Se

co
nd
the
BABY
Ed
iti
on

BEAR
BOOK
A Practical Guide on
Paediatrics

Editors
Janil PUTHUCHEARY
Teng Hong TAN
Cheng Lim TAN
Kong Boo PHUA
 3

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 CONTENTS
SingHealth Academy Publishing Team:
Publisher: Neo Chia Reei
Editorial: Patricia Ng / Benny Chung Contents 3
Foreword 7
Marketing & Publicity: Michelle Lam / Lydia Ng
Preface 8
Editors and Contributors 9
Copyright © 2010 Singapore Health Services Pte Ltd and KK Women’s and
Children’s Hospital
CARDIOLOGY 11
All rights reserved. No part of this publication may be reproduced, stored in Cardiac Arrhythmias 11
Cardiac Failure 23
a retrieval system or transmitted, in any form or by any means, electronic,
Syncope — Diagnostic Approach 30
mechanical, photocopying, recording or otherwise, without the prior
Chest Pain 35
permission of the copyright owner. Request for permission should be
Approach to Possible Cyanotic Congenital Heart Defect (CHD) 41
addressed to The Publisher, c/o The Editorial Office, Hypercyanotic Spells 47
SingHealth Academy, 31 Third Hospital Avenue, #03-03 Bowyer Infective Endocarditis (IE) 49
Block C, Singapore 168753. Tel: (65) 6321-4862, fax: (65) 6221-6351. Email: Kawasaki Disease (KD) 60
publishing@singhealth.com.sg.

The publisher makes no representation or warranties with respect to CRITICAL CARE 69

the contents of this book, and specifically disclaims any implied warranties Children’s Intensive Care Unit (CICU) 69
or merchantability or fitness for any particular purpose, and shall in no event Recognition of the Critically Ill Child 77
be liable for any loss of profit or any other commercial damage, including but Paediatric Resuscitation 82
not limited to special, incidental, consequential, or other damages. Endotracheal Intubation 86
Code Teams 88
Emergency Management of Respiratory Failure 91
Emergency Management of Shock 94
Septic Workup in CICU 99
Central Venous Access 101
The Children’s Hospital Emergency Transport Service (CHETS) 104

ENDOCRINOLOGY AND METABOLISM 110

Adrenal Insufficiency 110
Hypoglycaemic Disorders 112
Diabetes Mellitus (DM) 115
Frequent Urination, Polyuria and Diabetes Insipidus (DI) 122
National Library Board Singapore Cataloguing in Publication Data Inborn Errors of Metabolism (IEM) 126
The baby bear book : a practical guide on paediatrics / Obesity 128
edtiors, Janil Puthucheary ... [et al.]. – 2nd ed. – Thyroid Crisis in Childhood 131
Singapore : Red Cells Series, c2010. Childhood Thyrotoxicosis and Graves’ Disease 134
p. cm. Recognising Normal Puberty and Disorders of Puberty 136
Includes bibliographical references.
ISBN-13 : 978-981-08-5105-7 (pbk.)
GASTROENTEROLOGY 140
1. Pediatrics¬ – Handbooks, manuals, etc. I. Puthucheary, Janil. Chronic Diarrhoea 140
Failure To Thrive (FTT) 145
RJ48 Management of Acute Gastroenteritis 151
618.92 – dc22 OCN536459172
4 5

Milk Formula Guide 165 Breastfeeding 353

Neonatal Jaundice (NNJ) 168 Classification of Newborn Babies 357
Recurrent Abdominal Pain 179 Common Skin Conditions 361
Guidelines for Admission to Neonatal Care 363
GENERAL AND AMBULATORY PAEDIATRICS 185 Referral of Newborn Babies for Neonatal Care 365
Child Abuse and Neglect 185 Guideline for Discharge of At-Risk Babies 366
Child Development 190 Hypoglycaemia 367
Adolescent Medicine (ADME) — Referral Guidelines Infant Formulae 369
and Workflow 201 Infection Control 371
Eating Disorders 202 Necrotising Enterocolitis (NEC) 372
Adolescent Health — HEADSS assessment 205 Neonatal Infection 373
Drug Overdose and Poisoning 207 Neonatal Jaundice 375
Neonatal Seizures 380
Patent Ductus Arteriosus (PDA) 381
GENETICS 235 Polycythaemia 383
Some Common Dysmorphic Conditions 235 Respiratory Distress 384
The Dysmorphic Child 244
Thalassaemia — Screening and Management 249
NEPHROLOGY 390
Approach to Haematuria 390
HAEMATOLOGY AND ONCOLOGY 258 Acute Nephritic Syndrome 393
Care of the Central Line in Oncology Patients 258 Nephrotic Syndrome (NS) 395
Bone Marrow Transplant (BMT) 262 Hypertension 402
Work-up — Checklist 262 Urinary Tract Infection (UTI) and Vesicoureteric Reflux (VUR) 406
Bleeding Disorders 264 Methods of Urine Collection 410
Febrile Neutropaenia 284 Approach to Investigations Following UTI 410
Acute Tumour Lysis Syndrome (ATLS) 288 Guidelines for Micturating Cystourethrography (MCUG) 413
Anaemia 290 Enuresis and Voiding Problems 417
Lymphadenopathy 294 Acute Renal Failure (ARF) 421
Checklist for Patients Newly Diagnosed with Leukaemia 298 Protocol for Renal Biopsy 428
Prophylaxis in Immunocompromised Oncology Patients 300
NEUROLOGY 429
INFECTIOUS DISEASES 304 Cerebral Palsy (Perinatal Encephalopathy) 429
Antibiotics for Specific Infections 304 Epilepsy 431
Chickenpox (Varicella) 312 Management of Status Epilepticus 440
Dengue Fever 316 Headache Disorders 442
Hand-Foot-and-Mouth Disease (HFMD), and Herpangina 319 Microcephaly and Megalocephaly 446
Bacterial Meningitis 320
Meningococcal Infections 324 PAEDIATRIC SURGERY 452
Needlestick Injuries 325 Common Neurosurgical Problems 452
Opthalmia Neonatorum 330 The Acute Abdomen 457
Tuberculosis (TB) 331
Incubation and Isolation Periods for Infectious Diseases 338
KK Hospital Vaccine Information Chart 2009 340 RESPIRATORY 464
Asthma 464
NEONATOLOGY 346 Empyema 478
Apgar Score 346 Flexible Bronchoscopy 480
At-Risk Newborns at Delivery 347 Sleep-related Upper Airway 482
Birth Trauma 347 Obstruction in Children 482
Resuscitation At Delivery 349 Upper Respiratory Tract Infections 489
6 7

RHEUMATOLOGY, IMMUNOLOGY & ALLERGY 494

Approach to Limb Aches and Joint Pains 494
Initial Investigations for Suspected Rheumatological Disorders
Juvenile Idiopathic Arthritis (JIA)
497
504
FOREWORD
Systemic Lupus Erythematosus (SLE) 512
Juvenile Dermatomyositis (JDM) 519
Drugs in Rheumatology 522 It has been many years now that the KK Women’s and Children’s Hospital
Disease Modifying Anti-Rheumatic Drugs (DMARDS) 526 brought the Paediatric Departments of Alexandra Hospital, Singapore
Primary Immunodeficiency (PID) 530 General Hospital (SGH) and Tan Tock Seng Hospital together as one
Recognition and treatment of Allergic Emergency
— Anaphylaxis 532 consolidated national Children’s Hospital. Together with the Department
Management of the Patient with a History of of Paediatric Surgery from SGH and the sizable Neonatology Department
Drug Hypersensitivity 533 from Kandang Kerbau Hospital, the hospital now provides the full range
Normal Ranges for Immunology 535 of specialty services for children. Over the years, these specialties have
Food Allergy 537 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.
APPENDIX I: GROWTH CHARTS 547
Children are our future and they deserve the best care when they fall
APPENDIX II: DRUGS 561 ill. This practical guide to Paediatrics will certainly help facilitate this.
Critical information that needs to be readily available when treating
APPENDIX III: USEFUL FORMULAE 598 a child is now encapsulated in this handy book. It is written in a clear
concise way that makes for easy reference and understanding. The step-
APPENDIX IV: RESUSCITATION ALGORITHM 600 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
KK Women’s and Children’s Hospital
8 9

PREFACE EDITORS AND CONTRIBUTORS

This Paediatric handbook is designed to be a quick guide for doctors, EDITORS
nurses and other healthcare professionals who care for children.
Dr Janil PUTHUCHEARY2 Prof TAN Cheng Lim1
This book is intended to be the definitive reference for the day-
Dr TAN Teng Hong2 Prof PHUA Kong Boo1
to-day management of paediatric patients, both in the hospital
and the outpatient clinic. The chapter topics have been chosen for
their frequent clinical presentation, updated knowledge and their CONTRIBUTORS
relevance to clinicians seeking a rapid update on important issues.
Mohammed Nazri Bin ABDUL A/Prof Annette JACOBSEN4
The contributors have been selected for their involvement, experience
GHANI8
and reputation as leaders in their field. Dr KHOO Poh Choo3
Dr PRATIBHA AGARWAL3
Dr Mona KIDON1
This book will be of value not only to practising paediatricians, and Dr Zubair AMIN9
Dr Mark KOH1
junior staff, but also to nurses, pharmacists and family members of Dr Annitha d/o ANNATHURAI11
KOO Siu Ling8
sick children. Dr Melissa BATILANDO3
Dr Angeline LAI1
Dr Emma BEST19
We would like to especially thank Dr Janil Puthucheary and Dr Warren LEE1
Dr Derrick CHAN1
Dr Tan Teng Hong for their hard work as editors, and their dedication Dr LIEW Woei Kang1
in ensuring the final completion of this handbook; as well as Dr Irene CHAN12
Dr LIM Kim Whee1
Prof Tan Cheng Lim and Prof Phua Kong Boo for their invaluable Dr CHAN Mei Yoke2
Dr LIM Kwang Hsien13
guidance throughout the process. Dr CHAN Yoke Hwee2
Dr Lilian LIM17
Dr CHAO Sing Ming1
Dr LOH Tsee Foong2
A/Prof CHAY Oh Moh1
Dr June LOU1
Dr CHIANG Wen Chin1 Dr Anita MENON1
Associate Professor Chong Chia Yin
Head, Department of Paediatric Medicine Dr CHONG Chia Yin1 Dr MOK Yee Hui1
KK Women’s and Children’s Hospital Dr CHOONG Chew Thye1 Dr Zainal MUTTAKIN14
Dr CHUA Mei Chien3 Prof Ivy NG1
CHUA Yew Lan8 Dr NG Kee Chong9
CHUNG Chin Wee8 Dr Winston NG1
Dr Natalie EPTON1 Angeline NG Yan Ying8
Dr Anne GOH1 Dr OH Jean Yin1
Dr Joseph Manuel GOMEZ3 Dr Vera OH1
HING Wee Chuan8 Dr Gene ONG9
Prof HO Lai Yun6 Dr OOI Boo Chye15
Dr HO Ling1 Cynthia PANG7
Dr Selina HO6 Dr Raquel PASIMIO1
10 11

Angeline PHOON Pei Lin8 Dr Allyson TAN17

Prof PHUA Kong Boo1 Prof TAN Cheng Lim1
Dr POON Woei Bing1 Dr TAN Ee Shien1 CARDIOLOGY
Dr Janil PUTHUCHEARY2 Dr Nancy TAN1
Dr QUEK Bin Huey3 Dr Natalie TAN1
Dr Vasanthi RAJALINGAM13 Dr TAN Teng Hong2 CARDIAC ARRHYTHMIAS
1
Dr Kumudhini RAJASEGARAN Dr Jenny TANG1
GENERAL PRINC
CIPLE
ES
Atika Mariam SALIM8 Dr Ellen TAY18 ™ Symptoms may vary depending on the age of the patient. A young
Dr Yvonne SEE16 Dr TEO Siak Hong1 child may complain of stomach or chest pain. Older children will be
Dr SEOW Wan Tew5 Dr THOON Koh Cheng1 able to give a history of palpitations
Dr Bhavani SRIRAM3 Dr Veronica TOH10 ™ Urgency of the work-up depends on symptom severity. Children
A/Prof TAN Ah Moy2 Dr Janice WONG1 with a history of congenital heart disease or syncope need prompt
investigation
Dr Fabian YAP1
™ 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
1
rule of thumb is to cardiovert for a tachyarrhythmia and resuscitate if
Department of Paediatrics
2
Department of Paediatric Subspecialties
the patient has a bradyarrhythmia
3
Department of Neonatology ™ Although certain groups of children may be at increased risk
4
Division of Surgery of primary arrhythmias, in the general paediatric population,
5
Neurosurgical Service rhythm disturbances are usually the result rather than the cause
6
Child Development Unit of emergencies. Children at risk of primary cardiac arrhythmias
7
Division of Nursing
8
Children’s Pharmacy
are those with myocarditis, cardiomyopathy, post-cardiac surgery,
9
Children’s Emergency congenital heart disease and drug ingestion
(1–9 are all in KK Women’s and Children’s Hospital, Singapore) ™ Urgently treat unstable rhythms:
10
Department of Neonatology, National University Hospital, Singapore Š Unstable rhythms that require treatment are those which
11
Paediatric Medicine, Raffles Hospital, Singapore compromise cardiac output and those which have the potential
12
Department of Accident & Emergency, Singapore General Hospital
13
Ikids Paediatric Practice to deteriorate into a lethal rhythm
14
Kinder Clinic Pte Ltd Š If the arrhythmia is stable, there is time to call the cardiologist to
15
Paediatric Centre (Rivervale) assess the patient and advise on treatment
16
Ooi Baby & Child Clinic Š Treating a stable patient with an arrhythmia might not only be
17
Dr Yvonne’s Clinic for Children & Babies unnecessary, but may actually worsen the situation
18
The Kids Clinic
19
Healthway Woman & Child Clinic
20
Department of Molecular Medicine, University of Auckland, and Middlemore BENIGN ARRHYTHMIAS
Hospital, Auckland, New Zealand Sinus Arrhythmia (Fig. 1.1, overleaf)
™ 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 monitor
12 The Baby Bear Book Cardiology 13

Further evaluation is not needed unless the PACs are associated with
some other condition that warrants investigation or treatment

Junctional Rhythm (Fig. 1.4)

Fig. 1.1: Sinus arrhythmia.
No P waves seen prior to QRS complex
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
Fig. 1.2: Wandering atrial rhythm. Arrows indicate position of P waves. Note varying P wave is indicated
morphology and PP intervals. Not to be mistaken for Junctional Ectopic Tachycardia (JET)

Premature Ventricular Contractions (PVCs) (Fig. 1.5)

Not associated with symptoms Premature QRS complex without preceding conducted P wave
Related to changes in vagal tone during respiratory phases — Heart Wide QRS complex whose morphology differs from a sinus
rate increases toward end of inspiration and decreases toward end of conducted beat
expiration Look for symptoms of dizziness or syncope
More evident during periods of low heart rate Causes:
Further evaluation not needed unless associated with other arrhythmias Benign ventricular ectopics
Structural heart disease
Wandering Atrial Rhythm (Wandering Atrial Pacemaker) Myocarditis
(Fig. 1.2) Cardiomyopathy
Irregular rhythm with ongoing changes in P wave morphology Electrolyte imbalance
Associated with changes in PP interval during more than two 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 Fig. 1.3: Premature atrial contractions. Arrowheads indicate the premature P waves. The AV
escape rate or vagotonic conditions conduction of the premature beats is normal.

Premature Atrial Contractions (PACs) (Fig. 1.3)

Premature P waves differing in axis and morphology from normal
sinus P waves
PR interval may be prolonged Fig. 1.4: Junctional rhythm in an asymptomatic boy. Note the absence of P wave preceding each
Atrioventricular (AV) conduction may be normal, aberrant or blocked QRS complex. The rate here is about 60 per minute.
PACs are generally benign and frequently seen in normal,
asymptomatic children
PACs may be seen in patients who have:
Myocarditis
Tumours
Electrolyte abnormalities Fig. 1.5: Two ventricular premature complexes (arrowheads) are seen in this rhythm.
14 The Baby Bear Book Cardiology 15

Treatment strategies:
Pharmacological Treatment
Adrenaline 0.01mg/kg (0.1ml/kg of 1:10,000) intravenous (IV)
Fig. 1.6: Sinus bradycardia in a five-year-old, heart rate of 54bpm. Note that each QRS complex is
bolus
preceded by a P wave and tha there is no AV dissociation.
Adrenaline infusion 0.1–1.0μg/kg/min
Atropine 0.02mg/kg (min 0.1mg) IV, may be repeated once
Benign PVCs are found in patients without underlying cardiac Isoprenaline infusion 0.01–2.0μg/kg/min
pathology Pacing, temporary or permanent
Further evaluation may include the following:
Echocardiogram Sinus Arrest (Fig. 1.7)
Holter Sudden absence of atrial activity
Treadmill to determine if suppression occurs at higher heart rates, The longest PP interval is not a multiple of the shortest PP interval
which usually suggests that the PVCs are benign Escape rhythms of atrial, junctional or ventricular origin are
sometimes seen
BRADYCARDIA AND CONDUCTION DISORDERS Presents with syncope
Sinus Bradycardia (Fig. 1.6) Indications for therapy are the same as in sinus bradycardia
Rhythm whose origin is the SA node (P wave is upright in leads I and
aVF) First Degree Atrioventricular (AV) Block (Fig. 1.8)
Rate is less than normal for age: Prolongation of the PR interval beyond the normal for age
Neonates/infants < 100bpm when awake Normal values:
One year to three years < 100bpm Newborn to two months: 0.06–0.14 second
Three years to nine years < 60bpm Three months to two years: 0.07–0.15 second
Above nine years < 50bpm Three to 11 years: 0.09–0.17 second
Causes of sinus bradycardia: 12–15 years: 0.09– 0.20 second
Hypoxia
Intubation
Hypothyroidism
Raised Intracranial Pressure (ICP)
Meningitis
Drugs (digoxin, beta-blockers)
Anorexia
Cardiac surgery (especially Fontan, Mustard, Senning procedures)
Fig. 1.7: Sinus arrest of 4.4-second duration seen in this Holter recording strip. The vertical
Long QT Syndrome
arrowheads indicate the position of the sinus P waves.
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
Fig. 1.8: First-degree atrioventricular block with a PR interval of 0.4 second.
Congestive cardiac failure (CCF)
16 The Baby Bear Book Cardiology 17

Third-degree (Complete) AV Block (Fig. 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
Fig. 1.9: Mobitz type I second-degree atrioventricular block. The arrowheads indicate the P waves escape pacemaker. The higher the pacemaker, the faster the rate and
that were not conducted. Note progressive lengthening of the PR interval prior to the dropped the narrower the QRS complex
beats. 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 > two weeks after surgery, then
Fig. 1.10: Mobitz type II second-degree atrioventricular block. The arrowheads indicate the P waves permanent pacemaker placement is indicated
that were not conducted. Note constant PR interval. Myocarditis and rheumatic fever can also cause complete
AV block but in most cases, this is temporary and resolves in
Causes: less than a week — Temporary transvenous pacing may be
Normal variant indicated
Increased vagal tone e.g. athletes Congenital Complete AV Block:
Congenital heart defects (CHDs) with atrial enlargement e.g. Causes:
Ebstein’s anomaly, atrial septal defect Congenital heart disease (congenitally corrected
Rheumatic fever, myocarditis, mumps, diphtheria transposition of the great arteries)
Duchenne muscular dystrophy, myotonic dystrophy Infants born to mothers with collagen vascular disease
Drugs e.g. digoxin, beta-blockers, calcium channel blockers Long QT Syndrome
Electrolyte abnormalities, hypoglycaemia Diagnosis is now often made by foetal echocardiography
Generally a benign condition Patient can be asymptomatic or present later in life
No specific treatment Symptoms:
Congestive heart failure, hydrops fetalis
Mobitz Type I Second-degree AV Block (Wenckebach) Syncope
(Fig. 1.9) Exercise intolerance
Progressive lengthening of the PR interval with an eventual dropped Easy fatigability
QRS complex (failure to conduct a P wave after the longest PR Evaluation:
interval) ECG with rhythm strip or long lead II
Suspect if: group beating, difference in PR interval > 0.02 second Echocardiogram to assess for congenital heart disease, LV
between the beats preceding and following the dropped beat size and function
Holter monitoring
Mobitz Type II Second-degree AV Block (Fig. 1.10) Treadmill or exercise test to assess work capacity and heart
Relatively constant PP interval rate response
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 Fig. 1.11: Complete heart block. Note atrioventricular dissociation.
18 The Baby Bear Book Cardiology 19

Sudden death has been associated with the following:

Severe bradycardia
Ventricular ectopy, especially with exercise
Prolonged pauses
Increased QRS width Fig. 1.12: SVT in an infant. Note monotony of the rhythm. P waves not evident; they are actually in
Prolongation of QTc interval the terminal part of the QRS complexes (the pseudo-Q waves).
Permanent pacemaker placement is indicated for the
following conditions: Wolff-Parkinson-White (WPW) syndrome is diagnosed when the
Documented symptomatic bradycardia accessory pathway is evident on ECG during sinus rhythm as a shortened
Wide QRS escape rhythm PR interval and a slurred upstroke of the QRS complex (delta wave)
Ventricular dysfunction The majority of SVT in childhood is narrow complex tachycardia
Infants with a ventricular rate of 50bpm to 55bpm or an Signs and symptoms:
infant with congenital heart disease and a ventricular rate In infants, up to half can present in heart failure
of < 70bpm Symptoms can be non-specific e.g. irritability, incessant crying,
An average heart rate < 50bpm beyond the first year of life poor feeding
Older children can complain of chest pain, palpitations or
TACHYARRHYTHMIAS abdominal pain
Paroxysmal Supraventricular Tachycardia (SVT) (Fig. 1.12) SVT might be difficult to differentiate from sinus tachycardia. Table 1-1
Most common significant arrhythmia in childhood contains general guidelines that may help to distinguish between them
Tachycardia from an accessory pathway is the most common type Acute Management of SVT (summarised in Fig. 1.13, overleaf ):
of SVT (AV re-entrant SVT) seen in infancy and early childhood. AV Haemodynamically Stable Patient:
nodal re-entrant SVT becomes more common in later childhood and Consider vagal manoeuvres
adolescence. Adenosine:
First dose: 0.1mg/kg (max 6mg)
Table 1-1: General guidelines that distinguish sinus tachycardia from supraventricular tachycardia Rapid IV bolus via a large proximal vein, followed by
(SVT). 5–10mls of normal saline rapid bolus
Second and subsequent doses: 0.2mg/kg (max 12mg/dose)
Sinus Tachycardia Supraventricular Tachycardia Run the ECG on continuous manual mode (leads I, aVF, V2)
Rate < 180bpm > 220bpm as adenosine is being given. This will give diagnostic
Consistent with volume loss, fever, Non-specific — Irritability, poor information on the mechanism of the SVT
History If SVT persists, the options are:
infection feeding, tachypnoea, sweating, pallor
Consistent with dehydration, fever, Poor perfusion IV digoxin loading — 0.01mg/kg, 0.005mg/kg and 0.005mg/kg
Physical sepsis, blood loss Signs of heart failure at time zero, eight and 16 hours, respectively. Check potassium
Examination Clear lungs (creps in chest infection) Fine crepitations in lungs Propranolol — 0.1mg/kg/dose over ten minutes (repeat 3
No hepatomegaly Hepatomegaly x PRN) then 0.1–0.3mg/kg/dose IV three to eight hourly
Non-specific, no cardiomegaly, Flecainide — 2–3mg/kg/dose (max 100mg) PO STAT and
Cardiomegaly, pulmonary congestion 12 hourly
CXR normal, or e.g. pneumonia as source
or oedema
of fever/sepsis Amiodarone — 5mg/kg/dose IV/IO. Repeat dose of 5mg/
Monotonous rhythm — Fairly fixed kg/dose up to a total of 15mg/kg/day
rate despite changes in activity. Avoid digoxin in wide complex tachycardia and when WPW
ECG Rarely helpful, usually normal
Sudden termination/initiation. with atrial fibrillation (AF) is being considered
Terminate with heart block Do 12-lead ECG post-conversion to sinus rhythm
20 The Baby Bear Book Cardiology 21

SVT Signs and symptoms:

Symptoms are rate-related and are usually seen with rates greater
than 150bpm
Consider Vagal Clear ABC Consider IV Adenosine Infants
Manoeuvres (carotid (while preparing for CHF, poor feeding and irritability
massage, ice pack, cardioversion and IV
Older children
valsalva) assess readily available)
Haemodynamically Stable? Chest pain, palpitations, syncope or sudden death
Causes of VT:
Yes No Myocarditis, cardiomyopathy
Structural heart disease, post-operative congenital heart disease
Long QT syndrome, arrhythmogenic right ventricle dysplasia
IV Adenosine 0.1mg/kg (max 6mg) Sync DC Cardioversion 0.5J/kg Metabolic (hypocalcaemia, hypokalaemia, hypoglycaemia,
hypothermia)
Drug overdose e.g. tricyclic antidepressants
IV Adenosine 0.2mg/kg (max 12mg) Sync DC Cardioversion 1.0J/kg Investigations:
May be repeated Electrolytes
Toxicology screen
Sync DC Cardioversion 2.0J/kg ECG with rhythm strip
Consider Sync DC Cardioversion Echocardiogram
Digoxin Treatment:
Propranolol
Consider Anti-arrhythmics Ventricular tachycardia should be treated as an emergency unless
Flecainide
Amiodarone the patient is haemodynamically stable
In the acute situation, synchronised cardioversion at 0.5–1.0J/kg
Fig. 1.13: Management protocol for supraventricular tachycardia. should be the first response. Do not delay
IV lignocaine:
Haemodynamically Unstable Patient: Loading: 1mg/kg. May repeat in ten to 15 minutes for two doses
Immediate synchronised Direct Current (DC) Cardioversion: Infusion: 20–50μg/kg/min
0.5J/kg, 1J/kg, 2J/kg Maintenance level: 1.5–5.0mg/L
IV adenosine can be considered while preparing for IV amiodarone is an alternative:
cardioversion and if IV access is readily available Slow bolus 5mg/kg
May repeat 5mg/kg/dose up to a total of 15mg/kg/day
Ventricular Tachycardia (VT) Watch for hypotension. Have CaCl2 ready
Characterised by a wide QRS tachycardia and AV dissociation
Rates vary from 120–300bpm POST-OPERATIVE ARRHYTHMIA
In children, a wide complex tachycardia should be treated as VT until Common arrhythmias seen in the post-cardiac surgery patients
proven otherwise include AV block, SVT and JET
Other causes of wide complex tachycardia: In post-operative patients, a key investigation is an ECG with one of
Antidromic AV re-entrant SVT the leads attached to the atrial pacing wire:
Atrial flutter or fibrillation with aberrancy Connect the limb leads as usual
Orthodromic AV re-entrant SVT with aberrancy Connect the V2 lead to the atrial pacing wire
SVT with pre-existing bundle branch block Switch to ‘Manual’ mode on the ECG machine
Select the leads to record I, aVF and V2
22 The Baby Bear Book
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 this group of
acutely ill patients
The mechanism appears to be enhanced automaticity of tissues in
the His bundle
ECG Characteristics:
QRS morphology the same as in sinus rhythm
AV 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 lead 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 sympathomimetic agents if possible since
the arrhythmia is catecholamine-sensitive
Correct metabolic abnormalities, hypovolaemia and anaemia
Sedation and neuromuscular blockade
Hypothermia 33–35°C
IV digoxin:
Loading dose: 0.01mg/kg, 0.005mg/kg and 0.005mg/kg at
time zero, eight and 16 hours, respectively
Maintenance dose: 0.01mg/kg/day BD or OM
IV amiodarone:
Loading dose: 5mg/kg (repeat once if needed)
Maintenance infusion: 5–15μg/kg/min
Watch out for hypotension and bradycardia. Ensure that
calcium chloride is available by the bedside
V procainamide:
Loading dose: 10mg/kg over 20 minutes
Maintenance infusion: Start at 20μg/kg/min, increase by
10μg/kg/min every 15 minutes 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
Cardiology 23
BIBLIOGRAPHY
1. Vetter V. Arrhythmias. In Moller JH, Hoffman JIE, editors. Pediatric cardiovascular medicine.
Philadelphia: Churchill Livingstone; 2000, p. 844–69.
2. Friedman RA. Sinus and atrioventricular conduction disorders. In Deal BJ, Wolff GS,
Gelband H, editors. Current concepts in diagnosis and management of arrhythmias in
infants and children. Armonk, NY: Futura Publishing; 1998, p. 89–107.
3. Deal BJ. Supraventricular tachycardia: Mechanisms and natural history. In Deal BJ, Wolff
GS, Gelband H, editors. Current concepts in diagnosis and management of arrhythmias in
infants and children. Armonk, NY: Futura Publishing; 1998, p. 117–135.
4. Case CL. Diagnosis and treatment of pediatric arrhythmias. Pediatr Clin North Am. 1999;
46(2):347–354.
5. Khan IA. Long QT Syndrome: Diagnosis and management. Am Heart J. 2002; 143(1):7–14.
6. 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):133–137.
CARDIAC FAILURE
INTRODUCTION
Cardiac failure is a physiological state and clinical syndrome that results
from the inability of the myocardium to meet the metabolic demand of
the body. This section does not cover cardiogenic shock (see “Paediatric
Resuscitation” p. 82).
AETIOLOGY
Cardiac output is a function of stroke volume and heart rate; stroke
volume is determined by pre-load, after-load and the intrinsic
contractility of the myocardium. Derangement of any of these factors
can lead to the syndrome of cardiac failure.
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)
Anaemia
Iatrogenic
24 The Baby Bear Book Cardiology 25

Diastolic under-filling: First week: Hypoplastic Left Heart Syndrome (HLHS), critical
Pericardial effusion aortic stenosis, large AV fistula, TAPVD
Restrictive cardiomyopathy Second week: Coarctation of aorta, other duct dependent
Constrictive pericarditis lesions
Afterload (Pressure overload): Fourth to eighth week: Large left-to-right shunts
Congenital: Coarctation of aorta, aortic stenosis, LV or RV outflow Coronary abnormalities: Anomalous left coronary artery from
obstruction pulmonary artery
Systemic hypertension Cardiomyopathies
Cor pulmonale Myocarditis
Intrinsic contractility dysfunction: Older children:
Myocarditis CHDs: First presentation of CCF after one year of age uncommon
Cardiomyopathies: Myocarditis
Idiopathic Cardiomyopathies
Post-chemotherapy
Inborn Errors of Metabolism (IEM) e.g. Pompe’s disease DIAGNOSIS
Metabolic e.g. hypothyroidism Very often an infant presenting with cardiac failure may already have a
Coronary abnormalities: prior diagnosis of a CHD — most commonly a left-to-right shunt lesion
Anomalous left coronary artery from the pulmonary artery e.g. VSD, PDA. Clues to the significance of the shunt and that the child
Kawasaki Disease (KD) might be in heart failure include moderate or large defect, already on
Post-cardiac surgery diuretics, history of previous heart failure and poor weight gain, or
Myocardial contusion Failure To Thrive (FTT).
Neoplasia: Myxoma, leukaemic infiltration
Arrhythmias: Clinical Findings
Bradyarrhythmia: Complete heart block The cardinal signs of cardiac failure are cardiomegaly, tachycardia,
Tachyarrhythmia: SVT, Permanent Junctional Reciprocating tachypnoea and hepatomegaly. Poor feeding and chest retractions also
Tachycardia (PJRT), JET feature prominently in the younger infants. The signs and symptoms of
heart failure are related to three factors: impaired myocardial function,
Age-related Time of Presentation pulmonary congestion and systemic venous congestion.
Although any aetiology of heart failure can occur at any age, specific
causes first present more commonly at certain ages. The age of onset of Signs of Impaired Myocardial Function
cardiac failure can serve as a guide to the differential diagnosis of the Cardiomegaly:
underlying aetiology: A fairly consistent sign of impaired cardiac function, secondary to
Foetus: ventricular dilatation and/or hypertrophy
Arrhythmias: SVT, heart block May be absent in early stages, especially with myocarditis,
Severe anaemia arrhythmias, restrictive disorders and pulmonary venous obstruction
Large Arterio-Venous Malformation (AVM) Tachycardia:
Premature neonates: Persistently raised heart rate > 160bpm in infants and > 100bpm
PDA in older children
Fluid overload Consider SVT if heart rate > 220bpm in infants and > 180bpm in
Infants: older children
CHDs are the most common. Usual age at presentation of failure: S3 and gallop rhythm
26 The Baby Bear Book
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 (BP) on inspiration. Seen in cardiac tamponade. Can be
detected by palpation of the peripheral pulses, or by looking at
the waveform on the pulse oximeter or invasive BP monitor
Pulsus alternans: Alternating strong and weak beats with a
constant beat-to-beat interval
FTT
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 minutes), 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 CHDs
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
Cardiology 27
Increased neck vein distension and pulsation:
Difficult to observe in infants
Peripheral oedema: Rare finding in children. Very late sign
Investigations
Chest X-ray (CXR)
Cardiomegaly
Pulmonary plethora
Pulmonary oedema
ECG
Sinus tachycardia, non-specific T wave and ST segment changes
Specific ECG features for the underlying cardiac defect might be present
Echocardiogram
Delineate underlying structural defect(s)
Assess cardiac chamber dilatation and hypertrophy
Demonstrate decreased myocardial contractility and cardiac function
Determine response to therapy
Arterial Blood Gas (ABG)
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 ventilationperfusion mismatch); marked hypoxaemia in patient
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 problem e.g. pneumonia,
the PaCO2 may be increased
Useful to guide need for further respiratory support e.g. Continuous
Positive Airway Pressure (CPAP) or intubation and ventilation
Urea, Electrolytes and Creatinine (U/E/Cr)
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
Make sure that patient is not hypokalaemic prior to starting digoxin
as this will potentiate its toxic effects
28 The Baby Bear Book
MANAGEMENT
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
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, six to eight
hourly PRN. In older patients, IV morphine infusion 10–20μg/kg/
hr (dilute 1mg/kg morphine in 50ml D5W and run at 0.5–1.0ml/
hr) can be considered. Beware of respiratory depression
Correct any negative inotropic factors e.g. acidosis,
hypoglycaemia, hypocalcaemia and anaemia
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, six to 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 and a potassium-sparing diuretic
PO 1mg/kg/dose (max 25mg) six to 12 hourly
Monitor urine output and serum electrolytes
Inotropic agents:
Dobutamine, dopamine:
In a patient with severe cardiac failure, consider starting
dobutamine ± dopamine infusion(s)
Start at 10μg/kg/min. Dilute 30mg/kg in 50ml of NS or D5, to
give a solution where 1ml/hr = 10μg/kg/min)
Titrate up or down as indicated, range 5–20μg/kg/min
Cardiology 29
Digoxin:
Prior to starting digoxin, do baseline ECG and check U/E/Cr
(no hypokalaemia and normal renal function)
Loading dose: 0.02mg/kg (max 1mg) over 24 hours: half,
quarter and quarter of the total loading dose given at zero,
eight and 24 hours, respectively. This is given orally or as a
slow IV bolus over half-an-hour
Maintenance dose: 0.01mg/kg/day (max 0.25mg) as BD
(preferred initially) or OM dosing, starting 12 hours after the
last loading dose. Given orally or as a slow IV bolus
Maintenance digoxin dose should be reduced in renal
impairment
Check serum digoxin level for validation of dose, assessing
compliance, presence of altered elimination states (renal
or hepatic diseases, drug interactions), or if no clinical
improvement with standard dosages, or toxicity suspected.
Routine checking of serum digoxin level not recommended
Digoxin should be used with extreme caution in patients with
myocarditis as it might precipitate arrhythmias
Drugs that increases digoxin level: quinidine, verapamil,
amiodarone, flecainide, indomethacin
Afterload reduction:
Contraindicated in patients with left-to-right shunts
Milrinone:
A phosphodiesterase 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 0.25–0.75μg/kg/min
Captopril:
Angiotensin-converting Enzyme (ACE) inhibitor
Contraindication: Hypotension, renal impairment,
hyperkalaemia, renal artery stenosis
Cautions: Hypotension on starting treatment; when
commencing therapy avoid aggressive use of diuretics,
especially potassium sparing agents
Start at 0.1mg/kg/dose (max 6.25mg) eight hourly. Increase
gradually if required to max of 1mg/kg/dose (max 25–50mg)
eight hourly. Tablets 25mg and 50mg
Beta-blockade with carvedilol:
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
30 The Baby Bear Book Cardiology 31

Start at 0.1mg/kg/dose (max 3.125mg) 12 hourly PO. If tolerated, CAUSES OF SYNCOPE

double the dose every one to two weeks to max of 0.4–0.6mg/kg/ Cardiac abnormalities:
dose (adult 12.5–25mg) 12 hourly Rhythm disturbances:
Contraindication: Decompensated heart failure, heart block, Tachyarrhythmias: WPW, long QT syndrome, Right Ventricular
bradycardia, asthma Outflow Tract (RVOT) tachycardia , idiopathic VT or Ventricular
Caution: Reduced heart function during initial stages of therapy, Fibrillation (VF), right ventricular dysplasia
hypotension, bradycardia Bradyarrhythmias: Heart blocks, sinus arrest
Options for intractable heart failure: Sick sinus syndrome
Options available in selected patients include Intra-aortic Balloon Coronary artery disease
Pump (IAPB), Extracorporeal Membrane Oxygenation (ECMO) and Outflow obstruction:
ventricular assist devices (Left Ventricular Assist Device (LVAD), Hypertrophic obstructive cardiomyopathy
Biventricular Assist Device (BiVAD)) Left atrial myxoma
Aortic stenosis
BIBLIOGRAPHY Severe pulmonary stenosis
1. Talner NS. Heart failure. In: Heart disease in infants, children and adolescents, 5th Edition.
Emmanouilides GC, Riemenschneider TA, Allen HD, Getgesell HP, editors. Baltimore:
Abnormal circulatory control — Abnormal vascular volume or tone:
Williams & Wilkins; 1995:1746–1773. Vasovagal syncope (neurocardiogenic syncope):
2. Lonn E, McKelvie R. Drug treatment in heart failure. BMJ. 2000;320:1188–1192. The most common cause of syncope in children
3. Bruns LA, Chrisant MK, Lamour JM, Shaddy RE, Pahl E, Blume ED, Hallowell S, Addonizio
LJ, Canter CE. Carvedilol as therapy in pediatric heart failure: An initial multicenter Mechanism: On standing, about 10% of blood volume
experience. J Pediatr. 2001;138:505–511. 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
SYNCOPE — DIAGNOSTIC APPROACH venous return to the heart results in vigorous cardiac
contraction. This stimulates the brain stem to decrease BP
Syncope is defined as a transient loss of consciousness with an inability and heart rate, which may cause dizziness and/or syncope.
to maintain postural tone that resolves spontaneously without surgical The decrease in the venous return stimulates vagal afferent
or medical intervention. It does not include seizures, shock, coma or fibres, which in turn leads to massive vagal discharge in the
other states of altered consciousness. It is a very common presentation brainstem thus causing the bradycardia or hypotension or
in the emergency department and the outpatient clinics; it can also be a both
major cause of concern for the family. Pallid infantile syncope
Orthostatic hypotension
Syncope can occur due to a variety of reasons, but it is vital to rule out Situational syncope
possible life-threatening aetiologies. It is also important to rule out other Pregnancy
causes of loss of consciousness such as seizures. Acute volume depletion
Chronic hypovolaemia
The workup of syncope includes a meticulous history, a detailed physical Metabolic: Hypoglycaemia, hypocalcaemia, hypomagnesaemia,
examination, an ECG, risk stratification and appropriately directed hypoxia, imbalances in the sodium, potassium or chloride levels
investigations. Psychological
Drugs
32 The Baby Bear Book
HISTORY-TAKING
Age of Patient
Gives clues to the most common aetiologies
Infants: 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, anaemia, 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
Situation under which it occurs
Posture or any change in posture when the episode took place
Any prodrome of warmth, diaphoresis, or lightheadedness
Any association with chest pain, or the prior presence of palpitations
Vasovagal syncope is often associated with prodromal symptoms
such as pallor, clammy skin, sweating, nausea, lightheadedness,
dizziness, weakness, blurred vision or visual grayout
There is also an entity called laryngeal syncope which is
characterised by attacks of coughing with unusual sensations such
as tickling in the throat followed by loss of consciousness
Background Medical History
Any heart defects or previous cardiac surgery. Post-operative cardiac
children can develop arrhythmias
Past history of syncope. History of near-drowning
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’s syndrome, mitral valve prolapse,
right ventricular dysplasia, etc.
Syncope which occurs while lying down, while exercising, in athletes,
or is associated with chest tightness needs to be thoroughly evaluated.
Cardiology 33
Other worrying factors are a background history of cardiac surgery,
heart failure or familial sudden death.
Exercise-induced syncope is not normal and should not be presumed to
be vagally mediated and thus warrants evaluation with exercise-testing
to exclude provokable ischaemia, heart block or ventricular tachycardia.
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.
PHYSICAL EXAMINATION
Vital signs: The pulse rate and BP, significant postural hypotension.
Syncope and tachycardia on standing up are 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 (FBC): Anaemia
U/E/Cr; serum calcium, magnesium and phosphate
Urine pregnancy test in female adolescents
ABGs indicated if hypoxia suspected
ECG: Mandatory e.g. WPW, Hypertrophic Cardiomyopathy (HCM),
long QT syndrome, right ventricular dysplasia
If a cardiac cause is suspected; Holter monitoring, echocardiography,
exercise stress testing, cardiac catheterisation and electrophysiological
studies might be indicated.
If a neurological cause is suspected, investigate further with EEG,
Computed Axial Tomography (CAT or CT) or Magnetic Resonance
Imaging (MRI) scans as indicated.
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 would be confirmed with a positive Tilt Table Test.
34 The Baby Bear Book
Management
At the emergency department:
Airway, breathing, circulation
IV access, oxygen administration, cardiac monitoring
Basic investigations as indicated above. Hypocount
A thorough history-taking and physical examination should be
performed after patient is stabilised. Indications for admission:
Exercise-induced syncope
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
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:
General advice:
Keep well-hydrated
Avoid sudden change in posture or prolonged standing
Increase salt intake
Drug therapy (seldom required):
Beta-blockade with propranolol is helpful in reducing the
syncopal episodes. It is however not clear whether a non-
cardioselective beta-blocker is preferable to a cardioselective one
such as metoprolol or atenolol
Fludrocortisone: Useful in patients with hypotensive rather than
the bradycardic type of neurocardiogenic syncope
Other drugs such as midodrine (alpha agonist), disopyramide,
theophylline, and serotonin reuptake inhibitors have been used
Cardiac pacing:
Employed in patients with malignant neurocardiogenic syncope
(recurrent syncope with significant injury or drug refractory
syncope)
Cardiology 35
The North American Vasovagal Study demonstrated an 85%
reduction in syncope among patients with drug refractory
syncope randomised to dual-chamber pacing compared to
conventional drug therapy
BIBLIOGRAPHY
1. Tadros GM, Oren JW, Costello JM. Syncope in young patients I: An approach to the patient
with syncope. Hospital Physician. 2002;38(4):47–54.
2. Tadros GM, Oren JW, Costello JM. Syncope in young patients II: Presentation and
management of specific causes of syncope. Hospital Physician. 2002;38(5):61–67.
3. Soteriade ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, Levy D. Incidence and
prognosis of syncope. New Eng J Med. 2002;347(12):878–885.
4. Heaven DJ, Sutton R. Syncope: A scientific review. Crit Care Med. 2000;28(10): N116–N120.
5. Morag R. Syncope. eMed J. 2001;12(8). Available from: Medscape.
http://www.emedicine.com/emerg/topic876.htm.
CHEST PAIN
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 pediatric population.
Patients less than 12 years old 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 more than three 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)
36 The Baby Bear Book Cardiology 37

Impact of pain on child’s lifestyle and activity level Crushing sternal chest pain with or without radiation to the left
History of trauma arm or neck
Systems assessment: Exercise-induced chest pain
Elicit symptoms of chronic disease e.g. fever, malaise, fatigue, Persistent tachycardia
weight loss, night sweats Persistent hypertension
Past medical and surgical history (in particular any cardiac surgery or Hypotension
disease) Gallop rhythm
Previous evaluation, treatment and diagnoses in patients with Syncope
recurrent chest pain Respiratory:
Medication Hemoptysis
Family history (in particular of syncope, sudden death or Dyspnoea
cardiovascular disease) Rales
Social history: Cyanosis
Smoking, alcohol or illicit drugs Gastrointestinal:
Recent family or peer problems Haematemesis
School performance including PE, NAPFA tests, ECAs, etc. Haematochezia
Melaena
PHYSICAL EXAMINATION Others:
A thorough and complete physical examination is fundamental to an Febrile
accurate diagnosis of chest pain. In particular: Life-threatening psychiatric illness e.g. psychosis or suicidal ideation
Vital signs (including BP)
General appearance i.e. cyanotic, distressed, anxious, sweaty, poor DIFFERENTIAL DIAGNOSES
perfusion Musculoskeletal (very common in pediatric patients; pain is sharp,
Evidence of trauma e.g. bruising nagging and localised but may radiate)
Rash or joint swelling (collagen vascular disease?) Costochondritis (mild to severe, localised, reproducible on
Abnormal breast enlargement, gynaecomastia in males palpation and coughing; may have a history of recent Upper
Localised chest swelling or tenderness Respiratory Track Infection (URTI))
Cardiac findings: Abnormal heart sounds, arrhythmias, murmurs, Muscle strain
muffled heart sounds, pericardial rub Trauma
Respiratory findings: Depth and rate of breathing, retractions, Child abuse (especially in younger children)
rhonchi, crepitations, decreased breath sounds, bronchial breathing Fibromyalgia (pain is continuous and lasts longer than three
or pleural rub months; tenderness may be elicited over multiple points)
Abdominal examination: Hepatomegaly, tenderness Precordial Catch or Texidor’s Twinge (sharp pain occurring at rest
Femoral pulses usually over the cardiac apex or left lower sternal edge; short
Extremities: Temperature, cyanosis, clubbing, oedema duration; frequency varies; worsens on deep inspiration)
Psychological state Tietze’s Syndrome (observed after minor trauma; localised,
moderate and associated with visible swelling; swelling may
SINISTER SIGNS AND SYMPTOMS remit and recur; associated with an elevated Erythrocyte
Cardiac: Sedimentation Rate (ESR)
Underlying congenital or acquired heart disease Slipping Rib Syndrome (occurs when the eighth, ninth or tenth
Arrhythmias rib overrides the rib above; onset sudden, may radiate to chest or
abdomen)
38 The Baby Bear Book Cardiology 39

Xiphoid-Cartilage Syndrome (occurs after vigorous running; pain Others:

or ‘stitch’ at insertion of xiphoid into the abdominal musculature; Breast disease (puberty, menstruation, pregnancy, mastitis may
pressure on xiphoid may reproduce the pain) cause pain in females)
Others: Tumours, connective tissue disorders, acute chest Mediastinal tumours
syndrome in sickle-cell anaemia Sickle-cell disease with vaso-occlusive crisis
Cardiac: Herpes zoster (intercostal neuralgia pain may occur days before
Congenital heart disease, in particular: appearance of vesicles)
Conditions with left ventricular outflow tract obstruction e.g. Cigarette-smoking (with or without chronic cough), cocaine use
aortic stenosis, HCM (palpitations, coronary vasospasm, Acute Myocardial Infarction
Mitral valve prolapse (chest pain probably results from (AMI), caffeine overdose, accidental ingestion or inhaled mercury
papillary muscle dysfunction and subendocardial ischaemia) vapour and trichloroethane aerosol)
Coronary artery anomalies
Acquired lesions (cardiomyopathy, endocarditis, myocarditis, MAJOR THREATS TO LIFE
AMI, rheumatic fever, accelerated atherosclerotic coronary artery Myocardial ischaemia or infarction
disease, dissecting aneurysm, pericarditis, KD) Pericarditis with tamponade
Arrhythmias: AF, atrial flutter, SVT, VT Aortic dissection or rupture
Respiratory: Pneumothorax, pneumomediastinum or pneumopericardium
Pneumothorax Pulmonary embolus
Pneumonia Perforated or haemorrhaging peptic ulcer
Pleural effusion
Pulmonary embolism (especially in adolescent females on oral INITIAL INVESTIGATIONS
contraceptives) ECG:
Foreign body inhalation Arrhythmias: SVTs, AF, atrial flutter, VTs
Chronic cough Acute ischaemic changes: ST segment depression or elevation,
Chronic pulmonary diseases e.g. cystic fibrosis, chronic asthma symmetrical T wave inversion or tall, pointed, upright T waves;
(with exercise-induced symptoms) rarely Q waves
Gastrointestinal: HCM: Left or biventricular hypertrophy
Oesophagitis Pericarditis: Decreased QRS voltages, generalised ST segment
Mallory-Weiss tear elevation
Gastroesophageal reflux CXR:
Hiatus hernia To exclude pulmonary causes of chest pain e.g. pneumothorax,
Referred pain from gastritis, peptic ulcer disease, cholecystitis, pneumonia, pleural effusion
pancreatitis If pulmonary congestion or cardiomegaly present, a thorough
Foreign body ingestion cardiac workup is required
Psychogenic: Others: Rib abnormalities, fractures, markedly dilated aorta (aortic
Hyperventilation syndrome dissection in patient with Marfan syndrome)
Somatoform disorder
Stress SPECIFIC INVESTIGATIONS, IF INDICATED
Depression Cardiac:
Panic attacks Echocardiogram, Holter monitor, exercise stress test, cardiac
Munchausen syndrome enzymes (CK, CKMB, Troponin)
40 The Baby Bear Book
Pulmonary:
CT chest, MRI chest, VQ scan, lung function test with and without
methacholine challenge, bronchoscopy
Gastrointestinal:
Endoscopy, pH probe, abdominal ultrasound, serum amylase,
liver function test (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 etiology
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. Leung AKC, Robson WLM, Cho H. Chest pain in children. Canadian Family Physician.
1996;42:1156–1164.
10. Selbst SM. Consultation with the specialist: Chest pain in children. Pediatr Rev.
1997;18(5):169-173.
11. 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.
Cardiology 41
APPROACH TO POSSIBLE CYANOTIC
CONGENITAL HEART DEFECT (CHD)
INTRODUCTION
Cyanosis is evident when there is more than 3–4mg/dL of
deoxyhaemoglobin in the blood. Central cyanosis (true cyanosis) should
be distinguished from peripheral cyanosis (acrocyanosis) — in the
latter, there is bluish discoloration of the hands and feet only. Central
cyanosis usually indicates significant arterial oxygen desaturation,
whereas peripheral cyanosis can be associated with fever, cold exposure,
hypovolaemia, heart failure, use of sympathomimetic/constrictive
agents, peripheral vascular diseases, hyperviscosity and any shock states.
Differential cyanosis and reverse differential cyanosis are forms of central
cyanosis that can be observed in newborns and (rarely) in older children:
Differential cyanosis:
The lower abdomen and lower limbs are diffusely cyanotic but
the face, right arm and often left arm appear less cyanotic or even
normal in colour
Indicates relative cyanosis in the post-ductal circulation
Seen in coarctation of the aorta with a PDA, interrupted aortic
arch, pulmonary hypertension with a PDA shunting right-to-
left, and in Persistent Pulmonary Hypertension of the Newborn
(PPHN)
Reverse differential cyanosis:
Opposite to that of differential cyanosis: Relative cyanosis of the
right arm, face, and sometimes the left arm when compared with
the abdomen and lower limbs
Indicates relative cyanosis in the pre-ductal circulation
Seen in TGA combined with PDA and pulmonary hypertension
Either condition may not be clinically obvious and may need
comparison between transcutaneous saturation or ABG PO2 from
sites representing pre-ductal circulation (right arm or hand) with that
representing post-ductal circulation (umbilical artery or feet).
42 The Baby Bear Book Cardiology 43

APPROACH TO A CHILD WITH POSSIBLE CYANOTIC Hyperoxia Test

HEART DISEASE Take pre-ductal SaO2/PaO2 while in room air (FiO2 = 0.21)
Administer 100% oxygen (FiO2 = 1) via close hood, mask or ETT for ten minutes
Interpretation of test as follows:
Cyanotic Child
Condition FiO2 = 0.21 FiO2 = 1.0
PaO2 (SaO2) PaO2 (SaO2)
Resuscitation and Stabilisation Normal 70mmHg (95%) > 200mmHg (100%)
Ensure ABC Pulmonary disease 50mmHg (85%) > 150mmHg (100%)
Septic workup Cardiac disease
History and physical examination Parallel circulation < 40mmHg (< 75%) < 50mmHg (<8 5%)
Restrictive pulmonary flow < 40mmHg (< 75%) < 50mmHg (< 85%)
Complete mixing without
restrictive pulmonary flow 50–60mmHg (85–93%) < 150mmHg (<100%)

Peripheral Central PPHN Pre-ductal Post-ductal

PFO no right-to-left shunt 70mmHg (95%) < 40mmHg (<45%) Variable
Causes: See “Some Causes of Cyanosis” p. 44 PFO with right-to-left shunt < 40mmHg (<45%) < 40mmHg (<45%) Variable
Manage accordingly
Hyperoxia Test In severe pulmonary disease, the readings at FiO2=1.0 could be much lower than
See blue box on next page stated; in cyanotic heart disease with adequate intercirculatory shunt like a large
PDA, the readings at FiO2=0.21 could be higher.

Newborn with PPHN CXR Pulmonary Disease

Possible Cardiac Aetiology

↑ Pulmonary Blood Flow ↑ Pulmonary Blood Flow Pulmonary Venous Congestion

Fallot’s tetralogy
Critical pulmonary stenosis
Pulmonary or tricuspid atresia
Ebstein’s anomaly
Any complex congenital heart disease
with significant pulmonary stenosis
Transposition of great arteries Total anomalous pulmonary venous
Truncus arteriosus return
Double outlet right ventricle with no Hypoplastic left heart syndrome
pulmonary stenosis
Univentricular heart complex with no
pulmonary stenosis

PGE1 0.01–0.1μg/kg/min

Correct acidosis, hypoglycaemia, electrolytes

Contact cardiologist, CICU/NICU
Fig. 1.14: Approach to a child with possible cyanotic heart disease.
44 The Baby Bear Book Cardiology 45

Some Causes of Cyanosis Obstructed/limited pulmonary flow:

Peripheral Cyanosis Tetralogy of Fallot
Fever Critical pulmonary stenosis
Hypothermia Pulmonary atresia
Hypovolaemia Tricuspid atresia
Shock states Ebstein’s anomaly
Cardiac failure/low cardiac output states Any complex congenital heart disease with significant
Polycythemia (haematocrit > 65%) pulmonary stenosis
Vasoconstrictive agents Methaemoglobinaemia:
Peripheral vascular disease Congenital:
Haemoglobin M
Central Cyanosis Methaemoglobin reductase deficiency
Respiratory pathology: Acquired:
Any causes of respiratory failure Nitrites (Amyl/butyl nitrate, nitrite contaminated well water/
Upper airway obstructions: Nasal obstruction, Choanal stenosis/ food additive, nitroglycerine)
atresia, Pierre-Robin sequence, retropharyngeal abscess, Nitroprusside
epiglotitis, laryngeal webs/cysts, tracheal obstructions (stenosis, Antimalarials
foreign body, vascular rings/slings, mediastinal tumours) Napthalene
Obstructive sleep apnoea Hydralazine
Chest wall defects: Severe pectus excavatum, flail chest EDTA
Infections: Pneumonia, bronchiolitis, ALTB
Severe asthma Chest X-Ray (CXR)
Aspiration A ‘classical’ CXR picture has been described for various cyanotic
Hypoplastic lung congenital heart diseases. Examples are:
Pleural effusions, pneumothorax TAPVD — ‘Snowman’ appearance of the heart and mediastinal
Pulmonary Arterio-Venous Malformation (PAVM) silhouette and ‘snow storm’ lung fields. This CXR appearance only
Pulmonary embolism occurs in supracardiac type of TAPVD and only if the ascending vein
PPHN draining into the innominate vein as well as the superior vena cava
Central/peripheral nervous system: have dilated enough to give rise to the ‘head’ of the snowman
Central hypoventilation syndrome Fallot’s tetralogy (FT) — ‘Boot-shaped’ cardiac silhouette and
Pickwickian syndrome oligaemic lung fiends
Over-sedation TGA — ‘Egg-on-string’ appearance with plethoric lung fields
Seizures Ebstein’s anomaly — Massive cardiomegaly and oligaemic
Neuromuscular disorders lung fields. The differential diagnosis in a neonate with massive
Cyanotic heart diseases: cardiomegaly includes Ebstein’s anomaly, pulmonary atresia with
Abnormal connections: intact ventricular septum, pericardial effusion, anomalous left
Transposition of the great arteries coronary artery from the pulmonary artery, cardiac/pericardial/
Total Abnormal Pulmonary Venous Return (TAPVR) mediastinal tumor and cardiomyopathies
Truncus arteriosus
Double outlet right ventricle The CXR is also used to assess pulmonary flow (normal, increased or
Univentricular heart complex decreased) and cardiac size as well as to exclude pulmonary pathology.
46 The Baby Bear Book
Electrocardiogram (ECG)
ECG changes are non-specific and not useful to aid in the diagnosis
in the emergency setting. However, the ECG is useful to exclude any
rhythm abnormality and as part of a pre-operative assessment.
Prostaglandin E1 (PGE1)
Post-natal closure of the PDA occurs in two phases:
Functional closure usually occurs within 12 hours after birth in a term
infant;
Anatomical closure is usually completed by two to three weeks of
life.
With closure of the arterial duct, the haemodynamic in patients with
‘duct-dependant’ CHDs is adversely affected, causing these patients
to become more and more symptomatic, e.g. increasing cyanosis in
patients with TGA or pulmonary atresia, cardiovascular collapse in
patients with coarctation of the aorta or interrupted aortic arch.
PGE1 infusion is used to open and maintain the patency of the arterial
duct. This can be tried in neonates of up to two to three weeks of age
(before anatomical closure of PDA). Opening the arterial duct has the
following effects:
In lesions with restrictive pulmonary flow or in TGA:
Mean increase in SaO2 of about 23–79%
The lower the pre-treatment SaO2, the larger the magnitude of
response
Left-sided obstructive lesions:
Increase systemic BP, decrease upper limb to lower limb BP
difference
Decrease acidosis
Poor response or deterioration after starting PGE1 in a baby with
suspected cyanotic heart defect is uncommon, possibilities include:
TAPVD, especially obstructed TAPVD
TGA with intact ventricular septum, and with small, restrictive Patent
Foramen Ovale (PFO)
Left atrial outflow obstruction – mitral stenosis, cor triatrium
When to start PEG1 in a newborn:
Known duct-dependant CHD
Unknown anatomical diagnosis:
Cardiology 47
Threshold lower in patients in extremis
Most useful clinical findings — Cyanosis
Cyanosed patient — Look for murmur
Acyanotic patient — Look for pulse abnormality
PGE1 administration:
Continuous IV infusion (T½ = five to ten minutes)
Rate: 0.0–0.1μg/kg/min
Titrate according to patient’s response
Side effects of PGE1 infusion:
Central nervous system (CNS): Fever, apnoea, seizures
Cardiovascular system (CVS): Flushing, bradycardia, tachycardia,
hypotension, cardiac arrest
Gastrointestinal system: Diarrhoea, regurgitation
Hematological: Bleeding, leukocytosis
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.
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 less than two years
of age.
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
48 The Baby Bear Book
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 less than three months of
age, 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 five to ten minutes; 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. IV Esmolol (0.5mg/kg over one minute; can be
given as an infusion at 50μg/kg/min) is an alternative
Alpha agonists: Phenylephrine (0.1mg/kg SC or IM, 0.01mg/kg
IV, or as an infusion 0.1–0.5μg/kg/min) or metaraminol (Aramine®)
(0.01mg/kg IV and repeated PRN, can be given as an infusion
0.1–1.0μg/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 stabilizing 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 six to 12
hourly, and can be slowly increased to maximum of 1mg/kg/dose six
hourly as needed
Cardiology 49
Sedation may be with chloral hydrate or diazepam. However, avoid
midazolam which reduces systemic vascular resistance further
Treat fever aggressively and ensure adequate hydration
Avoid epinephrine, dopamine, dobutamine, digitalis, and digoxin
which have positive inotropic effects and may therefore, worsen ‘tet
spells’
Advice to parents of a patient with FT:
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 five minutes,
bring to the nearest emergency department urgently
BIBLIOGRAPHY
1. Park MK. Paediatric cardiology for practitioners. 3rd edition. St. Louis: Mosby; 1996. 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.
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
edition. 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.
INFECTIVE ENDOCARDITIS (IE)
AT-RISK PATIENTS
Majority of patients with CHD
Post-operative hearts:
Cardiac surgery itself is an important risk factor for IE
Highest risk in children who had repair or palliation of cyanotic CHD
50 The Baby Bear Book
Incidence of IE in the first post-operative 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 two 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, six 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.
ORGANISMS CAUSING IE IN CHILDREN
Most common organisms are gram-positive cocci — viridans group
streptococci, staphylococci and enterococci
Less commonly — HACEK group (Haemophilus parainfluenzae,
H. aphrophilus, H. paraphrophilus, Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis, Eikenella species,
and Kingella kingae)
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 (GBS) and
streptococcus pneumoniae
CLINICAL FINDINGS
Due to four underlying phenomena:
Bacteraemia (or fungaemia)
Valvulitis
Embolic phenomenon:
Major arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages,
splinter hemorrhages and Janeway lesions
Immunologic responses:
Glomerulonephritis, Osler nodes, Roth’s spots
Cardiology 51
PRESENTATION
Indolent (generally):
Prolonged low-grade fever
Variety of somatic complaints, including fatigue, weakness,
arthralgias, myalgias, weight loss, rigors, and diaphoresis
Fulminant:
High, spiking fever
Rapidly changing symptoms
Acutely ill
Cardiac signs are variable:
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
DIAGNOSIS
Duke Criteria
High index of suspicion is important. IE should be suspected in a
child with CHD who presents with prolonged, unexplained fever
Diagnosis of IE remains clinical. The diagnosis is straightforward in
patients presenting with classical Oslerian manifestations. However,
these signs may be few or absent. To aid diagnosis, the diagnostic
strategy proposed by Durack et al (1994) from Duke University may
be used
The Duke Criteria classifies diagnosis of IE into three categories:
Definite IE:
Pathological criteria:
Micro-organisms demonstrated by culture or histology
in a vegetation, a vegetation that has embolised, or an
intracardiac abscess, or
Pathological lesions: Vegetation or intracardiac abscess
present, confirmed by histology showing active
endocarditis
Clinical criteria as defined below:
Two major criteria, or
One major criterion and three minor criteria, or
Five minor criteria
52 The Baby Bear Book
Possible IE:
Findings consistent with IE that fall short of ‘definite’ but not
‘rejected’
Rejected:
Firm alternative diagnosis for clinical manifestations, or
Resolution of clinical manifestations with antibiotic therapy
for ≤ four days, or
No pathological evidence of IE at surgery or autopsy, after
antibiotic therapy for ≤ four days
Major Clinical Criteria
Positive blood culture for IE:
Typical micro-organism consistent with IE from two separate
blood cultures as noted below:
Viridans streptococci, Streptococcus bovis, or HACEK group or
Community-acquired Staphylococcus aureus or enterococci,
in the absence of a primary focus, or
Micro-organisms consistent with IE from persistently positive
blood cultures defined as:
>two positive cultures of blood samples drawn >12 hours
apart, or
All of three or a majority of > four separate blood cultures
(with first and last sample drawn > one hour apart)
Evidence of endocardial involvement:
Positive echocardiogram for IE defined as:
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 or
New valvular regurgitation (worsening or changing of pre-
existing murmur not sufficient)
Minor Clinical Criteria
Pre-disposition: Pre-disposing heart condition or IV drug use
Fever: Temperature > 38.0°C
Vascular phenomena: Major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival
hemorrhages, and Janeway lesions
Immunologic phenomena: Glomerulonephritis, Osler nodes, Roth’s
spots, and rheumatoid factor
Cardiology 53
Microbiological evidence: Positive blood culture but does not meet
a major criterion as noted above or serological evidence of active
infection with organism consistent with IE
Echocardiographic findings: Consistent with IE but do not meet a
major criterion as noted above
INVESTIGATIONS
Blood Cultures
Important to obtain adequate volumes of blood from children e.g.
3mls/bottle in infants and young children, and 5–7mls/bottle in older
children
Three blood cultures are obtained by separate venepunctures on the
first day, and if there is no growth by the second day of incubation,
two more should be obtained
In patients who are not acutely ill and whose blood cultures are still
negative, antibiotics may be withheld for 48 hours or longer while
additional blood cultures are obtained
For patients with acute IE, three separate venepunctures for blood
cultures can be performed over a short period and empiric antibiotic
therapy started
Request forms for the blood cultures should indicate that IE is
suspected to ensure that the laboratory will incubate the cultures for
at least two weeks
If fastidious or unusual organisms are suspected, the microbiology
laboratory should be consulted
Miscellaneous Laboratory Tests
Anaemia: Can be due to haemolysis or anemia of chronic disease
Leukocytosis: Not a consistent feature of IE
Elevated acute-phase reactants e.g. ESR, C-Reactive Protein (CRP)
Renal/urine: Hematuria, Red Blood Cell (RBC) 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
54 The Baby Bear Book Cardiology 55

Table 1-2: Antibiotic regimens for IE caused by Viridans group streptococci, streptococcus bovis,
Inadequate in some circumstances:
enterococci and HACEK microorganisms (Adapted from Ferrieri et al, 2002; Wilson et al 1995).
Obese or very muscular adolescent
Post-cardiac surgery patients Dose*
Antimicrobial Dose Duration†
Presence of compromised respiratory function or pulmonary Organism (per kg per
Agent† Frequency (Weeks)
hyperinflation 24 hours)
Patients with poor echogenicity Patients able to tolerate Penicillin G or 200,000U IV q 4–6 H 4
Complex cardiac anatomy ß-Lactams Ampicillin or 300mg IV q 4–6 H 4
Penicillin-susceptible Ceftriaxone 100mg IV q 24 H 4
Limitations
streptococci Penicillin G or 200,000U IV q 4–6 H 2
Absence of vegetations on echocardiography does not rule out IE (MIC ≤ 0.1μg/mL) Ampicillin or 300mg IV q 4–6 H 2
Conversely, an echogenic mass can represent a sterile
Ceftriaxone 100mg IV q 24 H 2
thrombus, sterile prosthetic material, or normal anatomic plus Gentamicin 3mg IM or IV q8H 2
variation rather than an infected vegetation
Penicillin G or 300,000U IV q 4–6 H 4
Transesophageal Echocardiography (TEE): Streptococci, relatively
Ampicillin or 300mg IV q 4–6 H 4
Superiority of TEE over TTE in adults has been demonstrated. resistant to penicillin
Ceftriaxone 100mg IV q 24 H 4
However, data indicating similar results in children has not been (MIC 0.1–0.5μg/mL)
plus Gentamicin 3mg IM or IV q8H 2
published Enterococci‡, nutritionally
Useful in patients with poor transthoracic echogenicity and in variant viridans
Penicillin G or 300,000U IV q 4–6 H 4–6
post-operative patients streptococci or highly
Ampicillin 300mg IV q 4–6 H 4–6
Useful for detecting complications of left ventricular outflow tract penicillin-resistant
plus Gentamicin 3mg IM or IV q8H 4–6
endocarditis and endocarditis of prothetic valves streptococci
(MIC > 0.5μg/mL)
ANTIMICROBIAL TREATMENT Ceftriaxone 100mg IV or IM q 24 H 4
General Principles or
HACEK micro-organisms
Ampicillin 300mg IV q 4–6 H 4
Prolonged course of IV therapy for at least four weeks duration or
plus Gentamicin 3mg IM or IV# q 8 H# 4
three weeks afebrile
Patients unable to
Consider six weeks antibiotics if:
tolerate ß-Lactams
Prosthetic valve IE Native valve
Highly virulent organisms Streptococci Vancomycin 40mg IV q 6–12 H 4–6
Relative antibiotic resistance of organism Enterococci‡ or
Dual or more antibiotics for synergistic effect Vancomycin 40mg IV q 6–12 H 6
nutritionally variant
Outpatient antibiotic therapy can be considered in uncomplicated plus Gentamicin 3mg IM or IV# q 8 H# 6
viridans streptococci
cases on a case-by-case basis, after the initial hospital treatment
Prosthetic devices/valves
Vancomycin 40mg IV q 6–12 H 6
Streptococci
COMPLICATIONS OF IE plus Gentamicin 3mg IM or IV# q 8 H# 2
Congestive heart failure Enterococci‡ or
Embolic events e.g. cerebral, pulmonary, renal, coronary, Vancomycin 40mg IV q 6–12 H 6
nutritionally variant
plus Gentamicin 3mg IM or IV# q8H 6
gastrointestinal tract viridans streptococci
Periannular extension of abscess * Dosage for patients with normal renal and hepatic function. Maximum dosages per 24 hours: penicillin 18 Mega-units;
ampicillin 12g; ceftriaxone 4g; gentamicin 240mg.
Arrhythmias, heart block † The two-week regimens are not recommended for patients with symptoms of infection > three months, those with an
Prosthetic device dysfunction extracardiac focus of infection, myocardial abscess, mycotic aneurysm, or infection with nutritionally variant viridans streptococci.
‡ For enterococci resistant to penicillins, vancomycin or aminoglycosides, treatment should be guided by consultation with a
Valvular dehiscence specialist in infectious diseases. Cephalosporins should not be used to treat enterococcal IE regardless of in vitro susceptibility.
Graft or shunt occlusion # Adjust gentamicin dosage to achieve peak and trough concentrations in serum of approximately 3.0 and < 1.0μg/mL,
respectively.
56 The Baby Bear Book Cardiology 57

Table 1-3: Antibiotic regimens for IE caused by staphylococci (Adapted from Ferrieri et al, 2002).
ANTIBIOTIC PROPHYLAXIS
Dose* † Whether a patient with heart disease needs antibiotic prophylaxis, and
Antimicrobial Dose Duration
Organism (per kg per what the appropriate antibiotic(s) would be depends on three factors:
Agent† Frequency (Weeks)
24 hours) Risk category of the patient’s heart defect,
Native valve (no Type of procedure the patient is about to undergo, and
prosthetic materials) Allergy status of the patient
Methicillin-susceptible Cloxacillin 200mg IV q 4–6 H 6
± Gentamicin¶ 3mg IM or IV# q 8 H# 3–5 days
Risk Stratification by Type of Heart Defect
Cefazolin§ 100mg IV q 6–8 H 6
The American Heart Association (AHA) stratifies the type of heart
± Gentamicin¶ 3mg IM or IV# q 8 H# 3–5 days
ß-lactam allergic defects into high-, moderate- and negligible-risk categories. Antibiotic
or
Vancomycin 40mg IV q 6–12 H 6 prophylaxis is only recommended for the high- and moderate-risk
Methicillin-resistant Vancomycin 40mg IV q 6–12 H 6 categories:
Prosthetic device or other
prosthetic materials High-risk Category
Methicillin-susceptible Cloxacillin or 200mg IV q 4–6 H ≥6 Prosthetic cardiac valves, including bioprosthetic and homograft
Cefazolin§ 100mg IV q 6–8 H ≥6 valves
plus rifampicin† 20mg PO q8H ≥6 Previous history of bacterial endocarditis
plus gentamicin 3mg IM or IV# q 8 H# 2 Complex cyanotic congenital heart disease e.g. single ventricle
Vancomycin 40mg IV q 6–12 H ≥6 states, transposition of the great arteries, tetralogy of Fallot
Methicillin-resistant plus rifampicin† 20mg PO q8H ≥6 Surgically constructed systemic-pulmonary shunts or conduits
plus gentamicin 3mg IM or IV# q 8 H# 2
* Dose for patients with normal renal and hepatic function. Maximum dose per 24 hours: cloxacillin 12g; cefazolin 6g; Moderate-risk Category
gentamicin 240mg; rifampicin 900mg.
¶ Gentamicin therapy in these cases should be used only with gentamicin-susceptible strains. Most other congenital cardiac malformations (other than those in
# Adjust gentamicin dose to achieve peak and trough concentrations in serum of approximately 3.0μg/mL and < 1.0μg/mL. high- and low-risk categories)
§ Cefazolin or other first-generation cephalosporins in equivalent doses may be used in patients who do not have a history of
immediate type hypersensitivity (urticaria, angioedema, anaphylaxis) to penicillin or ampicillin. Acquired valvular dysfunction e.g. rheumatic heart disease
† Doses suggested
HCM
Mitral valve prolapse with valvular regurgitation and/or thickened
Persistent bacteremia or fungemia leaflets
Metastatic infection
Mycotic aneurysms Negligible-risk Category (No Greater Risk Than the General
Glomerulonephritis or renal failure Population)
Isolated secundum atrial septal defect
INDICATIONS FOR SURGERY Surgical repair of atrial septal defect, ventricular septal defect, or PDA
Progressive cardiac failure — without documented residual leak, beyond six months of surgery
Valvular obstruction Previous coronary artery bypass graft surgery
Perivalvular extension of infection Mitral valve prolapse without valvular regurgitation
Fungal endocarditis Physiological, functional, or innocent heart murmurs
Persistent bacteremia despite appropriate antibiotic therapy Previous KD without valvular dysfunction
Unstable prosthesis Previous rheumatic fever without valvular dysfunction
Ruptured sinus of Valsalva or ventricular septum Cardiac pacemakers (intravascular and epicardial) and implanted
Significant embolic events defibrillators and stents
Especially when the aortic or mitral valve is involved
58 The Baby Bear Book Cardiology 59

Type of Procedures Others:

Prophylaxis Recommended Cardiac catheterisation, including balloon angioplasty
(Unless otherwise stated, prophylaxis recommended for patients with Implanted cardiac pacemakers, implanted defibrillators, and
high- and moderate-risk cardiac conditions): coronary stents
Dental procedures: Incision or biopsy of surgically scrubbed skin
Majority of dental procedures Circumcision
Respiratory tract:
Tonsillectomy and/or adenoidectomy Appropriate Antibiotic(s) to Use
Surgical operations that involve respiratory mucosa Dental, oral, respiratory, or oesophageal procedures:
Bronchoscopy with a rigid bronchoscope Standard general prophylaxis:
Gastrointestinal tract*: PO amoxicillin 50mg/kg (max 2g) one hour before procedure
Sclerotherapy for esophageal varices Unable to take oral medication:
Oesophageal stricture dilation IV ampicillin 50mg/kg (max 2g) within 30 minutes before
Endoscopic retrograde cholangiography with biliary obstruction procedure
Biliary tract surgery Allergic to penicillins:
Surgery that involves intestinal mucosa PO clindamycin 20mg/kg (max 600mg) one hour before
Genitourinary tract: procedure, or
Prostatic surgery PO cephalexin 50mg/kg (max 2g) one hour before procedure,
Cystoscopy or
Urethral dilatation PO azithromycin or clarithromycin 20mg/kg (max 500mg) one
hour before procedure
Prophylaxis Not Recommended Allergic to penicillins and unable to take orally:
Shedding of primary teeth IV clindamycin 20mg/kg (max 600mg) within 30 minutes
Respiratory tract before procedure, or
Endotracheal intubation IV vancomycin 20mg/kg (max 1g) over two hours, complete
Bronchoscopy with a flexible bronchoscope, with or without infusion within 30 minutes before procedure
biopsy‡ Genitourinary or gastrointestinal procedures:
Tympanostomy tube insertion High-risk patients:
Gastrointestinal tract: IV ampicillin 50mg/kg (max 2g) + IV gentamicin 1.5mg/kg
TEE‡ (max 120mg) within 30 minutes of procedure;
Endoscopy with or without gastrointestinal biopsy ‡ Followed six hours later by IV ampicillin or PO amoxicillin
Genitourinary tract: 25mg/kg (max 1g)
Vaginal hysterectomy‡ High-risk patients allergic to penicillins:
Vaginal delivery‡ IV vancomycin 20mg/kg (max 1g) over two hours + IV
Cesarean section gentamicin 1.5mg/kg (max 120mg); complete injection/
In uninfected tissue: Urethral catheterisation, uterine dilatation infusion within 30 minutes before procedure
and curettage, therapeutic abortion, sterilisation procedures, Moderate-risk patients:
insertion or removal of intrauterine devices PO amoxicillin 50mg/kg (max 2g) one hour before procedure,
or
* Prophylaxis is recommended for high-risk patients; optional for medium-risk patients. IV ampicillin 50mg/kg (max 2g) within 30 minutes before
‡ Prophylaxis is optional for high-risk patients.
procedure
60 The Baby Bear Book
Moderate-risk patients allergic to penicillins:
IV vancomycin 20mg/kg (max 1g) over two hours; complete
infusion within 30 minutes before procedure
BIBLIOGRAPHY
1. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis:
utilization of specific echocardiographic findings. Am J Med. 1994;96(3):200-9.
2. Ferrieri P, Gewitz MH, Gerber MA, Newburger JW, Dajani AS, Shulman ST, et al. Unique
features of infective endocarditis in childhood. Paediatrics. 2002;109(5):931–943.
3. Wilson WR, Karchmer AW, Dajani AS, Taubert KA, Bayer A, Kaye D, et al. Antibiotic
treatment of adults with infective endocarditis due to streptococci, enterococci,
staphylococci, and HACEK microorganisms. JAMA. 1995;274(21):1706–1713.
4. Dajani AS, Taubert KA, Wilson W, Bolger AF, Bayer A, Ferrieri P, et al. Prevention of
bacterial endocarditis: Recommendations by the American Heart Association. JAMA.
1997;277(22):1794–1801.
KAWASAKI DISEASE
DISEA SE (KD)
INTRODUCTION
KD is an acute systemic inflammatory/vasculitic disease of unknown
origin, affecting predominantly children below five years of age. It was
first described by Dr Tomisaku Kawasaki in 1967, and is now considered
to be the main cause of acquired heart disease in developed countries.
In Singapore, the incidence is at least 32.5 per 100,000 children less than
five years old per year. This incidence is one of the highest outside Japan,
and very similar to that of Hong Kong and Taiwan. In KK Women’s and
Children’s Hospital (KKH), we see an average of about 70 to 75 new cases
a year.
DIAGNOSIS
A specific diagnostic or confirmatory test for KD does not exist. 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.
Diagnostic Criteria
Fever persisting for at least five days† and presence of at least four of
the following‡:
Cardiology 61
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 five 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 other imaging
modalities.
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)
ECG changes: Arrhythmias, prolonged PR interval, abnormal ST
segment changes, abnormal T wave changes, abnormal Q waves,
or low voltages
CXR: 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
62 The Baby Bear Book
Neurological:
Striking irritability, inconsolable crying
Facial palsy or other mononeuritis (rare)
Mononuclear pleocytosis in the Cerebrospinal Fluid (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
Haematological:
Raised ESR and CRP
Mild anaemia 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 in the face of 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
Leptospirosis
Yersinia pseudotuberculosis infection (rare)
Rickettsial infection (rare in Singapore)
Autoimmune or immune complex diseases: Systemic Lupus
Erythematosus (SLE), Juvenile Rheumatoid Arthritis (JRA),
polyarteritis nodosa, Reiter’s syndrome, Behçet’s disease,
inflammatory bowel disease, post-infectious
Sarcoidosis (rare)
Mercury poisoning (rare)
Clinical Course
The course of KD can be described in three clinical phases:
Acute phase: Lasting seven to 14 days, characterised by fever and
inflammatory changes
Subacute phase: Typically lasts from approximately Day 10 to Day 25
after onset of illness. Fever, rash and lymphadenopathy resolve, but
Cardiology 63
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 six to
ten weeks after onset
A small subgroup of patients with KD (< 10%) has persistent or
recrudescent disease after the initial treatment.
Up to 1–3% of patients may have relapses or recurrent of KD after
recovering from the first episode.
INVESTIGATIONS
FBC, ESR, CRP
U/E/Cr, LFTs
Blood culture
Urine microscopy, biochemistry, and culture
Cardiac enzymes and troponin (if myocardial involvement/
myocarditis suspected)
ECG
CXR
Echocardiogram: Performed at Day 14, and three months, after onset
of KD. Subsequent echocardiograms arranged by cardiologist if the
first two are abnormal. Earlier echocardiography can be arranged
for the patient with diagnostic issues or who is suspected of having
cardiovascular complications
MANAGEMENT
Intravenous Immunoglobulin (IVIG):
IVIG is the primary treatment for patients with KD
Giving IVIG in the acute phase reduces this risk of coronary
aneurysm by at least three- to five-fold.
IVIG should be administered once KD is diagnosed, and ideally
within the first ten 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
In general, IVIG is not prescribed for the patient with a history
consistent with KD but with a fever which has subsided for many
days, as IVIG is unlikely to prevent coronary disease after the
acute inflammatory response is over
64 The Baby Bear Book
Dose: 2g/kg as a single infusion
Infuse over eight to 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 minutes, then
1.0ml/kg/hr x 15 minutes, then
2.0ml/kg/hr x 15 minutes, then
4.0ml/kg/hr till completion
Monitoring during infusion:
Temperature, pulse and respiration (TPR), BP q five minutes x
3, then
TPR, BP q 10 minutes x 3, then
TPR, BP q 15 minutes x 3, then
TPR, BP q 30 minutes x 3, then
TPR, BP hourly till completion
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 sub-acute 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 or QDS 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 two weeks from the
onset on KD
Cardiology 65
Should a patient present late when acute inflammation has
subsided, low-dose aspirin can be started
Aspirin therapy can be stopped after six to eight 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
two categories, dipyridamole can be converted back to aspirin
after four to six weeks
Steroids:
Controversial, as 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 only reserved for patients with persistent or
recrudescent fever after the second course of IVIG
Pulsed methylprednisolone (30mg/kg/day as a single
infusion over two to three hours, for one to three days) or oral
prednisolone (2mg/kg/day for two weeks then wean down
slowly) can be considered
Supportive measures:
Non-pharmacological management of fever
IV drip if not feeding well
Explanation to parents
PATIENTS WITH INCOMPLETE PRINCIPAL FEATURES
The following are recommendations for approach to patients with
prolonged fever and do not meet the classical diagnostic criteria for KD:
If KD is the most probable clinical diagnosis, and after having
excluded other causes, treat as for KD
Patient has two to three principal diagnostic criteria in addition
to prolonged fever ≥ five days) with some laboratory supporting
results and no confirmed source of infection can be determined,
recommend an early echocardiogram:
If echocardiogram shows coronary dilatation/aneurysm, treat as
for KD
66 The Baby Bear Book Cardiology 67

If echocardiogram is normal, INVESTIGATE AND TREAT based on

clinical suspicion and order echocardiogram at Day 14 of illness if
provisional/discharge diagnosis is KD or possible/incomplete KD
A normal early echocardiogram DOES NOT exclude KD. Coronary
Table 1-4: Long-term management and follow-up of patients with Kawasaki Disease.
abnormalities can still develop over the course of the illness even
if the early echocardiogram shows normal coronary arteries Risk Drug Therapy Physical activity Follow-up and Investigations
Beware of common pitfalls in the diagnosis of KD: I Aspirin x six to eight No restriction beyond By general physician, cardiovascular
Children less than one year old and adolescents often present weeks six to eightweeks risk assessment, counselling at
with incomplete features five-year interval
Rash mistaken for allergy or viral exanthem II Aspirin x six to eight No restriction beyond By general physician, cardiovascular
Pyuria: Mistaken for Urinary Tract Infection (UTI) i.e. sterile pyuria weeks, or until ectasia six to eight weeks risk assessment, counselling at
KD mistaken for lymphadenitis — Enlarged and tender resolves three- to five-year interval
cervical nodes is an important criterion for KD, hence cervical III Aspirin till coronary ≤ Ten years old: No Follow-up by cardiologist
lymphadenitis is not a good diagnosis of the cause of fever if abnormalities resolve restriction beyond Annual echo + ECG
six to eight weeks Stress test with myocardial
there are other signs of KD
> Ten years old: activity perfusion scan recommended
The principal features of KD may NOT be all present at the same level guided by every two years, in patient > ten
time; ask for features of KD when taking history stress-testing years old, if necessary
To order echocardiogram, speak to cardiologist on-call directly Competitive, contact Angiography if stenosis suspected
sports and endurance
FOLLOW-UP OF PATIENTS WITH KAWASAKI DISEASE training discouraged
Long-term management and follow-up of patients with KD depends on IV Long-term aspirin ≤ Ten years old: no Follow-up by cardiologist
the degree of coronary artery involvement. Risk stratification by AHA: warfarin for giant restriction beyond Annual/six-monthly echo + six-
aneurysm (target six to eight weeks monthly ECG
IRN 2.0–2.5) > Ten years old: activity Annual stress test with myocardial
Risk Level Patient Profile ± Clopidogrel for level guided by perfusion scan recommended in
No coronary artery changes on echocardiography at multiple/complex annual stress-testing patient > ten years old
I aneurysms Competitive, contact Angiography if stenosis suspected,
any stage
sports, endurance or electively in certain cases
II Transient coronary ectasia which resolves on follow-up training and
strenuous exercise
Small to medium solitary coronary artery aneurysm on strongly discouraged
III
echocardiogram
V Long-term aspirin Competitive, contact Echo + ECG six-monthly. Annual
Large or giant coronary aneurysm, or multiple or ± warfarin sports, isometrics and Holter + stress test with
IV
complex aneurysms, without obstruction Consider ß-blocker weight training to be myocardial perfusion scan
avoided Angiography and repeat with new-
V Coronary artery obstruction confirmed by angiography Other activity onset or worsening ischaemia
recommendations
guided by stress-
In KKH, echocardiograms are done at the following times after onset: testing or perfusion
two weeks, three months, six months, 12 months, 18 months and two scan
years. Thereafter, echocardiograms at six- or 12-monthly interval as
indicated. No further echocardiography required once two consecutive
echocardiograms document normal coronary arteries.
68 The Baby Bear Book 69

BIBLIOGRAPHY
1. Tan TH, Wong KY, Heng JT. 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.
CRITICAL CARE
2001;103(2):335–336.
3. Dajani AS, Taubert KA, Gerber MA, Shulman ST, Ferrieri P, Freed M, et al. Diagnosis and
therapy of Kawasaki Disease in children. Circulation. 1993;87(5):1776–1780.
4. AS Dajani, KA Taubert, M Takahashi, FZ Bierman, MD Freed, P Ferrieri, et al. Guidelines for
long-term management of patients with Kawasaki Disease. Circulation. 1994;89:916–922.
CHILDREN’S INTENSIVE CARE UNIT (CICU)
5. Durongpisitkul K, Gururaj VJ, Park JM, Martin CF. The prevention of coronary artery
aneurysm in Kawasaki Disease: A neta-analysis on the efficacy of aspirin and The CICU is a specialised area with personnel, facilities and resources to
immunoglobulin treatment. Pediatrics .1995;96(6):1057–1061.
6. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. AHA Scientific care for critically ill patients who have major organ dysfunction or who
Statement: Diagnosis, treatment, and long-term management of Kawasaki Disease. require intensive monitoring. As such, it provides:
Circulation. 2004;110:2747-2771.
™ Constant nursing care with a nurse-to-patient ratio of 1:1 to 1:2
™ Constant medical supervision by a specialist trained in critical care
™ Advanced and specialised therapies
™ Continuous monitoring and surveillance of the patient’s condition

ADMISSION STANDARDS AND CRITERIA

All admissions must be notified to the attending CICU Registrar during
office hours or CICU Registrar-on-call after office hours. If the Registrar is
not available, the Consultant Intensivist should be informed.

