs.
 Refer to KKH CE Guidelines for further details and the Westley
Croup Score that is often used for assessing croup severity.
BRONCHIOLITIS
 Lower respiratory tract infection affecting primarily the small airways
(bronchioles)
 Affects children younger than 2 years old, peak between 2–10 months
 Most commonly caused by respiratory syncytial virus, other viruses
include rhinovirus, influenza virus, adenovirus
 Usually begins with symptoms of upper respiratory tract infection
and fever, progressing to tachypnoea, wheezing and respiratory
distress over a few days. Crepitations and /or wheezing present on
auscultation. Symptoms tend to worsen over the first 3–5 days of
illness, and peak between fifth to seventh day of illness for most
children. The symptom of cough resolves by 2–3 weeks in most
children.
 Diagnosis is clinical
 Chest x-ray not indicated for typical presentation, but should be
done if complications or alternative diagnosis is suspected.
 Symptoms and signs overlap with recurrent viral induced wheeze
and asthma in young children. If recurrent episodes of wheeze,
diagnosis should not be bronchiolitis.
 “Red flag” symptoms and signs

 Prolonged symptoms with paroxysmal/staccato cough in young
infants — Consider chlamydia trachomatis, pertussis
 Recurrent apnea, altered sensorium — Indication for ICU care
 Risk factors for severe disease — Low threshold for admission and
close monitoring
 Prematurity
 Age below 3 months
 Underlying lung disease, e.g. chronic lung disease of prematurity
 Congenital airway abnormality, e.g. tracheal stenosis
 Congenital heart disease
 Immunodeficiency
 Neuromuscular disorder
 Management
 Minimal handling
 Supplemental oxygen to keep SaO2 ≥95%
 Adequate hydration and nutrition — Small frequent oral feeding,
NG feeding or intravenous hydration if required.
 Relieve nasal congestion — Normal saline nasal drops, gentle
nasal suctioning
 Treatment with bronchodilator is not routine — A trial of
nebulised salbutamol (0.5ml 0.5% salbutamol with 3.5ml normal
saline driven by 8L/min oxygen) or salbutamol (100mcg) MDI
2–4 puffs may be considered in children with family or personal
history of atopy or in moderate/severe respiratory distress.
Continue bronchodilators as needed 4–6 hourly ONLY if there is
clinical response to intervention. Refer to the KKH Bronchiolitis
Clinical Pathway for details and the Respiratory Index Score to
assess response.
 Consider discharge when SaO2 ≥95% on room air when awake,
child is adequately hydrated and able to feed, with minimal or no
retractions and end expiratory or no wheeze. Caregivers should
also confident with the monitoring and care of the child before
discharge.
PNEUMONIA
 Lower respiratory tract infection involving the lung parenchyma.
 Affects all ages, higher incidence in children younger than 5 years.
 Streptococcus pneumoniae is the most common bacterial cause. See
Table 14-4 for common infective aetiology for different age groups.
Respiratory 509
 Typically presents with fever, cough and tachypnoea, but symptoms

vary with age and different infective aetiology. Young children may
present with isolated fever, malaise, altered mental state, abdominal
pain or vomiting.
 Adventitious sounds on auscultation may be subtle in young
children with shallow breathing
 “Red flag” symptoms and signs — Recurrent pneumonia (e.g.
immunodefiency, congenital airway/lung abnormality), pleuritic
chest pain (empyema), night sweat, weight loss (pulmonary
tuberculosis), clubbing, chronic wet/productive cough
(bronchiectasis)
 Chest x-ray not mandatory for diagnosis of pneumonia, but indicated
when there is respiratory distress, prolonged symptoms, suspicion of
complicated pneumonia, “red flag” symptoms/signs, and if admission
is required.
 Full blood count, C-reactive protein may guide initial choice of
antibiotics, but are not specific in differentiating infective aetiology.
Blood cultures are specific but not sensitive. Other investigations
would be guided by the suspected infective aetiology e.g.sputum
gram stain and culture (if child able to expectorate), polymerase
chain reaction and immunofluorescence rapid diagnostic tests,
serology, Mantoux test.
 Management
 Maintain SaO2 ≥95% with supplemental oxygen
 Maintain normal vital signs, fluid resuscitation if hypotensive
 Antibiotic therapy is guided by the age, clinical presentation,
immune function, co-existing diseases, travel and contact
of the child, as well as prior antibiotic treatment and local
antibiotic resistance patterns. See Table 14-4 for the KKH
Pneumonia Clinical Pathway for antibiotic guide for children
with normal immune function. First dose antibiotic should be
administered within 4 hours of hospital arrival.
 Maintain adequate hydration, monitor serum sodium and watch
for syndrome of inappropriate secretion of anti-diuretic hormone
if on intravenous fluids.
 Refer to Respiratory Medicine/Infectious Disease Service if
complicated pneumonia is suspected.
Table 14-4: Infective aetiology and empiric antibiotics guide from the KKH Pneumonia Clinical
Pathway
Age Infective Oral Antibiotics Intravenous Antibiotics
aetiology
First-line No response
≥48–72 hours
Neonate Group B NA IV Ampicillin IV Ampicillin
Streptococcus + +
E. coli IV Gentamicin IV Cefotaxime
Listeria
Gram-negative
bacilli
1–3 Viruses Afebrile Febrile
months C. trachomatis
S aureus PO Clarithromycin* IV Ampicillin IV Ampicillin
B. pertussis + +
S. pneumoniae IV Cloxacillin IV Cloxacillin
+
PO Clarithromycin*
3 months– Viruses Well looking Toxic looking
5 years S. pneumoniae
H. influenza If suspect S. IV Ampicillin Consider
M. catarrhalis pneumonia 200mg/kg/day complications of
Mycoplasma pneumonia
PO Amoxycillin If moderate/
severe RDS or HD/ IV Ampicillin 300mg/
If suspect ICU admission kg/day
Mycoplasma (e.g. requires +
supplemental O2 PO Clarithromycin/IV
PO Clarithromycin or non-invasive Erythromycin
ventilation)
+ If <1 year and suspect
PO Clarithromycin* S. aureus
If <1 year and +
suspect S. aureus IV Cloxacillin
+
IV Cloxacillin
≥5 years Mycoplasma IV Ampicillin Consider
S. pneumoniae 200mg/kg/day complications of
C. pneumoniae If moderate/ pneumonia
severe RDS or HD/
ICU admission IV Ampicillin 300mg/
(eg requires kg/day
supplemental O2 +
or non-invasive PO Clarithromycin/IV
ventilation) Erythromycin
+
PO Clarithromycin*
*If unable to tolerate PO Clarithromycin, consider PO Erythromycin or PO Azithromycin
Respiratory 511
 Convert to oral antibiotics when the child is afebrile for 24–48 hours.
 Follow-up CXR not necessary in asymptomatic children
with uncomplicated pneumonia. Repeat CXR 4–6 weeks
after discharge if complicated pneumonia (e.g. abscess,
parapneumonic effusion, extensive pneumonia), severe
atelectasis, unusually located infiltrates, round pneumonia or
a history of recurrent pneumonia on presentation. If child has
persistent symptoms or abnormal auscultatory findings on follow
up, CXR should also be repeated.
Bibliography
1. Selwyn BJ. The epidemiology of acute respiratory tract infection in young children:
comparison of findings from several developing countries. Coordinated Data Group of
BOSTID Researchers. Rev Infect Dis. 1990;12 Suppl 8:S870−S888.
2. Denny FW, Clyde WA Jr. Acute lower respiratory tract infections in non-hospitalized
children. J Pediatr. 1986;108(5 Pt 1):635−646.
3. Yun BY, Kim MR, Park JY, Choi EH, Lee HJ, Yun CK. Viral etiology and epidemiology of acute
lower respiratory tract infections in Korean children. Pediatr Infect Dis J. 1995;14(12):1054–59.
PARAPNEUMONIC EFFUSION
AND EMPYEMA
DEFINITION
Parapneumonic effusion is defined as an abnormal collection of
fluid in the pleural space in association with underlying pneumonia.
Uncomplicated small parapneumonic effusions are sterile exudates that
often resolve with appropriate antibiotic treatment of the pneumonia.
Complicated parapneumonic effusions occur when there is bacterial
invasion into the pleural space and fibrinopurulent changes, and
often require drainage in addition to antibiotic treatment. Empyema
occur when frank pus develops from a parapneumonic effusion, with
organisation and formation of loculations and pleural peels. Empyema
complicate about 1–2% of childhood pneumonia.
Aetiology
The most common organisms are Streptococcus pneumonia,
Haemophilus influenzae, Mycoplasma pneumonia and Staphylococcus
aureus, depending on the age of the child. In neurologically impaired
children and aspiration related pneumonia, anaerobic bacteria may be
the causative organism.
Diagnosis
Parapneumonic effusion is suspected when the CXR shows
consolidation with pleural fluid accumulation in a febrile child with
signs and symptoms of lower respiratory tract infection. Complicated
parapneumonic effusion or empyema development should be
suspected if fever persists, or fever and respiratory symptoms worsen
despite 48 hours of antibiotics. Pleuritic chest pain and referred
abdominal pain may be present.
The choice of ultrasound thorax or CT chest for evaluation of the

empyema should be discussed with the Respiratory Consultant and
Paediatric Surgeon. In general ultrasound thorax is preferred unless it is
a complicated case.
Differential diagnoses
 Transudative
 Heart failure
 Hypoalbuminaemia, e.g. nephrotic syndrome, liver disease,
protein losing enteropathy, malabsorption
 Exudative
 Tuberculosis
 Connective tissue disease, e.g. SLE
 Malignant effusion
 Abdominal infection/inflammation, e.g. hepatic abscess,
pancreatitis
 Chylothorax
 Other diagnoses, e.g. lung abscess, atelectasis, malignancy, e.g.
pleuropulmonary blastoma
Management
Refer to the Respiratory Medicine Service if a complicated
parapneumonic effusion or empyema is suspected. Management is
often individualised taking into consideration the presentation, prior
treatment, complexity of the effusion and patient factors. Figure 14-1
shows the KKH algorithm to guide management.
 Antibiotics — The choice of antibiotics depends on the likely

infective organism, guided by the age, contact history, immune
status and the mechanism causing the pneumonia. High dose IV
ampicillin is the first-line treatment if S. pneumoniae is suspected.
Antibiotic choice should be reviewed once microbiological results
are available or if there is poor response to treatment. Treatment
Respiratory 513
Parapneumonic effusion on CXR
IV antibiotics
No IV antibiotics and observe.

Large effusion and/or respiratory distress Consider diagnostic tap
Yes
Loculated effusion?
No Uncertain/yes
IV antibiotics and Ultrasound thorax/

chest tube CT scan thorax
Not loculated Loculated Loculated

No suggestion of No suggestion of Thick pleural peel
pleural peel pleural peel Duration >10 days
Duration <10 days Duration <10 days Lung compression ≥50%
Lung compression <50%
Chest tube
Medical option Early surgical option
Chest tube and VATS

fibrinolytic therapy
Figure 14.1: Algorithm for the management of parapneumonic effusion and empyema
should be intravenous until the child is afebrile for at least 24–48

hours and the chest drain removed. In most cases this would be at
least 7–14 days depending on severity of the disease and response to
treatment and drainage. This is followed with oral antibiotics and the
total duration of antibiotic treatment should be at least 3–4 weeks.
Pleural fluid antibiotic levels are comparable to serum levels. The
exception is aminoglycosides, which penetrate poorly into purulent
pleural fluid.
 Chest tube drainage — Large parapneumonic effusions causing
respiratory distress and complicated effusions require drainage in
addition to antibiotics. As an alternative to a chest drain insertion
by the medical team, ultrasound guided pigtail catheter placement
by the interventional radiologist may be considered if the drainage
is not urgent for relief of respiratory distress, or if the location of the
effusion is better accessed with ultrasound guidance.
 Intrapleural fibrinolytic therapy — If the pleural fluid is turbid or
there is evidence of early loculation on the ultrasound thorax,
consider fibrinolytic therapy with chest tube drainage. 6 doses of
intrapleural urokinase is given twice daily for 3 days. Each dose is
40,000U in 40mls normal saline (10,000U in 10mls normal saline if
child <10kg), to leave to dwell in the pleural cavity after instillation
for 4 hours before unclamping the chest tube.
 Video-assisted thoracoscopic surgery (VATS) — If there are significant
loculations and adhesions, these need to be broken down for
effective drainage of the pleural cavity. Thick pleural peels may
entrap lung if not decorticated. Video-assisted thoracoscopic surgery
is the procedure of choice for these purposes, and may be associated
with a shorter hospital stay.
Bibliography
1. Sasse SA. Parapneumonic effusions and empyema. Curr Opin Pulm Med. 1996;2(4):320–326.
2. Hardie W, Bokulic R, Garcia VF, Reising SF, Christie CDC. Pneumococcal pleural empyemas
in children. Clin Infect Dis. 1996;22(6):1057–1063.
3. Sahn SA. Management of complicated parapneumonic effusions. Am Rev Respir Dis.
1993;148(3):813–817.
4. Bilaceroglu S, Cagirici U, Cakan A, Kumcuoglu Z, Perim K. Management of complicated
parapneumonic pleural effusions with image-guided drainage and intrapleural urokinase
or streptokinase: A controlled randomized trial. Eur Respir J. 1997;10:325S.
5. Wait MA, Sharma S, Hohn J, Dal Nogare A. A randomized trial of empyema therapy. Chest.
1997;111(6):1548–1551.
6. Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D, et al. BTS guidelines
for the management of pleural infection in children. Thorax. 2005;60(Suppl 1):i1–i21.
Respiratory 515
OBSTRUCTIVE SLEEP APNEA
INTRODUCTION
Sleep-related upper airway obstruction exists in a continuum:
 Primary snoring — Snoring without associated apnea,

hypoventilation, hypoxaemia, hypercarbia, sleep disruption or
daytime symptoms.
 Upper airway resistance syndrome — Partial upper airway
obstruction sufficient to cause sleep disruption and daytime
symptoms but not associated with gas exchange abnormalities.
 Obstructive sleep apnea (OSA) — Prolonged partial upper airway
obstruction and/or intermittent complete or partial upper airway
obstruction during sleep, usually associated with episodic reduction
in oxygen saturation, hypercarbia and sleep fragmentation.
The incidence of OSA is estimated to be 1–3% in pre-school and
school-aged children. Untreated OSA can be associated with
significant morbidity, including neurocognitive deficits, growth failure,
cardiovascular consequences, and even death in severe cases.
Risk factors and high risk groups

OSA can be caused by any factor that affects the neural control,
dimensions or intraluminal pressure of the upper airway. The most
common risk factors in children are adenotonsillar hypertrophy
associated with atopy (allergic rhinitis), and obesity. Other important
high risk groups are children with:
 Trisomy 21 (hypotonia, macroglossia, mid-face hypoplasia, obesity,
hypothyroidism)
 Genetic disorders, e.g. achondroplasia, Prader-Willi syndrome,
mucopolysaccharidoses,
 Craniofacial syndromes, e.g. Apert syndrome, Crouzon syndrome,
Pierre-Robin sequence
 Upper airway abnormalities, e.g. laryngomalacia, glottis/subglottic
stenosis, choanal stenosis, cleft palate
 Neuromuscular disorders, e.g. Duchenne muscular dystrophy, spinal
muscular atrophy, myasthaenia gravis
 Spina bifida/Chiari malformation
 Prematurity
 Family history of OSA
Presentation
Habitual snoring (3 or more nights per week) is the key presentation
in children with OSA. It is estimated that up to 6–12% of children
have habitual snoring, while the incidence of OSA in children is 1–3%.
However, not all children with OSA present with a history of snoring,
possibly due to limited awareness and observation by caregivers, or
misinterpretation of snoring as other respiratory noises at night, e.g.
wheezing, nasal congestion.
Symptoms and signs suggestive of OSA in snoring children include
 Observed cyanosis/apnea, snorting, gasping during sleep
 Laboured/paradoxical breathing during sleep
 Unusual sleeping position, hyperextended neck
 Restlessness and frequent awakening
 Diaphoresis
 Frequent daytime mouth breathing
 Difficulty getting up in the morning
 Unrefreshed after an overnight sleep
 Morning headaches
 Excessive daytime sleepiness
 Enuresis or nocturia
 Behavioural and learning problems, e.g. hyperactivity, inattention,
aggressive behaviour, poor school performance
 Failure to thrive or obesity
In addition to those mentioned above, other consequences of long

standing untreated significant OSA include
 Systemic hypertension, pulmonary hypertension, cor pulmonale
 Gastroesophageal reflux
 Insulin resistance and metabolic syndrome
 Obesity hypoventilation and death in severe cases
History
As children with OSA may have other co-existing sleep disorders, in
addition to the risk factors, symptoms and features above, history
should also include
 Bedtime, wake time, sleep duration and regularity on school days
and weekends
 Sleep hygiene, e.g. activity before sleep, sleep environment
 Bedtime problems, e.g. bedtime resistance, insomnia,
 Parasomnias, e.g. sleep walking, confusional arousals
Respiratory 517
If there is moderate to severe excessive daytime sleepiness (e.g. sleep

attacks, falling asleep during exams, while talking to someone), consider
narcolepsy and screen in the history for cataplexy (sudden loss of
muscle tone triggered by strong emotions, e.g. laughter, surprise, anger),
sleep paralysis and hypnagogic (sleep onset) hallucinations.
If there is restless sleep with reported leg movements, consider restless

leg syndrome and periodic leg movement disorder and screen in the
history for an urge to move the legs, accompanied by uncomfortable
or unpleasant sensations in the legs. The urge and sensations often
begin or worsen during periods of rest/inactivity (e.g. lying, sitting), are
partially or totally relieved by movement (e.g. walking, stretching), and
worse in the evening/night than during the day.
Physical examination
 Growth parameters, BMI — Obesity, failure to thrive
 Blood pressure — Hypertension
 Nasal patency — Signs of allergic rhinitis, deviated nasal septum
 Adenotonsillar hypertrophy — Enlarged tonsils (grade the tonsillar
hypertrophy), mouth breathing, nasal speech
 Craniofacial features — Mid-face hypoplasia, flat nasal bridge, facial
asymmetry, retrongathia, microngathia
 Oropharynx examination — Oropharyngeal narrowing, large tongue,
cleft palate, Mallampati classification
 Noisy breathing — Stridor, hoarse/weak voice
 Chest deformity — Pectus excavatum
 Pulmonary hypertension — Loud second heart sound
Investigations
If OSA is suspected, refer to the Sleep Clinic for review and scheduling
of an overnight polysomnography (PSG), which is the gold standard for
diagnosis of OSA.
Overnight oximetry is easier and less costly to perform, but is not

routinely recommended because of its limitations, e.g. low sensitivity,
inability to differentiate between obstructive and central apnea. It may be
considered in specific situations, e.g. for a child who is unable to cooperate
with placement of multiple leads, sensors and belts required for PSG.
If narcolepsy is suspected, a multiple sleep latency test (MSLT) may be

considered. The MSLT is performed the next day after an overnight PSG.
Management
Management for each child depends on the cause(s) and severity of
the OSA, extent of impairment from the OSA, and co-existing medical
conditions (e.g. congenital heart disease, metabolic complications of
obesity). Treatment options may involve one or a combination of the
options below:
 Tonsillectomy and adenoidectomy (T&A) — First-line treatment
for children with enlarged tonsils or adenoids, with good response
in most children. Outpatient surgery is not recommended in
children, in particular, children with increased risk of post-operative
respiratory complications, e.g. younger than 3 years, severe OSA,
severe obesity, failure to thrive, co-existing cardiac/respiratory
conditions, cor pulmonale, craniofacial anomalies, neurological/
neuromuscular disorders, Trisomy 21 and achondroplasia. These
children require close post-operative monitoring. As they are also
at higher risk of incomplete resolution of the OSA after T&A, a low
threshold for repeat evaluation is recommended, especially if there
are persistent or recurring symptoms. Nutritional counseling and
physical activity advice should be provided to overweight children,
as T&A may be associated with increased weight gain in children
after surgery.
 Continuous positive airway pressure (CPAP) therapy — Long term
use is indicated in children with significant OSA where surgery has
no role (e.g. OSA due to obesity without adenotonsillar hypertrophy),
or children with significant residual OSA after T&A. Bi-level positive
airway pressure may be used for better tolerance in severe OSA
requiring high CPAP, or children with certain neuromuscular
disorders. Although CPAP therapy is effective, acceptance and
adherence can be a limiting factor in children. CPAP education
before initiation of CPAP, behavioural interventions and supportive
interventions for side effects of CPAP use can help to improve
adherence with CPAP therapy. Regular titration PSGs are necessary as
pressure requirements can change in a growing child.
 Weight loss — Important part of management for overweight
children with OSA. All overweight children should be given
nutritional and physical activity counseling. Referral to a weight
management clinic should be considered if a child has difficulty
with weight management, metabolic complications of obesity, or is
morbidly obese.
 Medications — Nasal steroids and/or oral montelukast may be
treatment options in children with mild OSA where parents are
reluctant to pursue surgical options. Children on medications alone
Respiratory 519
for treatment should be reviewed for response, and treatment

options reconsidered if there is no improvement, or worsening of the
OSA. Medications that help with maintaining nasal passage patency,
e.g. nasal steroids, nasal saline are also important adjunctive therapy
for OSA, particularly for children on CPAP therapy.
 Other surgical techniques — Uvulopharyngopalatoplasty,
epiglottoplasty, tongue base reduction, tracheostomy, mandibular
advancement and other craniofacial surgery are treatment options
considered only in a select group of children with complex OSA and
not routinely performed.
 Orthodontic procedure — Rapid maxillary expansion may be
considered in a select group of children with OSA related to maxillary
constriction.
Most children with mild to moderate OSA due to adenotonsillar
hypertrophy alone have good response to T&A with complete resolution
of symptoms. Repeat PSG after surgery to evaluate for residual OSA is
indicated in children with partial resolution of symptoms, severe OSA,
and children with significant risk factors, e.g. Trisomy 21, morbid obesity.
Children with high risk for OSA should have long term follow up with
the Sleep Clinic to monitor for recurrence, while children with low risk
and resolution of symptoms after T&A can return to follow up with their
primary care physicians.
Bibliography
1. Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J et al. Diagnosis
and management of childhood obstructive sleep apnea syndrome. Pediatrics.
2012;130(3):e714–e755.
2. Section on Paediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome,
American Academy of Paediatrics. Clinical practice guideline: Diagnosis and management
of childhood obstructive sleep apnea syndrome. Paediatrics. 2002;109(4);704–712.
3. American Thoracic Society. Cardiorespiratory sleep studies in children: Establishment of
normative data and polysomnographic predictors of morbidity. Am J Respir Crit Care Med.
1999;160(4):1381–1387.
4. McColley SA, Carroll JL, Curtis S, Loughlin GM, Sampson HA. High prevalence of allergic
sensitization in children with habitual snoring and obstructive sleep apnea. Chest.
1997;111(1):170–173.
5. Tang JPL, Rosen CL, Larkin EK, DiFiore JM, Arnold JL, Surovec SA, et al. Identification
of sleep-disordered breathing in children: Variation with event definition. Sleep.
2002;25(1):72–79.
520
RHEUMATOLOGY
APPROACH TO LIMB/JOINT PAIN
AND LIMPING
Important history that will help with differential diagnosis:
 Location: bone, joint, anatomic site
 Onset: acute or chronic (6 week-mark)
 Severity: related to activity of daily living
 Time of the day for most or maximal pain/disability: morning, end of
the day or nocturnal
 Things that aggravate or alleviate pain: massage, medication(s),
resting
 Associated signs or symptoms — for systemic diseases
Physical examination:
Arthritis: signs of inflammation include swelling (effusion and/or
synovial thickening), warm, tenderness, redness (usually absent with
non-infectious chronic arthritis) and limitation of range of motion (ROM)
— objective signs
Arthralgia: perceived pain in the joint — subjective symptoms
Inflammatory causes: infectious (septic) or non-infectious (reactive or

idiopathic arthritis)/part of systemic diseases, malignancy associated
arthritis, etc.
Mechanical causes: trauma, fracture, ligament or tendon tears, overuse,
hypermobility.
Table 15-1: Differentiation between inflammatory and mechanical joint pain

Inflammatory type Mechanical type
Onset usually insidious sudden
AM stiffness >30 mins none
Limitation of ROM gradual abrupt/acute
Aggravation of pain at rest with use or movement
Joint swelling synovial hypertrophy, effusion warm effusion
Rheumatology 521
Figure 15.1 Algorithm for joint pain in emergency room situation

* Red flags are defined as presence of systemic signs, i.e. prolonged

fever, unwell child, distressed child, hepatosplenomegaly,
lymphadenopathy, non-weight bearing, severe joint pain, signs
suggestive of autoimmune diseases (i.e. rash, oral ulcer)
** Abnormal blood tests are defined as unexplained anemia for age,
bicytopenia, white blood cell counts of >15,000/ml, ESR ≥40mm/first
hour, CRP ≥30mg/L, presence of early WBC .
Nocturnal pain:
 Benign nocturnal pain of childhood or “growing pains”
 Never during the day and only at night
 Affects 4–12 years old, male almost equal to female in distribution
 Usually lower limb and bilateral
 Relieved by massage and/or analgesics
 Normal joint examination and all investigations
 Bone tumors
 Benign tumours: osteoid osteoma, bone cyst, etc.
 Malignant bone tumours
 Primary bone cancers
 Secondary bone tumors or metastasis — leukaemia,
lymphoma, neuroblastoma
Table 15-2: Transient synovitis vs. septic arthritis
Number of predictors* Predicted probability of septic arthritis (%)
0 <0.2
1 3.0
2 40.0
3 93.1
4 99.6
*4 predictors: 1. History of fever, 2. Non-weight bearing, 3. ESR >40mm/hr, 4. Total WBC >12K/ml
Adapted from Kocher MS et al. J Bone Joint Surg. 1999.
Musculoskeletal Manifestations of Systemic Disease

 Infection: Infectious, reactive, rheumatic fever
 Malignancy: Leukaemia, lymphoma, neuroblastoma, bone/
cartilaginous tumour
 Bone/connective tissue disorder: osteochondrodysplasia, Marfan and
Ehlers-Danlos syndromes
 Metabolic diseases: mucopolysaccharidoses/mucolipidoses
 Haemophiliac arthropathy
Rheumatology 523
 Endocrine: Hypothyroidism, pancreatitis

 Immunodeficiency-associated arthritis
 Periodic Fever syndromes
 Familial Mediterranean fever (FMF)
 Hyper IgD
 Periodic fever, aphthous stomatitis, pharyngitis and adenitis
(PFAPA)
 Neonatal onset multisystem inflammatory disease /chronic
infantile neurologic cutaneous articular syndrome (NOMID/CINCA)
 Familial cold urticaria syndrome (FCUS)
 Muckle-Wells syndrome (MWS)
 TNF receptor associated periodic syndrome (TRAPS)
SELECTED RHEUMATOLOGICAL
INVESTIGATIONS
Table 15-3: Acute phase reactants
Proteins that increase Proteins that decrease
CRP Albumin
Serum amyloid A Transferrin
Fibrinogen Alpha-fetoprotein
Ferritin Thyroxine-binding globulin
Plasminogen Insulin-like growth factor I
Protein S Factor XII
Complements
C3
C4
C9
Factor B
C1 inhibitor
C4b-binding protein
Mannose-binding lectin
Angiotensinogen
Phenomenon
Fever, somnolence, and anorexia
Anemia of chronic disease
Leukocytosis
Thrombocytosis
Osteoporosis
Increased hepatic lipogenesis
Increased lipolysis in adipose tissue
Cachexia
Adapted from Gabay C and Kushner I. NEJM 1999
ESR
 Nonspecific test which indicates the presence and intensity of
inflammation
 Non diagnostic but can be used to follow inflammatory activity
 Takes longer time to rise and fall
 SingHealth: Westergren method
 Normal values
 Male: 1–10mm/hr
 Female: ≤50 years 3–15mm/hr; >50 years 3–20mm/hr
Table 15-4:. Factors that interfere with ESR level

Increase Decrease
Increase in fibrinogen, gamma or beta globulins Abnormal RBC shape, i.e. sickle cell, spherocyte,
Macrocytosis microcytosis
Hypercholesterolaemia Hypofibrinogenaemia
Drugs (dextran, methyldopa, penicillamine, High WBC, polycythaemia
theophylline, vitamin A) Congestive heart failure
Technical factors High dose adrenal steroids
Tilted tube Cachexia
High room temperature Drugs (aspirin, quinine, drugs causing high sugar
Female level)
Pregnancy Technical factors
Smoking Low room temperature
Delay test >2 hours
Clotted blood sample
Excess anticoagulation
Bubbles in tube
Adapted from Wallach J. Interpretation of Diagnostic Tests, 8th ed. 2007
CRP
 Appears within 24–48 hours with the peak 72 hours and negative
after 7 days of stimulation removal
 Increase indicates active inflammation except in SLE and related
diseases unless infection is present
 No increase in pregnancy, asthma, seizures, angina, CVA
 Not affected by environmental factors, i.e. room temperature,
gender, age
 SingHealth: Immunoassay, turn-around time 3–5 hours
 Normal values: 0.2–9.1mg/L
Rheumatoid Factor (RF)

 Antibodies against Fc portion of IgG
 Commercially available assay usually measures IgM isotype
Rheumatology 525
 Non-specific tests can be increased in certain infections and many

other systemic autoimmune disorders
 Limited use in pediatrics as RF positive JIA is uncommon (<10–15%
of all JIA population)
 Can be used as adjunct test in cryoglobulinaemia
 SingHealth, immunoassay (turn-around time 3–5 hours)
 Normal values
 <10.3U/ml
Antinuclear Antibodies (ANA)

 Detected by immunofluorescence (IF) or ELISA
 Non-specific even for autoimmune disorders
 Could be positive in non-systemic autoimmune diseases including
infections, malignancy, old age especially female, chronic active
hepatitis
 SingHealth: Immunofluorescence, turn-around time 2–4 days
 Start dilution at 1:100, normal <1:100 titer
Table 15-5: Pattern of immunofluorescence staining
ANA pattern Autoantigen detected
Homogenous dsDNA, histone
Speckled Acid extractable nuclear antigens (Ro/SSA, La/SSB, RNP, Sm
Nucleolar PM-Scl, Scl-70 (topoisomerase-I)
Centromere centromere
Rim/Peripheral dsDNA (animal cell line IIF)
Cytoplasmic Mitochondrial, Jo-1 other cytoplasmic antigens
Anti-dsDNA
 Present in 60–90% of childhood onset SLE (cSLE), ~90% of local cSLE
 Aids in SLE diagnosis and often fluctuates with lupus disease activity
especially lupus nephritis in some patients
 Crithidia assay detects antibodies that bind to double-stranded DNA
located at Crithidia luciliae kinetoplast (a protozoan organism with
a double-stranded circular DNA structure at one pole). This assay
detects antibodies to double stranded DNA almost exclusively.
 Should not be used alone in following cSLE patients disease activity
or predicting flare
 SingHealth: offers both ELISA and Crithidia IIF, turn-around time 1–4
days
 Normal: <25 U/ml (ELISA), <1:10 (IIF)
Table 15-6: Prevalence of ANA and RF in Pediatric autoimmune diseases**

Diseases ANA (%) RF (%)
SLE 98* 15–35
JIA Up to 85 <10
Juvenile dermatomyositis 10–85 -
Systemic sclerosis 81–97 -
Localised scleroderma 23–73 -
Sjogren syndrome 71–96 -
*KKH data
**Adapted from Cassidy JT, Petty RE, Laxer RM, Lindsley CB ed. Textbook of Pediatric
Rheumatology 6th ed. 2011
Antiphospholipid Antibodies (APA)

 Bind chiefly to negatively charged phospholipids like cardiolipin
 Three tests available which detect slightly different but overlapping
populations of antibodies:
 Venereal Disease Research Laboratory test false positive —
Limited use
 Lupus anticoagulant — More sensitive functional coagulation
assay
 Anti-cardiolipin antibodies (ACA)
 SingHealth: Enzyme Immunoassay (turn-around time 1 week)
 Significant value: >40 GPL/MPL (IgG or IgM)
 Anti-beta2 glycoprotein I
Persistently raised levels especially of IgG associated with thrombosis
(especially arterial thrombosis), recurrent fetal loss, thrombocytopenia,
neurological disorders
Antiphospholipid antibdoy syndrome may occur in isolation as part of a

connective tissue disease
Antineutrophil Cytoplasmic Antibodies (ANCA)

Binds to antigens in cytoplasm of neutrophils
Two patterns on alcohol-fixed IIF:
 Cytoplasmic ANCA (cANCA; cytoplasmic diffuse staining)
 Perinuclear ANCA (pANCA; peripheral staining around edge of
nucleus)
Specific antibody tests:
 SingHealth: Enzyme immunoassay, turn-around time 1 week
Rheumatology 527
 Anti-proteinase 3
 Normal value <10 U/ml
 Anti-myeloperoxidase
 Normal value <5 U/ml
Table 15-7: Common disease association with ANCA
ANCA pattern Antigens Disease association Frequency (%)
cANCA Proteinase 3 (PR3) Wegener’s granulomatosis 30–90
Churg-Strauss 25–50
pANCA Myeloperoxidase (MPO) Microscopic polyangiitis 25–75
Others Ulcerative colitis 40–80
Crohn’s disease 10–40
Sclerosing cholangitis 65–85
Actin Autoimmune hepatitis type I 70–75
Adapted from Cabral D and Benseler. Textbook of Pediatric Rheumatology 6th ed. 2011
Immunoglobulin levels
 Polyclonal IgG elevation is a non-specific reflection of an acute-phase
response to systemic inflammation
 KKH reference information, Turnaround time: 3–5 hours
IgG , serum
 Specimen required:
1.3ml plain blood for paediatric and
3ml plain blood for adult.
 Method: Immunoturbidimetry
Reference interval:
Table 15-8: Ig G, serum reference
Age Gender Reference Interval (g/L)
0–14 days All 3.20–14.00
15 days–<1 year All 1.10–7.00
1–<4 years All 3.20–11.50
4–<10 years All 5.40–13.60
10–<19 years All 6.60–15.30
19–80 years Male 5.40–18.22
19–80 years Female 5.52–16.31
Ig M, serum
 Specimen required: 1.3ml plain blood for paediatric and
 Reference interval:
Table 15-9: Ig M, serum reference

0–14 days All 0.10–0.40
15 days–<13 weeks All 0.10–0.70
13 weeks–<1 year All 0.20–0.90
1–<19 years Male 0.40–1.50
1–<19 years Female 0.50–1.90
19–100 years Male 0.22–2.40
19–100 years Female 0.33–2.93
Ig A, serum
Table 15-10: Ig A, serum reference

0–<1 year All 0.00–0.30
1–<3 years All 0.00–0.90
3–<6 years All 0.30–1.50
6–<14 years All 0.50–2.20
14–<19 years All 0.50–2.90
19–60 years Male 0.63–4.84
19–60 years Female 0.65–4.21
Complement
 Complement cascade plays central role in cell lysis, opsonisation of
bacteria, clearance of immune complexes
Rheumatology 529
 Elevated in inflammation as part of acute-phase response

 Fall with immune complex consumption (especially active lupus
nephritis, cytopenia, haemolysis)
 KKH reference information, turn-around time 3–5 hours
Complement C3, serum

Table 15-11: Complement C3, serum reference

0–14 days All 0.50–1.21
15 days–<1 year All 0.51–1.60
1–<19 years All 0.83–1.52
19–80 years Male 0.82–1.85
19–80 years Female 0.83–1.93
Complement C4, serum

Table 15-12: Complement C4, serum reference

0–<1 year All 0.07–0.30
1–19 years All 0.13–0.37
19–80 years Male 0.15–0.53
19–80 years Female 0.15–0.57
Imaging
Plain film
 Always do bilateral films to compare
 Good for bony lesions and mechanical problems including fracture,
dislocation or subluxation
Ultrasonography
 Good to detect fluid, cyst, mass
 Hard to read as affected by surrounding gas or air, pressure or
operator dependent
 Real time assessment
Computed tomography (CT)

 Good to detect bony lesion and blood
 Very high radiation exposure thus not suitable for serial studies
Magnetic resonance Imagings (MRI)

 Good to detect soft tissue, adjunct in arthritis management
 With contrast enhancement — aids in detecting active inflammation,
specific method can help detecting active vasculitis in large and
medium sized vasculitides
 No radiation but costly and takes longer time to do
JUVENILE IDIOPATHIC ARTHRITIS (JIA)

 Is an idiopathic chronic arthritis that begins in childhood
 Different from adult rheumatoid arthritis
 Aetiology unknown. Genetic predisposition with environmental
triggers leads to cytokine mediated inflammation (such as
interleukin 1 (IL1), interleukin 6 (IL6) and TNF alpha). Possibly a
complex genetic trait associated with HLA genes and cytokine gene
polymorphisms (HLA B27, DR1, 4, 5, 8)
 The incidence ranges widely from 0.8–22/100,000 worldwide. In
Singapore, the incidence is estimated to be 4–5/100,000 children
at risk, below the age of 16 years. Asian children lack the female
predominance and uveitis described in the west
DIAGNOSIS AND CLASSIFICATION

 Clinical and by exclusion. Current recommended definition
and classification is by International League of Associations for
Rheumatology (ILAR):
 Arthritis for ≥6 weeks
 Exclusion of secondary causes
 Arthritis: Joint swelling, or two out of three of pain, warmth,
restriction of movement
Rheumatology 531
 'Dry synovitis' may have progressive contracture without effusion

 Different classification systems have been developed by the
European League Against Rheumatism (EULAR) , the American
College of Rheumatology (ACR) and ILAR (see Table 15-13 next
page). ILAR is recommended for universal application.
 The three classification systems have some differences; important
to be aware of this when interpreting literature
 Each joint is counted separately except cervical spine, carpus,
tarsus, which are each counted as one joint
 Positive RF — Detected on 2 occasions, 3 months apart
 Systemic disease (9% of local JIA)
 Arthritis with or preceded by daily spiking fever for 2 weeks,
(quotidian pattern documented for at least 3 days) and
 One of the following:
 Typical rash (evanescent, erythematous)
 Hepato/splenomegaly
 Generalised lymphadenopathy
 Serositis
 Uncommon locally, typically in very young but can occur at
any age, including adults called “Still’s Disease”
 Can be challenging if initial presentation without arthritis
 May be complicated by pericarditis and macrophage
activation syndrome (MAS)
 Polyarticular disease (20% of local JIA)

 Arthritis affecting five or more joints during the first 6 months
of disease
 Almost 1/2 of local JIA and requiring Disease-modifying Anti-
rheumatic Drugs (DMARDs)
 14% RF-negative, typically younger age at onset
 6% RF-positive, usually older girls/adolescents, mimics adult
RA with early erosive disease
 Oligo-articular disease (23% of local JIA)

 Oligo-persistant disease: classically younger girl with the
swollen knee, commonly ANA positive
 Arthritis is usually easily treated with NSAIDs or intra-articular
steroid injection but chronic uveitis is common and can lead
to blindness if untreated.
 Extended disease, i.e. more than four joints after the first 6 months
Table 15-13: The three classification systems

ACR EULAR ILAR
Term Juvenile Rheumatoid Juvenile Chronic Arthritis Juvenile Idiopathic Arthritis
Arthritis (JRA) 1976 (JCA) 1977 (JIA) 1997
Duration of arthritis ≥6 weeks ≥3 months ≥6 weeks
Onset types Three Six Seven
Systemic Systemic Systemic
Polyarticular Polyarticular (RF-positive) Polyarticular (RF-positive)

Polyarticular (RF-negative) Polyarticular (RF-negative)
Pauciarticular Pauciarticular Oligoarticular

Persistent
Extended
Juvenile Psoriatic Arthritis Psoriatic Arthritis
Juvenile Ankylosing Enthesitis-related Arthritis

Spondylitis (JAS)
Undifferentiated
arthritis (fulfil criteria of
more than one type
or none)
* ACR system: Excludes seronegative spondyloarthropathies (JAS, psoriasis and related diseases)
* EULAR system includes spondyloarthropathy. JRA in EULAR refers only to IgM RF-positive disease
 Enthesitis-related arthritis (ERA), most common locally (one-

third of local JIA)
 Arthritis and enthesitis, or arthritis or enthesitis with at least
two of the following:
 Sacroiliac joint tenderness and/or inflammatory spinal
pain
 Presence of HLA-B27
 Family history in one or more first-degree relative(s) of
medically confirmed HLA-B27-associated disease
 Anterior uveitis that is usually associated with pain,
redness or photophobia
 Onset of arthritis in a boy after 6 years of age
Rheumatology 533
 This is more common in boys in late childhood or adolescence, tends

to be HLA-related. It can involve peripheral joints (knees, hips, MTP
joints), tendoarchilles, plantar fascia, back (stiff with poor posture),
and have acute anterior uveitis (painful red eye). There is a spectrum
of disease ranging from mono-articular arthritis or enthesitis to
progressive erosive disease, sacroiliitis and ankylosing spondylitis
 Juvenile psoriatic arthritis

 Arthritis and psoriasis, or arthritis and at least two of the following:
 Dactylitis (sausage digit)
 Nail pitting or onycholysis
 Family history of psoriasis in a first-degree relative
 Arthritis may predate onset of psoriasis by many years
COMPLICATIONS OF JIA
 Limb pain, swelling, deformity
 Loss of function, independence and ambulation
 Contracture, limb overgrowth, limb length discrepancy
 Osteoporosis, fracture, avascular necrosis
 Growth and pubertal delay (short stature, FTT)
 Uveitis, loss of vision, blindness
 Social and financial cost — Loss of schooling, social development,
poor self-image, hospitalisation
CLINICAL EVALUATION OF A CHILD WITH SUSPECTED JIA

Aims
 Determine any evidence of synovitis/arthritis/enthesitis
 Exclude secondary causes for limb symptoms (especially infection,
malignancy, reactive arthritis)
 Assess subtype of arthritis, severity and complications
History
 Pain, swelling, limited range of movement, loss of use of limb, e.g. limp
 Early morning stiffness and improvement with activity — Typical of
inflammatory arthritis
 Rash, fever, malaise, weight loss
 Preceding URTI, vaccination, chickenpox, rubella (reactive),
gastroenteritis, urethritis (HLA-B27 disease), travel (Lyme disease)
 Family history (arthritis, backache, other immune disease, psoriasis),
country of origin, socioeconomic status (rheumatic fever, TB)
 Functional status — Dependency, limitation by pain or stiffness
(home, activities of daily living, school, work)
Physical Findings
 Growth, pubertal status — Any
delay (chronic illness)
 Systemic features — Fever,
Rash (salmon pink evanescent/
psoriatic/vasculitic), nail pitting,
organomegaly, lymphadenopathy
 Musculoskeletal — Wasting,
abnormal gait (e.g. waddling),
kyphosis
 Mark joint/tendon findings on the
skeleton in Figure 15.2 for easier
visualisation and review
 Joints — Peripheral (include
temporomandibular/sacro-iliac)
 Axial skeleton — Cervical, thoracic,
lumbo-sacral (touch toes, measure
distance from the floor) Figure 15.2: Skeleton to mark joint/tendon
 Tendonitis/enthesitis — Including findings
plantar fascia, tendon achilles
 Synovial swelling over tendon sheaths, e.g. dorsum of hand, feet
 Deformities (contractures, varus, valgus, dropped wrists, swan neck
or Boutonniere)
 Measure limb length discrepancy
INVESTIGATIONS
No investigation is pathognomonic of JIA, but several are useful for
differentials.
At Onset
 Any evidence of inflammation, send immune markers
 New JIA panel:
 Full blood count, ESR, CRP, BUN/Cr, LDH/uric acid
 Antinuclear antibody, RF, HLA-B27 (if suspicious)
 Free thyroxine/TSH
 Peripheral blood film for blasts, bone marrow, CT abdomen
if suspicious of malignancy, e.g. pale, hepatosplenomegaly,
distension, uncharacteristic joint aspirate like few cells
 Aspirate joint (to exclude infection, blood)
 Juvenile idiopathic arthritis: Neutrophils predominate, gram stain
and cultures negative, long-standing effusions tend to be thick
and viscid, recent effusions more watery and clear
Rheumatology 535
 Infection: Turbid, proteinaceous, send for gram stain and culture.

TB or fungus if suspicious
Blood: Haemophilia, trauma, villonodular synovitis
 Liver function, renal function (baseline if starting NSAIDS)
 Eye (ophthalmological screening) — For all JIA and especially
pauci/oligoarticular disease
 Imaging
 X-rays — To exclude other diseases (infection, malignancy).
 Bony changes in JIA are relatively late
 Early: Peri-articular osteopenia, ↑ joint space
 Late: Erosions, sclerosis, ↓ joint space/subluxation
 Very late: Abnormal bone shape, joint collapse, ankylosis,
compression fracture, dislocations, avascular necrosis
 Bone densitometry (DEXA scan) for osteoporosis and bone
age (for long-standing disease at referral, especially if on
steroids or growth failure)
 Others as necessary — Ultrasound (fluid), MRI (localised
tendinitis), CT (tumour), bone scan
At Follow Up
 Full blood count, ESR, CRP
 Liver function, renal function (for medication side-effects)
 X-rays for progression of disease (usually for polyarticular disease,
ERA for sacroiliac disease)
TREATMENT OF ARTHRITIS
Goal: Suppression of inflammation and prevention of deformity and
disability, with minimum toxicity
Team approach: Patients, parents, medical, rehabilitative therapists,

school, social support
Table 15-14: Slit lamp examination for JIA patients

JIA subtype Frequency (months)
Systemic onset 12
Oligo JIA
ANA positive 3
ANA negative 6
Poly JIA 6
ERA 12
Psoriatic arthritis 6
 Correct diagnosis, exclusion of secondary disease

 Physical — Rest, pain relief, physiotherapy, occupational therapy
 Medical:
 Conventional (NSAIDS — Oral, gels, plasters, Cyclo-oxygenase
(COX-2) inhibitors, steroids — oral, iv, intra-articular, methotrexate,
sulphasalazine, hydroxychloroquine, IVIG, immunosuppressants)
 New therapies (biologicals against TNF, IL1, IL6, leflunomide,
thalidomide, combinations, bisphosphonates for osteoporosis)
 Alternative and traditional (massage, acupuncture, herbs, etc.)
 Regular eye review for uveitis and toxicity of medication (steroid-
induced cataracts, glaucoma)
 Future — Stem cell transplant
 Surgical (orthopaedic)
 Patient education, support (social, financial, emotional) —
Support club, social worker
Pain Relief
 Rest during active inflammation (including splinting), but minimise
time spent immobilised
 Warm or cold pack (ice)
 NSAIDS, massage, Transcutaneous Electrical Nerve Stimulation
(TENS)
Physiotherapy
 Early mobilisation is key to good joint and limb function
 Maintains range of motion, coordination, strength
 Posture, stretches, repetitions, weights
Occupational Therapy
 Splints and casts to maintain position after stretching (e.g. sleep), for
function (wrist paddles)
 Aids (thick pencil, handles), ambulation if really necessary (crutch,
rollator, stroller, wheelchair)
 Home adaptations (ramps, rails, height of table, chair, fittings)
 School (ramps, lifts, locker, class location)
Rheumatology 537
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

 Systemic lupus erythematosus is a multi-systemic disease of immune
dysregulation characterised by circulating antibodies to nuclear
and other tissue antigens (99% positive ANA). Autoantibodies and
immune complexes mediate tissue injury
 Wide variety of clinical features, can evolve with time, affecting
different organ systems; renal, neurological, cardiac disease and
infection are major causes of mortality
 Aetiology unknown, probably an interplay between genetic factors
and environmental triggers
 More common in females overall, possible due to hormonal
differences. In adults five to ten times more in females, local ratio of
9:1. Equal sex distribution below the age of 5 years
 Sometimes familial
 Rare in children. In Singapore, analysis of KKH figures (1997–2003)
indicate the incidence is at least about 1.5/100,000 children at risk
per year, which is about three times the reported western incidence,
and the overall sex ratio is 3:1 (female predominance). In KKH, we see
about 10–15 new SLE cases per year
EVALUATION AND DIAGNOSIS

 Definite diagnosis of SLE is made when four out of eleven of ACR
classification criteria are present (at any time) and no alternative
explanation exists
 However, lupus should be considered when characteristic features
occur in combination or evolve over time. Treatment should be
started if clinical disease is significant even if less than four criteria
are met
 High ESR and normal CRP, low complement levels (especially C3) are
suggestive of active SLE
Other Features of SLE

 Constitutional — Lupus fever, malaise, loss of appetite, loss of weight
 Dermatological — Alopecia, periungal erythema, vasculitis rash,
livedo reticularis, Raynaud’s Phenomenon, gangrene
 Liver, spleen, lymph node enlargement
 Musculoskeletal — Arthritis, arthralgia, tenosynovitis, myopathy
 Cardiac — Myocarditis, endocarditis, valvulitis, Libman-Sacks
vegetations, cardiac failure, Ischaemic Heart Disease (IHD)/AMI (can
be related to APS, hyperlipidaemia)
 Respiratory — Pneumonitis, pulmonary hypertension, pulmonary

haemorrhage, pulmonary atelectasis, shrinking lung (diaphragmatic)
 Gastrointestinal — Lupus gut (colitis), peritonitis
 Thrombotic events, APS
 Neurolupus — Central or peripheral manifestations
 Nephritis — Clinically or asymptomatic biochemical anomaly
 Anemia from any cause
 Fundus — Exudates, cytoid bodies, papilloedema, retinopathy
Renal Disease
 Nephritis is a major cause of morbidity and mortality in SLE.
 Untreated it can lead to hypertension, renal failure and death
 Can present clinically (as nephritic or nephrotic syndrome,
mixed picture, hypertension, acute or chronic renal failure); or an
asymptomatic biochemical abnormality (haematuria, proteinuria,
raised creatinine, abnormal creatinine clearance test)
 May have family history of SLE, renal lupus
 Follow up closely for evolution of renal disease (clinical oedema,
urinalysis, BP)
 Renal biopsy — Guide to management when considering
immunosuppression such as cyclophosphamide or if there is doubt
about reversibility of renal damage to prognosticate
 Evaluation of lupus nephritis:
 Urinalysis — For sediments and casts; culture if white blood cells
present
 Measurement of glomerular function:
 Plasma creatinine, urea nitrogen
 Creatinine clearance
 Radionuclide Glomerular Filtration Rate (GFR)
 Measurement of proteinuria
 Spot Protein: Creatinine Ratio
 24-hour protein excretion
 Immunologic tests — Anti-dsDNA antibody level, complement
assay
 Renal ultrasonography and biopsy — Light Microscopy (LM),
Electron Microscopy (EM), IF
 World Health Organisation Classification of Lupus Nephritis (Renal
biopsy)
 Class I Normal
 Class II Minimal change (A)/mesangial glomerulitis (B)
 Class III Focal and segmental proliferation
Rheumatology 539
Table 15-15: Criteria for the classification of SLE (ACR 1997)

Criteria Features/explanations
Malar (butterfly) rash Fixed erythema, sparing naso-labial folds
Discoid lupus Red raised scaly patch, later may have atrophic scarring
Photosensitivity
Oral or nasopharyngeal ulcerations Painless usually
Non-erosive arthritis (two joints) Tenderness, swelling, morning stiffness
Renal Disorder‡ Persistent proteinuria >0.5g/dL or 3+
cellular casts (red cell, Hb, granular, tubular, mixed)
Neurological Disorder‡ In the absence of offending drugs or metabolic derangements,
e.g. uraemia, ketoacidosis, electrolyte imbalances
Seizures
Psychosis
Serositis‡ Pleuritis (pain, rub, effusion)
Pericarditis (ECG, rub, effusion)
Haematological Disorder‡ In the absence of offending drugs
Haemolytic anemia with reticulocytosis
Leucopenia (<4,000/mm3)
Lymphopenia (<1,500/mm3)
Thrombocytopenia (<100,000/mm3)
Positive antinuclear antibody test In the absence of drugs associated with 'drug-induced lupus'
Immunologic Disorder‡ Antibodies to dsDNA
Antibodies to Smith nuclear antigen
Positive finding of antiphospholipid antibodies

 IgG or IgM ACA
 LAC
 False positive serologic test for syphilis for at least 6 months
(false positive VDRL) confirmed by Treponema Pallidum
Immobilisation (TPI) or Fluorescent Treponemal Antibody
(FTA) absorption test
Any one of the features on the right-side column will do

‡
 Class IV Diffuse proliferative Glomerulonephritis (GN)

 Class V Membranous GN
 Class VI Glomerular sclerosis
Combinations are possible, e.g. Class II and V. Class may change with
time and treatment
Antiphospholipid Syndrome (APS)

 Antiphospholipid syndrome is present if one of the clinical
manifestations and one of the laboratory tests on two or more
occasions (at least 12 weeks apart) are demonstrated — recurrent fetal
loss or vascular thrombosis (arterial and venous) plus LA or aCL IgG or
IgM, ≥40 GPL/MPL (or >99th percentile) or anti-beta 2 glycoprotein 1
IgG or IgM (moderate to high titres) in serum or plasma.
 Other features not included in the classification criteria include leg
ulcer, livedo recticularis, haemolytic anemia and thrombocytopenia
Neurolupus
 Clinical features may be due to leucostasis, vasculitis, APS with
thrombosis, infarct, haemorrhage
 May be overt (seizures, stroke) or subtle (mood change, behavioural
change, deterioration in schoolwork)
 May result in loss of independence for activities of daily living,
deterioration in schoolwork and socialisation
 Central or peripheral nervous system manifestations:
 Central nervous system: Cerebrovascular disease (stroke/
Transient Ischaemic Attack (TIA)), seizures, headache (excluding
migraine and Benign Intracranial Hypertension (BIH)),
demyelinating syndrome, movement disorder (chorea), acute
confusional state, anxiety disorder, cognitive dysfunction, mood
disorder, psychosis
 Peripheral nervous system: Acute inflammatory demyelinating
polyradiculoneuropathy (Guillain-Barré Syndrome), autonomic
disorder, mononeuropathy, single/multiplex, myasthaenia gravis,
cranial neuropathy, plexopathy, polyneuropathy
Investigations (Baseline)
 Full blood count, reticulocyte count, ESR, CRP, urea, creatinine, ALT,
AST, GGT, C3, C4, ANA, anti dsDNA, ENA profile, lupus anticoagulant,
anticardiolipin IgM/IgG, TGAb, TRAb, TPOAb, anti beta 2 glycoprotein
IgM/IgG
 Urinalysis, spun urine for casts, urine protein/creatinine ratio
Investigations (Follow-up)
 Full blood count, reticulocyte count, ESR, CRP, urea, creatinine, ALT,
AST, GGT, C3, C4, anti dsDNA
 Urinalysis, spun urine for casts, urine protein/creatinine ratio
 Eye review — Q6 months
 DEXA — Q12 months
Rheumatology 541
Clinical Review at Each Visit

 Vital signs (BP, HR)
 Disease activity, disease damage, any new organ involvement, drug
toxicity
 Compliance to treatment
 Growth, pubertal development, general health
 Clinical
THERAPY
 No cure. Aim to bring disease under control and prevent progressive
tissue damage
 Individualised and try to prevent flare
 Combined care: Medical assessment by rheumatologist,
nephrologist, ophthalmologist.
 Treat flares, hypertension, infection early and appropriately
Supportive Measures
 Explanation, understanding by patient and family of disease, drugs.
 Episodic flares likely. Long-term review. Reassurance that serious
complications are rare, most patients have normal life expectancy if
compliant with medication and appropriate medical review
 Avoidance of triggering factors (sun or fluorescent-light exposure,
fatigue, intercurrent infection) which provoke exacerbations. Use
Ultraviolet A and B sunscreen SPF 50, hats, long sleeves
 Raynaud’s phenomenon: Avoid cold exposure, cigarettes, caffeine,
 Support groups — JLC (Juvenile Lupus Club), Club Rainbow
Medical Drugs
 Steroids
 Mainstay of treatment for flares and maintenance treatment (low
dose)
 Oral steroids: 0.5–2mg/kg/day, max 60mg/day. Taper slowly as
inflammation is controlled
 Intrvenous pulsed steroids (methylprednisolone) associated with
faster clinical improvement especially for rapidly progressive CNS
or renal disease. Dose 10–30mg/kg/dose for 1–3 consecutive days
(max 1g)
 Monitor for toxicity especially BP, eye, osteoporosis and growth
failure.
 Aim to achieve disease control by using optimal dose with
minimal side effects from medications
 Hydroxychloroquine
 Useful for rash, arthritis, serositis and malaise, help alleviate risk
of thrombosis in APS when use in combination with aspirin and
prolongs remission.
 Reduces cholesterol level, seizure and flare episodes
 Dose 4–6mg/kg/day
 Azathioprine
 Used as first-line and maintenance therapy for nephritis and
moderate lupus manifestations
 Oral 2–3mg/kg/day
 Cyclophosphamide
 For proliferative lupus nephritis, neurolupus
 Intravenous pulse 0.5–1g/m2/monthly for 6 months
 Mycophenolate (Mofetil)
 Could be used as first-line or maintenance therapy
 Dose 600mg/m2 BD oral/IV (0.5–2.0g/day max) or 30–50mg/kg/
day
 Cyclosporin A
 For nephritis
 Dose 3–5mg/kg/day, keep trough level <200ng/ml
 Enalapril
 For proteinuria, hypertension
 Dose 0.2–1.0mg/kg/dose (max 40mg) once a day
 Biologics — Used in refractory cases
 Others: Antihypertensives, antibiotics, anticonvulsants, splenectomy as
necessary
For APS
 Acute phase — Aspirin, heparin, low-molecular-weight heparin like
enoxaparin, prostacyclin
 Prophylaxis if major vessel thrombosis — Warfarin, keep INR 3–4
(arterial), 2.5–3 (venous)
Plasmapheresis
 For rapid removal of antibodies and immune complexes, together
with steroids and cytotoxic drugs
 Anecdotal reports of short-term benefit in acute, life-threatening SLE
Other therapeutic options include renal dialysis, organ transplant, and

stem cell transplant.
Rheumatology 543
In general for active nephritis

 Class II Steroids suffice
 Class III Steroids + immunosuppressant, e.g. azathioprine/
cyclophosphamide
 Class IV Usually needs aggressive treatment with
cyclophosphamide/MMF
 Class V Usually nephrotic, respond to steroids well,
use cyclosporine/MMF
 ACE inhibitors like enalapril help decrease proteinuria or Angiotensin
receptor antagonist like losartan
Differentiating between lupus flare and infection