The Consultant Intensivist on call must be informed at the earliest

possible time of any emergency admissions from Children’s Emergency
(CE), the operating theatres (OTs) or general wards.

In the event that admission to the CICU is denied, the CICU Registrar
must review the patient and document the assessment in the patient’s
notes. The CICU Registrar should review the patient’s condition at a later
time. The Consultant Intensivist should be informed of the refusal and
the information passed on to the Registrar-on-call.

For elective admissions from OTs, the attending CICU Registrar should be
notified 24 hours prior to surgery. If beds cannot be confirmed, attempts
should be made to re-confirm a CICU bed before surgery begins.

If beds are unavailable for admission, the Consultant Intensivist must

be contacted to review possible patient discharge to the High-
Dependency (HD)/Step-down Unit or decant to other Intensive Care
Units (ICUs) in KKH.

Patients requiring admission to the CICU are those who:

™ Require intensive care treatment with specialised equipment for
major organ failure e.g. mechanical ventilation, critical care dialysis
70 The Baby Bear Book
Need continuous nursing care and skills that do not exist in other
areas to initiate therapy or provide sophisticated monitoring
May require intensive care skills at very short notice e.g. airway
control and intubation
ADMISSION CRITERIA
Respiratory Conditions
Patients with severe or potentially life-threatening pulmonary or airway
diseases. Conditions include, but are not limited to:
Endotracheal intubation or potential need for emergency endotracheal
intubation and mechanical ventilation, regardless of aetiology
Rapidly progressive pulmonary, or airway disease of high severity
with risk of progression to respiratory failure and/or total obstruction
High supplemental oxygen
Newly placed tracheostomy
Acute barotrauma compromising the upper or lower airway
Requirement for inhaled or nebulised medications continuously
or more frequently than can be administered safely by the general
pediatric patient care unit (according to institution guidelines)
Cardiovascular Conditions
Patients with severe, life-threatening, or unstable cardiovascular
diseases. Conditions include, but are not limited to:
Shock
Post-cardiopulmonary resuscitation
Life-threatening dysrhythmias
Unstable congestive heart failure
Congenital heart disease with unstable cardiorespiratory status
After high-risk cardiovascular and intra-thoracic procedures
Need for monitoring of arterial, central venous, or pulmonary artery
pressures
Need for temporary cardiac pacing
Neurological Conditions
Patients with actual or potential life-threatening or unstable
neurological diseases. Conditions include, but are not limited to:
Seizures unresponsive to therapy or requiring continuous infusions
of anti-convulsive agents
Acutely and severely altered sensorium where neurological
deterioration or depression is likely or unpredictable, or coma with
the potential for airway compromise
Critical Care 71
After neurosurgical procedures requiring invasive monitoring or
close observation
Acute inflammation or infections of the spinal cord, meninges,
or brain with neurological depression, metabolic and hormonal
abnormalities, respiratory or haemodynamic compromise or the
possibility of increased ICP
Head trauma with increased ICP
Pre-operative neurosurgical conditions with neurological
deterioration
Progressive neuromuscular dysfunction with or without altered
sensorium requiring cardiovascular monitoring and/or respiratory
support
Spinal cord compression or impending compression
Placement of External Ventricular Drainage (EVD) device
Stroke, or a differential diagnosis of stroke
Haematological/Oncological Conditions
Patients with life-threatening or unstable haematological/oncological
diseases, or active life-threatening bleeding. Conditions include, but are
not limited to:
Exchange transfusions
Plasmapheresis or leukopheresis with unstable clinical condition
Severe coagulopathy
Severe anaemia resulting in haemodynamic and/or respiratory
compromise
Severe complications of sickle-cell crisis, such as neurological
changes, acute chest syndrome, or aplastic anaemia with
haemodynamic instability
Initiation of chemotherapy with anticipated tumour lysis syndrome
Tumours or masses compressing, or threatening to compress, vital
vessels, organs or airway
Endocrinal/Metabolic Conditions
Patients with life-threatening or unstable endocrinal or metabolic
diseases. Conditions include, but are not limited to:
Severe Diabetic Ketoacidosis (DKA) requiring therapy exceeding
institutional patient care unit guidelines
Other severe electrolyte abnormalities, such as:
Hyperkalaemia, requiring cardiac monitoring and acute
therapeutic intervention
Severe hypo- or hypernatraemia
72 The Baby Bear Book
Hypo- or hypercalcaemia
Hypo- or hyperglycaemia requiring intensive monitoring
Severe metabolic acidosis requiring bicarbonate infusion,
intensive monitoring, or complex intervention
Complex interventions to maintain fluid balance
IEM with acute deterioration requiring respiratory support, acute
dialysis, haemoperfusion, management of intracranial hypertension,
or inotropic support
Gastrointestinal Conditions
Patients with life-threatening or unstable gastrointestinal diseases.
Conditions include, but are not limited to:
Severe acute gastrointestinal bleeding leading to haemodynamic or
respiratory instability
After emergency endoscopy for removal of foreign bodies
Acute hepatic failure leading to coma, haemodynamic or respiratory
instability
Surgical Conditions
Post-operative patients requiring frequent monitoring and potentially
requiring intensive intervention. Conditions include, but are not limited to:
Cardiovascular surgery
Thoracic surgery
Neurosurgical procedures
Otolaryngologic surgery
Craniofacial surgery
Orthopaedic and spinal surgery
General surgery with haemodynamic or respiratory instability
Organ transplantation
Multiple trauma with or without cardiovascular instability
Major blood loss, either during surgery or during the post-operative
period
Renal Conditions
Patients with life-threatening or unstable renal diseases. Conditions
include, but are not limited to:
Renal failure
Requirement for acute hemodialysis, peritoneal dialysis, or other
continuous renal replacement therapies in the unstable patient
Acute rhabdomyolysis with renal insufficiency
Critical Care 73
Multi-system and Other Conditions
Patients with life-threatening or unstable multi-system diseases.
Conditions include, but are not limited to:
Toxic ingestions and drug overdose with potential acute
decompensation of major organ systems
Multiple organ dysfunction syndrome
Suspected or documented malignant hyperthermia
Electrical or other household or environment (e.g. lightning) injuries
Burns covering > 10% of body surface (institutions with burn units
only; institutions without such units will have transfer policy to cover
such patients)
Special Intensive Technological Needs
Conditions that necessitate the application of special technological
needs, monitoring, complex intervention, or treatment including
medications associated with the disease that exceed individual patient
care unit policy limitations.
DISCHARGE/TRANSFER CRITERIA
Patients in the CICU will be evaluated and considered for discharge if
there are reversals of the disease process or resolutions of the unstable
physiologic conditions that prompted admission to the CICU, and if
there is no longer a need for complex intervention exceeding general
ward patient care unit capabilities.
Transfer/discharge will be based on the following criteria:
Stable haemodynamic parameters
Stable respiratory status (patient extubated with stable ABGs) and
airway patency
Minimal oxygen requirements that do not exceed patient care unit
guidelines
IV inotropic support, vasolidators, and antiarrhythmic drugs are no
longer required or, when applicable, low doses of these medications
can be administered safely in otherwise stable patients in the
designated patient care unit
Cardiac dysrhythmias are controlled
ICP monitoring equipment has been removed
Neurologic stability with control of seizures
Removal of all haemodynamic monitoring catheters
Chronically mechanically ventilated patients whose critical illness
has been reversed or resolved and are otherwise stable may be
74 The Baby Bear Book
discharged to a designated patient care unit that routinely manages
chronically ventilated patients, when applicable, or to the home
Routine peritoneal or haemodialysis with resolution of critical illness
not exceeding general patient care unit guidelines
Patients with mature artificial airways (tracheostomies) who no
longer require excessive suctioning
The healthcare team and the patient’s family, after careful
assessment, determine that there is no benefit in keeping the child in
the CICU or that the course of treatment is medically futile
DOCUMENTATION
Admission
For each new admission, the CICU Registrar will take a full handover
from the accompanying physician. The Medical Officer (MO) will write
a full history and detailed physical examination in the admitting CICU
notes. A comprehensive assessment of the various issues at hand must
be summarised together with the plan of management. This should be
communicated to the CICU consultant. The attending intensivist and
primary physician (if any) must be notified. All unscheduled admissions
not known to the primary physician will require the latter to be informed
as appropriate to the management of the patient.
Progress
CICU round annotation is written in the standard SOAP format. For
the morning rounds, the MO on duty the night before will detail any
significant events that occurred the previous day, treatments and
outstanding issues. A summary of past parameters, vital signs and
current treatment measures as well as the latest relevant investigations
should be entered.
The CICU consultant will lead the morning round with the CICU team
comprising of CICU Nurse Manager or her Designate, Registrar and MOs.
Relevant points concerning the patient’s care and state, assessment
of his condition and daily care plans will be written in the patient’s
progress notes during the morning rounds. A problem-oriented
assessment of the issues at hand will be noted. Instructions to nursing
staff should be clearly written in the doctor’s orders sheet and made
aware to the attending nurse. Pre-existing and new medication orders
must be reviewed by CICU Registrar during the rounds.
During the evening and night rounds, updates of patient’s condition and
any changes to the care plan must be noted.
Critical Care 75
Communications with the patient’s parents and caregivers should be
noted in the continuation sheet. Document the parties involved in the
conversation as well as the contents of the communication. The note
should detail any follow-up actions that may be needed by both parents
and medical personnel.
All notations should include the date and time when the note was
written and by whom. Post-dated documentation should not be
inserted between notes that have been written. Mistakes should be
crossed out and not painted over or removed physically. A signature and
designation should follow at the end of every documentation.
Orders
Patients coming from the wards for admission to the CICU will have all
of their previous orders reviewed and a fresh set of CICU orders written
by the MO.
Admissions directly from the OTs will have their orders written by the
MO.
All orders must be written clearly in the patient’s orders sheet. They
should have a date and time, and must be signed. The nurse in charge
of the patient must be informed and, if necessary, the order is to be
explained.
Orders written by other Medical and Surgical Services should be
reviewed or notified to the CICU physicians before implementation.
Discharge
Whenever possible, if a patient within the CICU is identified as being
ready for discharge, the discharge summary should be written
before actual discharge. The final CICU discharge summary should
be updated and countersigned by the CICU Registrar before it is filed
into the patient’s casenotes. The final discharge summary must detail
any outstanding care plans (treatment and investigations), current
medications that the patient will require and the accepting primary
attending physician. Where possible, the primary physician should be
notified by the MO before actual patient discharge.
PATIENT PLACEMENT IN CICU
A patient admitted to the CICU is assigned to a specific bed space.
Ideally, the patient should remain in this bed space until discharge.
76 The Baby Bear Book
To avoid subsequent unnecessary and unsafe rearrangements of this
assigned bed space, the following guidelines should apply to all patient
admissions:
Severity of illness — Prior to admission, consideration should be
given to the severity of illness and the anticipated monitoring and
supportive care required. Most unstable or critically ill patients
(requiring one-to-one nursing) can be placed in an open (four-bed)
room to provide easy and quick access for personnel and emergency
equipment. Placement in an open room allows continuous close
observation and assistance from other nursing personnel working in
the same room. Where possible, admissions should be cohorted into
surgical post-operative cases and medical cases
Single room (isolation) admissions — The medical criteria for
the admission of a patient to a single room is in the instance of
a patient with contagious infections or who requires protective
isolation e.g. immunocompromised. When an isolation room is not
available, the Nurse Manager/Designate and the CICU Registrar will
determine how the proposed admission can best be accommodated.
Consideration should be given to the risks and advantages to that
patient, together with the risks involved in moving an unstable
patient from an Isolation Room. Alternatives should be considered
e.g. isolating the patient in an open room. Reverse isolation can only
be achieved through single room isolation
Occasionally, a patient may be admitted to a single room because of
certain therapeutic needs e.g. scavenging for inhaled gases/drugs or
on multiple treatments. Rarely, a single room will afford privacy in an
end-of-life situation
Non-infectious elective admissions e.g. post-operative cardiac cases,
head traumas, etc. — These patients ideally should not be nursed
beside patients who have primary infections or acquired colonisation
e.g. nasotracheal colonisation with pseudomonas or viral infections.
Nursing assignments should also reflect this principle
Due to high occupancy and overcrowding, these guidelines are often
difficult to implement. Under these circumstances, the following should
also be considered when rearranging bed allocations:
A stable patient may be moved to a particular room to provide
appropriate safe nursing support. Clinical stability will be defined by
the medical staff in discussion with the Nurse Manager/Designate
Unpredictable emergency admissions will not automatically
necessitate movement of stable patients unless nursing assignments
cannot meet the anticipated demands of that patient
Critical Care 77
The availability of additional critical care nurses should be explored
before patients are rearranged
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 cardio-
pulmonary instability.
ANATOMIC AND PHYSIOLOGICAL CONSIDERATIONS
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.
Cardiac output is a function of stroke volume and heart rate. An infant has a
limited ability to increase stroke volume in response to shock, and therefore
mounts a tachycardic response to compensate for a drop in cardiac output.
In addition, children have a higher oxygen consumption per kilogramme
body weight than adults. As a result, they tolerate hypoxia poorly, and may
manifest with tachycardia as a first sign of compensated shock.
78 The Baby Bear Book Critical Care 79

HISTORY VITAL PARAMETERS

Functionality of the child is a simple but effective measure of how ill the Hypotension is defined as systolic BP:
child is. Questions to ask include: < 60mmHg in a neonate
Level of activity/play < 70mmHg in infants (one to12 months)
Conscious level/irritability < 70mmHg + [2 x (Age in Years)] in children one to ten years
Feeding/fluid intake < 90mmHg in children > ten years age
Urine output
Mean arterial pressure can be calculated as {50 + [2 x (Age in Years)}
Red flags in the history include: mmHg.
High-pitched cry/inconsolable crying
Grunting Pulse pressure (systolic minus diastolic BP) is usually greater than
Cyanosis 20mmHg. A widened pulse pressure is present in distributive shock, a
Apnoeic episodes narrow pulse pressure may suggest hypovolemic or cardiogenic shock.
Pallor, cool and clammy peripheries
Shortness of breath or dyspnoea Unexplained tachycardia may be one of the first signs of compensated
Acute change in mentation shock.
Focal seizures
Bloody stool in a neonate PHYSICAL EXAMINATION
Clinical states which can rapidly progress and are life-threatening
There should be a low index of suspicion in the very young, or if there is include:
a significant medical history such as: Impending respiratory arrest
Maternal history of GBS (in a neonate) Cardiovascular instability/cardiogenic shock
Congenital cardiac defects Sepsis/septic shock
Primary immunodeficiency syndromes Severe dehydration
Chronic steroid usage Seizures/altered mental state
Haem-oncological disorders on active chemotherapy Trauma
History of adreno-cortical deficiency e.g. hypopituitarism, congenital
adrenal hyperplasia, hypothalamic or pituitary lesions Red flags in the physical examination which may indicate an unwell
child include:
General appearance:
Table 2-1: Table of normal heart rate, respiratory rate and systolic blood pressure by age.
Mottling of the skin
Heart Rate Respiratory Rate Systolic blood Pallor
Age
(bpm) (min) (pressure/mmHg) Cool peripheries
Neonate 120–180 40–60 60–80 Lethargy/irritability
Infant (one month to one year) 110–160 30–40 70–90 Bulging tense fontanelles
Toddler (one to two years) 100–150 25–35 80–95 Purpuric rash
Young child (two to seven years) 95–140 25–30 90–110 Bruising/petechial rash
Hyper-pyrexia (> 40°C)
Older child (seven to 12 years) 80–120 20–25 100–120
Respiratory system:
Cyanosis
Tachypnoea/bradypnoea by age
80 The Baby Bear Book Critical Care 81

Kussmaul’s respirations FBC, U/E/Cr and group and match

Grunting Imaging: CXR to exclude pulmonary pathology, cardiomegaly. CT
Nasal flaring/retractions head if there are concerns regarding intracranial pathology
Audible stridor with drooling Septic screen including blood and urine cultures if sepsis is
Cardiovascular: suspected. Consider CSF cultures if an intra-cranial infection is
Delayed capillary refill time (> two seconds) suspected
Weak/thready pulses LFT/coagulation profile if suspected liver dysfunction/bleeding
Tachycardia/bradycardia by age diathesis
Cardiac arrhythmias Serum lactate if available. This reflects tissue hypoperfusion and can
New onset murmur be used as a marker of response to therapy
Gallop rhythm Metabolic screen if there is unexplained severe metabolic acidosis/
Absent femoral pulses (neonate) hypoglycaemia
Neurological: Drug toxicology screen if suspected
Focal neurological signs
Rapidly decreasing conscious level or Glasgow Coma Score (GCS) ACUTE TREATMENT
< 13 Ensure adequate oxygenation: Administer 100% oxygen non-
Change in mentation rebreather facemask if hypoxia is present
Asymmetrical pupillary reflex Assess and maintain a patent airway: Consider intubation and
Trauma: assisted ventilation if there are concerns about hypoventilation or
Penetrating injury of chest or abdomen inability to maintain airway reflexes
Suspected spinal cord injury Evaluate for haemodynamic compromise: Secure IV access early,
Flail chest consider intra-osseous access if venous access is difficult. Administer
Skull fracture fluid resuscitation if there are signs of shock e.g. tachycardia,
Facial burns or burns involving > 10% Body Surface Area (BSA) prolonged capillary refill time, cool peripheries. Give IV crystalloids
in aliquots of 20ml/kg boluses and watch for response. If there is
If a red flag is present in the history and/or physical examination, suspicion of cardiogenic shock, give fluids cautiously and consider
consider the following: early inotropic support
Admit for observation Correct rapidly reversible, potentially life-threatening derangements.
Call for senior help if there is evidence of severe respiratory distress, This includes:
poor perfusion and/or hypotension, obtundation/change in Hypoglycaemia: IV dextrose 10% 4–5ml/kg or dextrose 25%
mentation, prolonged seizure or cardiac arrhythmias 1–2ml/kg
Activate the paediatric Code Team if there is imminent Hyponatraemia: IV 3% NaCl 2ml/kg over 30 minutes
cardiopulmonary arrest, severe respiratory compromise needing Hyperkalaemia: IV insulin 0.1units/kg + IV dextrose 50% 2ml/kg
intubation, or there is difficulty stabilizing the patient e.g. difficult and/or sodium polystyrene sulphonate PR/oral 0.5–1g/kg
venous access, no response to therapeutic interventions, potential Hypocalcaemia: IV 10% Calcium chloride 0.2ml/kg over ten
difficult airway minutes)
Early antibiotic therapy if sepsis is suspected
INVESTIGATIONS Transfer patient to an appropriate care facility after initial
Hypocount: Exclude hypoglycaemia or DKA as a cause for stabilisation
obtundation
Blood gas analysis with electrolytes: Evaluate for severe acidosis,
sodium/potassium/calcium derangements
82 The Baby Bear Book
MONITORING
Continuous pulse oximetry, heart rate and respiratory rate monitoring
Close BP monitoring: Consider invasive BP monitoring if there are
concerns about haemodynamic instability
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.
PAEDIATRIC RESUSCITATION
In children, cardiopulmonary arrests are usually secondary to hypoxia or
circulatory failure that arise from a variety of causes. Because the chances
of successful resuscitation are small when a child reaches this stage,
it is important for healthcare professionals to be able to recognise an
impending arrest, and to intervene before it occurs. Mortality of children
with pre-hospital cardiac arrests can be as high as 97%, and survivors are
usually neurologically devastated. There are anatomical and physiological
differences between adults and children, hence the application of
cardiopulmonary resuscitation (CPR) differs. Pre-hospital arrests in
children are often a result of a deteriorating respiratory condition, hence
the need to focus on early CPR and ventilation rather than defibrillation
MANAGEMENT
A rapid cardiopulmonary assessment can be done in 30 seconds by
assessing the Airway, Breathing and Circulation (ABCs). If cardiac
arrest has occurred, activate the Code Team
Clear the airway by brief suction of mouth and pharynx if secretions
are present
Bag and mask the patient with high flow oxygen; use the head
tilt-chin lift method to open up the airway, or use an oropharyngeal
airway in an unconscious child. Do not waste time trying to intubate
the patient initially
Critical Care 83
Commence External Cardiac Massage (if HR < 80/min in neonates
< 60/min in child). A second doctor should do this. Place the patient
on a firm board and the lower third of the sternum is compressed in
the midline about a third of the Anterior-Posterior (AP) diameter of
the chest. Use two fingers for an infant and the heel of your hand for
an older child. Compression should be about 100/min in all patients.
Ventilation should occur at ten breaths per minute. Do not interrupt
chest compressions for ventilation
Pass in a nasogastric tube if abdominal distension is marked
Endotracheal intubation should be done by an experienced doctor.
Uncuffed tubes are used in children and in the young infant, use
a straight-bladed laryngoscope. Use a 2.5mm tube for premature
babies, a 3mm tube for a neonate and a 3.5–4mm tube for an infant.
After infancy, use the following Endotracheal Tube (ETT) size:
[4 + (Age / 4)]mm
Set a large bore IV line. Intraosseous (IO) access into the anterior
tibial bone marrow (about 1–3cm below the tibial tuberosity) can be
used if venous access is difficult. The Endotracheal Route (ET) can be
used to give lipid-soluble emergency drugs (adrenaline, lignocaine,
atropine, naloxone) at higher doses (ten times for adrenaline) diluted
in 5mls normal saline followed by five manual ventilations. Central
venous cannulation or a saphenous cutdown may be performed if
expertise available
Drugs used:
IV or IO: 0.1ml/kg 1:10,000 adrenaline solution
ET: 0.1ml/kg 1:1,000 adrenaline
Repeat dose after every three to five mins of resuscitation
0.5–1mEq/kg of sodium bicarbonate IV/IO may be given for acidosis
during cardiac arrest. Priorities before bicarbonate infusion for
arrest include securing the airway, adequate ventilation and chest
compressions
IV calcium is not recommended in CPR unless there is documented
hypocalcemia, hyperkalaemia, hypermagnesemia or calcium channel
blocker overdose
For ventricular defibrillation confirmed by ECG, DC defibrillation is
given with 2J/kg for first attempt and 4J/kg for subsequent attempts
(see Appendix IV p. 604)
Details of events and treatment must be recorded. Do the necessary
investigations and monitor the progress of the child
Where there is no response after 20 minutes of adequate resuscitation,
the senior doctor should decide how long efforts should be continued.
84 The Baby Bear Book Critical Care 85

Assess, support ABCs

Initiate CPR: Secure airway, ventilation Pulse Present?

VT/VF Asytole, PEA
12-lead ECG if practical
Defibrillate 2J/kg Adrenaline Evaluate QRS duration
CPR five cycles IV/IO: 0.1m/kg 1:10,000
ET 0.1m/kg 1:10,000
And for every three to five
Adrenaline IV/IO: 0.1m/kg 1:10,000 minutes of CPR During evaluation
ET 0.1m/kg 1:10,000 Support ABCs
Evaluate the
Defibrillate 4J/kg CPR five cycles Confirm continuous monitor/pacer attached
tachycardia
Consider cardiology consultation
Prepare for cardioversion (consider sedation)
Repeat cycles of:
Drug and shock (within one minute of drug)
Followed by five cycles of CPR
Identify and treat possible causes
Consider alternative medication:
Amioradone 5mg/kg IV/IO Hypoxemia Tamponade
Lignocaine 1mg/kg IV/IO/ET Hypovolemia Tension pneumothorax
Magnesium 25–50mg/kg for torsades/hypomagnesemia Hyperthermia Toxins/poisons/drugs
Hyper-/hypokalemia/ Thromboembolism
metabolic disorders Pain
Possible sinus tachycardia Probable supraventricular tachycardia
History compatible History incompatible
P waves present/normal P waves absent/abnormal
HR often varies with activity HR not variable with activity Probable supraventricular
Variable RR with constant PR Abrupt rate changes tachycardia
Infants: rate usually < 220bpm Infants: rate usually > 220bpm Immediate cardioversion 0.5–
Children: rate usually < 180bpm Children: rate usually > 180bpm 1.0 J/kg (consider sedation,
do not delay cardioversion)

Consider vagal manoeuvres

Consider alternative medication:
Consider alternative medication: Amioradone 5mg/kg IV over 20–60 minutes
Adenosine 0.1mg/kg (6mg max). or
0.2mg/kg (12mg max). Lignocaine 1mg/kg IV bolus (wide-complex only)
Cardioversion 0.5–1J/kg, 2J/kg Consult paediatric
Consult pediatric cardiologist
Fig. 2.1: Tachycardia algorithm for children with poor perfusion (Adapted from Guidelines, 2005).
86 The Baby Bear Book Critical Care 87

ENDOTRACHEAL INTUBATION overcome by bag and mask technique, allowing correction of

hypoxaemia and preparation for intubation
Nasal intubation should only be attempted once oral intubation is
INDICATIONS established and the patient is stable. It should not be performed
To secure the airway if a basal skull fracture or severe facial injury is suspected, or when
Severe airway obstruction recent corrective surgery has been performed around the area
Unprotected airway e.g. coma, prolonged seizures The technique of intubation should be learned under controlled
To deliver high-oxygen concentration when adequate arterial circumstances e.g. in the OT. Elective intubation guided by an
oxygenation cannot be delivered by simple means e.g. O2 mask or individual experienced in the technique. For a description of the
hood technique, see Fuhrman 1998.
To deliver positive pressure ventilation e.g. in respiratory failure with
CO2 retention or exhaustion that does not respond to other therapy INDUCTION AGENTS
All agents should be administered via an IV cannula, although in an
TECHNIQUE emergency intra-muscular injections may be used. The choice of agents
Intubation should NOT be attempted by the inexperienced if more will depend on the clinical condition, speed of induction needed,
skilled personnel are available pre-existing medications and experience of the physician. As a rule, the
Apart from the intubating physician, an assisting physician and agents should have quick onset and short duration of action. Bag and
critical care nurse should be available mask should be given and seen to be effective after sedation, before
In the apnoeic patient, positive pressure ventilation by bag and paralysis is instituted. Avoid paralytic and sedative agents in a patient
mask with oxygen should be made ready and administered before with a difficult airway.
attempts at laryngoscopy
Ready suction and intubation equipment. Emergency trolley on Sedation
stand-by Midazolam 0.1–0.5mg/kg, or
In a haemodynamically unstable patient, prepare fluid for acute Diazepam 0.1–0.5mg/kg
resuscitation. Give a smaller dose of sedatives and titrate to effect Analgesia
An extra ETT (smaller) should be readied. An ETT stylet and Morphine 0.1–0.5mg/kg, or
oropharyngeal airway should be available Fentanyl 1–4μg/kg
Induction medication should be drawn up and labeled. The correct Relaxant
doses should be checked Succinylcholine 1–2mg/kg IV, 1–4mg/kg IM or
Establish and confirm that the IV access is secure Rocuronium 0.5–1.0mg/kg, or
Check function of all equipment before proceeding with Atracurium 0.5mg/kg
administration of medication Others
The exact intentions and sequence of interventions the intubating Ketamine 0.5–1mg/kg IV, 1–4mg/kg IM
physician requires should be clearly communicated to assisting Atropine 0.02mg/kg (minimum 0.1mg)
personnel
Pre-oxygenation and a rapid sequence induction with cricoid ENDOTRACHEAL TUBES
pressure should be used in any elective intubation in the emergency Size
department unless there is anatomic airway obstruction The correct size ETT is a compromise between the risks of pulmonary
Muscle relaxant and sedating drugs must NEVER be used in patients aspiration and laryngeal mucosal ischaemia
with anatomic airway obstruction. Intubation in these patients must The appropriate ETT is the largest one which allows a leak of air
NEVER be attempted by the inexpert unless a dire emergency exists. around the tube when 25–30cmH2O of positive pressure is applied
Apparently complete airway obstruction can often be partially A rough guide to ETT size is [4 + (Age / 4)]mm = Internal diameter
88 The Baby Bear Book Critical Care 89

Expect to use a smaller ETT in: ROLES

Patients with trisomy 21 The roles of the Code Team members, including at least one doctor and
Patients with a history of airway obstruction two nurses from the clinical area of the code, are:
The ICU Registrar will be the Code Team leader. He/she will stand
Position at the foot of the patient, and call out for assessment or treatment.
Correct position is with the ETT tip at the mid-tracheal level, confirmed The team leader must be clearly identified to the other members
by X-ray; check for equal chest movement and breath sounds. A rough of the team and should be the only person to give orders. This
guide for distance from skin to mid-trachea: does not mean that suggestions from other team members are not
Oral ETT = {[2 x (Tube Size)] + 4}cm considered, but a good team leader should use the input of all the
Nasal ETT = {[1.5 x (Weight in kg)] + 6}cm (only use for patients ≤ 4kg) other staff in the room and set priorities. He should bring poise and
Six to 12 months: 12–13cm discipline to the team effort. The staff in the area will give a brief
> One year: (Age + 13)cm history of the patient and events occurring to the team leader so that
resuscitation can be continued effectively
FURTHER CARE The Anaesthetic Registrar will be in charge of the airway. He/she
Securely fix ETT will perform bag and mask ventilation, or intubate if necessary. The
Restrain arms and legs or sedate as needed to prevent self-extubation decision to intubate will be made by the Code Team leader. The
Transfer to appropriate area where facilities for continuous nursing Respiratory Therapist, if available, will assist the Anaesthetic Registrar.
and medical care are available He will stand at the head of the patient. If the respiratory therapist is
CXR to confirm placement not available, the nurse in the area of event will assist with the airway
Ascribe further breathing difficulty to ETT blockage until proven The doctor from the area of collapse (Ward/A&E Registrar) will
otherwise perform External Cardiac Massage (ECM) and obtain vascular
In-line suction catheter should be considered when mechanical access. IV medication orders will be called out by the team leader.
ventilation is expected to be required for more than three days or Blood-taking may be necessary. Peripheral IV insertions should be
when frequent chest toilet is needed limited to three attempts or about two minutes. If peripheral venous
cannulation is difficult, or delayed, a femoral venous cathether or
BIBLIOGRAPHY intra-osseus (IO) needle should be inserted. If time permits, a venous
1. Fuhrman BP, Zimmerman JJ, editors. Pediatric Critical Care. 2nd ed. St Louis: Mosby; 1998.
p. 115–116.
cutdown can be done. If no venous assess is available, drugs like
adrenaline, naloxone, lignocaine and atropine can be given via the
ETT
The Code Team nurse from the ICU will dilute the drugs to be given
and record the events and drugs given in the code sheet
The nurse from the area (ward/A&E) will assist in the code; assisting
CODE TEAMS doctors in the airway or ECM or IV assess. The resuscitation trolley
will be pushed to the patient by the nurse in charge of the area
where the collapse has occurred
INTRODUCTION In cases of multiple trauma or a trauma code, the Paediatric
Cardiac arrest in children is usually not a sudden event, and the Surgeon will be the team leader. He will perform primary and
recognition of a sick child followed by appropriate intervention will secondary survey and call out for management. The ICU Registrar will
usually prevent an arrest. The two most common causes of deterioration then assist the Paediatric Surgeon in the code or help doctor from
in children are associated with respiratory or circulatory problems. The the area with vascular access
CICU organises Code Teams to conduct any paediatric code in the hospital.
Resuscitation requires a team effort that must be efficient and organised.
90 The Baby Bear Book
The staff in the area where the code has occurred will commence
resuscitation until the Code Team takes over.
All activated staff will stop what they are doing (non-emergency) and
attend to the Code Blue. Should any member be held up by another
emergency, they should send a replacement for the Code Team.
At the end of the resuscitation, the team leader will add a brief note of
the events of the resuscitation in the patient’s casenotes. If the patient
survives and is transferred to the ICU, the events can be recorded by ICU
and ward doctors there.
TO ACTIVATE THE CODE TEAM
Staff of the area where the collapse has occurred will dial 5555 and
inform the operator “Code Blue Children’s at location”. In the case
of a trauma code (usually from the Accident and Emergency (A&E)
Department) where the paediatric surgeon is required, the operator
will be informed of “Trauma Code at location”
Operator will immediately announce the Code on the Public
Announcement (PA) system
ICU and anaesthesia staff will run to the place where collapse has
occurred
Code Team arrives at the area and will run the code
If the Code Team does not appear within five minutes of activation, the
staff will contact the operator again. The operator will then activate the
code again, followed by a direct call to the CICU or OT for the respective
team members.
Team members should note that the stairs will be locked (one way) after
office hours. They are to take the elevators, if needed, to get to the area
of the code.
Resuscitation of a child can be carried out by the primary team if the
Code Team is not required. But once the Code Team is activated, the ICU
Registrar will run the code. If assistance in resuscitation is required, the
ICU Registrar may be called down without activation of the Code Team.
It is preferred that the Code Team be activated for all codes.
Critical Care 91
EMERGENCY MANAGEMENT
OF RESPIRATORY FAILURE
GENERAL CONSIDERATIONS
Respiratory failure is the inability of the respiratory system to meet the
body’s demand for oxygen delivery and carbon dioxide elimination.
It can be due to a multitude of conditions including pulmonary,
neurological, cardiac and multisystem disorders.
COMMON SIGNS OF RESPIRATORY DISTRESS
Decreased or absent breath sounds
Tachypnoea or bradypnoea/apnoea
Severe retractions and use of accessory muscles
Restlessness or stupor/hypotonia/weak gag
Grunting
In obstructive failure: Drooling/stridor/wheeze (depending on the
level of the obstruction) with speech difficulty
PaO2 < 60mmHg or cyanosis (desaturations < 90% on pulse oximeter
despite supplementary oxygen) while PaCO2 may be low or normal:
Usually seen in failure due to ventilation-perfusion mismatch e.g.
pneumonia, sepsis, asthma — called Type I failure
PaCO2 high or increasing: Seen in hypoventilation e.g. coma,
paresis, obstruction or terminal stages of Type I failure when fatigue
develops — called Type II failure
Signs of sympathetic stimulation e.g. tachycardia, sweating, cool
peripheries
IMMEDIATE MANAGEMENT
Provide humidified oxygen to all patients with respiratory distress
Severe respiratory distress e.g. recurrent apnoea (i.e. respiratory
arrest), either Type I or II respiratory failure, warrants prompt
endotracheal intubation for assisted ventilation (see “Endotracheal
Intubation” p. 86)
Non-invasive assisted ventilation may be considered in less
emergent circumstances e.g. if the patient is alert with respiratory
distress; manage expeditiously
If the patient is stuporous/weak, consider first improving the airway
with correct positioning and airway control maneuvers
Note: With upper airway obstruction, children may be made more
restless by the method of oxygen delivery or attempts at airway
control. It is important to achieve this without causing too much
92 The Baby Bear Book
distress and to allow the patient to breath spontaneously in a
position of comfort. Sedation should be avoided in most instances.
Minimal handling while monitoring vital signs closely is the key,
since deterioration can be precipitous and hypoxia is the most
common cause of cardiac arrest in children. Also note that in these
patients hypoxia is an indication for relieving obstruction as well as
for oxygen administration, hence administering high-flow oxygen to
this group may mask these indications.
Retinopathy of prematurity and chronic obstructive airways disease
should never be excuses to avoid oxygen in acute respiratory
distress; they are merely indications to monitor that therapy more
closely. In these patients, the limits of oxygen saturation may be
lowered.
Establish IV access if patient:
Is unable to feed because of distress
Is likely to be intubated
Requires IV medications/rehydration
Note: In children with upper airway obstruction, the anxiety
produced by insertion of the IV cannula may exacerbate the
respiratory distress.
The level of monitoring needs to be increased. Continuous ECG,
respiratory rate and oxygen saturation in the HD ward is required
in moderate respiratory distress. In situations where assisted
ventilation of any form is required or respiratory distress is expected
to deteriorate, monitoring in the CICU may be needed
INVESTIGATIONS
Blood gases (but be careful in upper airway obstruction: Clinical
assessment is usually just as helpful in determining therapy whereas
the distress associated with drawing the sample may precipitate
complete obstruction)
CXR: Consider pneumothorax/effusion as cause of distress
Obtaining a lateral neck X-ray should never delay the establishment
of an artificial airway in severe airway obstruction, and should only
be performed if the highest level of supervision in the radiology suite
is available
OTHER MANAGEMENT
Aerosols: Consider salbutamol when there is evidence of
bronchoconstriction on clinical assessment; nebulised epinephrine
for subglottic oedema
Critical Care 93
Pharyngeal suctioning: Avoid in upper airway obstruction
Fluids: Adequate hydration is necessary to ensure secretions do
not become inspissated; humidification of inspired gases reduces
respiratory fluid losses so that usual maintenance fluid volumes
may represent over-hydration and risk interstitial oedema in these
patients
Intubation:
Provides a means of guaranteeing a high inspired oxygen
concentration
Protects and secures the airway
Facilitates tracheobronchial toilet
Permits mechanical ventilation
The indication for intubation will depend on the current trend of
the illness and severity of distress. Remember, when intubation is
indicated, oxygen delivery with positive pressure should always be
attempted with bag and mask until expertise at intubation arrives.
Positive pressure is often required in Type II failure whereas CPAP
with supplemental oxygen may be adequate in some cases of Type
I failure.
Physiotherapy may be of value for conditions in which secretions
block major bronchi
An in-line suction catheter is recommended for the patient who is
anticipated to require prolonged mechanical ventilation (> five days)
or who needs frequent chest toilet with minimum disruption of
ventilation
Specific therapy for underlying aetiology of respiratory failure e.g.
antibiotics after culturing blood and secretions in pneumonia, anti-
failure therapy in heart disease, salbutamol for asthmatic attacks,
steroids for acute laryngotracheobronchitis
BIBLIOGRAPHY
1. Task Force on Guidelines, Society of Critical Care Medicine. Recommendations for services
and personnel for delivery of care in a critical care setting. Crit Care Med. 1988;16(8):809–
811
2. Task Force on Guidelines, Society of Critical Care Medicine. Recommendations for critical
care unit design. Crit Care Med. 1988;16(8):796–806
94 The Baby Bear Book
EMERGENCY MANAGEMENT OF SHOCK
Shock is defined as a state of inadequate tissue perfusion due to poor
circulatory flow or increased cellular needs. A series of compensatory
mechanisms are activated to cope with the initial shock state which
results in clinical manifestations. Untreated, shock states can rapidly
deteriorate into failure of multiple organ systems and eventually
irreversible shock. Recognition of pre-shock states is important so early
goal-directed therapy can be instituted. The regime of resuscitation
includes fluid boluses, airway intervention and inotropic support. The
key is early shock recognition and prompt action.
Recognise some of the following:
Sick-looking/lethargy
Tachypnoea
Tachycardia/Hypotension
Pallor
Cyanosis — Central or peripheral (if Haemoglobin (Hb) adequate)
Poor capillary refill
Acidaemia (metabolic or mixed acidosis)
CNS disturbance
Oliguria
Agitation or depression
FORMS OF SHOCK
Hypovolaemic
Septic
Cardiogenic
Anaphylactic
Neurogenic
Different forms of shock may merge in a pathophysiological sense:
It will not be unusual for a patient in shock to have a number of
different pathologies, for example hypovolaemia from dehydration
in a septic child
Most of the shock states that are dealt with in the CICU are either
hypovolaemic (gastroenteritis, blood loss, DKA), septic (community-
acquired sepsis, nosocomial infections), cardiogenic (post-cardiac
surgery, heart failure) or a combination (hypoxic-ischaemic events)
In many scenarios, it may be difficult to differentiate septic shock from
the other types of shock states and empirical therapy for sepsis has to
be started before subsequent investigations confirm otherwise
Critical Care 95
Most children who are ill for even a short period of time may have
some degree of dehydration arising from poor intake. However,
when the amount of fluid loss from history or clinical examination
does not correlate with the degree of shock, an alternative diagnosis
should be looked for
Cardiac failure is usually due to decreased myocardial contractility
(myocarditis, after cardiac surgery), overload states (left-to-right
shunt lesions) while rhythm disturbances are less common.
Cardiomegaly is usually seen. In most cases of heart failure, there is
biventricular involvement; therefore, hepatomegaly is often seen.
Neurogenic shock is uncommon and the management strategy
usually depends on the triggering neurological event
This section will focus on general shock management although some
differences in managing the different forms of shock will be mentioned.
IMMEDIATE TREATMENT
Improve Oxygenation and Ventilation
Oxygen by mask, nasal cannula or hood
Consider intubation
Ventilate if there is severe hypoxia, respiratory failure, severe
respiratory distress or marked acidaemia. Ventilation will reduce
work of breathing and cardiac demands, especially in cardiogenic
and septic shock
Volume Replacement
Establish IV access; perform blood work including microbiological
cultures
Replete circulating blood volume with normal saline, plasma,
albumin or blood in hypovolaemic shock
In septic shock, volume status must be restored quickly and should
be given before starting inotropes
In cardiogenic shock, fluid resuscitation should be given with
caution. Dobutamine or epinephrine is usually started once volume
state is optimised
Start with aliquots of 10–20ml/kg and reassess
In early resuscitation, both colloids and crystalloids can be given.
Subsequent fluid therapy in post-resuscitation stabilisation period
will usually require a combination of colloids and crystalloids,
depending on the clinical state and disease pathophysiology. Blood
products should be considered in cases of anaemia, ongoing blood
loss or bleeding tendency
96 The Baby Bear Book
Rate of infusion depends on clinical state; in acute resuscitation,
volume should be given as IV push/bolus; in shock states, each fluid
bolus can be given over 15 minutes; in less acute situations, the
timing may be prolonged to one hour
Increase Cardiac Contractility
Correct pH:
Ventilate if respiratory acidosis
NaHCO3 if pH is still < 7.20 and ventilation is adequate
[(Weight) x (Base Deficit) x 0.15]mEq
Repeat if necessary
Inotrope infusion: Inotrope therapy is usually indicated if the
perfusion remains poor after fluid state is restored or there is poor
or no response after fluid therapy of 60ml/kg in septic shock. In
cardiogenic shock, inotropes should be considered early:
Dopamine 5–10μg/kg/min
Dobutamine 5–10μg/kg/min
Milrinone 0.3–0.7μg/kg/min
Noradrenaline 0.1–1.0μg/kg/min
Adrenaline 0.1–1.0μg/kg/min
In patients with cardiogenic shock whose cardiac contractility is
decreased, adrenaline should be started. Afterload reduction agents
(dobutamine and/or milrinone) are useful to decrease the work
against which the ventricles must perform, thereby decreasing
myocardial oxygen consumption and increasing cardiac output
Paediatric septic shock, unlike adults, presents usually as cold shock
rather than warm shock. In cold shock, circulatory flow is decreased
either from poor myocardial effort or increased systemic vascular
resistance. Patients with cold shock usually have decreased mixed
venous saturation (normal SvO2 is 30% less then a paired arterial
saturation). When BP is decreased, epinephrine can be titrated to
achieve normal BP limits. When BP is normal, an afterload reduction
agent e.g. dobutamine or milrinone can improve cardiac output by
decreasing systemic vascular resistance (SVR)
In warm shock, the cardiac output is increased but end organ
perfusion is diminished because the SVR is low. Using a vasopressor
agent will increase SVR and improve flow. Noradrenaline at lower
doses (< 0.5μg/kg/min) or adrenaline at high doses (> 0.4μg/kg/
min) will have such effects. In adult studies, dobutamine with
noradrenaline have been shown to improve splanchnic flow
Critical Care 97
When high doses of inotropes are needed or the shock state does
not respond to inotrope therapy, other therapeutic measures should
be considered:
Vasopressin at low dose of 0.001μg/kg/min
Hydrocortisone should be given initially to all patients who are
at risk of adrenal insufficiency e.g. prolonged steroid use. This
group of patients will require stress doses of hydrocortisone. In
addition, certain patients with septic shock who require high
catecholamine support may have relative adrenal insufficiency.
These patients have low baseline cortisol levels (< 18mg/dl)
or poor Adrenocorticotrophic Hormone (ACTH) stimulation
response (< 9mg/dl increase after ACTH). These patients may
benefit from hydrocortisone given at higher doses
Inotropes, with the exception of dobutamine and milrinone,
should always be administered through a central line, though in an
emergency lower doses (dopamine < 10μg/kg/min, noradrenaline
and adrenaline < 0.1μg/kg/min) may be administered peripherally
for a short period until central venous access is established
Monitoring
All patients with shock who require > 20ml/kg fluid resuscitation
should be considered for CICU admission. Upon admission, they
should be on hourly parameters, saturation monitoring and strict
input-output (I/O) charting
Urinary catheterisation is needed to quantify output and for initial
urine cultures
Arterial line should be inserted for invasive BP monitoring
Central venous pressure can be trended via central venous access
Nasogastric tube and empty stomach to decrease risk of aspiration
In severe shocked states, more invasive monitoring using pulse
contour continuous cardiac output monitor may be indicated to
titrate inotrope use as well as to guide fluid therapy
Mixed venous saturations and serum lactate levels may be useful to
gauge end-organ oxygen deficit
Serum cortisol levels should be taken before hydrocortisone
treatment
FURTHER MANAGEMENT
Detailed history, best obtained by another doctor during initial
resuscitation
98 The Baby Bear Book Critical Care 99

Detailed physical examination should proceed as the resuscitation SEPTIC WORKUP IN CICU
process progresses
Assess neck veins, fontanelle, mucous membranes, skin turgor for
signs of hypovolaemia INDICATIONS
Note: beware pneumothorax and/or cardiac tamponade if full neck Post-operative Fever
veins and shock are both present Fever within the first 24 hours post-operation is unlikely due to
Fever, focal signs of infection (may be minimal); beware rash wound infection, except for fulminant group A steptococcus wound
consistent with meningococcemia infections. Atelectasis is a more likely cause
Signs of heart failure, especially gallop rhythm, cardiomegaly, pulse
differential, lung crackles, hepatomegaly Neonates:
Urticaria, mucosal oedema, bronchospasm in anaphylaxis Signs of sepsis in the newborn may be subtle
Clinical signs include feed intolerance, apnoea, bradycardia,
INVESTIGATIONS hypothermia, hyperthermia, respiratory distress
Blood: Laboratory signs include metabolic acidosis, hypo- or
FBC hyperglycaemia, lipid intolerance (if on Total Parenteral Nutrition
Blood gases and acid base (TPN)), increase or decrease in White Blood Count (WBC), decreased
Electrolytes, Blood Urea Nitrogen (BUN), creatinine platelet count, elevated CRP
Coagulation profile
Group and cross-match, if necessary Fever in Patients with Indwelling Vascular Lines:
CXR Nosocomial bacteraemia is the most common nosocomial infection
Cultures from blood, urine, respiratory secretions; full septic workup in CICU
if appropriate
Consider: Cerebrospinal Fluid (CSF) Culture or CSF Drain
Disseminated Intravascular Coagulation (DIC) screen CSF culture via Lumbar Puncture (LP) or CSF drain is indicated as part of
LFT the septic workup in the presence of:
Serum cortisol Persistent fever with no focus
Serum lactate New or changing neurologic symptoms/signs
Mixed venous saturation All newborns with suspected sepsis
Further management based on diagnostic clues and response to Presence of intracranial monitoring device
initial therapy
Pneumonia
BIBLIOGRAPHY Suspect in febrile or tachypnoeic patient with new infiltrates on
1. Task Force of the American college of Critical Care Medicine, Society of Critical Care
Medicine. Practice parameters for hemodynamic support of sepsis in adult patients. Crit
X-ray, or increase or predominance of polymorphs in ETT aspirate or
Care Med. 1999;27(3):639–660. Bronchial Alveolar Lavage (BAL)
2. 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. EXAMINATION
Always look carefully for otitis media, especially in children < three
years of age, and anyone on a ventilator
Check perianal area in all immunocompromised, neutropenic
patients
Inspect all vascular access sites
Inspect all wounds
100 The Baby Bear Book Critical Care 101

CULTURES CENTRAL VENOUS ACCESS

Gram stain, smear and culture of all wound exudates
Blood cultures:
Both peripheral and drawn back through vascular catheters. If INDICATIONS
possible, obtain 3–5mls of blood for culture in older child, and Central venous pressure monitoring
1–2mls in the newborn infant. Cultures inoculated with > 3mls Delivery system for fluids, drugs, blood products, parenteral
have a higher positivity rate for pathogens than those inoculated hyperalimentation
with < 2mls
Respiratory tract: SITES
Bacterial cultures of sputum or ETT aspirates should be taken, Femoral vein
with gram stain and smear in order to determine quality of Internal jugular vein
sample. Samples with predominance of squamous epithelial Subclavian vein
cells over polymorphs are worthless because the epithelial External jugular vein
cells indicate contamination with oral secretions. Expectorated Antecubital vein
sputum or oral suctions are least reliable, ETT next, and BAL
or biopsy most reliable samples for diagnosing the cause of COMPLICATIONS
pneumonia Bleeding
Viral specimens: Swab for direct fluorescent antibody detection of Venous thrombosis
respiratory viruses consists of wire nasal swabs which are inserted Arterial puncture
to nasopharynx. Swab is then placed in viral transport media and Air embolism
sent to the virology lab. Aim is to obtain mucosal cells for staining Arrhythmias
to detect viral antigens Pneumothorax (neck lines)
Urinary tract: Heart perforation (neck lines)
Bag collection of urine samples for culture is reliable only if bag is
placed on infant correctly, observed for urine every 15 minutes, FEMORAL VENOUS LINE
removed as soon as child has urinated, and transported to the lab Position the patient with the leg slightly abducted and laterally
within 30–60 minutes, or refrigerated rotated
Best samples are catheter (straight catheter) or supra-pubic Clean and drape as per standard sterile procedure
aspirate. Cultures from indwelling bladder catheters may be Insert needle with syringe attached approximately 2cm below the
unreliable indicators of infection inguinal crease and 0.5–1cm medial to the femoral pulse (Fig. 2.2)
Diarrhoea: Aim towards the umbilicus at an angle of 15–30 degrees above the
Stool samples should be sent to both virology and bacteriology. skin
Culture and toxin for Clostridium difficile (C. difficile) should Gently aspirate with the syringe as you advance until a backflow of
be considered in at-risk patients (prolonged broad-spectrum venous blood
antibiotics, immunocompromised, long CICU stay) Proceed with the Seldinger method:
Fungal infections: Detach the syringe from the needle while holding the needle in
If disseminated candidiasis suspected, obtain ophthalmology place with the other hand
consult for complete fundoscopic exam. In immunocompromised Insert the guide wire through the needle into the femoral vein
patients or those at risk of fungal infections (long CICU stay, (Fig. 2.3, overleaf )
prolonged TPN, indwelling lines, open wounds, post-operation) Remove the needle, leaving the guide wire in the femoral vein
fungal cultures should be taken (Fig. 2.4, overleaf )
102 The Baby Bear Book Critical Care 103

Gently insert the dilator over the guide wire to dilate the path
(Fig. 2.5)
Remove the dilator
Insert the catheter over the guide wire, making sure the guide
wire is withdrawn, until the tip is visible at the distal end of the
catheter (Fig. 2.6)
Holding the tip of the guide wire, advance the catheter until the
desired length is inserted
Remove the guide wire
Connect to the desired infusion

Fig. 2.5: Gently insert the dilator over Fig. 2.6: Insert the catheter over the
the guide wire to dilate the path guide wire, making sure the latter is
withdrawn until the tip is visible at the
distal end of the catheter.

INTERNAL JUGULAR VENOUS LINE

Fig. 2.2: Insert needle with syringe
attached approximately 2cm below the
inguinal crease and 0.5–1cm medial to
the femoral pulse.
Fig. 2.3: Insert the guide wire through
the needle into the femoral vein.
Position the patient with the head turned to the contralateral side
and the shoulder elevated with a roll or towel
Clean and drape as per standard procedure
Identify the landmarks: Apex of the sternal and clavicular heads of
the sternocleidomastoid muscle, ipsilateral nipple
Insert the needle, with a syringe attached, at the apex of the two
heads of the sternocleidomastoid muscle
Aim the needle caudally, laterally towards the ipsilateral nipple and
30 degrees posteriorly while gently aspirating with the syringe until
a backflow of venous blood occurs
Do not advance more than 2cm before blood return due to the risk
of puncturing the dome of the pleura
Proceed with the Seldinger method (as for femoral venous line)

LONG LINES
(PERIPHERALLY INSERTED CENTRAL CATHETERS)
Identify a suitable vein
Clean and drape the site
Flush the line with normal or heparinised saline
Puncture the vein using the needle provided
Thread the line through the needle into the vein (Fig. 2.7, overleaf )
Fig. 2.4: Remove the needle, leaving the Advance the line until the desired length is reached
guide wire in the femoral vein. Remove the needle
104 The Baby Bear Book Critical Care 105

Consent must be obtained for every transfer

Fig. 2.6: Thread the line through the
needle into the vein.
Secure the line with sterile tapes and dress with transparent sterile
dressings (Fig. 2.7)
THE CHILDREN’S HOSPITAL EMERGENCY
TRANSPORT SERVICE (CHETS)
Fig. 2.7: Secure the line with sterile
tapes and dress with transparent
sterile dressings.
The decision to activate the transfer team must be made by a
consultant
After the child has been stabilised and prepared for transfer, the
decision to depart from the referring centre must be made by a
consultant. This requires that the transfer team call and present the
details, for every patient
Documentation must be complete. This includes all forms of
communication, verbal, written and via phone
A receiving team and primary physician must have accepted the
patient before transfer
All transfers involve increased risk to the patient which must be
balanced by benefit as a result of being transferred to the receiving
centre
Once the patient is in the care of the transfer team:
Monitoring must not be interrupted; this requires ‘double’
monitoring at points of physical transfer between sets of
equipment
The patient, all team members and the equipment travel as one
unit and should not separate
Any unexpected clinical finding, logistic problem or change from
the planned transfer arrangements should be discussed with the
consultant in charge of the transfer
The minimum level of care and intervention by the transfer team
should be what the patient would have received if already at KKH

In summary: Make it safe, take no short-cuts, communicate thoroughly

BACKGROUND and repeatedly.
As specialised paediatric and neonatal services become centralised,
there is an increasing need to have available a means to transfer INDICATIONS FOR ACTIVATING CHETS
critically ill patients who present to centres which do not have facilities Any child requiring intensive care
for complete long-term intensive care of children. Neonates requiring further care
(Potentially) unstable airway
PRINCIPLES (Potential) haemodynamic or respiratory compromise, or collapse
The level of care, monitoring and therapy provided to the patient Depressed consciousness
should always be maintained or increased as a result of the transfer Any child requiring emergency surgery with unstable physiology, or
team’s efforts a need for resuscitation pre-procedure
The primary aim is to provide a safe transfer Any child who is already a patient in an ICU, but needs transfer
The personnel, equipment, resources and skills available for the The service can also be activated to transfer patients to the HD ward.
transfer should cover the worst-case scenario(s). The gas and power If in doubt, discuss the case with the CHETS consultant on call
supplies should be sufficient for double the estimated total transfer
time
106 The Baby Bear Book
ACTIVATING AND USING THE SERVICE
Call +65-63941779 and ask to speak to the registrar or consultant,
stating that you wish to activate the transfer team
Try to have as much of the patient’s details, history, findings, and
results on hand. Present the patient’s problems
Make sure the CHETS team has your contact details. Ask for an
Estimated Time of Arrival (ETA) of the transfer team at the referring
centre
Explain to the parents:
You have contacted the transfer team and their child will be
transferred to KKH
They need to stay with the child until the team arrives so that
they can give consent for transfer
They will not be able to travel in the ambulance
Update the team if a significant change in the clinical status occurs
before the transfer team arrives. Call the number above
When the team arrives arrange for a handover to be given. Copies of
the results, X-rays, drug prescriptions and observation charts are very
useful to the receiving ICU team. A letter to the receiving primary
physician should accompany the patient
Within Singapore, the team will usually arrive in less than an hour
from the decision to transfer. The transfer team will usually spend
between one to two hours preparing the patient for the journey
before departing. International transfers involve more planning and
an increased journey time
TAKING A CHETS CALL
Be polite, be clear, be helpful
If you are not the person who is meant to be answering the call
(usually the CICU Registrar), stop. Multi-channel multi-party
communication causes immense confusion in an already time-
sensitive and difficult situation; it is to be avoided at all costs. Get the
right person to speak to the referring centre. If at all possible only
one physician in KKH should be talking to the referring physician.
Document all conversations
Take the history; if necessary, direct the caller to addressing the ABCs,
presumed diagnosis, interventions and vitals. Use the CHETS form as
a guide
Give your name and contact number; get the caller’s name and
contact
If possible, get the parents’ contact
Critical Care 107
Give advice about the management of the patient if appropriate;
be sensible about what can be reasonably achieved by the referring
team. Give a clear order of priority if making multiple suggestions.
Document advice given
The CHETS or ICU consultant must make the decision to activate the
team. A primary physician must be identified
Inform the unit Nurse Manager-on-duty of the transfer, who will
activate the CHETS nurse, arrange for the ambulance and assist in the
preparation of the equipment. The nursing staff will need to know
the patient’s age, weight and working diagnosis. If there are special
needs (equipment or drugs) that can be predicted for the child,
inform the CHETS nurse
Help prepare the equipment:
Stretcher vs incubator?
Need for spinal protection?
How many syringe pumps? Three is standard
Which transport ventilator? Check using the test lung
How many oxygen and air cylinders?
PERFORMING A CHETS TRANSFER
For local retrievals, aim to leave the hospital within 15 minutes of the
decision to transfer, two hours for international
Make sure your in-hospital patients are adequately covered
Assist in preparing the equipment as above
Get the CHETS mobile phone from the Nursing Manager
Check that the drugs from the fridge and the controlled drugs have
been collected
Collect the i-STAT and enough cartridges
If there has been a delay in departing KKH, phone the referring
hospital as you leave and update them on your ETA
Team members: Who is going with you? Is extra man-power needed?
Can you take someone extra for training? The total number of people
in the ambulance must not exceed five, this includes driver and
patient
Before leaving, double-check patient’s location, adequate gas and
power, both CHETS bags, CHETS forms, primary physician identified
and accepted, CHETS consultant informed
Load ambulance — Check that it is the correct vehicle, (CICU
ambulance). Stow and secure equipment properly
In transit: Calculate the expected drug doses and infusions, discuss
the plan of management and intervention with the other members
of the team
108 The Baby Bear Book
On arrival, assist the referring team in the resuscitation if necessary
(remember that you are helping them with their patient in their
hospital; be polite). Otherwise, obtain handover from the referring
physician. The nurse should obtain a full set of parameters before any
intervention by the CHETS team
Introduce yourselves to the parents, obtain consent, explain any
planned interventions. Ensure that they understand that the transfer
has risks
Prepare the patient for transfer and commence/adjust treatment as
appropriate:
Examine the patient, go through the ABCs, check all tubes, lines
and catheters for position, patency and security. If needed, re-site,
or re-secure; be paranoid about this
Look at the ventilator settings, the charts and the blood results.
Examine the drug prescription and infusions, check the doses
If any treatment or procedure needs to be done before transfer,
consider involving the referring team. They are likely to be
interested and helpful. At the very least, they can provide extra
pairs of hands
The next four steps can be done in any order, but do them one at
a time:
Connect to CHETS monitors before disconnecting the
monitoring already in place
Transfer infusions to CHETS syringe pumps
Transfer the patient across to the stretcher/incubator
Transfer to the CHETS ventilator
If indicated, perform an ABG sampling
Obtain another set of parameters
Call the CHETS or ICU consultant in charge of the transfer. Present
the case history, interventions by the referring team, transfer team
findings (Airway, Breathing, Circulation, Deficit, Exposure (ABCDE);
etc.) and interventions, current status, your plans. Perform any
further suggested interventions
Update the parents, inform them of the proposed destination ward.
Give them the CHETS contact number. Explain that they should not
hurry to KKH and should drive safely
Before departure, draw up any drugs or prepare any intervention
that might be anticipated in transit
Load ambulance, securing all equipment and patient
In transit: Complete documentation, including all times and the
CHETS audit form
Critical Care 109
If drugs or simple treatments are needed in transit, administer them.
However, if any procedures (IV, ETT, chest tube) are necessary, ask the
ambulance driver to stop, do the needful and only continue when
the patient is stabilised
Call the ICU nursing staff with an ETA
Parameters should be taken and recorded every 15 minutes
If unstable on arrival to KKH, divert to CE, otherwise unload and take
the child to the ICU or HD unit
Hand over to the duty registrar, ensure that the primary physician
has been contacted. Introduce the parents to the ward team
Obtain a last set of parameters. If indicated, perform an ABG
Transfer the patient to the ward/ICU bed. This process should be
the reverse of the process that occurred at the referring centre and
should be performed with the same care. Perform one step at a time.
Do not interrupt monitoring
Complete the documentation. Ensure that a photocopy of the
transfer record (NOT the audit form) goes into the patient’s clinical
notes. The originals should be given to the CICU Nurse Manager for
audit and filing
RECEIVING A CHETS TRANSFER
Obtain a handover from the transfer team
Transfer over to the ICU/Ward equipment in stages (see above). The
transfer team should be allowed to control this process
Go through the ABCs again
Examine the patient. Check all lines, tubes and catheters
Check the ventilator, drug doses and infusions
Inform the CHETS/ICU consultant
Inform the primary physician/surgeon
Introduce yourself to the parents and re-take the history
110 Endocrinology and Metabolism 111

™ Eosinophilia
™
ENDOCRINOLOGY AND METABOLISM ™
Elevated ACTH (in primary adrenal insufficiency)
Elevated renin
™ Inadequate cortisol rise to synacthen stimulation

ADRENAL INSUFFICIENCY REPLACEMENT THERAPY FOR ADRENAL INSUFFICIENCY

™ Although the basal cortisol secretion rate is 8mg/m2/day, larger doses
Glucocorticoids are important in carbohydrate, protein and fat are required when taken orally because of hepatic first-pass effect
metabolism; they also play an integral role in the stress response. ™ Maintenance hydrocortisone dose: 10–15mg/m2/day in three divided
Mineralocorticoids deal with water retention as well as sodium and doses because of the relatively short half-life of hydrocortisone
electrolyte balance. Adrenal insufficiency results in deficiencies of one or ™ Cortisone acetate may be used but has to be converted in vivo to
both of these steroids. cortisol, the bioactive agent
™ Longer-acting glucocorticoids like prednisolone (2–4mg/m2/day)
CAUSES OF ADRENAL INSUFFICIENCY and dexamethasone (0.25–0.375mg/m2/day) are options after final
Primary Adrenal Insufficiency adult height has been achieved
™ Congenital adrenal hyperplasia ™ For mineralocorticoid: Fludrocortisone 0.05–0.2mg/day oral
™ Autoimmune adrenalitis
™ Autoimmune polyglandular syndromes (APS) Types 1 and 2 GLUCOCORTICOIDS DURING STRESS
™ Infections — Tuberculosis (TB), fungal, Acquired Immune Deficiency ™ The body requires increased levels of cortisol to deal with stress.
Syndrome (AIDS) During febrile illnesses, vomiting, diarrhoea, trauma, surgery or
™ Congenital adrenal hypoplasia anesthesia, the child requires two to three times his maintenance
™ Adrenal hemorrhage/infarction dose of hydrocortisone
™ Adrenoleucodystrophy ™ Insufficient cortisol in the face of stress may lead to symptoms of
™ ACTH receptor defect adrenal insufficiency and crisis
™ Triple-A syndrome (Addison’s, Alacrimia, Achalasia) ™ There is no need to increase fludrocortisone doses as cortisol at high
doses has mineralocorticoid properties
Secondary Adrenal Insufficiency (ACTH Deficiency)
™ Withdrawal from glucocorticoid therapy Steroid Cover for Surgery
™ Hypopituitarism ™ Minor surgery — Bolus dose of hydrocortisone at induction (doses as
™ Hypothalamic tumours for adrenal crisis) followed by double the usual for 24 hours or until
™ Irradiation of CNS patient is well
™ Major surgery — Doses as for adrenal crisis
FEATURES OF ADRENAL INSUFFICIENCY
Clinical MANAGEMENT OF ACUTE ADRENAL INSUFFICIENCY
™ Weakness, lethargy (ADRENAL CRISIS)
™ Anorexia, weight loss This is an endocrine emergency.
™ Dehydration ™ Correction of dehydration and electrolyte imbalance
™ Hypotension and shock Š A patient in shock may require normal saline boluses of
10–20ml/kg stat and then IV fluids for maintenance and
Biochemical replacement of fluid deficits
™ Hypoglycaemia Š Correct hyperkalaemia if necessary (potassium is withheld from
™ Hyponatraemia, hyperkalaemia the drip until serum potassium level is normal)
112 The Baby Bear Book Endocrinology and Metabolism 113

™ Treatment of hypoglycaemia: In short, as fasting proceeds, the metabolic response is for the glucose
Š Dextrose 10% 2ml/kg bolus levels to be low and the FFA and ketone body levels high. The hormonal
Š Then ensure that there is adequate dextrose substrate in the responses are for insulin to be suppressed; whilst GH, glucagon and
maintenance drip (5% dextrose/saline) cortisol levels are raised.
™ IV hydrocortisone doses during stress:
Age Dose CAUSES OF HYPOGLYCAEMIA
< Three years 25mg, followed by ™ Decreased influx from food (starvation):
25–30mg/day four to six hourly Š Delayed feeding of a neonate (first breast milk feed allows rise of
Three to12 years 50mg, followed by 1–1.5mmol/l)
50–60mg/day four to six hourly Š Inadequate feeding (30ml 5% dextrose contains 6cal; 30ml milk
Adolescents/adults 100mg, followed by has 24cal)
100mg/day four to six hourly Š Vomiting
™ Decreased influx from preformed glycogen stores:
BIBLIOGRAPHY Š IUGR/prematurity
1. Joint LWPES/ESPE CAH Working Group. Consensus statement on 21-hydroxylase
deficiency from the Lawson Wilkins Pediatric Society and the European Society for
Š Maternal starvation
Pediatric Endocrinology. J Clin Endocrinol Metab. 2002;87(9):4048–4053. Š Smaller twin
2. Miller WL. The adrenal cortex and its disorders. In: Brook CG, Hindmarsh PC, editors.
Clinical pediatric endocrinology. 4th ed. Oxford: Blackwell Science, 2001. p. 321–376.
Š Thin older child with poor glycogen stores
™ Decreased influx from gluconeogenesis and glycogenolysis:
Š Galactosaemia
Š Fructosaemia
Š GH deficiency
HYPOGLYCAEMIC DISORDERS Š Adrenocortical insufficiency
Š Glycogen storage disease
™ Increased efflux into stores (hyperinsulinism):
DEFINITION Š Infant of diabetic mother
Hypoglycaemia is defined as a Blood Sugar Level (BSL) less than Š Excessive maternal IV glucose
2.5mmol/L; or less than 3.0mmol/L if the child is symptomatic. Š Persistent Hyperinsulinaemic Hypoglycaemia of Infancy (PHHI)
Š Islet cell adenoma
METABOLIC AND HORMONAL RESPONSES TO FASTING Š Beckwith-Wiedeman syndrome
When fasting occurs, the body changes from carbohydrate-based Š Drug-induced
energy usage to fat-based energy usage. As the blood glucose level ™ Increased efflux due to increased glucose utilisation:
falls with fasting, insulin levels fall and growth hormone (GH) as well as Š Sepsis, shock, hypothermia or asphyxia
cortisol levels rise. The low insulin levels allow peripheral fat stores to be Š Polycythaemia, hyperviscosity or fever
broken down (lipolysis) and free fatty acids (FFA) are released. Tissues Š Fatty acid oxidation defects prevents synthesis of ketone bodies
such as brain cells and muscle are able to metabolise FFAs directly for and complete oxidation of FFA
energy. The liver is also able to take up FFAs, where they are oxidised for
energy through a process called beta-oxidation. FFAs are also converted CLINICAL SYMPTOMS
in the liver to ketone bodies (betahydroxy butyrate and acetoacetate), ™ Autonomic — Tremors, sweating, pallor and irritability
which are released into the circulation and are available as an alternate ™ Neuroglycopaenic — Apnoea, cyanosis, hypotonia, coma, seizures,
metabolic fuel. poor feeding
114 The Baby Bear Book
INVESTIGATIONS
™ Estimate the glucose utilisation needs from the IV glucose infusion
rate:
Š Glucose infusion rate >10mg/kg/min is usually due to
hyperinsulinism. Occasionally seen in severely asphyxiated neonates
Š Glucose infusion rate < 10mg/kg/min is due to other causes of
hypoglycaemia
™ Obtain blood and urine samples at the time of hypoglycaemia
— This is usually the most important step as levels taken at the
appropriate time will usually be diagnostic:
Š Hormonal — Insulin, cortisol and growth hormone
Š Metabolic — Glucose and ketones
Š Urine — Metabolic screen
™ A fasting study may need to be done to induce hypoglycaemia for
diagnostic purposes. The duration of fast will depend on the child’s
age and clinical condition:
Š Low glucose, low ketones, low FFAs occur in hyperinsulinism
Š Low glucose, low ketones, high FFAs occur in fat oxidation defects
Š Low glucose, high ketones, high FFAs occur in starvation,
disorders of gluconeogenesis and glycogen synthesis,
adrenocortical deficiencies and growth hormone deficiency
™ Further tests may be needed to define:
Š Hormonal abnormality (adrenal or pituitary)
Š Hepatic enzyme function
TREATMENT
™ Prevention through adequate prenatal and post-natal feeding
™ Treat the underlying cause where possible:
Š Sepsis/RDS/hypothermia/polycythaemia
Š Hyperinsulinism or endocrine deficiency
Š Metabolic disorder
™ Administer IV glucose (remember to obtain blood samples before
giving glucose):
Š Bolus 2ml/kg of 10% dextrose
Š Maintenance IV dextrose at starting rate of 4–8mg/kg/min
Š The rate must be adjusted to achieve and maintain glucose at
least 3–4mmol/L
™ Hydrocortisone 3–5mg/kg:
Š Hydrocortisone for hypoglycaemia is usually used in the neonatal
period, as an insulin antagonist
Š The approximate basal hydrocortisone production rate is 1mg/
kg/day
Endocrinology and Metabolism 115
™ Glucagon 0.5 units IV/IM/SC stat dose
Š Glucagon will only elevate the blood glucose acutely in
hyperinsulinism when there are good glycogen stores
Š Glucagon can be used as a continuous IV infusion at 5–20μg/kg/h
in severe ongoing hyperinsulinism
Š Glucagon infusions have a role to play in neonatal hypoglycemia
associated with immaturity of glyconeogenic enzyme systems by
inducing these enzymes
™ Hyperinsulinism may require specialised forms of treatment (please
consult the endocrinologist):
Š Diazoxide (PO) — 5–15mg/kg/d at six to 12 hourly intervals
Š Nifedipine/Chlorothiazide in conjunction with diazoxide
Š Somatostatins — Safety issues in its use
Š Total or sub-total pancreatectomy
DIABETES MELLITUS (DM)
DM can present as early as the first month of life. Neonatal DM can
be temporary or permanent. In pre-pubertal patients, the most likely
diagnosis is Type 1 DM associated with autoimmune destruction of
pancreatic beta cells. However, in the pubertal and post-pubertal age
group, both Type 1 and Type 2 diabetes, as well as Maturity Onset
Diabetes in the Young (MODY) can occur. Both Type 1 and Type 2
patients can present with DKA and low initial serum insulin levels.
Antibody tests, presenting clinical features and an Oral Glucose
Tolerance Test (OGTT) with simultaneous insulin levels can help
differentiate the two, but at times, the definitive diagnosis can only be
determined after three to six months. For the features of diabetes in
childhood, please see Table 3-1 overleaf.
Both types of diabetes may co-exist in the same patient as many families
in Singapore have strong family histories of Type 2 diabetes and the
(dys)metabolic syndrome. If in doubt, treat as for Type 1 DM. It must be
remembered that Impaired Glucose Tolerance (IGT) and very often Type 2
DM may be asymptomatic; it must be looked for in the obese child with a
family history of DM or gestational diabetes, Intrauterine Growth Restriction
(IUGR) or Large for Gestational Age (LGA), acanthosis nigricans, hypertension
for age, and obstructive sleep apnoea. In case of doubt, an OGTT with
simultaneous insulin levels may be ordered.
116 The Baby Bear Book Endocrinology and Metabolism 117

Table 3-1: Features of diabetes mellitus in childhood.

In DKA, the child may be in coma with hyperpnoea. There is also acidosis
Type 1 Type 2 MODY (pH < 7.3, serum HCO3 < 15mmol/L), ketonuria, Kussmaul respiration
Insulin resistance not a usual with acetone detectable in the breath, a potassium deficit, hyperosmolar
Insulin deficient Insulin resistant ± deficient
feature dehydration and the possibility of sepsis. In a known diabetic, always
Lean > obese Obese > lean Lean usually consider the possibility that insulin was omitted.
Strong family history of Type AD pattern of DM (three
5% with family history ™ Not all Insulin-Dependent Diabetes Mellitus (IDDM) present in DKA,
2 DM generations) in lean individuals
DKA in 20-40% DKA possible Not associated with DKA not all DKAs are dry
™ The total body potassium is low, even though the initial serum K+
GAD, ICA likely GAD/ICA negative GAD/ICA negative
level may be normal
MODY: Maturity Onset Diabetes in the Young; DKA: diabetic ketoacidosis; GAD: glutamic
acid decarboxylase; ICA: islet cell antibody ™ The endpoint of treatment is not euglycaemia but the correction of
ketoacidosis
™ Never stop or omit insulin because of hypoglycaemia. IV insulin has a
INVESTIGATING DIABETES very short half-life
DKA is defined by the following criteria: ™ Rehydrate slowly and evenly over 48 hours to reduce the risk of
™ Blood glucose > 15mmol/L cerebral oedema. If the corrected sodium is in the hypernatraemic
™ Acidosis, pH < 7.30 range, rehydrate over 72 hours
™ Low serum bicarbonate level < 15mmol/L ™ Brain herniation due to cerebral oedema can be sudden and
™ Urine ketones > 2+ unpredictable. If suspected, treat immediately
™ The patient is usually in a state of dehydration and has lost a great
deal of sodium and potassium Monitoring
™ Nurse heads-up. Admit to HD or ICU if very ill
Patients with DKA should have the following tests done: ™ Hourly parameters (heart rate, respiratory rate, temperature x 24
™ Blood glucose hours)
™ Arterial or venous blood gas ™ Hourly blood glucose monitoring
™ FBC ™ U/E/Cr and BSL two to four hourly
™ Serial serum urea and electrolytes ™ NB: Creatinine may be spuriously raised because ketones interfering
™ Serum Insulin (to be taken for every episode of DKA whether or not with the assay
recurrent admissions) ™ Head chart (a complaint of headache may herald cerebral oedema or
™ Serum C-peptide hypoglycaemia)
™ Serum cortisol ™ Nil by mouth except for ice chips (consider a nasogastric tube)
™ Blood or urine ketones ™ Take blood for: Cultures, FBC, ESR, serum insulin and C-peptide, ICAs,
™ Blood culture if septic Glutamic Acid Decarboxylase (GAD) antibodies, HbA1c (in an EDTA
tube), random cortisol
MANAGEMENT OF DIABETIC KETOACIDOSIS (DKA) ™ Test urine for ketones until negative, and eight hourly thereafter
Children with DKA will need close monitoring and serial investigations. This
is best done in a HD or ICU environment. While older children with mild Resuscitate if in Shock
disease may be considered for treatment in the general ward, children < five (Hypotension, Peripheral Shutdown, Oliguria)
years and all patients with moderate to severe disease should be managed ™ 10–20ml/kg normal saline, plasma or plasma expander (5% albumin)
in a HD or ICU setting. Hypokalemia is often present once treatment is ™ Repeat as necessary to improve perfusion
started. Regular assessment of the patient’s GCS and neurologic status is
mandatory as cerebral oedema is a rare but dreaded complication of DKA.
118 The Baby Bear Book
Rehydrate if Clinically Dehydrated
™ Give deficit + maintenance fluids evenly over 48 hours
Deficit = (% dehydration) x (Body weight)
™ Start with normal saline — DKA plasma is usually hyperosmolar. Add
potassium (see “Potassium” below)
™ After 12 hours or when the BSL is 12–15mmol/L, change to D/S(R) or
N/S + 2.5% Dextrose
™ If BSL falls to 12–15mmol/L before 12 hours, give normal saline and
5% dextrose to maintain IV fluids for at least 12 hours. If necessary, use
10% Dextrose in saline to maintain a blood glucose of 5–10mmol/L.
Never use plain dextrose drips, as this may cause hyponatraemia (see
“Sodium Trends” below)
Sodium Trends
™ A falling serum sodium during resuscitation could indicate overly fast
rehydration and increases the risk of cerebral oedema
™ However, a high BSL causes a falsely low reading of sodium. Rehydrate
over 72 hours if hypernatremic (adjusted sodium > 150mmol/L) or if the
‘adjusted sodium’ level falls too rapidly (> 2mmol/L/hr)
‘Adjusted sodium’ = {(Measured Na+) + [1.6 (BSL - 5.5 )] / 5.5}mmol/L
Potassium
™ Potassium should be added to the initial drip unless anuric
™ Commence potassium replacement at 3–5mmol/kg/day
e.g. If < 30kg, add KCL 40mmol/L rehydration fluid
If > 30kg, add KCL 60mmol/L fluid
™ Maintain K+ at 4–5mmol/L
Bicarbonate
™ Acidosis usually subsides with rehydration
™ Bicarbonate use may worsen risk of cerebral edema
™ If pH is persistently < 7.1, despite correction of perfusion, consider
use (discuss with a senior doctor first)
Insulin Infusion in DKA
™ The preferred route is via an infusion or syringe pump. Administer
this at a rate of 0.1U/kg/hr if the blood glucose is > 15mmol/L (0.05U/
kg/hr if the blood glucose is < 15mmol/L or the child is < three years
old). The aim is to reduce the BSL by about 4–5mmol/L/hr
™ Dilution of insulin (whatever the method used, the same method
should be used consistently within a given ward or unit and for each
individual patient, so as to minimise the possibility of error):
Endocrinology and Metabolism 119
Š Dilute soluble insulin (Actrapid or Humulin R) 50 units with
49.5ml of normal saline to make a solution containing 1U/ml of
soluble insulin. Flush the line (10ml) to saturate insulin binding
sites on the tubing, or
Š Dilute 5U/kg of insulin in a 50ml syringe and make up the volume
to 50ml with normal saline. 1ml/hr of the resulting solution
delivers 0.1U/kg/hr. Flush the line (10ml) to saturate insulin
binding sites on the tubing
™ If venous access is not available, give IM-soluble insulin 0.25U/kg stat,
then 0.1U/kg hourly till BSL is 12–15mmol/L, then give four to six hourly
™ Never stop the infusion because of hypoglycemia. IV insulin has
a very short half-life of four to five minutes. Instead, increase the
dextrose concentration in the drip to maintain BSL at 5–10mmol/L.
IV insulin rate may be lowered to 0.02U/kg/hr as necessary. When
converting to subcutaneous insulin, wait for a mealtime, continue
the infusion for half-an-hour after the subcutaneous insulin injection
before stopping the infusion if subcutaneous regular insulin is used
Cerebral Oedema
™ This is an uncommon, but potentially fatal, complication of
treatment for DKA, occurring usually six to 12 hours after starting
treatment, but can also occur before treatment
™ The risk is greater for children < five years old, when initial pH <
7.0, when control has been chronically poor, when there is initial
hyponatraemia or hypernatraemia, and if rehydration is excessive in
volume or rapidity
™ If suspected, treat. Do not wait for CT scan
Oral Feeds
™ Start after 24–36 hours and when the patient is stable (pH > 7.30,
HCO3 > 15 and BSL < 12), conscious and able to retain small feeds
Subsequent Insulin Dosage
™ After correction of acidosis (pH > 7.3, serum bicarbonate normal and
ketonuria resolved), and when the child can take well orally (usually
24–36 hours after starting treatment), subcutaneous insulin can be
started. The total amount of insulin per kg used in the preceding 24
hours is a guide. The insulin infusion should only be stopped half-an-
hour after the first subcutaneous insulin injection (if regular insulin
and not rapid-acting insulin is used)
120 The Baby Bear Book Endocrinology and Metabolism 121

MANAGEMENT OF DIABETES MELLITUS (NON-DKA) DISCHARGE PLANNING

Investigations Diabetes education is of the utmost importance. A child should not be
Patients who are not in DKA and who are peri-pubertal should have an discharged without the child and family knowing what to do and how
OGTT (1.75g/kg glucose, max 75g) taken before starting treatment. to go about doing the necessary if the child has a diabetic emergency. A
child with diabetes should not go home without:
Time 0 60 120 minutes ™ All of the adult caregivers at home knowing the basics of diabetes care
Glucose + + + ™ A blood glucose meter and someone who knows how to use it
Insulin + + + ™ Ability to give injections and draw insulin, where possible
C-Peptide + + ™ Knowledge of what diabetes is and signs of DKA
HbA1c + ™ Knowledge of emergency home management of hypoglycaemia and
Fasting lipids + sick days
U/E +
GAD Antibody + Metformin
ICA + Metformin is usually used for obese Type 2 diabetics, but is also used
together with insulin in obese Type 1 diabetes patients as adjunctive
Insulin Therapy therapy. A starting dose of 250–500mg BD is usual. If in doubt about
Treatment with insulin should be started before a meal. An initial dose of whether the patient is Type 1 or 2, do not start with metformin in
0.2U/kg/dose will usually suffice. monotherapy. The thiazidolidinediones are currently being investigated
for possible use as monotherapy or adjunctive therapy in Type 2
When starting or converting from IV insulin, try not to use > 0.2U/kg six diabetes in childhood.
hourly as the child may go hypoglycaemic in the night. Use the last 24
hours’ total insulin dose as a guide; insulin requirements usually drop SICK DAYS
after the initial DKA, then may rise or fall again before discharge. Give Watch out for DKA. Never omit insulin when the child is sick and not
about 35–40% of the total daily dose in the evening, and 60–70% of the taking well. Insulin resistance goes up transiently during intercurrent
total daily dose of insulin in the morning/day. Start with a BD or TDS illness and may require two to three times the usual doses. If the child is
insulin regime. taking well, encourage fluids and give the normal insulin, with top-up
doses every four to six hourly (each dose is 5–10% of the total daily dose
A sample regime: e.g. if a child is on 25U/day total insulin, each top-up is two to three units
Time Long-acting Short-acting of short-acting insulin). If the child is not taking well, give a maintenance
Breakfast 30–40% 10% drip with DS(M) or 5% DS(M) and 2mmol/kg of KCl, and the usual insulin.
Lunch Nil 10–15% Alternatively, give insulin intravenously, starting with the total daily dose
Dinner 20–30% 10–15% divided into 24 hours, then titrate to keep blood glucose at 5–10mmol/L.
Or Monitor urine ketones eight hourly, and U/E at least daily. You may need
Breakfast 40% 15% to convert to treating for DKA if the child deteriorates.
Dinner 30% 15%

Typical doses are shown below

Pre-pubertal child 0.5–0.7U/kg/day
Pre-pubertal, sedentary child 0.8–1.0U/kg/day
Pubertal child 1.0–2.0U/kg/day
122 The Baby Bear Book
FREQUENT URINATION, POLYURIA
AND DIABETES INSIPIDUS (DI)
™ Polyuria is an important endocrine symptom which requires careful
evaluation to determine its cause
™ Numerous non-polyuric states resulting in frequent urination
must be recognised to avoid unnecessarily extensive endocrine
investigations for polyuria
™ Both frequent urination and polyuria are symptoms of DI in children
DEFINITIONS
™ Polyuria refers to the passage of abnormally large volumes of urine,
characteristically greater than 4ml/kg/hr. Polyuria usually leads to
increased urinary frequency
™ Frequency refers to the increased occurrence of usually voluntary
episodes of micturition compared to normal; however, it may be
either large or small volumes of urine each time. Hence, frequency
does not necessarily imply a polyuric state
™ Incontinence refers to the inability to retain urine voluntarily,
leading to leakage of urine. It may be mistaken for increased urinary
frequency
™ Enuresis refers to involuntary episodes of micturition in children >
six years, leading to bedwetting
BASIC INVESTIGATIONS FOR FREQUENT URINATION
™ Basic investigations for all children with frequent micturition must
include:
Š Urine biochemistry/microscopy (especially specific gravity,
glucose)
Š Urine culture
Š Urine calcium/creatinine
Š Serum U/E/Cr
™ If DI is suspected or needs exclusion, include:
Š Urine osmolality as part of an overnight water-deprivation test
Š Serum osmolality
] to determine the exact underlying pathology
™ Based on the clinical presentation, formal water-deprivation test
(with intranasal Desmopressin (DDAVP) test) may be required in
equivocal cases
DIAGNOSIS OF DI
™ The diagnosis of DI is usually made clinically:
Š Thirst, often craving cold water
Endocrinology and Metabolism 123
Š Nocturia and marked polyuria
™ The diagnosis is confirmed by laboratory investigations where in an
appropriate clinical setting, we can usually assume DI to be present if:
Š Urine volume > 4ml/kg/h for > two consecutive hours, and
Š Urine specific gravity < 1.005 and/or urine osmolality <
200mOsm/kg H2O (before hydration)
Š Serum sodium and osmolality (nears or exceeds 300mOsm/kg)
may be elevated but may also be within normal ranges if child
has free access to fluids
SPECIFIC INVESTIGATIONS FOR DI
Although the diagnosis is usually made clinically, the following tests
may be carried out if conclusive evidence is needed, bearing in mind
this principle: ‘Investigations done at a point of maximal dehydration
tolerable usually yields the best result’. Conversely, one cannot exclude
DI on the basis of normal paired serum and urine osmolality if the test is
carried out in a compensated state.
™ Paired serum and urine osmolality:
Š Tests to be done simultaneously
™ Overnight water-deprivation test:
Š No fluids after bedtime and at breakfast
Š Attend clinic/laboratory at 8:00am to 8:30am for paired serum
and urine osmolality
Š Useful as a screen to rule out DI
Š Patients with complete central DI may not be able to tolerate
overnight fluid deprivation
Š Those unable to tolerate overnight water deprivation will require
formal testing
™ Formal water-deprivation test (with intranasal DDAVP test)
Š Test is done as an inpatient
Š Consult the endocrinologist for a test protocol
™ As the presence of central DI is a symptom in itself, MRI of the brain,
in particular the hypothalamus and pituitary region, will be needed
TREATMENT OF DI
The treatment of central DI hinges on replacing fluids and anti-
diuretic hormone (ADH). The former is dependent on functional
thirst mechanisms as well as the child’s ability or inability (e.g. mental
impairment, post-operative states, neonates and infants) to source for
and consume fluids independently.
124 The Baby Bear Book Endocrinology and Metabolism 125

Fluids should be relatively hypo-osmolar (water can be taken orally; if Type Causes Characteristics
for IV, 5% dextrose or D/S(M) are appropriate choices) and adequate to Non-polyuric Incontinence
replenish daily requirements. (cont’d) ™ Detrusor instability Clues: “Always wet”, “persistent dribbling”.
Most common voiding disorder in
ADH can be administered orally (Tab Minirin 0.1–0.4mg as an initial paediatrics. Causes urge and urge
incontinence as the bladder contracts
dose), intranasally (intranasal Minirin 1–5μg as an initial dose followed
during filling. Needs bladder training.
by maintenance doses of 2–40μg per day) and where indicated through Always exclude ectopic ureter, especially in
injections either subcutaneously or intravenously. female infants.
™ Asymptomatic Affects children age three to five years
CAUSES OF FREQUENT URINATION IN CHILDREN daytime incontinence who delay urination because of intense
concentration on play or TV. Otherwise
Type Causes Characteristics normal voiding pattern. Clears within two
Polyturic Water Diuresis Urine SG < 1.005 indicates water diuresis. weeks without intervention.
™ > 4ml/kg/h ™ Psychogenic Polydispia ™ Giggle incontinence Complete bladder evacuation induced by
™ Usually with ™ Diabetes Insipidus laughter.
nocturia Š CDI
Incontinence
Š NDI
™ Nocturnal Enuresis Believed to be due to deficient nocturnal
Solute Diuresis Diuresis from osmotically active solutes. DDAVP secretion. Role of DDAVP therapy.
™ Diabetes Mellitus
™ Hypercalcaemia
™ Diuretic therapy
Osmotic Diuresis The urine and serum osmolality is almost
™ Resolving ARF equal. CAUSES OF DI
™ Renal tubulopathy
™ Mannitol treatment Type Cranial DI Nephrogenic DI
Non-polyuric Frequency Familial ™ Familial Neurohypophyseal ™ X-linked Nephrogenic Diabetes
™ < 4ml/kg/h ™ Urinary Tract Infection Pollakiuria is more common than UTI. Diabetes Insipidus (FNDI) — Insipidus
™ Must exclude However UTI must be excluded to diagnose Autosomal Dominant ™ Autosomal Recessive
incontinence, pollakiuria. Dysuria is present. ™ DIDMOAD or Wolfram Syndrome Nephrogenic Diabetes Insipidus
voiding disorders ™ Vulvovaginitis Dysuria is present. Acquired ™ Trauma (head injury, ™ Chronic Renal Disease
Urethritis Rule out pinworm infestation. neurosurgery) ™ Post-obstructive Uropathy
Local Irritants ™ Tumours (craniopharyngioma, ™ Osmotic Diuresis
™ Pollakiuria Pollakiuria is defined as frequent daytime germinoma, glioma) Š Glucose (Diabetes Mellitus)
(Extraordinary urination that may occur as often as every ™ Infections (meningoencephalitis, Š Calcium (Hypercalcemia)
Daytime Urinary five minutes, although usually the child congenital CMV/toxoplasmosis) Š Mannitol (Drug induced)
Frequency) urinates three to four times per hour. This ™ Granulomatous Disease (TB,
is a common paediatric complaint and the sarcoidosis, histiocytosis)
parents are usually concerned that their ™ Hypoxic Brain Injury
child has diabetes or UTI. The majority of ™ Vascular Malformations
children are between four to six years of
age. Symptoms may last for years, but on
average for up to seven to12 months. No
treatment is needed.
126 The Baby Bear Book
INBORN ERRORS OF METABOLISM (IEM)
INTRODUCTION
IEM or inherited metabolic diseases are individually rare, but collectively
common. Establishing the diagnosis is important as definitive treatment
and prenatal diagnosis is available for some.
Some common fallacies about IEM are:
™ These conditions are so rare that we do not see them at all.
Collectively, IEM incidence is estimated to be as common as 1-in-
5,000. In some populations, the incidence of organic acidurias alone
is 1-in-5,000
™ The complex pathways need to be understood before a
diagnosis is made.
The pathophysiology of these diseases suggests a pattern of
how these conditions present, thus one can investigate the
patient broadly but with specific differentials in mind. A variety
of investigations can lead to a likely diagnosis, and this can be
confirmed by enzyme/DNA assays if possible. A definitive diagnosis
is crucial if prospective prenatal counselling is to be considered
™ When all diagnoses fail, consider IEM.
When all else fails, it is difficult to make a diagnosis. When the patient
is oliguric, it is difficult to get a good quantity of urine for tests. Even
in IEM patients, when there is multiple end-organ failure, secondary
changes can confuse the metabolic picture, e.g. secondary lactic
acidosis follows any severe decompensation of the organic acidurias
and this can mask the underlying condition
DIAGNOSIS
The classification of IEM into two main groups based on the ‘size’ of the
offending molecule is a good start to the understanding of IEM and thus
their diagnoses:
™ For the ‘large’ molecule group, the prototypical condition is
the storage diseases. They have distinctive features, usually
multisystemic, predominantly neurological and the clinical
presentation is gradual and causes chronic clinical problems
™ The ‘small’ molecule group is more relevant to this discussion as they
present more acutely and with more devastating effects; they are
also more likely to present early in life. The diagnosis is crucial as such
patients usually die quickly. As they are mainly autosomal recessive
conditions, the proband usually is an unexpected presentation.
Endocrinology and Metabolism 127
The patients usually are relatively well and suddenly become sick.
The toxic metabolites are mainly ammonia, amino acids (glycine,
allo-isoleucine), acids (lactate, ketone) or organic acids, and sugars
(glucose, galactose)
Pointers to IEM
A high index of suspicion is needed:
™ Family history of other affected children, early neonatal or infant
deaths in siblings, siblings with neurological/mental retardation
™ Consanguinity in parents — Uncommon diseases occur commonly
within the affected families
™ Neonates who are unwell after a period of being apparently healthy
™ Urinary ketones in an acidotic neonate
™ Recurrent encephalopathic episodes
™ Persistent and recurrent acidosis
™ Recurrent clinical problems despite negative results
™ Thrombocytopaenia, leucopenia
INVESTIGATIONS
Consult a metabolic/genetic physician early for advice.
™ FBC
™ Biochemistry, electrolytes, creatinine, bicarbonate
™ BSL
™ Ammonia (lithium heparin tube)
™ Urine ketones (dipstix — Ward level)
™ Lactate (fluoride tube)
™ Pyruvate (fluoride tube)
™ Plasma amino acid (lithium heparin tube)
™ Urine organic acid profile
™ Blood spots/EDTA blood (before any blood transfusion)
™ Blood spot for expanded newborn screening
PRACTICAL POINTS
™ In the course of investigating a sick neonate, a plasma ammonia
level is helpful and should be considered. Results should be traced
urgently
™ Ammonia level of above 200μmol/L is significant. Any level between
100–200μmol/L may require a repeat sampling depending on the
patient’s condition
™ In the face of an elevated plasma ammonia level, check the anion
gap [(serum Na) - (serum Cl) - (serum HCO3)]. With a high anion gap
of 12, check the urine ketones. A positive urine ketones in a neonate
128 The Baby Bear Book Endocrinology and Metabolism 129

is pathognomonic of an organic aciduria. A normal anion gap EVALUATION

suggests hyperammonaemia, commonly a urea cycle defect While most cases of obesity are due to excessive caloric intake coupled
™ With a normal ammonia level and a non-acidotic baby who is with low physical activity, the initial evaluation of an obese child should
encephalopathic, consider non-ketotic hyperglycinaemia be geared towards excluding an endogenous cause of the problem.

TREATMENT Causes of Childhood and Adolescent Obesity

Aim of initial treatment: ™ Exogenous obesity
™ Reduce offending substrates and increase excretion/clearing of toxic ™ Endocrine:
metabolites ŠCushing Syndrome
™ Induce anabolism and overcome catabolism ŠGrowth hormone deficiency
ŠHyperinsulinaemia
In the acute situation: ŠHypothyroidism
™ Nil by mouth ™ Hypothalamic dysfunction:
™ IV hydration: about 5–10% more than the daily requirement Š CNS tumours
™ Note renal function; if impaired, consider dialysis Š Previous CNS surgery
™ IV 10% dextrose (some lactic acidosis may get worse) ™ Syndromes:
™ Carnitine: IV 100mg/kg/day in four divided doses (expensive; do not Š Prader-Willi Syndrome
waste!) for organic acidurias Š Down Syndrome
™ Sodium benzoate: IV 25mg/kg over one hour and then 250mg/kg Š Klinefelter’s Syndrome
over the next 24 hours (for hyperammonaemia) Š Laurence-Moon-Biedl Syndrome
™ Vitamin cofactors: Biotin/thiamine/cyanocobalamin Š Alstrom Syndrome
™ Dietary manipulation: Restriction of the offending food groups with Š Pseudohypoparathyroidism
enough caloric intake to induce anabolism (refer to the dietician ™ Psychological/psychiatric
early)
™ To induce anabolism, start oral feeding as early as the child can ™ A thorough history of the child with regards to birthweight,
tolerate feeds. If not possible, consider TPN antenatal history, family history, concomitant medical conditions and
medications (in particular oral steroids and traditional cures) should
be taken
™ The feeding habits and food preferences of the entire family are
important
OBESITY ™ Physical activities or the lack thereof should be looked into
™ Oligomenorrhea and/or amenorrhea are features of polycystic ovary
Obesity is an increasing problem worldwide among adults and children. disease
There is evidence that 80% of obese adolescents grow up to become ™ Hypertension, acne, hirsutism, truncal obesity and violaceous striae
obese adults at risk for the associated co-morbidities. may point towards Cushing Syndrome
™ Acanthosis nigricans identifies those with hyperinsulinism and
Obesity is defined as a body mass index above the 95th percentile for insulin resistance
age. Obesity may be due to exogenous or endogenous causes. While ™ Dysmorphism, neurological abnormalities like hypotonia and delayed
exogenous (simple) obesity is environmental and behavioural in origin, milestones help flag the children with hypothyroidism and syndromes
endogenous causes may be secondary to endocrine, hypothalamic, or ™ Hypogonadism is a frequent association in Prader-Willi, Laurence-
genetic disorders; as well as syndromes. Moon-Biedl and Alstrom Syndromes and other distinguishing
features should be sought
130 The Baby Bear Book Endocrinology and Metabolism 131

™ The affect of the child may provide clues to psychological problems.
Poor self-image and depression may lead to eating disorders. Bulimia
needs to be considered in the adolescent with dental erosions and
calluses on the digits
™ Children with simple obesity from over-nutrition are often tall
for their age with heights in or above the 50th percentile and
have a good growth velocity. On the other hand, children with an
underlying pathology tend to be short with falling centiles and
growth velocities
™ Further investigation may be required in suspected cases of
endogenous obesity. Hormone assays, genetic tests and MRI scans of
the head may be required depending on the clinical scenario
MANAGEMENT OF OBESITY
In the case of exogenous obesity, management is aimed towards
gradual weight loss and weight maintenance as well as close monitoring
for the associated complications of obesity.
identified early. Hypertension and dyslipidaemia may respond to weight
reduction.
Weight reduction is achieved by changes in diet and increased physical
activity through behaviour modification and family involvement. A
healthy lifestyle needs to be adopted by the entire family in order for
there to be long-term compliance. Realistic goals help in sustaining
the child’s weight loss and self-esteem. Parental support is paramount
while compassion and sensitivity for the patient go a long way towards
inculcating the right attitudes for the development of a healthy lifestyle.
BIBLIOGRAPHY
1. Barlow SE , Dietz WH. Obesity evaluation and treatment: Expert committee
recommendations. Pediatrics. 1998;102(3):e29.
2. Strauss RS. Childhood Obesity. Pediatr Clin North Am. 2002;49(1):175–201.
3. Brown WM, Sibille K, Phelps L, McFarlane KJ. Obesity in Children and Adolescents. Clin
Fam Pract. 2002;4(3):603–621.
4. Hintz RL. Management of Disorders of Size. In: Brook CGD, Hindmarsh PC, editors. Clinical
Pediatric Endocrinology. 4th ed. London: Blackwell Science; 2001. p. 124–139.

Complications associated with childhood/adolescent obesity:

™ CVS:
Š Arteriosclerosis
Š Hypertension THYROID CRISIS IN CHILDHOOD
Š Dyslipidemia
™ Neurologic: ™ A thyroid crisis (storm) is a life-threatening state of uncontrolled
Š Pseudotumor cerebri thyrotoxicosis characterised by exaggerated signs and symptoms
™ Endocrine: of hyperthyroidism associated with fever (in the absence of an
Š Type 2 DM infection) and an altered mental state
Š Polycystic ovary syndrome, irregular menses ™ It is very rare for a thyroid storm to present in childhood. If it
™ Gastrointestinal tract: occurs, it is usually precipitated by an intercurrent infection or less
Š Gallstones commonly, post-surgery or radioiodine treatment
Š Steatohepatitis ™ In thyrotoxicosis, the number of binding sites for catecholamines
™ Orthopedic problems: increases, so that cardiac and nerve tissues have increased sensitivity
Š Slipped capital femoral epiphyses to circulating catecholamines. In addition, there is decreased binding
Š Blount’s Disease (tibia vara) to TBG, leading to elevation of T3 and T4. In this setting, an acute
™ Respiratory: illness, infection or surgical stress can trigger an outpouring of
Š Sleep apnoea catecholamines precipitating the acute problem
Š Pickwickian Syndrome
Š Restrictive lung disease CLINICAL FEATURES
The most striking clinical diagnostic feature of a thyrotoxic crisis is
Additional cardiovascular risk factors like hypertension, hyperpyrexia out of proportion to other findings.
hypercholesterolaemia, hypertriglyceridaemia and DM need to be
132 The Baby Bear Book Endocrinology and Metabolism 133

Table 3-2: Features of uncomplicated thyrotoxicosis and thyroid storm.

Block Thyroid Hormone Secretion
Uncomplicated Thyrotoxicosis Thyroid Storm ™ Administer potassium iodide three to five drops at least one hour
™ Heat intolerance, diaphoresis ™ Hyperpyrexia, temperature in excess of after the first dose of thioamide, followed by three to five drops every
™ Sinus tachycardia, HR 100-140/min 41ºC eight to 12 hourly, or
™ Diarrhoea, hyperphagia with loss of ™ HR > 140/min, hypotension, atrial Administer IV potassium iodide 1mg as a slow infusion over 30
weight dysarrhythmias, CCF minutes, followed by 1mg every eight to 12 hourly, if unable to take
™ Anxiety, restlessness ™ Nausea, vomiting and diarrhoea, medication by mouth
hepatocellular dysfunction, jaundice With the above therapy, one can expect marked improvement within 24
™ Confusion, agitation, delirium, frank hours, otherwise consider:
psychosis, seizures, stupor
™ Ipodate (Oragrafin) or Iopanoic Acid (Telepaque) — Gallbladder
contrast agents that block peripheral conversion of T3 and T4
™ Plasmapheresis or exchange — Removes thyroid hormone
MANAGEMENT ™ Orally administered ion-exchange resin (20–30g/day as Colestipol-
Thyroid storm is a medical emergency best managed in an intensive HCl) can trap hormones in the intestine and prevent recirculation
care setting. Management comprises: ™ Dialysis
™ Supportive measures
™ Blocking peripheral action of thyroid hormone (β-blockade) CONGENITAL HYPOTHYROIDISM
™ Blocking thyroid hormone synthesis (Thioamide) Clinical Features
™ Blocking thyroid hormone secretion (Iodine) Detection is almost invariably by routine cord blood screening for Thyroid
Stimulating Hormone (TSH). In Singapore, there is a 99% chance of a
Supportive Measures newborn having congenital hypothyroidism if his cord TSH is above
™ Correct any dehydration using normal saline fluid boluses of 23mIU/L and a 99.9% chance if the cord TSH is above 50mIU/L. The
20ml/kg in severe dehydration or shock. Central venous pressure diagnosis is confirmed on repeat thyroid function testing on Day 3–5 of life.
monitoring is recommended in the presence of CCF
™ Control fever using paracetamol, tepid sponging and cooling Urgent evaluation is required (within 48 hours) and should include
mattresses. Avoid aspirin because it displaces thyroxine from protein additional history of maternal diet, drugs (thioamides, iodine-containing
binding medications) or autoimmune disease. The baby should be assessed for
™ Provide broad-spectrum antibiotic cover if sepsis cannot be excluded clinical signs of hypothyroidism, goitre, jaundice, growth parameters
™ Administer IV hydrocortisone 5mg/kg/day six hourly or prednisolone and signs of other congenital problems (small increase in risk of other
2mg/kg/day or dexamethasone 1mg six hourly, to cover for possible congenital problems, especially heart disease).
adrenal insufficiency and to further inhibit peripheral conversion of
T4 to T3. Investigation
Investigations should include thyroid function tests (TSH and free T4),
Block Peripheral Action of Thyroid Hormone plasma bilirubin if indicated and a diagnostic thyroid scan (usually
™ Administer IV propranolol 0.1mg/kg (max 2mg) over ten minutes technetium99). Maternal and baby thyroid antibodies measurement will
followed by IV propranolol 0.1mg/kg six hourly or PO propranolol be indicated where there is a history of maternal autoimmune thyroid
1mg/kg/day BD or TDS disease. A bone age X-ray of the knee is optional. Thyroid ultrasound
may also be indicated if there is no uptake on thyroid nuclear scan.
Block Thyroid Hormone Synthesis
™ Administer PO propylthiouracil at a loading dose of 150mg followed Therapy
by 5–10mg/kg/day six hourly, or Treatment with thyroxine should commence as soon as the diagnosis
Use rectal propylthiouracil if unable to take medication by mouth is confirmed (preferably the same day). Current common practice is to
134 The Baby Bear Book
use a starting thyroxine dose of 10μg/kg daily in a single daily dose.
The appropriate tablet dose is given by crushing and mixing with a
small quantity of water or milk; suspensions are not sufficiently stable.
Thyroid function tests (TFTs) are usually repeated at one to two weeks,
six weeks, three months and thereafter two to three monthly until three
years and then four monthly (more often if unstable). Dosage is adjusted
according to TFTs aiming to keep the free T4 concentration in the upper
third of the normal range and TSH suppressed into the normal range.
After the early infancy period, thyroxine doses are commonly in the
region of 100μg/m2 BSA per day.
In patients with suspected dyshormonogenesis, hearing tests should
be performed regularly for at least the first year of life. Developmental
progress should be monitored and formal assessment performed
if indicated. Despite early treatment, some evidence suggests that
children with severe congenital hypothyroidism may have a lower
IQ or exhibit mild psychomotor abnormalities, learning difficulties or
behavioural problems.
Other Advice
™ Limit intake of goitrogen-containing foods: Asparagus, broccoli,
brussel sprouts, cabbage, lettuce, peas, soya beans and spinach
™ Soy-based formula may decrease the absorption of thyroxine
™ Thyroxine is not stable as a suspension
CHILDHOOD THYROTOXICOSIS
AND GRAVES’ DISEASE
DEFINITIONS AND DIFFERENTIALS
Hyperthyroidism refers to thyroid gland over-activity leading to excess
thyroid hormone synthesis. Thyrotoxicosis refers to the clinical effects
of unbound thyroid hormone, whether or not the thyroid gland is
the primary source. Graves’ disease is the most common cause of
thyrotoxicosis in childhood.
Differentials include:
™ Toxic adenoma or toxic multi-nodular goitre
™ Hashitoxicosis (acute phase or Hashimoto’s thyroiditis)
Endocrinology and Metabolism 135
™ Subacute (viral) thyroiditis
™ Consider pituitary adenoma, pituitary resistance to T4
™ Consider McCune Albright Syndrome, Human Chorionic
Gonadotrophin (hCG)-secreting tumours, Jod-Basedow Effect
CLINICAL FEATURES
Symptoms and signs may include tachycardia, tremor, sweating,
restlessness, poor sleeping, weight loss, diarrhoea, eye signs (Graves’
disease), proximal muscle weakness or arrhythmia. Graves’ disease is
the most common cause, in which a diffuse goitre is usually present and
there may be eye signs. Severe thyrotoxicosis can cause life-threatening
thyrotoxic crisis or thyroid storm (see “Thyroid Crisis in Childhood” p. 131).
Early specialist referral is required for evaluation and management of
thyrotoxicosis. Refer to an ophthalmologist if eye signs are severe.
INVESTIGATION
Investigations should include TSH, free T4, free T3 and thyroid antibodies
(usually thyroid receptor stimulating antibodies (TRAb), thyroid
peroxidase antibodies (TPOAb) and thyoglobulin antibodies (TgAb)).
Thyroid imaging is not commonly indicated in typical Graves’ cases, but
is helpful in other situations.
THERAPY
Anti-thyroid drug treatment (carbimazole or propylthiouracil) is
common first-line treatment, often used in association with thyroxine
in a block-and-replace regimen. Serious side-effects of anti-thyroid
treatment are uncommon, but can include ahranulocytosis,
hepatotoxicity or aplastic anemia. Beta-blockers are often used as an
adjunct to treatment in the first few weeks for symptom control (caution
in asthmatics).
Radioactive iodine treatment is also a viable first-line option in mild
disease after initial control by anti-thyroid drugs, or for definitive
treatment if there is relapse after a course of anti-thyroid treatment.
Thyroidectomy surgery is rarely used as first-line therapy but may be
indicated as definitive therapy in a certain patients. Thyroid storm may
require additional measures such as iodine or steroid therapy and
general supportive measures (see “Thyroid Crisis in Childhood” p. 131).
Neonatal thyrotoxicosis arises from transplacental transfer of thyroid-
stimulating antibodies from mothers with current or previous Graves’
136 The Baby Bear Book
disease, although this occurs in only about 2% of at-risk babies. High
maternal Thyroid Stimulating Immunoglobulin (TSI) and suppressed
cord TSH are predictive. Measure thyroid function from Day 2 and twice
weekly until the course is clear; thyroxicosis will usually manifest by Day
9 unless there is an unusual balance with blocking antibodies. Untreated
neonatal thyroxicosis has high morbidity and mortality. Treatment is
with beta-blockers and anti-thyroid drugs (alone or in a block-and-
replace regimen with thyroxine). Additional measures such as iodine
or steroid treatment can be required in severe cases. Antibody levels
decline and treatment can usually be tapered and stopped by 12 weeks.
RECOGNISING 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 outcome of normal puberty is:
™ Normal adult height and
™ A sexually functional adult
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 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.
Endocrinology and Metabolism 137
™ Breast development is the first signal of normal female puberty:
Š This may commence as early as seven to eight years or as late as
13–14 years
™ Breast development is followed by height acceleration, body fat
distribution and vaginal discharge:
Š Vaginal discharge is initially random, then cyclical and precedes
menstruation
™ Menarche typically occurs two to three years after the onset of breast
development
™ Menarche is the penultimate event of normal puberty
™ The final event of normal puberty is epiphyseal fusion and occurs
one to two years after menarche
The appearance of pubic and/or axillary hair, mediated by adrenal and
ovarian androgens, is dependent on genetic factors, race, ethnicity as
well as body mass, especially fat mass.
NORMAL MALE PUBERTY
The physical changes of normal male puberty are primarily the result
of rising levels of testicular androgens.
™ The attainment of a testicular volume of 4ml represents the onset of
normal male puberty:
Š This may occur as early as eight to nine years or as late as 14–15
years
™ 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.
138 The Baby Bear Book Endocrinology and Metabolism 139

3. Auchus RJ, Rainey WE. Adrenarche: Physiology, biochemistry and human disease. Clin
Precocious sexual hair development occurs when axillary/pubic hair Endocrinol. 2004;60(3):288–296.
develops before breast development in females and before a testicular 4. Gluckman PD, Hanson MA. Evolution, development and timing of puberty. Trends
Endocrinol Metab. 2006;17(1):7–12.
volume of 4mls in males. These children must be referred for evaluation. 5. Ibáñez L, Jiménez R, de Zegher F. Early puberty-menarche after precocious pubarche:
Relation to prenatal growth. Pediatrics. 2006;117(1):117–121.
GUIDELINES FOR REFERRAL TO A PAEDIATRIC
ENDOCRINOLOGIST
Refer Disorders of TIMING
Note: Early normal puberty is not precocious puberty and care should
be taken not to ‘medicalise’ an otherwise normal condition.
™ Girls with breast development before the age of seven years
™ Girls with both breast development and pubic/axillary hair
development before the age of eight years
™ Girls with no evidence of breast development by the age of 13 years
™ Boys with testicular volumes of ≥ 4ml before the age of nine years
™ Boys with testicular volumes of ≤ 4ml by the age of 14 years

Refer Disorders of SEQUENCE:

Note: Pseudo-precocious puberty is usually not normal and needs to be
evaluated.
™ 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 whose testicular volumes
are ≤ 4ml

Refer Disorders of TEMPO:

Note: The typical duration from onset of breast development to
menstruation is two-and-a-half years (normal range two to three 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.
™ Girls with breast development who fail to menstruate by the age of
15 years
™ Girls who start breast development when they are ≤ 120cm tall

BIBLIOGRAPHY:
1. Abbassi V. Growth and normal puberty. Pediatrics. 1998;102(2):507–511.
2. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. The timing
of normal puberty and the age limits of sexual precocity: Variations around the world,
secular trends and changes after migration. Endocrine Reviews. 2003;24(5):668–693.
140 Gastroenterology 141

Inflammatory diarrhoea:

GASTROENTEROLOGY Result of inflammatory changes that occur in bacterial

gastroenteritis, inflammatory bowel disease or allergic colitis
Loss of intestinal surface area:
Decreased intestinal surface area for digestion and absorption
CHRONIC DIARRHOEA resulting in diarrhoea is seen in short bowel syndrome from
various causes, and in coeliac disease
Alteration in intestinal motility:
DEFINITION Hypomotility allows for bacterial over-growth and diarrhoea.
Diarrhoea that has persisted for more than two weeks. Diarrhoea is Malnutrition and pseudo-obstruction syndromes are some of the
defined as increased stool water content as manifested by increased causes of intestinal hypomotility
stool frequency, fluidity or volume. This would result in stool Mutational defects in transport protein:
output of greater than 10g/kg/24hrs or more than 200g/24hrs. For These defects result in secretory diarrhoea that presents at birth
epidemiological studies, more than three stools/24hrs indicates the
presence of diarrhoea. CAUSES OF CHRONIC DIARRHOEA
Gastrointestinal infection:
MECHANISMS LEADING TO CHRONIC DIARRHOEA Bacterial — Salmonella, campylobacter, enteroaggressive E. coli,
Osmotic diarrhoea: C. difficile
Caused by presence of non-absorbable solutes in the Parasitic — Giardia, cryptosporidium, amoeba
gastrointestinal tract Viral — Rotavirus, adenovirus
Commonly the result of mal-absorption of carbohydrates. The Diet:
colonic bacteria ferment the non-absorbed carbohydrates to Lactose intolerance
short-chain fatty acids generating an osmotic load causing water Sorbitol or excessive fructose ingestion
to be secreted into the lumen Extra-intestinal infection
These acids results in acidic stool with a pH of < 5.5, and perianal Enteropathies:
excoriation Cow’s milk allergy or other food allergy
The mal-absorbed sugars can usually be detected in the stool as a Immunodeficiency — Including primary, secondary and Human
> 0.5% concentration of reducing substances Immunodeficiency Virus (HIV)
Stool osmotic gap is greater than 100mmol/L; calculate using the Inflammatory bowel disease
formula: 290 - 2 x [(Na+) + (K+)] Coeliac disease
Diarrhoea usually settles within 24–48 hours of fasting Malnutrition
Secretory diarrhoea: Lymphangiectasia
Caused by the activation of intracellular mediators such as Intraluminal disorders:
Cyclic Adenosine Monophosphate (cAMP), Cyclic Guanosine Bile salt deficiency or malabsorption e.g. chronic cholestasis
Monophosphate (cGMP) or calcium, which stimulate chloride Pancreatic insufficiency
secretion and inhibit neutral coupled sodium chloride absorption Bacterial over-growth
Examples include cholera, enterotoxigenic Escherichia coli (E. coli), Anatomic disorders:
C. difficile and rarely vasoactive peptide secreting tumours Short gut
Diarrhoea tends to be watery and of high volume Blind loop
Stool sodium content is more than 70mmol/L Congenital disorders:
Diarrhoea continues with fasting Microvillous inclusion disease
Congenital chloride or sodium diarrhoea
142 The Baby Bear Book Gastroenterology 143

Glucose-galactose mal-absorption General:

Deficiency of disaccharidases Well or sick
Abetalipoproteinaemia Wasting
Motility disorders: Pallor
Pseudo-obstruction Jaundice
After repair of Hirschsprung’s Disease Oedema
Vasculitis: Digital clubbing
SLE Abdominal distension:
Henoch-Schönlein Purpura (HSP) Gaseous
Tumours: Ascites
Vasoactive intestinal peptide producing tumour Organomegaly
Lymphoma Abdominal mass: Inflammatory, tumour or faeces
Drug-induced: Inspection of perineum to exclude fissure, fistula and prolapse
Antibiotics Examination of stool:
Laxatives Watery:
Chemotherapy Osmotic diarrhoea from carbohydrate mal-absorption
Chronic non-specific diarrhoea Disaccharidase deficiency
Monosaccharide transport defect e.g. glucose-galactose
CLINICAL EVALUATION mal-absorption
Careful History Transport overload: High-sugar drinks, excessive fruit juice
Confirm presence of chronic diarrhoea or sorbitol
Description of stools: Frequency, amount, colour, consistency (such Secretory diarrhoea:
as watery, pale and bulky), smell and the presence of blood or Bacterial toxin e.g. C. difficile
mucous Deconjugated bile salts
Age of onset — Aggressive evaluation required when presenting in Secretory tumour
the early neonatal period Congenital transport defects e.g. chloridorrhoea (rare)
Relation to diet or dietary changes Blood and mucous present:
History of surgery Infective colitis
Associated symptoms: Allergic colitis
Weight — If FTT is present, consider: Inflammatory bowel disease
Poor intake from anorexia or iatrogenic restriction
Mal-absorption Investigations
Vomiting Stool:
Thirst pH and reducing substances
Abdominal pain If sucrose is suspected, hydrolyse stool with hydrochloric acid
Recurrent infections Microscopy:
Family history Red and white blood cells
Fat globules: Present when there is inadequate lipase or bile salts
Detailed Physical Examination Fatty acid crystals: When there is damaged mucosa from
This would include: protein hypersensitivity, coeliac disease or lymphatic disease
Anthropometric measurement and nutritional assessment Ova, cysts or parasites
Culture and C. difficile toxin
144 The Baby Bear Book Gastroenterology 145

Routine blood tests: Cow’s milk allergy:

FBC and ESR Cow’s milk allergy results in enteropathy and mal-absorption
Serum U/E/Cr and glucose Symptoms may persist for weeks upon elimination of milk
Serum albumin and total protein products
Urine microscopy and culture Young babies with suspected cow’s milk allergy require urgent
Investigations to detect specific disease: nutritional support while being investigated. If the baby does
Immune status not require parenteral feeding, he should be fed with a protein-
Evaluate anatomy by barium meal and follow through, or barium hydrolysate milk such as Pregestimil™ or Alfare™. Amino-acid-
enema based formulae such as Neocate™ can be introduced if protein
Evaluate intestinal morphology via endoscopy and intestinal hydrolysate is not tolerated. A formula based upon comminuted
biopsy chicken with supplements should be considered when all milk
Study for secretory diarrhoea by estimating stool electrolytes and formulae fail
osmolarity Chronic non-specific diarrhoea:
Evaluate for secretory tumour with urine Vanillylmandelic Acid Children with this condition usually pass large loose stools with
(VMA) and serum Vasoactive Intestinal Polypeptide (VIP) undigested food particles
Study intestinal absorption with D-xylose absorption test, 72 Growth parameters are normal
hours faecal fat, lactose breath test and nitrogen balance No associated underlying pathology can be elicited
Detect bacterial over-growth with duodenal fluid culture, breath There may be high intake of fruit juice or low dietary fat intake
hydrogen test Short bowel syndrome
Antigliadin and antiendomysial antibodies to screen for coeliac
disease PRACTICAL APPROACH
Estimate stool protein loss through stool alpha-1-antitrypsin Confirm presence of chronic diarrhoea
clearance Be aggressive when onset is during early neonatal period or when
Sweat test there is weight loss
Serum zinc level Consider possible diagnosis after a carefully taken history and
thorough physical and stool examination
COMMON CAUSES OF CHRONIC DIARRHOEA IN Investigate systematically to confirm diagnosis
SINGAPORE Treat the cause when feasible. Parenteral nutrition and dietary
Post-infectious diarrhoea: manipulation can reduce morbidity and mortality
Secondary lactose intolerance:
Absorption of the lactose in milk products is impaired BIBLIOGRAPHY
1. Kerry KR, Anderson CM. A ward test for sugars in faeces. Lancet. 1963;1(7340):981.
because of secondary lactose deficiency. Unabsorbed lactose
is fermented by the colonic bacteria to gases (hydrogen,
methane and carbon dioxide) and acids (lactic, acetic,
proprionic or butyric)
The watery, acidic stool causes perineal excoriation. There
is also gaseous abdominal distension, discomfort and FAILURE TO THRIVE (FTT)
borborygmus
Diagnosis can be confirmed by stool pH and stool Clinitest FTT is a symptom describing a disproportionate failure of weight gain
Treatment consists of lactose-free diet until recovery of the in infants and young children from insufficient caloric intake because of
intestinal lactase not eating, not being offered or not retaining.
Secondary cow’s milk allergy
146 The Baby Bear Book Gastroenterology 147

A child, usually under the age of three years, is said to have FTT in the Gastroesophageal reflux
presence of one of the following: Food allergy
Growth deceleration to less than the third percentile Mal-absorption
Weight loss by two or more major percentiles over three to six Hirschsprung’s Disease
months Inflammatory bowel disease
Weight less than 80% mean weight for age Chronic liver disease
Persistence of deceleration from established pattern Cardiac disease:
Congenital
AETIOLOGY Acquired
Causes of FTT can be classified under organic, where a major disease Infection:
exists, or non-organic, where FTT arises from an aberrant caregiver-child Chronic recurrent infections
interaction or environmental factors. Although some children have a single Human Immunodeficiency virus
cause for their growth failure, in others both medical and environmental TB
factors contribute to their failing to thrive. It is important to recognise all Respiratory disorders:
the causative factors to allow for the best treatment for the child. Chronic lung disease
Upper airway obstruction
Psycho-social factors: Genetic disorders:
Emotional deprivation Chromosomal abnormalities
Depressed caregiver Genetic syndromes e.g. Russell-Silver Syndrome
Withholding of food: Renal disorders:
Intentional Chronic renal failure
Unintentional Renal tabular acidosis
Inadequate volume: Endocrine disorders:
Ignorance DM or DI
Difficult feeder with feeding problems Hypopituitarism
Inappropriate food for age: Hypo- or hyperthyroidism
Low-cholesterol diet Metabolic diseases
Excessive fruit juice Hematologic and oncologic diseases
Vegetarian diet Toxic substances
Inappropriate preparation of formula Orthopaedic causes
Normal variants:
Familial short stature CLINICAL EVALUATION
Constitutional growth delay Comprehensive history:
Antenatal factors, resulting in Small for Gestational Age (SGA) Medical history:
Neurological problems: When did FTT begin?
Cerebral palsy Symptoms pointing to medical illness
Mental retardation Past illness, hospitalisation, medication
Structural abnormalities Growth history and pattern
Degenerative diseases Activity level
Diencephalic syndrome Neonatal history:
Gastrointestinal disorders: Gestational age
Hare lip and/or cleft palate Birth weight and presence of SGA
148 The Baby Bear Book Gastroenterology 149

Mode of delivery, Apgar scores and complications

Antenatal history
Developmental history
Dietary history:
Difficulty with sucking or swallowing
Quantity and quality of food consumption
Parental restrictions or misconceptions
Dietary recall
Prospective dietary diary of intake for three days
Family and social history:
Height and weight of parents and siblings
Heritable disease, mental illness, alcohol or drug abuse
Maternal age Fig. 4.1: FTT grouped into three major anthropometric categories.
Caregiver-child interaction
Family composition, financial status, support and stress
Thorough examination: The diagnosis can be simplified by grouping FTT into three major
Serial measurements of height, weight, upper and lower segment anthropometric categories (diagrams extracted from Roy, Silverman &
Accurate anthropometrics Alagille 1995):
Search for signs of organic disease Type I Retardation of weight with near-normal or slowly decelerating
Presence of dysmorphic features height and head growth.
Look for clinical manifestations of malnutrition This pattern is typical of under-nutrition from any aetiology.
Detect evidence of abuse or neglect Type II Near-proportional retardation of height and weight, and normal
Developmental screening head growth.
Observe child’s activity and behaviour This pattern is typical of:
Observe feeding and non-feeding caregiver-child interaction Constitutional growth delay
Investigations: Genetic short stature
Conduct simple screening tests and minimise special investigations, Endocrinopathies
except for those indicated by findings on history and examination: Bony dystrophies
FBC and ESR Bone age estimation is useful in this category:
Urine microscopy and culture Bone age equal to chronological age:
Stool examination Genetic short statue
Serum protein, albumin, urea and electrolytes Bony dystrophies
Bone age, if indicated Bone age less than chronological age:
Special tests to detect specific disease Bone age approximates that of height age —
Constitutional growth delay
CLINICAL APPROACH Bone age less than height age — Endocrinopathies
Attempt to make a positive diagnosis for the underlying causative Type III Concomitant retardation of weight, height and head growth
condition. This can be achieved by evaluating the child, the family and This pattern is typical of:
the environment for the presence of risk factors in both organic and In-utero and perinatal insults
non-organic aspects simultaneously. Chromosomal aberrations
CNS abnormalities
Rarely familial
150 The Baby Bear Book Gastroenterology 151

History and physical examination MANAGEMENT

Successful management involves a multi-disciplinary team approach
and addressing the following:
Organic disease if present
No obvious organic disease Organic disease Diet and eating pattern
Developmental intervention
Education in nutrition and child’s development
Counselling and outpatient Confirm diagnosis with Psycho-social support
dietary treatment appropriate investigation
When to hospitalise:
Severe malnutrition
Medically unstable with associated organic disease or dehydration
Good response Poor response Treat High risk of child abuse
Failure of outpatient therapy
Need to confirm diagnosis and observe caregiver-child interaction
Replace milk/milk substitute etc
Extreme parenteral anxiety

Continue treatment
till growth normalised
Primary physician
PROGNOSIS
Good response Poor response In FTT, not only growth is compromised; emotional, intellectual and
developmental deficits may also occur. The ultimate aim is to institute
prompt treatment to minimise permanent effect on the physical and
Consider further investigation mental health, educational deficiencies and personality disorders.
BIBLIOGRAPHY
Negative Positive 1. Roy CC, Silverman A, Alagille D. Pediatric clinical gastroenterology. 4th ed. Saint Louis:
Mosby; 1995. p. 4–8.

Hospitalisation for enteral or parenteral feeding

Good response
MANAGEMENT OF
Wean to oral feeding after three to six months
ACUTE GASTROENTERITIS

DEFINITION
Successful Not successful Acute gastroenteritis is defined as a diarrhoeal disease of rapid onset,
of less than ten days duration, with or without accompanying symptoms
and signs, such as nausea, vomiting, fever or abdominal pain.

Gastrostomy Continuation of ongoing nasogastric feed

Most patients meeting the criteria of this parameter will have viral
or self-limiting bacterial diarrhoea. Occasionally, children can have
Fig. 4.2: Approach to a child with FTT.
152 The Baby Bear Book Gastroenterology 153

bacterial dysentery or rarely, protozoal disease with sepsis and may

Table 4-1: Evaluation of dehydration.
need specific antimicrobial therapy.
Mild
Minimal or no Moderate Severe
Fig. 4.3 (overleaf ) shows the suggested gastroenteristis pathway. The key dehydration
Symptoms/ dehydration dehydration dehydration
issues to be addressed are: (3–5% loss of
signs (<3% loss of (6–9% loss of (>9% loss of
loss of body
Rehydration body weight) body weight) body weight)
weight)
Correction of electrolyte abnormalities
Mental status Well, alert Normal Normal to Apathetic,
Refeeding
listless lethargic,
Medications unconscious
Thirst Drinks Slightly Moderately Very thirsty or
REHYDRATION normally or increased increased, too lethargic
Evaluation of Dehydration may refuse thirsty, eager to indicate or
To evaluate if the patient is dehydrated, use Table 4-1. liquids to drink drink
Capillary refill time — Helpful adjunctive measure to determine the Heart rate Normal Normal Normal to Tachycardia,
degree of dehydration. Although refill can be affected by fever, ambient increased with
temperature and age, delayed capillary refill (> two seconds) should be bradycardia in
considered a sign of significant dehydration until proven otherwise severe cases
If an accurate recent weight is available, determination of the Quality of Normal Normal Normal Weak, thready
percentage of weight lost is an objective measure of dehydration pulses to slightly Impalpable
If unsure of the category of dehydration into which a patient falls, reduced
therapy for the more severe category should be used Blood Normal Normal Normal Normal
pressure Wide pulse
pressure
Include: Reduced
Age ≥ three months Breathing Normal Normal Normal Deep
Acute diarrhoea ± vomiting to slightly
Exclude: Not pathway- increased
Toxic appearance or ICU eligible. Treat
required Pathway-eligible? according to Eyes Normal Normal Slightly Deeply sunken
Diarrhoea > seven days patient-specific sunken
Immunocompromised clinical condition Tears Present Present Decreased Absent
Other major co-morbidities Mouth and Moist Slightly dry Dry Parched
e.g. short bowel syndrome, tongue
ileostomies, congenital
Skin turgor Instant recoil Instant recoil Recoil in < Recoil in >two
heart disease, renal disease
two seconds seconds
Vomiting with no Clinical assessment
accompanying diarrhoea for dehydration Capillary refill Normal Normal Prolonged > Prolonged
Bilious vomiting two seconds
FTT Extremities Warm Warm Cool Cold, mottled,
Chronic metabolic disorders cyanotic
Urine output Normal Slightly <1ml/kg/hr Minimal
Use dehydration evaluation list decreased
(see Table 4-1 next page)
Fig. 4.3: Suggested gastroenterology pathway.
154 The Baby Bear Book Gastroenterology 155

Mode of Therapy If the patient does not respond to rapid bolus rehydration,
Oral Rehydration Therapy (ORT) consider the possibility of an underlying disorder such as septic
ORT is the preferred treatment of fluid and electrolyte loss caused by shock, toxic shock syndrome, myocarditis, cardiomyopathy or
diarrhoea in children with mild to moderate dehydration pericarditis. Use of colloids and inotropes should be considered
A glucose-electrolyte solution with sodium concentration of IV therapy (patient not in shock):
45–50mmol/L and osmolarity < 250mmol/L is recommended See departmental fluid guidelines
Oral Rehydration Salt (ORS) has no effect on stool volume or the ORT:
duration of diarrhoea, unlike cereal-based solutions When the patient’s condition has stabilised and mental status is
Practical tips: satisfactory, ORT may be instituted, with the IV line kept in place
Administer in small amounts initially to allow the child to get until IV therapy is no longer needed
accustomed to the taste
Add flavours to make the solution more palatable Mild to Moderate Dehydration (3–9%)
Freeze the solution into an ice-pop form Trial of ORT
Composition of available ORS: Failed trial of ORT — Proceed to IV rehydration according to
Per Litre Pedialyte departmental guidelines
Sodium (mmol) 45
Potassium (mmol) 20
ORS 25ml/kg over two hours
Chloride (mmol) 35
Citrate (mmol) 30
Dextrose (g) 25 Good intake No
Osmolarity 250 and retention Failed trial

Intravenous (IV) Therapy

ORS 25ml/kg over two hours
Required in a child who is:
Severely dehydrated and in a state of shock or near shock
Moderately dehydrated and cannot retain oral liquids because of Successful trial
persistent vomiting
Fig. 4.4: ORT of recommended volume of 50ml/kg over four hours.
Unconscious or has ileus
Child may show considerable improvement after a period of IV therapy
A child who is not severely dehydrated may go home and complete Table 4-2: Volume of ORS to be given per hour (Body weight (kg) / 5)
rehydration orally, if proper follow-up is available, after receiving IV
Body Weight (kg) Number of satchets (one satchet = 62.5ml)
fluids for several hours in an emergency department or a similar facility
5 1
Recommendation for Rehydration 7.5 1.5
Severe Dehydration (10%) 10 2
Severe dehydration causes shock or a near-shock condition and is a 12.5 2.5
medical emergency 15 3
Resuscitation: 17.5 3.5
For shock: IV bolus 20ml/kg crystalloid (normal saline, Hartmann’s
20 4
solution) over 15 minutes
22.5 4.5
≥25 5
156 The Baby Bear Book Gastroenterology 157

Dehydration status PAEDIATRIC INTRAVENOUS FLUIDS GUIDELINES

This guideline is applicable to paediatric patients older than 28 days
Maintenance fluids per day should be calculated using the ‘100-50-25’
rule (also known as the ‘4-2-1’ rule, where the calculation is per hour
None Mild/moderate Severe rather than per day)
100ml/kg/day for the first 10kg = 4ml/kg/hr for the first 10kg
50ml/kg/day for the second 10kg = 2ml/kg/hr for the second 10kg
Assess risk of 25ml/kg/day for every kg thereafter = 1ml/kg/hr for every kg thereafter
dehydration
Treat emergently: Table 4-3: Maintenance fluids per day.
IV bolus Weight (kg) ml/day ml/hour Weight (kg) ml/day ml/hour
Low risk: High risk: normal saline
U/E/Cr 3 300 12 14 1,200 48
Age ≥ six months Age < six months
Vomits ≤ four/day Vomit > four/day 4 400 16 16 1,300 52
Stools ≤ eight/day Stools > eight/day 5 500 20 20 1,500 60
6 600 24 30 1,750 70
7 700 28 40 2,000 80
Continue with child’s successful Trial of ORS failed Rehydrate with 8 800 32 50 2,250 90
preferred usual and (see Fig. 4.4 intravenous fluids 10 1,000 40 60 2,500 100
age-appropriate previous page) (see “Paediatric
diet (if vomiting, Intravenous Fluids 12 1,100 44 70 2,500 100
offer frequent small Guidelines” next page)
feedings)
There are a number of clinical conditions that will affect the baseline
infusion rate:
Consider increasing the infusion rate if:
Fever, hyperventilation, ongoing losses (diarrhoea, polyuria)
Good Consider decreasing the infusion rate if:
hydration No
Hypothermia, oliguira, anuria, inactivity, fluid retention, excessive
maintained?
ADH (pneumonia, meningitis)
If the child is dehydrated, water deficit is calculated by multiplying
Yes body weight by percentage of dehydration to obtain the deficit in litres
Risk of evidence of
Yes e.g. 10kg child, 3% dehydration, 10 x 0.03 = 0.3 litres = 300ml deficit
serious bacterial infection Antibiotics
(see Fig. 4.6 p. 161 and (see Table 4-4 overleaf for the fluid deficits in mls)
Table 4-5 p. 162) The fluid used to rehydrate is the same as the fluid used to provide
the maintenance infusion. Rehydration should be carried out evenly
over at least 24 hours. If the dehydration is 10% or greater, then
No rehydration should be carried out over a longer period.
e.g. 15kg child, 5% dehydration
Consider probiotics Maintenance 1,250ml/day
Discharge education
No other medication Deficit 750mls
Therefore prescribe 2,000mls/day (80mls/hr) for the first 24
Fig. 4.5: Suggested treatment pathway once dehydration status is established. hours, 1,250mls/day thereafter.
158 The Baby Bear Book Gastroenterology 159

Table 4-4: Fluid deficit in mls.

Nevertheless, any patient admitted to CICU or HD with a sodium
Dehydration (%) → 3 5 10 15 <130 or >150 should be reported to a member of the workgroup
3kg 90 150 300 450 for audit and follow-up. Other patients, where there is a concern by
5kg 150 250 500 750 the treating team that an adverse serum sodium or water balance
10kg 300 500 1,000 1,500 may be the result of this guideline should also be reported
15kg 450 750 1,500 2,250
ELECTROLYTE DERANGEMENTS
20kg 600 1,000 2,000 3,000
Most episodes of dehydration caused by diarrhoea are isonatraemic
30kg 900 1,500 3,000 4,500 and serum electrolytes measurements are not mandatory
40kg 1,200 2,000 4,000 6,000 Serum electrolyte levels should be measured in moderately
50kg 1,500 2,500 5,000 7,500 dehydrated children whose histories or physical findings are
inconsistent with straightforward diarrhoeal episodes and in all
severely dehydrated children
e.g. 30kg child, 10% dehydration In children receiving IV therapy, electrolyte levels should be
Maintenance 1,750ml/day measured initially and as therapy progresses
Deficit 3,000mls
Plan to correct the deficit over 48 hours. Hypokalaemia
Therefore prescribe 3,250ml/day (1,500+1,750) (135ml/hr) for Maintenance: 2mmol/kg/24hrs (1mmol = 1ml KCl 7.45%)
the first 48 hours, followed by maintenance of 1,750ml/day Replacement: [0.6 x (Deficit) x (Body weight in kg)]mmol to be given
thereafter over 24 hours
Fluid composition: Cautions:
The standard fluids available for House Officers to prescribe will be: IV fluids should not contain more than 40mmol/L of potassium
Dextrose 5% + 0.45% saline Maximal rate of potassium infusion should not exceed 0.4mmol/
Dextrose 5% + 0.9% saline (Use as guided by senior physician, kg/hr
not recommended if < 10kg, or < one year) KCl 7.45% should NEVER be given undiluted
These two preparations will also be available with pre-added KCL Potassium should only be given when there is urine output
to a concentration of 10mmol per 500ml
0.9% Normal saline can be prescribed by junior staff for volume Hyperkalaemia
resuscitation in aliquots of 10–20ml/kg ECG monitoring during corrective measures
Dextrose 10% can be prescribed by junior staff for the treatment of IV 10% calcium gluconate: 0.5–2.0ml/kg over two to four minutes.
hypoglycaemia, dose 5ml/kg Effective for 30–60 minutes
Other fluids available for more senior staff to prescribe: IV sodium bicarbonate: 1–2mmol/kg.
Dextrose 5% Effective for one to two hours
Dextrose 10% IV insulin by slow infusion with glucose 0.5–1g/kg.
Normal Saline 0.9% Dosage of insulin: one unit to every 4g of glucose
Hartmann’s and Ringer’s Resonium A: 1g/kg/24hrs in divided doses, orally or rectally
Audit and quality assurance: Peritoneal dialysis
These guidelines represent a change in recommendations locally,
although have become standard in other institutions for some Hyponatraemia (Na < 130mmol/L)
time Maintenance: 2mmol/kg/24hrs (1mmol = 0.29ml NaCl 20%)
Replacement: [0.6 x (Deficit) x (Body weight in kg)]mmol over 24–48 hours
Hyponatraemic seizure: IV bolus 3–5ml/kg of 3% NaCl
160 The Baby Bear Book Gastroenterology 161

Hypernatraemia (Na > 150mmol/L) Investigations

If in shock: 10–20ml/kg of plasma or normal saline Routine stool cultures and rotavirus are not recommended as the
Water deficit: {0.6 x [(Current sodium / 140) - 1] x (Body weight in kg)}L results do not influence therapy if the child is well
Correct water deficit over 48–72 hours Perform stool cultures if:
Avoid rapid correction as this may lead to cerebral oedema and fits < three months
Serum sodium should decrease by 1mmol/hr or less Immunocompromised
Septic/toxic
REFEEDING Bloody stools
Children who have diarrhoea and are not dehydrated should Foreign travel
continue to be fed age-appropriate diets Specific community outbreak
Children who require rehydration should be fed age-appropriate Diarrhoea > five days
diets as soon as they have been rehydrated
When used with glucose-electrolyte ORT, early feeding of age-
appropriate diet can reduce stool output and duration of diarrhoea.
Early feeding has the added benefit of improved nutrition Special group (not
included in pathway:
Yes
Milk < three months
Breastfeeding should be resumed Immunocomprised
Septic/toxic
Eighty percent or more of children with acute diarrhoea can tolerate
full-strength milk safely
Lactose-containing solutions seem to be tolerated better when
combined with complex carbohydrates in weaned children No

Food
Children who are on regular diet may resume eating, although Bloody stools
certain foods are tolerated better than others Foreign travel
Yes
Recommended foods include complex carbohydrates (rice, wheat, Specific community
potatoes, bread, and cereals), lean meats, yogurt, fruits and vegetables outbreak
Diarrhoea > five days
Avoid fatty foods and foods high in simple sugars (e.g. juices and soft
drinks) Stool culture and treat
Supplement feeding with an oral electrolyte solution, 10ml/kg for specific pathogen when
each diarrhoeal stool and the estimated amount vomited for each No indicated
emesis

MEDICATIONS Supportive care

As a general rule, pharmacologic agents should not be used to treat
acute diarrhoea
Many of the agents have systemic toxic effects that are augmented See Table 4-5 overleaf
in infants and children or in the presence of diarrhoeal disease. Most
are not approved for children < two or three years
Probiotics may improve the outcome of acute gastroenteritis Fig. 4.6: Decision tool for obtaining stool culture.
162 The Baby Bear Book Gastroenterology 163

Table 4-5: Treatment for specific pathogen when indicated. Organism Indication for Preferred Alternative Comments
Organism Indication for Preferred Alternative Comments Antibiotic Use Agent Agent(s)
Antibiotic Use Agent Agent(s) Shigella PO Norfloxacin#
Salmonella Bacteraemia IV Ampicillin PO Self-limiting (cont’d) 800mg divided
(non-typhoidal) Invasive disease 200mg/kg/ Cotrimoxazole* disease 12 hourly for
Those with risk day (max 4g) TMP 10mg/ three to five days
factor(s) for invasive divided six kg/day (max Antibiotics
disease, including: hourly for up to 320mg) plus SMX may prolong PO Ciprofloxacin#
Age < three 14 days 50mg/kg/day Salmonella 1g divided 12
months (max 1,600mg) carriage. hourly for three
Functional or (consider divided 12 hourly Increasing risk to five days
anatomical asplenia stepping down for 14 days of bacteriologic Vibrio cholerae Persistence of PO PO Cotrimoxazole Use of
Malignancy from IV to PO relapse (cholera) diarrhoea Tetracycline** TMP 10mg/ tetracycline is
AIDS antibiotics IV Ceftriaxone Decrease fluid 50mg/kg/ kg/day (max contraindicated
Chronic after two to 75–100mg/kg/ requirements day (max 2g) 320mg) plus SMX in children
gastrointestinal three days day (max 4g) Disease control divided six 50mg/kg/day younger than
tract disease afebrile and no once or twice a hourly for three (max 1600mg) eight years of
Hemoglobinopathy complications) day for up to 14 days divided 12 hourly age. However
Immunosuppressive days for three days in severe cases,
therapy or the benefits
IV Cefotaxime may outweigh
200mg/kg/day PO the risk of
(max 4g) divided Doxycyline** staining the
six hourly for up 6mg/kg (max developing
to 14 days 300mg) as a teeth.
E. coli No antibiotics except IV Ampicillin PO Antibiotics single dose
for severe cases 200mg/kg/ Cotrimoxazole* may increase Campulobacter Persistence of PO Twenty percent
day (max 4g) TMP 10mg/ likelihood of jejuni diarrhoea Erythromycin of cases have
divided six kg/day (max haemolytic 50mg/kg/ a relapsing,
hourly for up to 320mg) plus SMX uraemic day (max 2g) prolonged or
seven days 50mg/kg/day syndrome in divided five severe illness.
(max 1,600mg) cases of E. coli hourly for seven Antibiotics
divided 12 hourly (O157:H7) to ten days shorten the
for seven days infections duration of
Shigella Disease control PO or IV PO or IV Treatment is excretion of
Persistence of Cotrimoxazole* Ampicillin based on local C. jejuni from
diarrhoea TMP 10mg/ 100mg/kg/day susceptibilities the faeces,
Severe disease kg/day (max (max 4g) divided but it does
320mg) plus six hourly for not shorten
SMX 50mg/ five days IV or the duration
kg/day (max IM Ceftriaxone of diarrhoea,
1600mg) 50mg/kg/day unless given
divided 12 (max 4g) once a within four
hourly for five day for up to five days
days days of illness
164 The Baby Bear Book Gastroenterology 165

Organism Indication for Preferred Alternative Comments BIBLIOGRAPHY

Antibiotic Use Agent Agent(s) 1. American Academy of Pediatrics, Provisional Committee on Quality Improvement,
Subcommittee on Acute Gastroenteritis. Practice guideline: The management of acute
Yersinia Bacteraemia Third- gastroenteritis in young children. Pediatrics. 1996;97(3):424–435.
enterocolitica Invasive disease generation 2. Sandhu BK; European Society of Pediatric Gastroenterology Hepatology Nutrition
Immunosuppressed cephalosporin (ESPGHAN ) Working Group on Acute Diarrhoea. Practical guidelines for the management
of gastroenteritis in children. J Pediatr Gastroenterol Nutr. 2001;33(Suppl 2):S36-S39.
host in combination 3. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U, Baumer H. An evidence-
with an and consensus-based guideline for acute diarrhoea management. Arch Dis Child.
aminoglycoside 2001;85(2):132–142.
4. Guarino A, Albano F, Guandalini S; Working Group on Acute Gastroenteritis. Oral
Amoeba Disease control PO PO Tinidazole Treatment is rehydration: Toward a real solution. J Pediatr Gastroenterol Nutr. 2001;33(Suppl 2):S2–S12.
Metronidazole 50–60mg/kg/ determined by 5. Farthing MJ. Oral rehydration: An evolving solution. J Pediatr Gastroenterol Nutr. Jun
35–50mg/kg/ day as a single the degree of 2002:34 (Suppl 1):S64–S67.
6. Hahn S, Kim YJ, Garner P. Reduced osmolarity oral rehydration solution for treating
day divided dose for three tissue invasion dehydration due to diarrhoea in children: Systemic review. BMJ. 2001;323(7304):81–85.
eight hourly for days or extended 7. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious
ten days to five days if diarrhea in infants and children: A systemic review of published randomized, double-
blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr. 2001;33(Suppl 2):S17–S25.
there is hepatic 8. Sandhu BK; ESPGHAN Working Group on Acute Diarrhoea. Rationale for early feeding in
Eradication: involvement childhood gastroenteritis. J Pediatr Gastroenterol Nutr. 2001;33(Suppl 2):S13–S16.
PO
Paromomycin Eradication:
25–35mg/kg/ PO Diloxanide
day divided furoate 20mg/
eight hourly for kg/day divided
seven days eight hourly for MILK FORMULA GUIDE
ten days
Giardia lambia Disease control PO
Metronidazole INFANT FORMULAE (< SIX MONTHS)
22.5mg/kg/day Whey predominant:
divided eight
Enfalac A+
hourly for seven
days or 30mg/ Friso 1
kg/day once a Mamex Gold Step 1
day for three Nan 1
days S26 Gold
Cryptosporidium Immunocompromised PO Similac Excellence
host Paramomycin Casein -redominant:
25–35mg/kg/ Dumex with Iron Step 1
day divided Lactogen 1 with DHA
eight hourly for Partially hydrolysed whey formula:
14–28 days in
Enfalac HA
combination
with Nan HA
azithromycin
* cotrimoxazole is contraindicated in children with G6PD deficiency FOLLOW-ON MILK (> SIX MONTHS)
** tetracycline and doxycycline are contraindicated in children < eight years old Dumex with Iron Step 2
# norfloxaclin and ciprofloxacin cautioned in children < 12 years old Enfapro A+
Friso 2
Lactogen 2 with Prebio
166 The Baby Bear Book Gastroenterology 167

Mamil Gold Pediasure (one to ten years)

Nan 2 Progress Gold (one to three years)
Promil Gold Promise (three to seven years)
Similac Excellence
LACTOSE-FREE INFANT FORMULAE
FULL-CREAM MILK (CHILDREN > ONE YEAR) Dumex Lactose-free
For one to three years old: Enfalac Lactose-free
Dumex 1 Plus Enfapro Lactose-free (six to 18 months)
Enfagrow A+
Fernleaf 1 Plus SOY PROTEIN
Friso 3 Frisosoy
Gain IQ Isomil Infant Formula/Follow-on
Mamil Gold Step 3 Nursoy
Neslac 1 Plus
Nespray Prebio 1 Plus FORMULAE FOR PREMATURES
Sustagen Junior Enfamil Premature (Lipil)
For three to six years old: Pre Nan
Dumex 3 Plus S26 Low Birthweight
Enfakid A+ Similac Special Care with Iron 24
Fernleaf 3 Plus
Grow SPECIAL MILK FORMULAE
Mamil Gold Step 4 High Medium Chain Triglycerides (MCT) formula for impaired fat
Neslac 3 Plus absorption:
Nespray Prebio 3 Plus Monogen
Sustagen Kid Prebio Protein-modified formulae for cow’s milk allergy or protracted diarrhoea:
For > six years old: Protein hydrolysate, disaccharide-free and MCT formulae:
Dumex 6 Plus Casein-based — Pregestimil
Fernleaf 6 Plus Whey-based — Alfare
Nespray 6 Plus Calci-N Peptamen Junior (one to ten years)
Sustagen School Peptamen (> four years)
For all ages: Elemental formulae:
Dumex Instant Neocate (infants)
Dutch Lady Neocate Advance (> one year)
EveryDay Full Cream Gastroesophageal reflux:
Fernleaf Instant Enfalac AR
Nespray Full Cream Friso comfort

HIGH-CALORIE FORMULAE (CHILDREN > ONE YEAR)
Enercal Plus (> four years)
Ensure (> four years)
Nutren Junior (one to ten years)
Nutren Optimum (> four years)
INBORN ERRORS OF METABOLISM (IEM)
Contact the Nutrition and Dietetics Department or Department of Paediatric
Gastroenterology for specific special formulae or other information.
168 The Baby Bear Book Gastroenterology 169

NEONATAL JAUNDICE (NNJ) Inclusion Criteria Exclusion Criteria Neonatal

jaundiced babies
Jaundiced infant: Jaundiced infant:
NNJ is probably the most common reason for readmission soon after in Children’s
≤ 14 days of life ≥ 15 days of life
birth. The primary objectives in the management of these babies are: Emergency
and OR
Prevent kernicterus ≥ 2kg and ≥ 35 Sepsis Manage in
Diagnosis of pathological causes for NNJ e.g. biliary atresia weeks gestation (Manage in Paediatric Paediatric Ward
No
at birth Medicine Ward) Clinically well? Ward 56
Private ward
Yes Wd _______
No
Neonatal Jaundice SB result (before CE Check SB result available?
Prolonged Jaundice visit): ________ SB level
Total SB > 50μmol/l after D14 life Taken at (Time): Yes
Check admission criteria ____________
Yes
SB level at Exchange
Screen LFT, TFTs and UFEME Transfusion level?
Admit to ward Three hours No
elapsed from
Repeat SB Yes the time SB Yes SB level within
No
Prepare for exchange taken to time 35mol/L of Exchange
level
transfusion Prolonged babies reaches Transfusion level? Yes
conjugated CE?
hyperbilirubinaemia No
SB result (taken from No
Exchange CE): ________ SB level reaches
Phototherapy Taken at (Time): Phototherapy level?
transfusion Discharge
OR No
____________ with advice
SB level within 10mol/L of given
Phototherapy criteria ≤ 72
Stop phototherapy Prolonged conjugated hours?
hyperbilirubinaemia
Yes
Direct SB > 15% No
Discharge with or Manage in:
follow-up at polyclinic Direct SB > 35μmol Ward 31 – Subsidised cases Turns
Ward 71 – Private cases clinically
(With rooming-in of mother) unwell
Jaundice resolves. Perform initial Follow-up weekly No
No follow-up required investigations bilirubin
Rise in SB to exchange level?

Refer to GI clinic Consider referral to
GI clinic if persistant
jaundice
Fig. 4.7: Management of neonatal jaundice — Summary flowchart.
Yes
Admit to Special Care
Nursery (Isolation Room) for
Exchange Transfusion
Fig. 4.8: Neonatal jaundice clinical pathway (Children’s Emergency).
170 The Baby Bear Book Gastroenterology 171

Table 4-6: Risk factor, admission and therapy guidelines. Jaundiced infant needing phototherapy

Yes See Fig. 4.10 overleaf and

SB at Exchange Transfusion level? Fig. 4.11 p. 173
Normal Risk Factor No Yes
Clinically well Yes
No known major risk factors for jaundice SB at double blue level? Manage on SB at
double blue Exchange
Age in Hours/ Single Double Exchange No Transfusion
Home Admit
Day of Life Blue Blue Level Manage on single blue level?
≤ 24 hours Repeat SB in
No
four hours
> 24 to ≤ 48 hours 190 210 220 300 340 Continue to
* Repeat SB
> 48 to ≤ 72 hours 220 250 260 320 360 in 12 to 24 Yes manage on
> 72 to ≤ 120 hours 220 260 260 360 400 hours double blue
SB rising?
> 120 hours to Day 14 260 300 300 360 400
Yes SB at Exchange Yes See Fig. 4.10
SB rising? Transfusion overleaf and No
level? Fig. 4.11 p. 173
Manage on Repeat SB in
No No double blue four hours
SB ≤ home SB at double
High Risk Factor level and blue level or Yes
No rate of rise ≥ Repeat in
Jaundice observed in first 24 hours had at least
5μmol/L/hr 12 hours
Blood group incompatibility with positive direct Coomb’s test, or antibodies titre > 128 24 hours of
G6PD deficient phototherapy? No No
Gestation age 35–36 weeks at birth Continue to SB level stable and at
Significant Cephalohaematoma or bruising manage on least 40μmol/L below
Exclusive breastfeeding, only if not nursing well single blue double blue?
Infant is not nursing well if one or more of the following are present: Yes Yes
Weight loss > 10% from birth weight
Clinically evidence of dehydration Repeat SB in # Convert to single blue
< five wet diapers per day eight hours
Age < 72 hours and mother’s blood group O+ and baby’s blood group unknown Repeat SB in six to 12 hours
Age < 72 hours and both parents’ blood group unknown Home — Repeat SB in OPD within
24 hours. Off phototherapy and Yes
Age in Hours/ Single Double Exchange discharge home same day unless: SB level rising to double
Home Admit No blue level?
Day of Life Blue Blue Level • **< 72 hours of age
≤ 24 hours 90 130 140 220 260 • **Prematurely < 37 weeks No
• **Direct Coomb’s Test Positive
> 24 to ≤ 48 hours 160 180 190 250 290 • **Anaemia with Hb < 12g/dl Continue single blue
> 48 to ≤ 72 hours 190 210 220 280 320 • G6PD Deficiency (keep Yes SB ≤ home for 12 hours
> 72 to ≤ 120 hours 190 220 220 300 340 hospitalised for 14 days) level?
> 120 hours to Day 14 220 260 260 300 340 Repeat SB in six to 12 hours
* If SB near double blue level, repeat SB in six to eight hours
** Repeat SB in 12 to 24 hours. Home if SB ≤ home level
# An infant who has received Intense Phototherapy followed by double blue needs to be on
double blue for at least 24 hours before conversion to single blue
Fig. 4.9: Phototherapy management algorithm.
172 The Baby Bear Book Gastroenterology 173

Jaundiced infant with SB at Exchange Transfusion level Jaudiced baby needing Exchange Transfusion

Start Intense Phototherapy: Four lights phototherapy Two lights with foil Inform Blood Bank and get approval from BTS MO for blood
Urgent NNJ Profile done (blood to reach ward within two hours)
ABO traced
BTS informed re: potential Exchange Transfusion procedure
(Volume to be exchanged — 160ml/kg) [Plus 100mls for printing of tube] Set lines (consider IV + IA if technically unable to set umbilical line)
Infant has poor feeding: Yes
Weight loss > 10% from birth weight Commence Exchange Transfusion when blood is available
Clinical evidence of dehydration Total volume — 160mls/kg (max 500mLs)
Management: IV drip ordered Infant 2–4kg, withdraw blood in 10mls aliquot
U/E/Cr taken when setting drip Infant > 3kg, withdraw blood 20mls aliquot
Enteral feeding ordered
No
EBM feeds two to three hourly ordered (volume 10% above normal) During Exchange Transfusion
Formula feeds two to three hourly ordered (volume 10% above normal) Monitor rate of exchange as per Exchange Transfusion Protocol
Feeding under Phototherapy ordered Do hypocount, ionic Ca and optional ABG halfway during Exchange Transfusion
Note: Intense Phototherapy — Optimise exposed surface area e.g. nurse without diaper
Post-exchange Transfusion
Infant shows signs of acute bilirubin encephalopathy Continue double blue phototherapy
(Hypertonis, arching, opisthotonus, high-pitched cry, retrocollis) Yes Perform Exchange Remove UVC. Send tip for culture (optional)
or Transfusion Take U/E/Cr, Ca/Mg/PO4 and optional ABG
SB > 85μmol/L above Exchange Transfusion level? (see Fig. 4.11 next page)

No One Hour Post-exchange Transfusion

Continue Intense Phototherapy Trace result and correct abnormalities
Check hypocount

Repeat SB in three hours

Three Hours Post-exchange Transfusion
Order half feeds (if infant stable)
Rate of SB fall > 40mmol/l over three hours No
and
SB ≤ Exchange Transfusion level? Six Hours Post-exchange Transfusion
Yes Repeat SB and check FBC
No Exchange Transfusion Level
SB ≤ double blue level?
Normal Risk High Risk
Yes Factor Factor Repeat Exchange Yes SB level persistently high?
< 24 hours — 260 Transfusion (> exchange level)
Manage on double blue for at least 24 hours
(see Fig. 4.9 previous page) > 24 to ≤ 48 hours 340 290
No
Information BTS blood not needed for > 48 to ≤ 72 hours 360 320
See Fig. 4.9 p. 171
Exchange Transfusion > 72 to ≤ 120 hours 400 340 Continue double blue phototherapy
> 120 hours to Day 14 400 340 Full feeds and stop IV drip if taking well

Fig. 4.10: Intense phototherapy clinical pathway. Fig. 4.11: Exchange transfusion algorithm.
174 The Baby Bear Book Gastroenterology 175

INVESTIGATIONS Prolonged Conjugated Hyperbilirubinaemia

NNJ can be broadly divided into two major groups: It is important that pathological causes like obstructive jaundice
Early jaundice secondary to biliary atresia be diagnosed early. A specialist opinion
Prolonged jaundice (Bilirubin > 50μmol/L in a two-week-old child) should be sought for all patients with significant prolonged
conjugated hyperbilirubinaemia
Despite the following list of investigations, the history (e.g. pale stools
and dark urine) and physical examination (e.g. hepatosplenomegaly) are The following investigations are suggested as part of a workup:
often more useful in determining the aetiology of NNJ.
Investigation Pathology
Early Jaundice LFTs Direct/indirect bilirubin level
The most common cause of early hyperbilirubinaemia is Liver enzymes
physiological jaundice. This is due to the increased production Gamma Glutamyltransferase (GGT)
of bilirubin from breakdown of foetal blood cells, combined UFEME, urine culture Urinary infection
with transient limitation of bilirubin conjugation by the liver. TSH, fT4 Congenital hypothyroidism
Other potential causes include haemolysis (ABO incompatibility, TORCH Screen Intrauterine infection
cephalohaematoma), infection (e.g. UTI) and hypothyroidism. Thus, Hepatitis serology Hepatitis B, Hepatitis C
routine investigations should include: Hepatobiliary ultrasound or Obstructive causes e.g. Biliary Atresia,
Hepatobiliary Imino-Diacetic Choledochal cyst
Investigation Pathology Acid (HIDA) scan or
FBC, reticulocytes Infection, haemolysis, Liver biopsy
polycythaemia Metabolic screen
Direct Coomb’s test Haemolysis Urine reducing sugar Galactossaemia, fructosaemia
Maternal and Baby ABO studies Haemolysis (Anti-A, Anti-B, Rhesus) (consider confirmatory tests if +)
Daily aerum bilirubin (not LFTs) — Alpha-1-antitrypsin Alpha-1-antitrypsin deficiency
G6PD assay (if unknown) — Nitrosonapthol Tyrosinaemia
Consider: Screen for:
Urine Full Examination UTI WHEN TO REFER A PATIENT TO THE GASTROENTEROLOGY
Microscopy Elements CLINIC
(UFEME) (urine culture x 2) All patients with prolonged conjugated hyperbilirubinaemia should be
TFTs Congenital hypothyroidism referred to a specialist for further evaluation and management. Bilirubin
levels of most babies with prolonged unconjugated jaundice should
Prolonged Unconjugated Hyperbilirubinaemia resolve with time. Those with persistently high levels should also be
The most common cause of prolonged unconjugated referred to the gastroenterology clinic.
hyperbilirubinaemia is breast milk jaundice. Current guidelines
advocate the continuation of breastfeeding. Although cessation INFORMATION FOR PARENTS
of breastfeeding for one to two days may be useful in determining Bilirubin is a measure of your baby’s jaundice level
the cause, nursing should be resumed as soon as possible. Other Some jaundice occurs in all babies, known as physiological jaundice
potential causes of prolonged unconjugated hyperbilirubinaemia It starts soon after birth and is usually highest between Days 5–7
include hypothyroidism, haemolytic disease (e.g. G6PD deficiency, of life. It will then fall naturally to a normal level as your baby’s liver
hereditary spherocytosis) or congenital hyperbilirubinaemia matures
syndromes (e.g. Crigler Najjaar, Gilbert Syndrome) Most babies will have bilirubin levels that are not dangerous and
therefore will not need treatment
176 The Baby Bear Book
In your baby, the jaundice level is rising very fast and will most likely
go above the critical level (the purple line)
Above the critical level, there is a risk of brain damage
The effect of phototherapy will keep baby’s jaundice level below the
critical level (the green line)
We will need to monitor baby’s bilirubin level on a regular basis to
ensure that it does not continue to reach the critical level (the black
line). If this happens, we will need to perform more tests to find out if
baby has any liver illness
Phototherapy will be stopped after your baby’s bilirubin falls to a safe
level
If your baby’s bilirubin level reaches the critical level, we will need
to perform a procedure called an exchange transfusion in order to
protect the brain. This involves taking out blood slowly and replacing
it with fresh blood without the jaundice
GUIDELINES FOR EXCHANGE TRANSFUSION: UMBILICAL
VEIN CATHETER (UVC) METHOD
Preparation
Wet infant’s umbilical cord with gauze soaked with normal saline
Insert NG tube and aspirate all gastric contents
Restrain infant under warmer
Ensure proper lighting
Set up IV drip set (D10% Combi Drip without added potassium)
Do the following blood investigations:
U/E/Cr
Ca/Mg/PO4
Hypocount
Peripheral blood culture (optional)
Connect infant to cardiac monitor
Procedure
Insertion of umbilical venous catheter:
Cut cord about 1cm from skin
Identify two arteries and one vein
Cannulate umbilical vein (approximate 5–10cm) until blood is
obtained
Secure umbilical catheter
Connect umbilical catheter as seen in Fig. 4.12
Start by withdrawing blood from infant at 10ml/min
For infants 2–3kg, withdraw blood in 10ml aliquot. For infants > 3kg,
withdraw blood in 20ml aliquot
Gastroenterology 177
Fig. 4.12: Connecting the umbilical catheter.
After first withdrawing of blood, infuse whole blood at same rate.
Continue this process for the whole cycle
Ensure no air bubbles present while introducing blood
Stop exchange transfusion if respiratory distress, irritability, cardiac
arrhythmias, bradycardiac (HR < 110) or tachycardia (HR > 160),
pallor or cyanosis
Do ionic calcium, hypocount and optional ABG halfway during the
exchange transfusion. Correct any abnormalities if necessary
Consider calcium gluconate infusion
Post-exchange Transfusion
At the end of the exchange transfusion, remove UVC. Send tip for
culture (optional)
Take U/E/Cr, Ca/Mg/PO4 and optional ABG
One hour post-transfusion, trace results and correct any
abnormalities. Check hypocount
Three hours post-transfusion, start milk feeds
Six hours post-transfusion, repeat FBC and Serum Bilirubin (SB)
levels. Progress to full feeds and off drip if baby feeding well
GUIDELINES FOR EXCHANGE TRANSFUSION: UMBILICAL
VEIN CATHETER AND INTRA-ARTERIAL (UVC + IA) METHOD
Preparation
Wet infant ‘s umbilical cord with gauze soaked with normal saline
Insert NG tube and aspirate all gastric contents
Restrain infant under warmer
Ensure proper lighting
Set up IV drip set (D10% Combi Drip with no potassium)
178 The Baby Bear Book Gastroenterology 179

Do the following blood investigations: Stop exchange transfusion if respiratory distress, irritability, cardiac
U/E/Cr arrhythmias, bradycardiac (HR < 110) or tachycardia (HR > 160),
Ca/ Mg/ PO4 pallor or cyanosis
Hypocount Do ionic calcium, hypocount and optional ABG halfway during the
Peripheral blood culture (optional) exchange transfusion. Correct any abnormalities if necessary
Connect infant to cardiac monitor Consider calcium gluconate infusion

Procedure Post-exchange Transfusion

Set arterial line. Connect arterial line to a three-way tap as seen in At the end of the exchange transfusion, remove UVC. Send tip for
Fig. 4.13 culture (optional)
Insertion of umbilical venous catheter: Take U/E/Cr, Ca/Mg/PO4 and optional ABG from arterial line before
Cut cord about 1cm from skin removing it. Ensure haemostasis
Identify two arteries and one vein One hour post-transfusion, trace results and correct any
Cannulate umbilical vein (approximate 5–10cm) until blood is abnormalities. Check hypocount
obtained Three hours post-transfusion, start milk feeds
Secure umbilical catheter Six hours post-transfusion, repeat FBC and SB levels. Progress to full
If unable to set umbilical venous catheter, set an IV line feeds and off drip if baby feeding well
Connect umbilical catheter to infusion pump. Starts blood infusion
rate at 50ml/hr and increase as rate tolerated. Aim to complete
double volume exchange transfusion in one to two hours. Consider
manually infusing blood if necessary
Withdraw blood from IA line at the same rate as the infusion rate RECURRENT ABDOMINAL PAIN
(max rate 10ml/min)
Approximately 10–20% of school-aged children experience abdominal
pain frequently and severely enough to affect their activities. The majority
of these patients do not have an organic cause for their symptoms.