 Both can present with fever and ill health
 Infection can precipitate a flare
 Infection important cause of mortality, so have high index of suspicion
 Often infection will have high CRP, but active lupus has normal CRP
despite high ESR
 Look for sources of infection including respiratory, meningitis, skin
infection, TB; culture as necessary
 Look for evidence of active lupus: rash, arthritis, serositis, low C3,
high dsDNA titre
 If uncertain, may need to cover for both infection and active disease
flare until investigations return
PROGNOSIS OF SLE
 Vast improvement over the last 10 years
 Early studies: <5% survive 5 years (KKH 100% 5 year-survival from
2009–2013)
 Now 85–90% survive 5 years, 75–85% survive 10 years. Most patients
have near-normal life span
 Worst in Afro-carribeans, Asians, males, patients at extremes of age,
non-compliance with treatment, family history of severe lupus
 Infections, renal disease, CNS complications are major causes of
death
 Late in disease — Fracture, AVN, cardiovascular complications,
infection are major causes of morbidity
JUVENILE DERMATOMYOSITIS (JDM)

 Characterised by a diffuse microangiitis involving skin, skeletal
muscle, gastrointestinal tract, CNS, among others
 Not uncommon locally, under- and/or delayed diagnosis happens
often
 Aetiology unknown. Seems to develop after an acute viral infection
in many children
CLINICAL EVALUATION
 Commonly presents with muscle tenderness and weakness, rash on
face and extensor surface, constitutional symptoms
 Calcinosis, arthritis, muscle atrophy, alopecia common
 Gastrointestinal vasculitis and CNS disease potentially fatal
 Palatal and respiratory disease can result in aspiration pneumonia
and respiratory failure
 Unique characteristics of JDM (as opposed to adults):
 Vasculitis and calcinosis: Frequent and often severe, indicate
active disease
 Malignancy: Not associated
 Range of clinical features of JDM:
 Constitutional: Fever, malaise, loss of appetite, loss of weight
 Skin/mucosa: Heliotrope rash and periorbital oedema, malar rash,
Gottron papules (Metacarpophalangeal (MCP), Interphalangeal
(IP) joints; any extensor bone surface, e.g. knees, lateral malleoli),
erythroderma, erythematous rash, vasculitic rash, livedo,
telangiectasia, periungal capillary changes, skin ulcers, oral ulcers,
alopecia, panniculitis, calcinosis, subcutaneous fat atrophy (looks
muscular), mechanic’s hands (hyperkeratosis, fissures), palmar
plantar hyperkeratosis
 Muscle: Proximal muscle weakness, truncal weakness, speech
(nasal), swallowing, breathing difficulty (shortness of breath,
exertional dyspnea)
 Joints: Arthritis, arthralgia, contractures
 Gastrointestinal tract: Gut vasculitis (potentially life-threatening),
pancreatitis, hepatitis
 Central nervous system: Vasculitis with seizures, stroke, chorea
 Lung: Interstitial lung disease, pneumothorax, abnormal lung
function
 Cardiac: Pericarditis, myocarditis, arrhythmia, sinus tachycardia
Rheumatology 545
 Infection: Prone to infections of skin (calcinotic lesions, S. aureus

abscess), lung (suppurative, TB, Pneumocystis jirovecii pneumonia)
 Other unusual presentations (fluid collections, e.g. seroma of back)
DIAGNOSIS
 Five criteria of Bohan and Peter (rash, muscle weakness, elevated
enzymes, typical EMG and muscle biopsy) — Presence of all five
make diagnosis definite, four probable and three possible (see Table
15-16 for Peter and Bohan criteria)
 Can start treatment with positive clinical features (rash and proximal
weakness) and raised muscle enzymes (any one). Invasive EMG
and muscle biopsy are not done in children unless the diagnosis is
uncertain. MRI helps to localise an ideal site for biopsy as muscle
disease is patchy (vastus medialis of thigh is a good site). This
modality has become a replacement for muscle biopsy in recent
years.
 Skin
 Eyelids — Heliotrope (purplish) discoloration, periorbital oedema,
Gottron’s papules — erythematous, scaly rash over dorsal MCP
and Proximal Interphalangeal (PIP) joints
 Muscles
 symmetrical weakness of the proximal musculature
 ↑serum level of one or more of skeletal muscle enzymes — CK,
aldolase, AST, ALT, LDH
 Electromyography — Myopathy and denervation
 Muscle biopsy — Necrosis and inflammation
 'Dermatomyositis sine myositis' or Amyopathic JDM — Characteristic
skin disease (e.g. heliotrope rash, Gottron’s papules, vasculitis,
calcinosis) without muscle disease could be a variant, or muscle
disease may have subsided or may develop later
Table 15-16: Bohan and Peter's five criteria
 Skin
Eyelids — Heliotrope (purplish) discoloration, periorbital oedema, Gottron’s papules —
erythematous, scaly rash over dorsal MCP and Proximal Interphalangeal (PIP) joints
 Muscles — Symmetrical weakness of the proximal musculature
 ↑ serum level of one or more of skeletal muscle enzymes — CK, AST, LDH, aldolase
 Electromyography — Myopathy and denervation
 Muscle biopsy — Necrosis and inflammation
 Important to exclude other connective tissue disease (e.g. SLE,

MCTD or overlap syndrome)
 Check ANA, anti-dsDNA, u1 RNP), eczema, infective rash. Usually
no positive immune markers in JDM
MEDICAL TREATMENT
 Glucocorticoids
Initial:
Oral prednisolone 2mg/kg/day;
IV methylprednisolone 30mg/kg/day, max 1,000mg/dose x 1–3 days (for
severe disease — more rapid improvement);
Then:
Tapering oral prednisolone once clinical improvement is demonstrated
 Hydroxychloroquine
4–6mg/kg/day in addition to prednisolone for control of skin disease
 Immunosuppressives
Methotrexate: 0.3–1.0mg/kg/week or 10–25mg/m2/week (oral, IM or SC);
max 20–50mg/week
 Intravenous immunoglobulin
2g/kg/dose Q 28 days
Note: Do not use Every Other Day (EOD) steroid in JDM — tends to relapse
Prednisolone is given with calcium and vitamin D
Methotrexate is given with daily folic acid at 1mg/day
Review
At each visit, assess:
 Growth, pubertal development, general health and activity
 Rash — Increasing calcinosis or vasculitis ulcers, infection
 Muscle power — Limbs (proximal and distal), trunk, neck, speech,
swallowing, breathing
 Functional status — Activities of daily living, feeding, getting out
of bed, stairs, school
 Childhood Myositis Assessment Scale (CMAS) — Every visit
 Other organ disease — CNS, gut, respiratory
 Toxicity of medication — Cushingoid, BP
 Labs: JDM panel (FBC, ESR/CRP, CK/aldolase/AST/ALT/LDH, GGT, BUN/
cr, UFEME) and, if available, serum vWF:Ag and neopterin levels
Rheumatology 547
Investigations at Baseline
 Juvenile dermatomyositis panel
 Antinuclear antibody, Anti-dsDNA, ENA profile (as appropriate)
 Magnetic resonance imaging and/or EMG, MRI, muscle biopsy —
Only if myositis is uncertain
 Eye (ophthalmologist) — Baseline for steroids, hydroxychloroquine
SYSTEMIC VASCULITIDES
 Vasculitis is defined as inflammation of blood vessels.
 In KKH, systemic vasculitis is the most common rheumatic disease
encountered.
 Henoch-Schonlein purpura (HSP) is the commonest systemic
vasculitis seen locally, followed by Kawasaki disease (KD).
 Other vasculitides including polyarteritis nodosa (PAN) and Wegener
granulomatosis (WG) are uncommon locally
Classification of Systemic Vasculitides

 Predominantly large vessel vasculitis
 Takayasu arteritis (TA)
 Predominantly medium vessel vasculitis
 Childhood PAN
 Cutaneous polyarteritis
 Kawasaki disease
 Predominantly small vessel vasculitis
 Granulomatous
WG, Churg-Strauss syndrome
 Non-granulomatous
Henoch-Schonlein purpura, microsopic polyangiitis
Isolated cutaneous leucocytoclastic vasculitis
Hypocomplementaemia urticarial vasculitis
 Other vasculitides
 Behcet disease
 Vasculitis associated with connective tissue disease
 Vasculitis secondary to infection (Including hepatitis B associated
PAN), malignancies, drugs (hypersensitivity vasculitis)
 Primary angiitis of central nervous system
 Cogan Syndrome
 Unclassified
Table 15-17: Classification Criteria

Henoch-Schonlein Purpura
ACR 1990 Criteria (Sensitivity 87.1%, Specificity 87.7%) EULAR/PRINTO/PRES Criteria 2008 (100% Sensitivity, 87% Specificity)
Presence of at least two of the followings: Purpura or petechiae (mandatory) with lower limb
 Age ≤20 years at disease onset predominance and at least one of the following criteria:
 Palpable purpura  Abdominal pain
 Acute abdominal pain  Histopathology (typical leucocytoclastic vasculitis
 Biopsy showing granulocytes in the walls of small with predominant IgA deposit or proliferative GN with
arterioles/venules predominant IgA deposit)
 Arthritis/arthralgia
 Renal involvement (proteinuria or haematuria)
Polyarteritis Nodosa (PAN)
ACR 1990 Criteria (Sensitivity 82.2%, Specificity 86.6%) EULAR/PRINTO/PRES Criteria 2008 (Sensitivity 89.6%,
Specificity 99.6%)
Presence of at least three of the ten following criteria: Histopathology (evidence of necrotizing vasculitis) or
 Granulocyte or mixed leucocyte infiltrate in an arterial angiographic abnormalities (Mandatory) plus one of the five
wall on biopsy following criteria:
 Angiographic abnormalities  Skin involvement (livedo reticularis, skin nodules,
 Livedo reticularis superficial/deep skin infarction)
 Myalgia  Myalgia/muscle tenderness
 Diastolic blood pressure >90mmHg  Hypertension (SBP/DBP >95th percentile)
 Mono- or polyneuropathy  Peripheral neuropathy (sensory/motor)
 Elevated blood urea nitrogen or creatinine  Renal involvement (proteinuria/haematuria/impaired
 Testicular pain/tenderness renal function)
 Hepatitis B reactants
 Weight loss >4kg
Wegener Granulomatosis (WG)
ACR 1990 Criteria (Sensitivity 88.2%, Specificity 92%) EULAR/PRINTO/PRES Criteria 2008 (Sensitivity 93.3%,
Specificity 99.2%)
Presence of at least two of the following: At least three of the six following criteria:
 Abnormal urinary sediment (Haematuria, >5 RBCs/hpf)  Histopathology
 Abnormal findings on chest radiograph (nodules, cavities  Upper airway involvement (chronic purulent or bloody nasal
or fixed infiltrates) discharge or recurrent epistaxis/crusts/granulomata, nasal
 Oral ulcers or nasal discharge septum perforation, chronic or recurrent sinus inflammation)
 Granulomatous inflammation on biopsy  Laryngo-tracheo-bronchial involvement
(subglottic,tracheal or bronchial stenosis)
 Pulmonary involvement (CXR or CT showing nodules,
cavities, fixed infiltrates)
 ANCA positivity (MPO/p or PR3/c ANCA)
 Renal involvement
Takayasu Arteritis (TA)
ACR 1990 Criteria (Sensitivity 91%, Specificity 98%) EULAR/PRINTO/PRES Criteria 2008 (Sensitivity 100%,
Specificity 99.9%)
Presence of at least three of the following: Angiographic abnormalities of the aorta or its main branches
 Arteriographic evidence of narrowing or occlusion of the and pulmonary arteries showing aneurysm/dilatation
entire aorta, its primary branches, or large arteries in the (mandatory criteria) plus one of the five following criteria:
proximal, upper or lower extremities  Pulse deficit or claudication
 Decreased brachial artery pulse  4 limbs BP discrepancy
 Claudication of an extremity  Bruits
 Systolic BP >10mmHg difference in systolic BP between arms  Hypertension
 Bruit over subclavian arteries or the aorta  Acute phase reactant
 Age at disease onset ≤40 years
Rheumatology 549
HENOCH-SCHONLEIN PURPURA (HSP)
 Acute small vessel leucocytoclastic IgA1-mediated vasculitis

 The commonest small vessel vasculitis affecting children in
Singapore
 History of preceding infection is implicated in majority
 Self-limiting but can recurs in up to a third of affected children
 Cutaneous Purpura (Non-thrombocytopaenic)
 Classically non-blanchable palpable purpura, predominantly
affecting the dependent area especially lower limbs and buttock
 Rash may vary from petechiae to ecchymosis, purpura and
bullous type
 Rash may persist for weeks to months
 Bruise-like rash is due to deep seated vasculitis. These
ecchymoses are often associated with underlying subcutaneous
oedema
 The presence of subcutaneous oedema may precede or
associated with gastrointestinal involvement.
 GI Involvement
 Secondary to bowel wall swelling
 May present with bloody stool, abdominal pain (colicky if
intussuception presents), acute abdomen (if perforation occurs)
 Stool can be normal but with occult bleeding
 GI symptoms may precede onset of rash in small number of
children
 Arthritis/arthralgia
 Presence of arthritis may be confused with underlying
subcutaneous oedema. Differentiation between arthritis and
subcutaneous oedema is important in the management of
patient
 May be migratory, involvement of knees and ankles are common
 Usually transient, does not result in deformity
 Renal Involvement
 Microscopic haematuria (common), proteinuria, renal
impairment, end-stage renal failure
 May develop months after onset of HSP
 Atypical presentations
 Scrotal swelling, occult pulmonary involvement
Diagnosis
Based on EULAR/PRINTO/PRES Criteria
Investigations
 Blood tests are often not needed unless clinical suspicion of
thrombocytopenia/coagulation defect presents
 Immunoglobulin A may be normal/elevated
 Urinalysis (to look for haematuria/proteinuria). Urine Protein/
Creatinine ratio or 24 hours urine protein collection may be required.
 Abdominal ultrasound is sometimes required if history/clinical
assessment is suggestive of intussuception (may also show
thickened bowel wall, suggestive of enteritis/colitis)
 Stool occult blood (for occult GI bleeding secondary to colitis/
enteritis)
 Skin biopsy is often not required (unless in atypical cases)
Treatment
 Supportive (adequate hydration, monitoring of GI and renal
involvement)
 Nonsteroidal anti-inflammatory drugs for arthritis
 Use of steroids is still controversial. However, the use of steroid is
well-accepted in patients who have abdominal pain. In some studies,
steroid use has shown to reduce duration and severity of abdominal
pain, hospitalisation stay and the need for surgery.
 Early use of steroids does not prevent the progression of renal
disease or changing the course of illness.
 In the presence of subcutaneous oedema, steroids may be helpful in
reducing the swelling and GI associated complications.
 Serial urinalysis at routine clinic visit is required for 2 years from the
disease onset, particularly important for the first 6 months.
 Immunosuppression therapy (cyclophosphamide or azathioprine)
may be necessary in refractory or relapse cases or those with renal
and/or major organ involvement.
Prognosis
 Self-limiting, good prognosis
 <1% develop end-stage renal failure
 Recurrence rate of 10–30%
Rheumatology 551
KAWASAKI DISEASE
 Acute febrile mucocutaneous lymph node syndrome with

multisystem medium sized and small sized vasculitis affecting
commonly children younger than 5 years
 Unknown aetiology
 If left untreated, the risk of coronary artery lesions is about 20%
(dilatation, aneurysm, thrombosis, myocardial infarction and sudden
death)
 Incidence in Singapore: 32.5 per 100,000 children younger than 5
years old per year
 Average of 70–75 cases a year
Diagnostic Criteria
Fever of unknown aetiology persisting for 5 days or more (temperature
spike from 38oC–40oC) with at least four out of the five following criteria:
 Changes in peripheral extremities
 Initial stage: Reddening of palms and soles, indurative oedema
 Convalescent Stage: membranous desquamation from nail bed
 Polymorphous exanthem
 Bilateral Non-suppurative conjunctivitis
 Changes in the lips and oral cavity: Reddening of lips, strawberry
tongue, diffuse injection of oral and pharyngeal mucosa
 Cervical lymphadenopathy (lymph node size ≥1.5cm)
If patient does not fulfill the above criteria, patient may have incomplete
KD.
Irritability is a very important clinical feature in KD
Clinical Course
 Acute phase: 7–14 days, characterised by fever and inflammatory
changes
 Subacute phase: 10–28 days, resolution of fever and rash.
Desquamation of fingers and toes. Coronary abnormalities and
thrombocytosis is common
 Convalescent phase: 4–10 weeks after onset. Begins when all clinical
signs disappear and continues until acute phase reactants return to
normal.
Atypical KD presentation
 Aseptic meningitis, encephalitis, extreme irritability, cranial nerve
palsies, sensorineural hearing loss
 Hepatic dysfunction, gall bladder hydrops

 Congestive cardiac failure
 Arthritis
 Pleural effusion/infiltrates
 Macrophage activation syndrome
Frequent Pitfalls in Diagnosis of KD

 Children younger than 1 year and adolescents often present with
incomplete features
 Rash mistaken for allergy/viral exanthem
 Pyuria — Mistaken for UTI due to sterile pyuria
 Lymphadenopathy mistaken for lymphadenitis secondary to
infection
 Cerebospinal fluid pleocytosis may be misdiagnosed as viral
meningitis
 Kawasaki disease is not considered in a patient with FUO (fever of
unknown origin)
Important Clues in KD
 Fingertip desquamation, even in the absence of the other principal
symptoms especially in incomplete KD cases, is a strong indicator of
KD
 Mild conjunctival injection or red lips with prolonged fever can be
manifestations of KD which may warrant an echocardiogram.
Laboratory Findings
 There is no specific or diagnostic laboratory findings in KD
 Leucocytosis with a predominance of immature and mature
granulocytes
 Anemia may be present
 Thrombocytosis (Platelet 500,000–1 million/mm3, in the second
week). Thrombocytopenia if present may be a sign of DIVC. Low
platelet count is also a risk factor for coronary aneurysm.
 Important to look for elevated acute phase reactants (raised
C-reactive protein, ESR) — Elevation of ESR (but not CRP) can be
caused by IVIG therapy. Therefore, ESR should not be used as the sole
determinant of severity of inflammation post-IVIG treatment.
 Sterile pyuria
 Mild–moderate transaminitis, low albumin
Rheumatology 553
Echocardiography in KD
 Used to detect coronary artery dilatation, aneurysm, thrombosis,
stenosis, pericardial effusion, valvular regurgitation, perivascular
“brightness”/echogenicity
 For uncomplicated cases, echocardiogram should be done at 2
weeks and at 6–8 weeks after onset of disease
 In patients with normal echo findings at 4–8 weeks, repeat echo
at 1 year after the onset of illness is unlikely to reveal coronary
abnormalities.
 Useful in incomplete KD cases
Evaluation of Suspected Incomplete KD

For those who have fever ≥5 days and 2–3 clinical criteria, first step is to
evaluate the CRP and ESR levels.
 If patient has CRP <3.0mg/dL and ESR <4mm/hr, patient should be
followed on daily basis. Re-evaluation with ESR and CRP is needed if
fever continues. If fever resolves, echocardiogram is required only if
typical peeling occurs during subacute phase.
 If patient has CRP ≥3.0mg/dL and/or ESR ≥40mm/hr with three or
more supplemental laboratory criteria, echocardiogram should be
performed and treatment should be started
 If patient has CRP ≥3.0mg/dL and/or ESR ≥40mm/hr with less than
three supplemental laboratory criteria, echocardiogram should be
performed. Treatment should only be started if echocardiogram
is positive. Otherwise, patient should be followed on daily basis.
Repeat echocardiogram may be indicated if fever persists.
* Supplemental laboratory criteria include albumin ≤3.0g/dL, anemia for

age, elevation of ALT, Platelet after 7 days ≥450,000/mm3, white blood
cell count ≥15,000/mm3 and urine ≥10WBC/hpf
Principles in treatment of KD
 Treatment should be started within the first 10 days of illness.
 Infants 6 months or younger on Day 7 or more of fever without
other explanation should undergo laboratory testing. If evidence of
systemic inflammation is found (especially when irritability presents),
echocardiogram should be done even in the absence of clinical
criteria
 Treatment should be given even in those who have KD beyond
day 10 with clinical and laboratory signs of on-going inflammation
(raised ESR, CRP)
Risk Scoring for IVIG Resistance
Kobayashi Score
2 points each Sodium ≤133mmol/L
≤4 days of illness before initial treatment
AST ≥100 IU/L
Neutrophil ≥80%
1point each CRP ≥10mg/dL

Age ≤12 months
Platelet count ≤30,000/mm3
*Risk score of ≥5 points is high risk for IVIG resistance
Egami Score
2 point ALT ≥80 IU/L
1 point each Age ≤6 months

≤4 days of illness
Platelet count ≤30,000/mm3
CRP ≥8mg/dL
*Risk score of ≥3 points is high risk of IVIG resistance
Harada Score (determine the risk of coronary artery aneurysms)
 WBC ≥12,000/mm3
 Platelet count ≤350,000/mm3
 CRP ≥3+
 Haematocrit ≤3.5g/dL
 Age ≤12 months
 Male sex
*IVIG is given to a child who fulfill four of the above criteria assessed
within 9 days of onset of illness
Treatment
IVIG
 First-line treatment for KD
 Should be administered within first 10 days of illness. Even if beyond day
10, if systemic signs of inflammation still present, IVIG is still indicated.
Rheumatology 555
 By giving IVIG, it reduces risk of coronary artery complications from

20% to 5%
 Dose: 2g/kg as a single infusion, infusion lasts for 8–12 hours
 Infusion rate increment and monitoring during infusion is as per
ward protocol
 Complications: Chills/rigor, hypotension, drug reaction i.e.
anaphylaxis, infections
 Consider pre-medication to be given 30 mins before IVIG:
Diphenhydramine 1mg/kg/dose (max dose 50mg) and Paracetamol
15mg/kg/dose (max dose 1g)
 Consider reducing infusion rate or stopping infusion if complication
occurs
 Risk of IVIG resistance is about 10–20%
Aspirin
 Used as antiplatelet agent
 Lack of additional benefit of adding aspirin to IVIG treatment in the
prevention of coronary complications
 More important during convalescent phase when the risk of
coronary artery thrombosis is higher (especially when co-existing
thrombocytosis and hypercoagulable state)
 Dose: Vary from 30–50mg/kg/day to 80–100mg/kg/day during acute
phase. Once fever subsides, aspirin dose is reduced to 3–5mg/kg/day
 Aspirin can be stopped after 6–8 weeks if the latest echocardiogram
is normal. Continue aspirin in patients with persistent coronary
abnormalities
 Complications of aspirin: Allergy, gastritis, GI bleeding, chronic
salicylism, Reye’s Syndrome
 Patients allergic to aspirin, or who have contracted varicella while
on aspirin, or intending to have varicella vaccination: Alternative —
dipyridamole 1–2mg/kg/dose (adult 50–100mg) TDS or clopidogrel
1mg/kg/day (adult 75mg)
Steroid
 Used as second-line agent for refractory KD
 When compared to second dose of IVIG, there is no difference in
term of coronary outcome
 Reduces fever and acute phase reactant more rapidly than second
dose of IVIG; highly effective in refractory cases
 Dose: Pulse methylprednisolone may vary from 15–30mg/kg/day for
1–3 days or oral prednisolone 1–2mg/kg/day before weaning
Others
 Unfractionated heparin/low molecular weight heparin/warfarin (for
coronary thrombosis)
 Streptokinase/urokinase/tissue plasminogen activator (for coronary
thrombosis)
 Infliximab (used as third-line therapy in refractory cases)
 Surgery: coronary artery bypass, percutaneous transluminal coronary
recanalisation
Severe complications
Myocardial infarction, ventricular dysfunction, heart failure, severe
arrhythmias, post-infarction angina
Prognosis
Recurrence 3%; Fatality rate <1%
TAKAYASU ARTERITIS
 Chronic nonspecific granulomatous vasculitis affecting large vessels
i.e. aorta and its branches, coronary and pulmonary arteries
 Female predominance, more commonly seen in Asian
 Most common during third decade of life
 Pathogenesis: unclear, multifactorial i.e. genetic, environment,
autoimmunity
 Tuberculosis was implicated in 50% of TA cases in some reports.
 Resulting in stenosis, occlusion, aneurysm of blood vessels
 Course of disease: active and quiescent phase
Clinical Presentations
 Acute early phase: Non-specific constitutional symptoms, i.e. fever,
muscle pain, abdominal pain, arthralgia, fatigue, weight loss, night
sweats, headache, giddiness, hypertension, visual loss
 Non-specific symptoms or asymptomatic at early phase of disease →
leads to long lag period to diagnosis
 Chronic phase: limb claudication
Rheumatology 557
Clinical Signs
 Hypertension (the most commonly found presentation at diagnosis)
 Arterial bruit (carotid, renal)
 Decreased or absent pulse, radio-radial or radio-femoral delay
 Difference in blood pressure of >10mmHg
Criteria for Diagnosis

EULAR/PRINTO/PRES 2008 Criteria
ACR 1990 Criteria
Figure 15.3: TA Angiographic classification
Type I Type IIa Type IIb Type III Type IV Type V
Adapted from Hata A, et al. 1996
 Type 1 Branches from the aortic arch

 Type IIa Ascending aorta, aortic arch and its branches
 Type IIb Ascending aorta, aortic arch and its branches,
thoracic descending aorta
 Type III Thoracic descending aorta, abdominal aorta and/
or renal arteries
 Type IV Abdominal aorta and/or renal arteries
 Type V Combined features of Type IIb and IV
Involvement of coronary and pulmonary arteries is
designated as C(+) and P(+) respectively
Involvement of blood vessels

 Abdominal aorta (commonly involved)
 Aortic arch and branches
 Renal artery stenosis (associated with hypertension, headache is common)
 Pulmonary artery (often under-reported)
Investigation
 Definite diagnosis of TA in acute phase is difficult
 Gold standard: conventional angiography (depicts luminal changes better
but not vessel wall, not sensitive in detecting early vascular changes)
 Other imaging modalities: CT angiography or MR angiography
(depicts mural changes better), colour doppler ultrasonography,
F-FDG-PET Scan (more superior in detecting blood vessel wall
inflammation, may be more useful than MRA in early stage of TA)
Treatment
 Early diagnosis and prompt treatment are indispensable to prevent
irreversible vessel damage and organ damage
 Mainstay of treatment: corticosteroids (as bridging therapy)
 Early use of high dose corticosteroids is initially used for induction of
remission
 Adjunctive treatment: methotrexate, azathioprine, mycophenolate
mofetil, cyclophosphamide
 Anti-platelet treatment
 Some reports of successful treatment by using anti-TNF agent i.e.
Infliximab and IL-6 blockers, e.g. tocilizumab
 Surgical treatment: Percutaneous transluminal angioplasty, artery
bypass graft, renal autotransplantation
DRUGS IN RHEUMATOLOGY
A wide array of drugs are available for symptomatic, anti-inflammatory
and immunomodulation of rheumatic disease, to control pain, damage
and progression:
 Nonsteroidal anti-inflammatory drugs
 Steroids
 Disease-modifying antirheumatic drugs
 Cytotoxics
 Biologics: Anti-TNF, anti-IL1 agents
Rheumatology 559
Other modalities of treatment include:

 Plasmpheresis — Anecdotal use in severe SLE, in combination with
immunosuppression
 Bone marrow/stem cell transplant — Limited number of successful
reports for SLE, JIA other rheumatic disease refractory to other treatment
 B cell immunosuppresion rituximab for refractory SLE
NSAIDS
 Most common medication taken worldwide
 First-line of treatment for arthritis (together with intra-synovial steroids)
 Inhibit the activity of COX enzymes
 Dose dependent effects:
 Low dose anti-platelet
 Low-medium anti-pyretic
 Medium analgesic
 High anti-inflammatory
Aspirin (Acetylsalicylic Acid)