Functional causes of abdominal pain can be classified into (ROME II

guidelines):
Functional dyspepsia
Irritable Bowel Syndrome (IBS)
Abdominal migraine
Aerophagia
Functional abdominal pain

FUNCTIONAL DYSPEPSIA
Dyspepsia refers to pain or discomfort centred in the upper abdomen.
Discomfort may be characterised by fullness, early satiety, bloating,
belching, nausea, retching or vomiting.

Fig. 4.13: Connecting the arterial line to a three-way tap.

180 The Baby Bear Book
Diagnostic Criteria
In children old enough to provide an accurate history, at least 12 weeks*
(not necessarily consecutive) within the preceding 12 months of:
Persistent or recurrent pain or discomfort centred in the upper
abdomen (above the umbilicus); and
No evidence (including at upper gastrointestinal endoscopy) that
organic disease is likely to explain the symptoms; and
No evidence that dyspepsia is exclusively relieved by defaecation
or associated with the onset of a change in stool frequency or
stool form
* Within each week, symptoms are only required for one of the seven days.
Classification
Functional dyspepsia can be divided into:
Ulcer-like dyspepsia — Pain is the predominant symptom.
Dysmotility-like dyspepsia — Discomfort associated with early
satiety, bloating or nausea are the predominant symptoms
Unspecified (non-specific) dyspepsia — Symptoms do not fit into the
above two categories
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 should be normal with no signs of
inflammatory bowel disease
Differential diagnoses include peptic ulcer disease, reflux
oesophagitis, H. pylori gastritis, inflammatory bowel disease,
pancreatitis and biliary disease
Unlike adults, children have a much lower risk for malignancy,
hence endoscopy can be delayed and a trial of empiric therapy
instituted. However, patients presenting with weight loss, vomiting,
haematemesis, odynophagia or dysphagia require early endoscopy
Management
Dietary/lifestyle changes:
Avoid high fat foods, large meals, caffeine, alcohol and cigarette-smoking
Acid reducing agents:
H2 blockers, proton pump inhibitors, sucralfate for ulcer-like dyspepsia
Prokinetic agents:
Domperidone, metoclopramide, erythromycin for dysmotility-like
dyspepsia
Gastroenterology 181
Antidepressant:
Low-dose tricyclic antidepressant therapy is often helpful in patients
not responding to acid-reducing or prokinetic agents
Environmental modification, behavioural therapy, coping strategies
and relaxation techniques may be useful
IRRITABLE BOWEL SYNDROME (IBS)
In IBS, an altered bowel habit is associated with the abdominal pain
which is usually relieved with defaecation.
Diagnostic Criteria
In children old enough to provide an accurate pain history, at least 12
weeks, which need not be consecutive, in the preceding 12 months of:
Abdominal discomfort or pain that has two out of three features:
Relieved with defaecation
Onset associated with a change in frequency of stool
Onset associated with a change in form (appearance) of stool
No structural or metabolic abnormalities to explain the symptoms
The following symptoms cumulatively support diagnosis of IBS:
Abnormal stool frequency (> three bowel movements per day or <
three 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
Irritable Bowel Syndrome Classification
Constipation predominant IBS
Diarrhoea predominant IBS
Variable stool pattern IBS
Assessment
A history which fulfills the ROME II criteria for IBS together with a
normal physical examination and growth is consistent with IBS
Differential diagnoses include infective causes, carbohydrate
intolerance or inflammatory conditions such as inflammatory bowel
disease, coeliac disease and eosinophilic gastroenteritis
Features suggesting the possibility of organic disease include
nocturnal pain or diarrhoea, rectal bleeding, weight loss, fever,
arthritis and a family history of inflammatory bowel disease
182 The Baby Bear Book Gastroenterology 183

Laboratory screening tests include: Family history of migraine

FBC Headache confined to one side only
ESR An aura or warning period consisting of either visual disturbances
Stool analysis for enteric bacterial pathogens and parasites (e.g. blurred or restricted vision), sensory symptoms (e.g.
Breath hydrogen test or a trial of milk-free diet for lactose mal- numbness or tingling sensation) or motor abnormalities (e.g.
absorption slurred speech, inability to speak, paralysis)

Treatment
Patient education and reassurance
Stress management/psychotherapy — Many studies have
shown improvement of pain with the use of adjunctive cognitive
behavioural therapy
Dietary changes:
Restrict foods high in fat, caffeine or alcohol
High-fiber diet is useful in constipation predominant IBS
Medication:
Anticholinergics/anti-spasmodics (dicyclomine, hyoscine,
mebeverine) are commonly used for diarrhoea predominant or
variable pattern IBS although there are no controlled studies
confirming efficacy
Laxatives — May be useful with constipation-predominant IBS
Tricyclic antidepressant in low doses improves symptoms in
adults with IBS
Newer medications act on the serotonin receptors 5HT3 and
5HT4. Examples include alosetron (available on a restricted basis
in the US), tegaserod and prucalopride
Assessment
The diagnosis is straightforward in the presence of a family history of
migraine
Abdominal ultrasonography: To evaluate for abdominal masses,
cholelithiasis or renal abnormalities
Upper gastrointestinal study: To rule out malrotation or isolated
areas of inflammation
Cranial imaging (indicated in those with recurrent headache and
vomiting): To rule out space-occupying lesions and raised ICP
Management
Management is aimed at prevention of the pain episodes
Pizotifen, cyproheptadine and propranolol are the main prophylactic
agents used. Other medications that have been used include tricyclic
antidepressants and carbamazepine
AEROPHAGIA
Aerophagia is a condition where excessive air swallowing causes
progressive abdominal distension.

ABDOMINAL MIGRAINE Diagnostic Criteria

Abdominal migraine is characterised by acute, intense, non-colicky, At least 12 weeks, which need not be consecutive, in the preceding 12
midline abdominal pain that lasts for hours. It occurs intermittently with months of two or more of the following signs and symptoms:
long symptom-free periods. Air swallowing
Abdominal distension due to intraluminal air
Diagnostic Criteria Repetitive belching and/or increased flatus
In the preceding 12 months, three or more paroxysmal episodes of
intense, acute midline abdominal pain lasting two hours to several Assessment
days; and Repeated audible swallows can be observed in the patient
Evidence of metabolic, gastrointestinal and CNS structural or Symptoms and abdominal distension resolve during sleep
biochemical disease is absent; and Carbohydrate mal-absorption should be excluded by breath
Two of the following features: hydrogen test
Headache during episodes Stressful life events or anxiety is a frequent cause of excessive air
Photophobia during episodes swallowing
184 The Baby Bear Book
Management
™ Reassurance and explanation of the symptoms
™ Discourage carbonated beverages or chewing gum
™ Address stress and anxiety problems
FUNCTIONAL ABDOMINAL PAIN
™ In functional abdominal pain, the symptoms do not fit into any
of the previous categories of functional gastrointestinal diseases,
nor do they suggest chronic diseases such as peptic ulcer disease,
pancreatitis or Crohn’s Disease
™ The pain is usually periumbilical and does not relate to any specific
activity
Diagnostic Criteria
At least 12 weeks of:
™ Continuous or nearly continuous abdominal pain in a school-aged
child or adolescence; and
™ No or only occasional relation of pain with physiologic events (e.g.
eating, menses, or defaecation); and
™ Some loss of daily functioning; and
™ The pain is not feigned (e.g. malingering); and
™ The patient has insufficient criteria for other functional
gastrointestinal disorders that would explain the abdominal pain
Assessment
Physical examination, growth and laboratory screening tests (urinalysis,
FBC, ESR, blood chemistries, stool for occult blood, ova and parasites,
breath hydrogen test) are normal.
Management
™ Reassurance and explanation of symptoms
™ Environmental modification/psycho-social aspects:
Š Attention to the psycho-social aspects and psychological support
for personal, family and school difficulties are important
™ Dietary modification such as a high-fibre diet can be tried but
improvement is usually slight
™ Medication — The use of drugs such as anticholinergics is
controversial. There is anecdotal evidence of improvement but no
published data has confirmed their efficacy
185
GENERAL AND AMBULATORY PAEDIATRICS
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
186 The Baby Bear Book
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
General and Ambulatory Paediatrics 187
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 in
non-organic FTT.
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 five-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. three to four 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
188 The Baby Bear Book General and Ambulatory Paediatrics 189

Neglect ™ Child rocks, sucks or bites self

Some Physical Signs ™ Being very shy, passive, compliant
™ Consistent and regular hunger ™ Being aggressive and constantly seeking attention
™ Malnutrition ™ Low self-esteem, negative statements about self
™ Low weight for age ™ Inability to mix with other children
™ Gaining weight when hospitalised or placed in alternative care
™ Poor language skills and coordination Sexual Abuse
™ Poor hygiene (child constantly unwashed) Some Physical Signs
™ Poor teeth, gum disease, untreated sores, not immunised against ™ Pain, itching, discharge or bleeding in genital area
illness ™ Bruises to breasts, buttock, lower abdomen or thighs
™ Consistent lack of supervision ™ Vaginal infections with or without associated UTIs
™ Abdominal pain suggestive of pelvic inflammatory disease
Some Behavioural Symptoms ™ Recurrent headaches which are not neurological in origin
™ Poor bonding with parents ™ Sexually-transmitted diseases
™ Clings to any adults, goes too easily with strangers ™ Painful urination, bedwetting inappropriate for age
™ Unusually tired, listless or motionless ™ Pregnancy, especially teenage pregnancy
™ Feeds hungrily or hardly at all ™ Torn, stained, bloody underclothes
™ Hungry for adult affection and attention ™ Symmetrical bruises over the medial aspects of both thighs which
™ Habitual school truant or late-comer suggest that the child’s hips were forcibly abducted during the act of
™ Poor school performance, learning difficulties sexual assault
™ Reluctance to go home
™ Rocking, sucking, head-banging Some Behavioural Symptoms
™ Fear of being hurt during dressing/nappy change
Emotional or Psychological Abuse ™ Inappropriate sexual activity
Emotional abuse can harm children just as much as other forms of ™ Fear of being alone with a particular adult
abuse. It can be difficult to identify because it does not leave any ™ Extreme reactions, e.g. phobia to the opposite sex
physical injuries and it often goes unrecognised until a child shows signs ™ Depression or low self-esteem
of emotional problems. ™ Distorted self-perception, e.g. being dirty or unclean
™ Uncontrollable crying and screaming
Some Key Features ™ Sexual themes/fears in artwork, stories or play
™ Stunted growth: Non-organic FTT ™ Strong fear/anxiety (especially about going home)
™ Accelerated growth away from family ™ Child reports having dreams or fears that seem to have sexual overtones
™ Feeding behaviour grossly disturbed ™ Exhibit self-destructive behaviour such as self-mutilation, alcohol/
™ Delayed mental and emotional development substance abuse, excessive risk-taking that may endanger life, and
™ Unusual patterns of urination and defecation suicidal attempts
™ Poor social adjustment, anti-social behaviour, unhappy, irritable and ™ Eating disorders including anorexia nervosa
defiant ™ Child demonstrates sexual behaviour beyond his/her years and
supposed knowledge, e.g. hyper-sexualised behaviour
Some Behavioural Symptoms ™ Delinquent, aggressive or truant behaviour at school not explained
™ Changes in behaviour by other causes in a previously well-behaved child
™ Lying and stealing ™ Regressive behaviour, e.g. sudden return to wetting or soiling
™ Destructive or violent behaviour ™ Unwilling to participate in normal physical or social activities
190 The Baby Bear Book
™ 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
CHILD DEVELOPMENT
NORMAL DEVELOPMENT
Children usually attain developmental skills in the same orderly
sequence. The normal developmental milestones are shown in Table
5-1 (at the end of this section). Developmental screening should
be performed at each patient contact and those identified to have
abnormal development should be referred to a developmental
paediatrician for further evaluation.
PATTERNS OF ABNORMAL DEVELOPMENT
™ Developmental Delay:
Š Development follows the normal sequence but is delayed
Š May be a specific or global developmental delay
™ Developmental Disorder:
Š Development does not follow the normal pattern and is
General and Ambulatory Paediatrics 191
aberrant or bizarre e.g. persistence of primitive reflexes, atypical
developmental profiles
™ Developmental Arrest or Regression:
Š A period of normal development is followed by a failure to
acquire new skills or loss of previously established skills
Š This may signify a serious underlying condition e.g.
neurodegenerative/metabolic disorder, Landau-Kleffner
Syndrome, Rett Syndrome
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.
Points to Consider in the Assessment
History
™ Antenatal and neonatal history:
Š Cord thyroid-stimulating hormone level, Apgar Score (see “Apgar
Score” p. 346), prematurity, perinatal events, intrauterine infection
™ Medical history:
Š Chronic medical illness, seizures including absence seizures
(staring spells), otitis media, significant head injury
™ Drug history:
Š Drugs (e.g. steroids or theophylline) can affect behaviour
™ Social history:
Š Recent stressors, family dynamics, main caregiver(s), spoken
language at home, environmental deprivation, financial difficulty
™ Family history:
Š Consanguinity
Š Hearing impairment, seizures, neurological disorders, genetic/
metabolic disorders
Š Developmental delay, mental retardation, learning disability,
schooling difficulty, behavioural disorder, autistic spectrum
disorder (ASD), attention deficit hyperactivity disorder (ADHD),
psychiatric illness
™ Sleep history:
Š Obstructive sleep apnoea
™ Feeding history:
Š Feeding/swallowing difficulties
™ Developmental history:
Š Gross motor, fine motor, speech/language, social/play, activities
of daily living
192 The Baby Bear Book General and Ambulatory Paediatrics 193

Š Atypical development Developmental Delay

Š Early temperament in infancy (e.g. response, feeding, sleeping,
crying) A. History
Š Developmental regression
Š Behaviour in different settings e.g. home, school. B. Examination
™ School performance:
Š Academics, behaviour, socialisation skills C. Investigations
Š Report from teachers
™ Report from professionals working with the child e.g. therapists Assessment Surveillance: Review
™ Co-morbid conditions normal in six months

Examination Areas of Delay

™ Growth parameters (weight, height, Occipito-frontal Circumference
(OFC))
™ Syndrome identification — Dysmorphism Specific Delay Global Delay
™ Eyes, ears
™ Cleft lip/palate
™ Neurocutaneous stigmata Motor Delay Speech/Language Delay
™ Full neurological examination (tone, reflexes, gait, cranial nerves,
cerebellar) Evaluate: Evaluate:
™ Spine, hips ™ Gross motor ™ Speech
™ Behaviour: ™ Fine motor ™ Language (receptive,
Š Social interaction — Eye contact, communicative intent, joint expressive)
attention, social appropriateness, response to family and strangers Consider:
Š Play — Free play, pretend play ™ Hearing impairment
Š Activity level, attention span Consider: ™ Otitis media
™ Oromotor problems e.g. cleft
Š Sensory aversion/seeking behaviour, self-stimulatory behaviour,
palate
perseverative behaviour
™ Selective mutism
™ Understanding environment
Investigations ™ Language opportunity
Investigations should only be done when clinically indicated. Some
investigations that should be considered include:
™ TFTs Consider:
™ Muscle enzymes ™ Hypothyroidism
™ Urea/electrolytes/glucose, calcium/magnesium ™ Cerebral palsy
™ Neuroimaging (Ultrasound/CT/MRI head) ™ Cognitive impairment
™ EEG ™ Autistic spectrum disorder
™ Karyotyping, specific probes — Prader-Willi, Williams, Fragile X ™ Neuromuscular disorder
™ Syndromes
™ IEM study
™ IEM
™ Visual assessment
™ Hearing assessment
Fig. 5.1: A brief approach to a child with developmental delay.
194 The Baby Bear Book General and Ambulatory Paediatrics 195

Developmental Delay ™ Speech is the expression of language in the verbal mode

Š Speech disorders include articulation difficulties, dysfluency
A. History (stuttering)
™ Children frequently present with one of the following:
B. Examination Š Expressive language disorder
Š Mixed receptive-expressive language disorder
C. Investigations Š Speech articulation/fluency problems
Assessment Surveillance: Review
normal in six months Autistic Spectrum Disorder (ASD)
The core clinical features of ASD constitute a triad of impairments in
social interaction, communication and imagination, often associated
< five years > five years with a restricted range of interests and repetitive stereotypical
behaviours. Other associated features include sensory issues and
splinter skills.
Consider: Consider:
™ Developmental delay ™ ADHD Characteristics
™ Cognitive impairment ™ Learning disability
™ Impaired social interaction e.g. impaired non-verbal behaviour (poor
™ Autistic spectrum disorder ™ Depression, anxiety
eye contact, poor use of gestures and facial expressions), impaired
™ Reaction to environmental ™ Conduct disorder
problems ™ Oppositional defiant disorder
ability to make peer relationships, lack of spontaneous seeking
™ Medical conditions to share enjoyment, interests or achievements, lack of social or
Epilepsy emotional reciprocity
Thyroid disorder ™ Impaired communication/imagination e.g. delayed speech,
Visual/hearing impairment abnormal or inappropriate speech content or production, inability to
CNS e.g. tumour initiate or sustain a conversation with others, idiosyncratic language,
™ Medication e.g. theophylline,
lack or delay in imaginative or pretend play, inappropriate play
steroids
™ Restricted, repetitive and stereotypical behaviour e.g. stereotyped
repetitive body movements or activities, preoccupation with objects
Fig. 5.2: A brief approach to a child with behavioural concerns. or subjects, restricted interests, rigid
™ Sensory issues e.g. under- or over-reaction to certain sensory stimuli
such as noise, textures
It is important to remember that children often present with ™ Splinter skills e.g. isolated advanced skills such as hyperlexia
combinations of problems and the two approaches are only a guide.
Attention Deficit Hyperactivity Disorder (ADHD)
Some Specific Conditions The diagnosis is based primarily on reports of characteristic behaviours
Speech and Language Delay from various observers, in different settings over an extended period of
Speech and language are components of communication. time (at least six months). When considering a diagnosis of ADHD, it is
™ Language is a system of symbolic representation that is used to important to remember that inattention, hyperactivity and impulsivity
communicate meanings, feelings, ideas and intentions are common till three years old. The symptoms should result in
Š Receptive language (language processing): Comprehension of impairment in social and academic functioning in two or more settings
language (e.g. at home and at school). These symptoms should also be present
Š Expressive language (language production): Facial expression, before the age of seven years.
gesture, speech, semantics, syntax, pragmatics
196 The Baby Bear Book General and Ambulatory Paediatrics 197

Features of this disorder include: MANAGEMENT

™ Inattention e.g. easily distracted, careless, fails to complete tasks, The early detection of abnormal development and behavioural
does not follow through on instructions, forgetful, difficulty problems facilitates the institution of early intervention such as speech/
organising tasks, loses things necessary for activities, not listening language therapy, occupational therapy, physiotherapy and behaviour
when spoken to directly management. Some children will require placement in special schools.
™ Hyperactivity e.g. fidgets, will not sit still, runs or climbs excessively Referral should be made to the relevant medical specialists.
in inappropriate situations, difficulty engaging in leisure activities
quietly, often ‘on the go’, talks excessively Common concomitant problems in children with special needs:
™ Impulsivity e.g. blurts out answers before questions have been ™ Visual and hearing impairment — Minimise any impairment to
completed, difficulty waiting turn, often interrupts or intrudes others optimise child’s learning
™ Epilepsy
Learning Disability ™ Orthopaedic problems — Physiotherapy, aids to optimise posture
A specific learning disability refers to an underachievement in academic and mobility, prevent/reduce skeletal deformity (e.g. drugs, surgery)
skills (reading, mathematics or written expression) that is out of keeping ™ Chest infections
with a child’s age, level of intellect, education and culture. ™ Feeding problems — Oromotor incoordination, gastroesophageal
reflux, tube feeding
Some warning signs: ™ Bladder and bowel function (e.g. enuresis, encopresis, constipation)
™ Speech and Language: ™ Behavioural and psychiatric concerns
Š Speech delay, articulation deficits, difficulty with temporal (time) ™ Social issues
concepts, difficulty with word-retrieval and story-telling
™ Visual-motor: The following table outlines the normal development milestones for
Š Difficulty with laterality and identifying left and right children from times of birth to the time they are six years old.
Š Difficulty with writing and reading e.g. reversals
Table 5-1: Normal development milestones.
Š Difficulty discriminating size, shape and colour
Š Poor visual-motor coordination e.g. difficulty copying Note: For children born premature (< 37 weeks gestation), the corrected age should be used (up till two
Š Motor clumsiness years old) to assess development milestone
Š Poor gross motor skills e.g. difficulty riding a bicycle, swimming, Age Gross Motor Fine Motor — Speech — Personal —
Visual Language — Social —
playing ball games
Hearing Behavioural
Š Poor fine motor skills e.g. tying shoelaces, buttoning, writing
Birth Marked head lag Barely fixates/follows Alerts to sounds Reflex smile
™ Memory:
Grasp reflex Cries when hungry or Sleeps and feeds
Š Often poor, especially short-term memory uncomfortable
™ Organisation: Four to six Moderate head lag Fixates and follows Turns eyes to sounds Regards face
Š Poor organisational skills, difficulty with sequencing weeks Prone — Head up past midline Vocalises Social smile
™ Behavioural disturbances: 45°, rotates head Grasp reflex may
Š Impulsive, hyperactive, difficulty concentrating, distractible, poor Makes alternating be lost
social judgement, poor peer relationships cycling movements
Three Mild head lag Follows 180° Turns head to sounds Initiates social smile
months Prone — Head up Unfists mostly at ear level Smiles and vocalises
It is important to exclude learning problems due to an underlying
90°, props up on Hand regard Vocalises/laughs/ at mirror
medical condition (e.g. visual/hearing impairment, motor handicap, forearms Holds object placed squeals with Excites at toy or
seizures, thyroid disorders), cognitive impairment, ADHD, environmental in hand pleasure familiar pleasant
disadvantage or emotional disturbance. Reaches situations e.g.
feeding, bathing
198 The Baby Bear Book General and Ambulatory Paediatrics 199

Note: For children born premature (< 37 weeks gestation), the corrected age should be used (up till two Note: For children born premature (< 37 weeks gestation), the corrected age should be used (up till two
years old) to assess development milestone years old) to assess development milestone
Age Gross Motor Fine Motor — Speech — Personal — Age Gross Motor Fine Motor — Speech — Personal —
Visual Language — Social — Visual Language — Social —
Hearing Behavioural Hearing Behavioural
Six months Prone — Head up Fixes on small object Imitates speech Plays peek-a-boo and 18 months Stoops and recovers Scribbles Ten to 20 single Domestic mimicry
90°, props up on Follows falling sounds imitative games Walks alone, runs spontaneously words Meaningful play
hands with arms objects Polysyllabic babbling Stretches arms out to Walks backward Builds tower of four Mature jargoning with toys
extended Reaches out to grasp be lifted Carries toy while cubes (includes intelligible Plays alone but near
Rolls over (palmar grasp) Excited by approach walking Turns two to three words) familiar people
Sits with support Transfers to opposite of familiar people Up/down steps with pages at a time Points to named Emotionally
Bears weight on legs hand support body parts, pictures, dependent on
Mouths Climbs onto chair objects familiar adult
Grasps own feet and Points to indicate Likes sitting on
gets feet to mouth needs knee and looking
Ten months Sits alone and plays Looks for hidden toy Locates sounds well Claps hands Obeys simple at books for a few
Gets to sitting and uncovers it Jabbers Waves bye-bye instructions minutes
position Bangs two cubes Says “papa”, “mama” Starts to explore Uses spoon
Crawls forward held in hand indiscriminately environment Drinks from cup
Pulls to stand Pincer grasp Reacts to Takes off shoes/ socks
Stands with support encouragement and Assists dressing
Cruises discouragement Aware and
Holds own bottle disapproves of
Finger feeds wetness
One year Stands alone Casting Responds well to Stranger anxiety, Two years Up/down steps, two Holds pencil in fist Two- to three-word Enjoys solitary play,
Walks with support/ name closely attached to feet per step Copies lines phrases alongside peers
alone Single-finger familiar adult Jumps Builds tower of six Knows 50 words (parallel play)
pointing Shows affection Propels tricycle by cubes Understands two- Pretend play
Indicates needs (not Joint attention pushing with feet Turns pages one at part instructions Not sharing
by crying) Imitates actions on floor a time Listens to simple Possessive,
Pushes things away Enjoys putting Kicks and throws ball stories egocentric, resistant
he/she does not objects in and out Enjoys nursery Constantly demands
want of boxes, emptying rhymes and jingles attention
Calls “papa”, “mama” cupboards Clings to mother
specifically Cooperates with Tantrums when
Two to three single dressing not understood or
words with demands not met
meaning Dresses with help
Understands simple Washes hands
words/phrases Indicates toilet needs
Understands “no” Helps put things
Gives toy on request away
Obeys one-step
command with
gesture
200 The Baby Bear Book General and Ambulatory Paediatrics 201

Note: For children born premature (< 37 weeks gestation), the corrected age should be used (up till two Note: For children born premature (< 37 weeks gestation), the corrected age should be used (up till two
years old) to assess development milestone years old) to assess development milestone
Age Gross Motor Fine Motor — Speech — Personal — Age Gross Motor Fine Motor — Speech — Personal —
Visual Language — Social — Visual Language — Social —
Hearing Behavioural Hearing Behavioural
Three years Up/down steps, Handedness > three-word Names friend Six years Backward heel-to- Copies a diamond Adds single numbers Play with particular
alternate feet Awkward tripod phrases Group play toe walk Writes name, simple Spells and reads themes
Broad jump grasp of pencil Knows > 200 words Cooperative play words Knows right from left
Walk on tip-toe Copies circle Holds conversation (shares toys, takes Knows days of week
Pedals tricycle Builds tower of nine Gives name/age/sex turns)
cubes Uses pronouns, Constructive play
Threads beads plurals, prepositions Separates from
Matches two colours Asks questions — mother easily,
BIBLIOGRAPHY
1. Lim HC, Chan T, Yoong T. Standardisation and adaptation of the Denver Developmental
what, who, where waiting developing Screening Test (DDST) and Denver II for use in Singapore children. Singapore Med J.
Rote counts one Understands good 1994;35(2):156–60.
to ten and bad 2. American Psychiatric Association (APA). Quick reference to the diagnostic criteria from
Recites songs, Brushes teeth with DSM-IV-TRTM. Washington D.C.: American Psychiatric Press; 2000.
3. Aylward GP. Practitioner’s guide to developmental and psychological testing. New York:
nursery rhymes help Plenum Publishing Corporation; 1994.
Dresses/undresses 4. Parker S, Zuckerman B. A Handbook for Primary Care: Behavioral and Developmental
except buttons Pediatrics. Boston: Little, Brown and Company; 1995.
Know front from back
Toilet-trained
Four years Hops Dynamic tripod grasp Speaks Complicated
Balances on either of pencil grammatically and imaginative play
foot for five seconds Copies cross, square clearly alone and with ADOLESCENT MEDICINE (ADME) —
Climbs ladder Draws person with Gives address other children
three parts Asks questions — Dresses alone REFERRAL GUIDELINES AND WORKFLOW
Colours picture why, how Brushes teeth
Uses scissors Relates events/ Buttons clothes The ADME team comprises paediatricians conversant with adolescent
stories issues and ADME resource nurses who will cover the wards and
Names colours, outpatient clinics.
shapes
Five years Skips Copies triangle Speaks fluently Comforts siblings/
Heel-to-toe walk Draws person with Long descriptions friends in distress
WHOM TO REFER AND WHEN ?
Enjoys climbing, seven parts and explanations Protective of younger ™ ADME patients are teenagers (ten to 19 years old) and young adults
swings, slides Understands complex sibling (> 20 years old), but not all teens need to be referred to the ADME
Catches bounced ball instructions Makes and chooses team
Plays ball games Enjoys riddles, jokes own friends ™ ADME as a discipline is concerned with teens and young
Knows time of day Plays complicated
adults whose healthcare issues may include aspects of organic,
Recognises numbers, cooperative games
letters with rules psychological and social aetiologies and whose healthcare needs
Counts Competitive games would be beyond the resources of any one disease or organ system-
Independent self- based subspeciality in a tertiary-care hospital like KKH
help skills ™ Cases that ADME will see include, but are not limited to, eating
Carries out simple
disorders, substance abuse, self-harm, behaviour issues in and out
domestic tasks
Runs errands of hospital, school and home, at-risk behaviours, complex psycho-
Ties shoe laces social situations, ongoing chronic illness with adherence/compliance
issues, and unexplained symptoms
202 The Baby Bear Book General and Ambulatory Paediatrics 203

Table 5-2: DSM criteria for anorexia nervosa (AN) and bulimia nervosa (BM).
™ The ADME team’s role for hospital inpatients would often be
supportive and secondary. Such inpatients should continue to be Anorexia Nervosa (AN) Bulimia Nervosa (BN)
under the care of relevant medical or surgical teams, medical social ™ Refuse to maintain body weight at or ™ Recurrent episodes of binge-eating
workers etc. while in hospital, with input from the General and above a minimally normal weight for age characterised by both of the following:
Ambulatory Paediatrics (GAP)/ADME team members as needed and height Š Eating, in a discrete period of time
™ Intense fear of gaining weight or becoming (i.e. within any two-hour period), an
™ The ADME clinic is a key resource for outpatient care of the
fat, even when underweight amount of food that is larger than
complicated adolescent patient. For continuity of care, timely ™ Disturbance in the way in which one’s body most people would eat during a similar
inpatient referrals should be made weight and shape are experienced period of time
™ In post-menarchal females, amenorrhea, Š A sense of lack of control over-eating
HOW TO REFER the absence of at least three consecutive during the episode
™ Ward teams may make a formal referral to the ADME team menstrual cycles ™ Recurrent inappropriate compensatory
™ The ADME team doctor or resource nurse may identify a patient with behaviours
needs and will then approach the ward team to suggest a referral ™ Binge and inappropriate compensatory
behaviours both occur, on average, at least
™ Direct external referral or self-referral to ADME as outpatient or
twice a week for three months
inpatient

WORKFLOW CLINICAL MANIFESTATION

Upon receiving the referral, the ADME team doctor will review the
patient, but follow up as an inpatient may primarily be by the ADME
resource nurse.
If the adolescent ward is in operation, priority for beds will be given
to the older adolescents (> 18 years), then middle adolescents (14–17
years) and then young adolescents (ten to 13 years) as well as patients
requiring longer stays.
Upon discharge, the ADME team doctors will see the patient in
conjunction with the nurse in the ADME clinic or Private Children’s Clinic.
EATING DISORDERS
Most cases of anorexia nervosa would present to the medical practitioner
when there has been a noticeable amount of weight loss over a short
duration of time. In bulimia nervosa, presentation is usually late as the
history is more insidious. The following features can be associated:
™ Pre-occupation 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
™ Frequent attempts at dieting
™ Weight determines self-esteem
™ Evidence of binge-eating and purging
™ Over-eating in response to stress
™ Frequent weight fluctuations
™ Use of laxatives, diuretics, diet pills, emetics, excessive exercise
™ Secretive vomiting

Several types of eating disorders can present in children and Physical signs that may be seen in anorexia nervosa are listed below.
adolescents. Among the spectrum of eating disorders, two clinical types Cases of bulimia nervosa may not have any physical abnormality.
have been well-described — anorexia nervosa and bulimia nervosa. ™ Weight loss
However, there are many clinical variants. The Diagnostic and Statistical ™ Failure to make appropriate gains in weight and height
Manual of Mental Disorders (DSM) criteria for the two types are listed in ™ Hypothermia
Table 5-2. ™ Bradycardia
™ Orthostatic pulse and BP
™ Dull, thinning scalp hair
204 The Baby Bear Book General and Ambulatory Paediatrics 205

™ Lanugo hair BIBLIOGRAPHY

1. APA. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.:
™ Emaciated, wears over-sized clothes American Psychiatric Association Press; 1994.
™ 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 ADOLESCENT HEALTH —
eating pattern. HEADSS ASSESSMENT
SUGGESTED INVESTIGATIONS
™ ECG INTRODUCTION
™ FBC, U/E/Cr, CaMgPO4, LFT, TFT, Luteinising Hormone (LH)/Follicle- Adolescence is generally a healthy period of life in comparison to early
stimulating Hormone (FSH)/oestradiol childhood and old age. As healthcare professionals in contact with
this group of individuals, it is important to understand adolescent
MEDICAL INSTABILITY AND CRITERIA FOR ACUTE development and to have effective communication and consultative
ADMISSION skills to better guide treatment and management.
™ Resting heart rate < 50bpm
™ ECG abnormalities e.g. prolonged QTc The Home, Education/Employment, Activities, Drugs, Sexuality, Suicide/
™ Significant postural and/or haemodynamic changes: Depression (HEADSS) assessment is an excellent guide to obtain a
ŠHypotension bio-psycho-social biopsy and an opportunity to build rapport with the
ŠSystolic BP drop > 20mmHg from lying to standing position adolescent. It aids in risk assessment as well as helps guide intervention.
ŠDiastolic BP drop > 10mmHg from lying to standing position
ŠHeart rate increase of > 30bpm from lying to standing position HEADSS COMPREHENSIVE ADOLESCENT PSYCHO-SOCIAL
™ Dehydration SCREENING INTERVIEW
™ Temperature < 35.5°C
™ Electrolyte abnormalities Home
™ Who lives with the patient ? Where ? Own room?
ON ADMISSION TO THE GENERAL PAEDIATRIC WARD ™ What are the relationships like at home?
™ Keep Complete Rest in Bed (CRIB) ™ What do parents and relatives do for a living?
™ Monitor vital parameters four to six hourly depending on medical ™ Ever institutionalised? Incarcerated?
status ™ Recent moves — Run-away episodes
™ Cardiac monitoring
™ Postural BP and heart rate BD Education (and/or Employment)
™ Blood investigation and/or ECG as above if not already done ™ School/grade performance — Any recent changes? Any dramatic
™ Refer to the ADME team — Inform ADME doctor, resource nurse and past changes?
nutritionist ™ Favourite/worst subjects
™ Suicidal precautions if high risk ™ Any years repeated/classes failed?
™ Suspensions or termination, dropping out history
If medically stable and not high risk for suicide, all new patients with an ™ Future education/employment plans/goals
eating disorder can be referred to the ADME service as an outpatient. ™ Any current employment?
Please call the ADME physician to discuss these cases.
206 The Baby Bear Book General and Ambulatory Paediatrics 207

™ Relations with teachers, school attendance ™ History of past suicide attempts, depression, psychological
™ Bullied/bullies counselling
™ History in family or peers
Activities ™ History of drug/alcohol abuse, acting out/crime, recent change in
™ With peers (What do you do for fun? Where and when?) school performance
™ With family ™ History of recurrent serious ‘accidents’
™ Club/school functions ™ Psychosomatic symptomatology
™ Sports, regular exercise ™ Suicidal ideation (including significant current and past losses)
™ Church attendance and club projects ™ Decreased affect on interview, avoidance of eye contact
™ Hobbies — Other home activities
™ Reading for fun — What?
™ TV — How much weekly? Favourite shows?
™ Favorite music
™ Does patient have car, use seatbelts? DRUG OVERDOSE AND POISONING
™ History of arrests — Acting out, crime

Drugs GENERAL PRINCIPLES OF POISONS MANAGEMENT

™ Used by peers Presentation of poisoned paediatric patients to the Emergency
™ Used by patient; include alcohol and cigarettes Department demands prompt action to prevent poisoning by using
™ Used by family members decontamination, to enhance elimination or to treat poisoning with
™ Amounts, frequency, patterns of use/abuse and car use, while supportive care and, for a few poisons, antidotes. The cornerstone in the
intoxicated management of the poisoned child remains supportive.
™ Source — How is it paid for?
Fig. 5.3 (overleaf ) outlines the management of acute ingestions.
Sexuality Remember to treat the patient and not the poison.
™ Orientation
™ Degree and types of sexual experience and acts Clinical Presentation
™ Number of partners Child with an Acute Movement Disorder
™ History of pregnancy/abortion ™ Dyskinesia: Amphetamines, anticholinergics, antihistamines, cocaine,
™ Sexually transmitted diseases — Knowledge and prevention gamma-hydroxybutyrate
™ Contraception ™ Dystonia: Antipsychotics and metoclopramide, selective serotonin
reuptake inhibitors and tricyclic antidepressants
Suicide/Depression ™ Rigidity: Malignant hyperthermia, neuroleptic malignant syndrome
™ Sleep disorders (usually induction problems, also early/frequent and phencyclidine
waking or greatly increased sleep and complaints of increasing
fatigue) Sympathomimetic Syndrome
™ Appetite/eating behaviour changes ™ Clinical presentation: CNS excitation, seizures, tremors, hyperreflexia,
™ Feeling bored? hyper/hypotension, tachycardia
™ Emotional outbursts and highly impulsive behaviour ™ Biochemical: Low potassium, raised blood glucose, acidosis
™ History of withdrawal/isolation ™ Management: Supportive, prevent hyperthermia
™ Hopeless/helpless feelings ™ Toxic agents: Amphetamines, theophylline, salbutamol, cocaine
208 The Baby Bear Book General and Ambulatory Paediatrics 209

Acute Ingestion Serotoninergic Syndrome

™ Clinical presentation: A primary neuroexcitation spectrum of toxicity

Maintain Vital Signs involving predominantly 5-HT2 receptors with abnormalities of:
Airway Š Mental status: Agitation/restlessness/confusion/hypomania
Breathing Š Motor system: Clonus/myoclonus inducible/spontaneous/ocular
Circulation (monitor electrolytes/ECG) tremour/shivering, hyperreflexia/hypertonia/rigidity
Š Autonomic nervous system: Diaphoresis/tachycardia/flushing/
mydriasis
™ Course: Up to several days to weeks after discontinuing treatment
Conscious, Conscious, Unconscious ™ Differential diagnosis: May resemble anticholinergic and neuroleptic
Non-toxic Definite Toxicity ™ Recovery position. malignant syndromes
™ Reassure parents ™ Activated charcoal ™ Oral airway/ intubate. ™ Management: Supportive
™ Educate parents 1g/kg for absorbable ™ I/V line, KIV fluid ™ Agents involved: Monoamine Oxidase Inhibitors (MAOIs),
on ‘child-safe’ poisons resuscitation. Take clomipramine, SSRIs, tryptophan (particularly in combination)
environment ™ Milk for household blood for sugar &
™ Remarks: This clinical picture may resemble an acute infection and,
™ Discharge after review detergent ingestions. toxicology (Li Hep
™ Substances which do tube) KIV do ABG. therefore, may be easily overlooked
not bind to charcoal Consider immediate
Conscious, include strong antidote therapy : - Nueroleptic Malignant Syndrome
Intermediate Toxicity acids, alkalis, Fe, Li, Š 10%Dext.(2ml/kg) ™ Clinical presentation: Hyperthermia, muscle rigidity, metabolic
™ e.g. Paracetamol cyanide, KI, small ionic Š Naloxone (0.1mg/ acidosis and confusion
ingestions still within molecules. kg, max 2mg) ™ Toxic causes: Use of antipsychotic agents
therapeutic range, ™ Admit all cases to Š Atropine (0.02mg/
™ Management: Supportive, body cooling
& serum levels at general ward or kg)
™ Specific antidote — Bromocriptine
least 20 units below High Dependency Š 4.2% NaHCO3
toxic range in the as indicated for (1–2ml/kg) ™ Remarks: Bear in mind that this presentation may resemble the
normogram. monitoring, KIV Š Flumazenil (5μg/kg serotoninergic syndrome
™ Observe for four to six antidote therapy. stat I/V, repeat every
hours post-ingestion 60sec to max 40μg/ Anticholinergic Toxidrome
™ Discharge after review kg (max 2mg)) ™ Clinical presentation: Dry flushed skin, dry mouth, mydriasis,
™ Educate parents on Š Digibind
delirium, hallucinations, tachycardia, ileus, urinary retention,
safety precautions ™ Gastric lavage with
hyperthermia, coma and respiratory arrest
and to return to wide bore N/G tube
after airway control ™ Management: Supportive
clinic/hospital if
symptomatic ™ Contraindications: ™ Specific antidote: Physiostigmine (contraindicated if ECG or has
™ May need clinic review Corrosives, Caustics, underlying heart disease)
Acids, Petroleum ™ Remarks: The syndrome may be overlooked due its resemblance to
distillates fever and infection. It may also resemble sympathomimetic overdose
Note : ™ CXR if aspiration/
™ Look out for various toxidromes
chemical pneumonitis/ Cholinergic Toxidrome
™ If ingestion was ≤1 hour, activated charcoal or gastric
mediastinitis
lavage for gastrointestinal decontamination may be ™ Clinical presentation:
suspected
considered if indicated ™ Admit to ICU with Š Muscarinic effects: Incontinence (diarrhoea/urinary), abdominal
™ If child’s GCS is ≤8, secure airway and resuscitate before cramps, miosis, bradycardia, emesis, lacrimation, salivation
transport monitor
performing gastrointestinal decontamination respiratory hypersecretion, diaphoresis
Fig. 5.3: Management of acute ingestions.
210 The Baby Bear Book General and Ambulatory Paediatrics 211

Š Nicotinic effects: Tachycardia, hypertension, muscle fasciculation, ™ No signs to suggest non-accidental injury or neglect
paralysis, tremour, muscle weakness, agitation, seizures and coma ™ No signs to suggest willful ingestion/suicidal intent (in teenagers)
™ Management: Supportive ™ Where ‘time bomb’ ingestions are ruled out e.g. lithium, iron, MAOIs,
™ Specific antidotes: Atropine and pralidoxime phenytoin, carbamazepine, slow-release medications
™ Toxic agents: Organophosphates and carbamates
™ Clinical tip: The syndrome may be diagnosed by the specific response Gastrointestinal Decontamination
to antidotes, and by lower levels of the cholinesterase enzyme ™ Ipecac and other pro-emetic agents: Not recommended for routine
use in paediatric poisonings
Opioid Toxidrome ™ Carthartics are currently not recommended in paediatric poisoning
™ Clinical presentation: Miosis, CNS depression, (sedation and lethargy ™ Poisons with delayed gastric emptying:
to coma), respiratory depression, hypoxia, pulmonary oedema Š Aspirin
™ Differential diagnosis: Other sedative hypnotics typically do not Š Digoxin
cause miosis Š Tricyclic antidepressants
™ Management: Supportive Š Phenobarbitone
™ Specific antidote: Naloxone Š Delayed-release preparations
™ Remarks: Lomotil (diphenoxylate poisoning) and codeine in cough
mixtures
Table 5-3: Gastrointestinal decontamination — Methods, doses, indications, contraindications
and complications.
Biochemical Presentation
Child with Increased Osmolar Gap Method Dose Indications Contraindications Complications
™ Osmolar gap = (Measured osmolality) – (Calculated osmolality) Activated 1g/kg ™ ≤ one hour of ™ Unprotected ™ Aspiration
(normal 0mOsm/kg ± 5mOsm/L) Charcoal (serve with ingestion of airway ™ Peritonitis from
™ Calculated osmolality: 2 × (Na+ in mEq/L) + (Glucose in mg/dL) / 18 + (AC) syrup to increase significantly ™ Poor adsorped perforated
(BUN in mg/dL) / 2.8 = ± 290mOsm/L palatability) toxic substance substances intestines
™ ≥ one hour if Š Hydrocarbons ™ Pseudo-
™ Toxic agents: Acetone, ethanol, ethyl ether, ethylene glycol, isopropyl
delayed gastric (e.g. kerosene, intestinal
alcohol, mannitol, methanol, renal failure and ketoacidosis (diabetic emptying or camphor) obstruction
and alcoholic) sustained release Š Alcohols (e.g. (especially
preparations Methanol, with repeated
Child with an Increased Anion Gap Acidosis Ethylene charcoal doses
™ Anion gap = (Na+) – [(Cl–) + (HCO3–)] (Normal: 8–12mEq/L) glycol, and dehydration)
™ Toxic causes: Severe paracetamol poisoning, beta-adrenergic agents, Ethanol, etc)
Š Metals and
carbon monoxide, cyanine, iron, isoniazid, salicylates, theophylline,
Inorganic salts
toxic alcohols and valproic acid (e.g. Fluoride,
Iron, Lithium,
The following criteria must be satisfied before the child is discharged Potassium
from the clinic/hospital: Š Alkali and
™ Asymptomatic Mineral acids
™ No biochemical abnormalities, for example, hypoglycaemia,
metabolic acidosis
212 The Baby Bear Book General and Ambulatory Paediatrics 213

Method Dose Indications Contraindications Complications Antidotes

Gastric ™ ≤ one hour ™ Combative alert ™ Perforation of ™ Specific toxins may need specific antidotes
Lavage of significant patients oesophagus or ™ From N-acetyl-cysteine (NAC) for paracetamol poisoning to digibind
amounts of ™ Unprotected stomach for digitalis toxicity and desferoxamine for iron poisoning, the only
substances of airway ™ Nasopharyngeal
difference with regards to paediatric poisoning is in the dosage that
intermediate ™ Sustained trauma
has to be tailored to the individual paediatric-sized patient
toxicity and even release products ™ Intratracheal
small amounts or enteric coated placement ™ However some antidotes though available may not be required.
of substances of tablets (whole ™ Vomiting and Instances of seizures have occurred in benzodiazepine overdose
high toxicity bowel irrigation aspiration when support measures were sufficient till effects resolve
™ ≥ after one hour, preferable)
can still consider ™ Corrosive Enhanced Elimination
gastric lavage substances, a ™ Enhance and promote the clearance of the toxin from the system
for poisons hydrocarbon
™ Their roles depend on the substance concerned and the respective
with delayed with high
absorption aspiration pharmacokinetics with their respective volumes of distribution
potential, ™ Multiple-dose Activated Charcoal (MDAC):
rapidly absorbed Š Acts as a ‘gastric dialysis’ and has a role in specific agents
substances Š MDAC is administered as 0.5–1g/kg two to four hourly, which has
(e.g. alcohols, been shown to be useful for theophylline, phenobarbitone and
imidazoline carbamazepine poisonings, and also, theoretically, drugs with
products used in small volumes of distribution and that are not strongly protein–
over-the-counter
bounded
preparations for
nasal and ocular Š The loading dose is 10:1 (Activated charcoal-to-drug ratio), or
decongestion, 1–2g/kg if drug unknown
such as Š Doses vary from 0.25–0.5g/kg every one to six hours (adults
oxymetazoline, 20–60g) every one, two, four and six hours
naphazoline,
tetrahydrozoline) Quantitative Toxicology Tests
™ high risk of
haemorrhage or Table 5-4: The more common medications and the optimal time for screening their serum toxic
gastrointestinal levels.
perforation due
to pathology, Drug/Toxin Optimal Time after Ingestion
recent surgery Paracetamol * Four hours
or other medical Carbamazepine Two to four hours
complications
Carboxyhaemoglobin Immediate
Whole ™ Osmotically- ™ Sustained ™ Unprotected
bowel balanced agents: released airway or altered Digoxin Four to six hours
irrigation GoLytely, preparations conscious status Ethanol Half-an-hour to one hour
(WBI) Polyethylene ™ Enteric-coated ™ Intestinal Ethylene glycol Half-an-hour to one hour
glycol (PEG) to medicines obstruction
Iron Four hours
be given ingested
™ 35mL/kg/hr Lithium Two to four hours (repeat six to 12 hours later for sustained released
(max 500mL/hr) preparations)
* Follow normograms if it is an acute ingestion
214 The Baby Bear Book General and Ambulatory Paediatrics 215

Drug/Toxin Optimal Time after Ingestion Table 5-7: Substances of which one teaspoon or one tablet that can kill a 10kg child.
Methanol Half-an-hour to one hour No of Tablets/Spoonfuls
Minimum Potential Dose
Drug that can Potentially
Methaemoglobin Immediate (mg/kg)
Cause Fatality
Phenobarbitone One to two hours
Tricyclic antidepressants
Phenytoin One to two hours ™ Amitriptyline 15 1–2
Salicylates* Two to six hours (repeat six to 12 hours later for sustained released ™ Imipramine 15 1
preparations) ™ Desipramine 15 1–2
Theophylline One to two hours (repeat six to 12 hours later for sustained released Antipsychotics
preparations) ™ loxapine 30-70 1–2
™ Thioridazine 15 1
™ Chlorpromazine 25 1–2
Table 5-5: Household products and plants that are ‘toxic’ for children. Antimalarials
™ Chloroquine 20 1
Acid/Alkali: Boric acid, bowl Alcohols: Ethanol, ethylene Antiseptics: Camphor, ™ Hydroxychloroquine 20 1
cleaners, clinitest tablet, disc glycol, methanol, isopropyl hydrogen peroxide, phenol, ™ Quinine 80 1–2
battery alcohol pine oil
Anti-arrythymics
Cyanide Hydrocarbons: Aliphatics, Industrial chemicals: ™ Quinidine 15 1
aromatics Burtyrolactone (solvent ™ Disopyrimide 15 1
foracrylate), methylene ™ Procainamide 70 1
chloride, selenious acid (gun
Calcium channel blockers
blueing), zinc chloride
™ Nifidepine 15 1–2
Mothballs: Napthalene Nail products: Acetone Pesticides: ™ Verapamil 15 1
(polish remover), acetonitrile Organophosphates, carbamate ™ Diltiazam 15 1
(sculptured nailremovers),
Camphor 100 1 teaspoon
methacrylic acid (artificial
nailprimer), nitromethane Methylsalicylate 200 < 1 teaspoon
(artificial nail-remover) Theophylline 8.4 1
Plants: Aconite, cantharidin, Rodenticides: Arsenic, Weed/Bug killers: Lindane, Narcotics
castor bean, clove oil, comfrey, hydroxycoumarin, nicotine, paraquat ™ Codeine 7–14 1–2
fox glove, na hwang, specific indanediones, strychnine ™ Hydrocodone 1.5 < 1 teaspoon
mushrooms, nutmeg, oleander, ™ Methadone 1–2 1
pennyroyal oil Oral hypoglycaemics
™ Chlorpropamide 5 1
™ Glibenclamide 0.1 1
Table 5-6: Commonly ingested non-toxic substances. ™ Glipizide 0.1 1
Air fresheners, aluminium foil, antiperspirants, baby lotions, baby Wipes, ball-point pen ink, Podophyllin 25% 15–20 1ml
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 (< three paper books), newspaper,
PARACETAMOL POISONING
paraffin, pencils (contain graphite), plaster, plastics, silica gel, stamp pad link, sunscreen
products, thermometers (< 0.5ml elemental mercury), water colour paints Paracetamol poisoning is the most common form of pharmaceutical
poisoning. It is usually accidental in young children and non-accidental
in the adolescents.
216 The Baby Bear Book
Pharmacokinetics
Absorption: Paracetamol is rapidly absorbed and peak concentrations
occur within one to two hours for standard tablet or capsules and
even quicker (< half-an-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 four hours post-overdose with standard-release
preparations and within two hours in liquid preparations.
Metabolism and elimination: The half-life of paracetamol in therapeutic
use is one-and-a-half to three hours. In overdose, the clearance of
paracetamol becomes saturated and the half-life may be greater than
four 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 (see Fig. 5.6 p. 224)
™ Clinical presentation
Toxic Ingestion
Toxic ingestion is defined as follows:
™ Acute single-dose poisoning:
Š 200mg/kg or more or 10g (whichever is less) (both paediatric and
adults)
™ Repeated supratherapeutic ingestion:
Š > 24 hours staggered dose :
y In children < six years or high-risk group: 4g or more 100mg/
kg/day (whichever is less)
y > six years old: 6g or 150mg/kg/day (whichever is less)
™ Symptomatic patients:
Š This includes patients following ingestion of paracetamol that
presents with repeated vomiting, abdominal tenderness in the
right upper quadrant, or mental status changes
General and Ambulatory Paediatrics 217
Š If an unknown dose has been ingested, one should always err
on the assumption that a potentially toxic amount has been
ingested
Š Early toxic ingestion of paracetamol is usually largely
asymotomatic, apart from vomiting and nausea
Š 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 Fig. 5.6 p. 224).
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 four hours or more post-ingestion (as with standard
preparations) and repeated four 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 four 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 “Repeated supratherapeutic
toxic ingestion“ p. 222 and Fig. 5.5 p. 223). Treatment should start if
above the ‘150-line’.
218 The Baby Bear Book General and Ambulatory Paediatrics 219

Indications for Admission Aysmptomatic

™ Patient is symptomatic (irrespective of dose) Symptomatic (irrespective
™ If toxic dose is consumed (see “Toxic Ingestion” p. 216) of time of ingestion)
™ Unknown dose taken Repeated vomiting,
™ Suspected non-accidental ingestion (irrespective of dose) < two hours Two to eight > eight hours right-upper quadrant
™ Poor home support (lives alone, inability of caregivers to monitor) post-toxic hours post- post-toxic abdominal tenderness,
ingestion toxic ingestion ingestion or mental status changes
Clinical Symptoms and Signs of Paracetamol Poisoning
™ Post-acute ingestion (< 24 hours): Asymptomatic to non-specific
gastrointestinal irritation (e.g. nausea, vomiting abdominal pain) Activated Measure serum Commence IV NAC
™ 24–48 hours: Tender hepatomegaly with jaundice charcoal paracetamol investigations:
™ Day 4–5 post-poisoning: Acute liver and renal failure
1g/kg level within Serum paracetamol levels
four to eight Glucose
Other features: Erythema, urticaria, haemolytic anaemia, pancreatitis,
hours post- ALT/AST
haemorrhage ingestion INR/PT
Urea/Creatinine
Investigations in Suspected Paracetamol Poisoning Blood gas
Plot serum
Serum paracetamol level: Taken four hours post-ingestion
paracetamol
PT: Abnormal by 24–36 hours level on
LFTs: Alanine Aminotransferase (ALT)/Aspartate Transaminase (AST) normogram
begin to rise by 12 hours, peaks at 72–96 hours

Management UNDER OVER normogram

™ Resuscitation: normogram (line of probable
Š Immediate threats to the airway, breathing and circulation are (line of probable hepatic toxicity – Admit
hepatic toxicity – 150mg/L at four
extremely rare in isolated paracetamol overdose
150mg/L at four hours)
Š In exceptional cases, massive ingestion causing extremely high hours)
serum paracetamol levels (i.e. > 800mg/L) may be associated Continue IV NAC
with an early decrease in level of consciousness and with lactic
acidosis Measure ALT
If symptomatic:
Š Supportive management is appropriate in such cases, with NAC Consider co-
Commence IV NAC and at end of NAC
administered in routine doses, although prolonged infusions may perform investigations if infusion
ingestions, admit
be required not done prior:
and investigate
Glucose
Š Recovery is usual with supportive care ALT/AST
Š Any alteration of conscious state should prompt bedside ALT ↑
INR/PT
testing of the patient’s serum glucose level and correction of If asymptomatic: Urea/Creatinine
hypoglycaemia No further medical Blood gas
Š Presence of hypoglycaemia may be secondary to hepatic failure treatment required Continue IV NAC
and intensive care monitoring is required and monitor
™ Decontamination:
Š Activated charcoal: ALT Normal
y Activated charcoal (1g/kg or up to 50g) can be given if less
than two hours Fig. 5.4: Acute accidental paracetamol poisoning management flow chart.
220 The Baby Bear Book
y May have a role in sustained-release preparations even after
two hours of ingestion
Š Haemoperfusion:
y 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:
Š NAC:
y 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
y When risk assessment indicates that NAC is required, it is
administered as a three-stage infusion, totaling 300mg/kg
over 20 hours
y IV NAC is supplied as a 20% solution (200mg/ml) in 30ml vials.
It is diluted with dextrose 5% (not in normal saline)
y Note that excessive diluent volume may cause
hyponatremia and secondary seizures in children while
too highly concentrated a solution may increase the risk of
anaphylactoid reactions
y 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
y A loading dose of 150mg/kg over 15 minutes followed by
50mg/kg over the next four hours, then 100mg/kg over the
next 16 hours
Table 5-8: Dosage for children in different weight ranges.
Dosage for children weighing less than 30kg:
™ IV NAC 150mg/kg diluted with 3ml/kg of D5% over 15 to 30 minutes, then
™ IV NAC 50mg/kg diluted with 7ml/kg of D5% over four hours, then
™ IV NAC 100mg/kg diluted with 14ml/kg of D5% over 16 hours
Dosage for children weighing 30kg to 50kg:
™ IV NAC 150mg/kg diluted with 100ml of D5% over 15 to 30 minutes, then
™ IV NAC 50mg/kg diluted with 250ml of D5% over four hours, then
™ IV NAC 100mg/kg diluted with 500ml of D5% over 16 hours
Dosage for children weighing more than 50kg:
™ IV NAC 150mg/kg diluted with 200ml of D5% over 15 to 30 minutes, then
™ IV NAC 50mg/kg diluted with 500ml of D5% over four hours, then
™ IV NAC 100mg/kg diluted with 1,000ml of D5% over 16 hours
General and Ambulatory Paediatrics 221
y If hepatic injury is suspected after the three infusion stages,
NAC is continued at the rate of the last infusion stage (100mg/
kg each 16 hours or 150mg/kg/24hrs) until there is clinical and
biochemical evidence of improvement
y 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)
y 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)
y The occurrence of an anaphylactoid reaction does not
preclude the use of NAC on another occasion if indicated
y 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
Š Methionine:
y Methionine can considered as an alternative antidote for
paracetamol poisoning especially in the setting of known
allergy to NAC
y It is given orally 50mg/kg/dose (max. 2.5g) 4H for four doses. It
is associated with more adverse reactions than NAC
™ Management of non-accidental toxic ingestions:
Š Admission irrespective of levels for non-accidental ingestion
Š Serum levels mandatory
Š Management of toxicity poisoning accordingly
Š Consider multi-drug poisoning:
y Four to eight hours : Measure paracetamol levels (at or after
four hours post-ingestion)
ƒ Plot paracetamol level on normogram
ƒ Start IV NAC if over normogram at 150mg/L (1,000μmol/L)
at four hours (line of possible hepatotoxicity)
y > eight hours: Commence IV NAC (do not wait for levels)
ƒ Obtain paracetamol levels as possible
ƒ Obtain ALT stat and repeat at the end of IV NAC infusion or
12 hourly, whichever comes first
ƒ If the serum paracetamol level is subsequently found to be
below the normogram line, NAC may be ceased; if above
222 The Baby Bear Book General and Ambulatory Paediatrics 223

the line, it should be continued till below and ALT static or Adults and Children > 6 years High Risk Factors* And / Or
normal with no risk factors Children < 6 years
ƒ Obtain FBC (platelet), International Normalised Ratio (INR)
or Prothrombin Time (PT), U/E/Cr, glucose and ABG (if Ingested > 6g/day or >150mg/ Ingested > 4g/day or >100mg/
venous bicarbonate is low) and repeat as indicated kg/day (whichever is less) kg/day (whichever is less)
A baseline serum ALT level, international normalised ratio and
platelet count provide useful baseline data for later risk assessments.
™ Symptomatic patients (clinical or biochemical): Commence IV NAC
Š Start IV N-acetycyteine without waiting for levels (even < eight
hours) if symptomatic or has biochemical abnormalities
INVESTIGATIONS:
Š Obtain paracetamol levels, ALT/AST, FBC (platelet), INR or PT, U/E/ ™ Serum paracetamol levels
Cr, glucose and ABG stat ™ ALT/AST
Š If symptomatic and paracetamol levels are below the ™ Other investigations: Glucose, INR/PT, Urea/Creatinine, Blood gas
normogram, consider toxic co-ingestions
™ Repeated supratherapeutic toxic ingestion:
Š Commence IV NAC (do not wait for levels) ALT Normal Any other results
Š Obtain paracetamol and ALT/AST levels as soon as possible AND
Š If paracetamol <10mg/L and ALT/AST normal, nil further Serum Paracetamol
<10-20mg/L Admit and Continue IV NAC infusion
treatment, stop infusion
Š Obtain INR or PT, U/E/Cr, glucose and ABG (if bicarbonate
abnormal) at admission Repeat serum paracetamol level
Š Repeat ALT/AST and serum paracetamol levels at eight to 12 Stop IV NAC infusion and ALT at 8–12 hours
hours
Š If ALT/AST normal or static and paracetamol < 10mg/L, stop If asymptomatic:
infusion No further medical ALT Normal or Any other results
Š If abnormal, continue IV NAC infusion and repeat ALT/AST 12 treatment required decreasing
hourly and investigations as indicated (Grade D, Level 5)
™ Unknown time of ingestion: ™ Continue IV NAC infusion
No further
Š Start IV NAC If symptomatic: ™ Monitor ALT 12 hourly
treatment required intervals
Š Investigations and management are similar to supratherapeutic Consider co-ingestions,
admit and investigate ™ Other monitoring
repeated dose ingestion
and investigations as
™ Severe paracetamol poisoning: indicated
Š Hepatocellular necrosis is the major toxic effect of paracetamol ™ Refer to specialist
poisoning
Š Biochemical evidence of maximal damage may not be attained High-risk Groups*
until 72–96 hours after ingestion of the overdose ™ Regular ethanol consumption >21 units/week in males, 14 units/week in females
Š Severe liver damage in the context of paracetamol poisoning has ™ Conditions causing gluthathione depletion — Malnutrition, HIV, eating disorders, cystic fibrosis
been defined as a peak plasma ALT activity exceeding 1,000IU/L. ™ Regular use of enzyme-inducing drugs:
For those institutions who do not have ready access to ALTs, AST Š Anti-epileptics — Carbamazepine, phenytoin, phenobarbitone
may be used instead Š Anti-TB drugs — Isoniazid, rifampicin
Š Other drugs — St John’s Wort

Fig. 5.5: Repeated supratherapeutic ingestion management flow chart.

224 The Baby Bear Book General and Ambulatory Paediatrics 225

Š 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
Š Resuscitation and intensive care monitoring is required
Š One should consider need for transfer post-stabilisation to a liver
transplant unit

Indicators of Severe Paracetamol Poisoning

™ Metabolic:
Š Metabolic acidosis (pH < 7.3 or bicarbonate < 18) despite
rehydration
Š Hypotension despite adequate fluid resuscitation
Š Hypoglycaemia
™ CNS:
Š Encephalopathy or signs of rasised ICP
™ Liver function/coagulopathy:
Š INR > 2.0 at or before 48 hours or > 3.5 at or before 72 hours
Š Consider measuring INR every 12 hours
Š Peak elevation occurs around 72–96 hours
Š LFTs are not good markers of hepatocyte death
™ Renal:
Š Renal impairment (creatinine > 200μmol/L)
Š Monitor urine output
Š Serial U/E/Cr
Š Consider haemodialysis if > 400μmol/L

Fig. 5.6: 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).
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.
226 The Baby Bear Book General and Ambulatory Paediatrics 227

Table 5-9: Types of salicylate poisoning.

™ Salicylic acid (HS) is a weak acid that exists in a charged
Salicylate Conversion Type of Use Remarks (deprotonated) and uncharged (protonated) form: H+ + sal- <—> HS
Factor ™ Treatment of salicylate intoxication is directed toward increasing
Aspirin 1.00 Oral, suppositories systemic and urine pH and driving the above reaction to the left,
Bismuth 0.50 Oral Pepto-Bismol®, Maalox Total ‘trapping’ the salicylate anions in the blood and urine (by preventing
subsalicylate Stomach Relief®, Kaopectate® back-diffusion across the renal epithelium into the systemic
contain 262mg (regular circulation)
strength) or 525mg (extra-
strength) of bismuth salicylate Admission for Further Evaluation and Management
per 15ml; which yield 8.7 or
™ All symptomatic patients should be admitted irregardless of dose
17.5mg/ml of aspirin equivalent
ingested e.g. haematemesis, tachypnoea, hyperpnoea, dyspnoea,
Choline magnesium 1.30 Oral
tinnitus, deafness, lethargy, seizures, unexplained lethargy, or
salicylate
confusion
Choline salicylate 0.75 Oral
™ All patients with known or suspected suicidal intent or non-
Magnesium 1.21 Oral accidental ingestion (e.g. child abuse) irrespective of amount
salicylate ingested
Methyl salicylate 1.18 Dermal, flavouring ™ Poor home support (lives alone, inability of caregivers to monitor)
agent ™ If asymptomatic and had suspected toxic ingestion
Oil of wintergreen 1.40 Dermal, flavouring Contains methyl salicylate 98% ™ Acute ingestion of aspirin or aspirin equivalent of an amount that
agent w/w, 1ml = 1.4g aspirin exceeds 150mg/kg or 6.5g, whichever is less
Salicylic acid 1.30 Dermal > 6% may cause tissue ™ Ingestion of oil of wintergreen (98% methyl salicylate) if:
destruction on contact or Š Under six years of age and greater than a lick or taste
ingestion
Š Patients six years of age and older > 4mL
Salsalate 1.40 Oral
Sodium salicylate 1.13 Oral Determination of Severity
Trolamine salicylate 0.63 Dermal In the initial assessment of the severity of toxicity the four following
areas should be considered:
™ Dose ingested
Pharmacokinetics ™ Salicylate concentration
™ The type of formulation (e.g. liquid, effervescent, extended-release, ™ Clinical grading of toxicity
enteric-coated) affects the degree of absorption ™ Acid-base grading of severity
™ With therapeutic dosing of regular aspirin tablets, peak plasma
concentrations are usually achieved 15–60 minutes after ingestion. Toxic Ingestion
Peak concentrations following ingestion of extended-release or
Table 5-10: Assessment of acute salicylate intoxication based on dose ingestion (Temple, 1981).
enteric-coated preparations typically occur between four to 14 hours
after ingestion Ingested Dose (mg/kg) Estimated Severity
™ Peak concentrations in overdose may be delayed as a result of < 150 No toxic reaction expected
pylorospasm or bezoar formation 150–300 Mild to moderate toxic reaction
™ Exhibits saturation kinetics in overdose in high doses; half-life of 300–500 Serious toxic reaction
salicylate is greatly increased (may be up to 30 hours)
> 500 Potentially Lethal
™ For children on chronic salicylate therapy, even a slight change in
dose may result in a great increase in plasma concentration
228 The Baby Bear Book General and Ambulatory Paediatrics 229

Chronic toxicity can develop from doses of 100mg/kg/day. Patients with Biochemical Presentation
cirrhosis, low protein states or renal impairment develop toxicity with In children with salicylate poisoning, plasma concentrations six hours
lower doses. after an acute overdose very roughly correlate with toxicity as follows:

Clinical Presentation Severity of Acute Toxicity Serum Concentration (Post-six hours)

™ The triad of salicylate poisoning consists of hyperventilation, tinnitus, Mild Toxicity 30–50mg/dL
and gastrointestinal irritation (classic salicylism) Moderate Toxicity 50–70mg/dL
™ Paediatric patients may not manifest respiratory alkalosis Severe Toxicity > 75mg/dL
™ In children: Hyperventilation, dehydration and neurological
dysfunction are greater in chronic overdoses compared with single Salicylate Concentration Conversion Factor:
acute ingestions mg/dL x 0.0072 = mmol/dL
™ Pyrexia: Mild pyrexia is common and is due to increased metabolic mmol/dL ÷ 0.0072 = mg/dL
activity
™ Gastrointestinal effects: Nausea and vomiting are common. The use of Done Normogram formulated may have limited applicability
Less common are epigastric pain and haematemesis. Vomiting in aspirin-poisoned patients.
contributes significantly to electrolyte imbalance and dehydration.
Aspirin, especially enteric-coated formulations, are known to develop Metabolic acidosis: Major feature of salicylate poisoning as a result of
concretions and bezoars in the stomach and act as a direct GI irritant ‘uncoupling of oxidative phosphorylation’ which leads to:
leading to nausea, vomiting, and abdominal pain ™ Increase in metabolic rate
™ Increased oxygen consumption
CNS effects: CNS symptoms can occur with declining salicylate ™ Increased CO2 formation
concentrations because of CNS trapping of ionised salicylate. ™ Increased heat production
™ Increased glucose utilisation
CNS Effects in Salicylate Poisoning Clinical Manifestations
Mild Nausea, vomiting, tinnitus This may be exacerbated by:
Moderate Confusion, hyperventilation ™ Accumulation of organic acid metabolites
Severe Hallucinations, seizures, ™ Starvation and dehydration induced ketosis
coma, cerebral oedema ™ Lactic acidosis

™ Others: Non-cardiogenic pulmonary oedema and renal failure occur Glucose Metabolism
occasionally and always in association with other signs of significant Hypoglycaemia: Intracellular > extracellular
poisoning May occur due to:
™ Increased peripheral glucose demand
™ Increased rate of tissue glycolysis
™ Impaired rate of glucose synthesis
Table 5-11: Clinical grading of salicylate toxicity.
Note that tissue may be lower than plasma glucose.
Severity Clinical features
Mild Nausea, vomiting, tinnitus Hyperglycaemia: May occur due to increased glycogenolysis.
Moderate Confusion, hyperventilation
Severe CNS: Hallucinations, seizures, coma, cerebral oedema Hypokalaemic patients or patients with total body potassium depletion
Respiratory: Pulmonary oedema are unable to produce an alkaline urine.
230 The Baby Bear Book General and Ambulatory Paediatrics 231

Coagulation effects: Salicylates competitively inhibit Vitamin Differential Diagnosis

K-dependent synthesis of factors II, VII, IX and X, reflected in an increased ™ DKA (glucose high but in salicylate poisoning tends to be low)
INR. A prolonged PT, usually > twice normal, occurs predictably in ™ Severe dehydration/gastroenteritis with metabolic acidosis
significant overdoses. Vitamin K will correct the PT rapidly. As in ™ Sepsis syndrome
therapeutic use, aspirin, but not other salicylates, impairs platelet ™ IEM
aggregation. ™ Other forms of poisoning such as ethylene glycol or ethanol
intoxication
Hepatic effects: Rises in transaminases occur not uncommonly, are
usually not clinically significant, and resolve over several days. Management of Salicylate Poisoning
™ The goals of treatment of salicylate intoxication are to correct fluid
and electrolyte imbalance and to enhance excretion
Table 5-12: Biochemical investigations.
™ Treatment of salicylate intoxication is directed toward increasing
Biochemical Investigations Timing Comments systemic and urine pH by the administration of sodium bicarbonate
Full blood count Baseline Salicylate excretion depends on the following factors:
Coagulation profile Baseline Any coagulopathy should be ™ Dose of salicylates
corrected with IV Vitamin K ™ Blood and urine pH: An alkaline urine (pH >7.5) dramatically
Urea, calcium, creatinine, Baseline and repeat as Keep K in the optimal range of increases salicylate clearance by ion-trapping
glucose necessary in moderate to 4–4.5mmol/L ™ Potassium concentration: In the presence of hypokalaemia, urine
severe salicylate poisoning alkalinisation is impossible
Arterial blood gas Baseline and repeat as ™ Hypokalaemia may be noted only when the serum pH is corrected
necessary in moderate to as the acidosis may mask severe potassium depletion (particular
severe salicylate poisoning common in chronic poisoning)
Urinalysis and urine pH Baseline and repeat as Keep urine pH between 7.5–8 ™ Pre-existing liver or renal failure
necessary in moderate to Titrate bicarbonate infusion as
severe salicylate poisoning necessary Resuscitation
Plasma salicylate Six hours post-ingestion Repeat salicylate level ™ Airway:
concentration every two hours until levels Š Intubation of the salicylate-poisoned patient can be detrimental
declining then as necessary and should be avoided unless necessary
Š If intubation is necessary for severe obtundation, hypotension,
hypoventilation, or severe metabolic acidosis, ensure
Table 5-13: Acid-based grading of severity of salicylate toxicity.
appropriately high minute ventilation and maintain alkalaemiae
Stage Blood pH Urine pH Comment (via serial blood gas analysis)
I > 7.4 >6 Respiratory alkalosis Š Consider haemodialysis for patients who require intubation
Increased urinary excretion of NaHCO3, K+ ™ Breathing:
& Ca2+ Š Supplemental oxygen should be administered as needed.
II > 7.4 <6 Metabolic acidosis with compensating Pulmonary oedema and acute lung injury may occur and should
respiratory alkalosis be treated with oxygen and if available non-invasive ventilation.
Intracellular K+ depletion, urine H+ Intubation with positive end-expiratory pressure (PEEP) may be
excretion necessary, but should be avoided if possible (Grade D, Level 5)
III < 7.4 <6 Severe hypokalaemia and metabolic
acidosis
232 The Baby Bear Book
™ Circulation:
Š IV fluids should be administered as necessary to replace
insensible fluid losses (one-and-a-half to two times maintenance)
from hyperpyrexia, vomiting, diaphoresis, and elevated metabolic
rate
Š There should be judicious administration of fluids in presence of
suspected pulmonary oedema or cerebral oedema
™ Supportive treatment:
Š Supplemental glucose:
y Salicylate intoxication may decrease CNS glucose levels
despite a normal peripheral glucose level
y Supplemental glucose should be given to patients
with altered mental status regardless of serum glucose
concentration
Š Potassium repletion:
y Hypokalemia, if present, must be treated aggressively as it
results in ineffective urine alkalinisation
y 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 four hours for 24 hours in a
dose of 1g/kg (maximum 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:
Š Alkalinisation with sodium bicarbonate (i.e. urinary and serum
alkalinisation) is an essential component of management of the
salicylate-poisoned patient
Š Alkalaemia from respiratory alkalosis is not a contraindication to
sodium bicarbonate therapy
Š In severe salicylate poisoning with systemic pH < 7.4, give a slow
bolus of 1–2mEq/kg/h of NaHCO3. Bicarbonate should be added
to the main drip with IV infusion rates of starting at a rate of at
least one-and-a-half to two times the maintenance fluids and
General and Ambulatory Paediatrics 233
adjusted to maintain a urine output of 1.5–2mL/kg/hour with
urine pH 7.5–8
Haemodialysis
™ Hemodialysis is the definitive treatment to prevent and treat
salicylate induced end-organ injury
™ The indications for hemodialysis are primarily clinical and include:
Š Severe acidosis or hypotension refractory to optimal supportive
care (regardless of absolute serum aspirin concentration)
Š Evidence of end-organ injury i.e. seizures, rhabdomyolysis,
pulmonary oedema
Š Renal failure
Š 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
Š 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 two to three hourly until both
the plasma salicylate level is falling and the acid-base status is stable
or improving for two consecutive readings
™ Aim to achieve a urine pH of 7.5–8.0:
Š Adjust the rate of sodium bicarbonate infusion if the urine pH
remains < 7.5
™ Check urea and electrolytes every three to four 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
234 The Baby Bear Book 235

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. GENETICS
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 foetal 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:
Š 1-in-650 live births, can vary between 1-in-600 to 1-in-2,000
among different opulations
Š Overall incidence rises after maternal age of 35 years
™ Features:
Š 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. A hundred percent have at least four features and 89%
have six or more features
236 The Baby Bear Book
Š 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
Š Short stature
Š Developmental delay, intellectual disability. Intelligence Quotient
(IQ) is typically between 25 and 50
Š CHDs in about 40% of cases. The common defects are: VSD, AVSD,
ASD, FT and PDA
Š Gastrointestinal malformations in about 15% of cases, including
tracheooesophageal fistula (TOF), pyloric stenosis, duodenal
atresia, annular pancreas, Hirschsprung’s Disease and imperforate
anus
Š Haematologic disorders: Neonatal polycythaemia, leukaemoid
reaction and acute leukaemia (characteristically AML-M7). The
incidence of leukaemia in Down Syndrome is about 1%.
Š Thyroid disorders are common, thus annual TFTs are
recommended
™ Cause:
Š 95% have trisomy for chromosome 21, due to non-disjunction
Š 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
Š < 1% have mosaic trisomy 21
™ Diagnosis:
Š Karyotype
Š In the case of an unbalanced translocation, parental karyotyping
is indicated
™ Recurrence risks:
Š For trisomy 21, the recurrence risk after one affected child is
generally accepted to be 1%
Š 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
Genetics 237
Š 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%
Š 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:
Š About 1-in-8,000 live births
™ Features:
Š Pre- and postnatal growth restriction
Š Polyhydramnios and decreased foetal activity
Š Dysmorphic features: Prominent occiput, micrognathia, low-set
malformed ears, overlapping flexed fingers, prominent calcaneus,
short sternum, undescended testes
Š Severe mental deficiency
Š Neonatal hypotonia, followed by development of hypertonia
Š CHD in about 85% of cases, including valvular heart disease, VSD,
PDA, etc. Cardiopulmonary abnormalities are the chief cause of
mortality
Š Urogenital and gastrointestinal anomalies
™ Cause:
Š Majority have trisomy for chromosome 18, which is associated
with advanced maternal age
Š A few have translocations
Š Diagnosis by karyotype
™ Recurrence risk:
Š 0.5% for trisomy 18 after one affected child
Trisomy 13 (Patau Syndrome)
™ Birth incidence:
Š About 1-in-30,000 live births
238 The Baby Bear Book
™ Features:
Š Mean birth-weight is 2,600g. Postnatally, they characteristically
have feeding difficulties and FTT
Š 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
Š Severe developmental retardation. Holoprosencephaly is
common
Š CHDs and structural renal anomalies are common
Š An interesting haematologic finding is that of nuclear projections
in polymorphonuclear leukocytes, which has been reported in
25–80% of cases
™ Cause:
Š Majority have trisomy for chromosome 13, which is associated
with advanced maternal age
Š Diagnosis by karyotype
Š Recurrence risk low for trisomy 13
Turner Syndrome
™ Birth incidence:
Š About 1-in-3,000 liveborn girls
Š 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:
Š In neonates, lymphoedema of hands and feet and excess nuchal
skin
Š Short stature. Mean untreated adult height is about 145cm
Š Pubertal failure, infertility due to streak gonads
Š Dysmorphic features: Webbed neck, increased carrying angle
of elbows, broad (shield) chest, widely spaced nipples, narrow
hyperconvex nails, multiple-pigmented naevi
Š CHDs in 23%, most commonly bicuspid aortic valve, coarctation
of the aorta and aortic valve disease
Š Structural renal anomalies
Š Majority have normal intelligence, but may have specific learning
difficulties
Š Hypothyroidism, DM and inflammatory bowel disease occur more
frequently in girls and women with Turner Syndrome, than in the
general population
Genetics 239
Š Patients with a 45,X/46,XY karyotype have an increased risk of
gonadoblastoma
™ Cause:
Š 50% have 45,X karyotype
Š About 20% have isochromosome X
Š About 30% have mosaicism (45,X/46,XX or 45,X/46,XY)
Š A small proportion have other rarer karyotypes
Š Diagnosis by karyotype
Š Early endocrine referral is recommended for assessment
regarding growth hormone treatment
Fragile X Syndrome
™ Incidence:
Š 1-in-4,000 males
Š This is the most common form of inherited intellectual disability
™ Features:
Š Intellectual disability of variable severity
Š Dysmorphic features: Macrocephaly, long face, prominent jaw
(which develops during adolescence), big ears, post-pubertal
macro-orchidism
Š Delayed developmental milestones
Š Shy personality
Š Behavioural problems: Autism, ADHD and hyperactivity
™ Cause:
Š 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
Š The FMR1 gene consists of a sequence of CGG triplet repeats.
Normally, there are 5–55 CGG triplet repeats
Š 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
Š 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
240 The Baby Bear Book
Š 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:
Š Cytogenetics: Culture of cells in folate-deficient medium
Š Molecular 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.
However, in a child with intellectual disability who has not had
any investigations, karyotype analysis should be done to exclude
other chromosomal abnormalities
Š 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:
Š 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
Š Cleft palate, submucous cleft palate, velopharyngeal
incoordination or incompetence (resulting in nasal regurgitation,
hypernasal voice and recurrent serous otitis media)
Š CHDs, including VSD, right-sided aortic arch, FT, pulmonary
atresia with VSD, interrupted aortic arch. Conotruncal defects are
the most characteristic
Š Learning difficulty and mild intellectual disability
Š Structural renal anomalies in about 35% of cases
Š T-lymphocyte dysfunction and hypocalcaemia in infancy may
occur, which are features of DiGeorge Syndrome
Š Psychiatric illness in up to 20% of affected adults, in particular
schizophrenia
™ Cause:
Š Submicroscopic deletion of chromosome 22q11
Š Inheritance is autosomal dominant, with variable expressivity
Š Majority of cases represent new mutations; about 15% have
inherited the microdeletion
Genetics 241
™ Diagnosis:
Š Fluorescent in-situ hybridisation (FISH)
Š 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%
Š 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:
Š Dysmorphic features: Epicanthic folds, periorbital fullness, stellate
iris pattern, flat midface, depressed nasal bridge, anteverted
nostrils, long philtrum, thick lips
Š Growth deficiency
Š Infantile hypercalcaemia
Š CHDs, most commonly supravalvular aortic stenosis and
pulmonary artery stenosis
Š Intellectual disability
Š Characteristic personality: Unreserved, gregarious pattern of
speech, described as ‘cocktail party’ manner
™ Cause:
Š Deletion of chromosome 7q11.23 that includes the elastin (ELN)
gene in 95% of patients
Š 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 do not reproduce
™ Diagnosis by FISH
OTHER DISORDERS
Noonan Syndrome
™ Incidence 1-in-1,000 live births
™ Features:
Š Short stature
Š Dysmorphic features: Hair may be wispy in infancy and become
curly and woolly in childhood. The facial features change with age
Š 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
242 The Baby Bear Book
Š 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
Š CHDs in about 65%, most commonly dysplastic pulmonary valve
and/or pulmonary valve stenosis. HCM, obstructive or non-
obstructive, occurs in 20–30%
Š 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
Š Mild intellectual disability in 35%. Mean IQ ranges from 64 to 127.
There may be specific learning problems, especially with speech
and articulation
Š Structural renal anomalies
Š Lymphatic abnormalities, including lymphoedema
Š Bleeding abnormalities in 50–65%, including factor XI, XII or
VIII deficiency, von Willebrand Disease (vWD) and Platelet
Dysfunction
™ Cause:
Š 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
Š Mutations in a gene called PTPN11 (chromosome locus 12q24.1)
have been identified in about 50% of people with Noonan Syndrome
Š Diagnosis is clinical
Marfan Syndrome
™ Incidence 1-in-5,000 to 1-in-10,000
™ Features:
Š Tall stature and disproportionately long limbs, resulting in a
decreased upper-to-lower-segment ratio and an increased arm-
span-to-height ratio
Š Other musculoskeletal features: Arachnodactyly, joint
hypermobility, reduced elbow extension, pectus excavatum or
carinatum, flat feet, scoliosis
Š Facial features: Dolichocephaly, long face, high-arched palate
with dental crowding
Š 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
Genetics 243
or aortic dissection and rupture. These are the leading causes of
death in people with Marfan Syndrome
Š Ocular abnormalities: Lens dislocation in 50–80% of cases
(usually upward), flat cornea, increased axial length of the globe,
hypoplastic iris or ciliary muscle
Š Pulmonary apical bullae, spontaneous pneumothorax (frequency
is low: 4.4%)
™ Cause:
Š Autosomal dominant inheritance, with very high penetrance.
About 25% of patients represent new mutations
Š 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. Genetic heterogeneity in Marfan Syndrome
is also possible, with at least one other possible locus being
mapped. Thus, in a person who fulfils the Ghent criteria for
Marfan Syndrome, not finding a mutation in FBN1 does not
exclude the presence of Marfan Syndrome. For all these reasons,
diagnosis of Marfan Syndrome remains clinical. Mutation analysis
is usually embarked on, if there are considerations about prenatal
diagnosis or pre-implantation genetic diagnosis
™ Diagnosis:
Š Clinical criteria (the Ghent diagnostic nosology)
Š 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.
244 The Baby Bear Book Genetics 245