 Traditional drug, but frequent dosing (qid), and toxicity have led to
increased use of other drugs
 Dose:
 Anti-inflammatory: 80–100mg/kg/day (max 3.6g/day), adjust to
keep levels 20–30mg/dl, given with food
 Anti-platelet: 3–5mg/kg/day
 Adverse reactions:
 Gastric irritation (50%)
 Tinnitus and/or diminished hearing (15%)
 Hepatotoxicity (50%, 15% cessation of therapy)
Table 15-18: Traditional NSAIDs that have been RDA-approved for children
NSAID Dosage Comments
Well-tolerated, approved for
Ibuprofen 30–40mg/kg/day (tds, qds)
children
Approved for children older
Tolmetin 20–40mg/kg/day (tds, qds)
than 2 years
Approved for children older
Naproxen 10–20mg/kg/day (bd)
than 2 years
Diclofenac (Voltaren) 1–3mg/kg/day (tds)
For children older than 14 years;
Indomethacin 1–2.5mg/kg/day (tds, qds)
higher CNS and gastric toxicity
 Reye’s syndrome (rare)

 Hypersensitivity (in asthma) (rare)
 Salicylism
 Mild: lethargy, dizziness, headache, diaphoresis, nausea
 Moderate: confusion, hyperpnea, metabolic acidosis,
respiratory alkalosis
 Severe: hyperpyrexia, convulsions, cardiovascular collapse
Cyclo-oxygenase-2 (COX-2) Selective Inhibitors

 Selectively inhibit COX- 2 enzyme with minimal effect on COX-1
enzyme at recommended doses, thus safer (gastrointestinal) and
comparably effective for acute and chronic pain relief
 Potentially useful in patients with:
 Poor gastrointestinal tolerance of traditional NSAIDs
 Low platelet patients
 Sensitivity to traditional NSAIDs
 Limitations
 Not yet approved for children
 Gastrointestinal toxicity (though much less than traditional NSAIDs)
 No effect on platelets. Can cause fluid retention and hypertension
 Cost
 Formulation: no liquid form locally
Steroids
 Among the most potent anti-inflammatory drugs. Mainstay of
treatment for many severe rheumatic diseases such as SLE, JDM,
vasculitis and rarely, arthritis. Dramatic effects but prolonged
administration at high dose gives unacceptable toxicity, therefore limit
the dose and duration of treatment.
 Use as bridging therapy for ALL rheumatic diseases
 Irreversible adverse reactions in children includes
 Posterior subcapsular cataract
 Osteonecrosis/AVN
 Striae rubrae
 Others
 Intrasynovial steroids — Infection, transient crystal synovitis,
if repeated cartilage damage, most common are atrophic skin
changes, asymptomatic calcifications
 Intra-ocular — Glaucoma
Rheumatology 561
 Oral steroids especially longer, high dose

 Suppression of hypothalamic-pituitary axis
 hypoadrenalism as steroids are tapered
 Immune suppression
 More susceptible to infection (e.g. TB, herpes virus) to avoid
crowded places, seek treatment early if febrile, contact with
chickenpox, measles. Signs of infection may be masked, so
have high level of suspicion
 Physical appearance changes: Cushingoid habitus, weight
gain, rounded face, buffalo hump, acne, stretch marks,
hirsutism can be very disturbing
 Advise regarding controlled-calorie, low-fat, low-sugar diet
 Easy bruising, poor wound healing — Physical care to avoid
injury
 Metabolic changes: hyperglycaemia, hypercholesterolaemia,
sodium and water retention, hypokalaemia
 Hypertension
 Neurological: euphoria, depression, mood lability, psychosis,
pseudotumour cerebri
 May be difficult to distinguish from neuropsychiatric
manifestations of SLE
 Musculoskeletal: osteopenia, proximal myopathy, avascular
necrosis
 Advice regarding diet, calcium supplement, exercise,
consider bisphosphonates
 Growth suppression on doses as low as 3mg/day — Risk
higher at higher dose
 Eye review regularly — Cataract, glaucoma
 Risks of steroid withdrawal — Adrenal crisis, flare of disease,
headache (benign raised intracranial hypertension)
 Never abruptly stop steroids due to adrenal crisis risk especially in
sick patients
DISEASE MODIFYING ANTI-RHEUMATIC DRUGS (DMARDS)

 Slow or even reverse bony erosion and cartilage loss, thus affects
natural course of RA
 Act slowly over weeks or months
Methotrexate
 Effective and generally well-tolerated in children
 Dose 0.3–1mg/kg once a week oral/SC (better absorption and efficacy)
 Give with folic acid daily, avoid sulphur drugs and alcohol
 Monitor carefully because of potential for toxicity (once in stable
dose, Q8–12 weeks)
 Bone marrow suppression (megaloblastic anemia, lymphopenia)
 Hepatic (enzyme elevation)
 Gastrointestinal including nausea, oral ulcers
Sulphasalazine
 Dose: 40–50mg/kg/day (BD or TDS)
 Before use: ensure no sulfa allergy and/or G6PD deficiency
 Side-effects include rash, gastritis, liver dysfunction, renal
dysfunction and bone marrow suppression
Hydroxychloroquine
 Anti-malarial drug with moderate anti-inflammatory properties
 Used for arthritis and SLE (skin, joint, serositis, malaise, prolong
remission, APS prevention)
 Dose 4–6mg/kg/day (max 400mg/day)
 G6PD deficiency — Relative contraindication
 Side-effects:
 Regular eye review Q 6 months — Macular degeneration, corneal
deposit (must stop)
 Gastric irritation
 Skin rash — Reversible, dark skin discoloration
IMMUNOSUPPRESSIVES AND CYTOTOXICS
Cyclophosphamide (CTX)
 Alkylating agent with potent anti-inflammatory action, use limited
by toxicity
 Used for lupus nephritis (Class IV), CNS lupus, vasculitis
 Dose IV 0.5–1g/m2 monthly for 6 months then 3 monthly for 1 year
(CNS lupus), up to 3 years (for Class IV nephritis)
 Daily oral dosing may give higher cumulative doses and long-term
toxicity
Rheumatology 563
 Side-effects:
 Nausea and vomiting
 Myelo- and immunosuppression greatest in second week post IV
pulse (fall in total WBC)
 Liver toxicity
 Haemorrhagic cystitis — Ensure adequate hydration (>2L/m2/24
hours) with diuresis and mesna (2-mercaptothanesulfonic acid)
70% of CTX dose if at higher dose/or prone to it
 Long-term risk of secondary malignancies (myeloproliferative,
bladder and skin cancer)
 Gonadal damage with hormonal deficiency and sterility, least
risk in prepubertal children, greatest risk in gonadally mature
individuals
 Rare: SIADH
Mycophenolate Mofetil (MMF)

 Immunodulating drug — Prodrug (rapidly hydrolysed to
mycophenolic acid)
 Inhibits purine synthesis in T and B cells (selective non-competitive
inhibitor)
 Useful in SLE nephritis intolerant of cyclophosphamide, and JIA
uveitis resistant to MTX and localised scleroderma failed MTX
 Awaits controlled studies in children
 Dose oral 600mg/m2 BD (max 2.0g/day)
 Monitoring once on stable dose, Q8–12 weeks
Azathioprine
 Purine analogue. Traditional drug treatment for SLE, JDM, PAN,
systemic sclerosis — Nephritis, thrombocytopenia, haemolytic anemia
 Dose 0.5–2.5mg/kg OD/BDS
 Side-effects:
 Oral ulcers, gastrointestinal, bone marrow suppression,
liver toxicity increased by enzyme deficiency (thiopurine
methyltransferase [TPMT]) can be predicted by measuring TPMT
levels or PCR for genotype (not routine)
Cyclosporin A
 T-cell mediated immunosuppression (calcineurin inhibitor)
 For lupus nephritis, refractory JIA, uveitis, macrophage activation
syndrome, haemophagocytic panniculitis, JDM (MAS — Fever,
abnormal LFT, high triglycerides, sharp fall in counts, ESR, DIC, bone
marrow haemophagocytosis diagnostic but not necessarily present)
 Dose 2–3mg/kg/day (max 5mg/kg/day)
 Side-effects: Alopecia, hirsutism, gingival hyperplasia, tremors,
parasthesia, hypertension, renal damage, nausea and vomiting
 Must monitor:
 Trough levels (125–175mcg/ml, but do not correlate well clinically)
 Grapefruit juice can increase levels of cyclosporin significantly
BIOLOGICALS
IVIG
 First-line for Kawasaki disease, as adjunct therapy in other rheumatic
diseases
 Dose:
 Replacement therapy: 400–500mg/kg/dose
 Anti-inflammatory: 2gm/kg/dose
 Premedicate as other biologic infusion with paracetamol 15mg/kg
and diphenhydramine 1mg/kg IV/PO 30 mins prior to infusion)
Etanercept
 Tumour necrosis factor (TNF) receptor analogue — Competitively
binds TNF and inhibits natural receptors from binding
 Approved by Food and Drug Administration (FDA) for JIA —
moderately to severely active polyarticular JIA refractory to other
MTX and uveitis
 Combination MTX and Etanercept increases efficacy with acceptable
toxicity
 Dose 0.8mg/kg/dose up to max 25mg/dose SC once a week (can be
combined into 1 dose)
 Side-effects: Injection site reactions are not uncommon
 No increased rate of infection, but try to complete immunisation
before starting etanercept; if contact with chickenpox, give VZIG or
PO/IV acyclovir
Rheumatology 565
Infliximab
 Chimeric monoclonal antibody to TNF alpha
 For JIA (especially uveitis, ankylosing spondylitis), Crohn’s and
rheumatoid arthritis; not yet FDA-approved for JIA
 Dose infusion 5–10mg/kg over 2 hours at time 0, 2 weeks, 6 weeks, 8
weeks after initial infusion
 Risk of anaphylaxis, reactivation of tuberculosis
 Contraindicated in tuberculosis, heart failure and during intercurrent
infection
Adalimumab
 Humanised monoclonal antibody against TNF alpha
 Dose for children 4–17 years:
 24mg/m2 2-weekly or
 15–<30kg: 20mg every other week
 ≥30kg: 40mg every other week
 Side-effects similar to Etanercept
566
APPENDIX I: GROWTH CHARTS
16
15
14
13
12
11
10
0
0 2 4 6 8 10 12 14 16 18 20 22 24
Anthropometric Study on Pre-school Children in Singapore, 2000

National Health Group Polyclinics
Appendix I: Growth Charts 567
16
15
14
13
12
11
10
0
0 2 4 6 8 10 12 14 16 18 20 22 24

32
30
28
26
24
22
20
18
16
14
12
10
6
24 28 32 36 40 44 48 52 56 60 64 68 72

36
34
32
30
28
26
24
22
20
18
16
14
12
10
6
24 28 32 36 40 44 48 52 56 60 64 68 72

96
94
92
90
88
86
84
82
80
78
76
74
72
70
68
66
64
62
60
58
56
54
52
50
48
46
44
42
40
0 2 4 6 8 10 12 14 16 18 20 22 24

96
94
92
90
88
86
84
82
80
78
76
74
72
70
68
66
64
62
60
58
56
54
52
50
48
46
44
0 2 4 6 8 10 12 14 16 18 20 22 24

130
125
120
115
110
105
100
95
90
85
80
75
70
65
60
24 28 32 36 40 44 48 52 56 60 64 68 72

130
125
120
115
110
105
100
95
90
85
80
75
70
65
60
24 28 32 36 40 44 48 52 56 60 64 68 72

24
22
20
18
16
14
12
10
0 2 4 6 8 10 12 14 16 18 20 22 24

24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
0 2 4 6 8 10 12 14 16 18 20 22 24

24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
24 28 32 36 40 44 48 52 56 60 64 68 72

24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
24 28 32 36 40 44 48 52 56 60 64 68 72

54
54
52
52
50
50
48
48
46
46
44
44
42
42
40
40
38
38
36
36
34
34
32
32
30
30
0 2 4 6 8 10 12 14 16 18 20 22 24
0 2 4 6 8 10 12 14 16 18 20 22 24
Age (months)

54
54
52
52
50
50
48
48
46
46
44
44
42
42
40
40
38
38
36
36 34
34 32
32 30
0 2 4 6 8 10 12 14 16 18 20 22 24
30 Age (months)
0 2 4 6 8 10 12 14 16 18 20 22 24

56
56
55
55
54
54
53
53
52
52
51
51
50
50
49
49
48
48
47
47
46
46
45
45
44
44
43
43
42
42
24
24 28
28 32
32 36
36 40
40 44
44 48
48 52
52 56
56 60
60 64
64 68
68 72
72
Age (months)

5656
5555
5454
53
53
52
52
51
51
50
50
49
49
48
48
47
47
46
46
45
45
44
44
43
43
42
24 28 32 36 40 44 48 52 56 60 64 68 72
42
24 28 32 36 40
Age
44
(months)
48 52 56 60 64 68 72

180
175
170
165
160
155
150
145
140
135
130
125
120
115
110
105
100
95
90
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
190
185
180
175
170
165
160
155
150
145
140
135
130
125
120
115
110
105
100
95
90
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
100
90
80
70
60
50
40
30
20
10
0
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
100
90
80
70
60
50
40
30
20
10
0
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
36
35
34
33
32
31
30
29
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
6 7 8 9 10 11 12 13 14 15 16 17 18
36
35
34
33
32
31
30
29
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
6 7 8 9 10 11 12 13 14 15 16 17 18
590
APPENDIX II: DRUGS

INFECTIONS
Note:
Neonatal dosing to be used till postmenstrual age (PMA) of 44 weeks.
PMA is equivalent to gestational age plus postnatal age, e.g. for a baby
born at 28 weeks gestation and now 21 days old, PMA would be 31 weeks.
For PMA >45 weeks, refer to dosing indicated for child.
ANTIBIOTICS
Drug Preparation Route Dosage Remarks

Amikacin Inj 500mg/2ml vial IM/IV Neonate: Nephrotoxic and
PMA ≤29 weeks: (≤7 days: 18mg/kg/dose ototoxic.
Q48H; 8–28 days: 15mg/kg/dose Q36H; Therapeutic level:
≥29 days: 15mg/kg/dose Q24H) Target peak:
PMA 30–34 weeks: (≤7 days: 18mg/kg/dose 30–40mcg/ml
Q36H; ≥8 days: 15mg/kg/dose Q24H) Target trough:
PMA 35–44 weeks: 15mg/kg/dose Q24H <10mcg/ml (* ideal:
Child: 4–5mcg/ml),
15–22.5mg/kg/day Q8–12H * especially
Adult: if existing
15mg/kg/day Q8–12H; max 1.5g/day nephrotoxic drugs
or poor renal
function
Infuse over 30–60
mins.
Amoxycillin Mixt 125mg/5ml Oral Neonate: Mixture stable for
Cap 250mg Preterm neonate: 20–30mg/kg/day Q12H 7 days.
Term neonate: 50mg/kg/day Q8H
Otitis media due to resistant pneumococci:
80–90mg/kg/day Q8H
Child:
50mg/kg/day Q8H
Otitis media due to resistant pneumococci:
Appendix II: Drugs 591

Amoxycillin + Mixt 200mg + Oral Neonate: Mixture stable for 7
Clavulanic Acid 28.5mg/5ml PO: days at 4°C (store in
(Augmentin) Preterm neonate: 30mg (Amoxycillin refrigerator).
Tab 500mg + component)/kg/day Q12H Not suitable for IM
125mg Term neonate: 50mg (Amoxycillin route.
component)/kg/day Q12H Use higher oral dose
Inj 1,000mg + IV IV: for intermediate
200mg Augmentin 30mg/kg/dose susceptibility/
(<7 days: Q12H; ≥7 days: Q8H) resistant
Child: pneumococcus.
Oral:
50mg (Amoxycillin)/kg/day Q12H
Severe infections:
Up to 80–90mg (Amoxycillin)/kg/day
IV:
Augmentin 30mg/kg/dose Q8H (up to 40mg/
kg/dose Q8H)
Ampicillin Inj 500mg/vial IM/IV Neonate: Allergic or
IV: anaphylactic
Bacteraemia: reactions may occur.
50mg/kg/dose Rubella-like rash
common with many
Meningitis or GBS infection: viral infections;
100mg/kg/dose does not equate to
PMA ≤29 weeks: (≤28 days: Q12H; >28 ampicillin allergy.
days: Q8H)
PMA 30–36 weeks: (≤14 days: Q12H; >14
days: Q8H)
PMA 37–44 weeks: (≤7 days: Q12H; >7
days: Q8H)
Child:
IV:
Mild/moderate:
Severe/meningitis:
200–400mg/kg/day Q4–6H
Continued overleaf

Ampicillin + Tab 375mg Oral Neonate:
Sulbactam (220mg + 147mg) IV:
(Unasyn) Term neonate: 150mg/kg/day (ampicillin) Q12H
Syr 250mg/5ml Preterm neonate: 100mg/kg/day (ampicillin) Q12H
For severe or multi-drug resistant infection:
Inj 750mg/vial, IV/IM 100mg/kg/dose (ampicillin)
1.5g/vial PMA ≤29 weeks: (≤28 days: Q12H; >28
days: Q8H)
PMA 30–36 weeks: (≤14 days: Q12H; >14
days: Q8H)
PMA 37–44 weeks: (≤7 days: Q12H; >7 days: Q8H)
Child:
Oral:
(<30kg: 25–50mg/kg/day (ampicillin)
Q12H; ≥30kg: 375–750mg/dose Q12H)
IV:
Mild/moderate:
100–150mg/kg/day (ampicillin) Q6–8H
Severe:
200–400mg/kg/day (ampicillin) Q6H (adult
6–12g/day, i.e. 8g of ampicillin and 4g of
sulbactam daily)
Azithromycin Cap 250mg Oral Child: Dosage for respiratory
(Zithromax) Susp 200mg/5ml 10mg/kg OM (max 500mg) on Day 1, tract infections.
then Avoid in known
5mg/kg OM (max 250mg) on Days 2–5 macrolide allergy.
or
10mg/kg OM x 3 days
Cefazolin (Kefzol, Inj 1g/vial IM/IV Neonate: First-generation
Ancef) 25mg/kg/dose cephalosporin.
≤2kg: (≤7 days: Q12H; >7days: Q12H) Not indicated for
>2kg: (≤7 days: Q12H; >7days: Q8H) initial therapy of
Child: neonatal bacterial
Mild–moderate infections: infections.
Severe infections:
Cefepime Inj 1g/vial IM/IV Child: Fourth-generation
Mild/moderate infections: cephalosporin.
100mg/kg/day Q12H (adult 1–2g/day) Has no activity against
Severe infections: Enterococcus spp.,
150mg/kg/day Q8H (adult 2–6g/day) methicillin-resistant
S. aureus, Bacteroides
fragilis.

Cefotaxime Inj 500mg/vial IM Neonate: Third-generation
(Claforan) IV IV/IM: cephalosporin.
Sepsis/meningitis: Adjust dosing interval
50mg/kg/dose in renal failure.
Gonococcal infection:
25mg/kg/dose
Gonococcal Ophthalmia prophylaxis:
Single dose 100mg/kg.
PMA ≤29 weeks: (≤28 days: Q12H; >28
days: Q8H)
PMA 30–36 weeks: (≤14 days: Q12H; >14
days: Q8H)
Child:
Mild/moderate:
Severe:
Meningitis:
Up to 300mg/kg/day Q6H
Ceftazidime Inj 1g/vial IM/IV Neonate: Third-generation
IV 50mg/kg/dose cephalosporin.
PMA ≤29 weeks: (≤28 days: Q12H; >28 Activity against
days: Q8H) Pseudomonas.
PMA 30–36 weeks: (≤14 days: Q12H; >14 Adjust dosing interval
days: Q8H) for renal failure.
Child:
Mild/moderate:
90–150mg/kg/day Q8H (adult 3g/day)
Severe/meningitis:
200–300mg/kg/day Q8H (max 6g/day)
Ceftibuten Susp 36mg/ml Oral 9mg/kg/day Q12H or Q24H (max 400mg) Oral third-generation
(Cedax) cephalosporin.
Continued overleaf

Ceftriaxone Inj 250mg IM/IV Neonate: Third-generation
500mg, 1–2g/vial <2kg: (≤7 days: 50mg/kg/dose Q24H; >7 days: cephalosporin.
50mg/kg/dose Q24H) Avoid use in
≥2kg: (≤7 days: 50mg/kg/dose Q24H; >7 days: hyperbilirubinemic
75mg/kg/dose Q24H) neonates and in
Ophthalmia neonatorum, treatment: neonates requiring
IM, IV: calcium-containing
25–50mg/kg as a single dose; max single dose: solutions (parenteral
125mg nutrition).
Child:
50–100mg/kg/day Q12–24H
Meningitis:
100mg/kg/day Q12–24H (max 2g Q12H)
Cefuroxime Axetil Susp 125mg/5ml Oral Child:
(Zinnat) Tab 250mg 20–30mg/kg/day Q12H (adult 1g/day)
Treatment of Otitis media:
Higher dose recommended
Cephalexin Cap 250mg, Oral Neonate: First-generation
(Keflex) Susp 125mg/5ml Mild infection, UTI: cephalosporin.
50mg/kg/day Q8H
Severe infection:
25mg/kg/dose (<7 days: Q12H; 7–21 days:
Q8H; ≥22 days: Q6H)
UTI prophylaxis:
15–17mg/kg/dose ON
Child:
25–50mg/kg/day Q6–8H (max 4g/day)
Otitis media:
Osteomyelitis:
Chloramphenicol Tab 250mg Oral Child: Aplastic anemia.
Susp 125mg/5ml PO: Grey baby syndrome.
Inj 1g/vial IV 50–100mg/kg/day Q6H (adult 1–2g/day)
IV:
50–100mg/kg/day Q6H (adult 2–4g/day)

Ciprofloxacin Tab 250mg Oral Child: Caution: Safety
Inj 200mg/100ml Oral: in children not
IV 20–30mg/kg/day Q12H (adult 0.5–1.5g/day) established yet.
IV:
20–30mg/kg/day Q8–12H (adult
800–1200mg/day Q8–12H)
Clarithromycin Tab 250mg Oral Neonate and Child: Avoid in known
(Klacid) Susp 125mg/5ml 15mg/kg/day Q12H (adult 1g/day) macrolide allergy.
Clindamycin Cap 150mg Oral Neonate: Diarrhoea is a
Inj 300mg/2ml IV PO/IV: common side-effect.
5mg/kg/dose May cause pseudo-
PMA ≤29 weeks: (≤28 days: Q12H; >28 days: membraneous colitis.
Q8H)
PMA 30–36 weeks: (≤14 days: Q12H; >14
days: Q8H)
PMA 37–44 weeks: (≤7 days: Q12H; >7 days:
Q8H)
Child:
Oral:
10–40mg/kg/day Q6–8H (adult
600–1800mg/day)
IV:
Mild/moderate:
20mg/kg/day Q6–8H (adult 600mg–1.2g/day)
Severe:
20–40mg/kg/day Q6–8H (adult 1.2–2.7g/day)
Cloxacillin Cap 250mg Oral Neonate: Hypersensitivity
Syr 125mg/5ml IV: reactions.
Inj 500mg/vial IV/IM 50mg/kg/dose Diarrhoea.
PO:
25mg/kg/dose
<2kg: (≤7 days: Q12H; >7 days: Q8H)
≥2kg: (≤7 days: Q8H; >7 days: Q6H)
Child:
PO:
IV:
Severe infection:
100mg/kg/day Q6H
Meningitis:
200mg/kg/day Q6H
Continued overleaf

Co-trimoxazole TMP80mg + SMZ Oral Neonate: Not to be used in
(Bactrim, 400mg (AdultTab) PO: G6PD deficiency
Septrim) (8mg TMP + 40mg SMZ)/kg/day Q12H Generally, not to be
TMP40mg + SMZ IV: used in <2 months
200mg/5ml (Syr) (6–12mg TMP + 30–60mg SMZ)/kg/day of age
Q12H
TMP80mg + SMZ Severe or multi-drug resistant infection:
400mg/5ml (Inj) IV IV:
(15–20mg TMP + 75–100mg SMZ)/kg/
day Q6H
Child:
PO:
(8–12mg TMP + 40–60mg SMZ)/kg/
day Q12H
For PCP:
IV/PO:
(20mg TMP + 100mg SMZ)/kg/day Q6H
Doxycyline Tab 100mg Oral Child: Not recommended for
2–4mg/kg/day Q12–24H (adult children <8 years.
100–200mg/day)
Erythromycin Ethylsuccinate Oral Neonate: Drug of choice
Syr 200mg/5ml PO/IV 10mg/kg/dose for pertussis and
(Erythromycin <1kg: (≤14 days: Q12H; 15–28day: Q8H) Mycoplasma.
base) ≥1kg: (≤7 days: Q12H; 8–28day: Q8H) IV Infuse over 30–60
Tab 250mg (Base) Child: mins.
Inj 500mg/vial IV Oral:
(Lactobionate) 30–50mg/kg/day (Erythromycin base)
Q6–8H (adult 1–2g/day)
IV:
Ethambutol Tab 400mg Oral Child: May cause optic
15–25mg/kg/day OM (max 2.5g/day) neuritis.
Baseline vision tests
recommended.
Fusidic Acid Susp 50mg/ml Oral Child: Infuse over 2–4 hours.
Tab 250mg Oral: To be used in
Inj 500mg/vial IV 20–50mg/kg/day Q8H combination therapy
(<1 year: 50mg/kg/day Q8H; 1–5 years: for MRSA infections.
250mg Q8H; >6 years: 500mg Q8H)
IV:
20mg/kg/day Q8H (adult 500mg Q8H,
max 2g/day)

Gentamicin Inj 80mg/2ml IM/IV Neonate: Nephrotoxic and
PMA ≤29 weeks: (≤7 days: 5mg/kg Q48H; ototoxic (not to be
8–28 days: 4mg/kg Q36H; ≥29 days: 4mg/ given by IV bolus
kg Q24H) injection).
PMA 30–34 weeks: (≤7 days 4.5mg/kg Infuse over 30–60
Q36H; ≥8 days: 4mg/kg Q24H) mins.
PMA 35–44 weeks: 4mg/kg Q24H Therapeutic level:
Child: Target peak:
5–7.5mg/kg/day Q8H 8–10mcg/ml
UTI: Target trough:
5mg/kg/day Q24H (uncomplicated cases, <2mcg/ml
>1 month old) (ideal*: <1mcg/ml)
* especially if existing
nephrotoxic drugs
or poor renal
function
Imipenem + Inj 500mg + IM/IV Child: Not recommended for
Cilastatin 500mg 15–25mg/kg/dose Q6H (max 4g/day) meningitis.
(Tienam) Dosage based on imipenem component May cause
of Tienam convulsions.
Adjust dose in renal
dysfunction.
Isoniazid Tab Oral 10–20mg/kg/day Q24H (max: 300mg/day) Hepatitis.
(INH) 100mg Prophylaxis: Hypersensitivity
10–15mg/kg/day Q24H reactions.
Levofloxacin Tab 250mg Oral Child: Caution: Safety
(Avelox) Inj 250mg/50ml IV <5 years old: 10mg/kg/dose Q12H in children not
≥5 years old: 10mg/kg/dose Q24H (max established yet.
750mg/day)
Linezolid (Zyvox) Tab 600mg Oral, Neonate: Myelosuppression
Susp 100mg/6ml IV IV/PO: may occur.
Inj 600mg/vial Preterm neonate: 10mg/kg/dose
(<7 days: Q12H; ≥7 days: Q8H)
Term neonate: 10mg/kg/dose Q8H
Child:
10mg/kg/dose Q8H (max 600mg/doseQ12H)
Continued overleaf

Meropenem Inj 500mg IV Neonate:
Sepsis:
20mg/kg/dose
PMA <32 weeks: (≤14 days Q12H; >14
days Q8H)
PMA ≥32 weeks: (≤7 days Q12H; >7 days:
Q8H)
Intra-abdominal and non-CNS Sepsis:
20mg/kg/dose
Meningitis/pseudomonas sepsis:
40mg/kg/dose Q8H (for all ages)
Child:
Sepsis:
20mg/kg/dose Q8H (adult 3g/day)
Meningitis:
40mg/kg/dose Q8H (adult 6g/day)
Metronidazole Tab 200mg Oral Neonate: For anaerobic
(Flagyl) Inj 500mg/100ml IV IV/PO: infections.
Loading dose 15mg/kg, Peripheral
then neuropathy, metallic
maintenance dose 7.5mg/kg/dose (begin taste.
one dosing interval after loading dose) at the
following dosing interval:
PMA ≤29 weeks: (≤28 days: Q48H; >28 days:
Q24H)
PMA 30–36 weeks: (≤14days: Q24H; >14
days: Q12H)
PMA 37–44 weeks: (≤7days: Q24H; >7 days:
Q12H)
Child:
PO:
IV:
22.5–40mg/kg/day Q6–8H
Neomycin Tab 500mg Oral Child: For suppression of
Sulphate 50–100mg/kg/day Q8H (adult 1–2g Q6H) intestinal aerobic
bacteria.
In premature and
newborn babies, 10%
may be absorbed.

Nitrofurantoin Tab 50mg Oral Child: Haemolytic anemia
Susp 5mg/ml 5–7mg/kg/day Q6H (adult 400mg/day) in G6PD-deficient
Prophylaxis: patients.
1–2mg/kg/day Q24H (adult 100mg/day) Peripheral neuropathy.
Not recommended for
neonates.
Penicillin Inj 2.4MU/vial IM Neonate: Long-acting penicillin.
Benzathine Congenital syphilis:
Single dose 50,000U/kg/dose
Child:
Rheumatic fever prophylaxis:
<27.3kg: 0.6 million units once a month
≥27.3kg: 1.2 million units once a month
Penicillin Inj 1MU/vial, IM/ Neonate:
Crystalline G 5MU/vial IV Bacteraemia:
(Benzylpenicillin) 50,000U/kg/dose
Meningitis:
500,000U/kg/day
PMA ≤29 weeks: (≤28 days: Q12H; >28 days:
Q8H)
PMA 30–36 weeks: (≤14 days: Q12H; >14
days: Q8H)
PMA 37–44 weeks: (≤7 days: Q12H; >7 days:
Q8H)
Congenital syphilis:
IV 50,000U/kg/dose Q12H on D1–D7,
then
Q8H for a total of 10–14 days
Child:
Mild/moderate:
100,000–150,000U/kg/day Q6H
Severe:
200,000–500,000U/kg/day Q4–6H
(max 24 million U/day)
GBS meningitis:
(≤7 days: 250,000–450,000U/kg/day Q8H;
>7 days: 450,000–500,000U/kg/day Q6H)
Penicillin V Tab 250mg Oral Child:
Rheumatic fever prophylaxis: 250mg Q12H
Continued overleaf

Piperacillin/ Inj 4.5g/vial IM/IV Neonate: For polymicrobial
Tazoactam (4,000mg 50–100mg (Piperacillin)/kg/dose infections including
(Tazocin) Piperacillin PMA≤29 weeks: (≤28 days: Q12H; >28 days: gram-negative
+ 500mg Q8H) bacteria, especially
Tazobactam) PMA 30–36 weeks: (≤14 days: Q12H; >14 Pseudomonas,
days: Q8H) anaerobes and
PMA 37–44 weeks: (≤7 days: Q12H; >7 days: Staphylococcus.
Q8H)
Child:
Mild/moderate:
80mg (Piperacillin)/kg/dose
(<2 months: Q8H; ≥2 months: Q6H)
(adult: 6–8gm/day)
Severe:
80mg (Piperacillin)/kg/dose
(≥2 months: Q6H) (adult: 12–18gm/day)
Pyrazinamide Tab 500mg Oral Child: Hepatitis.
20–40mg/kg/day Q12–24H (max 2g/day)
Quinopristin- IV Child: Not for Enterococcus
Dalfopristin 7.5mg/kg/dose Q8H faecalis.
(Synercid) Preferably given by
central line due to
thrombophlebitis.
arthralgia.
Rifampicin Cap 150mg, Oral TB: Urine, faeces, saliva,
Susp 100mg/5ml IV 10–20mg/kg/day Q12–24H tears and sweat
(max 600mg/day) stained orange/red.
Neisseria meningitidis prophylaxis:
Neonate:
5mg/kg/dose Q12H x 2 days
>1 month: 10mg/kg/dose Q12H x 2 days
(max 600mg/dose)
H. influenzae type B prophylaxis:
Neonate:
<3 months: 10mg/kg/dose Q24H x 4 days
≥3 months: 20mg/kg/dose Q24H x 4 days
(max 600mg/dose)
Streptomycin Inj 5g/vial, Inj IM only Child: Nephrotoxic and
1g/vial 20–40mg/kg/day Q12–24 (max 1g/day) ototoxic.

Tetracycline Tab 250mg Oral Child: Not recommended
35–50mg/kg/day Q6H for children below
(adult 3g/day) 8 years.
Can cause permanent
discolouration and
enamel hypoplasia of
the teeth.
Tobramycin Inj 20mg/vial IV Neonate: Infuse over 30–60
40mg/vial <2kg: (≤7days: 5mg/kg/dose Q48H; >7days: mins.
4–5mg/kg/dose Q24–48H) Nephrotoxic and
>2kg: (≤7days: 4mg/kg/dose Q24H; >7days: ototoxic.
4mg/kg/dose Q12–24H) Good activity against
Child: Pseudomonas.
IV:
3–7.5mg/kg/day Q8H or Q24H
Vancomycin Inj 500mg/vial IV Neonate: Nephrotoxic and
15mg/kg/dose ototoxic.
PMA≤29 weeks: (≤14 days: Q18H; >14 days: Each dose to be
Q12H) infused over a period
PMA 30–36 weeks: (≤14 days: Q12H; >14 of at least 60 mins.
days: Q8H) Therapeutic level
PMA 37–44 weeks: (≤7 days: Q12H; >7 days: Q8H) Peak: 30–40mcg/ml
Child: Trough: 15–20mcg/
15mg/kg/dose Q6H ml (complicated
(adult 2–4gm/day Q6–12H) infections);
10–15mcg/ml
(others)
Adjust dosing interval
in renal failure.
ANTIFUNGALS
Drug Route Dose Comments Side-effects

Amphotericin B IV 50mg/vial Neonate: Use higher dose Fever, chills, phlebitis,
(AmB, Fungizone) IV 1mg/kg/dose Q24H, 1–1.5mg/kg/dose for nephrotoxicity, ↓K,
infuse over 4–6 hours. Aspergillus, 0.5–0.6mg/ ↓Ca, ↓Mg, headache,
Child: kg/dose for C. albicans, hepatotoxicity, anemia.
IV: 0.7–1.0mg/kg for Rare: Neurotoxicity,
0.25–0.5mg/kg/dose non-albicans Candida. Not anaphylaxis.
Q24H initially, effective against Fusarium Pre-treatment for infusion
increase to or Scedosporium spp. reactions: Paracetamol,
0.5–1mg/kg/dose Q24H, diphenhydramine or
infuse over 2–4 hours. hydrocortisone.
Dilute in electrolyte-free Taper hydrocortisone
5% Dextrose at 0.1mg/ml over time as tolerance
develops to AmB.
Liposomal Inj 50mg/vial Child and Neonate: *See guidelines for Fever, chills, other
AmphotericinB Empiric therapy: the use of liposomal reactions as with AmB,
(L-Amb, 3mg/kg/day Q24H Amphotericin B. but less nephrotoxicity
Ambisome)* and hepatotoxicity.
Probable or proven
invasive fungal infection:
5mg/kg/day Q24H
Fluconazole Cap 50mg, Child: PO 3–6mg/kg/dose Rash, GI symptoms,
150mg cap; PO/IV: Q24H for oropharyngeal, hepatotoxicity.
IV 100mg/5ml 3–12mg/kg/dose Q24H esophageal candidiasis. Anaphylaxis.
Neonate: IV:
10–12mg/kg/dose Q24H
Systemic candidiasis: IV: if invasive Candida/
12–25mg/kg loading dose, Cryptococcus. Not for
then maintenance dose Aspergillus sp., Candida
IV/PO: krusei or glabrata.
10–12mg/kg/dose
PMA <30 weeks: (≤14 days:
Q48H; >14 days: Q24H)
PMA ≥30 weeks: (≤7 days:
Q48H; >7 days: Q24H)
Mucosal candidiasis:
PO 6mg/kg/dose on D1,
then
3mg/kg/dose Q24H
Fungal prophylaxis in
high risk infants (e.g.
birth weight<800gm):
IV:
3mg/kg/dose
(<14 days: Q72H; 14–28
days: Q48H; >28 days: Q24H)
Drug Route Dose Comments Side-effects

Itraconazole PO 5–10mg/kg/day OD or For Aspergillus, GI symptoms, rash,
10mg/ml BD. Solution best taken in mucocutanous Candida, oedema, headache, ↓K,
solution fasting state Penicillium marneffei, hepatotoxicity, ↓plt,
(150ml) Sporotrichosis, Scedosporium. ↓WBC.
Flucytosine PO 500mg Child: Used as adjunctive therapy Bone marrow suppression
(5-fluro-cytosine, IV 2,500mg/ IV/PO: with AmB for Candidal/ (especially if renal failure),
5FC) 250ml vial 50–150mg/kg/day Q6H Cryptococcal meningitis, renal dysfunction, GI
neonatal invasive candidiasis. symptoms, transaminitis,
Unable to do 5FC levels rash, neuropathy,
locally, use 50–75mg/kg/day confusion, hallucinations.
to avoid marrow suppression.
Nystatin Susp Neonate: Oropharyngeal GI symptoms, rash.
100,000U/ml Preterm: 100,000U Q6H candidiasis.
Term: 200,000U Q6H
Child:
400,000U TDS
Adult:
600,000U TDS
Caspofungin IV 50mg Load 70mg/m2/dose OD Second-line agent for May need adjustment
(CANCIDAS) vial or (max 70mg), invasive candidiasis in patients receiving
70mg vial then or aspergillosis a concomitant liver
50mg/m2/dose OD (max or for empiric therapy enzyme inducer and/or
50mg) or treatment of sensitive with moderate or severe
fungal infection hepatic impairment.
not responding to Fever, rash, pruritus, GI
Amphotericin therapy. symptoms, headache,
anemia, phlebitis.
Voriconazole Tab 200mg Child: Invasive aspergillosis. GI symptoms,
(VFEND) Inj 10mg/ml IV: Scedosporium species and photosensitivity rash
≤14 years old, <50kg: second-line antifungal especially with prolonged
9mg/kg/dose Q12H agent for invasive fungal therapy.
≥15 years old or >12 disease failing to respond Visual disturbance
years old, ≥50kg: to Amphotericin as first- (common, usually mild
6mg/kg/dose Q12H on D1, line therapy and reversible).
then IV 4mg/kg/dose Q12H Caution in hepatic
Oral: impairment.
<15 years old, <50kg:
PO 9mg/kg/dose Q12H
≥15 years old, <40kg:
PO 200mg Q12H on D1,
then 100mg BD
<15 years old, ≥50kg OR
≥15 years old, ≥40kg:
PO 400mg Q12H on D1,
then 200mg Q12H
Continued overleaf
* Guidelines for use of liposomal preparations of amphotericin in place of standard formulation Amphotericin B
Indications:
 Pre-existing renal impairment
 Development of amphotericin B nephrotoxicity whilst on therapy
 Patients where renal failure is expected to compromise underlying condition, e.g. renal transplant,
haematopoietic stem cell transplant or chemotherapy for haematological malignancy where HSCT is planned
 Failure of amphotericin B therapy, no improvement in signs or symptoms of infection at 7 days of treatment
with standard doses of amphotericin B
 For other moulds which are less susceptible to amphotericin B, it may be appropriate to use liposomal
amphotericin B at 5mg/kg/dose Q24H as first-line:
 Fusarium sp. or zygomycetes
 For Scedosporium species, voriconazole should be considered first-line therapy
Note: Infusion-related reactions to standard Amphotericin B are not an indication for change to lipid-based
formulation. The rate of infusion reactions is comparable between lipid and standard formulations.
Treatment of fevers and chills may be controlled by pre-medication such as paracetomol, antihistamine
and hydrocortisone and/or by slowing the infusion rate.
ANTIHELMINTHICS

Albendazole Tab 200mg, 400mg Oral 1–2 years 200mg Drug of choice for
(Zentel) Susp 400mg/10ml >2 years 400mg as a single dose roundworm, whipworm,
hookworm. Should be
 Roundworm, whipworm,
avoided during pregnancy
hookworm: Single dose and lactation, and in
 Pinworm: Repeat dose 2
children <1 year of age.
weeks later
 Strongyloides: OM x 3 days
ANTIMALARIALS

Chloroquine Tab 250mg Oral Treatment: Treatment for all plasmodia
Phosphate (150mg base) 10mg base/kg/dose (max except chloroquine-
600mg) followed by 5mg base/ resistant P. falciparum.
kg/dose (max 300mg) at 6 hours,
24 hours and 48 hours later
(total dose of 25mg base/kg
over 3 days) Start 1–2 weeks before
Prophylaxis: entering endemic area and
5mg base/kg/dose (max continue until 4 weeks after
300mg) once weekly leaving.

Mefloquine Tab 250mg Oral Treatment: The combination of
<45kg: 15mg/kg/dose mefloquine and quinine is
followed by best avoided.
10mg/kg/dose (max 500mg)
6–12 hours later
Adults: 750mg
followed by
500mg 6–12 hours later
Prophylaxis: Start 1 week before
≤9kg: 5mg/kg/dose, once a week entering endemic area
10–19kg: 1/4 tab, once a week (preferably start ≥2 weeks
20–30kg: 1/2 tab, once a week before, if possible) and
31–45kg: 3/4 tab, once a week continue until 4 weeks after
>45kg/adult: 1 tab, once a week leaving.
Primaquine Tab 15mg (base) Oral 0.5mg base/kg/dose (max Drug-induced haemolysis
Phosphate 30mg) OD for 14 days. 21 days may occur in G6PD
for infection in SEA or Western deficiency.
Pacific (prevention of P. vivax Avoid primaquine
and P. ovale relapses). in the presence of
0.75mg base/kg/dose haemoglobinuria.
(max 45mg) weekly for 8 weeks
(if G6PD deficient).
Prophylaxis: Start 1–2 days before entering
0.5mg base/kg (max 30mg) endemic area and continue
daily until 7 days after leaving.
Malarone Adult strength: Oral Treatment (OD x 3 days):
Atovaquone 250mg, 5–8kg: 125mg (atovaquone)/
Proguanil 100mg 50mg (proguanil)
9–10kg: 187.5mg/75mg
Paediatric strength: 11–20kg: 250mg/100mg
Atovaquone 62.5mg, 21–30kg: 500mg/200mg
Proguanil 25mg 31–40kg: 750mg/300mg
>40kg: 1,000mg/400mg
Prophylaxis (OD): Start 1–2 days before entering
5–8kg: 31.25mg/12.5mg endemic area and continue
9–10kg: 46.88mg/18.75mg until 7 days after leaving.
11–20kg: 62.5mg/25mg
21–30kg: 125mg/50mg
31–40kg: 187.5mg/75mg
>40kg: 250mg/100mg
Continued overleaf

Quinine Sulphate Tab 300mg Oral 30mg salt/kg/day Q8H for Use only for suspected
3–10 days (max 600mg salt/ chloroquine resistance.
dose) (Infections acquired in For chloroquine-resistant P.
SEA: Give 10 days of Quinine; falciparum (found in SEA)
3–7 days treatment for add —
infections acquired elsewhere). either
tetracycline 25mg/kg/day
(max 250mg/dose) Q6H
for 7 days
or
doxycycline 2.2mg/kg (max
100mg/dose) Q12H for 7 days
or clindamycin 20–40mg/kg/
day Q8H for 7 days.
(tetracycline/doxycycline/
clindamycin begin 2–3 days
after treatment with quinine).
ANTIVIRALS
Doses are per dose, OD = once daily, BD = twice daily, TDS = three times daily
Drug Preparation Dosage Indications/ Side-effects
Comments
Acyclovir Susp 200mg/5ml Neonatal HSV infection: ACV indications for IV:
(ACV) Tab 200mg IV: uncomplicated VZ: Crystalline nephropathy.
Inj 250mg/vial 20mg/kg/dose second-degree Rare encephalopathy.
PMA<34 weeks: Q12H household contact, Headache, dizziness,
PMA≥34 weeks: Q8H chronic lung/skin rash, ↓WBC, GI side-
For 14 days for skin/ disease, steroids, effects.
mucocutaneous disease, salicylate therapy.
21 days for disseminated/ VZ in immunosupressed:
CNS infection. IV x 7–10 days.
Varicella HSV encephalitis:
(uncomplicated): For 14–21 days
PO 20mg/kg/dose Q6H x 5 IV:
days (max 800mg 5x/day) Slow infusion with
adequate hydration as
HSV genital/labial (first ACV crystallises in renal
episode): tubules.
PO 20mg/kg/dose TDS
or
400mg TDS x 5–10 days
or
IV 5mg/kg/dose Q8H x
5–7 days

Comments
Acyclovir HSV genital/labial
(ACV) (recurrent):
(Continued) PO 400mg TDS x 5 days
Herpetic whitlow:
PO 400mg TDS x 10 days
HSV keratitis/
conjunctivits:
PO 20mg/kg/dose Q6H x
10 days + Acyclovir 3% eye
ointment 1 app 5x/day.
Varicella (complicated) or
HSV encephalitis or HSV in
immunosuppressed:
<1 year old: IV 10mg/
kg/dose Q8H
>1 year old: 500mg/m2/
dose Q8H
Ganciclovir Inj 500mg/vial IV induction: Infuse over 1–2 hours ↓WBC, ↓plt,
5mg/kg/dose Q12H x CMV pneumonitis in headache, seizures,
2–3 weeks (3–6 weeks transplant patients: hypertension, nausea,
if colitis), Add IVIG 500mg/kg rash, renal/liver
then EOD x 10 doses, then toxicity.
maintenance 5mg/kg/ 500mg/kg 2x per week
dose once daily x 8 doses.
or
6mg/kg 5x per week.
Congenital CMV
infection:
6mg/kg/dose Q12H
Continued overleaf

Comments
Valganciclovir Tab 450mg CMV maintenance Oral formulation of
(Valcyte) Syr 60mg/ml therapy given 3x per ganciclovir with better
week bioavailability. Toxicity
Dose = 7 x BSA x CrCl same as for ganciclovir.
or
CrCl >70ml/min:
520mg x BSA
CrCl 50–70ml/min:
260mg x BSA
CrCl <50ml/min:
130mg x BSA
or
16mg/kg/dose BD
Foscarnet Inj 6gm/vial CMV: IV induction: Hydrate with N/S first. Renal: ↓K, ↓Ca, ↓Mg,
60mg/kg/dose Q8H For CMV resistant to ↑Cr, nephrogenic
or GCV or HSV resistant DI, proteinuria,
90mg/kg/dose to ACV fever, nausea,
Q12H x 2–3 weeks, ↓WBC, ↑LFT, ↑BP,
then maintenance seizures, dizziness,
90–120mg/kg/dose OD. bronchospasm, GI
HSV: 40mg/kg/dose Q8H side-effects
or 60mg/kg/dose Q12H
until infection resolved.
Ribavirin Inhalation 25mg/kg/day Q8H on Only for RSV in Bronchospasm,
6gm powder D1, then 15mg/kg/day immunosuppressed conjunctivits,
Q8H from D2–10. patients*. teratogenic, ↓BP, rash,
haemolytic anemia
Inj1.2gm/vial For IV usage: Please Hepatitis C treatment. (both IV/PO) reversible
consult with Infectious with drug withdrawal.
Diseases Team and
Pharmacy.
Zanamivir Aerosol 5mg/ Treatment: Influenza A, B Bronchospasm.
inhalation 2x 5mg puffs BD x 5 days treatment Approved ≥7 years
Prophylaxis: old.
2x 5mg puffs OD x 10 days

Comments
Oseltamivir Tab 30mg, 45mg, Treatment: Influenza A, B Nausea, vomiting.
75mg 2mg/kg/dose BD (max treatment and
75mg BD) x 5 days prophylaxis
or
Children ≥12 months
old up to adult:
≤15kg: 30mg BD
>15–23kg: 45mg BD
>23–40kg: 60mg BD
>40kg or adult:
75mg BD
Children <12 months old:
(2mg/kg/dose BD)
<3 months: 12mg BD
3–5 months: 20mg BD
6–11 months: 25mg BD
Prophylaxis:
Dose as above OD x 10 days.
Zidovudine Syrup 10mg/ml Neonate: HIV treatment and Anemia, ↓WBC,
(ZDV, AZT) Cap 100mg <30 weeks: prevention. nausea, vomiting,
Inj 10mg/ml ≤28 days: PO 2mg/kg/dose nail pigmentation,
or headache. Rare:
IV 1.5mg/kg/dose Q12H; Myopathy, myositis,
>28days: PO 3mg/kg/dose hepatotoxicity.
or
IV 2.3mg/kg/dose Q12H
30–34 weeks:
≤14 days: PO 2mg/kg/dose
or
IV 1.5mg/kg/dose Q12H;
>14days: PO 3mg/kg/dose
or
IV 2.3mg/kg/dose Q12H
≥35 weeks:
PO 4mg/kg/dose or
IV 3mg/kg/dose Q12H
Continued overleaf

Comments
Zidovudine Syrup 10mg/ml Child:
(ZDV, AZT) Cap 100mg PO 240mg/m2/dose Q12H
(Continued) Inj 10mg/ml or
160mg/m2/dose Q8H
Adolescent:
200mg TDS
or
300mg BD
Lamivudine Susp 10mg/ml Neonate: HIV treatment and Well-tolerated.
(3TC) Tab 2mg/kg/dose BD prevention. Nausea, rash,
100mg,150mg Child: Hepatitis B treatment. vomiting, diarrhoea,
PO 4mg/kg/dose BD headache.
Adolescent:
150mg BD
Stavudine Capsule 30mg <30kg: 1mg/kg/dose BD HIV treatment. Can be given with
(d4T) 30–60kg: 30mg/dose BD food. Adjust dose with
>60kg: 40mg/dose BD renal impairment.
Do not use with ZDV
due to antagonistic
drug effect.
Nevirapine Tab 200mg Treatment: HIV treatment and Warn family to
Dose in stepwise manner. perinatal prevention of observe for rash.
2 months–8 years old: HIV transmission. Occurs within the first
200mg/m2/dose OD x 6 weeks of therapy.
2 weeks,
then Fever, nausea,
200mg/m2/dose BD. headache and
abnormal LFTs.
8–16 years old: Severe hepatitis
120–150mg/m2/dose and hypersensitivity
OD x 2 weeks, reaction (less
then common).
120–150mg/m2/dose BD.
Adolescent/adult:
200mg OD x2 weeks,
then
200mg BD.
Prevention:
1.5–2kg: 8mg/dose
>2kg: 12mg/dose
(within 72 hours of birth).

Comments
Lopinavir/ Solution If no concurrent NVP HIV treatment. Take with food.
Ritonavir 80mg LPV/20mg or EFV: Diarrhoea, headache,
(LPV/RTV) RTV per ml 7–15kg: 12mg/kg/dose nausea and vomiting,
‘Kaletra’ Paeds Tab 100mg LPV BD. rash (more common).
LPV/25mg RTV 15–40kg: 10mg/kg/dose ↑glucose,
Tab 200mg LPV BD. ↑triglycerides,
LPV/50mg RTV >40kg: 400mg ↑cholesterol (less
LPV/100mg RTV (2 tab) BD. common).
If on concurrent NVP
or EFV:
7–15kg: 13mg/kg/dose
LPV BD.
15–45kg: 11mg/kg/dose
LPV BD.
>45kg: 533mg LPV
(6.5ml) BD
or
500mg (Tab) BD.
Nelfinavir Tab 250mg ≥2 years old: 44–55mg/ HIV treatment and Diarrhoea,
(NFV) kg/dose BD prevention. rash, ↑glucose,
or ↑triglycerides,
23–35mg/kg/dose TDS ↑cholesterol.
Adolescent: 1250mg BD
or
750mg TDS.
* Recent trials have shown conflicting results in the efficacy of nebulised ribavirin against RSV in chronic lung disease
and for use against respiratory agents other than RSV in immunocompromised host. When deciding to use, weigh
against cost, route of administration and potential toxic side-effects in healthcare workers administering drug.
RESPIRATORY SYSTEM
ANTI-ASTHMA MEDICATIONS

Aminophylline Inj 250mg/10ml IV Loading dose: For use in acute severe
5mg/kg/dose over 30 mins asthma exacerbation.
followed by Omit loading dose for
Maintenance: patient on theophylline
15–20mg/kg over 24 hours therapy. Therapeutic
continuous infusion levels: 10–20mcg/ml.
Budesonide 200mcg/puff Inhalation Dosing depends on the
Turbuhalerl asthma severity/control.
Usual starting dose
>6 years old: 200–400mcg
daily.
500mcg/2ml Respules Inhalation Usual starting dose For children with asthma
250mcg 2x daily requiring long term
or controller therapy, ICS
500mcg once daily delivery via metered
dose inhalers and dry
powder inhalers are
preferred
Symbicort™ Symbicort™ 160/4.5 Inhalation Dosing depends on the Symbicort™ is NOT
160/4.5 Turbuhaler asthma severity/control. licensed in children <6
(Budesonide 160mcg/ Usual dose: years old
Formoterol 4.5mcg 1–2 puffs 2x daily SMART regimen NOT
per puff) recommended for
Quick relief during attack patients <18 years old
for patient on SMART unless under specialist
regimen: care.
1 puff as needed in Do NOT exceed max of
response to symptoms. 6–8 puffs per
If symptoms persist after day (inclusive of
a few minutes, another maintenance dose)
inhalation can be taken. during asthma
Max not >6 puffs on any exacerbation. Patient
single occasion. using >8 puffs daily
should be advised to
seek medical attention.