THE DYSMORPHIC CHILD ™ Developmental:

ŠEarly developmental milestones
The word ‘dysmorphic’ refers to an unusual appearance, usually of the ŠDevelopmental regression
face. A dysmorphic child may present with the following problems: ŠFormal developmental, hearing or vision assessments
™ One or more birth defects or malformations, e.g. cleft lip/palate or ŠBehaviour
CHD ŠSleep patterns, e.g. frequent nocturnal awakening and
™ Developmental delay or intellectual disability fragmented sleep in children with Smith-Magenis Syndrome
™ FTT or obesity Š Personality, e.g. gregarious ‘cocktail party’ personality in Williams
™ Short or tall stature Syndrome
™ Behavioural problems, e.g. ADHD ™ Medical:
Š Thorough list of malformations present
WHY IS IT IMPORTANT TO MAKE A DIAGNOSIS FOR A Š Medical problems, e.g. seizures
DYSMORPHIC CHILD? ™ Family:
In most situations, having a diagnosis for a dysmorphic child does Š A three-generation pedigree, noting consanguinity, miscarriages,
not mean that there is a specific intervention or treatment. Why, then, stillbirths and deaths of siblings
should we try to come to a diagnosis? Having a specific diagnosis:
™ Makes available to the parents and doctors all the accumulated CLINICAL EXAMINATION
knowledge about the condition ™ Overall appearance (gestalt)
™ Gives information about the possible complications, allowing early ™ Facial appearance:
detection, treatment and possibly prevention of complications Š Shape of head and face
™ Gives information about prognosis and risk of recurrence Š Spacing of eyes (hyper- or hypotelorism), length of palpebral
™ Gives families the option to access relevant support groups fissures, upslanting or downslanting palpebral fissures
™ Facilitates participation in research into identification of causative ™ Size and shape of nose and mouth
genes and therapeutic options ™ Shape and position of ears
™ Proportion of limbs, joint contractures, joint hypermobility
HISTORY ™ Hands and feet: Size, shape, number of digits, nails
™ Pregnancy: ™ External genitalia
Š Previous pregnancy losses ™ Skin changes, e.g. hyperpigmented or depigmented lesions
Š Maternal illnesses during the pregnancy, e.g. fever or rash ™ Birth defects, e.g. cleft lip
Š Exposure to medications, alcohol, cigarette-smoking, or ™ Cardiovascular examination
recreational drugs ™ Abdominal palpation for organomegaly
Š Results of prenatal tests, e.g. ultrasound scans, amniocentesis
™ Perinatal: Minor Anomalies
Š Details of the birth, including evidence of polyhydramnios, ™ These are defined as physical features present in < 5% of the general
oligohydramnios or foetal distress, gestation at birth, mode of population, which are of no clinical significance in themselves
delivery ™ They may be clues to the underlying diagnosis, especially if more
Š Birth-weight, length and head circumference of the baby at birth than three are present together
Š Condition of the baby soon after birth, including evidence ™ They are most common in the face, external ears, hands and feet
of respiratory distress, feeding problems and neonatal ™ They may be present as a familial trait. Parents and siblings should be
hypoglycaemia examined before ascribing significance to a particular anomaly
246 The Baby Bear Book
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 247
LABORATORY INVESTIGATIONS
Generally, ‘genetic’ investigations are labour-intensive and expensive.
Thus, they should be ordered judiciously.
Cytogenetics/Chromosome studies
™ Standard banded karyotype:
Š To be visible on a standard karyotype, a chromosome deletion or
duplication probably involves more than five million bases of DNA
Š 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:
Š 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
™ Practical points:
Š 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
Š 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 (Ghent diagnostic nosology)
™ Indications for undertaking molecular studies include:
Š When the diagnosis is not clear clinically
Š When the parents are at risk of a second affected child and would
like prenatal diagnosis
™ Potential limitations of molecular studies:
Š 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
Š 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
248 The Baby Bear Book
™ Practical points:
Š For molecular/DNA studies, send 3–5mls of blood in an EDTA
tube (purple-topped Vacuette) to the DNA laboratory
Š 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,
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
Genetics 249
™ 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.
THALASSAEMIA —
SCREENING AND MANAGEMENT
Thalassaemia is the most common genetic disease in Singapore with an
estimated 4% of the population carrying the disease gene. It is inherited
in an autosomal recessive manner. A couple who are both carriers of the
disease gene (heterozygotes) would be at 25% risk for an affected child
(homozygote) with thalassaemia major.
The main type of Hb present is HbA. This comprises 2α and 2β chains
in a tetramer (α2β2). The two main forms of thalassaemia are thus the
α-type and the β-type.
250 The Baby Bear Book Genetics 251

Β THALASSAEMIA
The β-globin gene is on chromosome 11. More than 200 mutations have
been described in this gene with resultant reduction in the production
of normal β-globin chains. Each population group has a characteristic
spectrum of mutations. FBC
MCV < 80
β Thalassaemia Minor or Trait MCH < 26
Diagnosis
FBC Microcytic anaemia
Hb 9–12g/dL
MCV < 80fL Hb Electrophoresis
Hb electrophoresis HbA2 increased HbH Inclusion bodies
HbF increased S. Ferritin, Fe / TIBC
HbH inclusion bodies Absent
Serum iron Normal

Treatment
™ No treatment necessary
™ Normal lifespan expected
™ Family screening and genetic counselling S. Ferritin ↓ S. Ferritin (N)
™ Refer to the National Thalassaemia Registry S. Fe ↓ / HbE positive HbA2 ↑ HbH positive HbA2 (N)
TIBC ↑ HbH (-)
β Thalassaemia Major
Clinical Presentation
™ Presents at < one year of age
™ Marked pallor
™ Mild jaundice HbE
™ Hepatosplenomegaly Consider α thal
Iron deficiency heterozygote / β thal minor α thal minor
minor
™ Thalassaemic facies homozygous

Diagnosis
FBC Severe microcytic anaemia
Hb < 6g/dL
MCV < 60fL DNA analysis
WBC and platelets normal of α– globin
Hb electrophoresis No HbA gene
Increased HbF and HbA2 Fig. 6.1: Suggested flow chart for thalassaemia screening.
HbH inclusion bodies Negative
Serum ferritin Normal
252 The Baby Bear Book Genetics 253

Treatment ™ Exjade®/Deferasirox
Transfusion Š Oral chelator
™ Hypertransfusion regime i.e. keep pre-transfusion Hb > 9g/dL Š Dose 20–30mg/kg/dose once daily
™ Give 20ml/kg packed cells, each pint over two to four hours Š Side effects: Rash, gastrointestinal disturbances, mild increases in
™ Blood transfusion reactions: serum creatinine that are rarely clinically significant
Š Fever Š Its efficacy in removing cardiac iron is not established yet
Š Urticaria Š Use is likely to be limited by high cost
Š Wheezing
Š Rarely, anaphylactic shock Haematopoietic Stem Cell Transplantation
™ Management of transfusion reaction: ™ Histocompatible marrow or cord blood donor, usually sibling
Š Stop transfusion ™ Disease-free survival of up to 82% in good-risk patients
Š Hourly BP, temperature, pulse rate and respiratory rate
Š Take blood for antibody studies Splenectomy for Hypersplenism
Š IV promethazine 0.5mg/kg stat ™ Preferably > five years old
Š IV hydrocortisone 4mg/kg stat ™ Absolute indications: ↓ total white, ↓ platelets
Š Consider pre-medication or washed cells for subsequent ™ Relative indications: Increasing blood requirements > 200mL packed
transfusions cell transfusion/kg/year, large size of spleen
™ Long-term complications of hypertransfusion regime: ™ Pneumococcal vaccine before splenectomy: 0.5ml IM
Š Excessive iron overload — Haemosiderosis: ™ Penicillin prophylaxis after splenectomy: 250mg BD
y Heart: Cardiomyopathy
y Liver: Cirrhosis Supplements
y Pituitary gland: Retardation of growth, delayed puberty ™ Folate 5mg OM
y Thyroid gland: Hypothyroidism ™ Vit C 100–200mg OM
y Parathyroid gland: Hypoparathyroidism ™ Multivitamins
y Pancreas: DM ™ Calcium
y Skin: Pigmentation
Š Blood-borne infections: Serial Monitoring Six-monthly or Yearly
y Hep B, Hep C, HIV, malaria, syphilis, CMV ™ FBC
™ Serum ferritin
Iron Chelation ™ LFTs
™ Desferal®/Deferoxamine: ™ Sugar
Š Start when serum ferritin > 1,000μg/L ™ Calcium/phosphate
Š Dose 25–50mg/kg/day, four to seven days/week ™ Thyroxine/TSH
Š Infuse subcutaneously over eight to 12 hours each night ™ Eye/hearing review
Š Side effects: Hard, painful swelling at injection sites; visual and ™ Cardiac: 2D Echo, MR T2* scan
auditory neurotoxicity; osteoporosis
™ Ferriprox®/Deferiprone: β Thalassaemia Intermedia
Š Oral chelator Causes
Š Particularly effective for myocardial iron removal ™ HbE/β thalassaemia
Š Dose 75–100mg/kg/day TDS (500mg per tablet) ™ Homozygous β+ thalassaemia genes
Š Danger of neutropaenia ™ Concomitant α thalassaemia
Š Monitor with weekly neutrophil count ™ Hereditary persistence of HbF
254 The Baby Bear Book Genetics 255

Clinical Presentation α1-Thalassaemia Trait

™ Presents at two years or older Diagnosis
™ Moderate pallor FBC Microcytic anaemia
™ Mild jaundice Hb 9–12g/dL
™ Hepatosplenomegaly MCV < 80fL
™ Thalassaemic facies Hb electrophoresis Normal
HbH inclusion bodies Usually positive
Diagnosis Serum iron Normal
FBC Moderate microcytic anaemia DNA analysis --/αα or -α/-α
Hb 6–9g/dL
MCV < 70fL Treatment
WBC and platelets normal ™ No treatment necessary
Hb electrophoresis No HbA ™ Normal lifespan expected
Increased HbF ™ Family screening and genetic counselling
Presence of HbE (In HbE/β thal) ™ Refer to the National Thalassaemia Registry
HbH inclusion bodies Negative
Serum iron Normal HAEMOGLOBIN H (HBH) DISEASE
Clinical Presentation
Treatment ™ Presents four years and older
™ Folate 5mg OM ™ Mild to moderate pallor
™ Transfusion therapy as necessary ™ Mild jaundice
™ Iron chelation if hypertransfusion needed ™ Hepatosplenomegaly
™ Splenectomy if indicated ™ Thalassaemic facies

α THALASSAEMIA Diagnosis
There are 4α globin genes — two on each chromosome 16. The FBC Moderate microcytic anaemia
α-thalassaemia syndrome results from deletion of one or more of the Hb 6–10g/dL
α-globin genes. In general, the severity is proportionate to the number MCV < 70fL
of α-globin genes deleted and this can be measured by DNA analysis. Hb electrophoresis Decreased HbA2
HbH 10–15%
Silent Carrier (α2-thalassaemia Trait) HbH inclusion bodies Positive
Diagnosis Serum iron Normal
FBC Normal DNA analysis --/-α or --/αcsα
Hb electrophoresis Normal
HbH inclusion bodies Negative Treatment
DNA analysis -α/αα or αcsα/αα ™ Folate 5mg OM
™ Transfusion as necessary
Treatment ™ Splenectomy if indicated
™ No treatment necessary
™ Normal lifespan expected
™ Family screening and genetic counselling
™ Refer to the National Thalassaemia Registry
256 The Baby Bear Book Genetics 257

FOETAL HYDROPS SYNDROME/BART’S HYDROPS FOETALIS and offered the option of prenatal diagnosis. The preferred method
Clinical Presentation for prenatal diagnosis is by Chorionic Villus Sampling (CVS) and this is
™ Maternal toxaemia during pregnancy done at ten to 12 weeks’ gestation. The sample is then subjected to DNA
™ Hydrops foetalis analysis.
™ Stillbirth or early postnatal death
BIBLIOGRAPHY
1. Weatherall DJ, Clegg JB. The Thalassaemia Syndromes. 4th Ed. Blackwell Science; 2001.
Diagnosis 2. Cao A, Rosatelli MC, Monni G, Galanello R. Screening for thalassaemia: A model of success.
FBC Severe anaemia Obstet Gynecol Clin North Am; 2002(29):305–28.
Hb < 3g/dL 3. NF Olivieri. The β-Thalassaemias. N Eng J Med. 1999;341(2):99–109.

Hb electrophoresis Hb Bart’s (γ4)

DNA analysis --/--

αβ THALASSAEMIA
Since both α and β thalassaemia are prevalent in the population,
double heterozygosity with both α and β thalassaemia can occur. This
presents a challenge in screening as it impacts on the genetic risks of
the individual.

Diagnosis
FBC Mild microcytic anaemia
Hb 10–12g/dL
MCV < 80fL
Hb electrophoresis Increased HbA2
HbH inclusion bodies Negative
Serum iron Normal
DNA analysis of both α and β genes — gold standard for diagnosis

Treatment
™ No treatment necessary
™ Normal lifespan expected
™ Family screening and genetic counselling
™ Refer to the National Thalassaemia Registry

GENETIC COUNSELLING AND PRENATAL DIAGNOSIS

All individuals with confirmed thalassaemia should be referred to the
National Thalassaemia Registry. This Registry collates national data on
thalassaemia, counsels families and offers extended screening including
DNA testing at subsidised rates.

Couples who are both heterozygous for the same type of thalassaemia
carry a 25% risk of having a child with the major phenotype. Through
counselling and screening, these couples can be prospectively identified
258
HAEMATOLOGY AND ONCOLOGY
CARE OF THE CENTRAL LINE
IN ONCOLOGY PATIENTS
The two most common central venous lines used in oncology patients in
KKH are the single-lumen Port-a-cath and the double-lumen Hickman
line. The lines can be kept in situ for the entire duration of treatment,
which can be as long as two years. Both lines are inserted under general
anaesthesia by paediatric surgeons. Before insertion of the central line,
ensure that the coagulation profile is normal and that the platelet count
is at least 50,000 x 109/L. After completion of therapy, the central line is
kept in situ for at least another six months. Removal of Port-a-cath is also
done under general anaesthesia as a day-surgery procedure. Removal
of Hickman line can be done under local or general anaesthesia by the
paediatric surgeon. Both types of central lines can be used immediately
after insertion, after checking that the line is in the correct place.
Strict aseptic technique should be adhered to for all procedures
involving central lines.
PORT-A-CATH
The Port-a-cath is an implantable subcutaneous drug delivery device
and thus, will require very little care at home. Patients can shower or
even swim with the device. The majority of our oncology patients have a
Port-a-cath inserted.
Care
After Port-a-cath is accessed, put a transparent dressing over the
needle so that the area around the port can be visualised, in case
there is inflammation or extravasation
The dressing needs to be changed every three days
IV lines need to be changed every three days
Port-a-cath needle needs to be changed every six days
During de-accessing of the Port-a-cath, use a 100U/ml heparin
saline solution to ‘heplock’ the port and remember to apply constant
positive pressure with the syringe when the needle is exiting to
minimise backflow of blood into the Port-a-cath tubing. See next
page for instructions to make 100U/ml heparin saline solution
Haematology and Oncology 259
Port-a-cath needs to be flushed with 10mls saline every month if not
in use. After flushing, ‘heplock’ with 100U/ml heparin saline solution
To make up the 100U/ml heparin saline solution:
Put 0.4mls of the 5,000U/ml heparin solution into 20mls of saline
Use 5–8mls to heplock the Port-a-cath
HICKMAN LINE
The Hickman line is a percutaneous external catheter that can have one
or more lumens. There is usually a subcutaneous Dacron cuff that acts
both as an anchor and as a barrier against infection. We normally insert
a double-lumen Hickman line in a patient going for BMT. A suitable
dressing (e.g. Opsite) 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.
Care
When the Hickman line is accessed, tape the tubing in a loop to
ensure that the weight does not pull on the exit site of the line
The dressing needs to be changed every three days
IV lines need to be changed every three days
Both lumens of the Hickman line need to be flushed every week
with saline and heplocked with ready-made heparinised saline.
Remember to apply constant positive pressure with the syringe
while the clip is being locked during heplocking
As the lumens of the Hickman line are separate, IV antibiotics must
be alternated between the two lumens. This is especially important
in suspected line infection
COMPLICATIONS OF CENTRAL LINES
Occlusion
Suspect occlusion of central line when it is difficult or impossible to
infuse fluids through the catheter. This may be due to:
Intraluminal obstruction e.g. a thrombosed line
Extraluminal obstruction e.g. a kink on the line
If there is resistance in withdrawing blood from the line in the face of
easy infusion of fluids, it may be due to:
Normally placed catheter in a small child
Hypotension
Mal-positioned or extravascular catheter
260 The Baby Bear Book Haematology and Oncology 261

Catheter tip lodged against the vessel wall
Small tubing
Ball-valve type obstruction
Infected Central Line
The central line can be infected as part of general septicaemia where
blood cultures taken from both the central line and peripheral vein
grow the organism. In these cases, the treatment will be the same as for
septicaemia.
However, if the peripheral blood cultures are negative and the central
line cultures are positive, and the child is febrile especially when the line
is flushed, then this is a true line infection. If the child is afebrile and well,
this is probably colonisation of the central line.
Isolated line infection
Suspected isolated line infection
Classically, fever occurs immediately after line is flushed
Peripheral blood cultures may be negative or positive
Central line tunnel infection
Suspect tunnel infection if:
The line tract under the skin is red, inflamed or tender
There is pus coming out of the exit site
Send pus for culture. Appropriate IV antibiotics should be given (IV
cloxacillin or vancomycin if previous Methicillin-resistant Staphylococcus
Aureus (MRSA)) and the surgeon consulted regarding removal of the line.
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 tissue damage, necrosis and secondary infection if the extravasation
is not recognised and treated early.
Suspected extravasation
Subcutaneous swelling under the skin
Pain at the Port-a-cath site with leakage of infused fluid
Stop the infusion immediately, but leave the needle in situ

Aspirate residual fluid and blood from needle

Previous line infection No previous line infection
Check previous organism and sensitivity IV Cloxacillin 100mg/kg/day six hourly
(e.g. MRSA, CONS) Check what fluid is being infused:
IV antibiotics based on previous Vesicant chemotherapeutic drugs or fluids*?
organism Yes No

Infiltrate area with appropriate antidote* Remove Port-a-cath needle after heplock
Change antibiotics if necessary when culture and sensitivity results back subcutaneously using 25G needle and apply cold compress (except etoposide
– apply hot compress)

Repeat line cultures after 72 hours

Elevate area / arm and order analgesia

Consider line removal if:

More than two line infections with the same organism
Fungal infection
No response to antibiotics and child is unwell
Fig. 7.1: Clinical pathway for a suspected isolated line infection.
Order GMS or antibiotic ointment as necessary
Plastic surgeon review necessary
* For vesicant drugs and their antidotes, see Table 7-1 overleaf
Fig. 7.2: Clinical pathway for suspected extravasation.
262 The Baby Bear Book Haematology and Oncology 263

Table 7-1: Vesicant drugs and their antidotes.

Virology/microbiology
Extravasated Drug Suggested Antidotes Dose CMV IgG and IgM, HSV IgG, VZV IgG
Actinomycin Ascorbic acid 50mg/ml 1ml EBV IgG, Measles IgG
Anthracyclines Hydrocortisone 100mg in 2ml water 2ml Hep A IgG, HBsAg, HBeAg (for carrier), Hep C IgG
Vincristine/vinblastine SC Hyaluronidase 15U/ml 1ml HIV serology
Toxoplasma serology
Bicarbonate or calcium SC Hyaluronidase 15U/ml 1ml
Others
ECG and CXR if indicated
Donor is given a medical examination and may be prescribed one
month of iron supplement before harvest
Autologous blood collection from the donor about three weeks
BONE MARROW TRANSPLANT (BMT) before date of harvest
WORK-UP — CHECKLIST Admit donor one day before harvest
Book OT for harvest of bone marrow from donor
When a Human Leukocyte Antigen (HLA) matched donor is identified,
the BMT coordinator will schedule a date for the family conference. RECIPIENT
Recipient investigations:
FAMILY CONFERENCE Haematology
BMT physician FBC, PT/PTT, ABO group/full GXM
BMT coordinator Engraftment Studies (VNTR)
BMT nurse Bone marrow aspirate
Medical social worker Morphology, cytogenetics, immunophenotype
Children’s Cancer Foundation representative Biochemistry
Business office representative U/E/Cr, LFTs
Parents, relative and patient Virology/microbiology
CMV IgG and IgM, HSV, VZV, EBV, Measles
The procedure of transplantation is explained fully. The indications and Hep A IgG, HBsAg, HBeAg (for carrier), Hep C IgG
risks are explained. HIV serology
Toxoplasma serology
Once the family agrees to the procedure, the donor and recipient will Specific antibodies
undergo a series of investigations. Isohaemagglutinins: Anti-A, Anti-B
Cardiopulmonary
DONOR CXR, lung function tests, ECG, echocardiogram
Donor investigations: Dental survey
Haematology Others
FBC, PT/Partial Thromboplastin Time (PTT), ABO group/full Bone age left wrist
Group and Cross Match (GXM) Schedule date of BMT and type of conditioning regime
Engraftment Studies (VNTR) Dental clearance at National Dental Centre at least one month before
Biochemistry BMT
U/E/Cr, LFTs Appointment to see radiation oncologist at Department of Radiation
Oncology, Basement 2, Block 2, SGH, if total body irradiation is
required in conditioning regime
264 The Baby Bear Book
Book OT for insertion of Hickman catheter for recipient. May need to
do LP and administer IT Methotrexate for leukemia at the same time
For peripheral stem cell harvest, administer SC G-CSF daily for several
days before and continue till harvest completed (usually three days).
Peripheral stem cell harvest is performed at Children’s Cancer Centre
with Cobe Spectra pheresis machine. Daily FBC
Inform laboratory technician of date of stem cell harvest. For
Autologous bone marrow or peripheral stem cell harvest,
cryopreservation of stem cells are then performed at National
Blood Bank
BLEEDING DISORDERS
PHYSIOLOGY OF HAEMOSTASIS
Haemostasis is an interplay between the platelets, the vascular
endothelium and the coagulation factors. It consists of a primary phase
which involves the production of a platelet plug. The secondary phase
involves the procoagulation proteins being activated in a cascade
fashion resulting in the formation of a cross-linked fibrin clot.
The haemostatic response can lead to thrombosis and tissue damage.
The patency of vessels in normal, uninjured tissues is maintained by:
Removal of activated factors through the reticulo-endothelial system
Anti-thrombotic pathway consisting of protein C, protein S and anti-
thrombin III
Fibrinolytic system which degrades fibrin, resulting in the formation
of Fibrin Degradation Products (FDPs) and D-dimers
HISTORY
Nature of the bleed:
Location and type — Skin, mucosal surface, petechiae and
purpura are typical of thrombocytopenia; whereas joints, muscles
and palpable ecchymoses are more likely to be a coagulation
defect
Duration — Bleeding that stops and then recurs quickly is
suggestive of a coagulation disorder
Time of onset — Acute bleeds over a period of days to weeks is
suggestive of an acquired disorder; bleeding shortly after birth
Haematology and Oncology 265
(e.g. oozing when cord separates, post-circumcision) suggests a
congenital condition
Menorrhagia in pubertal females and a history of menorrhagia
in their mothers or female relatives — Up to 20% girls with
menorrhagia at menarche have now been recognised to have a
bleeding disorder
Precipitating factors e.g. trauma, dental extractions and surgery
Family history and pedigree:
All members of the family
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)
Penicillins
Anticonvulsants causing thrombocytopenia
Procainamide (associated with acquired lupus anticoagulant)
Warfarin
Cold medications (e.g. guaifenisen)
PHYSICAL EXAMINATION
Skin for petechiae/purpura/telangiectasia
Mucosa, gingiva, nares
Joints — Swelling or chronic changes (e.g. contractures or distortion
of appearance with asymmetry) secondary to repeated bleeding
episodes
Deep tissue bleeds and intramuscular swelling
Self-induced purpura
Systemic illness (e.g. liver or collagen vascular disease)
Evidence of child abuse
LABORATORY STUDIES
FBC with a peripheral blood smear:
Look at all three cell lines:
Hb is decreased with significant blood loss. Normochromic
normocytic red cells indicate blood loss. Microcytosis suggests a
prolonged period of bleeding
Pancytopenia indicates a bone marrow failure syndrome or an
infiltrating marrow lesion like leukaemia/lymphoma
Platelet count to quantify the number, and platelet morphology
to look at the size of the platelets. A decreased count may
be the result of clumping of platelets from EDTA dependent
266 The Baby Bear Book Haematology and Oncology 267

antibodies. Normal or large platelets can indicate Idiopathic Thrombin time:

Thrombocytopenic Purpura (ITP). Large platelets can also indicate Time required to clot when thrombin is added to plasma
Bernard-Soulier Syndrome or May-Hegglin Anomaly. Decreased Increase can be due to:
platelet size may indicate Wiskott-Aldrich Syndrome. Platelet Low fibrinogen activity
morphology is important, as a mean platelet volume from an Dysfunctional fibrinogen
automated count may not accurately reflect platelet size Presence of fibrin split products
Bleeding Time (BT): Heparin contamination
Screen for primary haemostasis Reptilase clotting time — Not affected by heparin contamination
Increased BT with normal platelet count indicates a qualitative Fibrinogen measurement:
platelet defect, vWD or afibrinogenemia Quantitative measurement and functional activity to detect
The traditional test is a template bleeding time, which may have afibrinogenemia and dysfibrinogenemia
questionable sensitivity, specificity, and reliability. The PFA-100 is Platelet aggregation studies:
a laboratory device which is a substitute for BT These measure the degree and pattern of platelet aggregation
Varies with age after the addition of platelet agonists (adenosine diphosphate
PT and Activated Thromboplastin Time (aPTT): (ADP), adrenaline, collagen, thrombin, arachidonate, and
Surveys the secondary phase of haemostasis ristocetin)
Age-dependent, and in a newborn the aPTT may be mildly raised Allow for the assessment of storage pool defects, Bernard-Soulier
because of the immaturity of the coagulation system. Most revert and Glanzmann thrombasthenia
to adult levels by six months of age Recently, flow cytometry allows for the direct detection of
aPTT evaluates the intrinsic system and common pathway; can be platelet-surface glycoprotein expression which are lacking in
increased in: Bernard-Soulier and Glanzmann thrombasthenia
Heparin contamination
Circulating anticoagulants
Table 7-2: Interpretation of lab studies.
Inhibitors
Factor deficiency (the factor level is at least < 40% of the level Platelets PT aPTT Differential Diagnosis Follow up Studies
in pooled plasma before the aPTT becomes abnormal) vWD vWD studies
PT evaluates the extrinsic system and the common pathway. This Platelet dysfunction Platelet aggregation test
can be reported as the INR which is the patient’s PT/control PT. Factor XIII deficiency Urea clot lysis test
N N N
Normal is 1.0–1.1 Fibrinolytic defect Euglobulin lysis test
a2 antiplasmin
Mixing studies of PT and aPTT:
PAI-1, TPA, PFA-100
An abnormal study of PT and aPTT should be followed by a
PTT inhibitor aPTT mixing studies
mixing study. This indicates the presence of an inhibitor or a
vWD Factor VIII, IX, XI assays
factor deficiency N N ↑ Haemophilia A/B vWD studies
Equal volume of patient’s plasma is mixed with normal plasma: Factor XI, XIII deficiency TT/Reptilase studies
if the PT or PTT normalises, a factor deficiency is present. If it is Heparin contamination
persistent, an inhibitor is present (e.g. lupus anticoagulant) PT inhibitor PT mixing study
Factor assays: Vit K deficiency Factor II, VII, IX, X assay
When mixing studies indicate a factor deficiency, quantitate factors N ↑ N Warfarin ingestion
VIII, IX and XI as these deficiencies are associated with bleeding Factor VII deficiency
Decrease in factor XII, prekallikrein and high molecular weight Liver disease
kinninogen can cause an increase in the aPTT but is not
associated with bleeding
268 The Baby Bear Book Haematology and Oncology 269

Table 7-2: Interpretation of lab studies (cont’d). Table 7-3: Dosage of factor VIII and factor IX for different types of bleeds.
Platelets PT aPTT Differential Diagnosis Follow up Studies Type of Location Dose of factor VIII Dose of factor IX
Circulating inhibitor PT/aPTT mixing studies Bleed
Liver dysfunction TT/Reptilase time Mild Epistaxis Local pressure 20 minutes. 2mg/kg/day for two days
Vit K deficiency Fibrinogen assay Pack as needed. 30U/kg if above fails
N ↑ ↑ Factor II, V, X, VIII, IX, Factor assay Antifibrinolytic therapy (four hours after
fibrinogen deficiency 20U/kg if above fails antifibrinolytic dose)
Dysfibrinogenemia Moderate Haemathroses or 20U/kg 30U/kg
High dose warfarin/heparin Intramuscular bleed
DIC TT
↓ ↑ ↑ Liver dysfunction Fibrinogen assay Dental problems 20U/kg 30U/kg, antifibrinolytic
Kasabach-Merritt Factor assay, D-dimers four to six hours after
Acute ITP ANA concentrate
Chronic ITP Anti cardiolipin
Collagen disease DCT Haematuria Bed rest, fluids 1–1.5 x 30U/kg
Lack of platelet production: Immunoglobulin normal
Early bone marrow Complement 20U/kg
failure Marrow aspirate If uncontrolled, Prednisolone 1mg/kg/day
↓ N N Aplastic anaemia Marrow chromosomal prednisolone 2mg/kg/ for three days
Malignancy: analysis day for two days
Leukaemia/lymphoma Helicobacter antigen study Severe Iliopsoas 50U/kg, then 25U/kg 80U/kg, then 20–40U/kg
Platelet consumption: vWD multimer analysis 12 hourly for ten to 12–24 hourly for ten to
ITP (type IIB vWD) 14 days 14 days
Cyanotic heart Life- CNS, gastrointestinal 50U/kg, then continuous 80U/kg, then 24–40U/
Kasabach-Merritt threatening tract haemorrhage infusion 2–3U/kg/hr kg 12–24 hourly
Major surgery to maintain F VIII level to maintain F IX >
MANAGEMENT OF ACUTE HAEMORRHAGE IN Airway obstruction 100% for 24 hours. 30–40% for ten to
BLEEDING DIATHESIS Titrate to keep level > 14 days
Factor Replacement Therapy 30–40% for ten to14
days
Units of factor VIII = (Weight in kg) x (Desired % rise in factor VIII level) x 0.5
Units of factor IX = (Weight in kg) x (Desired % rise in factor IX level)
Initial first aid — Immobilise the joint and place an ice pack on the
For haemophilia A, replacement is with factor VIII concentrate or joint surface
cryoprecipitate where concentrates are not available. Haemophilia B can Early aggressive treatment will relieve symptoms and prevent
be managed by infusing with 10ml/kg Fresh Frozen Plasma (FFP) or use re-bleed into same joint (‘target’ joint) and hence joint damage. A
factor IX concentrate. 35–40% factor level should be targeted. Continuous treatment for
two to five days may be necessary to prevent the development of
See Table 7-3 next page for factor VIII and factor IX dosage applied to target joint bleed
different types of bleeds.
Muscle Bleeds
Haemarthroses Institute early and aggressive therapy to avoid potential long-term
Initial joints affected are usually the knees and elbows when the complications of muscle contractures
child begins to crawl; then ankles, shoulders, hips and wrists as the Compromise to the neurovascular bundle should be excluded
child becomes more mobile Factor replacement: Aim to achieve a target level of 30–40%
270 The Baby Bear Book
Haematuria
Usually painless and almost two-thirds of all patients will have at
least one episode
Bed rest and increased fluid intake is recommended
Anti-fibrinolytic treatment should be avoided
Neurologic Bleed
This is the most serious complication as CNS haemorrhage can occur
without trauma and early symptoms may be minimal. Late bleeding
can occur up to four weeks after the initial trauma
Immediate treatment with factor VIII to achieve 80–100% factor level.
No LPs to be done without prior factor replacement
Dental Bleed
Good dental hygiene and dental care is important. This will prevent
the need for restorative work which would require extensive factor
replacement
To prevent nerve damage and bleeding into the floor of the mouth,
a regional nerve block should never be given without factor
replacement
Anti-fibrinolytic therapy is recommended for dental work
Mucosal Bleed
Epistaxis can be troublesome. Treatment includes pressure on the
anterior nares for 20 minutes with the head flexed, chin touching the
anterior chest, keeping the head above the level of the heart. Repeat
if bleeding recurs
Advise patient not to blow nose for at least 12 hours to avoid
dislodging the clot
Nasal packing if the bleeding is not well-visualised or is profuse. Type
of pack includes compressed sponge, Vaseline gauze, gel foam or
topical thrombin packing. Anterior packs may be left in place for one
to five days except in an immune-compromised state where it should
then be removed after 24 hours. Antibiotic cover should be given in
immuno-compromised patients
DDAVP and antifibrinolytics can also be used if first aid measures
as outlined above do not work. This reduces the need for factor
replacement. However, if the bleeding persists, factor replacement
will be necessary
Haematology and Oncology 271
Desmopressin (DDAVP)
This is a synthetic analogue of vasopressin that leads to endothelial release
of factor VIII and von Willebrand Factor (vWF). This is used as treatment
and prophylaxis for mild bleeding episodes, especially epistaxis. Individual
response is variable and a therapeutic trial with pre and post factor VIII
levels and vWF-ristocetin measurement is recommended. Tachyphylaxis
can develop and this treatment should not be used more than once daily
without measuring factor VIII and vWF-ristocetin levels.
DDAVP can be given either intravenously or intranasally. The standard
intranasal DDAVP for DI should not be used, as this is too dilute. The
correct product is Octostim® or Stimate®.
Dose:
IV 0.3μg/kg in 50ml of N/S over 20–30 minutes for children >
10kg; dilute in 10ml for children < 10kg
Intranasal 150μg (1.5mg/ml) for children < 50kg and 300μg for
children > 50kg
Side effects:
Headache, facial flushing, hyponatraemia observed in patients
with repeated doses of DDAVP or large volumes of oral or IV fluids
Hyponatraemic seizures have been observed
Precautions:
Restrict fluids
Monitor urine output
Antifibrinolytic Treatment
Useful for control of mucosal bleeding as salivary enzymes possess
fibrinolytic activity — Minor dental surgical work like repair of
lacerations, dental extractions
Tranexamic acid 25mg/kg/dose six to eight hourly or Epsilon-
aminocaproic acid (EACA) 100–200mg/kg/dose (max 10gm) as an
initial dose and maintain with 50–100mg/kg/dose (max 5gm) every
six hourly
Tranexamic acid has been shown to be useful topically as a
mouthwash
Contraindicated in haematuria
Inhibitors
Overall, 10% patients develop inhibitors. Twenty five percent of
severe haemophiliacs develop antibodies to factor VIII, less often in
Haemophilia B. Routine screen also helps detect presence of inhibitors.
272 The Baby Bear Book
Measurement of inhibitor:
Bethesda Unit = dilution of plasma that inhibits 50% of normal
factor VIII or IX after incubation:
Low-titre responders (Bethesda Inhibitor Assay (BIA) < 10) —
These patients have a low titre of inhibitors and treatment with
high dose of factor concentrate will saturate the antibody
High-titre responders (BIA > 10) — This is a difficult group
to treat. These patients have an anamnestic response to
subsequent exposure to factor
Treatment can consist of one of the following:
Factor Eight Bypassing Activity (FEIBA)
Prothrombin Complex Concentrate (PCC)
The above two products have activated factors VII, X and thrombin
and factor IX, which bypass factor VIII leading to a fibrin clot
Recombinant factor VII (Novoseven®). Initial dose is 90μg/kg
every two hours till haemostasis is secured. Subsequent infusions
and duration of therapy depends on the clinical response and
situation
IV gamma globulin sometimes reduces and eradicates inhibitors
Immune-tolerance regimen uses high doses of factor concentrate
to eradicate inhibitor titres
Porcine factor VIII concentrate. Porcine antibody should be
obtained before instituting therapy. Starting dose is 100–150μg/
kg/dose
Others include plasmapheresis, cyclophosphamide, cyclosporine,
anti-plasmin and alpha-interferon
HAEMOPHILIA A AND B
Both are inherited in an X-linked recessive manner. Up to 30% of
haemophilia A patients occur as a spontaneous mutation and thus may
not have any family history. Majority is haemophilia A and about 12%
of cases are haemophilia B, due to a deficiency of factor VIII antigen
and factor IX, respectively. Both have similar presentations, although
haemophilia B may be milder.
Clinical Presentation
Oozing from the umbilicus following separation of the cord
Oozing after neonatal circumcision
Bruising and bleeding into joints and muscles when the child begins
to crawl and walk
Mild cases can go unnoticed until there is surgery or trauma
Classically, bleeding occurs into muscles or joints
Haematology and Oncology 273
Table 7-4: Classification of haemophilia.
Classification Factor VIII Level Clinical Features
Mild 6–30% of normal Bleeding secondary to trauma or surgery
(0.06 to 0.30 U/ml) Rarely spontaneous haemorrhage
Moderate 1–5% of normal Bleeding secondary to trauma or surgery
0.01 to 0.05 U/ml Occasional spontaneous haemarthroses
Severe < 1% of normal Spontaneous haemorrhage from infancy
(< 0.01 U/ml) Frequent spontaneous haemarthroses and bleeding
into other sites requiring factor replacement
Diagnosis
The reference standard factor level is 100% (1U/ml) in normal people.
Normal factor VIII level ranges from 50–200% (0.5–2.0U/ml)
The diagnosis is suspected in males with bleeding characteristic of
factor deficiency, a positive family history and a prolonged aPTT.
Factor assays have to be done to confirm the diagnosis
Factor VIII level in a newborn is the same as in adults. Factor IX is
usually lower initially until the liver matures at about six months of life.
Cord levels can be used in suspect cases but confirm with blood drawn
from venepuncture. Stress or minor illnesses can raise factor levels
Classification of haemophilia
Principles of Treatment
Correct with factor concentrates
Physical therapy
Hepatitis B vaccination — Blood products are being infused to patients
Prophylactic dental care
Emotional support
Genetic counselling
Medik Awas (Medic Alert) notification to school/hospital and medical
practitioners. Patient should be encouraged to wear a bracelet or
pendant to indicate that they have such a condition
Treatment is by replacement of factor in the form of factor
concentrates — Several preparations are available, plasma-based or
recombinant; the latter should be used wherever possible. Where
this is not available, cryoprecipitate can be used
Replacement treatment can be on-demand when there is a bleed,
or prophylactic where there is a regular schedule of factor treatment
given prior to onset of recurrent bleeds and to the development
of target joint bleeds. Epistaxis can be troublesome and treatment
includes pressure, DDAVP or antifibrinolytics
274 The Baby Bear Book
For details of treatment, see “Management of Acute Haemorrhage in
Bleeding Diathesis” p. 268
HAEMOPHILIA C
This is rare, affecting Ashkenazi Jews. It is inherited in an autosomal
recessive manner. Bleeding episodes occur in the setting of trauma or
surgery. Factor levels do not correlate with severity.
VON WILLEBRAND DISEASE (VWD)
This is the most common congenital bleeding disorder. It is usually
inherited in an autosomal dominant manner, affecting 1–3% of the
population. vWD can be due to a quantitative defect or a qualitative
defect in vWF. vWF is synthesised in the vascular endothelial cells and
megakaryocytes. It plays a role in platelet adhesion and aggregation,
and serves as a carrier protein for factor VIII, stabilising and prolonging
its half-life.
There are three major types:
Type 1 vWD — Partial quantitative defect (80% of all cases)
Type 2 vWD — Qualitative defect
2A — Decreased formation of high molecular weight vWF multimers
2B — Increased affinity for platelets, leading to significant
thrombocytopaenia
2M — Decreased affinity of the vWF molecule for platelet gp1b,
leading to significant bleeding
2N — Decreased affinity of the vWF molecule for factor VIII,
leading to a haemophiliac type of presentation
Type 3 vWD — Severe quantitative defect
Clinical Presentation
The bleeding is mild in most cases, usually in the mucosal areas resulting
in epistaxis, gingival bleeds after brushing, ecchymoses or menorrhagia.
Sometimes the bleeding follows surgery like tonsillectomy and dental
extraction. The severe types can be like that of a haemophiliac with
deep-muscle and joint bleeds.
Both vWF and factor VIII levels can fluctuate with stress (even with
phlebotomy) and result in a normal or abnormal screening test by PT
or aPTT or bleeding time. vWF is an acute-phase reactant and is raised
in post-operative states, pregnancy, liver disease and collagen vascular
disease; it is reduced in hypothyroidism. Thus, a normal result does not
exclude vWD and repeated tests may need to be done.
Haematology and Oncology 275
Diagnosis
In a patient who has frequent bruising and epistaxis, it is important to
get a family history of bleeding and to investigate for this condition.
In most cases, vWD can be diagnosed by one of the following tests:
Ristocetin cofactor measures the functional activity of vWF. Ristocetin
induces binding of vWF to gp1b receptor on fixed platelets. Slope of
platelet agglutination curve correlates with amount of plasma VWF
vWF antigen — Immunologic quantitation of vWF by immuno-
electrophoretic assay or enzyme linked immunosorbent assay
Factor VIIIC — Functional measurement of factor VIII that is carried by
vWF
Multimeric analysis — An agarose gel electrophoresis study to
identify quantitative or qualitative multimer abnormalities. Common
Type vWD (Type 1) has normal multimeric analysis
Treatment
This depends on the clinical subtype:
For mild Type 1 disease with mucosal bleeding and epistaxis, DDAVP
can be used. This stimulates endogenous release of vWF raising the
factor VIII level two- to four-fold within 15–30 minutes of infusion.
Half-life is 12 hours. For dental extraction, extended therapy may
be required to maintain vWF and factor VIII level till healing has
occurred. DDAVP should be given with tranexamic acid to block the
effect of concomitant release of tissue plasminogen activator
For severe bleeding in patients with Type 2 or 3 disease, treatment
with plasma-based products may be necessary. For major surgery,
plasma levels of vWF and factor VIII should be raised to 100U/dL pre-
operatively and then maintained at 50–100U/dL for three to seven
days after major surgery
For Type 3 disease, patients should be treated like a haemophiliac,
using factor concentrates that contain high levels of vWF to control
the bleeding
Type 2A patients who have small multimers may respond only
transiently to DDAVP. Serious bleeding should be treated with
plasma derived factor concentrates
Type 2B is associated with thrombocytopenia resulting from platelet
binding to an abnormal vWF. DDAVP is contra-indicated in Type
2B. For severe bleeds or post-surgery, patients should be given
factor concentrates. If profound thrombocytopenia exists, platelet
transfusion may be necessary
276 The Baby Bear Book Haematology and Oncology 277

VITAMIN K DEFICIENCY
Vitamin K is required for the creation of calcium-binding sites on specific
procoagulation factors II, VII, IX, X for proper activity. Absence of Vitamin
K leads to a production of functionally defective proteins. Bleeding can
be severe with significant gastrointestinal, deep tissue and intracranial
bleeding.
Vitamin K deficiency can arise from:
↓ intake
↓ absorption
↓ utilisation
Antagonists such as warfarin and warfarin-like compounds:
Warfarin therapy (1–3% incidence of significant haemorrhage)
Ingestion of rodenticide which are derivatives of warfarin with up
to 100 times biologic activity of medicinal warfarin and a longer
half-life
(i.e. all screening coagulation tests are normal). The mode of inheritance
is autosomal dominant.
Factor XIII serves to cross-link fibrin monomers, stabilising the clot and
making it resistant to fibrinolysis.
Only small amounts of factor XIII are required for haemostasis so
symptoms occur with severe deficiency.
Classic presentations are bleeding from the umbilical stump, post-
circumcision, poor wound healing, and delayed separation of cord.
There is a high incidence of intracranial bleeding.
The diagnostic test is factor XIII assay or if not available, the solubility of
the patient’s clot in 5mol/l urea or 1% monodichloroacetic acid. This is
corrected by the addition of normal plasma.

Treat with Vitamin K and FFP. THROMBOCYTOPAENIA

This is defined as a platelet count < 150 x 109/L.
HAEMORRHAGIC DISEASE OF NEWBORN (HDN)
Early HDN (first 24 hours) — This is associated with maternal A low platelet count needs to be confirmed by a review of the
medication (e.g. anticonvulsants which affect Vitamin K metabolism) peripheral smear especially in an asymptomatic child. False values
Classic (two to seven days) — There is a combination of inadequate (pseudothrombocytopaenia) can arise from aggregation of platelets in the
stores at birth and liver immaturity with respect to factor synthesis, syringe caused by agglutination by EDTA antibodies, and counting of non-
inadequate intake, and gut sterility (breastfeeding) platelet particles like fragmented red or white cells by automated counters.
Late (after the first week to few months) — Multiple factors are
involved: Causes of Thrombocytopaenia
Inadequate intake from breastfeeding Destruction of platelets:
Inadequate absorption e.g. chronic diarrhoea, antibiotic therapy, Immunologic:
cystic fibrosis, alpha-l anti-trypsin deficiency ITP
Warfarin-like compound ingestion Drug-induced
Autoimmune
Prevention: Give Vitamin K prophylaxis at birth. Post-transfusion
Post-transplant
FACTOR VII DEFICIENCY Hyperthyroidism
This is the only factor tested-for by PT. In the absence of an inhibitor, Non-immunologic:
isolated prolongation of PT is consistent with factor VII deficiency. Rare Microangiopathic
condition. Haemolytic anaemia and thrombocytopaenia
Haemolytic uremic syndrome
FACTOR XIII DEFICIENCY (FIBRIN STABILISING FACTOR) Thrombotic thrombocytopaenia
This is characterised by delayed or prolonged bleeding with normal Platelet consumption:
coagulation tests because PT/aPTT does not assess this factor activity DIC
278 The Baby Bear Book Haematology and Oncology 279

Giant haemangioma Conditions associated with thrombocytopenia:

Cardiac prosthesis Sick infant:
Impaired production: Congenital viral infection
Congenital and hereditary disorders: Asphyxia
Thrombocytopenia Absent Radii (TAR) Syndrome Respiratory Distress Syndrome
Fanconi’s Anaemia Necrotising enterocolitis
Bernard-Soulier Kasabach-Merritt Syndrome
Wiskott-Aldrich CHD
Glanzmann thrombasthenia Congenital leukaemia
Amegakaryocytic thrombocytopaenia Thrombosis
May-Hegglin ‘Well’ looking infant:
Chromosomal disorders: Allo-immune thrombocytopaenia (40% can occur in the first
Trisomy 13 and 18 pregnancy and 20% can have an intracranial bleed)
Acquired: Maternal auto-immune disease (intracranial haemorrhage less
Marrow infiltrative disorders, storage disorders, myelofibrosis frequent)
Drug-induced Wiskott-Aldrich
Severe iron deficiency Amegakaryocytic thrombocytopaenia
Sequestration: Trisomy 13 and 18
Hypersplenism
Hypothermia IMMUNE THROMBOCYTOPAENIA
Neonatal thrombocytopaenia: This is an acute self-limited condition usually occurring in two- to
Neonatal allo-immune thrombocytopaenia four-year-olds and usually lasting < six months. Children < one year
Neonatal auto-immune thrombocytopaenia old or > ten years old tend to have a more chronic course. The onset is
Congenital viral infections acute, usually after an antecedent viral illness one to three weeks earlier.
Birth asphyxia Symptoms include the sudden onset of petechiae, purpura, ecchymosis,
Sepsis epistaxis and less frequently haematuria and gastrointestinal tract
Giant haemangioma bleeding.
CHD
Respiratory distress syndrome Physical examination usually reveals a well child with no evidence
Prematurity of pallor, weight loss or chronic illness. The skin manifestations of
petechiae or purpura may be present. There is no hepatosplenomegaly
The most common cause of destructive thrombocytopenia is immune- or lymphadenopathy. Skeletal abnormalities are associated with bone
mediated destruction arising from an immunoglobulin G antibody marrow failure syndromes like Fanconi’s anaemia and TAR syndrome.
directed against a platelet membrane antigen from infection with an
organism or from drug exposure. Immunoglobulin M activation and A drug history is important — Aspirin, NSAIDs, anticonvulsants.
complement activation are less common.
Treatment
NEONATAL THROMBOCYTOPAENIA Most patients recover spontaneously but care should be taken to
The platelet count is normal in both pre-term and term infants (150–400 avoid contact sports, rough play, intramuscular injections and LPs.
x 109/L) as platelet production is established towards the end of the Drugs that interfere with platelet function should not be given (e.g.
first trimester of pregnancy. The incidence of thrombocytopenia in a aspirin and NSAIDs)
neonatal intensive care setting is 25%.
280 The Baby Bear Book
Decision to treat remains controversial. Treatment options include:
IV gamma globulin will bring the platelet count up in 24–72
hours, peaking in nine days. The dose is 1g/kg over four to six
hours and can be repeated with up to 2–3g/kg to be given 24
hours apart. Side effects include nausea, lightheadedness and
headache and are related to rate of infusion. Slowing the rate of
infusion down will alleviate the symptoms. Fever can be treated
with paracetamol
Corticosteroids — Before instituting steroid therapy, it is
advisable to do a bone marrow aspirate to exclude a malignancy
as the cause of thrombocytopaenia because steroids can mask
leukaemia for a short period. Dose is 1–2mg/kg for ten to 20 days
up to six weeks
Anti-D immunoglobulin — The response in children is better
than with adults. It is not effective in RhD negative patients.
Dose is 50μg/kg. The mechanism of action is postulated to be
the presence of anti-red cell antibodies, which induces a mild
haemolysis diverting the macrophages from destroying the
antibody-coated platelets
About 10–20% of children with acute immune thrombocytopaenia
develop chronic persistent thrombocytopaenia beyond six months.
A collagen disorder has to be excluded. Patients with chronic ITP
may not always need treatment if the platelet count is above 20 x
109/L. Platelet count alone does not predict for haemorrhage as
the platelets are often large and this may not be picked up by the
automated counter, the count being higher than if counted manually.
Spontaneous recovery can occur and can take up to two years after
the original diagnosis. In refractory patients, other modes of treatment
include anti-D immunoglobulin, vinca alkaloids, danazol, azathioprine,
cyclophosphamide and splenectomy.
NEONATAL ALLO-IMMUNE THROMBOCYTOPAENIA
The pathophysiology is similar to Rh haemolytic disease where the
mother is sensitised to platelet antigens present in the foetus. Platelet
antigen A1 (PA1) is the most common antigen implicated. This antigen
resides in the glycoprotein complex IIb/IIIa, a complex that is responsible
for the fibrinogen receptor activity of platelets and important in platelet
aggregation and platelet plug formation. Severe thrombocytopenia is
present and together with a qualitative platelet defect there is a high
Haematology and Oncology 281
risk of intracranial haemorrhage in the perinatal period as compared to
a neonate born to a mother who has auto-immune thrombocytopaenia.
In 40% of cases this condition can occur even in the first pregnancy.
Presentation
The typical presentation is a well newborn with petechiae and
purpura
The baby will have to be monitored for signs and symptoms of
intracranial haemorrhage. Early jaundice can occur as a result of
intracranial or intraorgan haemorrhage
Resolution of the thrombocytopenia occurs in three to six weeks
after delivery. Attempts to identify the platelet antigen should be
made, in order to prevent a recurrence and to identify the at-risk
mother where subsequent pregnancies can be monitored
Treatment
Transfuse with antigen-negative platelets wherever possible. As 98%
of the population are PA1 positive, this may not be possible. Hence
transfusion with maternal platelets may be necessary
Alternatively, IVIG at 1g/kg/day for one to two doses can be used
until the platelet count is > 50 x 109/L
The recurrence risk is high and the obstetrician for the next
pregnancy needs to be told of this condition so that the next foetus’
platelet count and the possibility of intracranial haemorrhage can be
monitored
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
An acquired haemorrhagic disorder resulting from an imbalance
between intravascular thrombosis and fibrinolysis, increased platelet
consumption, depletion of clotting factors and formation of fibrin. It
is a secondary phenomenon resulting commonly from septicaemia,
malignancy (acute promyelocytic leukaemia or neuroblastoma),
haemolytic transfusion reaction, trauma, birth asphyxia, respiratory
distress syndrome and disorder of the foeto-placental unit leading to a
release of tissue factor.
The disease ranges from asymptomatic (because sensitive lab tests are
capable of detecting the activation of both the coagulation as well as
the fibrinolytic systems) to fulminant disease with bleeding into the
microvasculature and large vessel thrombosis.
282 The Baby Bear Book Haematology and Oncology 283

Clinical features start with acute bleeding into the skin and mucosa
History and Physical Examination: at multiple sites. There is oozing from venepuncture sites, petechiae
Bruising and bleeding and purpura. There can be severe bleeding from the gastrointestines,
lungs and brain, leading to shock and end-organ failure. Microvascular
thrombi from venous or arterial sites also contribute to end-organ
Platelets PT, aPTT failure, especially in the kidneys and brain.

Diagnosis
decreased normal normal abnormal Thrombin time Platelet count, PT, aPTT, TT, d-dimer, fibrinogen level, fibrin split
products and a blood film to check for fragmentation of red cells
ITP Evaluate platelet Mixing studies normal These parameters will reflect on the extent of consumption of
Marrow failure function tests haemostatic components, presence of by-products of in vivo
syndromes thrombin generation and the extent of secondary fibrinolysis
Malignancies: not corrected abnormal
corrected Changes in two of three components with a decreased platelet count
Leukaemia
Lymphoma are consistent with DIC
Specific inhibitor
Congenital Antiphospholipid
and hereditary syndrome Treatment
syndromes Contaminated Depends on the underlying cause of DIC (e.g. antibiotics for sepsis,
Specific factor with heparin or debridement for crushed tissues)
abnormal normal assay: thrombolytics? Supportive care with volume replacement, correction of hypotension
vWD and hypoxia will improve the circulation as well as restoring the
Glanzmann disease abnormal Factor VII, VIII,
blood coagulation inhibitory functions
Drugs (aspirin) with IX deficiency
ristocetin Replacement with haemostatic products has always been quoted
Storage pool defect as ‘fuelling the fire’. In general, patients should be transfused if
Fibrinogen they have bleeding and reduced factor levels. Platelet transfusion
to maintain the platelets > 50 x 109/L, cryoprecipitate and FFP to
vWD studies correct coagulopathies and maintain fibrinogen level to > 100mg/dL
Factor VIII antigen normal abnormal
F VIII ristocetin BIBLIOGRAPHY
co-factor ↑FDP and 1. Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Frequency of inherited bleeding
F VIII vWF ↑D-dimers in DIC
disorders in women with menorrhagia. Lancet. 1998;351(9101): 485–489.
2. Kadir RA, Economides DL, Sabin CA, Pollard D, Lee CA. Assessment of menstrual blood loss
and gynaecological problems in patients with inherited bleeding disorders. Haemophilia.
1999;5(1):40–48.
Dysfibrinogenaemia 3. Burk CD, Miller L, Handler SD, Cohen AR. Pre-operative coagulation screening in children
normal abnormal Hypo-or undergoing tonsillectomy. Pediatrics. 1992;89(4 Pt. 2):691–695.
Afibrinogenaemia 4. Roberts IAG, Murray NA, Thrombocytopenia in the newborn. Curr Opin Pediatr. 2003;15(1):
17–23.
Bernard- vWD 5. Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn Uri. Williams Hematology. 6th ed.
New York: McGraw-Hill; 2000.
Soulier 6. Hastings C. The Children’s Hospital Oakland hematology/oncology handbook. St. Louis:
Uraemia Mosby; 2002.
7. Allen GA, Glader B. Approach to the bleeding child. Pediatr Clin North Am.
2002;49(6):1239–1256.
Fig. 7.3: Algorithm for investigating a bleeding child. 8. Manno CS. Difficult Pediatric Diagnosis. Pediatr Clin North Am. 1991;38:637–655.
284 The Baby Bear Book
FEBRILE NEUTROPAENIA
DEFINITION
In the management of febrile neutropaenia, fever is defined as a single
temperature of ≥ 38.5°C or two episodes of ≥ 38°C.
Neutropenia is defined as a neutrophil count of ≤ 1,000 cells/mm3.
Severe neutropenia is a neutrophil count of ≤ 200 cells/mm3.
Febrile neutropenia in an immunocompromised patient is a medical
emergency. Prompt attention, administration of appropriate antibiotics
and supportive treatment is critical for a favourable outcome.
INITIAL EVALUATION
History
Diagnosis — As in which cancer type e.g. a solid tumour vs
leukaemia
Chemotherapy schedule — On treatment or off treatment
If on treatment, what and when was the last dose given. This will
enable one to predict the severity and duration of the neutropenia
and plan accordingly. A low nadir in the neutrophil count and a
protracted neutropenia (e.g. < 500 cells/mm3 for ten days) are major
risk factor; in a patient with Acute Myeloblastic Leukaemia (AML),
certain drugs (e.g. high-dose cytarabine or methotrexate) can cause
severe mucositis
Associated symptoms e.g. cough, diarrhoea, abdominal pain
Systemic review
Allergy to drugs and to blood products
History of transplant
Physical Examination
A thorough examination should be done especially looking out for
evidence of occult infection
A high index of suspicion is required as the usual signs of
inflammation (i.e. erythema, induration, tenderness and pustulation)
may be blunted and barely obvious when a patient is neutropenic.
Thus minimal tenderness or swelling, if any, may be the only sign of
an abscess
The oral cavity and perineum must always be scrutinised for ulcers.
Look out for pallor or bleeding. Look for tenderness over the skin
including bone marrow aspiration sites, catheter sites and around
the nails
Haematology and Oncology 285
If history is suggestive, look for respiratory distress (early
pneumocystis infection)
Examine the abdomen for distension, tenderness and bowel sounds.
Think of typhilitis in the face of abdominal pain ± diarrhoea
Investigations
Appropriate investigations should be done immediately and include:
FBC, group and cross match
Blood cultures — Aerobic and anaerobic.
One set each from each individual lumen of the central line and from
the periphery. Ensure that peripheral blood culture is done before
accessing the port. 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 culture
is unnecessary unless rare or fastidious species are suspected. Send
fungal cultures only after discussion with infectious diseases service
or microbiology
U/E/Cr
LFTs, calcium/phosphate/magnesium as necessary
Coagulation profile
UFEME and urine culture x 2, urine fungal smear and culture
Stool culture/stool fungal smear and culture
CXR if required
Other imaging and blood investigations as required. 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
MANAGEMENT
General supportive and resuscitative measures as required
Hourly parameters. Look out for inappropriate tachycardia
(impending shock) or increased respiratory rate (early pneumocystis
infection). Monitor frequently, at least four hourly
Initial antibiotic cover:
Prompt empiric antibiotic cover is necessary as the progression
of infection in a neutropenic patient can be very rapid, especially
with gram-negative organisms which can cause fatality in a
matter of hours
In general, the first-line treatment is broad-spectrum and covers
for the pathogens unique to the particular hospital setting,
especially gram-negative organisms
286 The Baby Bear Book
First-line therapy in our department:
IV ceftriaxone 100mg/kg/dose (max 2g) STAT and 24 hourly, and
IV gentamicin 2mg/kg/dose (max 80mg) eight hourly.
This will cover for both gram-positive and gram-negative
organisms. With the frequent use of vascular access devices,
gram-positive organisms are becoming more common and,
in some centres, even more prevalent than gram-negative
organisms
If a gram-positive organism is suspected, add IV cloxacillin
100mg/kg/day in four divided doses. In order to prevent
resistance, IV vancomycin is used only when indicated e.g.
history of previous Coagulase-negative Staphylococcus (CoNS) or
Methicillin-resistant Staphylococcus Epidermidis (MRSE) infection,
no response to cloxacillin or a positive blood culture result
Methicillin-resistant organisms tend to cause infections which
are more indolent and hence a delay in specific therapy is
not detrimental to patient outcome. However, organisms
like staphylococcus aureus, streptococcus viridans and other
streptococci can cause fulminant infection
Supportive therapy:
Once broad-spectrum empiric antibiotic cover has been instituted, a
review of the FBC, coagulation and renal panel are essential.
Maintain Hb > 8g/dL; if there is respiratory distress or bleeding
maintain >10g/dL.
If a packed cell transfusion is required, order 20mls/kg over four
hours
Maintain platelets ≥ 30,000 if febrile or ≥ 20,000 if afebrile. If there
is active surface bleeding, maintain ≥ 50,000; gastrointestinal
bleeding ≥ 80,000 and intracranial bleeding ≥ 100,000
Correct electrolyte abnormalities.
Add maintenance potassium to the drip once the result is back
and patient has passed urine
Granulocyte Colony-stimulating Factor (GCSF) is indicated if
prolonged neutropenia is expected
Prophylactic fluconazole 6mg/kg as required
Specific supportive measures as required
Remember to stop any oral chemotherapy agents that patient may
be currently taking
Haematology and Oncology 287
Progress
If patient responds and temperature settles, continue same regime.
However, if fever persists and neutropenia lasts ≥ 72 hours, a
thorough review and repeat blood cultures are required
Second-line antibiotic cover includes IV ceftazidime 50mg/kg/dose
eight hourly and IV amikacin 7.5mg/kg/dose 12 hourly
If despite second-line cover, febrile neutropenia persists for another
72 hours, then IV amphotericin is added empirically:
A test dose and loading dose are not required. Pre-medication
with IV promethazine 0.25mg/kg (max 12.5mg unless patient
> 50kg) and IV hydrocortisone 5mg/kg are given prior to
amphotericin infusion
Pre-medication may be discontinued after several days if there
is no reaction but be prepared to reinstitute if patient develops
fever, chills, rigors or hypotension
Amphotericin is started at 0.5mg/kg in 5% dextrose (minimum
concentration is 1mg/10mls) and run over six hours. This is
increased by 0.2mg/kg daily until patient is afebrile or 1mg/kg/
dose is reached. A dose of 1.5mg/kg/dose is used if aspergillosis is
suspected
If fever persists despite the addition of amphotericin, then frequent
repeat blood cultures and imaging are required to exclude new
organisms or occult infections
A high index of suspicion, frequent reviews of the patient and
prompt reaction to investigation results are required in the
management of a patient with febrile neutropenia
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 neutropenia is expected, the role
of prophylactic empiric antifungals can be considered and an oral
agent (e.g. fluconazol)e given at a higher dose of 10mg/kg/dose
BIBLIOGRAPHY
1. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines
for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis;
2002;34(6):730–751.
2. Pizzo PA. Fever in immunocompromised patients. New Engl J Med. 1999;341(12):893–900.
288 The Baby Bear Book
ACUTE TUMOUR LYSIS SYNDROME (ATLS)
ATLS is a metabolic emergency that results from massive tumour cell
destruction. It is characterised by the abrupt occurrence of:
Hyperuricaemia
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
All the above are the by-products of rapid cell turnover. Anticipation
and vigilant monitoring are necessary to prevent acute renal failure
secondary to urate and phosphate deposition in the kidney. Sudden
death may occur from hyperkalaemia or hypocalcaemia.
Patients who are prone to tumour lysis are usually those with large
tumour burdens, high proliferation rates and exquisite sensitivity to
chemotherapy. Classically, these are patients with Burkitt’s lymphoma,
acute lymphoblastic leukaemia (ALL) and AML. However, it is
important to remember that tumour lysis can occur spontaneously
even before chemotherapy has commenced and in any lympho- or
myeloproliferative malignancy.
The mainstay of management is hydration and strict and close
monitoring of the patient’s total input and output.
Initial hydration starts at 3L/m2 BSA over 24 hours with no potassium
in the drip
One should not be afraid to hydrate the patient but care must be
taken that the urine output is adequate and fluid overload prevented
IV diuretics (e.g. frusemide) should be given freely to ensure a urine
output of > 100ml/m2/hour
Hydration fluids are increased according to the K+ and metabolite
levels, if they continue to rise despite 3L/m2/day
Care is required if the patient has underlying renal problems or
compromised renal function. The nephrologist should be informed
early in the management of ATLS. Renal clearance is the primary
mechanism for excretion of uric acid, potassium and phosphate
HYPERURICAEMIA
Aggressive hydration with adequate urinary output. Care must be
taken especially in the very small (< 10kg) to prevent fluid overload.
Strict and frequent input/output monitoring is required
Haematology and Oncology 289
Alkalinisation of the urine:
15ml of 8.4% NaHCO3 per 500ml dextrose/saline
Maintain urine pH between 7–7.5
Remember to stop NaHCO3 once chemotherapy has started
Some controversy exists with alkalinisation and there are some
who do not practice it
Over-alkalinisation can cause or aggravate hypocalcaemia
Administration of allopurinol 100mg/m2/day in three divided doses.
In severe uncontrollable rise, IV urate oxidase may be used
HYPERKALAEMIA
Should be anticipated
There should be no added K+ in the drip
Occasionally patients may be hypokalaemic. Add K+ very carefully
and gingerly, and monitor closely
Vigorous hydration with adequate urine output should be sufficient
to control the situation.
However, if K+ continues to rise and serum K+ levels approach
6mmol/L, then haemodialysis may be required. Again, anticipation
and proactive management are required and the nephrologist
should be alerted early
HYPERPHOSPHATAEMIA
Should be monitored closely and a rising trend noted. Try to keep
serum phosphate < 2mmol/L
Increase hydration accordingly to slow down and reverse rising
trend. Adequate urine output is essential (100ml/m2/hour)
Phosphate binders may also help
A phosphate level ≥ 2.5mmol/L should alert the physician and a level
of ≥ 3.5mmol/L will require dialysis
HYPOCALCAEMIA
Do not treat unless patient is symptomatic
Note that over-alkalinisation can precipitate CaPO4 deposition
MONITORING REGIME
Strict attention to fluid balance (input/output) especially in the very
young or those with renal compromise
An arterial line is useful for the frequent blood monitoring
290 The Baby Bear Book Haematology and Oncology 291

Table 7-5: Causes of true anaemia.

Monitor K+, uric acid, Ca and PO4 at least four hourly and more
frequently as necessary. Remember that tumour lysis can occur Decreased Production Increased Destruction / Loss
spontaneously, even before chemotherapy is given Nutritional deficit of - iron Blood loss
Close monitoring continues for at least 72 hours folate
Do not be in a hurry to decrease hydration volumes for at least 72 vitamin B12
hours. When hydration is reduced, monitor for at least 24 hours to ascorbic acid
ensure that the situation is truly stable Reduction in precursors Haemolysis (intrinsic to RBCs)
If large volumes (e.g. 5L/m2) are required to control the ALTS, it is aplasia haemoglobinopathies
malignancy enzyme deficiencies
critical to ensure adequate urine output.
myelofibrosis membrane defects
Once again, do not be in a hurry to reduce hydration if you have
Ineffective erythropoiesis Haemolysis (extrinsic to RBCs)
managed to curb a rising trend of PO4 or K+. Allow the situation to be
anaemia of chronic disease autoimmune or isoimmune
stable and be guided by the levels in subsequent monitoring thalassaemia infections
Have a renal team on standby as early as possible where necessary myelodysplastic syndrome physical or chemical agents

Anticipation, vigorous hydration and adequate urine output and close

and frequent monitoring of input/output and electrolytes are the Degree of reduction of oxygen-carrying capacity e.g. HbS gives
mainstay of successful management of tumour lysis syndrome. better tissue oxygenation so low Hb in sickle-cell anaemia is better
tolerated

ANAEMIA
DEFINITION
True anaemia 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 anaemia 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 anaemia
Speed of onset — Gradual onset better tolerated
Age and cardiovascular status of patient — Better tolerated in the
young
HISTORY
Previous blood tests and transfusion history — For comparison
Duration of symptoms — Recent or long-standing
Family history — Consanguinity, congenital anaemias, 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
Past medical history — Neonatal hyperbilirubinaemia in G6PD
deficiency
PHYSICAL EXAMINATION
Stature — Short in Fanconi’s Anaemia
Skin and sclerae — Pallor, jaundice, purpura, bruises, petechiae
Signs of nutritional deficiencies — Iron, ascorbic acid
Signs of chronic illness — Thyroid, renal
Cardiovascular — Heart failure
Organomegaly — Lymph nodes, liver, spleen
Rectal examination (if necessary) — Melaena
292 The Baby Bear Book Haematology and Oncology 293

INVESTIGATIONS Note: Iron deficiency may give a falsely low HbA2 result, making Hb
The FBC, Peripheral Blood Film (PBF) and reticulocyte count can give electrophoresis inaccurate. Therefore Hb electrophoresis may have to be
a lot of information and help in deciding what further investigations to repeated when iron deficiency is corrected.
do.
When to Do a Bone Marrow Aspirate?
Blood investigations like LFT, U/E/Cr, TFTs, Fe/TIBC, Hb electrophoresis, Malignancy is suspected — Blasts, primitive white cells in the PBF,
autoimmune markers, Vitamin B12 and folate are ordered on the basis of tumour elsewhere
the suspected diagnosis. Myelodysplastic change is seen — Hypogranular, hypolobulated
neutrophils
Aplasia is suspected — Reticulocytopenia, pancytopenia
Anaemia of uncertain origin

Table 7-6: Possible common causes of anaemia based on full blood count (FBC). A unilateral bone marrow aspirate is usually sufficient — Send samples
MCV/MCHC WBC Platelet for morphology, cell markers and cytogenetics.
↓/↓ Fe def ↓ Aplasia ↓ Aplasia
(hypochromic, Thalassaemia (leucopenia) Malignancy Malignancy Bone marrow aspirate and bone trephine are done if lymphoma or
microcytic) aplasia is suspected.
Chronic illness SLE Blood loss
↑/↑ Vit B12 def ↑ Blood loss ↑ Haemolysis
(macrocytic) Folate def (leucocytosis) TREATMENT
Haemolysis Fe deficiency
Drugs Treat underlying condition. In iron deficiency, remember to continue
Infections Myeloproliferative treating for months after Hb returns to normal to replenish body iron
disorders stores
N/N Blood loss Primitive Malignancy Treat symptoms of anaemia e.g. heart failure
(normochromic, Haemolysis (blasts etc) Myeloproliferative Transfuse when there is ongoing blood loss/haemolysis or if there is
normocytic)
symptomatic anaemia. In longstanding anaemia, there is no need to
Chronic illness Hypersegmented Vit B12 / Folate def transfuse if Hb is stable and patient is not symptomatic
neutrophils If Hb is very low, correct anaemia 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 ANAEMIA

Table 7-7: Possible common causes of anaemia based on reticulocyte count. Volume of packed cell transfusion (ml) =
Reticulocytes (Desired Hb in g/dl) - (Current Hb in g/dl) x (Body weight in kg) x 3.5
Blood loss
↑ Haemolysis Mentzer Index = Mean corpuscular volume (MCV) / Red blood cell (RBC)
(<13 more likely thalassaemia trait, >13 more likely iron deficiency)
Nutritional deficiency responding to treatment
Aplasia
↓
Malignancy
294 The Baby Bear Book Haematology and Oncology 295

LYMPHADENOPATHY Sarcoidosis
Histiocytosis
Storage diseases e.g. Gaucher Disease, Niemann-Pick Disease
DIFFERENTIAL DIAGNOSES Medications e.g. phenytoin
Infections:
Bacterial: HISTORY
Staphylococcus aureus Age
Streptococcus pyogenes Duration of symptoms
Bartonella (Cat Scratch Disease) Recurrent infections, recurrent skin sepsis
Brucellosis Constitutional symptoms e.g. fever, loss of appetite, loss of weight
Tularemia Rash, arthralgia
Viral: Drug history
Epstein-Barr virus (EBV) Travel history
Cytomegalovirus (CMV) Contact history
HIV Exposure to cats
Measles Animal scratches
Rubella
Mycobacterial: PHYSICAL EXAMINATION
Mycobacterium tuberculosis Examine enlarged lymph node for:
Mycobacterium avium-intracellulare Size, warmth, tenderness, overlying skin erythema, fluctuancy,
Mycobacterium scrotulareum mobility
Protozoan: Other lymph node involvement:
Toxoplasmosis Cervical, occipital, axillary, epitrochlear, inguinal, popliteal
Malaria Presence of pallor, jaundice
Fungal: Joints for swelling, tenderness, limited range of movement
Histoplasmosis Skin for vasculitis, petechiae, purpura
Coccidiomycosis Abdomen for hepatosplenomegaly, intra-abdominal masses
Cryptococcus Localised infection
Aspergillosis
Autoimmune conditions: INVESTIGATIONS AND MANAGEMENT
Juvenile chronic arthritis Please see Table 7-8 overleaf.
SLE
Immunodeficiency syndromes: If lymph node biopsy is to be done, consult oncologist and ID
Chronic granulomatous disease physician first. The biopsy specimen is usually sent for the following:
Hyper-IgE syndrome (Job Syndrome) Histology (inform pathologist beforehand if lymphoma is suspected
Leucocyte adhesion deficiency as a fresh specimen is often required)
Malignant conditions: Gram stain, culture and sensitivity
Leukaemia/lymphoma Acid Fast Bacillus (AFB) smear/AFB culture and sensitivity, AFB
Metastatic solid tumours e.g. neuroblastoma Polymerase Chain Reaction (PCR)
Miscellaneous: Fungal smear/fungal culture
KD
Kikuchi Disease
296 The Baby Bear Book Haematology and Oncology 297

Table 7-8: Investigations and management. Signs and Conditions Investigations Management
Signs and Conditions Investigations Management Symptoms Suspected
Symptoms Suspected Fever, vasculitic rash, Autoimmune FBC, ESR Steroid therapy
Isolated cervical Viral lymphadenitis None needed Observe arthralgia, arthritis, condition C3C4,
lymphadeonopathy, Await resolution in up hepatosplenomegaly, ANA, anti-ds DNA
Otherwise well to four to six weeks. generalised
Fever, lethargic, upper S. aureus infection FBC, Bld C/S IV Ampicillin and IV lymphadenopathy
respiratory tract S. pyogenes infection Ultrasound scan if Cloxacillin. Fever, loss of Malignant condition FBC, PBF, ESR Treat underlying
infection, pharyngitis, suppuration Incision and drainage appetite, weight loss, LDH, uric acid malignancy
otitis media suspected if abscess formation. petechiae, pallor CXR
Oral mucositis, dental Anaerobic oral flora FBC, Bld C/S Penicillin or hepatosplenomegaly, Excision biopsy
abscess Clindamycin supraclavicular lymph
node enlargement
School-going Infectious FBC, LFT, Symptomatic
age group, fever, mononucleosislike EBV IgM treatment Fever, rash, Kawasaki Disease FBC, Bld C/S High dose Aspirin
lethargy, white syndrome CMV IgM (Avoid Ampicillin) conjunctivitis, red CRP, ESR, IV Immunoglobulin
exudates on tonsils, lips, strawberry 2D Echocardiogram
hepatosplenomegaly, tongue, unilateral
generalised cervical lymph node
lymphadenopathy enlargement, swollen
or erythematous
Usually one to five Nontuberculous Mantoux test (50% Complete surgical hands or feet, BCG
years old, usually mycobacterium may be positive) excision. scar erythema or
multiple unilateral, infection Excision biopsy Antibiotics induration
firm lymph nodes. (Clarithromycin
May undergo rapid ± Rifampicin) for Infective Cause
suppuration or patients:
rupture and form With established
cutaneous sinus sinus tracts
tracts. At high risk for
facial nerve Bilateral lymphadenopathy Acute bilateral lymphadenitis
damage if excision Otherwise well Febrile and ill-looking
is done
With intra-parotid
adenitis Observe for up to four to six weeks Admit to hospital
With incomplete
LN excision
FBC, blood cultures
Unilateral or bilateral Tuberculous adenitis Mantoux test Treat as for PTB: U/S if suppuration suspected
Resolve Does not resolve, or
firm, discrete, CXR (normal in 70% Two months of
Progressive, or
non-tender lymph of cases) Rifampicin, Isoniazid
New signs and symptoms
nodes, often fixed to FBC, ESR and Pyrazinamide IV ampicillin and cloxacillin
underlying tissues, Lymph node biopsy followed by four
may progress to months of Rifampicin
become matted. May and Isoniazid Discharge FBC, PBF, ESR Incision and drainage if there
be associated with CXR is abscess formation
low-grade fever and Mantoux test
systemic symptoms.
Fig. 7.4: Suggested algorithm for an infective cause.
298 The Baby Bear Book Haematology and Oncology 299

Non-infected Cause Group and cross match

Blood culture if febrile

Bone Marrow Aspirate

Cytology
Autoimmune condition suspected Malignant condition suspected Immunophenotyping
Cytogenetics
Trephine biopsy is only done if there is a dry tap. Ask technician to
prepare a rolled film of the trephine specimen if unable to aspirate bone
FBC, ESR, C3, C4 FBC, PBF, ESR, LDH, uric acid marrow.
ANA, Anti-ds DNA Excision biopsy (inform pathologist
if lymphoma suspected so that fresh Lumbar Puncture (LP)
specimen is obtained for appropriate stain)
CSF for Full Examination Microscopic Examination (FEME)
Mantoux test
CSF for cytospin
Fig. 7.5: Suggested algorithm for a non-infected cause.
The first LP is to be done by a senior doctor as it will determine the
presence or absence of CNS disease, an important prognostic factor.
BIBLIOGRAPHY
1. Behrman RE, Kliegman RM, Arvin AM, editors. Nelson textbook of paediatrics. 16th ed.
Philadephia: WB Saunders Company; 2000.
Intrathecal Methotrexate is usually given with the first LP.
2. Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am.
2002;49(5):1009–1025. Platelet transfusion before LP if platelets < 50 x 109/L.
3. Peters TR, Edwards KM. Cervical lmphadenopathy and adenitis. Pediatr Rev.
2000;21(12):399–405.
4. Chesney PJ. Nontuberculous Mycobacteria. Pediatr Rev. 2002;23(9):300–309. Imaging Studies
CXR
Elective echocardiogram

TREATMENT
CHECKLIST FOR PATIENTS NEWLY Start hydration:
DIAGNOSED WITH LEUKAEMIA Usually IV D/S(M) at 3,000ml/m2/day
Add IV 8.4% NaHCO3 to drip and titrate to maintain urine pH
7.0–8.0
INVESTIGATIONS No K to be added to the drip
Blood Tests Start oral Allopurinol 100mg/m2/dose eight hourly
FBC, PBF IV antibiotics if febrile and neutropenic
Clotting profile — PT and aPTT
U/E/Cr, calcium/phosphate/magnesium, uric acid, Lactate MONITORING
Dehydrogenase (LDH) To watch and monitor for tumor lysis syndrome, hyperviscosity
LFTs syndrome and coagulopathy
Serum immunoglobulins — IgG, IgA, IgM Hourly parameters
Serology for EBV, CMV, Hep A, Hep B, Hep C, varicella, mumps, Strict Intake/Output (I/O) charting, with six hourly fluid tally
measles, Rubella and Herpes Simplex Virus (HSV) Urine pH
300 The Baby Bear Book
May need IV frusemide 0.5–1.0mg/kg/dose if urine output < 100ml/
m2/hr
Daily FBC, U/E/Cr, Ca/P/Mg, uric acid
Monitor K/Ca/PO4 every four to six hours
REFER/NOTIFY
Medical social worker
Children’s Cancer Foundation
Children’s Cancer Registry
FAMILY CONFERENCE (CONFIRM DATE AND VENUE WITH
ONCOLOGIST)
Oncologist
Nursing officer/staff nurse
Medical social worker
Children’s Cancer Foundation representative
Parents
PROPHYLAXIS IN IMMUNOCOMPROMISED
ONCOLOGY PATIENTS
GENERAL PRINCIPLES
Infections are a major cause of morbidity and mortality in
immunocompromised oncology patients. The following preventive
measures help to reduce the risk of infections:
All febrile neutropenic patients should be nursed in a ‘neutropenic
cubicle’ (in Ward 76, KKH) or in a reverse-barrier isolation room in
other wards
Examine the most immunocompromised child first, e.g. child
undergoing BMT, unless that child has a known infection with MRSA
or an Extended-Spectrum Beta-Lactamase (ESBL) organism
Strict hand-washing or alcohol rub before examination, in-between
each patient and after leaving the patient rooms
Reduce invasive procedures that can breach the integument, e.g.
urinary catheterisation, gastrointestinal scopes, rectal drugs or
rectal examination, and nasogastric tubes, particularly if they are
neutropenic or thrombocytopenic
Haematology and Oncology 301
Order appropriate mouthcare like chlorhexidine, Biotene® or Difflam®
mouthwash
Order oncology diet
Plants, dried or fresh flowers are not allowed in oncology rooms
because of the possible presence of moulds on these items
Oncology patients should have good perineal and hand hygiene —
Wash before eating, after going to the toilet, as well as before and
after touching any wounds
Visitors to oncology rooms must not have an URTI, active contagious
disease, recent exposure to contagious disease, active herpes zoster,
varicella-like rash within six weeks of live varicella vaccine, or history
of Oral Poliomyelitis Vaccine (OPV) in the past three to six weeks
Toys and play areas used by oncology patients should be disinfected
weekly
PROCEDURES
Oncology patients who have a central venous line, intraventricular
shunt, intramedullary rod, prosthesis for limb salvage, ureteric stents or
any other foreign body in situ should receive antibiotic prophylaxis (if
they are not already on antibiotics) for the following procedures:
Any dental procedures like extraction, filling, scaling
Bronchoscopy
Surgery of upper respiratory tract
Gastrointestinal surgery
Recommended antibiotic prophylaxis is the same as that for prevention
of IE in cardiac patients.
Infection Exposure
Oncology patients currently on treatment or within 12 months after
stopping treatment (24 months off treatment if child had an allogeneic
BMT) are at risk of severe chicken pox or measles if there is exposure.
Even if they have had chickenpox or measles or prior vaccination
before the diagnosis of malignancy, they are still at risk because the
immunosuppressive treatment for the malignancy may have obliterated
the memory T-cells.
Significant Contacts Include
Direct contact with an infected child in the same class or in the
playground
Staying in the same household with an infected child
302 The Baby Bear Book Haematology and Oncology 303