Fluticasone 50mcg/puff Evohaler Inhalation Dosing depends on the GINA 2014:
asthma severity/control. Children ≤5 years:
Usual starting dose: Low dose: 100mcg/day
125mcg/puff Evohaler Inhalation 100–200mcg daily.
Children 6–11 years:
Low dose: ≤200mcg/day
Medium dose:
200–500mcg/day
High dose: >500mcg/day
Children ≥12 years and
Adults:
Low dose: ≤250mcg/day
Medium dose:
>250–500mcg/day
High dose: >500mcg/day
Seretide™ Seretide™ Inhalation Dosing depends on the Seretide™ is NOT to
25/50 25/50mcg Evohaler asthma severity/control. be used during acute
(Salmeterol 25mcg/ Usual starting dose: asthma attack.
Fluticasone 50mcg 100mcg of fluticasone Seretide™ is NOT
per puff) component 2x daily licensed in children <4
Seretide™ Seretide™ Inhalation years old.
25/125 25/125mcg Evohaler Do NOT exceed max of
(Salmeterol 25mcg/ 100mcg salmeterol/day.
Fluticasone 125mcg
per puff)
Seretide™ Seretide™ Inhalation
50/100 50/100mcg Accuhaler
(Salmeterol 50mcg/
Fluticasone 100mcg
per puff)
Hydrocortisone Inj 100mg/vial IV 4–5mg/kg/dose 4–6 For use in moderate to
hourly. severe acute asthma
(max 100mg per dose) exacerbation
Ipratropium 20mcg per puff Inhalation <10kg: 2 puffs/dose Administer with
Bromide Metered Dose Inhaler ≥10kg: 4 puffs/dose every salbutamol for acute
20 mins for 3 doses asthma exacerbation,
0.025% (500mcg/2ml) Nebulisa- 0.5–1ml/dose every 20 refer to the KKH Asthma
Nebuliser Solution tion mins for 3 doses Clinical Pathway
Ketotifen 1mg/5ml Syp Oral 6 months to 3 years old:
Ketotifen SRO 2mg Oral 2.5ml (0.5mg) BD.
Tablet >3 years old: 5ml (1mg)
BD.
Continued overleaf

Magnesium Inj 49.3% IV Loading dose: For use in severe acute
sulfate (10mmol/5ml) 50mg/kg over 30 min asthma exacerbation
(max dose 2g/dose) Please refer to the KKH
Maintenance dose: protocol for details and
Start at 20mg/kg/hr monitoring protocol.
(range 20–40mg/kg/hr) (max dose 40g/day, max
infusion rate 40mg/kg/hr)
Montelukast 10mg Tablet Oral 12 months to 5 years old: For use of prevention
5mg Tablet 4mg once daily of exercise-induced
4mg Granules 6–14 years old: 5mg once bronchoconstriction,
daily administer dose at least
≥15 years old: 10mg 2 hours prior to exercise
once daily
Prednisolone 10mg/5ml Syp Oral 1–2mg/kg/day (max dose For use in acute asthma
20mg Tablet Oral 60mg) exacerbation
5mg Tablet
1mg Tablet
Salbutamol 100mcg/puff EVOhaler Inhalation 0.2–0.3 puffs/kg/dose For acute exacerbations
(min 2 puffs/dose, max 10 may administer up to 15-
puffs/dose for inpatient min interval with close
use, max 6–8 puffs/dose in review in healthcare
the written asthma action facility, depending on
plan) Q4–6H in written severity of exacerbation
asthma action plan and response. Please
refer to the KKH Asthma
Clinical Pathway.
0.5% w/v Nebulising Nebulisa- 0.03ml/kg/dose (max 2ml/ Close monitoring and
Solution or 5mg/ml tion dose) every 15 mins to 6 review required for
hourly interval depending frequency >4H. Please
on severity of exacerbation refer to the KKH Asthma
and response Clinical Pathway.
Inj 5mg/5ml IV Loading dose: For use in severe acute
5mcg/kg diluted to 10ml asthma exacerbation.
NaCl 0.9% over 10 min
Maintenance dose:
1–5mcg/kg/min (max rate
10mcg/kg/min)
COUGH MIXTURES AND MUCOLYTICS

Acetylcysteine Tab 600mg Oral 2–6 years old: 100mg Mucolytics are
(Fluimucil) Sachet 100mg BD- TDS. contraindicated in
>6 years old: 200mg BD-TDS. children <2 years
old because of risk
of aggravation of
respiratory symptoms.
Use with caution.
Off-label dosing:
<1 year old: 50mg BD
1–2 years old: 50mg TDS
Actifed DM Cough Per 5ml: Oral 2–5 years old: 2.5ml TDS.
Linctus Dextromethorphan 6–12 years old: 5ml TDS.
HBr 10mg >12 years old: 10ml TDS
Pseudoephedrine
HCl 30mg
Triprolidine HCl
1.25mg
Actifed Expectorant Per 5ml: Oral 2–5 years old: 2.5ml TDS.
Syrup Guaiphenesin 6–12 years old: 5ml TDS.
100mg >12 years old: 10ml TDS.
Pseudoephedrine
HCl 30mg
Triprolidine HCl
1.25mg
Diphenhydramine 10mg/5ml Oral 2–<6 years old: 6.25mg TDS
HCl (contains NH4Cl) (suggest 5mg TDS)
6–<12 years old: 12.5mg TDS
(suggest 10mg TDS)
≥12 years old: 25mg TDS
(suggest 20mg TDS)
Bromhexine HCl Tab 8mg Oral 2–6 years old: suggest Mucolytics are
Syr 4mg/5ml 2mg TDS contraindicated in
6–12 years old: 4mg TDS children <2 years
≥12 years old: 8mg TDS old because of risk
of aggravation of
respiratory symptoms.
Use with caution.
Off-label dosing:
<2 years old: 1mg TDS
Continued overleaf

Cetirizine (Zyrtec) Tab 10mg Oral 1–2 years old: 2.5mg BD.
Syr 1mg/ml 2–5 years old: 2.5mg BD, or
5mg daily.
≥6 years old: 10mg daily.
Chlorpheniramine Tab 4mg Oral 6 months to <2 years old:
Maleate (Piriton) Syr 4mg/5ml 0.1mg/kg BD
≥2 years old: 0.1mg/kg TDS
(max 4mg/dose, and 0.35mg/
kg/day)
Desloratidine Syr 0.5mg/ml Oral 2–5 years old: 1.25mg daily.
(Aerius) 6–11 years old: 2.5mg daily.
>12 years old: 5mg daily.
Loratadine Syr 5mg/5ml Oral ≥2 years old:
(Clarityne) Tab 10mg ≤30kg: 5mg daily
>30kg: 10mg daily
Promethazine Syr 5mg/5ml, Oral ≥2 years old: 0.125–0.25mg/ Contraindicated in
kg (usual max 10mg/dose) children <2 years old
TDS because of respiratory
depression
Fexofenadine Susp 6mg/ml Oral 2–11 years: 30mg BD
(Telfast) Tab 180mg ≥12 years: 60mg BD or
180mg OD
Rhinathiol Per 5ml: Oral 2–5 years: 2.5–5ml QDS Contraindicated in
Promethazine Carbocisteine 100mg 6–12 years: 7.5–12.5ml TDS children <2 years old
Promethazine HCl 12–15 years: 12.5–15ml TDS because of respiratory
2.5mg depression
NEUROLOGICAL SYSTEM
ANTI-CONVULSANTS

Acetazolamide Tab 250mg tab Oral 4–16mg/kg/day in 3–4 divided
doses;
Max: 30mg/kg/day or 1,000mg/
day (whichever is less)
Carbamazepine Tab 200mg Oral Initiate at 10mg/kg/day BD-TDS Therapeutic levels:
(Tegretol) CR Tab 200mg for 1 week and gradually 4–12mcg/ml.
Susp 100mg/5ml increase to 35mg/kg/day BD- Monitor haematologic
TDS over 2–4 weeks (adult dose and hepatic toxicity.
is 800mg TDS). HLA-B*1502 allele test
to be done for patient
of Asian descent before
starting therapy.
Look out for allergic
reaction up to 4–6 weeks.
Clobazam Tab 10mg Oral <2 years: 0.1–1mg/kg/day
(Frisium) 2–18 years: 5mg/day
Max: 60mg/day or 0.4mg/kg/
dose 8–12H
Clonazepam Tab 0.5mg Oral 0.05–0.1mg/kg/day BD or TDS Monitor haematologic and
(Rivotril) (adult dose 1.5mg/day TDS). hepatic toxicity.
Diazepam Inj 10mg/2ml IV 0.25mg/kg/dose. May repeat Give undiluted at no faster
(Valium) in 5 mins (not >0.6mg/kg in than 2mg/min.
(Stesolid) Oral 8 hours).
0.2–0.5mg/kg/day BD or TDS. For cluster seizures or
Rectal solution Rectal Children 1 month to 5 years: seizures of >5 mins.
5mg/tube 0.5mg/kg
Children 6–11 years: 0.3mg/kg
Children ≥12 years and Adults:
0.2mg/kg
Max 10–20mg/dose; dose may
be repeated in 4–12 hours if
needed; do not use >5x/mth or
more than once every 5 days
Gabapentin Tab 300mg Oral 30–60mg/kg/day TDS. Careful in renal
(Neurontin) impairment
Continued overleaf

Lamotrigine Tab 5mg, 50mg, Oral Dose with enzyme inducing Steady state 3–15 days.
(lamictal) 100mg anticonvulsants w/o VPA Allergy risk. To be started
0.6mg/kg/day for 2 weeks, then by neurologist only.
1.2mg/kg/day for 2 weeks, and
increase fortnightly by 0.6mg/
kg/day to 5–15mg/kg/day 12
hourly (maintenance); max
daily dose: 400mg/day
Dose with VPA 0.15mg/kg/
day for 2 weeks, and increase
fortnightly by 0.15mg/kg/day
to 1–5mg/kg/day 12 hourly
(maintenance); max daily dose:
200mg/day
Dose by itself or with
anticonvulsants other than
VPA and enzyme inducing
anticonvulsants: 0.3mg/kg/
day for 2 weeks and increase by
0.3mg/kg/day every 2 weeks
to 4.5–7.5mg/kg/day in 2
divided doses; max daily dose:
300mg/day
Levetiracetam Inj 500mg/5ml IV IV: Loading dose: 50mg/kg/
(Keppra) dose (max dose: 2500mg);
maintenance dose: 30–60mg/
kg/day divided 2x daily
Tab 500mg Oral Initiate at 20mg/kg/day BD for
2 weeks, and increase gradually
in at least weekly interval
Maintain at max 80mg/kg/day
or 3,000mg/day BD
Lorazepam Inj 2mg/ml IV 0.1mg/kg (up to 4mg). May Use in status epilepticus.
repeat in 5 mins same dose. Infuse at rate 1–2mg/min
(slow bolus).

Midazolam Inj 5mg/ml Intra- Intranasal (to divide dose IV preparation to be used
nasal/ between nares): for intranasal and buccal
buccal Infants 1–5 months: 0.2–0.3mg/ route.
kg once; max dose: 10mg
Infants and Children ≥6 For cluster seizures or
months: 0.2mg/kg; max dose: seizures of >5 mins.
10mg; may repeat once to a
total max of 0.4mg/kg
Buccal:
Infants ≥3 months, Children,
and Adolescents: 0.2–0.5mg/kg
once; max dose: 10mg
Nitrazepam Tab 5mg Oral Children ≤30kg: Oral: Usual
(Mogadon) dosage: 0.3–1mg/kg/day in 3
divided doses
Phenobarbitone Inj 20mg/0.5ml IV/IM IV loading: 20mg/kg over Therapeutic levels:
sodium Tab 10, 60mg Oral 30 mins. May repeat up to 15–40mcg/ml
Syr 15mg/5ml, Oral 60–80mg/kg. Dilute in Normal saline.
10mg/ml Maintenance: 3–6mg/kg/day BD. May cause respiratory
Neonates: 3–4mg/kg/dose BD. depression, hypotension
Steady state: 120–170 hours. and sedation.
Phenytoin Inj 250mg/5ml Slow IV Loading: 20mg/kg/dose over Therapeutic levels:
Sodium Tab 30, 100mg Oral 20 mins. 10–20mcg/ml
Syr 125mg/ml Oral Max rate: 1mg/kg/min
Max dose: 1,500mg Steady state: 23–140
May repeat 5mg/kg x 2 in status hours. To be diluted in
epilepticus. normal saline and run by
Phenobarbitone preferred syringe driver.
over phenytoin for patient <1 IV form may cause cardiac
year old arrhythmias
Load 10mg/kg/day BD or TDS
for 3–5 days, then maintain at
3–10mg/kg/day BD or TDS.
Pyridoxine Tab 10mg, 50mg Oral 10–200mg/day or 30mg/kg/day. Consider in refractory
(Vit B6) Inj 100mg/ml IV 50mg IV or 100mg IM stat. neonatal seizures.
Continued overleaf

Sodium Inj 400mg IV 10–15mg/kg/day increasing at Therapeutic level:
Valproate Tab EC 200mg, Oral 1-week interval to max of 60mg/ 40–100mcg/ml.
(Epilim) CR200mg, 300mg, Oral kg/day. Steady state: 35–50 hours.
500mg Syr and EC formulation: BD to TDS Monitor for hepatotoxicity
Syr 200mg/5ml CR formulation: BD especially in children
Inj: Total daily dose equivalent <2 years old
to oral total daily dose but to be
given 6 hourly
(adult dose: 750–4,000mg/day
BD-QDS)
Topiramate Tab 25mg, 100mg Oral Initiate at 1–2mg/kg/day BD for 1 Risk of hyperthermia and
(Topamax) week, and increase by 1–2mg/kg/ renal stones, so ensure
day BD weekly until maintenance adequate fluid intake.
at 1–10mg/kg/day BD
Vigabatrin Tab 500mg Oral Initiate at 50mg/kg/day, Primary indication is West
(Sabril) increase at 25–50mg/kg/day syndrome in infants
every 3 days to 150mg/kg/day
given at OD or BD
Zonisamide Tab 100mg Oral Initiate at 1–5mg/kg/day, Risk of hyperthermia and
increase every 2 weeks at 2mg/ renal stones, so ensure
kg/day adequate fluid intake.
Max: 12mg/kg/day or 600mg
SEDATIVES

Chloral Hydrate Syr 500mg/5ml Oral 25–50mg/kg/day divided every Contraindicated in hepatic
6–8 hours (max1g or 100mg/kg) or renal impairment.
Fentanyl Inj 500mcg/10ml IV Intermittent dose: 1–2mcg/kg/dose. Give IV over 3–5 mins.
Inj 100mcg/2ml Continuous IV infusion: 1–3mcg/ Rapid infusion may cause
kg/hr respiratory depression.
Ventilated 5–10mcg/kg/hr
Lorazepam Tab 0.5mg Oral 0.02–0.1mg/kg/dose Q4–8
Tab 1mg hourly (max 2mg/dose)
Inj 4mg/ml IV
Methadone Tab 5mg PO 0.1–0.2mg/kg/dose Q6–12
(Physeptone) hourly (max 10mg/dose).

Midazolam Inj 15mg/3ml IV 0.05–0.2mg/kg/dose (up to 0.5mg/ Antidote: Flumazenil
(Dormicum) Tab 15mg kg/dose); max 10mg/dose.
Continuous IV infusion: 3mg/kg in
50ml at 1–4ml/hr (1–4mcg/kg/
min). Titrate to desired effect
0.25–1mg/kg/dose
PO (max 20mg/dose)
Morphine Inj 10mg/amp IV 0.05–0.1mg/kg/dose slow bolus Antidote: Naloxone
Sulphate Syr 5mg/5ml every 2–4 hours (max 10mg/dose)
Continuous IV Infusion: 1mg/kg
in 50ml at 1–4ml/hr (10–40mcg/
kg/hr).
Oral 0.2–0.5mg/kg/dose every 3–4
hours (max 15–20mg/dose)
Pethidine Inj 50mg/ml IM 0.5–1mg/kg/dose every 2–3 Max dose: 75mg/dose
Slow IV hours.
MUSCLE RELAXANTS

Atracurium 25mg/2.5ml amp IV 0.3–0.5mg/kg bolus, followed Useful in patients with
by IV injection 0.1–0.2mg/kg as renal dysfunction.
needed, or continuous infusion
5–10mcg/kg/min.
Pancuronium 4mg/2ml IV 0.05–0.1mg/kg/dose 30–60
mins as needed or continuous
infusion.
0.4–0.6mcg/kg/min infusion.
Succinylcholine 100mg/2ml vial IV 1–2mg/kg/dose. Duration of action: 4–6
mins.
Side-effects include
hypotension, bradycardia,
arrhythmias and muscle
fasciculations.
Vecuronium 4mg/ml IV 0.1mg/kg/dose every 1–2 hours.
1–1.5mcg/kg/min.
Rocuronium 50mg/5ml IV RSI: 0.6–1.2mg/kg/dose stat
IV bolus: 0.6–1.2mg/kg stat,
then 0.1–0.2mg/kg bolus repeat
as needed
IV infusion: 5–15mcg/kg/min
Continued overleaf

Edrophonium Inj 10mg/ml IV Children <1 year old: Initial Atropine: 0.01mg/kg/
(Tensilon) test dose of 0.1mg, followed by dose (max 0.4mg) on
0.1mg/kg (max dose of 0.5mg) standby
once or twice.
Children >1 year old (<35kg):
Initial test dose of 0.5mg,
followedby subsequent 1mg
doses several minutes apart to a
max total dose of 5mg.
Children >1 year old (>35kg):
Initial test dose of 1mg, followed
by subsequent doses of 1–2mg
each administered several minutes
apart to a maximum total dose
of 10mg
Neostigmine Inj 2.5mg/ml IV Relaxant reversal: 0.05mg/kg/dose
IM (total dose not to exceed 5mg)
Pyridostigmine Tab10mg,60mg Oral 1–7mg/kg/day in 3–5 divided
(Mestinon) doses. Increase dose and frequency
according to response (max
absolute dose of 300mg/day).
ENDOCRINE SYSTEM

ACTH Synacthen IV 0–1 month old: 62.5mcg Short Synacthen test
[Tetracosactide IM 1–12 months old: 125mcg
(Cosyntropin) ] >1 year old: 250mcg
250mcg/ml vial
Carbimazole Tab 5mg Oral 0.25mg/kg/dose TDS (max 15mg) Watch for neutropenia
x 2 weeks, then 0.1mg/kg/dose and myalgia.
8–12 hourly
Desmopressin Intranasal solution Intranasal Diabetes insipidus: Monitor for
Acetate (DDAVP) 100mcg/ml (Intranasal) 1 month to 2 years: hyponatraemia and
Nasal spray 2.5–5mcg per 12–24 hourly fluid retention.
10mcg/dose (Intranasal) ≥2 years: 5–20mcg
per 12–24 hourly
Tab 200mcg Oral (Oral) 1 month to 2 years: 10mcg
(Minirin) per 8–12 hourly
(Oral) ≥2 years: 50mcg per 8–12
hourly
Nocturnal enuresis:
(Oral) 200mcg ON (up to 400mcg ON)
Vasopressin Inj 20U/ml SC/IM Diabetes insipidus: For diabetes insipidus.
(Soluble Pitressin) IV IM/SC: 2.5–10 units every 6–12
hourly
IV continuous: 0.0005 units/kg/hr
(max 0.01 units/kg/hr)
Dexamethasone Tab 0.5mg Oral To consult endocrinologist
Tab 4mg IM/IV regarding protocol for
Inj 4mg/ml dexamethasone suppression test
Fludrocortisone Tab 100mcg Oral 0.05–0.2mg/day Babies with CAH may
initially need higher
doses of 200–400mg/
m2/day plus NaCl
supplementation.
Glucagon 1mg (1unit) IM Hyperinsulinaemia: For hypoglycaemic
freeze-dried IV 0.1–0.2mg/kg/dose. Max 1mg. coma.
powder Hypoglycaemia:
0.5mg (<25kg) and 1mg (≥25kg)
IM/SC/IV: 0.2mg/kg/dose, max 1mg
IV infusion: 10–20mcg/kg/hr
Continued overleaf

Hydrocortisone Inj 100mg vial IM/IV Adrenal crisis: Triple the dose on
Sodium Tab 10mg IM/IV 100mg/m2, sick days orally or use
Succinate Oral immediately followed by parenteral route.
100mg/m2/day in 4–6 divided
doses until the clinical condition
stabilises
Peri-op:
Induction of anaesthaesia — IV
hydrocortisone 100mg/m2
IV hydrocortisone 100mg/m2/
day in 4–6 divided doses until the
major stress period is resolved
Physiological replacement dose:
Primary adrenal insufficiency:
12–15mg/m2/day
Secondary adrenal insufficiency:
8–10mg/m2/day
L-Thyroxine Tab 25mcg Oral To consult endocrinologist Dosing is variable and
50mcg, 100mcg regarding dosing titrated according
Inj 500mcg to TFT.
Pamidronate Inj 30mg/10ml IV To consult endocrinologist Monitor for
regarding dosing for osteogenesis osteonecrosis of
imperfecta the jaw.
Propylthiouracil Tab 50mg Oral 5–7mg/kg/day in 3 divided doses. High risk for
hepatotoxity in
children. To be used
in consultation with a
specialist in children
who are allergic to
carbimazole.
GASTROINTESTINAL SYSTEM
DRUGS FOR DYSPEPSIA AND GERD

Antacid with Magnesium trisilicate Oral >12 years old: 1–2 tab TDS. Separate apart from other
Simethicone 250mg, Aluminium medications by 2 hours
hydroxide 250mg, (may reduce absorption of
simethicone 30mg other medications).
Tab
Domperidone Tab 10mg Oral PO: 0.3–0.4mg/kg/dose Q6–8H Suspension is for use in
Susp 1mg/ml (max 10mg/dose) children >1 month old.
Supp 10mg Rectal Rectal: 1mg/kg/dose (max: Contraindicated in
30mg/dose) Q12H patients with cardiac
disease (MHRA alert).
Eviline Forte Magnesium Oral 2–12 years old (<20kg): Separate apart from other
Suspension hydroxide 400mg, 5ml TDS medications by 2 hours
Aluminium hydroxide >12 years old (>20kg): 10ml (may reduce absorption of
400mg, Simethicone TDS (max 40ml/day) other medications).
40mg Suspension
Famotidine Tab 20mg Oral 0.5–1mg/kg/dose Q12–24H.
Max: 40mg/dose, 80mg/day
Magnesium Magnesium Oral 1–2 years old: 2.5ml/dose Q8H Separate apart from other
Carbonate Carbonate 3% 2–5 years old: 5ml/dose Q8H medications by 2 hours
w/v Sodium 5–10 years old: 7.5ml/dose Q8H (may reduce absorption of
bicarbonate 5% >10 years old: 10ml/dose Q8H. other medications).
w/v (100ml)
Omeprazole Suspension Oral PO, IV: 0.7–3.3mg/kg/day once Take 30 mins before meal
2mg/ml daily Q8H (max: 40mg/dose) for best effects.
Cap 20mg Suspension is recommended
Tab 10mg MUPS for patients on tube feeding.
Inj 40mg IV Patients <1 month old,
to dilute 1 part with 4
parts water then feed (to
reduce osmolality).
Ranitidine Syr 150mg/10ml Oral PO: 2–4mg/kg/dose Q8–12H Tachyphylaxis can
Tab 150mg (max: 600mg/day) begin within 6 weeks of
Inj 50mg/2ml IV IV: 1mg/kg/dose Q6–12H treatment.
Simethicone Drops 100mg/ml Oral <2 years old: 0.2ml Q4–6H
2–12 years old: 0.4ml Q4–6H
>12 years: Consider using
Antacid tablet
CHELATE AND COMPLEXES

Sucralfate Tab 1,000mg Oral 1 month to 2 years old: 250mg Take 1 hour before meals
4–6 times daily
2–12 years old: 500mg 4–6
times daily
>12 years old: 1g 4–6 times daily
ANTI-DIARRHOEALS

Dioctahedral Sachet 3g Oral <1 year old: 1 sachet/day Q8–12H Separate apart from other
Smectite 1–2 years old: 1–2 sachet/day medications by 2 hours
(Smecta) Q8–12H (may reduce absorption of
>2 years old: 2–3 sachets/day other medications).
Q8–12H
ANTI-SPASMODICS

Hyoscine N Tab 10mg Oral 6–12 years old: 10mg 3 times Take ½–1 hour before food
Butylbromide Inj 20mg/ml daily
(Buscopan) IV >12 years old: 10–20mg 3–4
times daily
0.6mg/kg/dose Q6–8H
Trimebutine Susp 72mg/15ml Oral <6 months old: 2.5ml/dose Take ½–1 hour before food
maleate Tab 100mg Q8–12H
(Debridat ®) 6 months to 1 year old: 5ml/
dose Q12H
1–5 years old: 5ml/dose
Q8–12H
>5 years old: 10ml/dose
Q8–12H
>12 years old: 15–30ml/
dose OR
100–200mg tab/dose Q8–12H
PROBIOTICS

Lactobacillus 10 billion/sachet Oral 0.5–1 sachet/dose Q12H Lyophilised bacteria
acidophilus
(Lacteol Forte®)
Lactobacillus Drops 100 Oral Drops: 5 drops daily Drops to discard 3 months
reuteri million/5 drops after opening. Can be
(BioGaia) (sunflower oil, added to food/milk. Do
MCT oil) Tablet: 1–2 tab daily NOT add to hot food
Tab chewable 100 Separate from antibiotics
million for at least 2 hours
Lactobacillus Cap 20 billion Oral Child ½–1 cap daily Separate from antibiotics
GG (Lacto GG) Adults 1 cap daily (up to 2/day). for at least 2 hours
LAXATIVES

Bisacodyl Tab 5mg Oral 3–12 years old: 5–10mg once
daily or 0.3mg/kg/dose
>12 years old: 10–20mg/dose
Rectal 10mg Rectal <2 years old: 5mg/day
2–11 years old: 5–10mg/day
>12 years old: 10mg/day.
Fleet Solution 45ml Oral 5–9 years old: 7.5ml once Usually used for bowel
(monobasic 10–11 years old: 15ml once prep.
Na Phosphate ≥12 years old: 15ml once (max Mix with at least
7.2g, dibasic 45ml) 240ml of water for oral
Na phosphate administration.
2.7g/15ml)
Enema 66.6ml Rectal 2–11 years old: once
(Children)
Enema 133ml ≥12 years old: once
(adult) (Monobasic
Na Phosphate
19g, Dibasic
Na phosphate
7g/118ml delivered
dose)
Continued overleaf

Glycerin Infant Supp 2g Rectal <1 momth–0.5g as needed Lubricate with some water
suppository 1 month to 1 year old: 1g as before inserting into anus.
needed Insert high into the rectum
1–12 years old: 2g as needed and retain it for at least
>12 years old: 4g as needed 15 mins
Lactulose syrup Syrup 66.6%w/v Oral 0.5ml/kg/dose Q8–12H OR
Infant: 2.5–10ml/day
Older children: 40–90ml/day
Macrogol/ Sachet 10g Oral Maintenance dose: Mix in half glass (120ml)
Polyethylene 2–5 years old: ½–1 sachet/day. of water, beverages, fruit
Glycol 4000 (max: 2 sachets) juices or milk (not soda).
(Forlax ®) 6–12 year old: 1–2 sachets/day.
(max: 2 sachets) Separate from other
>12 years old: 1–3 sachets/day medicines by 2 hours
Sennosides Tab 15mg Oral 2–4 years old: 3.75mg–15mg OD
chewable 4–6 years old: 3.75mg–30mg OD
Tab 7.5mg >6 years old: 7.5mg–30mg OD
ANTI-EMETICS

Cyproheptadine Tab 4mg Oral 0.25–0.5mg/kg/day divided Cause increase in appetite,
Q8–12H (max: 12mg/day) increase in weight
Diphenhydra- Syrup 10mg/5ml Oral PO: >2 years old: 0.5–1mg/
mine kg/dose Q6–8H (max: 50mg/
dose or 300mg/day)
Inj 50mg/ml IV IV: 1–1.25mg/kg/dose
Q6–8H (max: 300mg/day)
Granisetron Inj 3mg/3m IV 0.01–0.04mg/kg (max 3mg/ Mostly used for
(Kytril) Tab 1mg Oral dose) OD-BD chemotherapy-induced
emesis
Ondansetron Tab 8mg Oral 0.1–0.2mg/kg (max 8mg/ Use with caution in
(Zofran) dose) BD-TDS patients with cardiac
Inj 4mg/2ml IV 0.15–0.2mg/kg (usual max disease
8mg/dose) BD-TDS
Prochlorperazine Tab 5mg Oral ≥1 years old and ≥10kg: May cause oculogyric crisis.
Maleate 0.2mg/kg (max 10mg/dose)
(Stemetil) BD-TDS.
Note: For management of antineoplastic therapy-induced nausea, please refer to section under
Haematology/Oncology
GENERAL PAEDIATRICS
ANTI-PYRETICS/ANALGESICS

Acetysalicylic Tab 100mg Oral Anti-inflammatory (Kawasaki
Acid (Aspirin) Oral Disease): 25mg/kg/dose Q6H
Antiplatelet: 3–5mg/kg daily
Analgesic: 10–15mg/kg/dose Q4–6H
(max 4g/day)
Diclofenac EC Tab 25mg Oral 0.3–1mg/kg/dose Q8–12H (max Not recommended
(Voltaren) Supp 12.5mg, Rectal 50mg/dose) for children <6
50mg months old.
Higher dose for anti-
inflammatory use.
Ibuprofen Syr 100mg/5ml Oral 5–10mg/kg/dose.Q6–8H (max Not recommended
(Brufen) Tab 200mg Oral 40mg/kg/day) for children <6
months old.
inflammatory use.
Indomethacin Cap 25mg Oral Anti-inflammatory: 0.5–1mg/
kg/dose TDS (max 4mg/kg/day or
200mg/day whichever is less)
Naproxen Tab 275mg Oral >2 years old: 5–10mg/kg/dose Not recommended
(Syn Flex) Q8–12H (max 1g daily) for children <2
years old.
inflammatory use.
Paracetamol Tab 500mg Oral 10–15mg/kg/dose Q4–6H
(Panadol) Syr 120mg/5ml Oral (max 4g daily)
Supp 125mg Rectal
Supp 325mg Rectal
Supp 650mg Rectal
VITAMINS AND IRON SUPPLEMENTS
Daily Content and

Vitamin Dosage Remarks
Requirement Preparation
Vit A Infants: 300mcg (RAE) Multivitamin Vit A deficiency: 5,000–10,000 The available
Older children: 300mcg (Appeton Infant units/daily Vit A capsule in
(RAE) to 750 (RAE) Drop: 1500 IU/ml; Measles Singapore comes
Nutroplex <6 months: 50,000 units daily in 10, 000 units/
1 RAE = 3.33 IU Multivitamin: 2500 for 2 days capsule.
IU/5ml) Measles 6–11 months: 100,000
units daily for 2 days
≥12 months to 5 years: 200, 000
units daily for 2 days
Xerophthalmia:
Administer the dosing below
(based on age group) as a single
dose, repeat the next day and
again after at least 2 weeks for a
total of 3 doses
<6 months: 50,000 units
6–12 months: 100, 000 units
Children/adolescents: 200,000 units
Vit B1 Infants: 0.28–0.38mg Multivitamin Thiamine Deficiency: 1–2mg/ Also available as
Older children: (Appeton Infant kg orally a Vit B Complex
0.4–1.2mg Drop: 0.5mg/ml; Metabolic Disease: 100mg Q8H consists of:
Nutroplex IV, IM, SC Vit B1 3mg,
Multivitamin: Vit B2 1.5mg,
10mg/5ml, Vit B6 0.5mg,
10mg Tab; Nicotinamide
Danueron/ (Vit B3) 10mg
Neurobion: Vit B1
100mg, B6 200mg,
B12 200mcg)
Riboflavin Infants: 0.4–0.6mg Multivitamin 5–10mg daily oral. Also available as
(Vit B2) Older Children: (Appeton Infant a Vit B Complex
0.6–1.8mg Drop: 0.6mg/ml; consists of:
Nutroplex Vit B1 3mg,
Multivitamin: Vit B2 1.5mg,
1.25mg/5ml Vit B6 0.5mg,
100mg Tab) Nicotinamide
(Vit B3) 10mg
Daily Content and

Vitamin Dosage Remarks
Requirement Preparation
Niacin Infants: 4–6mg Multivitamin Children and Adolescents: Also available as
Older children: 8–20mg (Appeton Infant For dyslipidemia: 100–250mg/day a Vit B Complex
Drop: 8mg/ml; (max dose: 10mg/kg/day) in 3 divided consists of:
Nutroplex doses with meals; increase weekly Vit B1 3mg,
Multivitamin: by 100mg/day or increase every 2–3 Vit B2 1.5mg,
12.5mg/5ml) weeks by 250mg/day as tolerated; Vit B6 0.5mg,
Evaluate efficacy and adverse Nicotinamide
effects with laboratory tests (Vit B3) 10mg
at 20mg/kg/day or 1,000mg/
day (whichever is less); increase
if needed and as tolerated;
re-evaluate at each 500mg
increment; doses up to 2,250mg/
day have been used.
* Routine use of Niacin
for dyslipidemia is not
recommended. This formulation
is not available in KKH.
Pyridoxine Infants: 0.1–0.3mg Multivitamin Dietary Deficiency: 5–25mg/day Also available as
Older Chidren: (Appeton Infant for 3 weeks then 2.5–5mg/day in a Vit B Complex
0.5–1.5mg Drop: 0.4mg/ml; multivitamin product consists of:
Nutroplex Treatment of Isoniazid induced Vit B1 3mg,
Multivitamin: neuropathy: Vit B2 1.5mg,
5mg/5ml, Neonate: 5–10mg daily Vit B6 0.5mg,
10mg, 50mg Tab; 1 month to 12 years: 10–20mg Nicotinamide
Danueron/ 2–3 times daily Vit B3) 10mg
Neurobion: (Vit B1 12–18 years: 30–50mg 2–3
100mg, B6 200mg, times daily
B12 200mcg) Pyridoxine Dependent Seizures:
100mg/ml Injection) 50mg IV or 100mg IM Stat
Vit C Infants: 35–45mg Multivitamin Oral: 35–100mg daily
(Ascorbic Acid) Older Children: (Appeton Infant Higher doses may be required for
30–100mg Drop: 35mg/ml, burn patients.
100mg Tab,
1,000mg
Effervescent Tab)
Vit D3 400 I.U Multivitamin 2,000 I.U daily for 6–8 weeks, Divide high doses
(Cholecalci- 1mcg: 40 IU (Appeton Infant followed by prophylactic into a few divided
ferol) Drop: 400 IU/ml; 400–1,000IU day. doses.
Nutroplex
Multivitamin: 200
IU/5ml,
1,000 IU Tablet)

Alfacalcidiol 0.25mcg tab Oral Neonatal: 0.05–0.1mcg/kg/ Persistent neonatal
(One-Alpha/1- 1mcg tab day (In neonates Up to 2mcg/ hypocalcaemia
Hydroxy Vit D3) 2mcg/ml Drops kg may be needed in resistant
cases)
<20kg: 0.015–0.03mcg/kg/day Prevention of Vit D
(max 0.5mcg ONCE daily) deficiency in renal/
>20kg: 0.25–0.5mcg/day cholestatic liver disease,
Max 1mcg hypophosphataemic
rickets,
Elemental Iron Ferrum Drops Oral Prophylaxis: 2mg/kg/day Some multivitamins
(50mg/ml) Treatment: 6mg/kg/day in may also contain Iron,
Ferrous Fumarate Tab divided doses for 3–4 months e.g. for Nutroplex each
(elemental 66mg) 5ml contains = 15mg
Sangobion/Floron elemental iron.
Tab (elemental
30mg)
Calcitriol Cap 0.25mcg Oral 1 month to 12 years: 0.02mcg/ Vit D dependent rickets,
(Rocaltrol/1,25 kg/day (max 0.25mcg/kg/day) hypophosphateamia
Dihydroxy increased slowly every 2–4 rickets, persistenet
Vit D3) weeks; max dose 0.25mcg hypocalcaemia due to
>12 years: initial 0.25mcg hypoparathyroidism.
daily, increased slowly every Ensure adequate calcium
2–4 weeks. Usual dose intake.
0.5–1mcg daily
CARDIOVASCULAR SYSTEM
PRESSORS

Adrenaline Inj IV Bradycardia/hypotension: For asystole/pulseless
1:10,000 ETT 0.1ml/kg IV/IO 1:10,000 (max: arrest, increased dosage
(1mg/10ml) 1mg or 10ml) Or no longer routinely
1:1,000 (1mg/ml) 0.1ml/kg ET 1:1,000 (max recommended.
2.5mg/dose) and subsequently
0.1ml/kg 1:10,000
IV/IO every 3–5 mins.
Infusion: 0.1–2mcg/kg/min
titrated to effect.
Dobutamine Inj 250mg/5ml IV 5–20mcg/kg/min Contraindicated
infusion in hypertrophic
cardiomyopathy.
Half-life 2 mins.
Dopamine Inj 200mg/5ml IV Low dose: 2–5mcg/kg/min. Increases renal blood flow.
infusion Minimal effect on HR and
cardiac output.
Intermediate dose: 5–15mcg/ Increases renal blood flow,
kg/min. HR, BP,cardiac output and
contractility.
High dose >15mcg/kg/min. Decreases renal perfusion,
prominent alpha
adrenergic effects.
Isoprenaline Inj 0.2mg/ml IV 0.05–2.0mcg/kg/min. Use with care in CHF,
infusion Start with low dose, increasing ischaemia, or aortic
every 5 mins until desired stenosis. Monitor for
effects or arrhythmias. arrhythmias, hypertension
and myocardial ischaemia.
Not used in cardiac arrests
unless bradycardia due to
heart block
Milrinone Inj 10mg/10ml IV 50mcg/kg over 15 mins
infusion (loading), 0.25–0.75mcg/kg/
min (maintenance),
max 1.13mg/kg/day.
Noradrenaline Inj 4mg/4ml IV 0.05–0.5mcg/kg/min, titrated
infusion to desired effect
max dose: 1–2mcg/kg/min
Vasopressin Inj 20U/ml IV 0.02–0.06 units/kg/hr Dose is for vasopressor
infusion effects.
DIURETICS

Frusemide Tab 40mg Oral 0.5–1.0mg/kg/dose Potentiates ototoxicity
Syr 5mg/5ml (max 20–40mg) 6–24 hours. and nephrotoxicity of
Inj 20mg/2ml IV Infusion 0.1–1mg/kg/hr. aminoglycosides.
Hydrochloro- Tab 25mg Oral 1–1.5mg/kg 12–24 hours K+ supplement needed.

thiazide Syr 5mg/ml
Spironolactone Tab 25mg Oral 0.5–1.0mg/kg/dose 6–24 Contraindicated in renal
Syr 5mg/ml hours failure.
May cause hyperkalaemia.
ANTI-ARRHYTHMIC

Adenosine Inj 6mg/2ml IV 0.1mg/kg/dose (max 6mg). For SVT. To be given rapidly
0.2mg/kg/dose (max 12mg) if no via the largest IV cannula
response for subsequent second and flushed quickly with
and third doses. 10–20ml N/S.
Atropine Sulphate Inj 0.6mg/ml IV 0.02mg/kg/dose (min 0.1mg. For severe bradycardia. May
max 0.5mg/dose for children, be given through the ETT.
max total dose 1mg).
Amiodarone Tab 200mg Oral 4mg/kg/dose (max 200mg) 8 Decrease doses of digoxin,
(Cordarone) Syr 5mg/ml hours x 1 week, then 12 hours x 1 warfarin and flecainide.
week, then 12–24 hours. Prolongs QT.
Inj 150mg/3ml IV Taper IV infusion over few days Caution: Can cause severe
after starting oral. hypotension and/or
bradycardia.
Loading 5mg/kg over 60 mins,
then 5–15mcg/kg/min
VT/VF 5mg/kg over 10 mins.
Flecainide Tab 100mg Oral 2–3mg/kg/dose (max 100mg) 12 For SVT including atrial
(Tambocor) hours. Can increase over 2 weeks arrhythmias. Minor
to 7mg/kg/dose (max 200mg) negative inotropic effect
8–12 hours. — caution in heart failure
or combination with beta–
blockers. Increases plasma
digoxin level, monitor
digoxin levels. Flecainide
dose to be reduced by 50% if
used with amiodarone.

Lignocaine Inj 10mg/ml (1%) IV Anti-arrhythmic: 1mg/kg/dose For ventricular arrhythmias.
(Xylocaine) slow bolus. May cause hypotension,
Infusion 15–50mcg/kg/min. seizure, cardiac or respiratory
arrest.
Procainamide Inj 1,000mg/10ml IV 0.4mg/kg/min for max 25 mins, For VT and flutter,
(Pronestyl) then 20–80mcg/kg/min supraventricular arrhythmia
(max 2g/day). unresponsive to digoxin.
QRS widening >0.02 sec
suggests toxicity.
Propranolol Tab 10mg, Oral 0.2–0.5mg/kg/dose (max For VT, digoxin-induced
Tab 40mg 10–25mg) 6–12 hours, slow arrhythmias and SVT not
Syr 5mg/5ml increase to max 1.5mg/kg/dose responsive to digoxin.
Inj 1mg/ml 6–12 hours (max 80mg). Contraindicated in asthma
IV and heart block. May
0.1mg/kg/dose over 10 mins. cause hypotension and
May repeat 1–3 times PRN then bronchospasm.
0.1–0.3mg/kg (max 5–15mg)
3–6 hours.
Verapamil Inj 5mg/2ml IV 0.1–0.2mg/kg (max 5–10mg) For SVT, atrial fibrillation
Tab 40mg over 10 mins under ECG and BP and flutter. If hypotension
monitoring. develops, give IV Ca
May repeat 30 mins later. Gluconate 10% 5ml/kg. If
bradycardia, give IV Atropine
Oral 1–3mg/kg/dose (max 0.01mg/kg.
80–120mg) 8–12 hours. Contraindicated with beta-
blockers.
Digoxin Tab 62.5mcg IV 15mcg/kg stat and 5mcg/kg after Monitor digoxin serum level,
Tab 250mcg 6H, then 3–5mcg/kg 12H slow Ca,K and Mg.
Syr 0.05mg/ml IV or oral (usual max 200mcg IV, If changing from oral
Inj500mcg/2ml 250mcg oral) solution or tablets to IV
Inj 100mcg/ml therapy, dosage should be
(Paed) reduced by 20% to 25%.
ANTI-HYPERTENSIVE

Captopril Tab 12.5mg Oral 0.1–2mg/kg/dose Q8–12H Caution in renal failure and
(max dose 450mg/day). hyperkalaemia.
Syr 1mg/ml
Enalapril Tab 5mg, Oral 0.1–0.5mg/kg/dose Q12H Caution in renal failure.
Tab10mg (max 1mg/kg/day 40mg/day).
Hydralazine Tab 10mg, Oral 0.4–1.5mg/kg/dose Q6–12H Use with caution in cardiac
Inj 20mg (max 200mg/day). disease.
IV 0.1–0.2mg/kg/dose Q4–6H Response may be delayed
4–6mcg/kg/min. and unpredictable in some
(max 20mg/dose, patients.
3.5mg/kg/day, May cause a drug-induced
60mg/day lupus-like syndrome (more
likely on larger doses, longer
duration).
Nitroprusside Inj 50mg/2ml IV 0.5–4mcg/kg/min Monitor thiocyanate levels if
Sodium (max 8–10mcg/kg/min) requiring prolonged infusion
(>3 days) or dose ≥4mcg/
kg/min or patient has renal
dysfunction.
Monitor cyanide blood levels
in patients with decreased
hepatic function; Monitor
for cyanide toxicity via acid-
base balance and venous
oxygen concentration.
Must be further diluted
with D5% in water before
administration.
Glyceryl Trinitrate Inj 10mg/10ml IV 0.25–0.5mcg/kg/min; titrate by Use non-PVC tubing
0.5–1mcg/kg/min every 3–5
mins as needed.
(max 5–20mcg/kg/min).
Amlodipine Tab 5mg Oral 0.05–0.2mg/kg once daily
(max 10mg/day).
Nifedipine Cap 5mg, Oral 0.25–0.5mg/kg/dose Q6–8H
Cap10mg (max 10mg/dose 3mg/kg/day
90mg/day).

Atenolol Tab 50mg, Oral 0.5–1mg/kg Q12–24H Contraindicated in cardiac
Tab100mg 2mg/kg/day failure
100mg/day
Labetolol Tab100mg Oral 1–2mg/kg/day Q12H (max10- Contraindicated in cardiac
Inj 25mg/5ml 12mg/kg/day, up to max failure.
IV 1200mg/day)
0.25–3mg/kg/hr (max 120mg/hr)
INFECTIVE ENDOCARDITIS
Infection Usual Suggested Therapy

Organisms
First-line therapy Alternative therapy
(if severe penicillin
allergy)
Native valve Streptococci IV Amoxicillin/Clavulanic IV vancomycin 60mg/kg/
(community (Viridans and acid 120mg/kg/day day Q6H
acquired) or other nutritional (Amox: 100mg/kg/day) Q8H PLUS
prosthetic valve >1 variants), PLUS
year post-implant S. aureus (more IV gentamicin 3mg/kg/
common in IV Gentamicin 3mg/kg/ day Q8H
neonates, IV drug day Q8H WITH/WITHOUT
users), Enterococci, WITH/WITHOUT PO rifampicin
HACEK organisms PO Rifampicin 20mg/kg/day Q8–12H
20mg/kg/day Q8–12H (if (if prosthetic device)
prosthetic device)
Nosocomial As Above & IV Piperacillin/Tazo. (Pip) IV vancomycin 60mg/kg/

(in presence of CoNS, MRSA, 320mg/kg/day Q6H day Q6H
vascular cannulae) uncommonly PLUS PLUS
Candida, GBS, S. IV gentamicin 3mg/kg/
Prosthetic devices/ pneumoniae IV Clindamycin 40mg/kg/ day Q8H
valve day Q6H PLUS
(≤1 year post- WITH/WITHOUT IV cefepime150mg/kg/
implant) PO Rifampicin day Q8H
20mg/kg/day Q8–12H WITH/WITHOUT
(if prosthetic device) PO rifampicin
20mg/kg/day Q8–12H
(if prosthetic device)
Pre-exposure Streptococci PO Amoxicillin 50mg/kg/ IV/PO clindamycin
Prophylaxis (Viridans & dose (max 2g) (preferred) OR 20mg/kg/dose
(see Appendix: other nutritional IV Ampicillin 50mg/kg/ OR
‘Antibiotic variants), S. aureus, dose (preferred if unable to PO clarithromycin 15mg/
Prophylaxis Enterococci tolerate PO) OR kg/dose
for Infective PO Cephalexin 50mg/kg/
Endocarditis’ dose (max 2g) OR
below) IV/IM Ceftriaxone 50mg/
(see Circulation kg/dose
2007; 116: 1736)
What to do if “cultures Duration Remarks

negative & patient
better”
Continue IV antibiotics at least 4 Native valve: See “Infective Endocarditis”

weeks. Stop Vancomycin (if used) 4 weeks; section in Baby Bear for
if no evidence of resistant Staph. (2 weeks Genta if uncomplicated diagnostic issues, complications,
or enterococci. endocarditis with penicillin and indications for surgery.
sensitive isolates with MIC >3 separate sets of blood
≤0.1mg/L) cultures separated by time
Prosthetic valve: and location are required;
≥6 weeks inform laboratory if unusual
(2 weeks Genta if uncomplicated organisms suspected. Two-week
endocarditis with penicillin regimen not recommended if
sensitive isolates with MIC clinical symptoms >3 months,
≤0.1mg/L) extracardiac focus of infx,
intracardiac abscess, mycotic
Continue IV antibiotics at least Nosocomial/prosthetic valve: aneurysm. Enterococci inherently
4–6 weeks. ≥6 weeks resistant to cephalosporins
Stop Vancomycin (if used) if no (2 weeks Genta if uncomplicated despite in vitro testing.
evidence of resistant Staph. or endocarditis with penicillin Refer ID for Rx of complicated,
enterococci. sensitive isolates with drug-resistant endocarditis
MIC ≤0.1mg/L) (any organism). NB: beta-
lactams clinically superior to
glycopeptides for beta-lactam-
sensitive organisms.
NA 1 dose For oral prophylactic antibiotics

(e.g. dental/minor procedures),
give 1 hour before surgery.
For IV prophylactic antibiotics
(major procedures), to give 30
mins before surgery.
ANTIBIOTIC PROPHYLAXIS FOR PREVENTION OF

INFECTIVE ENDOCARDITIS
Cardiac Conditions
• Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
• Previous infective endocarditis
• Certain congenital heart disease (CHD)
Unrepaired cyanotic CHD, including palliative shunts and conduits
Recommended
Completely repaired congenital heart defect with prosthetic material or device,

whether placed by surgery or by catheter intervention, during the first 6 months
after the procedure
Repaired CHD with residual defects at the site or adjacent to the site of a
prosthetic patch or prosthetic device (which inhibit endothelialisation), by
cardiac surgery or percutaneous technique
• Cardiac transplantation recipients who develop cardiac valvulopathy
• Left-sided valvular lesions
Aortic stenosis
Aortic regurgitation
Mitral stenosis
Resonable
Mitral regurgitation
• Patients who have previously received antibiotic prophylaxis, and who would like
to continue having it, despite the rationale for the change in policy has been fully
explained (even though lesion may not be part of the list of cardiac conditions listed
above)
• Any other form of CHD except for the conditions listed in ‘Recommended’
Not Recommended
Types of Procedures
• Dental procedures
All dental procedures requiring manipulation of the gingival or periapical region of the teeth
or perforation of the oral mucosa
• Respiratory tract procedures
Invasive procedure of the respiratory tract that involves incision or biopsy of the respiratory
mucosa, such as tonsillectomy and adenoidectomy
Invasive procedure to treat an established infection, such as drainage of drainage of an
abscess or empyema
• Procedures involving infected skin, skin structure, or musculoskeletal tissue
• As Above
• Dental procedures
Routine anaesthetic injections through non-infected tissue
Placement of removable prosthodontic or orthodontic appliances
Shedding of deciduous/primary teeth
Bleeding from trauma to the lips or oral mucosa
• Respiratory tract
Endotracheal intubation
Bronchoscopy
Tympanostomy tube insertion
• Gastrointestinal or genitourinary tract procedures (unless there is an established infection)
• Others
Cardiac catheterisation , including balloon angioplasty
Implanted cardiac pacemakers, implanted defibrillators, and coronary stents
Incision or biopsy of surgically scrubbed skin
Circumcision
642
APPENDIX III: USEFUL FORMULAE
Intubation — Sequence of Drugs

Normal Ranges
 Pre-medication (Atropine) Age (yrs) Breaths/min HR beats/min
 Sedation/analgesia <1 30–40 110–160
(midazolam/morphine) 2–5 20–30 95–140
 Neuromuscular blockade 5–12 15–20 80–120
(suxamethonium)
>12 12–15 60–100
Medications Suitable for Endotracheal
Administration Maintenance Fluid Requirements
Naloxone Fluids for neonates:
Atropine Day of Life ml/kg/day
Ventolin (salbutamol) Neb 1 60
Epinephrine (adrenaline 1:1,000) 2 90
Lignocaine 3 120
4–30 150
Formulae for Endotracheal Tube
For INFANTS and OLDER:
ETT size (internal diameter) =
for first 10kg 4ml/kg/hr
[(age in years ÷ 4) + 4]
for next 10kg 2ml/kg/hr
ETT length (oral) =
for every kg >20kg 1ml/kg/hr
[(age in years ÷ 2) + 12] cm
ETT length (nasal) =
[(age in years ÷ 2) + 15] cm Composition of Intravenous Fluids
Sodium Dextrose
Estimated Size/Length of ETT mmol/L g/ml
Age Wt (kg) Size Oral (cm) Nasal Normal Saline 154 (0.9%) 0
Neo 3 3.5 8.5 10
3
/12 5 3.5 10 12 D/S (A) 154 (0.9%) 0.05 (5%)
1 9 4.0 11 14 D/S (R) 77 (0.45%) 0.025 (2.5%)
2 12 4.5 12 15 D/S (M) 39 (0.23%) 0.0375
4 16 5.0 14 17 (3.75%)
8 24 6.0 16 20
12 38 7.0 18 22 Dextrose 50% 0 0.5
Dextrose 10% 0 0.1
ETT size for neonates:
Dextrose 5% 0 0.05
<1kg 2.5mm
1–2kg 3mm For admission to Children's ICU or to activate
>2kg 3.5mm the Children's Hospital Emergency Transport
Service (CHETS), call direct +65-6394 1778/9.
Appendix III: Useful Formulae 643
Normal Urine Output

Burns
Burn Depth: Neonates >0.5ml/kg/hr
1st degree Sunburn Infant–Above 1ml/kg/hr
2nd degree Blister (closed/open)
Fluid Resuscitation
3 degree
rd
Insensate (black/white eschar)
Estimate % BSA of burn: 1 child’s palm = 1% Bolus volume: 10–20ml/kg
BSA Fluid type: Normal saline, 5% Albumin,
Parkland Formula Blood,FFP
Volume replacement (2nd/3rd degree burns): Total Body Blood Volume: 80ml/kg
In first 24 hours, total volume = 4ml/kg per % BSA Expected Systolic Blood Pressure
burn For <1 month of age, SBP >60mmHg
Give half over first 8 hours after burn, half over the
For 1 month to 1 year, SBP >70mmHg
next 16 hours.
For >1 year, SBP >70 + (Age in years x 2) mmHg
RHYTHM DISTURBANCES
BRADYCARDIA
Stable Unstable — Signs of Shock Present
Close monitoring CPR (chest compressions + BVM)
Optimise oxygenation Adrenaline
Consider causes Atropine (if vagal aetiology)
Consider pacing
TACHYCARDIA
Stable Unstable — Signs of Shock Present
Narrow complex (SVT) Narrow complex (SVT)
Adenosine Synchronised cardioversion
Amiodarone, if refractory First dose 0.5–1 J/kg; second dose 2 J/kg
Wide complex (VT) Wide complex (VT)
Amiodarone As per SHOCKABLE RHYTHMS
Consider lignocaine
PULSELESS ARREST — all rhythms
Commence chest compressions and BVM with 100% O2
Secure airway; Obtain vascular access
NON-SHOCKABLE RHYTHMS
ASYSTOLE/PULSELESS ELECTRICAL ACTIVITY
Adrenaline every 3–5 mins
Consider causes
Hypoxaemia Hypoglycamia Trauma
Hypovolaemia Hypothermia Tamponade, Cardiac
Hydrogen ions (Acidosis) Thromboembolism Toxins
Hyper/hypokalaemia Tension pneumothorax
SHOCKABLE RHYTHMS
VENTRICULAR FIBRILLATION/PULSELESS VENT TACHYCARDIA
CPR
4J/kg each
Adrenaline every alternate shock, AFTER third shock. Max 10J/kg
CPR for 1–2mins, then assess if rhythm is shockable.
Amiodarone every alternate shock, AFTER third shock (max 3 doses).
Consider other antirrhythmics thereafter (lignocaine, magnesium sulphate).
644
APPENDIX IV: RESUSCITATION ALGORITHM

SUPRAVENTRICULAR TACHYCARDIA
In shock Not in shock
Sync DC 0.5–1 J/kg Ice bag

Vagal manoeuvres
Overdrive pacing
Double the dose
Adenosine 0.1mg/kg
(max 6mg)
Adenosine 0.2mg/kg
(max 12mg)
May be repeated
Consider
cardioversion/
consider other
antiarythmics
ASYSTOLE
CPR: Check ABCs

Secure airway
Hyperventilate with 100% oxygen
Obtain vascular access

0.1ml/kg 1:10,000 adrenaline IV/IO
0.1ml/kg 1:1,000 adrenaline ET
For second and subsequent doses, consider up to 0.1mg/kg
Appendix IV: Resuscitation Algorithm 645
BRADYCARDIA
Assess ABCs
Secure airway
If severe cardiopulmonary compromise

(poor perfusion, hypotension, respiratory distress)
Chest compression if:

HR <80/min in infant
HR <60/min in child

0.1ml/kg 1:10,000 adrenaline IV/IO
0.1ml/kg 1:1,000 adrenaline ET
For second and subsequent doses, consider up to 0.1mg/kg
Atropine 0.02mg/kg
May be repeated once
Consider external pacing
PULSELESS ELECTRICAL ACTIVITY/EMD
Identify and treat causes

(severe hypoxaemia, acidosis, hypovolaemia,
tension pneumothorax,
cardiac tamponade, hypothermia)
Treat as for Asystole

VENTRICULAR FIBRILLATION OR PULSELESS VT
Assess ABCs
Secure airway
Correct apoxia, acidosis, hypothermia
Consider drug or metabolic causes
Defibrillate up to 3 times
(4J/kg, 4J/kg, 4J/kg)
Adrenaline 0.1ml/kg 1:10,000 adrenaline IV/IO

ET: 0.1ml/kg 1:1,000
Defibrillate 4J/kg 30–60 secs after each medication
Lignocaine 1mg/kg
Defibrillate 4J/kg 30–60 secs after each dose

0.01–0.1ml/kg 1:1,000 adrenaline ET or
subsequent IV/IO
647
APPENDIX V: FLUIDS & ELECTROLYTES

MANAGEMENT OF FLUIDS
Maintenance fluid requirement
Neonates:
Day 1: 60ml/kg/day
Day 2: 90ml/kg/day
Day 3: 120ml/kg/day
Day 4: 150ml/kg/day
* In a sick neonate (>Day 3 of life), consider restricting IV fluids to

100–120ml/kg/day
** IV fluid requirements should be capped at 100ml/kg/day
Child:
Table 16-1: Calculating maintenance fluids in children
<10kg 100ml/kg/day
Or 4ml/kg/hr
10–20kg 1,000ml + 50ml/kg/day for each kg >10kg
Or 40ml/hr + 2ml/kg/hr for each kg >10kg
>20kg 1,500ml + 20ml/kg/day for each kg >20kg
Or 60ml/hr + 1ml/kg/hr for each kg >20kg
For example: the maintenance fluid requirement of a 35kg child would be

(100 x 10) + (50 x 10) + (20 x 15) = 1,800ml
Choice of IV fluids:
The recommended maintenance fluids for the various age groups are
as follows. The choice of fluids should also be based on the ongoing
physiological disorder and prevalent electrolyte or glucose abnormality.
Age <1 month: Dextrose 10% Combination drip

Age 1–3 months: Dextrose 5% with 0.45% NaCl
Age >3 months: Dextrose 5% with 0.9% NaCl
Special considerations
Higher fluid requirements: children who are febrile, under phototherapy,
or a radiant warmer, children with ongoing fluid losses (vomiting,
diarrhea, high stomal output, burns)
Lower fluid requirements: Stable post-operative children, children with
renal or cardiac failure, children with SIADH
Fluid deficit in dehydrated children

 Children with reduced intravascular fluid status should be assessed
early and preferably with a senior doctor.
 See Table 16-2 for a guide to the assessment of the intravascular fluid
status of a child. When in doubt, the more severe dehydration status
should be used.
 The rate of replacement of fluid deficit depends on the primary
pathology and its severity. For example, a slower replacement
rate should be used for children with diabetic ketoacidosis and
intracranial pathology, due to the risk of cerebral oedema.
 Oral rehydration therapy is discussed in the Gastroenterology chapter
under “Acute Gastroenteritis”.
Table 16-2 Assessment of hyration status

Mild Dehydration Moderate Severe Dehydration
(3–5%) Dehydration (>10%)
(6–9%)
General Condition Alert, thirsty Thirsty, restless or Drowsy, floppy, unconscious
lethargic/irritable
Eye Normal Sunken Very sunken and dry
Tears Present Absent Absent
Mouth/Tongue Moist Dry Very dry
Capillary Refill Normal Prolonged >2 secs Prolonged >2 secs
Skin Turgor Instant recoil Recoil in >2 secs Recoil in >2 secs
Skin Normal Normal Cold and clammy, mottled
Fontanelle Normal Sunken Very sunken
Urine Normal Reduced amount Anuria/severe oliguria
Pulse Rate Normal rate and volume Rapid and weak Rapid, feeble
Blood Pressure Normal Normal/low Low/unrecordable
Respiration Normal Deep/maybe rapid Deep and rapid
Weight Loss 3–5% 6–9% ≥10%
Appendix V: Fluids & Electrolytes 649
Table 16-3: Calculating fluid deficit