Table 7-9: Recommended vaccinations for post-BMT patients from 12 months onwards.
Proven contact with an infected child during the infectious period
(48 hours prior to and after appearance of rash) Vaccine 12 Months After 14 Months After 24 Months After
Shingles contacts only need prophylaxis if direct contact with Diphtheria, tetanus,
exposed vesicles has occurred pertussis
Age < seven years DaPT or DT DaPT or DT DaPT or DT
Chickenpox Age > seven years Td Td Td
If exposure to chickenpox is within 96 hours, IV Varicella Zoster Polio IPV IPV IPV
Immune Globulin (VZIG) should be given
Hepatitis B Hep B Hep B Hep B
The dose is 5–25 units/kg. Note that each vial comes in 125 units in
5mls Haemophilus Hib conjugate Hib conjugate Hib conjugate
influenza b
Start the infusion at 0.1ml/kg/hour and increase every 10 minutes to
a maximum of 1ml/kg/hour Pneumococcus PPV23 — PPV23
Protection conferred by VZIG lasts three to four weeks Measles, mumps, — — MMR
During the incubation period for chickenpox (21 days), withhold rubella
chemotherapy if possible Legend: DaPT — Diphtheria, acellular pertussis and tetanus; DT — Diphtheria, tetanus;
If chickenpox should develop, IV acyclovir should be given for seven Td — Tetanus, smaller dose diphtheria; IPV — Inactivated polio vaccine; PPV23 — 23-valent
pneumococcal polysaccharide.
days or until no new lesions have appeared for 48 hours:
< one year: IV 10mg/kg/dose eight hourly
> one year: IV 500mg/m2/dose eight hourly Not completely immunised:
No further vaccinations until 12 months after end of treatment,
Measles: then
If exposure is within six days, IVIG 0.5mg/kg should be given Restart primary immunisation schedule, replacing OPV with IPV
During the incubation period of 14 days, withhold chemotherapy if Follow rest of immunisation schedule when child goes to school
possible Recommended vaccination for post-BMT patients:
No vaccinations until 12 months after cessation of
VACCINATIONS AND TRAVEL immunosuppressive drugs (like cyclosporin A and steroids), then
During treatment and up to 12 months after cessation of treatment follow Table 7-9.
(at least 12 months after allogeneic BMT), no live vaccines should be
given. If the patient has a sibling who is receiving primary immunisation, Routine vaccination of hepatitis A, influenza, meningococcus not
ensure that the sibling receives Inactivated Poliomyelitis Vaccine (IPV) indicated. Varicella vaccine contraindicated in Haematopoietic Stem Cell
instead of OPV, to prevent transmission of the live poliovirus to the Transplantation (HSCT) recipients.
patient.
Any child on treatment or six months off treatment for cancer, who
Recommended vaccination for oncology patients after treatment: is going to travel to any high-risk country, should be referred to the
Previously completed primary immunisation: appropriate specialist for travel vaccine advice, keeping in mind any
No further vaccinations until 12 months after end of treatment, interactions there may be between any chemotherapy the child is
then currently taking and the prophylactic vaccines or drugs.
Boost with DT or dT/IPV/MMR
Boost with pertussis if < two years old
Boost with HiB if < four years old
Follow rest of immunisation schedule when child goes to school
304 Infectious Diseases 305

Common Aetiological
Condition Antibiotics
Agent(s)
INFECTIOUS DISEASES Acute Otitis Media ™ Streptococcus pneumoniae ™ Amoxycillin (50mg/kg/day q8H) x
™ Nontypable Haemophilus seven days
influenzae If < two years old, attends childcare,
™ Moraxella catarrhalis and had antibiotics in the past three
ANTIBIOTICS FOR SPECIFIC INFECTIONS ™ Group A Streptococcus months — consider higher dose
™ Staphylococcus aureus (80–90mg/kg/day)
™ Penicillin allergy: Erythromycin,
RESPIRATORY INFECTIONS Cotrimoxazole
™ Second-line (if no response after
Common Aetiological 72 hours): High-dose Amoxycillin/
Condition Antibiotics
Agent(s) Clavulanate, or Cefuroxime
Pharyngitis / ™ Group A Streptococcus ™ Penicillin V (50mg/kg/day (15–30mg/kg/day q12H)
Tonsillitis q6–12H) x ten days, or Amoxycillin NB: For < two years old, up to ten days may be
indicated
(50mg/kg/day q8H) x six days
™ Penicillin allergy: Erythromycin Pneumonia Neonate Group B ™ Ampicillin and Gentamicin (Neonatal
(50mg/kg/day q6–8H) x ten days Streptococcus dosing)
(GBS),
Acute Sinusitis ™ Streptococcus pneumoniae ™ Amoxycillin (50mg/kg/day q8H) x Escherichia
™ Haemophilus influenzae seven to ten days coli, Listeria
™ Moraxella catarrhalis ™ Penicillin allergy: Cotrimoxazole Gram-negative
(TMP 8mg/kg/day + SMX 40mg/kg/ bacilli
day q12H) x seven to ten days
™ Second-line (if no response after One to three Viruses, Afebrile:
72 hours): Amoxycillin/Clavulanate months Chlamydia ™ Erythromycin (50mg/kg/day q6–8h)
(Amoxycillin 50mg/kg/day + trachomatis, x 14 days
Clavulanate 7mg/kg/day q12H) Staphylococcus ™ Second-line: Azithromycin (10mg/
™ If still symptomatic after ten days, aureus, kg OD on Day 1, then 5mg/kg/day
continue for another seven days Bordetella OD for four days), or Clarithromycin
pertussis, (15mg/kg/day q12h) x seven to ten
Acute Diffuse ™ Staphylococcus aureus ™ Mild infection: Topical antimicrobial Streptococcus days
(Bacterial) Otitis eardrops pneumoniae Febrile:
Externa ™ Severe infection: Add oral Cloxacillin ™ Ampicillin (100mg/kg/day q6h) and
(50mg/kg/day q6H) x seven days Cloxacillin (100mg/kg/day q6h)
™ Penicillin allergy: Erythromycin ™ Second-line: Amoxicllin/Clavulanate
IV (120mg/kg/day q8h)
Three Viruses, Well-looking:
months to Streptococcus ™ *Amoxycillin (50mg/kg/day q8h) x
five years pneumoniae, seven to ten days
Haemophilus ™ Second-line: PO Amoxycillin/
influenzae, Clavulanate (50mg/kg/day q12h)
Moraxella ™ Macrolides if mycoplasma suspected
catarrhalis, or Penicillin allergy present
Mycoplasma * Higher dosage if drug-resistant Streptococcus
pnemoniae suspected
pneumoniae
306 The Baby Bear Book
Common Aetiological
Condition Antibiotics
Agent(s)
Pneumonia ≥ five years Mycoplasma Well-looking:
(cont’d) pneumoniae, ™ Erythromycin EES (50mg/kg/day q6-
Streptococcus 8h) x ten to 14 days, or Amoxycillin
pneumoniae, (50mg/kg/day q8h) x seven to ten
Chlamydia days (if no response to EES ≥ 48
pneumoniae hours)
™ Second-line: Azithromycin (10mg/
kg OD on Day 1, then 5mg/kg/day
OD for four days), or Clarithromycin
(15mg/kg/day q12h) x seven to ten
days
™ or PO Amoxycillin/Clavulanate
(50mg/kg/day q12h)(if no response
to Amoxicillin/Erythromycin ≥ 48
hours)
Pertussis Bordetella pertussis, Toxic-looking:
Bordetella parapertussis ™ IV Ampicillin (100mg/kg/day q6h)
and PO Erythromycin EES (50mg/kg/
day q6-8h)
™ Second-line: Amoxicllin/Clavulanate
IV (120mg/kg/day q8h)
™ Erythromycin EES (50mg/kg/day
q6-8h) x 14 days
™ Second-line: Azithromycin (10mg/
kg OD on Day 1, then 5mg/kg/day OD
for four days)
If < six months old: Azithromycin
(10mg/kg OD) x five days, or
Clarithromycin (15mg/kg/day q12h)
x seven to ten days
™ Cotrimoxazole (TMP (8mg/kg/day +
SMX (40mg/kg/day q12h) x 14 days
GASTROINTESTINAL INFECTIONS
Organism Remarks
Non-typhoidal Antibiotics only if:
Salmonella ™ Septicemia
™ < three months old
™ Immunocompromised
Salmonella typhi, Bacteremia or enteric
paratyphi fever
Campylobacter Antibiotics only for severe
ongoing disease
Escherichia coli Antibiotics only for severe
cases
Shigella Drug of choice (but some
strains are resistant)
Ampicillin-susceptible
strains
Cotrimoxazole and
ampicillin-resistant
strains
Resistant strains;
approved for > 17 years
of age
Infectious Diseases 307
Antibiotics
™ Cotrimoxazole [TMP 10mg/kg/dose
(max 320mg) + SMX 50mg/kg/day (max
1600mg) q12H] orally for up to 14 days
™ Ampicillin [200mg/kg/day (max 4g)
q6H] IV for up to 14 days
™ Ceftriaxone [75–100mg/kg/day (max
4g)] OD
™ Cefotaxime (200mg/kg/day q6h) IV for
up to 14 days
™ Ceftriaxone [100mg/kg/day (max 4g)]
OD IV for up to 14 days. Convert to oral
Cotrimoxazole or Ceftibuten (Cedax)
(9mg/kg/day q12h) to complete total
of 14 days, or Azithromycin (10mg/
kg/day) once clinically improved.
For Azithromycin conversion, divide
remaining days of treatment by two for
the number of Azithromycin days.
A longer duration of treatment is
required for localised invasive infections
and meningitis (six weeks)
™ Erythromycin [50mg/kg/day (max 2g)
q6H] x five to seven days
™ Cotrimoxazole [TMP 10mg/kg/dose
(max 320mg) + SMX 50mg/kg/day (max
1,600mg) q12H] orally for five to seven
days
™ Ampicillin [200mg/kg/day (max 4g)
q6H] IV x five to seven days
™ Cotrimoxazole [TMP 10mg/kg/day (max
320mg) + SMX 50mg/kg/day (max
1,600mg) q12H] orally or IV x 5days
™ Ampicillin [100mg/kg/day (max 2g)
q6H] orally or IV x five days
™ Ceftriaxone (50mg/kg/day) OD IV or IM
for up to five days
™ Nalidixic acid (50mg/kg/day q6H) orally
x five days
™ Norfloxacin (800mg q12H) orally x three
to five days
™ Ciprofloxacin (1g q12H) x three to five
days
308 The Baby Bear Book Infectious Diseases 309

Organism Remarks Antibiotics Common Empiric

Age Alternative Duration
Helicobacter pylori Treat if peptic ulcer ™ Omeprazole (2mg/kg/day q12h), and Organisms Antibiotic
disease or bastric mucoa- Clarithromycin (15mg/kg/day q12h), > three ™ Streptococcus Ceftriaxone Cefotaxime ™ Streptococcus
associated lymphoid and Amoxicillin (50mg/kg/day q12h) x months pneumoniae (100mg/kg/day (300mg/kg/day pneumoniae:
tissue type lymphoma or 14 days. Consider Omeprazole therapy ™ Hib q12–24h) q6h) Ten to 14 days
early gastric cancer beyond 14 days if still symptomatic. ™ Neisseria ± ± ™ Hib: Seven to
Amoeba ™ Metronidazole (35–50mg/kg/day q8H) meningitidis Vancomycin Vancomycin ten days
x ten days, or Tinidazole (50–60mg/kg/ (60mg/kg/day (60mg/kg/day ™ Neisseria
day) OD x three days q6h) q6h) meningitidis:
™ Follow with Paromomycin (25–35mg/ (add Vancomycin Five to seven
kg/day q8H) x seven days if very sick, days
CSF suggestive
Giardia ™ Metronidazole (22.5mg/kg/day q8H) x of bacterial
seven days meningitis or
OD = Once daily dosing CSF gram stain
shows G + cocci)

CENTRAL NERVOUS SYSTEM (CNS) DISORDERS Organism-specific Treatment

Meningitis
Duration of
Organism Recommended Alternative
Common Empiric treatment
Age Alternative Duration
Organisms Antibiotic Streptococcus pneumoniae
< one ™ GBS* Ampicillin Ampicillin ™ GBS, Listeria: Penicillin-sensitive: Penicillin G Ampicillin or Ten to 14 days
month ™ Escherichia coli + + 14–21 days (Meningitis: MIC < 0.06ug/ml, Ceftriaxone
™ Listeria Gentamicin Cefotaxime ™ Gram-negative Non-meningitis ≤ 2ug/ml)
(see dosage or bacilli: 21 days
Penicillin-resistant: Ceftriaxone Cefotaxime Ten to 14 days
for neonates Ceftriaxone (can
Meningitis: Resistant (MIC >
in ‘Antibiotics’ be used after
0.12ug/ml)
table, p. Day 7 of life and
Non–meningitis: Intermediate
565–572) in the absence
(MIC 4ug/ml, resistant > 8ug/
of neonatal
ml and Ceftriaxone-sensitive
jaundice)
(MIC < 0.5ug/ml)
One to three ™ GBS* Ampicillin Ampicillin ™ Streptococcus
Penicillin-resistant and Vancomycin Ceftriaxone Ten to 14 days
months ™ Escherichia coli (100–200mg/ (100–200mg/kg/ pneumoniae:
Ceftriaxone-resistant: + Ceftriaxone + Vancomycin
™ Listeria kg/day q6h) day q6h) Ten to 14 days
Meningitis: Intermediate (MIC + Rifampicin
™ Streptococcus + + ™ Hib: Seven to
1ug/ml) or resistant (MIC > (for meningitis
pneumoniae Ceftriaxone Cefotaxime ten days
2ug/ml) if susceptible to
™ Haemophilus (100mg/kg/day (300mg/kg/day ™ Neisseria
Non-meningitis: Intermediate rifampicin, if no
influenzae type q24h q6h) meningitidis:
(MIC 2ug/ml) or resistant (MIC clinical or CSF
b (Hib) Five to seven
> 4ug/ml) improvement)
™ Neisseria days
meningitidis ™ GBS, Listeria: Neisseira meningitidis Penicillin G Ampicillin or Five to seven
14–21 days Ceftriaxone days
™ Gram-negative Haemophilus influenzae type b Ceftriaxone Ampicillin Seven to ten
bacilli: 21 days (if sensitive) days
310 The Baby Bear Book Infectious Diseases 311

Duration of RENAL DISORDERS

Organism Recommended Alternative
treatment Upper Urinary Tract Infection
MRSA Healthcare- Severe infection: Vancomycin ± Gentamicin/Rifampicin
(Methicillin- associated Less severe infection: Vancomycin Age Antibiotics Duration
resistant S. (multi-drug- <28 days ™ Ampicillin 50–100mg/kg/day q6H Ten to 14 days
aureus) infection resistant) and IV therapy until afebrile for 48–72
Community- Severe infection: Vancomycin ± Gentamicin/ Rifampicin Gentamicin 5–7.5mg/kg/day hours before oral therapy
associated Skin/soft tissue: Clindamycin ( if susceptible) or q8–12H
(not multi-drug- Cotrimoxazole ™ Second line: Ceftriaxone
resistant) Pneumonia/bone/joint infections: Clindamycin ( if 50–100mg/kg/day OD, or
susceptible) Cefotaxime 50–200mg/kg/day
q6–8H
≥ 28 days ™ Gentamicin 5mg/kg/day once daily, IV therapy until afebrile for 24 hours
unless very ill or renal dysfunction before oral therapy
Drug Doses for Meningitis then 7.5mg/kg/day q8h
™ Second-line: Ceftriaxone

Body Weight
Body Weight
Body Weight
Body Weight 50–100mg/kg/day OD, or
< 2kg > 2kg Cefotaxime 50–200mg/kg/day
< 2kg > 2kg Children
Antibiotics Neonates Neonates q6–8H
Neonates Neonates > One Month
Seven to 28 Seven to 28
< Seven Days < Seven Days
Days Days
Penicillin G 250,000– 450,000units/ 250,000– 450,000units/ 400,000units/ Lower Urinary Tract Infection
450,000units/ kg/day q6H 450,000units/ kg/day q6H kg/day q4 –6H
kg/day q8H kg/day q8H Age Antibiotics Duration
Ampicillin 200–300mg/ 300mg/kg/day 200–300mg/ 300mg/kg/day 300–400mg/
< seven ™ Cotrimoxazole: TMP 8mg + SMZ Seven to ten days monotherapy
kg/day q8H q4–6H kg/day q8H q4–6H kg/day q4–6H
years old 40mg/kg/day q12H
Cefotaxime 100mg/kg/day 150mg/kg/ 150mg/kg/ 200mg/kg/ 225–300mg/ ™ Nitrofurantoin: 5–7mg/kg/day q6H
q12H day q8H day q8H day q6H kg/day q6–8H ≥ seven Seven to ten days monotherapy, or
years old ™ Cephalexin: 25–50mg/kg/day q8H Three days TMP + SMZ (especially
Ceftriaxone 50mg/kg/ 50mg/kg/ 50mg/kg/ 75mg/kg/ 100mg/kg/day ™ Trimethoprim: 8mg/kg/day q12H
day OM day OM day OM day OM q12–24H those >12 years old)
Vancomycin 30mg/kg/day 45mg/kg/day 30 –45mg/kg/ 45–60mg/kg/ 60mg/kg/day
q12H q8H day q8–12H day q6–8H q6H
Gentamicin 2.5mg/kg/dose 2.5mg/kg/dose 5mg/kg/day 7.5mg/kg/day 6mg/kg/day BACTERIAL SKIN INFECTIONS
q12–18H q8–12H q12H q8H q8H
* For GBS meningitis, a higher dose of penicillin or ampicillin is recommended. Gentamicin is added for Condition Antibiotics
synergistic effect with a penicillin antibiotic in the initial week of treatment. Impetigo First-line Cloxacillin 50mg/kg/day q6H x seven to ten days
Cephalexin 50mg/kg/day q8H x seven to ten
days
Penicillin allergy Erythromycin 30–50mg/kg/day q6H
Cotrimoxazole (TMP 8mg + SMZ 40mg/kg/
day) q12H
Ecthyma Cloxacillin 50mg/kg/day q6H x seven to ten days
Cephalexin 50mg/kg/day q8H x seven to ten days
Penicillin allergy: Erythromycin 30–50mg/kg/day q6H x seven to ten days
Blistering dactylitis Amoxycillin 50mg/kg/day q8H x seven to ten days
Penicillin allergy: Erythromycin 30–50mg/kg/day q6H x seven to ten days
312 The Baby Bear Book Infectious Diseases 313

Condition Antibiotics COMPLICATIONS

Folliculitis
Furunculosis/Carbuncle
Cellulitis/Erysipelas
Necrotising Fasciitis
Staphyloccoccal Scalded Skin
Syndrome (SSSS)
Toxic Shock Syndrome (TSS)
Cloxacillin 50mg/kg/day q6H x seven days ™ Secondary bacterial infections — Cellulitis, necrotising fasciitis
Cephalexin 50mg/kg/day q8H x seven days
™ Varicella pneumonitis
Penicillin allergy: Erythromycin 30–50mg/kg/day q6H x seven days
™ Encephalitis, cerebellar ataxia, meningitis, transverse myelitis
Cloxacillin 50mg/kg/day q6H x seven to ten days
Cephalexin 50mg/kg/day q8H x seven to ten days ™ Reye’s Syndrome
Penicillin allergy: Erythromycin 30–50mg/kg/day q6H x seven to ten days ™ Thrombocytopenia
Incision and drainage when fluctuant, iron supplementation ™ Hepatitis
Amoxycillin: 50mg/kg/day q6H and Cloxacillin: 50mg/kg/day q6H x seven ™ Arthritis
to ten days ™ Glomerulonephritis
Penicillin allergy: Erythromycin: 30–50mg/kg/day q6H x seven to ten days
Cephalexin: 50mg/kg/day q8H x seven to ten days ™ Disseminated varicella
Severe: IV Amoxycillin/ Clavulanate: 120mg/kg/day q8H ™ Herpes zoster
Urgent surgical debridement
Empiric: IV Cloxacillin 100mg/kg/day q 6H and IV Clindamycin 30mg/kg/ CONTAGIOUS PERIOD
day q8H Two days before onset of rash until all scabs have dried up (about one
Cloxacillin: 50mg/kg/day q6H week, longer in immunocompromised patients).
Staphylococcal TSS Cloxacillin 100mg/kg/day q6H and Clindamycin
30mg/kg/day q8H x ten to 14 days
TRANSMISSION
™ Person-to-person direct contact
Streptococcal TSS Penicillin G 250,000–450,000units/kg/day
q4–6H and Clindamycin 30mg/kg/day q8H x ™ Airborne and droplet spread of respiratory secretions and vesicle fluid
ten to 15 days ™ For herpes zoster: Direct contact with or droplet spread of vesicle fluid

TREATMENT
™ Immunocompetent Patients
Š Oral acyclovir only if:
CHICKENPOX (VARICELLA) y Secondary contact case in a family
y > 12 years old
y Chronic skin or pulmonary conditions
INCUBATION y On long-term salicylate therapy
Ten to 21 days, generally 14 to 16 days. Can be as long as 28 days in y On short- or long-term, intermittent or aerosolised steroids
patients given passive immunisation. Š Start oral acyclovir within 72 hours (preferably within 24 hours) of
rash onset
CLINICAL FEATURES Š IV acyclovir for complicated varicella e.g. encephalitis,
™ Prodrome of fever, cough, malaise and pruritus disseminated varicella
™ Generalised maculopapular rash which progresses to clear vesicles ™ Immunocompromised Patients
then cloudy vesicles and finally scabs Š IV acyclovir until all lesions have crusted, then oral acyclovir for
™ Skin lesions start over the face or trunk, appear in crops and spread another three days
outward to the limbs
™ Oral ulcers can occur Acyclovir Dose
™ Fever generally lasts three days to five days Oral 20mg/kg/dose six hourly
™ Suspect secondary bacterial infections if fever lasts > five days IV < one month old: 10mg/kg/dose eight hourly
™ Mild, atypical and inapparent infections can occur > one month old: 500mg/m2/dose eight hourly
314 The Baby Bear Book
Isolation
™ From seven days after exposure until all lesions have scabbed
™ Patient is contagious from about two 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 a single dose subcutaneously in children < 12
years old or two doses (four to eight weeks apart) if > 13 years old
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)
Š If result shows antibody positive, no action is required
Š If result shows antibody negative, give varicella immunoglobulin
(VZIG) within 96 hours of exposure (preferably as soon as
possible)
Š Dose: 5–25IU/kg, or 0.2–1ml/kg (vials of 25IU/ml)
Š Do NOT overdose, as this may lead to fluid overload and
hyperviscosity
Š 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 three weeks, VZIG is not
required.
BONE MARROW TRANSPLANT (BMT) PATIENTS
VZIG 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:
Infectious Diseases 315
™ 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 five days before delivery till two
days after delivery
™ Hospitalised premature < 28 weeks of gestation and mother has no
history of chickenpox and is varicella antibody negative
™ Hospitalised 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:
Š Varicella patient in the same two to four bedroom; or adjacent
beds in a large ward
Š Face-to-face contact with an infectious patient or staff member,
or visit by a person deemed contagious
Š 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.
316 The Baby Bear Book Infectious Diseases 317

DENGUE FEVER Š Rapid and weak pulse

Š Narrow pulse pressure of < 20mmHg
Š Hypotension
DENGUE INFECTION Š Cold, clammy skin
Causative agent: Dengue virus, serotypes 1–4 Š Altered mental status
Incubation period: Three to 14 days, usually five to seven days
Infectious period: One day before until five days after the onset of Usually develops three to six days after onset of symptoms.
illness, during the period of viraemia Signs of possible decompensation are:
Transmitted by: Aedes aegypti and Aedes albopictus mosquitoes, ™ Disappearance of fever
which bite during the day ™ Drop in platelets
™ Increase in haematocrit
DENGUE FEVER
An acute febrile illness lasting two to seven days, associated with two or OTHER COMPLICATIONS
more of the following: ™ CNS: Encephalopathy, encephalitis, aseptic meningitis, transverse
™ Maculopapular rash, flushing or petechiae; with islands of sparing myelitis, Guillain-Barre Syndrome
™ Headache ™ Myocarditis
™ Retro-orbital pain ™ Transaminitis
™ Myalgia ™ Haemoglobinuria — Intravascular haemolysis
™ Arthralgia ™ Vertical transmission to newborn babies

DENGUE HAEMORRHAGIC FEVER (DHF) INVESTIGATIONS

All the following four criteria must be fulfilled: ™ FBC: Thrombocytopenia, leucopenia or lymphocytosis with atypical
™ Fever, or recent history of acute fever lymphocytes, neutropenia, raised haematocrit
™ Hemorrhagic manifestations — Bruising and bleeding at ™ U/E/Cr: Hyponatremia
Not routine, only
™
venepuncture sites, gums or the gastrointestinal tract. Other
examples are epistaxis, a positive tourniquet test, or petechiae
™ Low platelet count (< 100 x 109/L)
™
™
LFTs: Elevated transaminases (AST > ALT)
Coagulation studies: Prolonged PT and PTT
Group and cross-match: May need transfusion
} if child unwell/has
possible features of
pre-shock/shock
™ Objective evidence of plasma leakage: ™ Dengue serology: Positive IgM antibodies (after day five of illness) or
Š Elevated haematocrit a four-fold rise in paired IgG titres, acute and convalescent
Š Low serum protein ™ Chest radiograph if chest signs present, or work of breathing
Š Ascites increased (pleural effusion)
Š Pleural or pericardial effusions
MANAGEMENT
The following suggest impending decompensation: Routine
™ Severe abdominal pain ™ Usually only supportive care is required
™ Prolonged vomiting ™ Paracetamol for fever (avoid NSAIDs)
™ Abrupt change from fever to hypothermia ™ Complete rest in bed if platelet count < 50 x 109/L
™ Change in level of consciousness (irritability or somnolence) ™ No intramuscular injections
™ IV access
DENGUE SHOCK SYNDROME (DSS) ™ Monitor vital signs including BP at least every four hours
™ The four criteria for DHF, and ™ Strict I/O chart. Maintain hydration
™ Evidence of circulatory failure: ™ Daily platelet count and haematocrit from third day of illness
318 The Baby Bear Book Infectious Diseases 319

™ Dengue is a notifiable disease — Notify using the prescribed form HAND-FOOT-AND-MOUTH DISEASE
within 24 hours (HFMD), AND HERPANGINA
HYPOVOLAEMIA
™ In patients with a rising haematocrit or falling platelet count, INTRODUCTION
administer an IV bolus of normal saline (10ml/kg to 20ml/kg) ™ Caused by Enteroviruses (EV)
followed by a dextrose/saline maintenance fluid infusion ™ About 25 EV have been shown to cause HFMD, especially enterovirus
™ Stop IV fluids when the haematocrit < 40% and adequate 71 (EV 71), Coxsackie A16 and echoviruses
intravascular volume is present; avoid volume overload ™ A variant of HFMD is herpangina, which presents with mouth ulcers
but no rash and is due to the same group of EV
BLEEDING
™ Platelet transfusion only for severe thrombocytopenia, especially CLINICAL
when rate of decline is very fast (prophylactic); or for bleeding ™ Generally a mild disease affecting young children
associated with any degree of thrombocytopenia (therapeutic) ™ Recovery in about a week
™ FFP is indicated if there is a consumption coagulopathy ™ Typically presents with fever for up to five days:
™ Use whole blood or packed cells to replace blood loss Š Mouth ulcers
™ Oxygen can be given for patients with respiratory symptoms Š Vesiculo-papular rash lasting seven days to ten days over the
palms, soles and buttocks
FURTHER MANAGEMENT Š Sometimes there are papules over the shins
Some indications for admission to CICU are: ™ Herpangina patients have multiple mouth ulcers over the posterior
™ Requirement for continuous monitoring pharynx, buccal mucosa and tongue, but no rash
™ Requirement for inotropic support ™ Complications are rare: Myocarditis, pulmonary oedema, interstitial
™ Significant bleeding, especially in the setting of severe pneumonitis, brainstem encephalitis, aseptic meningitis, acute
thrombocytopenia or coagulopathy flaccid paralysis and even death
™ Evidence of end-organ hypoperfusion e.g. altered mental status,
oliguria despite fluids INCUBATION PERIOD
™ Respiratory compromise e.g. secondary to pleural effusions Three days to five days (two days to two weeks)

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 edition. Philadelphia: WB
Saunders; 2000. p. 1005–1007.
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 three to four weeks from the saliva and
six weeks to 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
320 The Baby Bear Book Infectious Diseases 321

™ Close monitoring for complications: SYMPTOMS AND SIGNS

Š Vomiting, change in sensorium, seizures, myoclonic jerks
Š Hypertension/hypotension, tachycardia out of proportion to
fever (normally pulse increases by about 10bpm above baseline
for every 1°C rise in temperature)
Š Raised total white cell count
™ IVIG is a possible therapy for patients with complicated disease
™ Medical certificate for ten days after onset of illness
™ No swimming for next three months in order to decrease
transmission to susceptible hosts
All HFMD patients need to have stools for virus culture sent to the
Virology Laboratory at SGH for surveillance purposes; indicate on
the virology form: “Charge to QED” (Quarantine and Epidemiology
Department). For complicated patients, in addition to stools, send the
mouth swabs and vesicular fluid for virus culture, Nasopharyngeal
Aspirates (NPA) for EV PCR.
HFMD 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; 2000. p. 236–238.
2. Benenson AS. Coxsackieviruses: 1B Enterviral vesicular stomatitis with exanthem. In:
Control of Communicable Diseases Manual. 16th ed. 1995. Washington, DC: American
Public Health Association; 1995. p. 116–118.
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).
™ 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
™ LP — CSF for cell count, gram stain and culture:
Š Cells — Predominantly polymorphs (normal CSF in children > two
months old contains < 5Wbc/mm3 and no polymorphs; CSF Wbc
counts in the neonatal period should not exceed 11–22 x 106/L)
Š Protein — Elevated (normal CSF protein in children < ten years old
should be < 0.35g/L; CSF protein in neonates should be < 1.0g/L)
Š Glucose — Reduced (normal CSF glucose concentration should
be approximately two-thirds of serum levels)
Š 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
Š 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%)
Š PCR for detection of Hib, S. pneumoniae and N. meningitidis
322 The Baby Bear Book
Contraindications to LP:
Š Signs of raised ICP
Š Cardiorespiratory instability
Š Infection in the area through which the LP needle will pass
Š Evidence of coagulopathy
Interpretation of blood-contaminated CSF (‘Traumatic Taps’):
Š 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
Š 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)
Š It has been suggested by some authors that contamination of the
CSF by less than 10,000 red cells x 106 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
™ FBC
™ CRP — 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
MANAGEMENT
™ Antimicrobial therapy (see “Central Nervous System (CNS) Disorders”
p. 308)
™ 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 is 0.6–0.8mg/kg daily in two or three divided doses for two days
Infectious Diseases 323
™ 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 less than 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 one 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 heptavalent conjugate vaccine has 97% efficacy
against invasive infections caused by the pneumococcal serotypes
contained in the vaccine. Studies are ongoing to evaluate new 11-
and 13-valent vaccines. Children older than two 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 polysaccharide vaccine against A,
C, Y and W-135 strains is recommended for high-risk children
(e.g. asplenia) older than two years. Meningococcal serogroup C
conjugate vaccine is routinely administered in some countries
™ Chemoprophylaxis
Š Meningococcal disease (see “Meningococcal Infections” overleaf )
Š Hib — Rifampicin prophylaxis is recommended for all household
contacts
Dose:
Zero to three months: 10mg/kg once daily for four days
Three months to 12 years: 20mg/kg once daily for four days
>12 years and adults: 600mg once daily for four days
324 The Baby Bear Book
MENINGOCOCCAL INFECTIONS
™ Caused by Neisseria meningitides
™ Can result in bacteremia, meningitis, septic shock, DIC and focal
infections
™ Usually serogroups A, B, C, W35 and Y
™ Vaccination available against A, C, W135 and Y
™ Quadrivalent vaccine is a polysaccharide vaccine, and thus the
vaccine can only be given to children > two years of age. For children
three months to two years old, the vaccine may only be used to
protect against serogroup A
™ Children with terminal complement defects, properdin deficiencies,
functional or anatomic asplenia, are at high risk for meningococcal
infections
™ Incubation period one day to ten days, most commonly less than
four days
TREATMENT
™ Penicillin G (300,000units/kg/day), or
Ampicillin (200mg/kg/day to 400mg/kg/day), or
Ceftriaxone (50mg/kg/day)
™ Treat for five days to seven days if meningitis, ten days to14 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 three feet 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 seven days
Infectious Diseases 325
™ Direct exposure to patient’s secretions during the seven 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) 12H PO x two days, or
Ceftriaxone 250mg IM x one dose (pregnancy), or
Ciprofloxacin 500mg PO x one dose (liver dysfunction)
™ Children
Rifampicin: > One month old — 10mg/kg/dose (max 600mg) 12H x
two days
< one month old — 5mg/kg/dose (max 600mg) 12H x two days, or
Ceftriaxone 125mg IM x one dose (< 15 years old)
™ Note: One capsule rifampicin = 150mg
™ Prophylaxis for medical and nursing personnel NOT routinely
recommended for medical and nursing personnel. 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; 2000.
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
326 The Baby Bear Book Infectious Diseases 327

Blood-borne viruses that can be transmitted through needlestick and ™ Assess impact of result on person’s lifestyle
mucous membrane exposures include: Hepatitis B (6–30% risk ), C (3.5% ™ Assess patient’s support system and coping mechanisms
risk) and HIV (0.3% percutaneous, 0.09% mucous membranes). ™ Perform risk reduction education

All healthcare workers should ensure that they have immunity against
hepatitis B (see Table 8-1 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,
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.

anti-HIV drugs as prophylaxis may be recommended for four weeks (see

Table 8-2 p. 328).
Table 8-1: Recommendations for hepatitis B prophylaxis after percutaneous exposure to blood that
contains (or might contain) HBsAg*.
After suffering a needlestick injury, staff should:
™ Express blood from the puncture site Treatment When Source Is
Exposed Person
™ Irrigate the wound with normal saline HBsAg-Positive HBsAg-Negative Unknown or Not Tested
™ Wash with chlorhexidine detergent/soap and water Administer HBIG,# Initiate hepatitis B Initiate hepatitis B
Injuries requiring suturing should be treated as usual Unimmunised one dose and initiate vaccine series vaccine series
hepatitis B vaccine
In mucous membrane (eyes, mouth) exposure: Previously immunised
™ Flush the area with water or saline Known responder No treatment No treatment No treatment
™ All exposures should be reported to the relevant clinic (Women’s 24-
Known non-responder HBIG, two doses or HBIG No treatment If known high-risk
hour Clinic in KKH) one dose and initiate source, treat as if source
™ Report within two hours as this is the ideal time for starting anti-HIV immunisation† were HBsAg positive
prophylaxis Response unknown Test exposed person for No treatment Test exposed person for
anti-HBsΔ anti-HBsΔ
Staff and the source patient should be tested for hepatitis B surface antigen, ™ If inadequate ™ If inadequate, vaccine
anti-Hepatitis B IgG antibody, anti-hepatitis C IgG antibody and HIV IgG HBIG,# one dose booster dose‡
antibody. and vaccine booster
dose‡
In obtaining consent for HIV testing: ™ If adequate, no ™ If adequate, no
™ Explain need for testing in view of needlestick/mucosal exposure treatment treatment
™ Reassure patient about confidentiality * Modified from Centers for Disease Control and Prevention, 1997. HBsAg indicates hepatitis B surface antigen;
™ Assess risk factors e.g. patients who have had unprotected sex HBIG, hepatitis B immune globulin; anti-HBs, antibody to HBsAg.
#
Dose of HBIG, 0.06mL/kg, intramuscularly.
(oral/anal) with an infected partner of either sex, men who have †
Persons known NOT to have responded to a three-dose vaccine series and to reimmunisation with three
sex with men or both sexes, patients with multiple sexual partners, additional doses should be given two doses of HBIG (0.06mL/kg), one dose as soon as possible after exposure
intravenous drug abusers, recipients of blood products before and the second one month later.
Δ
1985, babies born to HIV-infected mothers, patients who have been Adequate anti-HBs is > 10mIU/mL.
‡
The person should be evaluated for antibody response after the vaccine booster dose. For persons who
exposed to possibly non-invasive procedures e.g. tattooing and received HBIG, anti-HBs testing should be done when passively acquired antibody from HBIG is no longer
scarification detectable (e.g. four to six months); if they did not receive HBIG, anti-HBs testing should be done one to two
™ Provide information about HIV antibody test (PCR, Western, Blot, months after the vaccine booster dose. If anti-HBs is inadequate (< 10mIU/mL) after the vaccine booster
dose, two additional doses should be administered to complete a three-dose reimmunisation series.
Serology)
328 The Baby Bear Book Infectious Diseases 329

Table 8-2: Post-Exposure Prophylaxis (PEP) for healthcare workers (HCWs) exposed to blood and/
or body fluids with HIV.
Source Patient Source Patient
Exposure Source Patient HIV (+) Considerations Exposure Source Patient HIV (+) Considerations
Unknown Unknown
Mucous membrane Low-titre No treatment Skin integrity is Intact skin PEP not needed unless it No treatment
or skin, Source patient asymptomatic compromised if is high exposure to blood
integrity and high CD4 counts — May there is evidence e.g. extensive area of skin
compromised not need PEP, discuss with of chapped Percutaneous exposed or prolonged contact
HCW skin, dermatitis, exposure with blood
™ Small (few drops abrasion or open
or short duration) High-titre wound ™ Less severe e.g. Low-titre If there is a Combination
Source patient has advanced solid needle, Source patient asymptomatic possible risk for of factors e.g.
AIDS, primary HIV infection, superficial scratch and high CD4 count — HIV exposure, large-bore hollow
high or increasing viral Recommend prophylaxis consider needle and
load or low CD4 count — with Zidovudine 600mg/day prophylaxis deep puncture
Consider prophylaxis with in two or three divided doses with Zidovudine contribute an
Zidovudine 600mg/day in and Lamivudine 150mg 600mg/day in increased risk for
two or three divided doses twice a day two or three transmission if
and Lamivudine 150mg divided doses source patient is
twice a day High-titre and Lamivudine HIV-positive
™ Large (several Low-titre If there is a Source patient has advanced 150mg BD
drops, major Source patient asymptomatic possible risk for AIDS, primary HIV infection,
blood splash and/ and high CD4 count — HIV exposure, high or increasing viral
or longer duration Recommend prophylaxis consider load or low CD4 count —
i.e. more than with Zidovudine 600mg/ prophylaxis Recommend prophylaxis
several minutes) day in two or three divided with Zidovudine with Zidovudine 600mg/ day
doses and lamivudine 150mg 600mg/day in in two or three divided doses
twice a day two or three and Lamivudine 150mg
divided doses twice a day and either
High-titre and Lamivudine Indinavir 800mg every eight
Source patient has advanced 150mg twice a hours or Nelfinavir 750mg
AIDS, primary HIV infection, day and either three times a day
high or increasing viral Indinavir 800mg ™ More severe e.g. Low- or high-titre
load or low CD4 count — every eight hours large-bore hollow Recommend prophylaxis
Recommend prophylaxis or Nelfinavir needle, deep with Zidovudine 600mg/ day
with Zidovudine 600mg/ 750mg three puncture, visible in two or three divided doses
day in two or three divided times a day blood on device, and Lamivudine 150mg
doses and lamivudine 150mg or needle used in twice a day and either
BD and either Indinavir source patient’s Indinavir 800mg every eight
800mg every eight hours artery or vein hours or Nelfinavir 750mg
or Nelfinavir 750mg three three times a day
times a day
Duration of prophylactic anti-HIV medications: Four weeks.
330 The Baby Bear Book Infectious Diseases 331

OPTHALMIA NEONATORUM Treatment

GONOCOCCAL INFECTION
™ Onset day two to five 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), two drops
every ten minutes x one hour, then two drops every 30 minutes x
two to four hours, then two drops every hour x three days
™ Ceftriaxone IM 50mg/kg x one dose x maximum 125mg
™ If ceftriaxone is contraindicated e.g. NNJ or first week of life, give
cefotaxime (Claforan®) IM/IV at 100mg/kg x one dose
™ If there is any suspicion of complicated gonococcal infection e.g.
septic arthritis, septicemia, give ceftriaxone or cefotaxime IV for
seven days x14 days if meningitis)
™ Send mother and partner/spouse to Kelantan DSC polyclinic for
screening and treatment
™ Oral erythromycin 50mg/kg/day divided six hourly (two 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 Kelantan DSC polyclinic for
screening and treatment
S. AUREUS, S. PNEUMONIAE, E. COLI, H. INFLUENZAE
INFECTIONS
™ Framycetin or gentamicin eyedrops two to four hourly (seven to ten
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; 2000. p.
1251–1256.
2. Pickering LK, ed. Red Book: Report of the Committee on Infectious Diseases. 258th ed. Elk
Grove Village, IL: American Academy of Pediatrics; 2009.
TUBERCULOSIS (TB)

CHLAMYDIA TRACHOMATIS INTRODUCTION

™ Onset day five to 14 of life, may be up to six weeks ™ Caused by Mycobacterium tuberculosis
™ Watery eye discharge ™ AFB
™ Progresses to become purulent ™ Transmission usually air-borne

Lab Investigation PRESENTATION

™ 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
™ 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 < four years
332 The Baby Bear Book Infectious Diseases 333

Latent Tuberculosis Infection (LTBI) ™ 26G tuberculin needle angled upwards

™ Asymptomatic infection with no abnormal physical findings
™ Positive or reactive mantoux test
™ CXR 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):
Š Most asymptomatic
Š Early manifestations include fever, weight loss, cough, night
sweats and chills
™ Lymphadenitis:
Š
Most common form of extrapulmonary TB
Š
Usually cervical, supraclavicular and submandibular nodes
Š
Can be unilateral or bilateral
Š
Lymph nodes generally firm and rubbery, non-tender and fixed to
underlying tissues
Š Can progress to affect several nodes
Š May be associated with active PTB
™ Meningitis/Miliary TB (rare):
Š Miliary disease is a disseminated form of TB which occurs when
massive bacteraemia causes disease in two or more organs
Š Clinical manifestations are protean depending on the site of
involvement
™ Tense intradermal wheal 6mm to 10mm should be obtained
immediately during injection
™ Do not cover or dress the injection site
™ Read mm of induration 48 hours to 72 hours later (transverse
diameter only)
™ Incubation period from infection to a positive MTT is two to twelve
weeks (median three to four 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 (< 12 years old)
> 15mm (> 12 years old)
> 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/Ligase Chain Reaction (LCR))

Other extrapulmonary involvement includes pericardium, pleura, Site Specimen

abdominal viscera, bone/joint, kidney. PTB Gastric lavage (early morning) x 3; sputum;
± bronchoalveolar lavage; ± pleural fluid
DIAGNOSIS Lymphadenitis Biopsy and histology of the affected lymph node(s)
Chest X-ray (CXR) Meningitis CSF
™ Hilar adenitis
™ Segmental lesions ™ Isolation of M. tuberculosis by culture from the above specimens
™ Collapse or consolidation establishes the diagnosis of TB
™ Calcification occurs > six months after infection ™ Organisms are isolated from fewer than 50% of children and 75% of
™ Multiple lung foci or cavitation infants with PTB
™ Pleural effusions (rare) ™ Culture material should be obtained from children with evidence of
™ Miliary disease TB disease especially when:
Š An isolate from the source case is not available
Mantoux Test (MTT) Š Immunocompromised e.g. HIV infection
™ Site: Clean volar surface of left forearm Š Extrapulmonary disease
™ 0.1ml of tuberculin injected intradermally
334 The Baby Bear Book Infectious Diseases 335

TREATMENT Management of the newborn infant whose mother (or other household
Site of TB Drugs and Duration of Treatment contact) has LTBI or TB disease:
PTB, lymphadenitis Six months — Two months HRZ followed by four ™ Based on categorisation of the maternal or household contact
months of HR; infection
or ™ Protection of the infant from infection is of paramount importance
Nine Months — HR ™ Separation of the infant from the mother or household contact
Extrapulmonary Nine to 12 Months — Two months HRZS followed should be avoided when possible
by seven to ten months HR
(H: Isoniazid; R: Rifampicin; Z: Pyrazinamide; S: Streptomycin)
Table 8-3: Management of the newborn infant whose mother (or other household contact) has
LTBI or TB disease
™ If drug resistance is suspected, initial therapy should include a fourth
drug, either ethambutol or streptomycin, until drug susceptibility Circumstances Recommendations Remarks
results are available Mother or household No separation required The mother usually needs
™ Pyridoxine is recommended if: contact has a normal treatment of LTBI i.e.
Š Diet deficient in milk and meat/nutritional deficiencies chest radiograph, Give BCG vaccine chemoprophylaxis. The
Š Symptomatic HIV-infected children asymptomatic newborn infant needs no
special evaluation or therapy.
Š Breastfed infants and their mothers The positive MTT result could
Š Pregnant adolescents and women be a marker of an unrecognised
™ Complete TB notification form on diagnosis case of contagious TB within
™ Refer to TB Control Unit for Daily Observed Therapy (DOT) if the household, thus other
compliance is a problem or multi-drug-resistant (MDR) TB household members should
have a MTT and further
PERSONS AT INCREASED RISK FOR DRUG-RESISTANT evaluation
TUBERCULOSIS INFECTION OR DISEASE Mother or household Infant should be separated from Other household members
™ History of treatment for active TB contact has an mother or contact until evaluation should have a MTT and further
™ Source case for the contact received treatment abnormal chest is complete evaluation
radiograph
™ Contacts of a patient with a drug-resistant contagious TB disease If TB disease is found, isolation
™ Foreign-born persons should continue until the mother
™ Residents of areas where the prevalence of drug-resistant TB is or contact is receiving appropriate
documented to be high anti-tuberculosis therapy
™ Persons whose source case has positive smears for AFB or cultures
after two months of appropriate anti-TB therapy Evaluate infant for TB disease. Test
mother or contact for HIV
CHEMOPROPHYLAXIS Mother or household ™ The infant should be evaluated for TB in the mother or
Indicated for contacts with reactive mantoux test but clear CXR or MTT contact has clinical congenital TB and tested for HIV contact should be reported
or radiographic infection immediately to the Department
conversion i.e. increase in induration by 10mm (e.g. from 3mm to 13mm)
evidence of possibly • An MTT, a CXR, a LP and of Clinical Epidemiology so that
when retested 12 weeks after last contact with index case. contagious TB appropriate cultures should be investigation of all household
™ Isoniazid-susceptible — Nine months Isoniazid daily performed promptly members can be performed
™ Isoniazid-resistant — Six months Rifampicin daily • Placenta should be sent for promptly
™ Isoniazid- and Rifampicin-resistant — Consult infectious disease histology and AFB smears and
specialist cultures All contacts should have a MTT,
CXR and physical examination
336 The Baby Bear Book
Circumstances Recommendations
Mother or household • Regardless of the MTT
contact has clinical results, treatment of the
or radiographic infant with congenital
evidence of possibly TB should be initiated
contagious TB promptly with isoniazid,
(cont’d) rifampin, pyrazinamide, and
streptomycin
™ If the infant is receiving
treatment, separation is not
necessary
™ If congenital TB is excluded, give
BCG vaccine and isoniazid until
the infant is three or four months
of age, at which time the MTT
should be repeated
™ If the MTT at three months is
positive, the infant should be
reassessed for TB disease. If
disease is not present, isoniazid
should be continued for at least
nine months
™ If the MTT at three 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
members. The infant and mother
or contact should be on DOT
therapy
Remarks
The infant should be evaluated
at monthly intervals during
treatment
Note: Patients with multiple
drug-resistant TB should be
on DOT therapy
Infectious Diseases 337
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 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 three,
and no cough
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. 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.
338 The Baby Bear Book
INCUBATION AND ISOLATION PERIODS
FOR INFECTIOUS DISEASES
Disease Incubation Period Isolation of Patient
Chickenpox Ten to 21 days (up to 28 days if VZIG From school and non-immune
is given) friends until last vesicle
has dried (one week after
appearance of rash)
Diphtheria Three to six 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 Three to six days Contact precautions for
duration of hospitalisation
Rubella 14 to 23 days Droplet precautions for seven
days after the onset of rash
Measles Eight to 12 days Airborne precautions for five
days after appearance of rash
Infectious Diseases 339
Disease Incubation Period Isolation of Patient
Meningococcal One to ten days Droplet precautions until
infection 24 hours after initiation of
effective therapy
Mumps 14 to 21 days Droplet precautions until nine
days after onset of parotid
swelling
Poliomyelitis Seven to 21 days Contact precautions for
duration of hospitalisation
or until stool cultures are
negative
Rabies Average four to six weeks Standard precautions for
duration of illness
Typhoid Fever Usually one to two 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 six to 20 days) Droplet precaution for five
days after starting antibiotics;
if unable/unwilling to start
antibiotics, precautions for
14 days
340 The Baby Bear Book Infectious Diseases 341

KK HOSPITAL VACCINE
INFORMATION CHART 2009

Brand Stability in Room Interchangeability Suggested Primary Course Booster Doses Dosage and
Disease Origin Type Other Content
(Volume, Company) Temperature Data Zero to one years One to five years Six to 12 years 13 to 16 years administration
Glycerol, Fe Infants < one year:
Reconstituted Ammonium citrate, 0.05mL Intradermal
Tuberculosis BCG Vaccine SSI® Mantoux test
Bacterial cells Live attenuated bacilli solution stable for No data Sodium glutamate, At birth NA NA Adults & Children
(multidose) (1.0 mL, SSI) before BCG
four hours MgSO4, L-asparagine ≥ one year: 0.1mL
monohydrate intradermal
Infanrix® Third, fourth and
Diphtheria, Toxoids, acellular 37°C for one week Same brand for first Al salts, 18th month: First
Bacterial cells (0.5mL prefilled fifth month: One NA NA All: 0.5mL i/m
Tetanus, Pertussis pertussis 21°C for two weeks three doses required 2-phenoxyethanol booster
syringe, GSK) dose per month
Diphtheria, ADT® Vaccine Store between Al phosphate, Primary 5: Second
Bacterial cells Purified toxoids Interchangeable NA NA NA All: 0.5mL i/m
Tetanus (0.5mL, CSL) 2–8°C Thimerosal 0.01% booster
Al salts,
Diphtheria, Boostrix®
Toxoids, acellular 37°C for one week 2-phenoxyethanol, Use as Primary 5 (Second booster) as an alternative to ADT
Tetanus, Acellular Bacterial cells (0.5mL prefilled Single dose only NA All: 0.5mL i/m
pertussis 21°C for two weeks polysorbate 80, (Indicated for > four years)
pertusis syringe, GSK)
glycine
Lactose, NaCl, KCl, Second, fourth and
Diphtheria, Toxoids, acellular Na2HPO4, 2-phenoxy- sixth month: One
Tetanus, Bacterial cells pertussis, inactivated ethanol, Al salts, dose per month
Infanrix-IPV +HiB® No alternative 5-in-1 18th month: One
Pertussis, Polio, Monkey kidney virus, capsular 21°C for one week glycine, polysorbate If using Infanrix NA NA All: 0.5mL i/m
(0.5 mL GSK) vaccine booster
H. influenzae cells (for polio) polysaccharide 80, M199, neomycin, Hexa, then use
(5-in-1) (PRP-OMP) formaldehyde, 5-in-1 for the fourth
polymixin month dose
Use only for babies
Lactose, NaCl,
Diphtheria, Toxoids, acellular born to HepB –ve
Bacterial cells Phenoxyethanol, Al
Tetanus, pertussis, inactivated mothers 18th month:
Monkey kidney salts, KCl, polysorbate
Pertussis, Polio, Infanrix Hexa virus, capsular Eight hours at 21°C No alternative 6-in-1 Second and sixth Use 5-in-1
cells (for polio), 20 and 80, glycine, NA NA All: 0.5mL i/m
H. influenzae, (0.5mL, GSK) polysaccharide after reconstitution vaccine month: One dose (Infanrix-IPV
Yeast cell (for formaldehyde,
Hepatitis B (PRP-T), viral surface each +HiB)
Hep B) neomycin, polymyxin,
(6-in-1) antigen Fourth month dose
M199
should be 5-in-1
NaCl, disodium
Tetavax For children seven years olds and above:
Formaldehyde Store between dihydrate phosphate,
Tetanus Bacterial cells (0.5mL, Sanofi No data Prophylaxis: Two i/m doses four weeks apart, third dose six to 12 months later All: 0.5mL i/m
detoxified toxoids 2–8°C monopotassium
Pasteur) Booster every ten years. For serious wounds, give booster if > five years since last dose
phosphate, WFI
Primary 1: Second
37°C for one hour Interchangeable with Neomycin, MgCl, Third, fourth and All: Two drops given
Poliomyelitis Monkey kidney Polio Sabin® Live attenuated virus 18th month: First booster
21°C for two days inactivated polio polysorbate 80, fifth month: One NA orally (use dropper
(multidose) cells (ten doses, GSK) (Types I, II and III) booster Primary 5: Third
12°C for one week vaccine sucrose dose per month provided)
booster
2-phenoxyethanol,
Primary 1: Second
formaldehyde, Third, fourth and
Monkey kidney Imovax Polio Inactivated virus Store between Interchangeable with 18th month: First booster
Poliomyelitis Neomycin, fifth month: One NA 0.5mL i/m or s/c
cells (Aventis) (Types I, II and III) 2–8°C live polio vaccine booster Primary 5: Third
streptomycin, dose per month
booster
polymycin B
Sucrose, dextran, First dose: Between six to 14 weeks of age
Live attenuated
Single human Rotarix Store between sorbitol, amino acid, Second dose: Between 14 and 24 weeks of age
Rotavirus (ORAL) human rotavirus No data All: 1mL orally
rotavirus strain (1mL, GSK) 2– 8°C DMEM, Xanthan, (off-label use: Second dose must be given by eight months 0 days)
RIX4414 strain
CaCO3 Interval between doses > four weeks
342 The Baby Bear Book Infectious Diseases 343

Brand Stability in Room Interchangeability Suggested Primary Course Booster Doses Dosage and
Disease Origin Type Other Content
(Volume, Company) Temperature Data Zero to one years One to five years Six to 12 years 13 to 16 years administration
Human diploid Rudivax® Store between Neomycin, sorbitol, Infants 15 months old — One dose, with booster at Primary 6
Rubella Live attenuated virus No data NA All: 0.5mL s/c
cells (0.5mL, Aventis) 2–8°C gelatin Adults: 0.5mL (no booster)
Neomycin, sorbitol,
All: 0.5mL s/c
hydrolysed gelatin,
Chick embryo and Contraindicated if
Measles, Mumps, M-M-R II ® human albumin, 15th month: One
human diploid Live attenuated virus One week at 37°C No data NA Primary 1: Booster NA anaphylactic or severe
Rubella (0.5mL, MSD) buffer, sodium dose
cells allergic reaction after
phosphate, NaCl,
egg ingestion
sucrose
Two to < seven months: Three doses one to two months apart
37°C for one week
with booster at 12–15th month Six weeks to six years
Capsular 21°C for two weeks
Hemophilus Hiberix® Use PRP-T regimen if Seven to < 12 months: Two doses two months apart with booster old: 0.5ml i/m (SC if
Bacterial cells polysaccharide Reconstituted — Tetanus toxoid, lactose NA
Influenzae (0.5mL, GSK) other products are used at 12–15th month (booster at least after interval of two months) thrombocytopenia or
(PRP-T) 37°C up to 24 hrs, OR
12 to < 15 months: Two doses two months apart bleeding disorder)
21°C up to five days
15–59 months: One dose
Na, K, phsophate, Mg, Six months to <
Cl, dodecahydrate, Six months to adult: One dose three years: 0.25ml
Influenzae A Embryo-nated No data (single dose
— Inactivated split virion 21°C for one week octoxynol 9, * Children < nine years old: Second dose after one month recommended for first-time i/m or s/c
and B eggs in adults)
polysorbate 80, vaccination ≥ three years: 0.5ml
α-tocopheryl i/m or s/c
No data available Sucrose, gelatin, EDTA, 15th month: First dose
Human diploid Varilrix® 37°C for one day Two doses given six
Varicella Live attenuated virus (single dose in pediatric neomycin, NA Repeat booster minimum of three months > one year: 0.5ml s/c
cell (0.5 mL,GSK) 21°C for one week to ten weeks apart
patients) L-glutamate later or at four to six years old
One to < 19 years:
0.5ml (720u) i/m
Havrix 720® Interchangeable, but Al(OH)3, phosphate,
≥ 19 years :1ml
Human diploid (0.5mL, GSK) Formaldehyde 37°C for one week preferable to complete K, Na, Cl,
Hepatitis A NA One primary dose with booster six to 12 months later (1440u) i/m
cell (720 ELISA Units/ inactivated virus 21°C for two weeks immunisation with phenoxyethanol,
(Apply firm pressure if
0.5ml) same product Formaldehyde
thrombocytopenia or
bleeding disorder)
Zero to 19 years: 3 x
Interchangeable; Aluminium hydroxide,
0.5mL i/m
the exception is the sodium chloride, All infants: Three doses at zero, first, and fifth or sixth months (0.5mL = 10μg)
Engerix B Ped® ≥ 20 years: 3 x
Recombinant DNA Store between two-dose hepatitis disodium phosphate * Infants of all HBsAg +ve mothers (regardless of Hbe Ag status): Three doses of 0.5ml
Hepatitis B (0.5 mL, GSK) Viral surface antigen 1.0mL i/m
vaccine 2–8°C B vaccination series dihydrate, sodium To also give 0.5mL HBIG together with first dose of vaccine. If HbsAg & Ab –ve at nine
(10μg/0.5ml) (SC if
for adolescents aged dihydrogen phosphate months old, give one booster dose of 0.5ml at one year
thrombocytopenia or
11–15 years dihydrate
bleeding disorder)
Aluminium
hydroxyphosphate
Human Gardasil® Virus-like particles sulfate, NaCl, Nine to 26 years: Three doses. Second dose two months after first dose and third dose
Yeast cells 25°C for three days No alternative vaccine All: 0.5mL i/m
Papillomavirus (0.5mL, MSD) (four strains) L-histidine, six months after first dose
polysorbate 80,
sodium borate, WFI
Aluminium
hydroxide,hydrated,
Human Cervarix ® Virus-like particles Ten to 25 years: Three doses at zero, one and six months
Recombinant DNA 37°C for one week No alternative vaccine 3-O-desacyl-4’- All: 0.5mL i/m
Papillomavirus (0.5ml) GSK (two strains) Second dose between one month and two-and-a-half months after first dose
monophosphoryl lipid
A (MPL)
344 The Baby Bear Book Infectious Diseases 345

Compiled By: Claire Seet

Vetted By: Dr Chong Chia Yin & Dr Thoon Koh Cheng
Dated: 17th November 2009

Brand Stability in Room Interchangeability Suggested Primary Course Booster Doses Dosage and
Disease Origin Type Other Content
(Volume, Company) Temperature Data Zero to one years One to five years Six to 12 years 13 to 16 years administration
Capsular Two to 11 months: Two doses six to eight weeks apart with
polysaccharide booster at 12 months
Streptococcus Prevenar® Store between Aluminium Phosphate,
Bacterial cells conjugate with No data 12–23 months: Two doses six to eight weeks apart > ten years: NA All: 0.5mL i/m
Pneumoniae (0.5mL, Wyeth) 2–8°C NaCl,
diphtheria CRM protein 24–59 months: One dose if imunocompetent, two doses if
(seven strains) immunocompromised
Phenol, NaCl, disodium
Capsular Two to ten years: One dose with booster after three to five years if at high risk of
Streptococcus Pneumo 23® phosphate dihydrate, > Two years: 0.5mL
Bacterial cells polysaccharide No data No data infection
Pneumoniae (0.5mL, Aventis) monosodium s/c or i/m
(23 strains) ≥ ten years: One dose with booster after ≥ six years if at high risk of infection
phosphate dihyrate

CAUTION: The above information is only applicable for products mentioned under the ‘Brand’ column M199 is a stabiliser containing amino acids, mineral salts, vitamins and other substances
STORAGE: Do not expose to light. Store at 2–8°C and discard if frozen Rotavirus: Rotateq® (MSD): All 3 x 2.0mL orally. First dose: Between six to 12 weeks of age. Third dose: Must be given by 32 weeks.
ROWS SHADED IN BLUE ARE IN MULTI-DOSE PREPARATIONS Interval between doses > four weeks. Not available currently in KKH pharmacy.

BIBLIOGRAPHY
1. Ministry of Health. Formulary of standard drugs. Singapore: Ministry of Health; 2009.
2. A Guide on Infectious Diseases of Public Health Importance in Singapore. 6th ed. Ministry
of Health, Singapore; 2004.
3. Gelman CR, Rumack BH, Hutchison TA, editors. DRUGDEX® System. Englewood, Colorado:
MICROMEDEX®, Inc.; 2006. Vetted by: Dr Chong Chia Yin and Dr Thoon Koh Cheng.
4. Pickering LK, editor. Red Book: Report of the Committee on Infectious Diseases. 28th ed.
Elk Grove Village, IL: American Academy of Pediatrics; 2009.
346 Neonatology 347

AT-RISK NEWBORNS AT DELIVERY

NEONATOLOGY 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:
APGAR SCORE Foetal distress:
Persistent late decelerations
Parameter O 1 2 Severe variable decelerations without baseline variability
Heart rate Absent < 100 > 100 Scalp pH ≤ 7.20
Respiratory effort Absent Slow or irregular Good cry Meconium-stained liquor or no liquor
Some flexion of Prolapsed cord
Muscle tone Limp Active movements Caesarian section
extremities
Reflex irritability No response Grimace Sneezing Antepartum haemorrhage
Multiple pregnancy
Pink body, blue
Colour Blue all over or pale Pink all over Estimated weight ≤ 2,000gm
extremities
Estimated gestation ≤ 34 weeks
Assisted breech delivery
Score in first and fifth minute of life; if the baby is still depressed and IDDM (poorly controlled)
needs resuscitation, repeat every five minutes until the score reaches Severe pre-eclampsia or eclampsia
≥ seven Suspected foetal anomalies
Premature babies may have lower scores due to their gestational age Transverse/oblique lie/breech
Valuable in monitoring the response of the newborn to resuscitation Maternal narcotic use within four to six hours of delivery
Only one of many measures of a baby’s well-being; it has to Oligohydramnios or polyhydramnios
interpreted in the context of other findings and parameters such as Maternal fever and/or prolonged rupture of membranes > 12–18 hours
ante-partum history and monitoring, cord-gas values, and clinical Rhesus sensitisation
status
Scores in later minutes are more predictive of neonatal outcome BIBLIOGRAPHY
1. Department of Neonatology. Department Guidelines. Singapore: KK Women’s and
than initial Apgar scores Children’s Hospital; 2002.
Many babies with poor Apgar scores have normal development
Conversely, many babies with neurological impairment had normal
Apgar scores

BIBLIOGRAPHY
1. Committee on fetus and newborn, American Academy of Pediatrics. Use and Abuse of
Apgar Score. Pediatrics. 1986;78:1148–1129
BIRTH TRAUMA

RISK FACTORS FOR BIRTH TRAUMA

Maternal factors:
Maternal diabetes
Obesity
Undersized pelvis
Primigravida
348 The Baby Bear Book
Foetal factors:
Macrosomia
Obstetric factors:
Abnormal presentation, especially breech
Shoulder dystocia
Prolonged second stage of labour
Instrumental delivery: Forceps, vacuum extraction
CAPUT SUCCEDANEUM
A diffuse swelling of the scalp that results 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.
This undergoes natural resolution within one to two days and no active
management is necessary.
CEPHALOHAEMATOMA
Sub-periosteal bleeding due to disruption of the periosteum from
the underlying bone. It does not cross the suture line. 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.
Neonatology 349
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.
KLUMPKE’S PARALYSIS
A more severe form of brachial plexus injury. The nerves involved are the
cervical seventh and eight 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.
RESUSCITATION AT DELIVERY
PREPARATION
Do not be overconfident. If a very sick infant or multiple births are
expected, call for help. Check the following:
Perinatal history to identify high-risk factors (ask about the infant’s
gestation, number of babies, presence of meconium staining, and
bleeding)
Radiant warmer is turned on and dry blankets are available
Oxygen source; ensure an adequate flow (5L/min to 10L/min) to fill
the bag
Resuscitator/anaesthetic bag and connecting tubing or self-inflating
bag with pop-off valve (blow off pressure set at 30cm H2O) Neopuff
(T-piece resuscitator) if available (able to set Peak Inspiratory Pressure
(PIP) and Positive End Expiratory Pressure (PEEP), and can give CPAP)
350 The Baby Bear Book Neonatology 351

Laryngoscopes with appropriate blades. Make sure the light is bright Insert ETT till the black vocal cord guide sits just beyond the vocal cords.
and extra batteries are available This should place the tip of ETT midway between the vocal cords and
Face masks of appropriate sizes carina, at the level of T2 on a CXR. Add 1.0cm for < 1.5kg baby and 2.0cm
ETTs of appropriate sizes (ETT 2.5, 3.0, 3.5, and 4.0) for >1.5kg baby for naso-tracheal intubation. Auscultate for equal air
Magill forceps entry, and consider withdrawing the tube in 0.5cm steps, especially if
Oropharyngeal airways (sizes 000, 00, 0) there is reduced expansion or air entry on the left.
Suction apparatus: Suction should not exceed 200mmHg and for
routine use, should be set at 100mmHg (= 120cm H2O) to prevent EXTERNAL CARDIAC MASSAGE (ECM)
damage to the oropharyngeal mucosa Indicated if there is no palpable pulse or no audible heart beat or the
Emergency umbilical vessel catheterisation set heart rate falls below 80/min (assess the pulse by palpating the base
A selection of syringes, needles and T-connectors of the umbilicus, or the brachial artery)
Drugs for resuscitation Place both thumbs at the junction of the middle and lower third of
the sternum, with the fingers wrapped around the back
Protect yourself: Gloves, masks, caps, goggles or visors, and gowns (if Compress the sternum 1–2cm at a rate of 100-120/min
indicated) Coordinate ECM with ventilation at a ratio of one breath to three
compressions
WHEN THE BABY IS BORN Continue ECM until heart rate is > 80/min and is steadily increasing
Place on warm table/under radiant warmer
Suction the oropharynx, and then the nares MEDICATION
If thick meconium is present and the baby is ‘flat’ or has marked The fastest and most reliable method of obtaining vascular access is by
respiratory distress, suction the oropharynx, intubate the baby and cannulating the umbilical vein. Insert the catheter about 3–4cm past the
suction the trachea using the meconium aspirator, before the onset abdominal wall. Ensure there is easy aspiration of blood. Although it is
of respiration possible to advance the catheter to a depth of 8–10cm into the inferior
Dry the infant, especially the head and face, and wrap in warm vena cava, it may become wedged in an undesirable location e.g. the
towels hepatic or portal vein.
Avoid deep pharyngeal suction and gastric aspiration soon after
birth as this may cause bradyarrhythmias from vagal stimulation
Table 9-2: Medication, dosage, routes and indications.
INTUBATION
Table 9-1 is only a guide. The length of the ETT should be assessed at Drug Route Dose Indication
intubation and also by radiograph. A correctly sized ETT should allow a NaHCO3 4ml/kg of 4.2% NaHCO3 (2mEq/
UVC, IV Metabolic acidosis
small leak. (1ml 8.4% = 1mEq) kg)
UVC 0.1–0.3ml/kg
Adrenaline (1:10,000) Asystole/bradycardia
ET 1ml/kg
Table 9-1: Intubation guide. Calcium gluconate Bradycardia, poor
UVC, IV 1–2ml/kg slowly
Weight (grammes) Lip-to-Tip Distance (cm) ETT Size (10%) cardiac output
<1,000 — 2.5mm 0.1mg/kg, repeat in five
1,000 7 3.0mm Naloxone (Narcan) UVC, IV, IM minutes PRN Narcotic depression
(= 0.25ml/kg of 0.4mg/ml)
2,000 8 3.0mm
2ml/kg of dextrose 10% (avoid
3,000 9 3.5mm Dextrose UVC, IV 25% dextrose as this may cause Hypoglycaemia
4,000 10 3.5mm rebound hypoglycemia)
352 The Baby Bear Book
VOLUME EXPANSION
Signs of shock at delivery: Pallor, tachycardia, tachypnoea, hypotension,
poor capillary filling and weak pulses.
Stabilise the heart rate and respiration
Provide volume expansion — O-negative packed RBCs, whole blood,
plasma or normal saline may be used
Give 10ml/kg through an umbilical venous catheter
If response is poor, look for causes of further blood loss
Hypotension may also result from cardiogenic shock rather than
hypovolaemia
Consider the use of dopamine, dobutamine
MECONIUM ASPIRATION
When thick meconium is present, the obstetric staff should attempt
to clear the nose and oropharynx using a wide-bore suction catheter
before the chest is delivered
Following completion of the delivery, the infant should immediately
be handed to neonatal staff. Intubation of the trachea under direct
laryngoscopy should occur before inspiratory efforts have been
initiated. Even if the infant has gasped, some meconium may still
be removed with direct tracheal suction. If the baby is vigorous and
crying with minimal respiratory distress, avoid intubation
Suction of 90–100mmHg may be required and should be applied as
the ETT is being withdrawn; repeat the procedure until the trachea is
cleared. The procedure should be completed rapidly, usually within
one minute, and ventilation with oxygen should be initiated before
significant bradycardia occurs
FAILURE TO RESPOND TO RESUSCITATION
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
Neonatology 353
Severe sepsis
Hypothermia
BREASTFEEDING
BENEFITS OF BREASTFEEDING
There is a great amount of empirical evidence supporting breastfeeding
as the preferred food of babies. A rich body of literature lists the
advantages of breastfeeding for the mother-and-baby pair, beyond
nutritional benefits and psychological bonding. Breastfeeding also
protects the baby from infections and allergic disorders. Interestingly,
the benefits are not limited to the period of breastfeeding; the protective
effects are easily noticeable many years later. Therefore, it is the
professional and moral obligation of healthcare providers to advocate
breastfeeding and support the mother and baby in every possible way. A
period of breastfeeding is probably 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
Protects from respiratory tract infections
Less frequent diarrhoea; promotes growth of healthy and non-
pathogenic bacteria in the intestine, prevents E. coli from binding
with the intestinal mucosa
Protects against viral infections
Protects premature babies from necrotising enterocolitis (NEC)
Protection against Atopy and Allergy
Breastfed babies are less likely to develop eczema, asthma and other
atopic diseases. Breastfeeding is especially beneficial to 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
354 The Baby Bear Book
Nutritional Benefits
Breast milk provides adequate nutrition for term babies up to six
months of age
The composition of breast milk evolves to reflect changing
nutritional needs as the baby gets older
Breast milk contains many compounds (e.g. cholesterol and 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 until six months
of age. Thereafter, other foods are gradually introduced. Baby can be
breastfed as long as possible up to two 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. Caloric density is about 67 calories/100ml.
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 75 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
Neonatology 355
STOOL AND URINE PATTERN IN BREASTFED BABIES
Breastfed babies have characteristic stool and urine patterns that help in
assessing adequacy of feeding and in monitoring the infant’s well-being.
First 24 hours:
Meconium two to three times
Urine once or twice
24–48 hours:
Urine two to three times per 24 hours
More meconium, appearance of transitional stool
48–72 hours
Transitional stool changing to yellowish stool
Urination frequency increases to three to four per 24 hours
Beyond 72 hours
Frequent loose yellowish stool (parents may confuse with
diarrhoea)
Urination frequency six to eight times per 24 hours
Failure to pass adequate amounts of urine and delayed
appearance of yellowish mature stools are objective indications
of inadequate feeding
PREPARATION FOR BREASTFEEDING
Breastfeeding education during pregnancy
A good preparation for breastfeeding starts during the antenatal
period. Antenatal counselling should focus on motivation of the
mother and the family, preparation of the spouse, identification of
problems that may arise during breastfeeding, and demonstration of
breastfeeding techniques
Early latch-on
The baby should be placed on the breast as soon as possible after
birth. Early latch-on helps in developing sustained imprinting about
breastfeeding. The baby is more alert and awake at this time and
success of proper latch-on and sucking is much higher
Demonstrate correct latch-on and positioning
Sucking milk from the breast is different from taking milk out of the
bottle. A proper demonstration of the correct latch-on technique
and positioning is imperative. Seek help from an experienced nurse
or lactation consultant
Rooming-in
Whenever possible, the mother and baby should be kept together. A
short separation may be necessary during medical examination and
procedures but this time should be limited as much as possible
356 The Baby Bear Book
Avoid supplemental feeding
Target for total breastfeeding except in situations where
supplemental feeding is medically warranted. If supplemental
feeding is indicated, continue with breastfeeding. Supplemental
feeding can be offered through a cup or spoon to avoid nipple
confusion
Feed frequently
A breastfed baby will feed frequently. Early and frequent feeding
helps establish mother’s milk supply, promotes clearance of
meconium, reduces incidence of jaundice, and minimises breast
engorgement
MONITORING THE ADEQUACY OF FEEDING
The mother-and-baby pair 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 sucking and swallowing pattern
Frequent feeding
No rapid weight loss
Wet diaper at least four to six times a day — See “Stool and Urine
Pattern in Breastfed Babies” previous page
Soft yellow stool by day three
Passage of yellow stool at least two to three times per day
Full-term breastfed babies most often regain birth weight by 14 days;
a weight loss of more than 7% of the birth weight during the first week
calls for comprehensive review of the mother-and-baby pair.
CONTRAINDICATIONS TO BREASTFEEDING
There are very few contraindications to breastfeeding:
Galactosemia in the baby
Maternal active TB
Maternal HIV: Breastfeeding is not recommended in Singapore
Maternal active herpes lesion: Breastfeeding is contraindicated in
presence of active lesions in the breast
Breast cancer or mastitis
Selected medication: 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.
Neonatology 357
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
High-risk infants: Premature, very-low-birth-weight babies, babies
with increased risk of NEC
Return to work
Anxious parents
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 seven days to the first day of last menstrual period and then
subtracting three 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 (Fig. 9.1 overleaf ): Performed 12–24 hours after birth
Ballard Score (Fig. 9.2 p. 359): A simplified version of the Dubowitz
score. Infant does not need to be alert or vigorous. Accuracy is ± two
weeks
358 The Baby Bear Book Neonatology 359

Fig. 9.2: Ballard Score.

Fig. 9.1: Dubowitz Score.

360 The Baby Bear Book Neonatology 361

The best estimate of neonatal GA is determined from both obstetric and
neonatal methods. If the two methods differ from each other by more
than two weeks, it is customary to take the neonatal estimate.
Pre-term: GA at birth is < 37 weeks
Term: GA at birth is 37–42 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
RELATIVE SIZE
SGA: Birth weight less than tenth percentile for estimated GA
Appropriate for Gestational Age (AGA): Birth weight between tenth
and 90th percentile for estimated GA
LGA: Birth weight more than 90th percentile for GA
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.

Common problems with LGA babies (especially > 4kg) are:

Birth trauma
Perinatal asphyxia
Hypoglycaemia COMMON SKIN CONDITIONS
Polycythaemia

SYMMETRICAL AND ASYMMETRICAL GROWTH ERYTHEMA TOXICUM

RETARDATION Very common
In symmetrical growth retardation, the baby is small but the growth Appears within the first 48 hours of life
parameters (head circumference, length, and weight) are proportionate Few millimetres area of redness (macule) — Flat or slightly elevated
to each other. This pattern commonly occurs in early pregnancy and Central tiny white elevated area
may be related to constitutional factors such as a genetic syndrome or Mostly occurs on face, trunk and upper extremities
an intra-uterine infection. No specific treatment is necessary

In asymmetrical growth retardation, head growth is relatively spared MILIA

as compared to length and weight. Babies are born appearing wasted Multiple 1–2mm raised area
and malnourished. Typically, this happens in late pregnancy. Common Usually white in color
causes include placental insufficiency, pregnancy induced hypertension, Mostly appears on forehead and face, especially nose bridge
and multiple pregnancies. Contains keratin
Ruptures and disappears after few days
Common problems in growth-retarded babies: No specific treatment is necessary apart from routine cleanliness
Hypothermia
Hypoglycaemia
362 The Baby Bear Book Neonatology 363

MOTTLING (CUTIS MARMORATA) HAEMANGIOMA

Scattered areas of erythema with pale areas in-between
Common following exposure to cold; becomes less obvious with
warming
Pathological associations: Hypothermia, poor perfusion, shock, CNS
disturbances and hypothyroidism
TRANSIENT NEONATAL PUSTULAR MELANOSIS
More common in dark-skinned babies
Maybe present at birth and last for four to five days
Heterogeneous with pustules and vesicles and areas of dark macule
Baby is clinically well
No specific treatment is necessary MONGOLIAN BLUE SPOT
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
May not be apparent at birth
Appears as red macule
Blanches with pressure; prominent dilated capillaries may be visible
at the base
Usual natural course is important for counselling
Most become elevated and undergo period of growth between two
to six months
Starts involution between 12–15 months
Very few require treatment
Refer large lesions or those present on critical areas of the body
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 for several years
No treatment is necessary

ACNE NEONATORUM GUIDELINES FOR ADMISSION

Rarely presents at birth
Appears in the first two to four weeks of life
Multiple blackheads or whiteheads on the forehead, face and body
Most undergo resolution without treatment
Advise against heavy application of emollient
NEVUS FLAMMEUS (SALMON PATCH, STORK BITES)
Patchy light-red areas
Common on forehead, eye-brow and nape of neck
Blanches on pressure
May persist for several months or years
Most do not require any 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
TO NEONATAL CARE
INDICATIONS FOR ADMISSION TO LEVEL THREE
(INTENSIVE CARE)
All babies at this level require continuous monitoring of respiration and
heart rate by apnea monitor, pulse oximeter, or by transcutaneous monitors
Critically ill babies
Assisted ventilation e.g. Intermittent Mandatory Ventilation (IMV),
CPAP, and in the first 24 hours following withdrawal of ventilatory
support
Recurrent apnoea requiring constant attention
Major surgery e.g. PDA ligation or other surgical conditions as
requested by the pediatric surgeon
Severe perinatal asphyxia (Apgar Score < three at five minutes)
Severe meconium aspiration syndrome
Infants weighing < 1,250g or pre-term deliveries ≤ 30 weeks
gestation
Convulsions
364 The Baby Bear Book Neonatology 365

Partial or total parenteral nutrition REFERRAL OF NEWBORN BABIES

Central lines (umbilical arterial or venous lines, per-cuteneously FOR NEONATAL CARE
inserted central catheter or long lines)
Undergoing major medical procedures, such as arterial All newborn babies should be seen by a physician trained in
catheterisation, peritoneal dialysis or exchange transfusion their assessment. Some babies require more attention. Careful
assessment and monitoring of these infants is essential to prevent any
INDICATIONS FOR ADMISSION TO LEVEL TWO (SPECIAL complications:
CARE NURSERY) Birth weight < 2,500g
Low-birth-weight infants 2,000g and below Birth weight > 4,000g
Pre-term deliveries 35 weeks gestation and below Pre-term and post-term
Five minutes Apgar score of four to six Multiple births
Requiring any form of resuscitation at birth IUGR
Continuous monitoring of respiration or heart rates by apnea Suspected congenital abnormalities
monitor, pulse oximeter or by transcutaneous monitors Suspected congenital infection
Additional oxygen Apgar scores < six at any time
Receiving IV glucose and electrolyte solutions and antibiotics Maternal disease such as gestational diabetes or pregnancy-induced
Tube-feeding hypertension
Barrier-nursing Foetal distress
Intensive phototherapy, at the discretion of specialist in charge Prolonged rupture of membranes (>12–18 hours)
Persistent hypothermia of ≤ 36ºC Maternal fever or urinary tract infection
Congenital malformations that require special care Chorioamnionitis
Minor surgery in the previous 24 hours Meconium-stained liquor
Requiring special monitoring other than those previously mentioned Cord prolapse
e.g. babies of diabetic mothers Breech and other complicated foetal presentations
Respiratory distress
ADMISSION TO LEVEL ONE (NURSERY) Instrumental delivery
In a Level One nursery, the care is provided by the mother under Birth injury
supervision from the nurse and the doctor. These babies require Polyhydramnios or oligohydramnios
minimum nursing and medical care. Babies with minor medical Maternal sedation within four to six hours of delivery
conditions can be kept in a Level One nursery at the discretion of the History of previous neonatal death
physician. Such conditions include G6PD deficiency, minor congenital Maternal GBS colonisation
abnormalities and simple phototherapy. The emphasis is on provision of Maternal substance abuse
mother-craft and encouragement of breastfeeding. Poor antenatal care or follow-up
Sexually transmitted disease
BIBLIOGRAPHY Out-of-hospital delivery
1. Department of Neonatology. Department Guidelines. Singapore: KK Women’s and
Children’s Hospital; 2002.
BIBLIOGRAPHY
1. Department of Neonatology. Department Guidelines. Singapore: KK Women’s and
Children’s Hospital; 2002.
366 The Baby Bear Book Neonatology 367

GUIDELINE FOR DISCHARGE HYPOGLYCAEMIA

OF AT-RISK BABIES
There is no universally agreed-upon definition of neonatal
At-risk babies to be discharged after meeting all the criteria below: hypoglycaemia. However, consensus and expert opinions suggest
Gestation of at least 35 weeks several important points. The risk of future neurodevelopmental
Weight around 2kg abnormalities increases with longer duration and more severe degrees
Medical problems resolved or manageable on an outpatient basis of hypoglycaemia. Also, symptomatic hypoglycaemia is thought to be
Able to suck, swallow and breathe in a coordinated fashion in order more dangerous than asymptomatic hypoglycaemia.
to take all feeds by mouth
Able to maintain body temperature outside the incubator at room Strictly speaking, pathological hypoglycaemia is present in the neonate
temperature if the BSL falls below the accepted norm, there is presence of symptoms
Apnoe-free for at least five days off respiratory stimulants ascribable to low sugar, and there is quick resolution of symptoms with
Gaining weight steadily while taking a standard diet of milk (breast correction of hypoglycaemia.
milk or formula)
The capillary heel-prick method frequently employs glucose oxidase
Prior to discharge, perform: and provides semi-quantitative or quantitative measures of blood
A complete physical examination glucose values. Although such methods are quick, economical and
Case-note review to identify any remaining problems practical, they are unreliable at lower blood glucose levels. Therefore,
Immunisation, and instruct parents on subsequent immunisations documentation of hypoglycaemia should be supported by a reliable
Parents must be ready to take baby home: laboratory method.
CPR training
Bathing/medications For management purposes in our centre, the diagnosis of
Prepare the home: hypoglycaemia is considered if the BSL is ≤ 2.5mmol/L (≤ 45mg/dl). A
Cot level of < 1mmol/L (< 18 m/dl) is considered critical. Urgent intervention
Nappies is also called for if the neonate is symptomatic.
Other children
Other support SCREENING STRATEGY
Any other special equipment required These babies are considered at risk of hypoglycaemia and are screened:
Ensure that there is appropriate medical follow-up; for example with: SGA
Neonatologist LGA
Ophthalmologist Infant of diabetic mother
Physiotherapist (early intervention therapy) Premature babies born < 37 weeks of gestation
Cardiologist Perinatal hypoxia
Paediatric surgeon Polycythaemia
Dietician Infants with a known syndrome that is associated with
Explore enrollment in a parent support group or similar forum hypoglycaemia
Critically sick babies
368 The Baby Bear Book Neonatology 369

BIBLIOGRAPHY
1. Department of Neonatology. Protocol for Hypoglycemia. Singapore: KK Women’s and
Children’s Hospital; 2002.