Body weight x % dehydration = Deficit in Litres
• e.g. 10kg child, 3% dehydration: Fluid deficit 10 x 0.03 = 0.3L = 300ml
Fluid used for rehydration is the same as maintenance fluids. Rehydration should be carried out
evenly over at least 24–48 hours
• e.g. 20kg child, 5% rehydration
Maintenance: 1,500ml/day, Deficit: 1,000ml
Therefore, prescribe 2,500ml/day for first 24 hours, 1,500ml/day thereafter
MANAGEMENT OF ELECTROLYTES
Introduction
Electrolyte abnormalities are frequently encountered in paediatric
practice. When encountering problems with fluid and electrolyte
imbalance, it is useful to think about what the expected renal response
is to a given situation, and evaluate the actual response. This is done by
measuring serum and urine parameters:
 Serum: urea, creatinine, sodium (Na), potassium (K), chloride (Cl),
calcium (Ca), magnesium (Mg), phosphate (PO4), osmolality, pH, PaCO2
 Urine: Na, K, Cl, osmolality, creatinine, pH
When considering the appropriate level of care that the patient requires
(general ward, high-dependency, CICU), particular attention should also
be given to the requirement for:
• Cardiac monitoring
• Haemodynamic monitoring/intervention
• Neurological monitoring: level of consciousness, seizures
• Frequency of blood sampling and availability of venous access
Table 16-4: Daily electrolyte requirement

Sodium 2–4mmol/kg/day
Potassium 1–2mmol/kg/day
Chloride 2–4mmol/kg/day
Calcium 0.5–1mmol/kg/day
Magnesium 0.2–0.4mmol/kg/day
Phosphate 2mmol/kg/day
Sodium abnormalities
Sodium abnormalities are more commonly the result of disruption in
fluid homeostasis, rather than sodium homeostasis. Assessment of the
intravascular volume status and anti-diuretic hormone (ADH) activity
(via comparison of serum and urine sodium and osmolality) provides a
guide to the underlying pathology.
Hypernatraemia
Definition:
 Serum sodium >150mmol/L
 Irritability, lethargy, hyper-reflexia, ataxia, seizures, coma
Assessment:
 See Figure 16.1 for a diagnostic approach
 Assess the fluid status
 Determine the urine volume
 Paired serum and urine osmolality and sodium, serum urea,
creatinine and chloride
HYPERNATRAEMIA
Hypovolaemia/Euvolaemia Hypervolaemia
Total body water (↓↓) Total body water (↑↑)
Total body Na (↓/Normal) Total body Na (↑↑)
Oliguria Urine Na>20 Urine Na<10

High urine osmolality Polyuria
(Uosm)
Excessive Na intake Retention of Na
Iatrogenic (↑ Na load) > water
Extrarenal loss of Salt intoxication Hyperaldosteronism
free water
Urine Na>20 Urine Na<10
Hypodipsia
Gut losses
Burns Renal losses Excessive renal loss
↑ insensible losses
Diuretics of free water
Osmotic diuresis Diabetes insipidus
(Diabetes mellitus,
catabolic states)
Intrinsic renal disease
Figure 16.1: Diagnostic approach to hypernatraemia

Management:
 Water deficit (L) = 0.6 x Weight (kg) x ([Current Na]/140 − 1)
 Aim: decrease of [Na] by no more than 0.5mmol/L/hr (max of
8–10mmol/L/day) due to risk of cerebral oedema
 Hypervolaemia: restriction and removal of excess Na with loop
diuretics and hypotonic fluids
 Hypovolaemia: give relatively hypo-osmolar fluid
 Treat underlying cause: e.g. Vasopressin for central diabetes insipidus
(DI), removal of exogenous Na
Hyponatraemia
Definition:
 Serum Na <135mmol/L
 Corrected Na levels: measured Na + 0.3 (glucose − 5.5) mmol/L
 Lethargy, weakness, altered sensorium, decreased level of
consciousness (LOC), seizures, coma
HYPONATRAEMIA
Exclude pseudohyponatraemia
(which has normal or increased Hypotonic Hyponatraemia
serum osmolality)
Hypovolaemic Euvolaemic Hypervolaemic
Urine Na>20 Urine Na<10 Urine Na<10 Urine Na>20

Uosm >100 Uosm <100
FeNa >1% FeNa <1% FeNa <1% FeNa >1%
Renal Na losses Extrarenal Excessive Excessive intake Retention of Na Retention of

Mineralocorticoid losses retention of free of free water and water water and loss
deficiency GI losses water Primary Congetive cardiac of Na
Addison’s disease Third spacing SIADH polydipsia failure Renal failure
Osmotic diuresis Burns Hypothyroidism Hypotonic fluid Cirhosis
Renal tubular Cortisol infusion Nephrotic
acidosis deficiency syndrome
Figure 16.2: Diagnostic approach to hyponatraemia

Assessment:
 Assess the hydration status
 Determine the urine volume
 Paired serum and urine osmolality and sodium, serum urea,
creatinine and chloride
Calculated serum osmolality = (2 x [Na]) + [Glucose] + [Urea]
Calculate the FeNa (%): [(UNa/PNa) / (UCreat/PCreat)] x 100
Management:
 Depends on chronicity of hyponatraemia and severity of symptoms
 Na deficit (mmol) = 0.6 x Body Weight (kg) x [135 − (current Na)]
 Aim: increase of [Na] by no more than 0.5mmol/L/hr (max of
12mmol/L/day) due to risk of central pontine myelinolysis (acute
paralysis, dysphagia, dysarthria)
If Na ≥120mmol/L, correct by restriction of free water
If Na <120mmol/L or severely symptomatic (e.g. hyponatraemic
seizures) correct to 125mmol/L (can be 1–2mmol/L/hr in the first few
hours) monitor for the resolution of symptoms and rate of rise of Na
and scale back the speed of correction accordingly
Drugs used:
 3% NaCl: 0.5mmol of Na per ml
 2ml/kg of 3%NaCl increases Na by approximately 1mmol/L
 Dextrose 5%/0.45% NaCl
 20% NaCl solution: 3.4mmol of Na per ml
 NaCl tablet (500mg): 8.5mmol of Na per tablet
 Na-citrate (Shohl’s solution): 1mmol of Na per ml
Potassium abnormalities
Hyperkalaemia
Definition:
 Serum potassium levels:
 Neonate: K >6.0mmol/L
 Older child: K >5.5mmol/L
 Exclude spurious results (e.g. blood taken from a vein proximal to a
drip containing potassium) or haemolysed sample
 Arrhythmias (with palpitations, syncope), ECG abnormalities (tall
T-waves, depressed ST-segment, decreased R-wave amplitude,
prolonged PR, small or absent P-waves, prolonged QRS, sine-wave,
ventricular fibrillation)
 Neuromuscular weakness (ascending from the legs to the arms and
trunk) or parasthesia, hyporeflexia
Table 16-5: In-patient emergency management of hyperkalaemia in children and neonates

Inclusion Criteria Exclusion Criteria
• Paediatric patient (>1 month age) with a serum • Post-operative cardiac patients in the intensive care unit
potassium level of ≥5.5mmol/L • Patients in the neonatal intensive care unit and
• Term neonatal patient (≤1 month age) with special care nursery
serum potassium level of >6mmol/L • Premature neonates
Caution:
• Exclude fictitious causes or lysed blood sample
• Check renal function if not done so (send urgent renal panel)
• Repeat with iSTAT if critical
• Review medications/infusions (look for exogenous K+ sources, drugs which decrease renal K+ excretion or
cause transcellular K+ shift)
Table 16-6: Emergency management of hyperkalaemia algorithm

Age >1 month old AND K+ ≥5.5mmol/L
Age ≤1 month, full term AND K+ ≥6mmol/L
Perform ECG immediately
Review all medications/infusions
Potassium K+ 5.5–6mmol/L K+ 6.1–6.9mmol/L ECG abnormal
level OR
K+ >7mmol/L
Initial If acute and ongoing • Cardiac monitoring • Cardiac monitoring
treatment cause: • To High Dependency • To CICU
1. Salbutamol neb • Inform senior staff • Inform senior staff
2. PR/PO resonium Administer: Administer:
If CRF patient: 1. Salbutamol neb 1. Calcium gluconate OR
1. PR/PO resonium 2. IV dextrose/Insulin Calcium chloride
2. Diet modification 3. PR/PO resonium (omit 2. Salbutamol neb
3. Inform nephrologist if served in the last 2 3. IV dextrose/Insulin
hours) 4. PR/PO resonium (omit if
4. +/− sodium served in the last 2 hours)
bicarbonate (if pH <7.2) 5. +/− sodium
bicarbonate (if pH <7.2)
Review Review K+ in 1 hour Review K+ and H/C in Review K+, H/C and ECG
1 hour in 30 mins
Further K+ improving: K+ improving: K+ improving:
management • Continue monitoring • Continue monitoring • Continue monitoring
until normalised until normalised until normalised
• If K+: 5.5–6, can • If K+: 5.5–6.9, can • can repeat salbutamol
repeat salbutamol Neb repeat salbutamol +/–dextrose/insulin
until normal +/− dextrose/insulin K+ NOT improving:
K+ NOT improving: until normal • re-evaluate for cause
• re-evaluate for cause K+ NOT improving: • If ECG changes persist,
• If K+ >6, escalate • re-evaluate for cause can repeat Calcium
to next level of • If K+ >6.9, escalate • Consider CRRT
management to next level of
management
Table 16-7: Emergency management of hyperkalaemia paediatric drugs
Drug Name Dosage and Route Onset of Duration Comments

Action
Salbutamol 0.5% Nebulised with 8L/gas flow: 30–60 mins 3–4 hours May cause tachycardia.
solution <25kg: 2.5mg in 4ml N/S Q1–2H May be repeated.
>25kg: 5mg in 4ml N/S Q1–2H
Insulin IV 0.1 unit/kg/dose 15–20 mins 4–6 hours 1 unit per 5g of glucose.
(max 10 units/dose) May cause hypoglycaemia.
To take 50 units using insulin **Monitor hypocount 1 hour
syringe and reconstitute to 50ml in after dose.**
normal saline
 Final concentration is 1 unit/ml May be repeated.
**Administer appropriate dose
using diluted solution.**
Dextrose 10% IV 5ml/kg/dose — — To administer with IV insulin.
Dextrose 50% IV 1ml/kg/dose — — To administer with IV insulin.
**Requires central venous or
large bore peripheral venous
access**
Sodium resonium PO 1g/kg/dose (max 15–30g/ 1–2 hours 4–6 hours Contraindicated if ileus, recent
(Sodium dose) Q8H abdominal surgery, or perforated
Polystyrene PR 1g/kg/dose (max 30–60g/dose) gut. Contraindicated in neonates
Sulfonate) Q2–6H (evacuate previous dose with reduced gut motility.
before administration) May cause nausea, constipation,
paralytic ileus or diarrhoea.
May be repeated.
10% Calcium IV 0.5–1ml/kg/dose over 10 mins 5–10 mins 30–60 May cause hypercalcaemia or
gluconate (max IV 30ml/dose) mins tissue necrosis.
(2.25mmol/10ml) May be repeated if ECG changes
persist.
10% Calcium IV 0.2ml/kg/dose (max 20ml) over — — May cause hypercalcaemia or

chloride 10 mins tissue necrosis.
(5.5mmol/10ml) **May use in place of calcium May be repeated if ECG changes
gluconate if fluid restricted** persist.
Sodium IV 1ml/kg/dose over 10–15 mins 4–6 hours 4–6 hours May cause sodium overload/
bicarbonate (max IV 50mmol/dose) hypertension. May use when
8.4% (1mmol/ml) To dilute with equal parts W.F.I. evidence of acidaemia present (pH
to make up 4.2% solution before <7.2; serum HCO3 <15mEq/L).
administration **Not to give simultaneously
with calcium.**
Comments
1. Salbutamol is a preferred first-line treatment for hyperkalaemia because of ease of administration while other treatments
are being prepared.
2. Concentrated insulin is a high-alert medication, and care should be taken in its dilution and preparation.
3. Salbutamol and insulin are short term treatments for hyperkalaemia, and can be repeated. Efforts should be made in the
meantime to identify and treat the underlying cause.
Figure 16.3: ECG changes in hyperkalaemia
Tall tented T-waves Widened QRS interval Flattened P Waves Sine wave pattern
(S and T waves merging)
Narrow peaked T waves, U waves, shortened QT intervals, prolonged PR intervals, prolonged QRS
intervals, loss of P wave, sine waves and ultimately ventricular fibrillation may be present in patients with
hyperkalaemia. ECG changes do not necessarily progress in the above order in relation to the degree of
hyperkalaemia, and there is poor correlation between ECG changes and serum potassium concentration.
Hyperkalaemia with ECG changes is a MEDICAL EMERGENCY and requires IMMEDIATE ATTENTION.
Causes:
 Increased intake: over-replacement via oral route, IV fluids
(containing excessive potassium), massive transfusion
 Transcellular movement of potassium: increased cellular injury
(rhabdomyolysis, tumour lysis, haemolysis), metabolic acidosis,
insulin-deficiency states
 Decreased renal excretion: decreased GFR (in kidney injury),
hypoaldosteronism or impaired sensitivity to aldosterone, impaired
renin-angiotensin-aldosterone system (congenital adrenal
hyperplasia, potassium-sparing diuretics, ACE inhibitors)
Management:
 Management guidelines are discussed in “Emergency management
of hyperkalaemia in Children Algorithm”
 It is crucial to correct the underlying cause of the hyperkalaemia
Hypokalaemia
Definition:
 Serum K+ <3.5mmol/L
Clinical manifestations:
 Arrhythmia, ECG abnormalities (prolonged PR, ST depression,
T-inversion), neuromuscular weakness
Management:
 Correction of hypokalaemia is more crucial in children with cardiac
disease or on digoxin
 Correct deficit on top of providing maintenance potassium. The required
maintenance may be higher depending on the underlying pathology (e.g.
severe dehydration in DKA, with expected requirement for IV Insulin)
 Correcting hypokalaemia
 K-Deficit (mmol): (Desired [K] − current [K]) x 0.3 x wt (kg)
 Non-urgent replacement:
 Oral K replacement is the preferred route
 Increase maintenance K in the IV drip
 Urgent replacement: consider IV replacement in the following cases:
 Severe hypokalaemia K <2.5mmol/L
 Symptomatic: severe weakness, arrhythmia, post-operative cardiac
 Unpredictable enteral absorption: significant enterocolitis, post-
major surgery
 Concentrated KCl
 Replacement of K-deficit over 2–3 hours
 Peripheral: dilute the 7.45% KCl into 0.9% NaCl (maximal
concentration of 40mmol/L)
 Central: dilute the 7.45% KCl into 0.9% NaCl (maximal
concentration of 150mmol/L)
 Max rate of 0.4mmol/kg/hr
 Replacement should be done under cardiac monitoring, and in
HD, Oncology wards or CICU
 IV 7.45% KCl should NEVER be given undiluted or as bolus
 Potassium-containing preparations
 Oral KCl: 1ml contains 1.34mmol of K
 Oral Span K (600mg): 8mmol of K/tablet
 IV 7.45% KCl: 1ml contains 1mmol of K and 1mmol of Cl
 KH2PO4: 1ml contains 1mmol of K and 1mmol of PO4
ACID-BASE DISORDERS
A good clinical evaluation is essential to guide the workup of acid base

disorders
 History of underlying medical problems (e.g. diabetes, cardiac failure)
 Symptomatology: e.g. vomiting, diarrhea
 Vital signs (e.g. shock, hypoxia)
 Respiratory status: rate and depth of breathing (e.g. Kussmaul’s respiration)
 Neurological status: level of consciousness
 Medication or drug use
Table 16-8: Primary acid-base disorder with the expected secondary response
Primary disorder Physiological Expected physiological response
disorder
Metabolic acidosis Low HCO3 Expected paCO2 = 1.5 [HCO3] + 8 ± 2
Metabolic alkalosis High HCO3 Expected paCO2 = 0.7 x ([HCO3] − 24) + 40 ± 2
Respiratory High paCO2 Acute: HCO3 rises by 1mmol/L per 10mmHg rise in
acidosis PaCO2 (above 40mmHg)
Chronic: HCO3 rises by 4–5mmol/L per 10mmHg rise in
PaCO2
Respiratory Low paCO2 Acute: HCO3 falls by 2mmol/L per 10mmHg fall in
alkalosis PaCO2 (below 40mmHg)
Chronic: HCO3 falls by 4–5mmol/L per 10mmHg fall
in PaCO2
Blood gas: determine the primary acid-base disorder

 Ascertain if there is acidaemia (pH <7.38) or alkalaemia (pH >7.42)
 Is this a primary respiratory or metabolic disorder
 Determine the appropriate physiological response to the primary
disorder. Hence, evaluate if there is a secondary component to the
acid-base disorder. See Figures 16.4 and 16.5.
 Evaluate the osmolar gap: measured serum osmolality − calculated
serum osmolality
 Calculated serum osmolality = 2[Na] + [glucose] + [Urea]
 Osmolar gap of >10mmol/L suggests the presence of toxic
alcohols (ethylene glycol, methanol), or the presence of
ketoacidosis or lactic acidosis.
Acidaemia
High Anion-gap Metabolic Acidosis (HAGMA)

 Overproduction of acid
 Ketoacidosis (DKA, starvation)
 Lactic acidosis
 Type A (hypoxic): shock, carbon monoxide and cyanide poisoning
 Type B (non-hypoxic): medications (propofol, metformin,
isoniazid, salicyclates), toxic alcohols (methanol, ethylene glycol)
 Impaired clearance of acid: severe renal injury, liver failure (lactate
clearance)
 Cell lysis: severe rhabdomylosis
Figure 16.4: Diagnostic approach to acidaemia
ACIDAEMIA
Metabolic acidosis Respiratory acidosis

(HCO3 <22mmol/L) (PaCO2 >42mmHg)
Assess expected respiratory response Assess expected metabolic response

Expected PaCO2 = 1.5 x [HCO3] + 8 ± 2 if there is [HCO3] increase of:
PaCO2 lower than expected: 1mmol/L per 10mmHg rise in PaCO2 (above 40):
additional respiratory alkalosis acute respiratory acidosis
PaCO2 higher than expected: <1mmol/L per 10mmHg rise in PaCO2:
additional respiratory acidosis additional metabolic acidosis
4–5mmol/L per 10mmHg rise in PaCO2:
chronic respiratory acidosis
Calculate Anion Gap (AG) >5mmol/L per 10mmHg rise in PaCO2:
[Na] − [Cl] − [HCO3]; additional metabolic alkalosis
Correct for hypoalbuminaemia: Increase AG by

2.5mmol/L for every 1g/dL decrease in albumin
Calculate A-a gradient
(FiO2 x 713) − PaO2 − (1.25 x PaCO2)
High AG
Normal AG (AG >12)
(AG ≤12) (lactate, keto-acids,
toxic alcohols) A-a ≤10mmHg A-a >10mmHg
Hypoventilation without intrinsic Hypoventilation with intrinsic lung
Calculate Urine AG lung disease disease and/or VQ mismatch
(UAG)
[Na] + [K] − [Cl]
Delta-delta (∆-∆) Osmolal gap

Ketoacidosis: ∆AG − ∆[HCO3] (Measured − calculated osmolality)
Negative UAG Lactic acidosis: (0.6∆AG) − ∆[HCO3] Calculated osmolality = 2[Na] +
GI losses Positive UAG) ∆-∆ between −5 and 5: only HAGMA [glucose] + [urea] (mmol/L)
proximal RTA ∆-∆ >5: HAGMA with metabolic Osmolal gap >10mmHg: significant
alkalosis (metabolite or toxic alcohol)
∆-∆ <-5: HAGMA with NAGMA
Urine pH >5.5 Urine pH <5.5
Type 1 RTA Type 4 RTA
↑/Normal plasma
↓ Plasma aldosterone
aldosterone
Aldosterone resistance
Normal plasma
↓ Plasma cortisol
cortisol
Aldrenal insufficiency
Aldosterone deficiency
Normal Anion-gap Metabolic acidosis (NAGMA)

 Loss of bicarbonate
 GI losses: diarrhea, stomal losses, fistulae
 Renal losses: proximal RTA, medications (ifosfamide, topiramate,
acetazolamide)
Respiratory acidosis
 Acute
 Normal A-a gradient: depression of the respiratory centre by CNS
disease (meningoencephalitis) or drugs
 High A-a gradient: acute airway obstruction, acute lung disease
(ARDS, pneumonia)
 Chronic
 Normal A-a gradient: neuromuscular disease
 High A-a gradient: chronic lung disease (from broncho-
pulmonary dysplasia or bronchiectasis)
Alkalaemia
Metabolic alkalosis
 The kidney is highly efficient in excreting excess bicarbonate. Hence,
metabolic alkalosis usually requires the presence of excess intake of
alkali and the impairment of renal excretion of bicarbonate
 Evaluating the cause
 Assess for excessive loss of nasogastric fluid, diuretic use or
exogenous alkali intake
 Should the history not provide a clue to the cause, assess the
urinary chloride (Urine Cl)
 Chloride-responsive metabolic alkalosis: replenishment of
fluid volume, sodium chloride and potassium corrects the
metabolic alkalosis
 Chloride-resistant metabolic alkalosis: due to excessive renal
loss of sodium chloride
Respiratory alkalosis
 Acute
 Normal A-a gradient: Pain, fever, hyperventilation (in anxiety),
salicylate toxicity
 High A-a gradient: pneumonia, pulmonary oedema, sepsis,
aspiration, pulmonary embolism
 Chronic
 Normal A-a gradient: hyperthyroidism
 High A-a gradient: pulmonary embolism
Treatment of the acid base disorders will depend on the underlying cause
Figure 16.5: Diagnostic approach to Alkalaemia
ALKALAEMIA
Metabolic alkalosis Respiratory alkalosis

(HCO3 >26mmol/L) (PaCO2 <38mmHg)
Assess expected respiratory response Assess expected metabolic response

Expected PaCO2 = 0.7 ([HCO3] − 24) + 40 ± 2mmHg if there is [HCO3] increase of:
PaCO2 lower than expected: 2mmol/L per 10mmHg drop in PaCO2 (above 40):
additional respiratory alkalosis acute respiratory alkalosis
PaCO2 higher than expected: <2mmol/L per 10mmHg drop in paCO2:
additional respiratory acidosis additional metabolic alkalosis
4–5mmol/L per 10mmHg drop in paCO2:
chronic respiratory alkalosis
>5mmol/L per 10mmHg drop in paCO2:
Exclude HC03 Excess additional metabolic acidosis
Milk-alkali syndrome
Excessive NaHCO3 intake
Massive blood transfusion
Calculate A-a gradient
(FiO2 x 713) − PaO2 − (1.25 x PaCO2)
Urine Chloride
<25mmol/L
Urine Chloride
Chloride-sensitive
>40mmol/L A-a ≤10mmHg A-a >10mmHg
metabolic alkalosis
Chloride-resistant
Extra-renal loss metabolic alkalosis Hyperventilation without intrinsic Hypoventilation with intrinsic lung
Loss of gastric fluid (excessive renal loss of NaCl) lung disease disease and/or VQ mismatch
Chloride-wasting diuretics
Diuretics
Chloride-losing diarrhoea
Cystic fibrosis
Low/normal BP
High BP
Gitelman syndrome
(↓ Urine calcium) Mineralocorticoid excess
Bartter syndrome
(↑ Urine calcium)
Bibliography
1. BMJ Best practice: Evaluation of hyponatraemia. Accessed in February 2015.
2. Clinical Practice Guidelines: Hyperkalemia. Royal Children’s Hospital, Melbourne Australia
August 2011.
3. Emergency Management of Hyperkalemia. Pediatric Intensive Care Unit. Royal Hospital
for Sick Children. NHS Greater Glasgow and Clyde. Oct 2010.
4. Emergency interventions for hyperkalaemia (Review). The Cochrane Library 2009 Issue 3.
5. Hollander-Rodriguez JC, Calvert JF Jr. Hyperkalemia. Am Fam Physician. 2006 Jan
15;73(2):283–90.
6. Khanna A, White WB. The management of hyperkalemia in patients with cardiovascular
disease. Am J Med. 2009 Mar;122(3):215–21.
7. Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis and management of hyperkalemia.
Pediatr Nephrol 2011;26: 377–384.
8. Lexicomp online: Accessed in January 2015.
9. Masilamani K, van der Voort J. The management of acute hyperkalaemia in neonates and
children. Arch Dis Child 2012;97:376–380.
10. Mildenberger E, Versmold HT. Pathogenesis and therapy of non-oliguric hyperkalaemia of
the premature infant. Eur J Pediatr. 2002 Aug;161(8):415–22.
11. O’Hare FM, Molloy EJ. What is the best treatment for hyperkalaemia in a preterm infant?
Arch Dis Child 2008;93:174–176.
12. Paediatrics in Review: Acid-BaseDisorders. Vol.32 No.6. June 2011.
13. Paediatrics in Review: Disorders of Water Metabolism in Children: Hyponatraemia and
Hypernatraemia. M.L. Moritz and J.C. Ayus. Vol 23 No.11 November 2002.
14. Paediatrics On The Go; Chapter: Fluids and Electrolytes. Loke Kah Yin, Nicola Ngiam
15. Phelps SJ, Emily BH, Crill CM. 2010. “Calcium Chloride”, in Pediatric Injectable Drugs — the
Teddy Bear Book. (9th ed). Maryland: American Society of Health-System Pharmacists, Inc.
16. Physiological Approach to assessment of acid-base disturbances. Kenrick Berend, Aiko P. J.
de Vries, Riik O.B. Gans. NEJM 2014; 371:1434–1445, October 2014.
17. Shingarev R, Allon M. A physiologic-based approach to the treatment of acute
hyperkalemia. Am J Kidney Dis. 2010 Sep;56(3):578–84.
18. Starship Children’s Health Clinical Guideline: Hyperkalemia. April 2011
19. The HSC Handbook of Paediatrics, Anne I. Dipchand.
20. Uptodate online: Hyponatraemia in children. Accessed in January 2015.
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SingHealth Academy Publishing Team:

All rights reserved. No part of this publication may be reproduced, stored in

The publisher makes no representation or warranties with respect to the

National Library Board Singapore Cataloguing in Publication Data

1. LCSH: Pediatrics—Handbooks, manuals, etc. I. Soh, Shui Yen.

GENERAL AND AMBULATORY PAEDIATRICS 148

HAEMATOLOGY AND ONCOLOGY 226

Thrombosis and Thrombophilia in Paediatric Patients 263

IMMUNOLOGY & ALLERGY 311

INFECTIOUS DISEASES 326

Protocol for Renal Biopsy 448

PAEDIATRIC SURGERY 481

Juvenile Dermatomyositis (JDM) 544

APPENDIX I: GROWTH CHARTS 566

APPENDIX II: DRUGS 590

APPENDIX III: USEFUL FORMULAE 642

APPENDIX IV: RESUSCITATION ALGORITHM 644

APPENDIX V: FLUIDS & ELECTROLYTES 647

It has been my pleasure and privilege to be associated with this book,

[This page intentionally left blank]

Figure 1.1: Sinus arrhythmia.

 Related to changes in vagal tone during respiratory phases — Heart

Wandering Atrial Rhythm (Wandering Atrial Pacemaker)

Premature Atrial Contractions (PACs) (See Figure 1.3)

 Indwelling central venous lines with tip/line in the right atrium

Junctional Rhythm (See Figure 1.4)

Premature Ventricular Contractions (PVCs) (See Figure 1.5)

BRADYCARDIA AND CONDUCTION DISORDERS

Figure 1.8: First-degree atrioventricular block with a PR interval of 0.4 sec

 Adrenaline infusion 0.1–1.0mcg/kg/min

Sinus Arrest (See Figure 1.7)

First Degree Atrioventricular (AV) Block (See Figure 1.8)

Mobitz Type I Second-degree AV Block (Wenckebach)

Mobitz Type II Second-degree AV Block (See Figure 1.10)

Third-degree (Complete) AV Block (See Figure 1.11)

Figure 1.11: Complete heart block. Note atrioventricular dissociation

 Myocarditis and rheumatic fever can also cause complete AV

 Older children can complain of chest pain, palpitations or

 Intravenous verapamil — 0.1–0.2mg/kg/dose (max

Consider Vagal Clear ABC Consider IV Adenosine

IV Adenosine 0.1mg/kg (max 6mg) Sync DC Cardioversion 0.5J/kg

IV Adenosine 0.2mg/kg (max 12mg) Sync DC Cardioversion 1.0J/kg

Sync DC Cardioversion 2.0J/kg

Figure 1.13: Management protocol for supraventricular tachycardia

Ventricular Tachycardia (VT)

JUNCTIONAL ECTOPIC TACHYCARDIA (JET)

 Intravenous boluses of 1mg/kg over 10 mins (max 5mg/kg

CARDIOMYOPATHY AND HEART FAILURE

Table 1-2. Cardiomyopathies in children

Characteristics Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Restrictive

Epidemiology 60% idiopathic, 30% Autosomal dominant Rare in children;

Structural Dilated, poorly Hypertrophied Dilated atrium

Pathophysiology Dilated poorly Stiff hypertrophied Non-compliant

Associated lesions Mitral regurgitation LVOTO

Clinical features Dyspnoea, Sudden death can be Dyspnoea,

Chest X-ray Cardiomegaly, Usually minimal Dilated atria,

Treatment Management of Activity restriction, Management of