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:
Galactosemia
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
Fig. 9.3: Guidelines — Hypoglycaemia algorithm (revised 1 November 2007).
absorption is hampered by phytates
370 The Baby Bear Book Neonatology 371

There is significant cross-sensitivity between cow-protein and INFECTION CONTROL

soy-protein; use with caution in documented cow-protein allergic
patients Thorough hand-washing is the single most important factor
in the prevention of infections in the hospital.
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 PEOPLE
prevention of allergy in babies who are at very high risk of developing All staff and visitors should wash their hands and forearms (to the
atopy. elbows) before entering the nursery
Long sleeves should be rolled up to elbows prior to washing
FORMULAE FOR PRE-TERM INFANTS Watches, bracelets and rings (other than simple wedding rings)
Caloric density: Higher than term formulae; usually 24 calories/oz should be removed
Protein: Higher protein content; up to 3gm/dl Hands should be considered contaminated unless they are washed
Carbohydrate: Glucose polymers and lactose just prior to and after handling an infant or his/her equipment, and
Fat: A large proportion of Medium Chain Tri-glycerides (MCT); after touching contaminated materials
40–50% of the fat may come as MCT oil The most useful antiseptics are chlorhexidine and providone-iodine
Minerals: Higher calcium and phosphorus After initial handwashing, hands may be disinfected with a a
Vitamins: Higher vitamin A and D chlorhexidine solution before and after handling patients. If dirty
Solute load and osmolar load: Lower or contaminated with blood, urine or faeces, the hands must be
Indications: Pre-term babies with higher energy requirement or thoroughly washed
those < 1.8kg at birth Whilst handling an infant, care should be taken not to touch one’s
face, hair, nose or mouth. A repeat wash is necessary should this
TRANSITIONAL FORMULAE occur
Generally used for pre-term babies upon discharge from hospital. Visitors and staff with acute respiratory, gastrointestinal or wound
Characteristics: infections should not be allowed in the nursery
Caloric density: 22 calories/oz
Protein: Intermediate protein content between term and pre-term EQUIPMENT
formulae Incubators should be cleaned regularly and changed at least weekly
Carbohydrate: Glucose polymer and lactose Humidifier water should be changed every 24 hours
Fat: 25% fat as MCT, rest as long chain fatty acids Ventilator tubing should be changed regularly e.g. every 72 hours or
Vitamins: Higher than term formula once per week
Minerals: Higher than term formula Thorough cleaning and drying of all equipment
Note: These are general guidelines on formula characteristics and Use individual stethoscopes for each baby
usages. Please consult individual product information sheet.
BABIES
BIBLIOGRAPHY: Avoid prolonged umbilical catheterisation or indwelling lines
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.
Keep entry site of invasive lines clean and dry
2. Lee L, Alexander L. Enteral Nutrition. In: Ng SCY, editor. Neonatal Nutritional Handbook. Keep the umbilical cord stump dry; there is no need to clean the
Singapore: Singapore Pediatric Society; 2002. p. 41–54. stump with cord spirit or apply antiseptic solutions
Skin folds (axillae and groin) should be kept dry
372 The Baby Bear Book
Isolate infants with infections and colonisations from resistant
organism e.g. MRSA, ESBL-producing organisms, multi-drug-resistant
pathogens
NECROTISING ENTEROCOLITIS (NEC)
RISK FACTORS
Prematurity: Single most important factor
IUGR
Perinatal hypoxia
Polycythaemia
Sepsis
Hypotension
Cyanotic heart disease
Inappropriately placed umbilical arterial catheters
A rapid increment of feeding is thought to be associated with an
increased risk. Breastfeeding and early initiation of very-small-volume
feeding (gut priming) are thought to be protective.
PRESENTATION
Background history of the above risk factors
May happen acutely or insidiously
Most commonly involves terminal ileum or colon; may involve entire gut
Clinical features: Feed intolerance, increasing gastric residue, bilious
or bloody gastric aspirates, bloody stools, abdominal distension,
apnoeas, desaturations, lethargy, hypotension and acidosis
Abdominal X-ray (AXR): Bowel distension, bubbly appearance indicating
gas in the bowel wall (pneumatosis intestinalis), portal venous gas, air
fluid levels, a stagnant loop, and features of bowel perforation
Often, serial x-rays are necessary to document those features
Two views are preferable to document free intra-peritoneal gas
Other investigations: FBC (features of sepsis), CRP, blood culture,
ABGs (acidosis and electrolyte disturbances)
Neonatology 373
MANAGEMENT
Mortality rate can be 20–40%
Ten to 15% of cases will develop long-term complications such as
stenosis
Some will develop recurrent NEC
Management is mostly supportive and medical unless signs of rapid
deterioration occur
Nil by mouth, antibiotics, correction of acidosis and electrolyte
disturbances, serial X-rays to determine progression and
complication, surgical referral
Surgery is indicated in presence of bowel perforation, necrotic loop,
and failure to respond to medical treatment
Late complications: Stenoses, strictures, short-bowel syndrome, and
malabsorption
NEONATAL INFECTION
COMMON ORGANISMS
In the immediate post-partum period, the organisms causing neonatal
infection are commonly acquired from the maternal birth passage.
The two most common organisms are GBS and E. coli. Less common
organisms are other gram-negative bacteria, enterococcus, listeria and
anaerobes.
Hospital-acquired (nosocomial) infection is a common problem in
hospitalised sick infants who are undergoing invasive procedures and
instrumentation. The pattern of organism and the sensitivity vary greatly
and are often unique to a particular nursery. A good surveillance system
is mandatory to identify nosocomial infections.
The common organisms in this category are Staphylococcus aureus
(including MRSA), coagulase negative staphylococcus, and gram-
negative bacilli such as klebsiella, pseudomonas, enterobacter,
acinetobacter and proteus. These organisms are often resistant to many
commonly used antibiotics. Candida albicans, a fungus, often causes
invasive infection in sick neonates.
374 The Baby Bear Book
KNOWN RISK FACTORS FOR PERINATAL INFECTION
Prematurity
Prolonged rupture of membrane > 18–24 hours (> 12 hours if
premature)
Maternal infection: Fever, chorioamnionitis, UTI
GBS carrier status
Perinatal hypoxia
CLINICAL PRESENTATION OF NEONATAL INFECTION
Clinical presentation is often subtle and non-specific. The common
symptoms are:
Respiratory distress (tachypnea, flaring, retraction, grunting)
Temperature instability (hypo- or hyperthermia)
Neurological symptoms: Lethargy, irritability, seizure
Gastrointestinal symptoms: Poor feeding, vomiting, pallor
Metabolic disturbance: Glucose intolerance, metabolic acidosis
“Baby is not doing well”
Apneas/desaturations
COMMON LABORATORY TESTS FOR SUSPECTED SEPSIS
FBC: Very high or low white cell count, increased immature to total
neutrophil ratio > 0.20, white cell abnormalities such as vacuolation
or toxic granulation, thrombocytopenia
Raised CRP: Serial estimation is often necessary
Blood culture
CXR
LP
Latex agglutination test for suspected organism
May include maternal vaginal swab
ANTIBIOTICS FOR NEONATAL INFECTION
In perinatally acquired infection, the first-line antibiotics for babies less
than seven days old should be gentamicin and penicillin G/ampicillin
(affords coverage for listeria). These antibiotics cover almost all of the
most commonly occurring organisms in perinatal infection and may
have synergistic actions against GBS. Third-generation cephalosporins,
although effective against gram-negative organisms, are not effective
against listeria. If GBS is the offending organism, ampicillin can be
substituted with penicillin.
In hospital-acquired infections, the choice of antibiotic depends
on known prevalence and sensitivity of organisms in the nursery.
Neonatology 375
Commonly cloxacillin, vancomycin (for MRSA and coagulase negative
staphylococcus), gentamicin, amikacin, ceftazidime and cefotaxine
are used in various combinations. Ceftriaxone is contraindicated
for use in newborns, especially those with jaundice. Suggested
antibiotic combinations for second-line coverage should include
cloxacillin and an aminoglycoside, or vancomycin (in place of cloxacillin)
if MRSA is the predominant organism. Third-line antibiotics should be
chosen depending on the prevalent gram-negative organisms or
colonising fibra.
NEONATAL JAUNDICE
The following guidelines are applicable to in-patient 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
ROUTINE INVESTIGATIONS
The following investigations should be carried out for all babies who are
started on phototherapy:
FBCs, including PBF and reticulocyte count
Blood group, rhesus type and direct Coomb’s test of the baby
Blood group, rhesus type and abnormal antibodies of the mother
SB, if > four 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
376 The Baby Bear Book Neonatology 377

Table 9-3: Phototherapy guidelines for babies born with birth weight < 2kg or at < 35 weeks PMA.
Increasing the amount of skin exposure to blue lights can enhance
bilirubin excretion Birth Weight Photo Level (mmol/L) Exchange Level (mmol/L)
Use eye covers to prevent damage to baby’s eyes (grammes) Normal Abnormal Normal Abnormal
< 1,250 150 120 220 190
Single Blue Phototherapy 1,250 – 1,499 170 140 250 220
The exposure of one plane of body surface (e.g. either the baby’s
1,500 – 1,999 200 170 310 270
front or back) to the phototherapy light
2,000 – 2,400 220 190 340 300
Regularly turning the baby helps to maximise the exposure of all
surfaces ≥ 2,500 260 230 400 340

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 rate of rise of SB is > 5umol/L/hr
Intensive Phototherapy
Involves the use of four 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 birthweight > 2kg (fall
under the NNJ Pathway; see “The NNJ Pathway” next page)
For babies born at less than 35 weeks PMA or with birth weight less
than 2kg (who do not fall under the NNJ Pathway), the phototherapy
guidelines in Table 9-3 (see next page) are used.
For this group, normal 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
Perinatal asphyxia
Sepsis
Significant cephalohaematoma or bruising
Double blue lights are used when the SB is < 35umol/L below the
exchange level or rate of rise of SB is > 5umol/L/hr
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 titre > 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
< five 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
Perinatal asphyxia
Low-risk: All others not belonging to high-risk group
378 The Baby Bear Book Neonatology 379

Table 9-4: High-risk phototherapy criteria.

Double Volume Exchange Transfusion:
Do Double If the SB is at exchange transfusion level:
Off Start Start
Admit for Volume
Age in Hours Phototherapy/
Phototherapy
Single Blue Double Blue
Exchange
A medical emergency: Admit the baby immediately for intensive
Discharge Phototherapy Phototherapy phototherapy
Transfusion
Day 1 Proceed with exchange if the SB does not fall below the desired
90 130 140 220 260 level within three hours of starting intensive phototherapy
(<24 hours)
Day 2 Exchange transfusion should be done immediately:
(>24 to 48 160 180 190 250 290 When the SB is > 85umol/L above the exchange level
hours) In any jaundiced infant with signs of kernicterus (or
Day 3 the intermediate to advanced stage of acute bilirubin
(>48 to 72 190 210 220 280 320 encephalopathy: Hypertonia, arching, retrocollis, opisthotonos,
hours) fever, high-pitched cry) even if the SB level is falling
Day 4 to 5 Discontinuation of phototherapy:
(>72 to 120 190 220 220 300 340 Once the ‘off phototherapy’ level has been reached
hours) Rebound SB does not need to be sent
>120 hours to The baby can be discharged immediately after discontinuation
220 260 260 300 340
Day 14 Parental and caretaker education:
Prior to discharging the baby, emphasise the importance of early
follow-up:
Table 9-5: Low-risk phototherapy criteria. Especially important for babies discharged before age 48 hours
Do Double Emphasise the risks and manifestations of acute bilirubin
Off Start Start encephalopathy and its consequences
Admit for Volume
Age in Hours Phototherapy/ Single Blue Double Blue
Phototherapy Exchange Breastfed babies:
Discharge Phototherapy Phototherapy
Transfusion
Give thorough breastfeeding advice
Day 2 Teach mothers and caregivers the signs of dehydration
190 210 220 300 340
>24 to 48hrs Borderline premature babies (35–36 weeks gestation):
Day 3 A vulnerable group:
220 250 260 320 360
>48 to 72hrs Tend to be discharged from hospital as early as full-term well
Day 4 to 5 babies because of their larger physical size and apparent maturity
220 260 260 360 400
>72 to120hrs At higher risk of developing jaundice requiring phototherapy
>120 hrs to Advice to parents of this particular group must be particularly
260 300 300 360 400
Day 14 instructive

BIBLIOGRAPHY
1. American Academy of Pediatrics. Clinical Practice Guideline: Management of
OTHER ISSUES hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics.
Feeding: 2004;114(1):297–316.
Feeding can be continued; nil by mouth if the baby needs 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.
exchange transfusion 1999;19(8 Pt 1):564–567.
Increase feeds by at least 10% over the usual expected intake 3. Newman TB, Liljestrand P, Escobar GJ. Jaundice noted in the first 24 hours after birth in a
managed care organization. Arch Pediatr Adolesc Med. 2002;156(12):1244–1250.
Continue breastfeeding 4. Wong HB. Singapore Kernicterus. Singapore Med J. 1980;21(3):556–567.
If not near or at exchange transfusion level, the baby can be taken 5. Kaplan M, Hammerman C. Severe neonatal hyperbilirubinemia: A potential complication
of glucose-6-phosphate dehydrogenase deficiency. Clin Perinatol. 1998;25: 575–590.
off the lights for up to 30 minutes to breastfed
380 The Baby Bear Book Neonatology 381

6. Tan KL. Decreased response to phototherapy for neonatal jaundice in breast-fed infants.
Arch Pediatric Adolesc Med. 1998;152(12):1187–1190. Physical examination
7. Martinez JC, Maisels MJ, Otheguy L, Garcia H, Savorani M, Mogni B, Martinez JC Jr. Basic laboratory tests:
Hyperbilirubinemia in the breast-fed newborn: A controlled trial of four interventions.
Pediatrics. 1993;91(2):470–473. FBC and CRP
8. Ennever JF. Blue light, green light, white light, more light: Treatment of neonatal jaundice. Electrolytes
Clin Perinatol. 1990;17(2):467–481.
9. Stern L, Denton RL. Kernicterus in small premature infants. Pediatr. 1965;35(3):483–485. Calcium, magnesium and phosphate
10. Maisels MJ, Kring E. Rebound in serum bilirubin level following intensive phototherapy. Blood glucose
Arch Pediatr Adolesc Med. 2002;156(7):669–672.
11. Yetman RJ, Parks DK, Huseby V, Mistry K, Garcia J. Rebound bilirubin levels in infants
Additional tests:
receiving phototherapy. J Pediatr. 1998;133(5):705–707. LP
Plasma ammonia
Plasma and urine amino acids
Toxicological screen
EEG
NEONATAL SEIZURES Neuroimaging: Ultrasound, CAT scan, or MRI

ACUTE MANAGEMENT
SEIZURE PATTERN Maintain airway and breathing
Subtle seizures constitute 50% of the seizures in the newborns. They Correct hypoglycaemia and electrolyte disturbances
may be in the form of tonic horizontal deviation and jerking of the Consider IV phenobarbitone 10mg/kg over 30 minutes; the dose can
eyes, repetitive blinking or fluttering of the eyelids, oral and buccal be repeated after an hour up to maximum cumulative dose of 40mg/
movements (drooling, sucking, yawning), tonic limb posturing, kg. Take precautions against apnoea, hypotension and desaturation
complex purposeless movement (‘swimming’, ‘bicycling’), apnoeas and If the seizure persists, consider additional drugs such as
rhythmic fluctuations of vital signs. Seizures may also present as focal or benzodiazepines. The usual dose of diazepam is 0.1–0.3mg/kg/dose.
multifocal clonic seizures, tonic seizures, and myoclonic seizures. Infuse slowly under cardio-respiratory monitoring. Or, midazolam
0.1–0.15mg/kg/dose slow IV push over five minutes
JITTERINESS VERSUS SEIZURE If the seizure is persistent, consider IV phenytoin 10–20mg/kg at a
A number of ‘seizure-like’ behavioral states may be confused with rate not more than 1mg/kg/min, with cardiac monitoring
seizures. These include jitteriness, movement during Rapid Eye Additional drugs:
Movement (REM) sleep, decorticate and decerebrate posturing, and Calcium gluconate (if hypocalcemic)
autonomic dysfunction. IV pyridoxine
Consult neurologist
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 PATENT DUCTUS ARTERIOSUS (PDA)
Predominant movement Tremor Jerking
The ductus arteriosus is present in all newborn babies. It closes
WORKUP FOR NEWBORN WITH SEIZURE spontaneously in healthy term infants soon after birth in response to an
Perinatal history including family history, risks for sepsis, drug usage, elevated PaO2. However, in pre-term babies, it may persist giving rise to
diabetes, and perinatal hypoxia a variety of problems.
382 The Baby Bear Book Neonatology 383

CLINICAL MANIFESTATIONS POLYCYTHAEMIA

Usually apparent between second and fourth day of life
May not be accompanied by a murmur, especially in very small
premature babies DEFINITION
Symptoms are often non-specific and a high degree of vigilance is A haematocrit value > 65% with symptoms, or > 70% without
necessary symptoms.
Clinical features include unexplained apnoeas, increased oxygen
requirements, respiratory distress, bounding pulses, hyperactive The haematocrit must be from good specimens, usually a free-flowing
precordium, widened pulse pressure, a systolic or continuous venous sample or an arterial sample. Haematocrit measured from a
systolic-diastolic murmur, metabolic acidosis and worsening capillary sample is unsuitable.
ventilatory status
An untreated PDA may lead to progressive heart failure, pulmonary Polycythaemia causes harm by making the blood more viscous. The
oedema, and pulmonary haemorrhage viscosity of the blood rises steeply once the haematocrit value exceeds
70%.
DIAGNOSIS
CXR shows cardiomegaly and pulmonary congestion RISK FACTORS
The diagnosis is confirmed with an echocardiogram, which also helps Delayed umbilical cord clamping
to exclude ductus dependent cardiac lesions where indomethacin is Growth retardation
contraindicated Infant of diabetic mother
Chronic intra-uterine hypoxia
MANAGEMENT Twin-to-twin transfusion
Restriction of fluid by 10–20ml/kg/day less than the daily requirement Maternal-foetal transfusion
Pharmacological closure with indomethacin is the mainstay of Dehydration
treatment in premature babies. Indomethacin inhibits prostaglandin,
which is essential for maintaining ductal patency COMPLICATIONS
The usual dose of indomethacin is 0.2mg/kg/dose 12 hourly (three Hypoglycaemia
doses). It is infused slowly over half-an-hour. Various modifications of Respiratory distress
the dosage regimen are practiced as well Heart failure
The course can be repeated 48 hours after the last dose Feed intolerance and NEC
Relative contraindications to indomethacin therapy (use with Haematuria and renal vein thrombosis
caution when the following conditions are present): Significant Cerebral vascular thrombosis
intraventricular haemorrhage, NEC, significant renal impairment, Seizures
thrombocytopaenia Peripheral gangrene
Monitor for diminishing urine output, gastrointestinal bleeding, and Accelerated jaundice
hyponatremia
Caution when using with nephrotoxic medications such as CLINICAL FEATURES
gentamicin and other aminoglycosides (monitor for nephrotoxicity Plethora
and renal insufficiency) Respiratory distress
Surgery is indicated if indomethacin is contraindicated, or if medical Feed intolerance, vomiting
treatment fails (usually after two courses fail to close the PDA) Jitteriness
Cyanosis
Evidence of complications (see “Complications” above)
384 The Baby Bear Book
MANAGEMENT
Adequate hydration
Correct underlying cause and treat complications such as
hypoglycaemia and hyperbilirubinaemia
Definite treatment is a partial exchange transfusion where blood is
taken out slowly and replaced with either normal saline or plasma.
The target is to attain a haematocrit value around 55%
Current haematocrit – Desired haematocrit
Volume of exchange (mls) = x Weight (kg) x 80
Current haematocrit
RESPIRATORY DISTRESS
GENERAL MANAGEMENT PRINCIPLES
Thermoneutral environment: Nurse in an incubator or under a
radiant warmer set to maintain skin temperature at 36.5 C (use servo
control)
Humidified oxygen: Give humidified oxygen via a head box or nasal
CPAP at a pressure of 4–5cmH2O. Use a transcuteneous O2 monitor or
pulse oximeter. Consider inserting an arterial line. Feed cautiously via
naso-gastric tube or keep the baby nil by mouth
Minimal handling: Minimise disturbance and handling. Group
together blood sampling and procedures. Any disturbance of a
sick baby may cause apnoea or a fall in oxygenation and BP. Use
non-invasive electronic monitoring to record heart rate, respiration,
temperature, oxygen saturation and TcPO2
Treat infection: Obtain blood cultures, FBC and other infective
markers, and start IV penicillin G or ampicillin and gentamicin. Obtain
a CXR
BP monitoring: Measure BP and give IV normal saline bolus 10ml/kg
if hypotensive. Oscillometric BP monitoring may over-read the BP in
very sick and very-low-birth-weight babies. Therefore, hypotension
may be missed. A more reliable method is invasive BP monitoring
using an intra-arterial line
Neonatology 385
Blood gas and pH monitoring: Peripheral arterial or umbilical
catheters should be considered, especially if the respiratory distress
is severe and persistent. During the acute stage of respiratory
distress, the ABG should be monitored every four to six hours and
soon after any change of ventilatory parameters
Other investigations: Blood glucose, repeat FBC and CRP, blood
urea, creatinine and electrolytes. In intubated baby, consider endo-
tracheal cultures twice weekly
CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP)
In CPAP, a continuous flow of heated and humidified oxygen enriched
air is circulated past the infant’s airway at a set pressure (usually 5cmH20)
while the infant breathes spontaneously. The air-oxygen mixture and
airway pressure can be adjusted. CPAP is usually delivered by nasal
prongs.
Indications for using CPAP:
Diseases with low functional residual capacity: Hyaline membrane
disease, transient tachypnoea of newborn, pulmonary oedema and
PDA
Recurrent apnoeas: CPAP may reduce or terminate attacks in pre-
term babies
Weaning from a mechanical ventilator
Airway closure disease: Broncho-pulmonary dysplasia, bronchiolitis,
tracheomalacia
Short trial in meconium aspiration syndrome
Failure of CPAP and indications for mechanical ventilation:
PaO2 < 50mm of Hg on 80–100% of oxygen
PaCO2 > 65mm of Hg
Marked retractions and frequent apnoeas and bradycardias while on
CPAP
Intractable metabolic acidosis
Cardiovascular collapse
Neuromuscular disease
Deep sedation and paralysis
Before intubation, exclude errors in blood gas sampling, machine
malfunction, improper CPAP application, and nasal obstruction by
secretions.
386 The Baby Bear Book
CONVENTIONAL MECHANICAL VENTILATION (CMV)
CMV is delivered using pressure-limited, time-cycled, continuous-flow
ventilators. There are many different models that provide numerous
variations and improvements. Below are some general principles
regarding CMV in newborn 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
FiO2: This is adjusted to maintain PaO2 between 50–70mmHg (SaO2
86–96%) in premature infants and PaO2 between 50–85mmHg (SaO2
93–98%) in term infants
Rate: The ventilator rate greatly depends on clinical status of
the baby. Initial setting is usually 20–30 breaths per minute and
is adjusted to maintain PaCO2 of 50–60mm of Hg (permissive
hypercarbia) if pH is maintained between 7.25–7.35. A lower PCO2 is
often indicated for patients with cerebral oedema
Inspiratory Time (TI) and Expiratory Time (TE): These two parameters
affect the ventilator rate. TI is generally kept between 0.4 to 0.5
seconds. On IMV, and below 0.30-0.35 on synchromised modes
(SIPPV, SIMV). TE should be longer than the TI
Peak inspiratory pressure (PIP): PIP is adjusted to ensure adequate
but not excessive chest movement. It is generally set between
15–20cmH2O pressure (higher PIP may be needed if the compliance
is low)
PEEP: Usually set at 5cm of H2O pressure. PEEP that is inappropriately
high over-distends alveoli, causes pneumothoraces, decreases
compliance, impedes venous return and diminishes cardiac output.
PEEP may be adjusted depending on clinical response/course of the
disease
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
minutes 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)
Neonatology 387
PaCO2 high: Increase rate by five to ten breaths per minute, increase
PIP, increase or decrease PEEP
Synchronised ventilation should be used whenever possible. Tidal
volume monitoring would be ideal.
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, or MgSO4).
DETERIORATION DURING VENTILATION
Sudden clinical deterioration: Usually manifests in the form of a
fall in oxygen saturation, hypotension, bradycardia, cyanosis and
hypercapnea.
Ensure the ventilator is working properly and there is no mechanical
problem such as a dislodged or kinked tube, 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
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
Consider re-intubation in cases of suspected blocked or dislodged
tube
Gradual deterioration: This is usually accompanied by a slow fall
in PaO2 and/or a gradual increase in PCO2. 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. Muscle relaxants are almost
never used. Synchronisation of ventilation usually avoids this problem
Intraventricular haemorrhage: Pallor, bulging fontanelle, seizures, fall
in Hb, sudden desaturation, hypotension and acidosis may indicate
haemorrhage. Confirm by cranial ultrasound
388 The Baby Bear Book Neonatology 389

PDA
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
Anaemia: Frequently due to iatrogenic causes such as blood
sampling (in the tiny baby) or may be congenitally present
Metabolic imbalance: Check U/E/ Cr
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 > 80%, 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
Cyanotic heart disease

WEANING OFF THE VENTILATOR

When the baby’s condition has improved, as shown by a consistent
PaO2 over 70mmHg and PaCO2 below 45–50mmHg, start to reduce PIP Fig. 9.4: Overview of neonatal resuscitation (from Kattwinkel 2006).
and FiO2 gradually as tolerated by the baby. Subsequently, ventilator
rate may be reduced when the baby demonstrates good spontaneous
respiration. When using tidal-volume controlled synchronised CNS damage
ventilation, pressure (rather than rate) should be progressively reduced. Infection, aspiration of milk, atelectasis
Sedation and muscle relaxant, if used, should be discontinued before Metabolic and electrolyte imbalance
reducing the ventilator rate. Administration of a loading dose of caffeine Inadequate nutritional status, anaemia
citrate should be considered in preterm infants of ≤ 34 weeks gestation.
Extubate the baby when the ventilator rate is reasonable for the baby’s BIBLIOGRAPHY
1. Kattwinkel J, editor. Textbook of Neonatal Resuscitation. 5th ed. Dallas: American Heart
age and condition. Consider CPAP or hood box O2 after extubation. Association , Elk Grove Village: American Academy of Pediatrics; 2006.
Monitor the baby for worsening respiratory distress. Monitor ABGs and
do a CXR.

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
Pulmonary oedema: PDA, fluid over-load
390 Nephrology 391

y Lower tract: Cystitis, urethritis, vulvitis, balanitis (gross

NEPHROLOGY haematuria is usually seen in cystitis)
Š Viruses: Adenovirus, CMV
Š TB — Rare
™ Glomerulopathy — Thin Glomerular Basement Membrane Disease,
APPROACH TO HAEMATURIA IgA nephritis, Alport’s Syndrome, etc.
™ Hypercalciuria with/without stones
™ Renal calculi
DEFINITION ™ Trauma
™ The diagnosis of gross haematuria is often straightforward ™ Other rare causes: Bleeding disorders, tumours, chemical cystitis
™ Microscopic haematuria is diagnosed when there are > five RBCs per
high-power field in three fresh urine specimens collected at different HISTORY
times ™ Associated symptoms:
Š Infection: Fever, dysuria, frequency, loin pain
A positive urine dipstix is not good enough for diagnosis. A false-positive Š Stone disease: Pain, passage of ‘sand’/stones
result may be casued by haemoglobinuria, myoglobinuria or improper Š Acute glomerulonephritis (AGN): Preceding URTI, oedema
use of strips. Microscopic examination is essential. Š Secondary cause: Fever, rashes, arthralgia/arthritis
™ Nature of haematuria: Terminal haematuria often suggests local
LOCALISING THE ORIGIN OF HAEMATURIA (GLOMERULAR causes such as urethritis/vulvitis
VS NON-GLOMERULAR) ™ Previous episodes of gross haematuria
™ Glomerular bleeding is suggested by the presence of RBC casts or ™ History of trauma
granular casts ™ Family history of haematuria, proteinuria, renal disease, deafness or
™ Phase contrast microscopy is performed on a fresh urine specimen. stone disease
RBC from glomeruli show distortion and variation in shape and size.
Lower tract bleeding gives RBC uniform in shape and size. Sensitivity CLINICAL EXAMINATION
and specificity is over 90% in detecting glomerular haematuria ™ Local examination
™ Presence of WBC casts suggests renal inflammation ™ Evidence of glomerulonephritis: Hypertension, oedema

CAUSES GROSS HAEMATURIA

™ Infection: Investigations (Symptom-directed)
Š Bacterial: ™ Urine culture
y Upper tract: Pyelonephritis (usually microscopic haematuria) ™ Urine calcium/creatinine ratio
™ FBC
™ Renal panel
Table 10-1: Categories of haematuria.
™ Clotting study where appropriate
Symptomatic Asymptomatic ™ Complement level (C3)
Gross haematuria Symptomatic gross haematuria Asymptomatic gross haematuria ™ KUB for radio-opaque calculi
Microscopic haematuria Symptomatic microscopic Asymptomatic microscopic ™ Renal ultrasound
haematuria haematuria ™ Other imaging studies/biochemical tests where appropriate
™ Intermittent
™ Persistent
™ With proteinuria
392 The Baby Bear Book Nephrology 393

Treatment ™ Hypertension
™ Treat underlying cause ™ Recurrent gross haematuria
™ Follow-up till resolution ™ Family history of glomerulonephritis (relative)

When to Refer? BIBLIOGRAPHY

™ Persistent beyond one week
™ Recurrent
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% are positive.
1. Postlewaite RJ, editor. Clinical paediatric nephrology. 2nd ed. Boston: Butterworth-
Heinemann; 1994.
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.

What Do I Do in a Child with Microscopic Haematuria? ACUTE NEPHRITIC SYNDROME

In the absence if proteinuria and symptoms, repeat urine microscopy.
If persistent in at least three samples over one month, then proceed to
investigate. DEFINITION
Sudden onset of symptoms of glomerular injury (haematuria,
Investigations (Symptom-directed) hypertension), and varying degrees of renal insufficiency.
™ Urine protein/creatinine ratio
™ Urine culture DIFFERENTIAL DIAGNOSIS
™ Urine calcium/creatinine ratio ™ Post-infectious:
™ Urine phase contrast microscopy Š Bacterial:
™ Renal ultrasound y Group A b-haemolytic streptococcus (most common)
™ Others as indicated y Pneumococcus sp.
y Staphylococcus sp.
How Often Do I Follow Up if the Above Investigations are y Klebsiella sp.
Normal? y Meningococcus sp.
Three times monthly for a year, examining the urine for proteinuria y Salmonella typhi
(protein/creatinine ratio > 20mg/mmol) at every visit. Thereafter, if y Mycoplasma pneumoniae
negative for protein, may be followed up yearly with urine microscopy, Š Viral:
looking in particular for proteinuria. y HIV
y Coxsackie:
What if Protein is Detected? ƒ Ebstein-Barr
™ Proceed to quantitate protein by doing timed urine collection ƒ Hepatitis B
™ If > 4mg/m2/hour, refer to a nephrologist ƒ Influenza
™ If < 4mg/m2/hour, follow-up closely for worsening proteinuria. If ƒ Mumps
proteinuria resolves, manage as for isolated microscopic haematuria ™ HSP with nephritis
™ SLE
Indications for Renal Biopsy ™ IgA nephropathy
™ Associated significant proteinuria (> 1g/1.73m2/day) ™ Membranoproliferative glomerulonephritis
™ Azotaemia
394 The Baby Bear Book Nephrology 395

™ Hereditary nephritis (Alport’s Syndrome) ™ Hypertension Diuretics (frusemide)

™ IE-related ± hydralazine, calcium channel blocker or
™ Shunt nephritis ACE inhibitor
If severe, refer to section on hypertension
HISTORY ™ Antibiotics Indicated in patients with positive cultures
™ History of URTI one to two weeks prior to onset of acute nephritis. Penicillin, or erythromycin in allergic
Latent period between pyoderma and onset of AGN is variable individuals
™ Facial swelling/oedema
™ Gross haematuria NATURAL HISTORY
™ Oliguria Resolution of:
™ May have systemic symptoms — Fever, malaise, anorexia, headaches Gross haematuria Two weeks
™ Extrarenal symptoms like arthritis, rash (systemic and extrarenal Oliguria Two weeks
symptoms are often seen in SLE nephritis) Azotaemia Two weeks
Hypertension Four weeks
PHYSICAL EXAMINATION Decreased C3 Six weeks
™ Hypertension Proteinuria Six months
™ Oedema Microscopic haematuria 12 months
™ Ascites
™ Circulatory congestion — Tachypnoea, tachycardia, hepatomegaly INDICATIONS FOR RENAL BIOPSY
™ Severe renal failure of unknown/uncertain aetiology
MANAGEMENT ™ Atypical features such as co-existent Nephrotic Syndrome (NS)
Supportive/symptomatic: ™ Delayed resolution
™ Bed rest
™ Salt and water restriction Insensible water loss (400ml/m2/day) plus PROGNOSIS
half urine output ™ Excellent in post-streptococcal AGN, with restoration of renal
function in more than 90%
™ Rapidly progressing glomerulonephritis (RPGN) in 1%
Table 10-2: Investigations.
Urine microscopy Dysmorphic RBC, RBC casts BIBLIOGRAPHY
Proteinuria (proportional to RBC) 1. Travis LB, Kalia A. Acute nephritic syndrome. In: Postlethwaite RJ, editor. Clinical paediatric
nephrology. 2nd ed. Oxford: Butterworth-Hinemann; 1994. p. 201–209.
Renal panel Elevated blood urea and creatinine 2. Barratt M, Avner E, Harmon B, editors. Pediatric Nephrology. 4th ed. Baltimore: Lippincott
Full blood count Anaemia (as in SLE) Williams & Wilkins; 1999.
± elevated WBC. Leucopenia, especially lymphopenia
is seen in SLE
Bacteriological and serological studies Throat swab (may be negative if treated)
↑ Anti-streptolysin O titre (ASOT), ↑ Antihyaluronidase
↑ Antideoxyribonuclease NEPHROTIC SYNDROME (NS)
Immunological markers Hypocomplementemia (CH50, C3, C4)
Autoimmune markers — ↑ Ds DNA, ANA titres in SLE
Radiology CXR: Cardiomegaly, pulmonary congestion/oedema INTRODUCTION
Renal ultrasound: Non-specific echogenic kidneys The term ‘Nephrotic Syndrome’ is applicable to any condition with:
™ Heavy proteinuria:
396 The Baby Bear Book Nephrology 397

Table 10-4: Definitions.

Š 40mg/m2/hr (timed urine collection), or
Š Protein/creatinine ratio > 200mg/mmol (random) Nephrotic syndrome Oedema; plasma albumin < 25g/L; heavy proteinuria: Urine Total
™ Significant hypoalbuminaemia (< 25g/L) Protein (UTP) > 2g/L or > 40mg/m2/hr or protein:creatinine ratio
™ Generalised oedema (dependent/pitting)
> 200mg/mmol
™ Hyperlipidaemia Remission UTP < 0.2g/L or protein:creatinine ratio < 20mg/mmol or Albustix
= 0/trace for three consecutive days
It is the most common cause of generalised oedema in children and the Steroid responsive Remission achieved with steroid therapy alone
most common presentation of childhood glomerulonephritis. Late responder Remission occurring after four weeks prednisolone 60mg/m2/day
without other drugs
It is presumably an immune-mediated disorder of glomerular Relapse UTP > 2g/L or protein:creatinine ratio > 20mg/mmol or Albustix >
permeability selectivity resulting in urine protein loss due to either ++ for three consecutive days, having previously been in remission
a primary glomerulopathy (most common being minimal change Frequent relapses Two or more relapses within six months of initial response, or four
disease) or secondary to a systemic disease (most common being SLE, or more relapses within any 12-month period
HSP). Steroid dependence Two consecutive relapses occurring during corticosteroid treatment
or within 14 days of its cessation
CLASSIFICATION AND DEFINITIONS Steroid resistance Failure to achieve response in spite of four weeks of prednisolone
Although histological classification is helpful in the management of 60mg/m2/day
childhood NS, renal biopsy is not necessary in the vast majority of Early non-responder Steroid resistance in the initial episode
patients and it is the clinical response to steroid therapy and the Late non-responder Steroid resistance
clinical course that determines the management and prognosis of
patients. Thus the broad clinical classification of Steroid-sensitive
Nephrotic Syndrome (SSNS) and Steroid-resistant Nephrotic Syndrome MANAGEMENT
(SRNS). The clinical course further divides SSNS to Steroid-dependent Principles
Nephrotic Syndrome (SDNS) and Frequently Relapsing Nephrotic ™ To induce remission and prevent complications:
Syndrome (FRNS). The clinical response and clinical course should be Š Prednisolone is the mainstay of treatment
accurately defined as they form the basis and rationale for treatment Š IV albumin with frusemide effectively reduces oedema but
(see Table 10-3 below and Table 10-4 next page). will not induce remission. It is used to resuscitate a severely
intravascularly contracted patient or to reduce severe
symptomatic oedema (e.g. scrotal oedema, severe anasarca,
Table 10-3: Glomerular histology in nephrotic syndrome*.
symptomatic hyponatraemia) while awaiting clinical response to
Glomerular Histology Steroid Response steroids
(%)
Š Common complications of the nephrotic state are:
Minimal-change nephrotic syndrome (MCNS) 93.1 y Infections (cellulitis, primary peritonitis — usually
Focal global glomerular sclerosis 75.0 streptococcus pneumoniae, UTI, chest infections)
Focal segmental glomerulosclerosis (FSGS) 29.7 y Thrombosis (renal vein, cerebral vein) — not common
Diffuse mesangial hypercellularity (DMH) 55.6 y Symptomatic hyponatraemia (may be due to overzealous fluid
Membranoproliferative glomerulonephritis (MPGN) 6.9 replacement)
™ Detection and early treatment of relapse:
Membranous nephropathy 0
Š Home monitoring and parent/patient understanding of the
Chronic glomerulonephritis 0
disease is important
* Histologic appearance and steroid response in 471 children with primary nephrotic syndrome.
™ Avoid or minimise untoward side-effects of therapy while awaiting
long-term remission or cure in the majority of children
398 The Baby Bear Book
POINTS TO REMEMBER
™ Newly diagnosed patients require hospitalisation as most have
severe oedema and severe hypoalbuminaemia that may require
monitoring and IV albumin/ frusemide before clinical response to
prednisolone
™ Albumin infusions are expensive and can be hazardous. They should
be reserved for patients with:
Š Hypovolaemia, oliguria with raised haematocrit and low urinary
sodium (1–2mmol/L)
Š Severe anasarca e.g. severe periorbital oedema, severe ascites,
pleural effusion
Š Scrotal oedema
Š Symptomatic hyponatraemia (CNS symptoms)
Majority of patients do not require albumin infusion.
IV Albumin is given as 1g/kg of 20% albumin (in preparations of
50ml/bag) over four hours with a bolus of IV frusemide 1–2mg/kg
midway through the infusion. In severe oedema, IV frusemide can be
repeated at the end of the infusion
™ First clinical response to steroid treatment will be increased urine
output and weight loss (before resolution of proteinuria) and usually
takes five to seven days
™ Diagnosis is often straightforward and does not require:
Š 24-hour urine protein measurement
Š Screening for systemic disease (e.g. SLE) if there is no clinical
suspicion
™ Patient can be safely discharged once clinical response is evident
(diuresis, weight loss), usually after five to seven days of treatment.
Complete remission however takes about two to four weeks
™ Explanation to parents is important for long-term management:
Š Use of albustix and early detection of relapse
Š Intercurrent infection may induce transient proteinuria (< seven
days). In the absence of oedema and with the presence of an
improving trend in albustix, no treatment is necessary
Š Relapsing course is expected in over 70% patients and parents
need to be forewarned that follow-up will be required for at least
one to two years
™ When faced with treatment failure, one must exclude non-
compliance (as in most chronic illnesses) and address this problem
first before upgrading the severity of the disease that may require
more aggressive treatment with more serious side-effects.
Nephrology 399
Helpful clinical features for non-MCNS that may necessitate renal biopsy:
™ Age < one year or > 12 years
™ Prominent or gross haematuria
™ Family history of chronic renal disease
™ Hypertension
™ Acute renal failure/azotemia
™ Evidence of systemic disease
™ Steroid resistance
TREATMENT REGIMENS
Treatment for initial presentation is usually prolonged as most
patients were in a nephrotic state for a protracted and prolonged
period with very low serum albumin. It is also intensive (as in most
immunosuppressive therapy) to ensure prolonged remission. Treatment
of relapses are less intensive as they are usually detected early due to
close monitoring and usually do not require hospitalisation.
Up to 80% of childhood NS has MCNS as the primary glomerulopathy
with the majority (93%) being sensitive to steroids. An excellent
prognosis with no long-term renal morbidity can be expected. However,
complications of the nephrotic state require prompt and effective
treatment and a frequently relapsing course or steroid dependency
may lead to serious steroid side-effects (especially retarded growth,
osteoporosis, cataract) which necessitates the use of more potent
immunosuppressive drugs (e.g. cyclophosphamide, cyclosporin) to
spare steroid toxicity. All immunosuppressive drugs have significant
side-effects and their use thus requires clear indications and careful
monitoring.
Calculation of prednisolone dose:
Weight (kg) x Height (cm)
Body Surface Area (m2) =
3600
Table 10-5: Prednisolone regimen for initial presentation of nephrotic syndrome.
Duration Dosage (single dose; can be in divided dose if necessary)
Four weeks 60mg/m2/day (max 80mg)
Four weeks 40mg/m2/alt. days (max 60mg)
Tapering alternate day doses of steroid over four weeks
400 The Baby Bear Book Nephrology 401

Nephrotic Syndrome Table 10-6: Prednisolone regimen for relapse of nephrotic syndrome.
Duration Dosage (single dose)
Prednisolone 60mg/m2/day (max 80mg/day) x four weeks At least two weeks or until remission 60mg/m2/day (max 80mg), then 40mg/m2/EOD for
four weeks

Steroid-responsive Steroid-resistant
TREATMENT GUIDELINE FOR RELAPSE OF NEPHROTIC
Prednisolone 40mg/m2/EOD x four weeks, then taper over four weeks Renal biopsy SYNDROME
Relapses in known NS are usually mild and can be treated as an
Cyclophosphamide outpatient as they are detected early with Albustix monitoring. It is
No relapse Relapse 2–2.5mg/kg/day x 12 weeks defined clinically as oedema + significant proteinuria (> 2+ or UTP >
or 2g/L) or sustained protenuria alone.
Prednisolone 40mg/m2/day Cyclosporin A 5–6mg/kg/day
x two weeks or longer until Treat hyperlipidaemia, oedema
Cured Indications for Admission
proteinuria-free for three days, with albumin, diuretics
™ Severe oedema/anasarca where quick relief of oedema may be
then taper over six weeks
necessary with IV albumin + frusemide before prednisolone effect
occurs in one to two weeks’ time
™ Symptomatic oedema — Hypotension/postural hypotension,
Infrequent relapses Frequent relapses Steroid-dependent respiratory difficulty, scrotal swelling
™ Complicated NS
Prednisolone 0.1–0.5mg/kg/EOD Š Fever or other systemic symptoms e.g. vomiting, diarrhoea
(school age) or 0.1–1.0mg/kg/EOD Š Non-MCNS (ascertain from history/health booklet) e.g. lupus
Prednisolone 60mg/m2/day (pre-school age) x six to 12 months nephritis, HSP, FSGS
for at least two weeks or till
remission, then 40mg/m2/EOD Unsuccessful
Treatment of Relapsed NS as Outpatient
™ Non-oedematous patient
Refer for evaluation. Longer Lowest alternate-day steroid with Š Ascertain sustained proteinuria i.e. UTP > 2g/L or Albustix > 2+ up
term EOD Prednisolone Cyclophosphamide 2.5mg/kg/day to five days
depending on steroid threshold x 12 weeks Š Unsustained proteinuria often occurs with intercurrent infection
when relapses occur or
e.g. URTI, but proteinuria should not be > seven days
Cyclosporin 5–6mg/kg/day
x one to two years Š Up to 25% of the relapses remit spontaneously and therapy can
or usually be safely deferred for up to five days
Levamisole 2.5mg/kg/EOD ™ Oedematous patient (swelling, sudden weight gain + significant
for six to 12 months proteinuria of > 2+) should be treated irrespective of whether there
is sustained proteinuria
Threshold < 0.5mg/kg/EOD Threshold > 0.5mg/kg/EOD
or steroid toxicity Treatment Regime for Relapsed NS
™ Oral prednisolone 60mg/m2/day (OM or in divided doses. OM
ensures compliance) for at least two weeks or till remission.
Prednisolone 0.1–0.5mg/kg/EOD Treat as for steroid dependency Once patient is proteinuria-free, prednisolone can be reduced
for six to 12 months progressively over four to six weeks at EOD doses.
Fig. 10.1: Algorithm for the management of childhood nephrotic syndrome.
402 The Baby Bear Book Nephrology 403

Table 10-7: Blood pressure levels for children between one to 17 years old. Adapted from Second
™ Biochemical documentation of relapse i.e. serum protein/albumin
Task Force on Blood Pressure Control in Children (1996).
is usually not necessary and diagnosis of relapse can be made on
clinical grounds Systolic BP Diastolic BP
Age
95th percentile (mmHg) 95th percentile (mmHg)
Immunisations One year 102–104 57–58
Though somewhat controversial, immunisations (especially live Two to five years 105–112 61–71
attenuated vaccines) are best deferred until patient is off steroids for at Six to nine years 111–117 73–79
least three months. Ten to 13 years 119–126 78–82
14–17 years 128–136 82–87
BIBLIOGRAPHY
1. Godfrey CA, Barratt M. Steroid-responsive nephrotic syndrome. In: Barratt M, Avner E,
Harmon B, editors. Pediatric Nephrology. 4th ed. Baltimore: Lippincott Williams & Wilkins;
1999. p. 731–748. ™ BP > 10mmHg above 95th percentile may be considered as severe
2. The primary nephrotic syndrome in children. Identification of patients with minimal hypertension for purposes of guiding investigation and treatment
change nephrotic syndrome from initial response to prednisone. A report of the
International Study of Kidney Disease in Children. J Pediatr. 1981;98(4):561–564. ™ Generally, hypertension is considered when BP in:
3. Brodehl J, Krohn HP, Ehrich JH. The treatment of minimal change nephrotic syndrome Infants > 90/60mmHg
(lipoid nephrosis): Cooprative studies of the Arbeitsgemeinschaft für Pädiatrische
Nephrologie (APN). Klin Padiatr 1982;194(3):162–165. Children > 120/80mmHg
4. Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic Above 12 years > 130/90mmHg
syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Lancet.
1988;1(8582):380–383.
5. Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. HYPERTENSIVE EMERGENCY
A report of “Arbeitsgemeinschaft für Pädiatrische Nephrologie”. Lancet. 1979;1(8113):401–
403. Consider if:
6. Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment ™ Diastolic BP > 110mmHg, or
of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische
™ Symptomatic — Headache, blurring of vision, altered sensorium,
Nephrologie. Eur J Pediatr. 1993;152(4):357–361.
7. Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid therapy in nephrotic syndrome: A convulsions. Look for neurological signs, cardiac failure and fundal
meta-analysis of randomised controlled trials. Arch Dis Child. 2000;83(1):45–51. changes (papilloedema, exudates and fundal haemorrhages)
8. Ekka BK, Bagga A, Srivastava RN. Single- versus divided-dose prednisolone therapy for
relapses of nephrotic syndrome. Pediatr Nephrol. 1997;11(5):597–599.
9. Nephrotic syndrome in children: A randomized trial comparing two prednisone regimens Treatment
in steroid-responsive patients who relapse early. Report of the international study of
kidney disease in children. J Pediatr 1979;95(2):239–243. ™ 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
™ Optimal rate of reduction: A third in first six hours, next third in next
24–36 hours, last third in subsequent 48–72 hours
HYPERTENSION ™ All cases of hypertensive crisis should be admitted to the ICU for
continuous BP monitoring. Pay attention to pupillary reactions,
Defined as sustained elevation (on at least three occasions) of systolic or consciousness level and neurological examination. Saline for volume
diastolic BP at or above the 95th percentile. expansion on standby in case of sudden hypotension
Beware of white-coat hypertension or unsustained hypertension. See Table 10-8 overleaf for the drugs used, in order of preference.

BLOOD PRESSURE LEVELS Drugs for Selected Hypertensive Emergencies

Table 10-7 next page outlines the BP levels for children between the See Fig. 10.2 p. 405.
ages of one and 17 years of age.
404 The Baby Bear Book Nephrology 405

Table 10-8: Drugs used for hypertensive emergency, in order of preference.

Drug/Route Dose Onset of Action Duration Precautions Hypertensive Head trauma Catecholamine production
IV labetolol 0.2–1mg/kg Five to ten Two to three Contraindicated Encephalopathy (phaeochromocytoma)
™ 5mg/ml bolus, then minutes hours in asthma. Raised ICP
™ 5ml vial 0.5–3mg/kg/ May cause Sudden and severe
hr continuous bradycardia and hypertension
infusion worsen heart
failure.
IV nitroprusside 0.5–8μg/kg/min Within seconds Short half-life Protect from
(seconds to light and
minutes) monitor blood
cyanide level Labetolol or Labetolol or nitroprusside Phentolamine
when infusing nitroprusside
for > 72 hours or Contraindicated:
in patients with Alternative: Hydralazine
renal failure. Hydralazine Diazoxide
Level should Diazoxide Calcium channel blocker
be < 12mg/
dl. May cause Fig. 10.2: Drugs for selected hypertensive emergencies.
hypotension,
reflex
tachycardia and HYPERTENSIVE URGENCY
raised ICP. Consider if:
IV hydralazine 0.1–0.3mg/ Ten to 30 Four to 12 hours May cause reflex ™ Diastolic BP > 110mmHg, but there is no evidence of acute end
kg bolus (max minutes tachycardia, organ damage/compromise
10mg), infusion headaches, ™ Possible progression. BP reduction by 25% of desired BP within
at 4–6μg/ flushing, 12–24 hours
kg/min (max fluid retention.
™ Choice of either IV or oral antihypertensives
300mg/kg/min) Contraindicated
in SLE
Treatment
IV diazoxide 1–5mg/kg bolus, One to three Eight to 24 hours Hyperglycaemia,
can be minutes fluid retention. The oral drugs used, in order of preference, are listed in Table 10-9
repeated after May cause severe below.
30–60 minutes, hypotension
then 2–5mg/kg/ with boluses.
dose six hourly Table 10-9: Oral drugs used for hypertensive urgency, in order of preference.
IV frusemide (in 1–2mg/kg/dose Rapid onset May cause Drug/Route Initial dose Max dose Precautions
AGN) six to 12 hourly hypokalaemia, PO nifedipine 0.25–0.5mg/kg 3mg/kg/day Hypotension
ototoxicity and four to six hourly (adult 80mg)
hypercalciuria. PO nifedipine 0.2mg/kg/dose 7.5mg/kg/day Contraindicated in SLE
six to eight hourly (adult 200mg)
PO propranolol 0.2–0.5mg/kg/dose Slowly increase to max Contraindicated in
six to 12 hourly 1.5mg/kg/dose (max asthma and cardiac
80mg) failure
six to 12 hourly
406 The Baby Bear Book Nephrology 407

BIBLIOGRAPHY
1. Hypertension. In: Barratt M, Avner E, Harmon B, editors. Pediatric Nephrology. 4th ed.
Baltimore: Lippincott Williams & Wilkins; 1999. p. 959–1050.
2. Ministry of Health. A Guide to Paediatrics. Singapore: Ministry of Health; 1997.
3 National High Blood Pressure Education Program. Update on the 1987 Task Force Report Table 10-10: Clinical classification of childhood UTI.
on High Blood Pressure in Children and Adolescents: A working group report from the
National High Blood Pressure Education Program. Pediatrics. 1996;98(pt 1):649–658. Clinical Features Upper Tract Infection Lower Tract Infection
4. Adelman RD, Coppo R, Dillon MJ. The emergency management of severe hypertension. Age Generally < two years Generally > two years
Pediatr Nephrol. 2000;14(5):422– 427.
5. Yap HK. Acute renal failure. In: Yip WCL, Tay JSH, editors. A practical manual on acute Renal involvement Neonates and young infants No risk
paediatrics. Singapore: P.G. Publishing; 1989. p. 273–288. are at high risk
Sex Female = Male in infancy Female > Male
Female > Male past infancy
Fever + —
(All febrile UTI have presumed
URINARY TRACT INFECTION (UTI) pyelonephritis)
AND VESICOURETERIC REFLUX (VUR) Voiding Problem — +
Dysuria — +
Frequency — +
INTRODUCTION
Suprapubic pain — +
UTI is one of the most common bacterial infections seen in children.
Incidence of acute pyelonephritis is high, especially during infancy Loin pain (older children) + —
(70–80%). Although the majority of children with UTI have an
excellent prognosis, there is a definite risk of renal damage following
pyelonephritis especially in those with VUR (see “Vesicoureteric Reflux
Table 10-11: Antibiotic treatment of upper urinary tract infection.
(VUR)” p. 414) or obstructive uropathy.
Choice of Antibiotics Duration of Treatment
CLINICAL CLASSIFICATION First-line Ten to 14 days
The epidemiology, pathophysiology and prognosis of UTI are Infant < 28 days old:
interrelated and differ according to age, sex and in particular the site of Ampicillin 50–100mg/kg/day six hourly, Infant < 28 days old:
infection. A useful classification is shown in Table 10-10 next page. and ™ IV therapy until no fever for
Gentamicin 7.5mg/kg/day eight to 12 48–72 hours, then oral therapy
hourly according to antibiogram
DIAGNOSIS AND MANAGEMENT ™ For those with bacteremia, parenteral
Upper Urinary Tract Infection Infants > 28 days old: therapy should be continued for
The cardinal symptom of pyelonephritis is unexplained high fever, often Gentamicin 5–6mg/kg/day as single dose seven to ten days
with chills and rigors. UTI should be suspected in such instances, especially
in infants. Cloudy urine is a more helpful symptom than smelly urine. Second-line Infants > 28 days old:
Ceftriaxone 50–100mg/kg/day once ™ Parenteral therapy until afebrile for
a day 24 hours, then oral therapy
A pre-treatment, properly collected mid-steam urine culture is
or
mandatory to establish a firm diagnosis of UTI, which will determine Cefotaxime 50–200mg/kg/day
subsequent management. However, up to 9% of patients with six to eight hourly
pyelonephritis may have equivocal or negative urine cultures. If
suspicion of pyelonephritis is high, especially in febrile infants, a
Dimercaptosuccinic Acid (DMSA) scan may be indicated to accurately
diagnose acute pyelonephritis at the time of infection.
408 The Baby Bear Book Nephrology 409

Table 10-12: Antibiotic treatment of lower urinary tract infection. Clinical Diagnosis of Urinary Tract Infection
Choice of Antibiotics Duration of Treatment
™ Cotrimoxazole*: Seven to ten days of antibiotics
TMP 8mg/kg/day divided 12 hourly Fever
™ Nitrofurantoin*: 5–7mg/kg/day divided > 12 years old: Three days TMP + SMZ
six hourly can be considered instead of standard No Yes
™ Cephalexin: 25–50mg/kg/day divided seven-day treatment
eight hourly
Lower Tract Infection Upper Tract Infection
™ Trimethoprim: 8mg/kg/day divided
12 hourly (useful for G6PD deficient
patient)
Urine Culture Urine Culture
(* Screen for G6PD deficiency)

Age Age

When early initiation of antibiotic treatment is necessary and there is no

time to wait for a mid-stream urine collection (e.g. neonatal pyrexia) an < 12 years ≥ 12 years < 28 days ≥ 28 days
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 (91% sensitivity) and Seven to Consider
Full septic
ceftriaxone (almost 100%) as an alternative. Although ceftriaxone has ten day three-day Toxic Non-toxic
work-up
almost 100% sensitivity, it is used as second-line treatment for fear course course
cotrimoxazole
of emergence of resistance. However, in patients with compromised
renal function, ceftriaxone is the antibiotic of choice. Ampicillin is
added in infants for enterococci UTI, which is not uncommon in this
age group ™ Cotrimoxazole* or IV Ampicillin and
™ Nitrofurantoin* or Gentamicin pending Admit ± Admit†
Refer to Table 10-11 on previous page for a list of antibiotic treatments ™ Cephalexin/Cefaclor or culture results until
™ Trimethoprim afebrile for 48–72 hours,
for upper UTI.
Revise antibiotics once culture then oral to complete ten
results are available to 14 day course
Lower Urinary Tract Infection Parenteral until asymptomatic
™ Common in young girls for 24 hours, then oral to
* Contraindicated in children with G6PD deficiency
™ Presents with voiding problems — Dysuria, frequency and †
Oral antibiotics for upper UTI are empirical; therefore admission is
complete 14-day course
strongly advised for all febrile UTI. If not admitted: ™ Gentamicin ± Ampicillin or
suprapubic pain due to cystitis
™ Send properly collected urine for culture ™ Ceftriaxone or Cefotaxime ±
™ Fever is not a feature Ampicillin
™ Treat with oral cephalosporin (cephalexin or cefuroxime) or
™ Though troublesome and often recurrent, no cause for alarm Augmentin
because there is no associated renal involvement ™ Review in two to three days and revise treatment accordingly to
culture and sensitivity result
Refer to Table 10-12 above for a list of antibiotic treatments for lower Fig. 10.3: Algorithm for the management of urinary tract infections in children.
UTI.
410 The Baby Bear Book Nephrology 411

METHODS OF URINE COLLECTION Firm diagnosis of febrile UTI/

DMSA evidence of APN
Specimen Method Significant Growth
Mid-stream, clean catch Initial part of urine stream Pure growth of a single
containing most of the organism > 105 colonies/ml Renal ultrasound
periurethral bacteria is (earliest convenient time)
discarded. Best to obtain two
specimens as this increases
the accuracy.
Catheterised specimen Pure growth of single Abnormal Normal
organism > 104 colonies/ml
Suprapubic aspiration Easy in infants as bladder is Any growth is significant
intraabdominal. Best done AB prophylaxis if
about an hour after a feed. age < one year
™ Place child supine Full investigations:
™ Swab the suprapubic area • MCU for VUR
with alcohol and iodine (as • DTPA for obstructive uropathy
for blood culture) • DMSA scan
™ Use a 2.5ml syringe with Female Male (all ages)
21G needle (blue needle)
™ Insert the needle vertically
downwards about 1–2cm
above the symphysis Age > Age two to Age <
pubis in the midline, while five years five years two years
applying constant negative
pressure with the syringe.
Urine is usually obtained at No Yes
a depth of 2–3cm. Evidence or suspicion MCU with
DMSA
of recurrent UTI bactrim cover
+
Follow up
Normal Abnormal DMSA
DMSA
APPROACH TO INVESTIGATIONS
FOLLOWING UTI Follow-up x one year

PRINCIPLE Recurrent UTI

Most laboratory and clinical evidence strongly supports the concept No Yes
that both VUR and UTI are responsible for acquired renal scarring and
that this damage takes up to six months to establish and to become
evident on the DMSA scan. Once formed, scarring is irreversible and Discharge MCU + DMSA
when extensive, it can significantly reduce the function of the affected Consider urodynamic
kidney (< 45% differential function). study if indicated
Fig. 10.4: Approach to Investigations following UTI.
412 The Baby Bear Book
An acute inflammatory response associated with renal parenchymal
infection is the pre-requisite for acquired renal scarring. VUR is the single
most significant risk factor for Acute Pyelonephritis (APN) and renal
scarring.
Risk of scarring correlates to:
™ Age (inversely) — < two years are at high risk
™ Severity of VUR — VUR ≥ Grade III being at higher risk
™ Recurrence of UTI
IMAGING STUDIES
Investigations should include renal ultrasound and DMSA ± Micturating
Cystourethrogram (MCU).
™ Renal Ultrasound:
Š To be done as soon as possible in all patients. Abnormalities
include:
y Hydronephrosis, hydroureter
y Abnormal renal size and/or position
y Cysts/calculi
Š Not sensitive in detecting VUR, pyelonephritis and renal scarring
™ DMSA Scans:
Š Useful to detect APN at the time of infection but may be difficult
to differentiate inflammatory changes from scarring
Š Done six months post-UTI to detect renal scars and to assess
differential renal function
Š Should be done in all patients
™ MCU:
Š Radiographic MCU is the standard for the diagnosis of VUR
Š Direct radioisotopic MCU (with catheterisation) has the
advantage of having significantly lower radiation than the
radiographic method but it is not accurate in the assessment of
the severity of VUR or the diagnosis of posterior urethral valve. It
should only be used as follow-up study of primary VUR
Š Indirect Diethylene Triamine Pentacetic Acid (DTPA) cystography
has the advantage of avoiding catheterisation but again, it is less
accurate and unable to detect lower-grade VUR. It also requires
cooperation from the patient. Generally used for children older
than six years, who can void on command, or patients who refuse
catheterisation
Nephrology 413
GUIDELINES FOR MICTURATING
CYSTOURETHROGRAPHY (MCUG)
BACKGROUND
MCUG is a fluoroscopically monitored definitive imaging study of the:
™ Lower urinary tract:
Š Bladder, urethra, vesico-ureteric junction
™ Upper urinary tract:
Š Only if VUR is present
Indications for doing MCUG must be clear and the disadvantages
include:
™ Invasive procedure requiring bladder catheterisation
™ Radiation risk to gonads, especially in females
INDICATIONS
When VUR, Posterior Urethral Valve (PUV) or neuropathic bladder is
suspected on clinical grounds or on renal ultrasound screening.
™ Most common indication is for the definitive diagnosis of VUR
following UTI or ultrasound evidence of dilated upper tract
™ Definitive diagnosis of PUV in boys, especially if bilateral dilated
upper tract is present on ultrasound
™ Part of work-up for neuropathic bladder, where bladder hypertrophy
and trabeculation can be seen on MCUG due to back pressure
changes from functional or anatomical bladder outlet obstruction
™ To assess urological abnormalities associated with small dysplastic/
hypoplastic kidneys or unexplained renal failure where urological
intervention may improve renal function
CONTRAINDICATIONS
MCUG is not an urgent procedure, although it should be done at the
earliest possible time.
™ MCUG should only be done when the UTI is adequately treated,
usually two to four weeks post-infection
™ After a UTI, antibiotic prophylaxis (usually cotrimoxazole 2–4mg/
kg ON) should be started, especially in infants and those with
ultrasound abnormalities, until MCU result is known. Recommended
prophylactic antibiotics in neonates would be ampicillin (BD dose)
or cephalexin (ON dose), and these antibiotics should be changed to
cotrimoxazole as soon as possible
414 The Baby Bear Book
™ 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 difficult group at risk of trauma
(especially female) and failure of procedure (e.g. catheter slips out).
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:
Š Infection:
y Minimise risk through proper aseptic technique
y Short-course cotrimoxazole cover in patients < two years
(because of higher risk of underlying abnormalities).
Cotrimoxazole (trimethoprim 8mg/kg/day in BD dose)
for three days (i.e. day of MCUG and the following two
days). Cotrimoxazole not to be used in patients with G6PD
deficiency; use cephalexin instead
Š Trauma:
Precautions to be taken:
y Adequate lubrication/anaesthesia with sterile 1% lignocaine
gel
y Correct-sized catheter. 5 to 8F feeding tube, depending on
patient size
y 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
y Avoid using force when resistance is met
y Consult senior doctor if difficulty encountered
™ Aftercare:
Š Ensure antibiotic cover and prophylaxis.
Š Advise on possible dysuria (rarely leading to retention of urine)
VESICOURETERIC REFLUX (VUR)
Treatment of VUR, especially high-grade, can be controversial. The first
line of treatment is medical and indications for surgical treatment are:
™ Failed medical treatment
Nephrology 415
™ Associated urological abnormalities e.g. urethrocele, duplex systems,
obstructive uropathy
Medical Treatment:
™ Daily low-dose antibiotics, minimal dose to prevent urosepsis. Choice
of antibiotic:
Š Bactrim: 2.5–5mls (2–4mg/kg) nightly
Š Nitrofurantoin: Usually 12.5–50mg (1–2mg/kg) nightly. Avoid if
there is peripheral neuropathy
Š Cephalexin: 25–50mg/kg nightly
™ Regular follow-up:
Š Until resolution of VUR or till patient is five years old
Š If high-grade VUR persists beyond five years old and if it
still causes UTI, treatment is surgical as there is little chance
of spontaneous resolution. A bladder urodynamic study is
sometimes indicated to exclude bladder instability in children >
five years old with persistent high-grade VUR
Severity of VUR Affects Choice of Treatment
™ Low grade (Grade I–II or reflux without dilatation) usually does not
require aggressive treatment:
Š Prophylactic antibiotics are recommended for young patients (<
one to two years old)
Š Repeat MCU is not mandatory especially if DMSA scan is normal
™ High grade (with renal tract dilatation or Grade III and above) needs:
Š Antibiotic prophylaxis
Š Follow-up MCU
Š Follow-up DMSA scan if there is recurrent UTI with possibility of
new scar formation
™ If child is > five years old with febrile UTI for the first time, antibiotic
prophylaxis is recommended for one to two years from time of
infection if VUR is present
VUR, in particular high-grade, is an important and common
predisposition to recurrent acute pyelonephritis. Thus it requires
appropriate and prompt treatment. However, beyond five years of age,
what appears more important is the sequelae of acute pyelonephritis
(renal scarring and the extent of scarring/function of the affected
kidney). Significant scarring (with decreased differential function)
is associated with hypertension, and if there is bilateral and more
extensive involvement, renal failure can ensue.
416 The Baby Bear Book
Vesicoureteric Reflux (VUR)
Low Grade (I & II)
Consider antibiotic
prophylaxis until one year
Follow up x one year no
recurrent UTI
Consider discharge
Persistent VUR beyond six years old
No scar
Repeat DMSA
Scar
Long-term follow-up if
significant scarring or reduced
differential function is present
Fig. 10.5: Clinical Approach to VUR.
Nephrology 417
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
High Grade (III & IV) ™ If there are complicated pathologies e.g. duplex, urethrocele,
trabeculated bladder
Medical Treatment Surgical Treatment
™ Antibiotic prophylaxis Indications: ENURESIS AND VOIDING PROBLEMS
and follow-up until ™ Failed medical
VUR resolves or until treatment:
Enuresis is a common, socially disruptive and stressful condition
six years of age Š Breakthrough UTI
™ MCU two-yearly Š DMSA deterioration
affecting 10% of school-going children with 1% continuing into
™ Repeat DMSA if Š Non-compliance adulthood.
recurrent UTI ™ Co-existent uropathy
™ Ultrasound for renal ™ Single normal kidney DEFINITIONS
growth if indicated ™ Grade V VUR Nocturnal Enuresis (NE)/bedwetting — Wetting while asleep beyond
five years of age and frequent enough to be disturbing. Usually two
times or more in a week.
Primary Nocturnal Enuresis — Never been dry for an extended period
of more than six months.
Primary Monosymptomatic Nocturnal Enuresis (PMNE) — Primary
Stop antibiotic and observe nocturnal enuresis that occurs as the only problem i.e. the patient is
otherwise well with normal voiding.
Recurrent UTI Secondary Nocturnal Enuresis — Was consistently dry for at least six
months and then bedwetting recurred.
No Yes
Unstable Bladder — Frequent micturition, urgency and wetting.
Holding manoeuvres like squatting, crossing legs to stop the urge.
Consider urodynamic studies
and surgery Incontinence — No control over voiding or involuntary wetting.
Constant wetting may be associated with UTI and clinical signs of
neuropathic bladder.
418 The Baby Bear Book Nephrology 419

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
Physical Examination
Clinical ™ Inspection of genital area
Assessment ™ Lumbosacral signs of spinal
dysmorphism
™ Neurological defects in lower limbs —
pes cavus, hyper-reflexia
™ Lumbosacral reflex activity when
indicated
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
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

one to three months.
Negative Positive
Primary Onset Indications for treatment:
Often positive family history ™ ≥ six years old
Normal voiding ™ Bed-wetting is frequent (> two times a week)
Negative clinical findings Voiding problems — Dysuria, urgency,
incontinence Treatment Modalities
Encopresis Two established treatment modalities are the use of DDAVP and the
Evidence of UTI/pelvic surgery
Urinalysis + Urine C/S enuresis alarm.
Secondary onset
Positive clinical findings
Tricyclic antidepressants (imipramine) cannot be recommended as
Negative first-line therapy because of its potential fatal side-effect in overdose.
Anticholinergics like oxybutynin can act as adjunctive therapy when
Primary Monosymptomatic detrusor overactivity is one of the aetiologic factors.
Nocturnal Enuresis (PMNE) Specialist Referral
Desmopressin Treatment
DDAVP is a synthetic analogue of the natural-occurring anti-diuretic
No further investigations, hormone or vasopressin (AVP) but is more potent in its anti-diuretic
offer treatment effect and thus it will always improve incontinence.

DDAVP treatment in NE is rarely associated with water intoxication.

Fig. 10.6: Initial clinical assessment of nocturnal enuresis. Nonetheless patients and their families need to be warned of potential
420 The Baby Bear Book Nephrology 421

Age > five years No adverse effects and avoid overdrinking before bedtime. Minor side-
Reassurance
Frequency > twice a week effects reported include headache, abdominal pain and aggressiveness.
Yes
The long-term effects of DDAVP treatment in PMNE for a year or more
have not been adequately studied. However, there is no significant long-
Discuss treatment options term side-effect or evidence of developing tolerance.

Enuresis Alarm
The enuresis alarm is effective with a reported success rate around 60–
DDAVP Enuresis alarm 80%. Alarm training has a reported relapse rate of 15–40%. Retreatment
is often effective.
Oral 0.2–0.4mg or
Intranasal 20–40μg
When compared with pharmacotherapy, alarm treatment appears to
for at least one month
Good have more sustained effect when off-treatment.
Poor response
response after three BIBLIOGRAPHY
months 1. Moffatt MEK, Kato C, Pless IB. Improvements in self-concept after treatment of nocturnal
enuresis: Randomised controlled trial. J Pediatr. 1987;110(4): 647–652.
Partial/good Poor response 2. Chao SM, Yap HK, Tan A, Ong EK, Murugasu B, Low EH, Tan SP. Primary monosymptomatic
response (wet nights nocturnal enuresis in Singapore — Parental perspective in an Asian community. Ann Acad
(wet nights reduced by < Med Singapore. 1997;26(2):179–183.
Reassess Off alarm 3. von Gontard A, Eiberg H, Hollmann E, Rittig S, Lehmkuhl G. Molecular genetics of
reduced by 50%) nocturnal enuresis: Clinical and genetic heterogeneity. Acta Paediatr. 1998;87(5):571–578.
50%) 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):
Good Poor 70–72.
compliance compliance Wet Dry
Continue Treatment
™ Three months or more
™ May reduce dose by DDAVP ± Counselling Discharge
half alarm
™ Reassess
ACUTE RENAL FAILURE (ARF)

DEFINITION
Dry/acceptable Enuresis alarm ± DDAVP Retry enuresis alarm 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.

Discharge/treat on May be classified into

special occasions Good response No response ™ Oliguric renal failure — Urine output is < 300ml/m2/day or
< 1ml/kg/hr
™ Non-oliguric renal failure — Urine output is maintained
Refer to specialist
Fig. 10.7: Treatment guidelines for primary monosymptomatic nocturnal enuresis.
422 The Baby Bear Book Nephrology 423

APPROACH Differentiate Between Pre-renal, Renal and Post-renal

Causes of Acute Renal Failure Causes
Urine for Microscopic Examination
Pre-renal Volume depletion Haemorrhage
Gastrointestinal losses: Vomiting, diarrhoea Cells Dysmorphic red cells Glomerulonephritis
Renal losses: Tubulopathies White cells Pyelonephritis
Third space loss Hypoalbuminaemic states: Nephrotic syndrome, Eosinophils Acute interstitial nephritis
liver disease Casts Red cell Glomerulonephritis
Burns, crush injury Tubular cells/epithelial cells
Capillary leak syndrome, septicaemia Crystals Uric acid
Cardiac failure and hypotension Calcium oxalate
Renal Glomerulonephritis Acute nephritic syndrome
Post-infectious AGN
HSP Urinary Indices
Lupus nephritis ™ Children
RPGN
Urine Urine/ Urine/ Urine FENa (%) Urine/ Renal
Vascular Haemolytic-uraemic syndrome osmolality plasma plasma sodium plasma failure
Renal artery and vein thrombosis (mOsm/ urea creatinine (mmol/L) osmolality index
Interstitial Allergic kg) (mmol/ (umol/
mmol) umol)
nephritis Post-infectious
Progress from pre-renal conditions Pre-renal > 500 20 > 40 < 10 <1 >2 <1
Nephrotoxins — Drugs (aminoglycosides, Renal < 350 <3 < 20 > 60 >1 <1 >2
amphotericin, ifosphamide, cisplatin,
radiocontrast dye)
Pigment injury — Haemoglobinuria, ™ Neonates
myoglobinuria
Post-renal Obstructive uropathy Posterior urethral valve Urine Urine/ Urine/ Urine FENa (%) Urine/ Renal
Ureteric obstruction of single kidney osmolality plasma plasma sodium plasma failure
(mOsm/ urea creatinine (mmol/L) osmolality index
Cystalluria Uric acid nephropathy
kg) (mmol/ (umol/
High-dose methotrexate mmol) umol)
Pre-renal > 400 > 10 > 30 < 30 < 2.5 > 1.5 < 2.5
Renal < 400 < 10 > 60 > 2.5 <1 > 2.5
Distinguishing Between Acute and Chronic Renal Failure
Features of chronicity include:
™ Growth failure Urine/plasma Na
™ Past or family history of renal disease Fractional excretion of sodium (FENa) =
Urine/plasma Cr
™ Chronic hypertensive retinopathy
™ Renal osteodystrophy or rickets
™ Small kidneys on renal ultrasound Urine Na
Renal failure index (RFI) =
Urine/plasma Cr
Features such as anaemia, hyperphosphataemia, and hypocalcaemia are
not distinguishing features as they may occur in ARF.
424 The Baby Bear Book Nephrology 425

Caveats to interpreting urinary indices: MANAGEMENT OF ACUTE RENAL FAILURE

™ Clinical picture to be taken into account as these indices are neither Reverse reversible factors:
sensitive nor specific ™ Hydration
™ Continuum between early and late pre-renal conditions ™ Hypotension
™ Large equivocal area in which indices may not indicate definitive ™ Infection
results ™ Nephrotoxicity
™ Obstruction
Blood Indices: Interpretation of Serum Urea and Creatinine
In most cases, management is conservative while awaiting recovery of
Serum urea/creatinine ratio (mmol/mmol) renal function. The aim of management is to:
™ Correct fluid/electrolyte abnormalities
Acute tubular necrosis Normal ratio, < 100:1
™ Provide adequate nutrition
Pre-renal failure > 100:1
Fluid Management
™ Principle: Replace Insensible Water Loss (IWL) plus renal and extra-
Exclude post-renal renal failure renal losses
™ A renal ultrasound to rule out obstruction is mandatory ™ IWL = 300ml/m2/day (normally, IWL = 400ml/m2/day. There is
increased endogenous water production of 100ml/m2/day from
Fluid Challenge increased catabolism in uraemia)
™ Replace urine output with IV fluid solutions of approximately same
Child with intravascular depletion, composition
oliguria and azotaemia ™ Aim for daily weight loss of 1% of body weight during oliguric phase
of ARF. Weight gain or hyponatraemia during this phase indicative of
fluid overload
Normal saline or FFP ™ IV frusemide (1mg/kg) promotes renal blood flow during the early
20ml/kg over one hour stage

Electrolyte Management
Hyperkalaemia
™ Prompt treatment if T wave changes on ECG or K+ > 6.5mmol/l
Persistent oliguria ™ Monitor ECG
™ Drugs
Good urine output IV 8.4% sodium bicarbonate 1ml/kg over 15 minutes
IV 10% calcium gluconate 0.5ml/kg over five minutes
IV frusemide 2–5mg/kg
PO or PR resonium 0.5g/kg/dose (max 30g) six hourly
IV 50% dextrose 1ml/kg
Pre-renal renal failure IV 50% dextrose + 1ml/kg +
Persistent oliguria IV soluble insulin (when blood sugar is 0.1U/kg
> 14mmol/L)
Nebulised salbutamol
Established renal failure
426 The Baby Bear Book Nephrology 427

Hyponatraemia Indications
™ Results from fluid overload The indications are not specific and should be individualised. Guidelines:
™ If Na ≥ 120mmol/L, correct by restriction of free water ™ Oliguria/anuria
™ If Na < 120mmol/L or symptomatic, correct to 125mmol/L with ™ Serum creatinine > 590μmol/L
hypertonic saline ™ Plasma urea > 35mmol/L
Na+ deficit = 0.6 x Body Weight (kg) x [(Desired Na+) - (Actual Na+)] ™ Hyperkalaemia > 6.5mmol/L unresponsive to conservative treatment
Correct slowly, raising serum Na+ by not more than 1mmol/hr ™ Intractable metabolic acidosis (serum bicarbonate < 10mmol/L)
™ Pulmonary oedema unresponsive to conservative therapy
Metabolic Acidosis ™ Symptomatic uraemia — Encephalopathy, pericarditis (generally
™ Judicious use of sodium bicarbonate when urea > 50mmol/L)
™ Be mindful that bicarbonate replacement will increase CO2 tension ™ Toxins
and an intact respiratory system is needed to eliminate CO2
produced Modes of Dialysis in ARF
™ Be aware of Ca++ levels as correction of acidosis will cause shift from ™ Peritoneal dialysis
ionised to non-ionised form ™ Haemodialysis
™ Haemofiltration
Hyperphosphataemia and Hypocalcaemia
™ Hyperphosphataemia is managed by dietary phosphate restriction OUTCOME
and phosphate binders (calcium carbonate). Aluminium hydroxide is Three phases:
best avoided, but may be used in the short term ™ Oliguric phase — Lasts few days to to weeks
™ Calcium replacement may be initiated when phosphate levels are ™ Diuretic phase
lowered ™ Recovery phase — May last for months

Nutritional Management Mortality

™ Minimum of 25% of the daily caloric requirement is necessary to Dependent on cause. Overall about 30%, usually if coincident with
reduce ongoing catabolism multi-organ failure.
™ May require up to 25% dextrose, infused via central line
™ Protein is restricted to 1g/kg/day BIBLIOGRAPHY
1. Ministry of Health. A Guide to Paediatrics. Singapore: Ministry of Health; 1997.
2. Yip WCL, Tay JSH, editors. A practical manual on acute paediatrics. Singapore: P.G.
Hypertension Publishing; 1989.
See “Hypertension” p. 402. 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. 4th ed. Baltimore: Lippincott
Drugs Williams & Wilkins; 1999.
5. Chan JC, Williams DM, Roth KS. Kidney failure in infants and children. Pediatr Rev.
™ Minimise use of nephrotoxic drugs. If necessary, monitor drug levels 2002;23(2):47–60.
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.
428 The Baby Bear Book 429

PROTOCOL FOR RENAL BIOPSY

NEUROLOGY
PREPARATION
™ Ensure patient is well and BP is normal
™ Obtain consent CEREBRAL PALSY
™ Take blood for FBC, PT/PTT, GXM and others as ordered (PERINATAL ENCEPHALOPATHY)
™ Set IV cannula
™ Inform nephrologist on admission. If not available, inform registrar-
on-call to review DEFINITION
™ Arrange with radiologist for ultrasound-guided biopsy and A collection of non-progressive disorders that manifests as abnormalities
laboratory technician for preparation and microscopy of motion and posture, and result from a CNS injury sustained in the
™ Fast patient six hours before procedure early period of brain development, usually defined as the first three to
™ Premedications to be ordered two hours before procedure five years of life.
™ Send patient to ultrasound room 15 minutes before procedure,
accompanied by a doctor and a nurse. Prepare monitor machine, PREVALENCE
midazolam and flumazenil as necessary. Bring along properly filled ™ About two per 1,000 live births
histology form and ultrasound request forms ™ This has not decreased with time because of the following factors:
Š Large numbers are due to congenital brain malformations
POST-BIOPSY CARE Š Improved survival rate of low-birth-weight infants
™ Monitor pulse/respiration/BP: q15 minute x 4, q30 minute x 2, hourly ™ Of the subtypes, there has been a great decrease of choreo-athetoid
x 4, then twice-hourly thereafter cases because of marked decrease in incidence of kernicterus. The
™ Inform senior doctor if diastolic BP < 60mmHg or systolic BP < increase in diplegic cases is due to the increased survival rate of low-
80mmHg or pulse >120/min birth-weight babies
™ Patient to lie flat in bed overnight
™ To inform senior doctor if there is: CLASSIFICATION
Š Abdominal pain ™ Spastic:
Š Fever Š Quadriplegia
Š Persistent gross hematuria Š Diplegia
Š Vomiting Š Hemiplegia
™ Ensure adequate fluids. If patient is drowsy, give fluids in ™ Dyskinetic:
maintenance IV drip until awake and able to feed Š Choreo-athetosis with variable tone or rigidity/dystonia
™ On discharge, issue excuse from PE/sports for six months ™ Ataxic
™ Mixed

AETIOLOGY
™ Prenatal:
Š First trimester:
y Teratogens
y Genetic syndromes
y Chromosomal abnormalities
y Malformations of the brain
430 The Baby Bear Book Neurology 431

Š Second to third trimester: Š Physiotherapy, occupational therapy and speech therapy

y Problems in foetal/placental functioning ™ Orthopaedic non-surgical interventions:
y Intra-uterine infections Š Orthosis, serial casting, braces, splints, special chairs
™ Labour and delivery: ™ Orthopaedic surgical interventions:
Š Pre-eclampsia Š Tendon lengthening, tendon transfer, bony fusion
Š Complications of labour and delivery ™ Selective dorsal rhizotomy (spinal reflex arc is interrupted leading to
™ Perinatal: decrease of spasticity)
Š Asphyxia ™ Pharmacologic agents:
Š Sepsis/CNS infections Š Baclofen — Oral or intrathecal (increase of Gamma-aminobutyric
Š Prematurity Acid (GABA) leading to decrease of spasticity)
™ Postnatal: Š Botulinum Toxin A (Botox) — Intramuscularly (muscle tone is
Š Meningitis/encephalitis decreased by blocking neuromuscular transmission). Effects are
Š Traumatic brain injury dose-dependent and transitory, needing few doses
Š Toxins ™ Management of associated problems e.g. seizures/feeding problems/
special schooling
DIAGNOSIS
™ Detailed history of antenatal, perinatal and postnatal events BIBLIOGRAPHY
1. Campbell WM, Ferrel A, McLaughlin JF, Grant GA, Loeser JD, Graubert C, et al. Long-term
™ Ask about consanguinity, family history of similarly affected siblings safety and efficacy of continuous intrathecal baclofen. Dev Med and Child Neurology.
™ History of developmental delay 2002;44(10):660–665.
™ Do not rely on isolated abnormal signs but a combination of motor/ 2. Polak F, Morton R, Ward C, Wallace WA, Doderlein L, Siebel A. Double-blind comparison
study of two doses of botulinum toxin A injected into calf muscles in children with
mental delay, positive neurological signs, primitive reflexes and hemiplegic cerebral palsy. Dev Med and Child Neurology. 2002;44(8):551–555.
abnormal postural reactions 3. Baker R, Jasinski M, Maciag-Tymecka I, Michalowska-Mrozek J, Bonikowski M, Carr L, et al.
Botulinum toxin treatment of spasticity in diplegic cerebral palsy: A randomized, double-
™ Serial examinations may be required, especially in early infancy blind, placebo-controlled, dose-ranging study. Dev Med Child Neurol. 2002;44(10):666–
675.
4. McLaughlin J, Bjornson K, Temkin N, Steinbok P, Wright V, Reiner A, et al. Selective dorsal
Differential Diagnosis rhizotomy: Meta-analysis of three randomized controlled trials. Dev Med and Child
™ Neurodegenerative disorders Neurology. 2002;44(1):17–25.
™ Lesions of the spinal cord
™ Neuromuscular disorders
™ Mental retardation

Clinical Examination EPILEPSY

Look out for:
™ Dysmorphism
™ Microcephaly or macrocephaly DEFINITION
™ Abnormalities of CNS — Abnormalities of muscle tone, choreo- Epilepsy is a neurological condition characterised by a tendency to
athetosis, dystonia, persistence of primitive reflexes, contractures recurrent seizures. Seizures are manifestations of abnormal excessive
™ Degree of mental and physical disabilities discharges of a set of cerebral neurons. The clinical manifestations
of seizures are sudden and transient. They include a wide variety of
MANAGEMENT motor, psychic and sensory phenomena, with or without alteration of
Refer to Neurology Specialist Clinic where structured programmes will consciousness.
be planned:
™ Rehabilitative therapy
432 The Baby Bear Book Neurology 433

Status Epilepticus (SE) is defined as > 30 minutes of a continuous ŠMeningitis/encephalitis

seizure activity or ≥ two sequential seizures without full recovery of ŠTumours
consciousness. Debate continues about the duration of time used to ŠStroke
define the condition, with some suggestions of a shorter length of time ŠCerebral degeneration
of ten minutes. ŠToxins/metabolic dysfunction/IEM
™ Cryptogenic — Symptomatic with lack of clear aetiology
Provoked seizures (acute symptomatic seizures) are seizures that have
an obvious and immediate preceding cause (e.g. an acute systemic, EVALUATION
metabolic or toxic intake) or an acute cerebral event. These seizures are ™ Determine whether patient does or does not have seizures (seizures
often isolated events and do not recur when the cause is removed. vs non-seizures)
™ Determine the seizure type or syndrome
PREVALENCE ™ Determine aetiology where possible
4.3–9.3 in 1,000. ™ Assess co-morbidity
™ Formulate a management plan
CLASSIFICATION OF EPILEPTIC SEIZURES
Epileptic seizures are classified into two main types by the International Diagnosis is based almost exclusively on a clinical history of two or more
Classification of Epilepsies and Epilepsy Syndromes: unprovoked seizures.
™ Careful and detailed history:
™ Generalised Seizures — The entire cortex demonstrates Š Seizure or non-seizure
simultaneous synchronous epileptic discharges Š Clear description of seizure episode, circumstances, precipitants,
Š Absence seizures — Brief loss of awareness, accompanied by frequency of attacks, symptoms before and during the
eyelid fluttering, lip-smacking or chewing movements attacks (including physical symptoms, psychic symptoms and
Š Myoclonic seizures — Sudden, jerky contraction movements of impairment of consciousness), duration of symptoms, symptoms
different muscles of the body, usually the arms or legs following the attack, incontinence
Š Atonic seizures — Sudden loss of muscle tone resulting in a fall Š Past medical history, including head injury, medications
Š Tonic seizures — Sudden stiffness of the limbs or the whole body, Š Developmental history
leading to a fall Š Social history
Š Clonic seizures — Repeated rhythmic contractions of the Š Family history
muscles, causing jerks or twitches of the limbs, body ™ Neurological and physical examination
Š Tonic-clonic seizures — A tonic stage followed by a clonic stage ™ Diagnostic studies:
™ Partial Seizures — Abnormal electrical activity starts in one cerebral Š Electroencephalography (EEG):
hemisphere or in one lobe of one hemisphere y Value: Confirming abnormal electrical activity and syndromic
Š Simple partial seizure — Level of consciousness or awareness is classification
unaffected during the seizure. Strange smell or taste, unexplained y Limitations:
fear, déjà vu, tingling/numbness ƒ Non-specific
Š Complex partial seizure — Consciousness is affected ƒ Interpretation requires special knowledge and experience
ƒ Easily affected by drugs, toxic or metabolic changes
AETIOLOGY ƒ Does not elucidate cause
™ Idiopathic y EEG cannot be used to make the diagnosis of epilepsy unless
™ Symptomatic — Underlying brain pathology an actual seizure is recorded
Š Hypoxia/trauma y As many as 40% of children with epilepsy never demonstrate
Š Malformations abnormalities on inter-ictal EEG
434 The Baby Bear Book Neurology 435

y A small percentage of normal children will have epileptiform Š Normal neurologic examination
activity on EEG but never have a seizure Š Resolution of inter-ictal EEG spike discharges
Š Brain imaging: ™ Children with the syndrome of Benign Epilepsy with Centro-temporal
y Indicated in: Spikes (BECTS) virtually always outgrow their seizures. Some epilepsy
ƒ Focal epilepsies syndromes like juvenile myoclonic epilepsy are characterised by life-
ƒ Neurological deficits long seizures
ƒ Suspicion of raised ICP
ƒ Exclusion of structural or developmental lesions Other Treatment Modalities
ƒ Severe seizures, worsening seizures ™ Surgery:
ƒ Young age ŠCortical resection e.g. lesionectomy, corticetomy, lobectomy
y Unnecessary if a firm diagnosis of idiopathic generalised ŠMultilobar resection
epilepsy is made ŠHemispherectomy
Š Laboratory tests, LP as indicated ŠCorpus callostomy
ŠMultiple subpial transection
TREATMENT ŠStereotactic radiosurgery
Aim of treatment is to reduce seizures while preserving patient’s quality ™ Special diets e.g. ketogenic diet
of life. ™ Brain stimulation e.g. vagal nerve stimulation
™ Establish firm diagnosis of epilepsy before starting treatment ™ Immunological treatments e.g. prednisolone, hydrocortisone, ACTH,
™ Take into account seizure type, severity, risk of recurrence, epilepsy gammaglobulin
syndrome, aetiology, associated morbidity, precipitating factors
™ Mainstay of treatment — Anti-epileptic Drugs (AEDs) WHEN TO SEEK NEUROLOGIC CONSULTATION
™ Status epilepticus
Indications to treat: ™ Refractory seizures
™ Recurrent seizures, severity, epilepsy syndrome ™ Multiple seizure types
™ Presence of risk factors ™ Change in type of seizures
™ Accompanying neurological, psychosocial problems ™ Neurological deficits
™ Doubts about diagnosis
Initiate treatment with monotherapy using appropriate medication,
beginning with low doses titrating up to a maintenance dose INTERNATIONAL CLASSIFICATION OF THE EPILEPSIES AND
™ Balance between drug efficacy and tolerability EPILEPSY SYNDROMES
™ Holistic approach — Psychosocial management and epilepsy The International League Against Epilepsy (ILAE) in 1989 revised a
support important classification of Epilepsies and Epileptic Syndromes encompassing
seizure types, anatomic localisation, EEG characteristics, findings on
Duration of Therapy examination and epidemiologic data. The classification acknowledges
™ The decision about duration of treatment must be individualised the complex interplay of factors underlying epilepsy, allowing for
™ Generally one to two years, however, the duration of treatment improved understanding of clinical course and prognosis.
ultimately depends on the syndrome diagnosis and therapeutic
response An epileptic syndrome is defined as an epileptic disorder characterised
™ About 70% of children with epilepsy who have become seizure-free by a cluster of signs and symptoms customarily occurring together.
for two years can successfully stop treatment Some syndromes represent a single disease, whereas others can be the
™ Factors that predict successful discontinuation of medication: result of many diseases, e.g. the Lennox-Gastaut Syndrome.
Š Generalised seizures
436 The Baby Bear Book
Table 11-1: ILAE classification of epilepsies and epilepsy syndromes.
™ Generalised
Idiopathic generalised epilepsies with
age-related onset (in order of age):
Benign neonatal familial convulsions
Benign neonatal convulsions
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Epilepsy with generalised tonic-clonic
seizures on awakening
Other generalised idiopathic epilepsies
not defined above
Epilepsies with seizures precipitated by
specific modes of activation
Cryptogenic or symptomatic generalised
epilepsies (in order of age):
West Syndrome
Lennox-Gastaut Syndrome
Epilepsy with myoclonic-astatic
seizures
Epilepsy with myoclonic absences
Symptomatic generalised epilepsies:
Non-specific aetiology
Early myoclonic encephalopathies
Early infantile encephalopathy with
burst suppression
Other symptomatic epilepsies not
defined above
Specific syndromes
Epilepsies in other disease states
™ Localisation-related
Localisation-related epilepsies —
Idiopathic with age-related onset:
Benign epilepsy with centrotemporal
spikes
Childhood epilepsy with occipital
paroxysms
Primary reading epilepsy
Localisation-related epilepsies —
Symptomatic:
Epilepsia partialis continua
Syndromes characterised by specific
modes
of precipitation
Temporal lobe epilepsies
Central region epilepsies
Frontal lobe epilepsies
Parietal lobe epilepsies
Occipital lobe epilepsies
Localisation-related epilepsies —
Cryptogenic:
Electrical status epilepticus in slow
wave sleep
Acquired epileptic aphasia
Other undetermined epilepsies (not
defined above) with unequivocal
generalised or focal features
™ Epilepsies and syndromes undetermined as
to whether focal or generalised
With both generalised and focal seizures
Neonatal seizures
Severe myoclonic epilepsy in infancy
™ Special syndromes
Febrile convulsions
Isolated seizures or isolated status
epilepticus
Seizures occurring only when there is
an acute metabolic or toxic event
caused by factors such as alcohol,
drugs, eclampsia, non-ketotic
hyperglycinaemia
Neurology 437
IMPORTANT PAEDIATRIC EPILEPSIES AND EPILEPSY
SYNDROMES
Infantile Spasms (West Syndrome)
™ A devastating seizure disorder of childhood
™ Incidence: 1-in-4,000 to 1-in-6,000 live births
™ Peak frequency: Four to six months of age
™ Seizures characterised by flexor or extensor myoclonic jerks,
occurring in clusters after sleep or a nap
™ EEG demonstrates a hypsarrhythmic pattern
™ Aetiology:
Š Idiopathic (< 5%)
Š Symptomatic:
y Disorders of cerebral development:
ƒ Neuronal migrational and other developmental
defects — Heterotopia, agyria-pachygyria, agenesis of
the corpus callosum, dysplasia, hemimegalencephaly,
holoprosencephaly, microcephaly, macrocephaly,
porencephaly, schizencephaly
ƒ Neurocutaneous syndromes — Tuberous sclerosis,
Sturge-Weber Syndrome, neurofibromatosis, incontinentia
pigmenti and linear naevus syndrome
y Metabolic and degenerative disorders:
ƒ Metabolic disorders — Phenylketonuria, non-ketotic
hyperglycinaemia, pyridoxine deficiency, Leigh’s Disease,
histidinaemia, hyperornithinaemia, hyperammonaemia,
homocitrullinaemia, maplesyrup urine disease
ƒ Degenerative disorders of uncertain aetiology —
Leucodystrophies, Alpers’ Disease, Sandhoff Disease, Tay-
Sachs Disease
y Perinatal or postnatal chronic acquired cerebral lesions:
ƒ Hypoxic-ischaemic encephalopathy and cerebral infarction
ƒ Cerebral trauma
ƒ Cerebral tumour
ƒ Maternal toxaemia
ƒ Metabolic and endocrine disorders
y Infantile spasms evolving from neonatal seizure syndromes
e.g. Ohtahara’s Syndrome or neonatal myoclonic
encephalopathy
™ Prognosis: Generally poor in symptomatic infantile spasms. More
than 90% have an intractable seizure disorder and major cognitive
impairments. A much smaller group of children with infantile spasms
438 The Baby Bear Book
who have probable idiopathic disease have normal development
before the onset of the infantile spasms, no serious developmental
deterioration with the onset of disease, and a good response to
treatment with no apparent neurologic sequelae
™ Treatment:
Š Corticosteroids or ACTH
y The mechanism of action of ACTH and corticosteroids remains
unclear
y These drugs alter the CNS concentrations of various biogenic
amines and increase GABA receptor affinity
y The reported efficacy rates vary considerably
Š Other drugs — Benzodiazepines, valproate, pyridoxine and
vigabatrin
Š Surgical treatment for underlying focal cortical dysplasias
Lennox-Gastaut Syndrome
™ Age of onset one to 14 years
™ Severe epileptic disorder with multiple seizure types, including
myoclonic, atypical absence, tonic and tonic-clonic seizures
™ EEGs characterised by diffuse, slow spike-and-wave 1–2.5 Hz
complexes superimposed over an abnormally slow background
™ Seizure precipitated by drowsiness, not by hyperventilation or photic
stimulation
™ Status epilepticus common, especially non-convulsive forms
™ Diffuse and severe cognitive impairments, learning disability
™ Aetiology: Many causes, about 25% are cryptogenic
™ Prognosis for seizure control and mental development poor
™ Treatment: Anti-epileptic medications include valproate,
benzodiazepines, topiramate and lamotrigine
Benign Rolandic Epilepsy
™ 15% of all childhood epilepsy; age of onset five to10 years
™ Simple partial seizures with secondary generalisation. Partial seizures
involve the face, oropharynx and upper limb
™ Seizures are typically during sleep and infrequent
™ No other neurological features; normal intelligence
™ Might have positive family history
™ EEG shows typical centrotemporal spikes
™ Excellent response to antiepileptic drugs
™ Excellent prognosis with remission by mid-teenage years
Neurology 439
Childhood Absence Epilepsy
™ Manifests in school-age children with a peak age of six to seven
years, accounting for 2–8% of all cases of epilepsy
™ Strong hereditary predisposition, 15–44% of first-degree relatives
have either seizures or paroxysmal EEG abnormalities
™ Normal neurologic examination
™ Absence seizures characterised by brief episodes (less than five
to ten seconds) of staring in conjunction with unresponsiveness,
sometimes associated with eyelid fluttering, automatisms, mild
clonic movement of the upper extremities, atonic features or tonic
components
™ Seizures not associated with a postictal phase and can be induced by
hyperventilation
Juvenile Absence Epilepsy
™ Many similarities to childhood absence epilepsy, as well as some
important differences
™ Genetically, it may be one of several phenotypic expressions for a
gene coding for primary generalised epilepsy syndromes
™ Absence seizures begin near or after puberty (in patients ten to 17
years old)
™ Generalised tonic-clonic seizures occur in almost 80%
™ Valproate is the drug of choice
™ Usually, the seizures are readily controlled, but the prognosis is not
clearly known. Remission is probably less likely than in childhood
absence epilepsy
Juvenile Myoclonic Epilepsy (JME)
™ A generalised epilepsy with a strong family history, mode of
inheritance probably multifactorial. Gene locus believed to be on the
short arm of chromosome 6
™ Characteristic early-morning sudden myoclonic jerks, generalised
tonic-clonic seizures. 33% have absence seizures
™ Onset typically in adolescence (range 12–18 years)
™ Interictal EEG: Generalised polyspike and spike-and-wave discharges
at 4–6 Hz
™ Valproate successfully controls seizures
440 The Baby Bear Book Neurology 441

Benign Neonatal Familial Convulsions Ensure ABCs

™ Seizures begin on second or third day of life — Clonic or apnoeic Check glucose, U&E, Ca, Mg
seizures multiple times per day If glucose < 3mmol/L, give 5ml/kg 10% dextrose IV
™ Self-limiting, remit by one to six months, prognosis for psychomotor
development good
™ Positive family history IV access No IV access
™ Gene identified on the long arm of chromosome 20
™ In approximately 10–14% of patients, epilepsy develops during
childhood or adulthood
Diazepam 0.25mg/kg IV
SUMMARY Max dose 10mg/dose Diazepam 0.4mg/kg PR
The successful management of epilepsy requires a holistic approach or Max dose 10mg/dose
Lorazepam 0.1mg/kg IV
beginning with a thorough and individualised evaluation to establish
Max dose 4mg/dose
the patient’s seizure type(s) and possible epilepsy syndrome. Selection Five minutes
of therapy (pharmacologic and nonpharmacologic) should be rational
and tailored to the child’s epilepsy condition. The impact of epilepsy Five minutes
on psychosocial functioning must be borne in mind and adequately IV access No IV access
addressed.
Repeat dose x one
BIBLIOGRAPHY Diazepam 0.4mg/kg PR
1. Zupanc ML. Update on epilepsy in pediatric patients. Mayo Clin Proc. 1996;71(9):899–916. Max dose 10mg/dose
2. Commission on Classification and Terminology of the International League Against
Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes.
Epilepsia. 1989;30(4):389–399.
Phenytoin† 20mg/kg IV over 20 minutes
• Give neat
• Infusion rate: Max 1mg/kg/min
• Max dose 1500mg
• Monitor ECG and BP
MANAGEMENT OF STATUS EPILEPTICUS • Avoid in patients already on phenytoin

Status epilepticus is a neurological emergency. It is defined as a

continuous seizure lasting > 30 minutes, or acute repetitive seizures
without return of consciousness inter-ictally for > 30 minutes. Recent Phenobarbitone 20mg/kg IV over 20–30 minutes
studies show that most unprovoked seizures abort spontaneously • Dilute with normal saline
within the first five to ten minutes, after which the risk of a prolonged • Infusion rate: Max 1mg/kg/min
• Monitor BP
seizure will be high.

Fig. 11.1 next page outlines the clinical pathway for the management of
status epilepticus. Transfer to CICU for anaesthesia under EEG monitoring

†
Under one month of age, use phenobarbitone first rather than phenytoin.

Fig. 11.1: Clinical pathway for the management of status epilepticus.

442 The Baby Bear Book Neurology 443

Table 11-2: The differential diagnosis for the various headache syndromes.
HEADACHE DISORDERS
Acute Severe Recurrent Chronic
Chronic Progressive
Headache is a common disorder in children. The prevalence of headache Headache Paroxysmal Non-progressive
Headache
increases from between 37–51% in preschoolers to between 57–82% in Headache Headache
adolescents. In general, headache disorders can be divided into primary Viral fever Migraine Brain tumour Chronic tension
and secondary. Migraine Tension headache Hydrocephalus headache
Tension headache Epileptic seizure Pseudotumour cerebri Post-traumatic/
Meningitis Cluster headache Brain abscess concussion
INTERNATIONAL HEADACHE SOCIETY CLASSIFICATION OF Concussion Chronic subdural headache
HEADACHES (1988) Epileptic seizure haematoma Transformed migraine
Primary headache disorders: Posterior fossa Vascular Medication overuse
™ Migraine tumour malformation New daily persistent
™ Tension headache Ventriculoperitoneal Vasculitis headache
™ Cluster headache shunt malfunction
Intracranial
™ Miscellaneous headache not associated with structural lesions
hemorrhage
Undetermined
Secondary headache disorders:
™ Associated with trauma
™ Associated with vascular malformation
™ Associated with non-vascular intracranial malformation HISTORY
™ Associated with substances or their withdrawal ™ Nature of headache:
™ Associated with non-cephalic infection Š Single or multiple types of headache
™ Associated with metabolic disorder Š Site, quality
™ Or facial pain associated with disorders of the cranium, neck, eyes, Š Onset, progression, frequency, duration
ears, nose, sinuses, teeth, mouth or other facial or cranial structures Š Precipitating, relieving or aggravating factors
™ Cranial neuralgia, nerve trunk pain and deafferentiation pain Š Associated symptoms e.g. aura, nausea, vomiting
™ Not classifiable Š “Do you stop what you are doing during a headache?”
™ Response to treatment
The onus on the physician is to rule out secondary causes of headache ™ Frequency of ingestion of oral analgesia
that may be potentially life-threatening, and to recognise the presence ™ Symptoms between headaches e.g. weakness, ataxia
of primary headache disorders so that appropriate treatment can be ™ Symptoms of raised ICP
prescribed. ™ Focal neurological signs/symptoms e.g. visual hallucination, vertigo,
hemiparesis, numbness of the mouth and extremities
HEADACHE SYNDROMIC DIAGNOSIS BASED ON ™ Social history pertaining to possible stressors (either at home or in
TEMPORAL PROFILES school)
Sometimes, it may be helpful to classify headache disorders into ™ Past medical history and family history
syndromes based on the temporal profile of their occurrence: ™ Systemic reviews:
™ Acute severe headache Š Polyuria/polydipsia
™ Recurrent paroxysmal headache Š Loss of weight and appetite
™ Chronic progressive headache Š Symptoms of obstructive sleep apnoea or poor sleep hygiene
™ Chronic non-progressive headache

The differential diagnosis is listed in Table 11-2 next page.

444 The Baby Bear Book Neurology 445

CLINICAL EXAMINATION ™ Investigations that may be helpful are imaging studies (either CT or
™ Vital signs (BP, temperature, pulse rate): MRI) and LP
Š Especially in the setting of acute severe headache ™ In view of the cost, CT head is sufficient in most cases unless
Š Hypertensive encephalopathy may be associated with a triad of pathologies of the posterior cranial fossa or white matter disorders
headache, seizures and visual impairment are suspected
Š Raised ICP may be associated with hypertension and bradycardia, ™ EEG is not helpful in the diagnosis of headache, unless it is unclear
especially if the mental status of the patient is deteriorating whether the symptoms are migrainous or related to complex partial
™ Signs of papilloedema, anisocoria (due to oculomotor nerve palsy) seizures
and decorticate/decerebrate posturing
™ Nuchal rigidity RELATIONSHIP BETWEEN BRAIN TUMOUR AND HEADACHE
™ Sinus tenderness It may be difficult to differentiate headache secondary to brain tumour
™ Head circumference (especially in toddlers) from benign headache at times. The location, quality and frequency of
™ Neurocutaneous stigmata headache are not diagnostic of a particular headache. There is some
™ Complete neurological evaluation and general systemic examination overlap in the symptomatology of headache secondary to brain tumour,
™ Extraocular movement, pupil size, fundoscopy, pronator drift, migraine and tension headache. In children with headache secondary
cerebellar signs (dysmetria, dysdiadochokinesia, ataxia), motor to brain tumour, the triad of headache, vomiting and papilloedema
power need to be checked thoroughly was only present in about 31% of cases, and progressive headache with
™ Always remember to walk the patient and examine the gait worsening in the morning and associated nausea was only seen in 17%
of cases.
WARNING SIGNS AND SYMPTOMS
One should have a lower threshold for imaging studies if these signs and Nevertheless, it is important to keep in perspective that headache is
symptoms are present: rarely an isolated symptom (< 1%) in brain tumours. There are usually
™ First and worst headache concomitant symptoms such as deteriorating school performance,
™ Signs and symptoms of raised ICP difficult walking, bladder symptoms and FTT. Other warning symptoms
™ Aggravation by valsalva maneouver are that of increasing severity or frequency of headache or increasing
™ Abnormal neurological findings frequency of vomiting. In 96% of cases, diagnostic clues appeared within
™ Papilloedema the four months after onset of headache.
™ Chronic progressive headache, with change in behaviour and
deteriorating academic performance As a general rule, if the headache has been there for > four to six
™ Early-morning vomiting months, in the setting of normal physical examination and the absence
™ Headache waking up patient from sleep of warning signs and symptoms as elaborated above, it is unlikely to
™ Immunosuppressed patients be due to a brain tumour. Children with suspected frequent severe
™ Neurocutaneous syndromes migraine may need to be reviewed carefully if they fail to respond to
™ Age < four years preventive therapy. An imaging study may be warranted then to rule out
secondary causes of headache.
INVESTIGATIONS
™ Most children who present to the emergency room with surgically MEDICATION OVERUSE HEADACHE
remediable conditions have clear and objective neurological signs This is a common problem in adults with chronic daily headache.
and symptoms The refractory headache arises as a result of frequent and excessive
™ Generally, routine blood investigations are not helpful in the use of symptomatic analgesia. As a general rule, regular analgesia
diagnosis of headache disorders should not be consumed for > five days per week. The nature of the
headache resembles that of tension and migraine headaches, typically
446 The Baby Bear Book Neurology 447

with worsening in the early morning when the effect of the analgesia y Dandy Walker Malformation
wears off. The headache will only improve after discontinuation of y Vein of Galen Malformation/aneurysm
the analgesia. However, there may be a wash-out period of eight to y Neoplasm, supratentorial or infratentorial
12 weeks, during which withdrawal-headache-associated nausea, Š Communicating:
abdominal cramps, diarrhoea, restlessness, sleeplessness and mental y Arachnoid cyst
anguish may occur. A short course of amitriptyline may be of help y Meningeal fibrosis or obstruction secondary to haemorrhage,
during this period. inflammation
y AVM
y Intracranial haemorrhage
y Choroid plexus papilloma
y Neurocutaneous syndromes, e.g. incontinentia pigmenti
MICROCEPHALY AND MEGALOCEPHALY y Hydranencephaly
y Porencephaly
All babies should have their OFC measured at birth and then routinely y Familial-AD, AR, XLR
as part of the child health surveillance at one, three, six, nine, 15 and ™ Megalencephaly:
18 months and then at three years of age. Any deviation from the Š Anatomic e.g. Sotos, familial asymptomatic, and symptomatic
expected head size and shape should prompt a thorough assessment to familial anatomic megalencephaly
determine the cause. Š Metabolic e.g. Alexander’s Disease, Canavan’s Disease, lysosomal
diseases
HOW TO MEASURE THE OCCIPITO-FRONTAL ™ Subdural fluid collection:
CIRCUMFERENCE (OFC) Š Haematomas
™ Extend a non-stretchable measuring tape laterally around the head Š Hygromas
from the occiput to the glabella over the eyebrows and record the Š Empyema
measurement Š Benign enlargement of subarachnoid space. Familial in origin,
™ Take an average of three measurements and plot it on a standardised males > females, neurological and developmentally normal child.
OFC chart according to age and sex OFC 90th centile at birth and can progress to > 97th centile but
™ The expansion of the skull by the growing brain produces the parallels the normal curve. CT head shows an enlarged frontal
standard OFC growth curve subarachnoid space, widening of the sylvian fissures and other sulci
™ During the first year, the OFC increases at an average rate of about with normal or minimally enlarged ventricular size. Management is
1cm per month to observe and if child develops normally, no need for shunts
™ Growth occurs most rapidly in the first six months ™ Cerebral oedema (chronic):
Š Toxins — Lead, vitamin A, tetracycline
APPROACH TO MEGALOCEPHALY Š Endocrine — Hypoparathyroidism, hypoadrenocorticism
Megalocephaly or macrocephaly describes an OFC that exceeds the Š Galactosaemia
97th percentile for the child’s age and gender. Megalocephaly may be Š Spongy degeneration of the brain
present at birth or a result of accelerated head growth postnatally. Š Pseudotumour cerebri
™ Thick skull or scalp:
Causes of Megalocephaly Š Familial
™ Hydrocephalus: Š Anaemia
Š Noncommunicating: Š Myotonia dystrophica
y Arnold-Chiari Malformation Š Cranioskeletal dysplasias e.g. rickets, osteopetrosis, osteogenesis
y Aqueductal stenosis imperfecta
448 The Baby Bear Book Neurology 449

History ™ Treat for any complications:

™ Details of antenatal history
™ Any birth trauma e.g. dystocia
™ Family history of hydrocephalus, mental retardation, IEM
™ Any significant past history e.g. meningitis, neoplasm, haemorrhage,
head injuries
™ Any symptoms of raised ICP such as early-morning headache,
vomiting, poor feeding and irritability with disturbed sleep pattern
™ Developmental history and any regression of milestones. Regression
indicates an ongoing active pathologic process rather than a static
one
Š Antiepileptic drugs for seizures
Š Rehabilitation for developmental delay
Š Special schooling
APPROACH TO MICROCEPHALY
Microcephaly is defined as the OFC being less than the third percentile
for the child’s age and gender. In most cases, the brain is small and
not well-formed. This can occur as a result of genetic or chromosomal
abnormality — primary microcephaly; or the brain forming normally but
a disease process impairing further growth — secondary microcephaly.

Examination Pathogenesis and Aetiology

™ Measure and plot the OFC of the child ™ Microcephaly vera — Genetic (AD, AR or XLR) or familial
™ Measure and plot the OFC of parents and siblings ™ Malformative microcephaly — Disorders of cytogenesis, macro/
™ Examine child’s head shape and feel all sutures and fontanelles. micro gyria, neuronal migration disturbances. The cause is usually
Examine the anterior fontanelle with child relaxed and in an upright genetic, teratogenic or infectious
posture. In infants and toddlers, increased ICP causes a convex ™ Destructive microcephaly — Normally developing brain that
bulging contour of the fontanelle and splaying of the sutures suffered a prenatal or perinatal insult. This results from inflammation,
™ Examine for other signs of raised ICP such as dilated scalp veins, sun- infection, anoxia, birth trauma or an exogenous teratogen
setting eyes ™ Malnutrition — Maternal, fetal or neonatal; most common cause of
™ Check pupillary reactions and perform fundoscopy to look for microcephaly worldwide
papilloedema ™ Most important differential of microcephaly is craniosynostosis and
™ Look for dysmorphic features abnormal head shape
™ Do a full neurological examination to look for impaired ocular
movements, ataxia and focal neurological deficits Common Causes of Microcephaly
™ Perform a developmental assessment appropriate for age ™ Infections:
™ Examine parents and siblings for any neurocutaneous stigmata Š Intrauterine infections (TORCH) — Toxoplasmosis, rubella, CMV,
herpes simplex
Investigations Š Varicella
™ Perform only if indicated — OFC crossing centiles, focal neurological Š Coxsackie B
deficits, raised ICP or development regression/delay Š Syphilis
™ CT head will suffice to look for gross pathology but MRI is the Š HIV
imaging modality of choice to look for white matter disease and ™ Drugs:
posterior fossa lesions Š Alcohol
™ Screen for any metabolic disorders that may cause megalocephaly Š Tobacco
Š Heroin
Management is Dependent on Cause Š Maternal ingestion of anti-cancer and anti-epileptic medications
™ Emergency management of acute raised ICP ™ Anoxia/ischaemia:
™ Refer to neurosurgery for drainage of hydrocephalus Š Generalised cerebral anoxia
™ Treat any potential treatable causes Š Post-status epilepticus
Š Placental insufficiency
450 The Baby Bear Book Neurology 451

™ Hereditary: ™ Examine the head of the child noting the shape, suture lines and
Š Asymptomatic (normal variant) familial microcephaly fontanelle. Sutures close earlier than normal in microcephaly but do
Š Mendelian pattern (AD, AR, XLR) symptomatic microcephaly not cause abnormal ridges
Š Craniosynostosis ™ Examine for any signs of craniosynostosis e.g. abnormal head shape,
Š Hereditary familial degenerative diseases e.g. neuronal ceroid ridging of suture lines and fusion, hypertelorism, syndactyly and
lipofuscinosis (Batten’s Disease) polydactyly
Š Amino and organic acidurias ™ Perform a full neurological examination
™ Syndromes/chromosomal abnormality: ™ Assess developmental age
Š Trisomies 21, 13, 18
Š Ring chromosomes, deletions Investigations
Š Miscellaneous syndromes mostly associated with dwarfism e.g. Neonates
Rubinstein-Taybi, Dubowitz, Smith-Lemli-Opitz ™ Screen for prenatal and perinatal infections:
™ Malformations: Š Toxoplasma serology IgM and IgG
Š Microcephaly vera Š Urine for CMV
Š Lissencephaly Š Rubella IgM and IgG
Š Holoprosencephaly Š HSV IgM and IgG
Š Encephalocele Š VDRL, FTA-IgM
™ Trauma: Š HIV PCR/culture
Š Post-shaken baby syndrome Š EV PCR
Š Post-birth trauma ™ Skull X-ray and/or CT head if craniosynostosis suspected
™ Perinatal metabolic/endocrine imbalances: ™ Cranial ultrasound to look for gross intracranial abnormalities and
Š Hypoglycaemia haemorrhages
Š Hypothyroidism ™ Chromosome cultures
Š Hypopituitarism
Š Hypoadrenocorticism Infants and Above
™ Malnutrition ™ To investigate as above if indicated
™ Antenatal maternal systemic illness ™ Screen blood and urine for IEM if indicated:
™ Familial small head Š Urine for organic acids
Š Serum for amino acids, ammonia, lactate and pyruvate
History Š Blood for phenylketonuria (rare in Singapore)
™ Antenatal and birth history including mother’s lifestyle e.g. nutrition, Š TFTs
drug ingestion, alcohol abuse ™ MRI to look for lesions of gray and white matter, abnormalities of
™ Neonatal history neuronal migration, sulcation and gyration and to reveal the pattern
™ Family history of microcephaly, mental retardation of myelin deposition and demyelination
™ Any past illness of significance e.g. meningitis
™ Any injuries of significance e.g. shaken baby syndrome Management
™ Developmental history e.g. delay, regression ™ Treat any treatable cause e.g. infections, hypothyroidism
™ Consider referral to plastic surgeon for craniosynostosis
Examination ™ Genetic counseling and prevention of microcephaly in subsequent
™ Measure and plot OFC of child along with height and weight children
™ Measure and plot OFC of parents and siblings ™ Monitor child for developmental delay and seizures
™ Note any dysmorphic features
452
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 more than 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 < two years old 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 < 2 years old with ‘boggy’ scalp haematoma
™ Suspected child abuse
CT head is the procedure of choice for assessment of acute head
injury in children. 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
Paediatric Surgery 453
Management of Minor Head injury (GCS 14–15)
™ Two hourly neurological observations for six hours, then reduce
frequency if stable
™ IV drip if child is dehydrated as a result of vomiting
™ Analgesic (paracetamol) if indicated
™ CT head if child deteriorates clinically
Management of Moderate Head Injury (GCS 9–13)
™ Resuscitate if necessary
™ Urgent CT head
™ Admit to CICU or HD, depending on clinical status
™ Hourly neurological observations
™ Nil orally, IV drip
™ Neurosurgical operation where indicated
Management of Severe Head Injury (GCS 8 and below)
™ Resuscitate — Intubation and ventilation mandatory
™ Urgent CT head
™ To OT directly for neurosurgical operation if indicated, or to CICU (ICP
monitoring indicated)
™ Manage according to severe head injury protocol
™ 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
™ 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 distort or disrupt part of the
nervous system e.g. intracranial hemorrhage, 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
454 The Baby Bear Book Paediatric Surgery 455

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 hemorrhage — 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):
Š Classical triad of loss of consciousness, unilateral pupillary
inequality (anisocoria) and contra-lateral hemiparesis
Š Seen for example, in extradural haematoma involving temporal
region
™ Cerebellotonsillar herniation:
Š Seen in rapidly expanding cerebellar mass lesion, e.g.
spontaneous cerebellar haemorrhage, or haemorrhage into a
medulloblastoma
Š Increasing drowsiness and sudden respiratory arrest are
presenting symptoms
Management of Brain Herniation Syndromes
™ Resuscitate ABCs — Intubation and ventilation if GCS ≤ 8
™ Hyperventilation
™ IV mannitol
™ Urgent CT head to determine cause
™ Surgical management of cause
™ Monitoring in CICU
sudden neurological deterioration and the diagnosis must be suspected
early and confirmed by clinical and radiological exams.
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
Surgical treatment
™ Ventriculostomy (EVD)
™ Shunt
™ Revise shunt (in shunted child)
™ 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

ACUTE HYDROCEPHALUS Investigations

Hydrocephalus is the result of an imbalance in CSF production and ™ CT scan (old films may be required for comparison)
resorption. The time course of ventricular enlargement is usually hours. ™ Shunt X-ray series
There must be clinical signs or evidence of raised ICP. Obstruction of CSF ™ Shunt flow studies
pathways with concomitant development of hydrocephalus can lead to ™ Shunt tapping
456 The Baby Bear Book Paediatric Surgery 457

Treatment SPINAL INJURIES

™ IV mannitol (to consult neurosurgeon before giving) ™ Traumatic spinal injury
™ Shunt tapping to release CSF (possible only if blockage is in distal ™ Spinal Cord Injury Without Radiologic Abnormality (SCIWORA)
end of shunt) ™ Spinal cord compression from epidural (extradural) masses
™ Urgent revision of shunt ™ Intraspinal hemorrhage (tumour, AVM, AV fistula)
™ Spinal infections
Child with Ventriculoperitoneal (VP) Shunt and Acute
Abdomen Management
™ Inform neurosurgeon ™ Spinal nursing if instability suspected
™ The shunt may need to be externalised even if no surgery is ™ IV dexamethasone or methylprednisolone where indicated
indicated for the acute abdomen ™ Urgent MRI
™ If laparotomy is required, externalisation of shunt can be done at the ™ Surgical decompression where indicated
same setting ™ Surgical stabilisation where indicated

SPONTANEOUS INTRACEREBRAL HAEMATOMA IN

CHILDREN
Causes
™ AVM rupture THE ACUTE ABDOMEN
™ Haemorrhage into tumour
™ Coagulopathy e.g. haemophilia
™ Vasculopathy — Moya-moya Disease, vasculitis INTRODUCTION
™ Post-operative haemorrhage Patients with acute abdominal conditions account for one-third to
™ Aneurysmal subarachnoid haemorrhage half the emergency admissions to Paediatric Surgery. While not meant
to be exhaustive, this chapter will enable you to assess and manage
Management appropriately the most common conditions.
™ Resuscitate as for mass lesion (see “Brain Herniation Syndromes” p. 454)
™ Urgent CT scan to determine cause HISTORY
™ Do PT, PTT and treat coagulopathy if present A carefully taken history is of utmost importance. The child, parents and
™ Cerebral angiogram and/or MRI/Magnetic Resonance Angiogram other caregivers may have to be interviewed. Important aspects of the
(MRA)/CT angiogram if indicated history include:
™ Neurosurgical treatment where and when appropriate ™ Feeding — Current feeding regime, appetite, feeding problems, last
meal or feed, and most importantly if the child will require surgery,
INTRACRANIAL INFECTIONS instruct NIL BY MOUTH, at least until further review
™ Epidural empyema, e.g. Pott’s puffy tumour ™ Vomiting — Nature of vomitus, volume, duration and frequency
™ Subdural empyema, e.g. secondary to sinusitis or HIB meningitis ™ Urine output — Hydration status
™ Intracerebral abscess ™ Bowel motions — Constipation, diarrhoea, presence of blood or
mucous in stools
Management ™ Abdominal complaints — Pain, distension, discolouration,
™ Diagnosis confirmed on CT scan +/- contrast enhancement peristalsis
™ Drainage by craniotomy or burrhole; aspiration or excision of ™ Pain — Intensity, site (visceral/referred pain, or direct/peritoneal
intracranial abscess pain), type (constant or intermittent), change in pain type or site.
™ Appropriate IV antibiotics for four to six weeks
458 The Baby Bear Book
Associated features (quiet or ‘rolling around’ with pain, drawn-up
legs, pallor etc). Quantify — Pain score charts
™ Previous history — Solitary or repeated events, previous surgery,
travel history
™ Medication and allergies — Smooth muscle-relaxant medication,
antibiotics, analgesia
CLINICAL EXAMINATION
A careful examination will very often give a tentative diagnosis.
However, we often need to repeat the examination, with varying
degrees of co-operation of the child. If the clinical examination is
persistently difficult, consider sedating the child, but do not give
analgesia without consulting a senior doctor.
™ General exam — Hydration, pallor, perfusion, skin (petechiae)
™ Vital signs — TPR, BP
™ Abdomen
Š Tenderness, masses, solid organs
Š Rebound tenderness, rigidity, peritonitis
Š Hernial orifices, and genitalia/perineum
Š Per rectal examination — This may be deferred until senior doctors
are available so as to limit the need for repeat examinations
INVESTIGATIONS
Judgment is required to order investigations that will give further
information without needlessly increasing cost. Pathways are available
for various conditions (acute appendicitis, gastroenteritis), but clinical
judgment will still be required.
™ FBC — Anaemia, blood loss, bacterial vs viral infections, platelets
™ Urea and electrolytes — Hydration status, electrolyte
derangements, pre-operative assessment
™ PT/PTT and group and cross match — For major surgery and if
other conditions such as liver impairment are co-existing
™ LFTs, amylase and urinary diastase — Usually not first-line
investigation unless liver or pancreatic disease is suspected
™ Urine FEME and culture — Pyuria and nitrite, ketones, haematuria
™ AXR — If intestinal obstruction is suspected, supine and erect or
lateral views should be done. Soft tissue masses, bowel gas pattern,
bowel distension, air/fluid levels, bowel wall thickness
™ CXR — Not commonly required, lower lobe pneumonia, effusion,
concomitant lung pathology, aspiration pneumonia
™ Abdominal ultrasound — Invaluable as an adjunct to the
examining hand in children. Bowel wall, free fluid, masses, abscesses,
Paediatric Surgery 459
appendix, vascularity, and relationship of vessels to the intestines
can be visualised
™ CT scan — Not commonly required. Obese patients, masses.
Postoperative evaluation. All major trauma
™ Barium studies — Swallow/meal to rule out volvulus, otherwise
not in a patient who is nil by mouth. Enema for reduction of
intussusception if air is not available (3ft height, three attempts, each
three minutes, ensure a good seal at the anus)
™ Air enema — Therapeutic in intussusception (gas pressure not >
100mm, three attempts, three minutes each, ensure a very good seal,
and accompany your patient to the Radiology Department; ensure
a well-functioning IV line before sending down, and have the baby
prepped for eventual surgery in case of failure of reduction)
™ Meckel’s Scan — Isotope scan; usually not done on an emergency
basis, as the child requires pre-scan preparation with H2 antagonists
MANAGEMENT
™ Fluid resuscitation — According to hydration status, urea/
electrolytes levels and estimated third space losses. Consider saline
10ml/kg boluses in addition to maintenance fluids. Replace specific
losses, and correct electrolyte imbalance. Monitor pulse, BP and urine
output to assess response
™ Rest intestine — Nil by mouth, nasogastric tube of sufficient caliber,
hourly aspiration and passive drainage in-between, until intestinal
function is ascertained or re-established. Replace losses using saline
with KCL
™ Surgery — Inform nursing staff to prepare child for surgery, obtain
consent from parent or 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. Inform surgeon of estimated time of surgery, especially if
any delay is anticipated and the surgeon is not stationed in-house
™ Laparoscopy — Investigation when other investigations fail to
give a diagnosis; it is also therapeutic for many conditions. Open vs
minimally invasive surgery must be discussed with the parents by
the surgeon
™ Pain management
Š While under observation, limit analgesia until the diagnosis has
been established
Š Treat as appropriate e.g. give an enema for constipation colic, and
the pain will subside
460 The Baby Bear Book
Š Post-operative morphine infusion: 1mg/kg body weight in
50ml of dextrose 5% to run at 1–2ml/hr. Use half this dose if at
all required in infants and neonates. Use a pulse oximeter for
all cases, and tail down the morphine as soon as the child is
comfortable
Š Consider regional analgesia, suppository paracetamol 15mg/kg,
or epidural analgesia. If on an epidural catheter, the child should
be nursed in the High Dependency Area
™ Review/observation — Some conditions presenting acutely are
not of a surgical nature, and all that is required is intestinal rest, IV
fluids, and regular review and observation. It is important to explain
to parents what is happening to the child, and what the plan of
treatment is, as otherwise they will invariable think that they spent
days in the hospital ‘and nothing was done’. In general, children
should not be sent home with persistent pain, but some judgment is
allowed. In a stable child with normal intestinal function and minimal
pain, home recovery may be allowed, with the proviso that parents
bring the child back in case of persistence or worsening of symptoms
COMMON CONDITIONS
Included below are the most common conditions seen, accounting
for 95% of cases here. Some, although not common, require mention
as a high index of suspicion is required for diagnosis, and immediate
treatment is required. Trauma is not covered here. Some conditions
are seen more commonly in certain age groups, and the conditions are
arranged in increasing frequency seen from infancy onwards.
Incarcerated Inguinal Hernia
™ Clinical examination should make the diagnosis immediately evident
™ Differential may include an encysted hydrocoele of the cord
™ 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
™ Immediate surgery if irreducible or on the next elective list. In infants
and neonates, bilateral herniotomies should be done
Malrotation and Volvulus
™ Typically occurs about Day 3 to Day 5 in an otherwise well child
™ 50% of patients who become symptomatic do so in the first month
of life. In older children, the presentation is that of chronic abdominal
pain and FTT. Incidence at autopsy is about 0.5–1% of the total
population.
Paediatric Surgery 461
™ Bilious vomiting may be the only presenting complaint
™ There may be absence of abdominal signs. If present, surgery is
urgent as volvulus may result in gangrene of the small bowel from
the duodeno-jejunal flexure to the ileocecal valve from superior
mesenteric artery pedicle torsion. A high index of suspicion is
required. AXR may show an abnormal gas distribution pattern, or
may be normal
™ Barium meal is diagnostic, showing a cork-screw appearance and
abnormal duodeno-jejunal position (lateral film)
™ Operative repair includes detorsion of the bowel and a Ladd’s
Procedure which includes an appendicectomy, placing the small
bowel in the right side of the abdomen and the large bowel on the
left side
Intussusception
™ Most commonly occurs around four to six months. Above two years,
consider a pathological lead point
™ Often preceded by URTI or a febrile episode
™ Episodes of severe abdominal colic with drawing up of legs and
pallor, vomiting and red-currant-jelly stools
™ Abdominal distension, palpable mass, most often in the right
hypochondrium
™ Typically really well-fed baby, with difficult venous access
™ AXR — Soft tissue mass and dilated small bowel with air-fluid levels
™ Ultrasound — Right hypochondrium mass, target lesion and pseudo-
kidney signs
™ Arrange for air enema reduction, and ensure fluid resuscitation
and secure venous access before going to Diagnostic Imaging
Department. Air enema success rate > 85%
™ Operative reduction with enema failure, or in a child presenting
in shock or with peritonitis, as there are clear contraindications for
barium enema reduction. At operation, reduction and resection of
any gangrenous bowel as well as inspection for pathological lead
point
™ Recurrent intussusception reported to occur in 2–20%, must be
explained to parents
Intestinal Obstruction/Ileus
™ Two to five years of age
™ Preceding gastroenteritis, and several visits to different doctors.
Often as a result of antispasmodics, and ileus secondary to the
gastroenteritis
462 The Baby Bear Book Paediatric Surgery 463

™ Abdomen generally distended, but soft blockers is positive in 85% of cases. Surgical resection may be open
™ AXR may show some air/fluid levels, generally very gaseous or laparoscopically assisted

Appendicitis Other Causes of Acute Abdomen in Children

™ Most common emergency admission diagnosis. Age typically four to ™ Constipation colic
15 years ™ Tonsillitis/‘tonsil tummy’
™ Pain: Peri-umbilical — Right iliac fossa ™ Gastroenteritis
™ Anorexia, fever, vomiting, diarrhoea, dysuria ™ Mesenteric adenitis
™ Tender, guarded, rebound tenderness in the right iliac fossa ™ Pancreatitis
™ Generalised tenderness, sepsis and peritonitis. Dehydration ™ Choledochal cyst
™ Symptoms and signs may be masked by prior antibiotics and ™ Duplication cyst
analgesia ™ Ovarian torsion
™ If unsure of the diagnosis — Observation and frequent review. ™ HSP, dengue, Peutz-Jegher Syndrome
Rehydration ™ Solid tumor rupture
™ Ultrasound may be helpful, as will a total white count, and urine
microscopy FURTHER READING
1. Current Surgical Diagnosis & Treatment, 11th Edition.L W Way, G M Doherty Ed. Lange
™ Differentials include mesenteric adenitis, constipation colic, Medical Books 2003
gastroenteritis, tonsillitis, lower lobe pneumonia, ovarian pathology, 2. Pediatric Surgery, 3rd Edition. Ashcraft, Murphy, Sharp, Sigalet, Snyder Ed. W B Saunders,
Meckel’s diverticulitis 2000.

™ Surgery will be open or laparoscopic

™ Clinical pathway for simple and perforated appendicitis available
™ Complications include pelvic abscess, wound infection and intestinal
adhesions

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
™ Blood loss is typically minimal to moderate
™ Clinical exam, stool examination, colonoscopy
™ Bleeding from a Meckel’s diverticulum is typically a very significant
bleed. Bleeding occurs when ectopic gastric mucosa causes an
ulcer in adjacent small bowel mucosa. Meckel Scan with pre-scan H2
464
RESPIRATORY
ASTHMA
INTRODUCTION
Bronchial asthma is a chronic disease affecting 1-in-5 children in
Singapore. Inappropriate or delayed treatment may have a long-term
impact on lung and somatic growth, and psychological well-being. This
ultimately affects health in adulthood.
DIAGNOSIS
In evaluating a child with suspected asthma, one has to ask several
questions.
™ What are the symptoms? Is it consistent with the clinical presentation
of asthma?
Š Asthma is a heterogeneous disease with varying severity and
presentation
Š Common features of asthma include recurrent breathlessness,
wheezing and cough
™ Can the symptoms be attributed to another diagnosis other than
asthma?
Š Presenting symptoms for asthma are common symptoms in
childhood and it is important to rule out other conditions before
a definitive diagnosis is made. This is particularly important below
the age of six years
Š Conditions that can mimic asthma:
y Viral-associated wheezing — Bronchiolitis, bronchitis
y Bacterial infections — Mycoplasma pneumoniae infection,
PTB, pertussis
y Recurrent aspiration — Gastro-oesophageal reflux,
swallowing dysfunction
y Chronic rhinitis
y Foreign body inhalation
y Chronic lung disease — Bronchopulmonary dysplasia, post-
infective interstitial lung diseases, bronchiectasis
y Structural anomalies — Tracheobronchomalacia, vascular
rings, tracheobronchial stenosis
y Airway compression — Mediastinal mass
Respiratory 465
y Cardiac failure
y Others such as cystic fibrosis and congenital or acquired
immunodeficiency states
™ If the child has asthma, can all the symptoms be attributed to
asthma? Are there concomitant illnesses?
Š Children with asthma frequently also have allergic rhinosinusitis.
There is an overlap in symptomatology and is important to bear
in mind the contributing symptoms from concomitant illness
when assessing the overall disease severity
The diagnosis can usually be made based on the history and clinical
examination. Sometimes, simple investigations may help to confirm the
diagnosis and assess the severity.
HISTORY
Asthma should be considered in children presenting with the following
features:
™ Chronic cough that is worse at night or aggravated by exercise
™ Recurrent episodes of difficulty in breathing or wheezing, especially
if associated with exposure to allergens or aggravated by exercise
™ Exercise-induced chest tightness
™ Strong family history of asthma
Always take a careful, detailed history to exclude other conditions which
may mimic asthma.
CLINICAL EXAMINATION
™ Growth parameters — Growth failure is often associated with chronic
illness e.g. bronchiectasis, immunodeficiency, PTB
™ Features of atopy — Allergic shiners, eczema, swollen mucosa of the
nasal turbinates
™ Signs of chronicity — Barrel-chested (increased AP diameter),
Harrison’s sulci, clubbing. When clubbing is present, need to exclude
bronchiectasis and chronic interstitial pneumonitis
™ Signs on auscultation — Stridor (diagnosis is probably not asthma),
rhonchi, heart murmur
INVESTIGATIONS
Usually not necessary, but useful in:
™ A very young child with onset of symptoms in the neonatal period —
need to exclude structural airway problems
™ Severe disease not responding as expected
466 The Baby Bear Book Respiratory 467

Table 13-1: Management of childhood asthma — Classification of severity*.

™ Unusual features e.g. sudden onset (may be foreign-body inhalation),
sole manifestation of chronic cough, exercise-induced chest PEF vs Predicted
Night-time
tightness or chest pain Severity Symptoms§ (children Step
symptoms§
> five years)
Chest X-ray Intermittent < 1x/week < 2x/month > 80%, variability Step 1
To look for PTB or foreign body. If a foreign body is suspected, do Frequent > 1x/month < 20%
expiratory (decubitus view with affected side down in a young child) Mild > 1x/week > 2x/month > 80%, variability Step 2
and inspiratory films. persistent < 1x/day 20–30%
Moderate Daily use of B2 > 1x/week 60–80%, variability Step 3
Pulmonary Function Tests persistent agonist, attacks > 30%
affect activity
™ Peak Expiratory Flow (PEF) measurement:
Š Simple, but effort-dependent Severe Continuous, limited Frequent < 60%, variability Step 4
Š Demonstration of clinical variation of > 15% (PEF measurement persistent physical activity > 30%
* When other illness with similar symptoms co-exist (e.g. chronic rhinitis) re-evaluate after treating the concomitant illness
morning and before bedtime) supports a diagnosis of asthma §
For an accurate assessment, careful inquires should be made for day and night symptoms, exercise-limitation, school-
Š Serial measurements give an objective measurement of response absenteeism, use of bronchodilators and current medication
to therapy
™ Spirometry:
Š Forced Expiratory Volume in One Second (FEV1) has good
baseline reproducibility and better sensitivity than PEF and is a Under the age of five years, the assessment of disease severity is based
good objective measure in children older than five years solely on the symptoms. In older children, the objective measurement of
Š Demonstration of bronchodilator response with improvement of PEF is included.
PEF/FEV1 by 15%, 15 minutes after administration of a short-
acting β-agonist supports the diagnosis of asthma MANAGEMENT
™ Bronchial challenge: A holistic approach is necessary to help patients prevent symptoms
Š Non-specific metacholine/mannitol challenge test or exercise and gain control; close monitoring is crucial in improving compliance
challenge test (six minutes of running), a fall of 15% in FEV1/PEF to therapy. To control symptoms, prevent worsening of the disease
is positive and suggests a diagnosis of asthma and prevent airway remodeling; one should initiate anti-inflammatory
™ Skin prick: therapy early in all except patients with very mild intermittent asthma.
Š Not done routinely, unless specific allergens suspected; if the
child has no evidence of atopy, a positive skin prick test may also In the young pre-school children presenting with recurrent episodes
demonstrate that sensitisation to the allergen has occurred of wheezing precipitated by viral infection, it is often difficult to
distinguish between early asthma, which is likely to worsen if left alone,
Others and recurrent viral infection with wheezing, which is likely to improve
Bronchoscopy to exclude foreign-body or structural airway anomalies, with age. Children who have persistent wheeze by six years are likely to
sweat test, immunoglobulins. continue wheezing.

ASSESSMENT OF SEVERITY The following are risk factors for developing asthma:
After confirming the diagnosis of asthma, it is important to make an ™ Frequent, severe wheezing
accurate assessment of the level of severity of the disease. A careful ™ Eczema
evaluation plays a pivotal role in the successful management of the ™ Strong family (parent) history of asthma
condition. ™ Allergen-associated wheezing
468 The Baby Bear Book
Pre-school children who have recurrent wheezing (three to four
episodes) and any of the above should be considered for early anti-
inflammatory therapy.
PHARMACOTHERAPY
Anti-inflammatory
Appropriate selection of an anti-inflammatory agent is pivotal to long-
term success of therapy. The treatment should be assessed every three
months and stepped up if control is not achieved or stepped down if the
child is well.
There are two main classes of anti-inflammatory agents:
™ Non-steroidal anti-inflammatory agents
Leukotriene modifiers or leukotriene-receptor antagonists is a new
class of anti-asthma drugs for use. There appear to have a bigger
role in young children with asthma, particularly if wheezing is
associated with viral infection. In children who remain symptomatic
on moderate doses of inhaled steroids, it also has a role as an add-on
therapy. There have been some promising results in the treatment
of children with recurrent viral-related wheezing and in Respiratory
Syncytial Virus (RSV) bronchiolitis children with prolonged
symptoms.
™ Steroidal anti-inflammatory agents
Š Inhaled corticosteroid
This is the most effective therapeutic agent in treatment of
most children with asthma. Doses of inhaled steroid, such as
budesonide (BUD) up to 400μg/day have not been associated
with stunting of growth. Inhaled steroids should be given via a
spacer device in young children to improve delivery and reduce
the incidence of oral candidiasis and hoarseness of voice. Older
children may use dry-powder inhalers such as the turbuhaler
or accuhaler. Increasing the dose of inhaled steroid beyond
beclomethasone (BDP) 400μg, or its equivalent, should be done
with care. The dose response curve is sigmoidal and these higher
doses are associated with more systemic side-effects with little
evidence of additional clinical efficacy
Š The combination of a long-acting β-agonist and inhaled steroids
is an attractive option as it simplifies the treatment regime for
patients with chronic asthma who need both a bronchodilator
and inhaled steroid for maintenance. This is an option which
should be considered in children who remain symptomatic
on moderate doses of inhaled steroids. There is good clinical
Respiratory 469
evidence of better efficacy as compared to increasing the dose of
the steroid or adding an anti-leukotriene agent.
Bronchodilator Therapy
™ A β2-agonist is the most effective bronchodilator and should be
given by inhalation. Intermittent usage is recommended because of
the possibility of increased bronchial hyperreactivity with chronic
use. Ipratropium bromide may be added as an adjuvant to β2-agonist
nebulisation therapy for acute asthma.
There is little advantage in using a nebuliser over an inhaler to
deliver β-agonists in acute asthma. Routine use of home nebulisers
is not recommended. During asthma exacerbations, as many as 12
puffs of salbutamol inhaler or 0.2–0.3puffs/kg may be used
™ Methylxanthines in acute asthma do not give additional benefit
when optimal doses of bronchodilators and steroids are used.
However, IV methylxanthines should be considered in children with
acute severe asthma, particularly if they are not responding to the
initial treatment
™ Long-acting bronchodilators
Long-acting β2-agonists (LABA) used in conjunction with inhaled
steroids improve symptom control and lung function. Long-term
use of a long-acting theophylline for chronic asthma should be done
under close monitoring of side-effects and serum levels. Long-
acting β-agonists, which are safer and more efficacious, should be
considered in place of theophylline
Long-acting bronchodilators cannot be used as rescue medication
with the exception of formoterol, which is a long-acting β2-agonist
with a rapid onset of action (three minutes)
™ Magnesium sulphate
The suggested mechanism of action is smooth muscle relaxation
secondary to inhibition of calcium uptake. A bolus dose of IV of
magnesium sulphate 50mg/kg (25–75mg/kg) and may be useful in
moderate to severe acute asthma
NON-PHARMACOLOGICAL MANAGEMENT
Education of the patient or caregiver to identify and avoid triggers
that make asthma worse forms an important part of successful asthma
therapy. Engaging them in a partnership to manage their own disease
and mild exacerbations is also important in achieving total control and
encouraging compliance.
470 The Baby Bear Book Respiratory 471

Table 13-2: Pharmocotherapy of childhood asthma.

LONG-TERM MANAGEMENT
It is prudent to initiate treatment appropriate for the level of severity.
However, a more aggressive approach, starting at a higher level and

Reduce
stepping down as control is achieved, is preferred for children with Level of Control Treatment Action
prolonged and troublesome symptoms. Rapid resolution of symptoms Controlled Maintain and find lowest controlling step
improves confidence in the treatment regime and encourages Partly-controlled Consider stepping up to gain control
compliance from patients and their parents.

Increase
Uncontrolled Step up until controlled
Exacerbation Treat as exacerbation
GOALS FOR GOOD CONTROL
™ Minimal or no chronic symptoms, including night symptoms
™ Minimal or no need for β2-agonist
™ No limitation of physical activities
™ Normal or near-normal lung function
™ Minimal or no adverse effects from therapy

See Table 13-2 next page for a guideline on pharmacotherapy and the Reduce Treatment Steps Increase
initiation and stepping up or down treatment.

IMPORTANT CONSIDERATIONS IN MANAGEMENT

Delivery Device Step 1 Step 2 Step 3 Step 4
The inhaled route is the best form of delivery. Delivery via a spacer Asthma education
Environmental control
device is as effective as using a nebuliser. It is important to take into
consideration the ability of the child or caregiver to handle the device. In As needed rapid-acting β2-agonist
very young children, a spacer device with a facemask is essential. Older Select one Select one Add one or more
children are comfortable with the use of breath-actuated devices such Low-dose inhaled Low-dose ICS Medium- or high-
ICS* plus long-acting dose ICS plus long-
as a turbuhaler, accuhaler or autohaler. A device which the child and
BDP/BUD ≤ 200 β2-agonist (not acting β2-agonist
caregiver are happy with will be the best option because it is likely to be FP ≤ 100 recommended for <
used and compliance improved. five years)
Controller options
Leukotriene modifier Medium- or high- Leukotriene modifier
Compliance to Therapy dose ICS
This is the greatest challenge. Prescribe a simple regime, preferably Initiation of therapy Lose-dose ICS plus
once-daily treatment, to facilitate easy administration and supervision based on severity of leukotriene modifier
symptoms BDP ≤ 400
and hence compliance to treatment. Reinforcement and education FP ≤ 200
on the need for early intervention, and addressing and revisiting the Pre-treatment ‰ Episodic ‰ Frequent ‰ Moderate ‰ Severe asthma
safety issues and concerns with parents help in improving compliance. assessment of asthma episodic or persistent
In a busy clinic, nursing staff can be taught to carry out simple asthma severity mild persistent asthma
education with the help of teaching aids. asthma

Use of Written Asthma Action Plan for Inter-current

Problems
Young children may suffer six to nine viral infections in a year. This often
triggers or exacerbates asthma symptoms, especially during the early
472 The Baby Bear Book Respiratory 473

Table 13-2: Pharmocotherapy of childhood asthma (cont’d).

Allergen Avoidance
Controlled Partial-controlled Uncontrolled House dust mites are one of the most common triggers in childhood
Check ‰ Good ‰ Poor ‰ Good ‰ Poor ‰ Good ‰ Poor asthma. Children spend relatively longer hours in the bedroom at
compliance
night and therefore controlling house dust mites in the bedroom is an
Duration ‰ Advice compliance ‰ Advice compliance ‰ Advice compliance important element in improving control. Washing linen in hot water
< three ‰ Maintain ‰ Check inhaler technique ‰ Check inhaler technique
months ‰ Check for triggers ‰ Check for triggers (> 60˚C), and keeping the room well-ventilated helps in reducing the
‰ Step up/maintain if ‰ Step up/maintain if house dust mite population. Cigarette smoke is another important risk
non-compliant non-compliant factor for wheezing in children. Household smoking should be strongly
Duration Step down and refer ‰ Treat allergic rhinitis ‰ Treat allergic rhinitis discouraged, not just because of passive smoking but because it is a
> three Polyclinic if BDP/BUD ≤ ‰ Step up ‰ Step up negative influence for an impressionable child. Families with asthmatic
months 200μg or FP ≤ 100μg
children should also avoid furred or feathered pets at home.
Duration ≥ Step down and refer ‰ Refer registrar ‰ Refer Respiratory for
six months Polyclinic if BDP/BUD ≤ ‰ Step up evaluation
200μg or FP ≤ 100μg ‰ Refer High-risk Asthma HIGH-RISK ASTHMA (HRA)
(HRA) if meet HRA This is a group of asthmatic patients with a high disease burden. They
critieria require frequent acute care or hospitalisations and frequently miss
‰ Step up
school. They need special medical attention, counselling support and
ICS: Inhaled corticosteroids; BDP: Beclamethasone; BUD: Budesonide; FP: Fluticasone
monitoring. HRA is not peculiar to paediatrics but identification is
even more difficult in children because of the difficulty in defining the
outcome.
stage of treatment. To assist the family in coping with inter-current
infections, it is important to provide a clear, written action plan. For most This cohort should be referred to the Respiratory Medicine Service for
children with mild asthma, intermittent use of β2-agonist is sufficient evaluation and management. The children at risk:
but for some an increase in the dose of inhaled corticosteroid may be ™ Have poor asthma control:
necessary. Mild exacerbations of asthma can be managed at home using Š ≥ two exacerbations per month needing acute care
the written action plan as a guide. Š Hospitalised for asthma ≥ two occasions in three months
Š Require rescue medicine (bronchodilators) > 3x/week
Physical Exercise (PE) and Physical Fitness Test Š Severe acute exacerbations needing HD/ICU care
Parents are concerned about exercise-induced symptoms and frequently Š Poor social support, compliance issues, etc.
ask for their child to be exempted from PE and the physical fitness test. ™ Are < three years old and require moderate doses of inhaled steroids,
The goal of therapy is to achieve a normal lifestyle with normal physical without the expected response
activities for the children. Thus, one should explain that good control ™ Are on BDP/BUD > 400μg/day, or the equivalent
will abolish Exercise-induced Asthma (EIA) and that asthmatic children ™ Are on low to moderate doses of inhaled steroids for six months and
should be able to exercise as much as they want. Adequate physical are still symptomatic
exercise is a key to good physical health and psychological well-being.
For children with EIA, inhaled β2-agonist 15 minutes before exercise is These children should be managed in a HRA clinic.
helpful to ablate the symptoms. For children with activities throughout
the day, a long-acting β2-agonist (formoterol or salmeterol) may be a Duration of Therapy
better alternative. Treatment is long-term. Total cessation of therapy after a mean of 22
months of treatment has been associated with relapse.

Control of asthma is assessed based on symptoms. A simple

questionnaire based on asthma symptoms (Asthma Control Test or
474 The Baby Bear Book Respiratory 475

Table 13-3: Severity of acute asthma.

ACT) is helpful in self-assessment and also in guiding control and
management. A score of ≥ 20 correlates with good control. Objective Severe or Life-
Mild Moderate
lung function measurement enhances the evaluation and is strongly threatening
recommended in children > six years. Breathless On exertion On talking At rest
Speaks in Sentences Phrases Words
In practice, most children needing regular therapy will have to be on Conscious level Normal May be agitated Agitated, confused,
treatment for at least one year. Close monitoring is required when drowsy
stepping down before the cessation of therapy, as step-up treatment Accessory muscle Nil + ++/paradoxical, thoracic
may become necessary. During the period of observation, it is important — abdominal movement
also to assess the pulmonary function as well as symptoms. Changes in Wheeze/rhonchi Variable Loud Loud/silent
airflow are often evident prior to relapse of symptoms. Pulse rate/minute < 100 100–200 > 200
Pulsus paradoxus Nil May be palpable, > 25mmHg, palpable, nil
MANAGEMENT OF ACUTE ASTHMA 10–25mmHg if exhausted
An acute exacerbation of asthma is a potentially serious complication
Physical exhaustion Nil No Yes (cyanosed)
and should be prevented with optimal long-term treatment.
SaO2 in room air ≥ 95 92–95 < 92
Children at Risk of Severe Exacerbations PEF (predicted/ ≥ 80% 60–80 < 60
™ Severe or poorly controlled asthma personal best)
™ Past history of near-fatal asthma Respiratory rate/ ↑ ↑↑ ↑↑↑/↓ (exhaustion)
™ Frequent visits to A&E for treatment minute
™ Hospitalisation for asthma
™ Rapidly progressive exacerbation, < three hours
™ Poor compliance General Principles
™ Psychosocial disturbance ™ Maintain oxygenation (SaO2 ≥ 95%) — Deliver oxygen via nasal
™ Poor perception, or underestimation of symptoms prongs/face mask
™ Underlying medical condition e.g. Bronchopulmonary Dysplasia ™ Relieve bronchospasm with intensive bronchodilator therapy
(BPD), neuromuscular disease Š Frequent low doses of inhaled salbutamol is more effective
Š Ipratropium bromide added on to β2-agonist improves the
Approach to Acute Exacerbations outcome of acute asthma
™ Confirm diagnosis — History of asthma, presenting with Š β2-agonist delivered via spacer is effective for moderate to severe
breathlessness, wheezing or persistent cough exacerbation of asthma
™ Exclude co-existing diagnosis e.g. pneumothorax, pneumonia Š Theophylline is not routinely recommended for acute asthma
™ Exclude alternative diagnosis e.g. foreign-body aspiration, cardiac Š Other agents: IV magnesium sulphate, helium-oxygen mixture,
failure nitric oxide and ketamine
™ Assess severity — Clinical features, objective assessment pulse rate, ™ Treat underlying inflammation
respiratory rate, Peak Expiratory Flow Rate (PEFR), SaO2 monitoring Oral steroids should be started early in children with a moderate to
(Table 13-3 next page outlines the severity of acute asthma) severe acute exacerbation. Children respond well to oral steroids and
hence IV hydrocortisone is not necessary in most cases
TREATMENT OF ACUTE ASTHMA ™ Treat concurrent bacterial infection
Use Clinical Care Path to guide management of acute asthma. The Antibiotics should not be a routine but given only when
guidelines are available at all acute care locations. superimposed bacterial infection is suspected
476 The Baby Bear Book Respiratory 477

Outpatient (and Emergency Department) Management of **Follow-Up Plan

Acute Asthma NB : All patients enrolled in the National High Risk Asthma Shared Care
Assess severity and always take into consideration treatment received (NASC) programme must continue follow-up at NASC Clinics.
prior to arrival.
™ If the child has received treatment prior to arrival, treat as more
Any criteria for HRA:
severe than the clinical signs would suggest
™ ≥ two attendances for acute care in one month
™ If the child has been on four hourly β2-agonist Metered Dose ™ ≥ two hospitalisations in three months
Inhaler (MDI)/nebuliser at home for > 48 hours, consider in-patient ™ Use of β2-agonist > 3x/week
management ™ Admitted to HD or ICU in the last six months
™ Educate the patient on trigger avoidance and self-care plans ™ Others e.g. poor supervision, non-compliance, defaulters
™ Identify frequent urgent-care users and high-risk patients, and refer
for specialist treatment Yes No

Management of Acute Asthma in Hospital

™ Patients should be carefully monitored and evaluated at regular Refer Respiratory Physician or HRA Follow-up by regular doctor
intervals, particularly in the initial phase of intensive therapy Clinic for review of new patients NASC
™ Hospitalisation because of asthma is an indication of poor control. Clinic for follow-ups
It is important to check on compliance and inhaler technique. It is
equally important to identify any trigger factors that can be avoided
™ Revisit maintenance therapy and step up accordingly BIBLIOGRAPHY
1. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on
™ Give a written asthma action plan upon discharge and organise
growth and pulmonary function in asthmatic children. Respir Med. 1994;88(5):373–381.
appropriate follow-ups 2. Laitinen LA, Laitinen A, Haahtela T. Airway mucosal inflammation even in patients with
newly diagnosed asthma. Am Rev Respir Dis. 1993;147(3):697–704.
3. Ministry of Health. Management of asthma. MOH Clinical Practice Guidelines 1/2008.
Guide to Medication for Acute Asthma Singapore: Ministry of Health; 2008. Available from:
http://www.moh.gov.sg/mohcorp/uploadedFiles/Publications/Guidelines/Clinical_
Practice_Guidelines/Asthma%20CPG%20booklet.pdf
Salbutamol MDI (100μg/puff ) 0.2–0.3puff/kg, not exceeding 12 puffs per time 4. Ducharme FM, Hicks GC. Anti-leukotriene agents compared to inhaled corticosteroids
Salbutamol Nebuliser (5mg/ml) 0.10–0.15mg/kg or 0.01–0.03ml/kg in the management of recurrent and/or chronic asthma. Cochrane Database Syst Rev.
2002;(3):CD002314.
Salbutamol Nebuliser (continous) 1–4ml neat 5. Lipworth BJ. Systemtic adverse effects of inhaled corticosteroid therapy: A systematic
Salbutamol IV (5mg/5ml) Bolus 5μg/kg over ten minutes review and meta-analysis. Arch Intern Med. 1999;159(9):941–955.
Start infusion at 5μg/kg/min, dose range 6. Verberne AA, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. Addition of salmeterol versus
doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study
1–15μg/kg/min, titrate to response Group. Am J Respir Crit Care Med. 1998;158(1): 213–219.
Ipratropium MDI (20μg/puff ) One puff (< 10kg), two puffs (> 20kg), two to three 7. Cates CJ, Rowe BH, Bara A. Holding chambers versus nebulisers for beta-agonist treatment
of acute asthma. Cochrane Database Syst Rev. 2002;(2):CD000052.
puffs (> 30kg), six to eight hourly 8. Tattersfield AE, Löfdahl CG, Postma DS, Eivindson A, Schreurs AG, Rasidakis A, Ekström
Ipratropium Nebuliser (250μg/ml) 0.25ml (< 10kg), 0.5ml (< 20kg), 1ml (> 20kg), T. Comparison of formoterol and terbutaline for as-needed treatment of asthma: A
six to eight hourly randomised trial. Lancet. 2001;357(9253):257–261.
9. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult
Steroids Oral Prednisolone 1–2mg/kg/day height in children with asthma. New Engl J Med. 2000;343(15):1064–1069.
Steroids IV Hydrocortisone 4–5mg/kg/dose four to six hourly 10. van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Kerrebijn KF. Remission
of childhood asthma after long-term treatment with an inhaled corticosteroid
(budesonide): Can it be achieved? Dutch CNSLD Study Group. Eur Respir J. 1994;7:63–68.
11. Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S, et al. Developmental and
cross-sectional validation of the childhood asthma control test. J Allergy Clin Immunol.
2007;119(4):817–825.
478 The Baby Bear Book Respiratory 479

EMPYEMA Parapneumonic effusion on CXR

Empyema is the collection of pus within the pleural cavity as a result of

the inflammatory response induced by bacterial pneumonia. IV antibiotics
™ Empyemas complicate about 1–2% of cases of pneumonia
™ Three stages — (1) initial thin fluid accumulation, (2) organised
fibroblast deposition and (3) entrapment of lung No IV antibiotics and observe.
™ Common organisms — S. aureus, H. influenzae, Mycoplasma Large effusion and/or respiratory distress
Consider diagnostic tap
pneumoniae and S. pneumoniae
Yes
TREATMENT
™ Antibiotics
Š Choice of antibiotic depends on likely organism Loculated effusion?
Š Empiric therapy — High-dose IV ampicillin, as S. pneumoniae is
the most common organism No Uncertain/yes
Š Therapy should be IV for at least ten to14 days and then replaced
with oral antibiotics. The total duration of treatment should be at
least four weeks IV antibiotics and Ultrasound thorax/
Š Pleural fluid antibiotic levels are comparable to serum levels. chest tube CT scan thorax
The exception is aminoglycosides, which penetrate poorly into
purulent pleural fluid
™ Video-assisted Thoracoscopic Surgery (VATS)
Š If there are loculations, the septae need to be broken down to
completely drain the pleural cavity Not loculated Loculated Loculated
Š VATS is the procedure of choice and is associated with a shorter No suggestion of No suggestion of Thick pleural peel
hospital stay pleural peel pleural peel Duration > ten days
Duration < ten days Duration < ten days Lung compression ≥ 50%
™ Intrapleural fibrinolytic therapy
Lung compression < 50%
Š If VATS is not available, this can be considered
Š Urokinase — 3,000U/kg (max 100,000U)
Š If there is no improvement in 72 hours, proceed to thoracotomy
with decortication Chest tube

Fig. 13.1 next page outlines the algorithm for the management of
parapneumonic effusion.

Medical option Early surgical option

Chest tube and VATS

thrombolytic therapy

Fig. 13.1: Algorithm for the management of parapneumonic effusion.

480 The Baby Bear Book Respiratory 481

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.
FLEXIBLE BRONCHOSCOPY
The flexible bronchoscopy can be used for diagnostic and therapeutic
purposes. Its other uses include bronchoscopy-assisted intubation.
COMPLICATIONS
™ Hypoxia (sedation, size of scope in relation to airway)
™ Cardiac arrhythmias due to vagal stimulation from inadequate
topical anaesthesia
™ Laryngospasm or bronchospasm due to inadequate topical
anaesthesia
™ Fever which is usually transient and following a bronchoscopic
alveolar lavage (usually four hours to six hours later)
Advantage of flexible bronchoscopy over a rigid scope:
™ Can be done under sedation and topical anaesthesia, and thus allows
the study of the dynamics of the airways
™ Access to the apices of the lung, the distal airways and the nasal
passages
™ Can be performed in patients in whom the passage of a rigid
scope is impossible e.g. mandibular hypoplasia, cervical or
tempromandibular ankylosis, unstable cervical spine
™ Complication rate lower

INDICATIONS — DIAGNOSTIC Disadvantages:

™ Atelectasis ™ Patient has to ventilate around the flexible scope, thus the patient’s
™ Stridor airway is partially obstructed throughout the procedure
™ Unexplained or persistent wheeze ™ Limited instrumentation. It is not the procedure of choice in the
™ Suspected foreign body extraction of foreign bodies from the airway
™ Recurrent pneumonia
™ Persistent radiographic infiltrates PROTOCOL FOR BRONCHOSCOPY
™ Haemoptysis ™ Assess fitness for general anaesthesia
™ Suspected congenital anomalies ™ Obtain consent
™ Suspected airway compression ™ Inform respiratory physician
™ Excessive bronchial secretions ™ Inform OT staff
™ Fast patient for six hours
INDICATIONS — THERAPEUTIC ™ Ensure forms are properly labelled and special culture media
™ Removal of mucous plugs obtained if BAL culture specimens are required
™ Removal of foreign body
POST-BRONCHOSCOPY CARE
RELATIVE CONTRAINDICATIONS ™ Monitor pulse, respiratory rate, and oxygen saturation hourly for four
™ Severe bleeding diatheses — Correct the bleeding disorder before hours
the scope ™ Keep nil by mouth for two to three hours if lignocaine spray has been
™ Severe airway stenosis — Can visualise up to the level of stenosis used
™ Severe hypoxia — This can be overcome by giving supplemental ™ Start with clear feeds and if this is tolerated, proceed to soft diet
oxygen during the procedure or the scope can be done through an
ETT while mechanical ventilation is continued
482 The Baby Bear Book Respiratory 483

™ Alert a senior doctor if there is increasing tachypnoea or hypoxia OSAHS has been defined as episodes of partial or complete upper
™ Respiratory physician to review before discharge airway obstruction during sleep, usually associated with a reduction in
oxygen saturation or hypercarbia associated with sleep disruption and
night-time and/or day-time symptoms.

Symptoms of Obstructive Sleep Apnoea Hypoventilation

SLEEP-RELATED UPPER AIRWAY Syndrome (OSAHS)
OBSTRUCTION IN CHILDREN
Night-time Symptoms Day-time Symptoms
™ Habitual snoring ™ Morning headaches, crankiness or irritability
INTRODUCTION ™ Snorting, gasping, choking ™ Excessive day-time sleepiness
Sleep-related upper airway obstruction exists in a continuum, ranging ™ Observed apnoea ™ Symptoms related to adenotonsillar hypertrophy:
from primary snoring with minimal or partial obstruction to Obstructive ™ Frequent arousals Š Mouth breathing
Sleep Apnoea Hypoventilation Syndrome (OSAHS) with maximal or ™ Disturbed, restless sleep Š Dry mouth
complete obstruction. ™ Increased work of breathing Š Nasal congestion
™ Unusual sleeping positions Š Frequent otitis media
™ Diaphoresis Š Frequent sore throats
OSAHS is increasingly being recognised in children with an incidence
™ Nocturnal enuresis Š Halitosis
of 1–3% in pre-school and school-aged children. Untreated OSAHS ™ Cyanosis Š Swallowing difficulties
can be associated with significant morbidity, including neurocognitive ™ Seizures Š Speech impairment
deficits, growth failure, cardiovascular consequences, or even death. ™ Complications of OSAHS
Nevertheless, despite years of symptoms, sleep-related upper airway
obstruction is often unrecognised in children because of the absence
of symptoms while awake and the more subtle clinical presentation. Physical examination while awake may be completely normal. However,
Polysomnography is invaluable for the evaluation. Advances in diagnosis the examination should include assessment of the child’s growth,
and management can alleviate much of the morbidity previously stigmata of allergic disease, presence of adenoid obstruction (e.g.
associated with untreated OSAHS. “adenoidal facies”, hyponasality, mouth breathing) other craniofacial
abnormalities, nasal patency, tonsillar size, oropharyngeal space, chest
CLINICAL FEATURES deformities, evidence of pulmonary hypertension, a full neurologic
Snoring is a vibratory sound produced by partial obstruction of the examination and a developmental assessment.
pharynx during inspiration and is the hallmark of sleep-related upper
airway obstruction. Epidemiology
About 9–10% of children snore during sleep every night or on most
Primary snoring is defined as snoring during sleep without associated nights and up to 20% do so on an intermittent basis. The prevalence
apnoea, hypoventilation, hypoxaemia or hypercarbia and with no of UARS is not known. The peak incidence occurs between two
associated sleep disturbance or associated daytime symptoms. to six years of age, coinciding with the developmental peak of
adenotonsillar hyperplasia; there is a second peak in middle- to late-
Upper Airway Resistance Syndrome (UARS) is defined as partial upper adolescence, although these patients usually present with adult-type
airway obstruction sufficient to cause sleep disruption and daytime symptomatology (i.e. night-time arousals and day-time somnolence).
symptoms but not gas exchange abnormalities. OSAHS occurs equally in pre-pubertal boys and girls while post-pubertal
gender distribution is that of male preponderance. There appears to be
no racial predisposition amongst the Singapore population. OSAHS is
more common in those with a positive family history, those exposed
484 The Baby Bear Book Respiratory 485

Tonsil and Adenoid ™ Neurocognitive dysfunction e.g. poor school performance; poor
Brainstem Sleep Hypertrophy memory, psychomotor skills and intellect
Abnormalities ™ Behavioural disorders e.g. inattention, hyperactivity, aggression,
Cerebral Palsy Decreased Acute Infection shyness, social withdrawal
or Abnormal Increased or ™ Increased incidence of parasomnias
Neuromuscular Pharyngeal Intraluminal Increased Nasal
Disorder Tone Negative Resistance
Pressure
Diagnosis
Laryngomalacia Infiltrative Clinical assessment by a trained physician does not reliably distinguish
Disorders OSAHS from primary snoring and does not have sufficient diagnostic
Small Upper
Airway Craniofacial sensitivity upon which to base a recommendation for surgery.
Structural Infiltrative Abnormalities Laboratory tests are of variable utility.
Disorder ™ Findings of polycythaemia or compensatory metabolic alkalosis
Obesity
support the diagnosis of OSAHS but are frequently absent in
Fig. 13.2: Factors involved in producing dynamic upper-airway obstruction.
paediatric patients
™ Right ventricular hypertrophy on electrocardiography, or dysfunction
to cigarette smoke and those with allergic sensitisation and airway on echocardiogram, are seen only in the more severe cases
inflammation i.e. asthma, allergic rhinitis, sinusitis. ™ Radiographic evaluations are helpful, but are often done awake,
upright or with the child sedated for the procedure and do not
In high-risk populations (e.g. morbid obesity, craniofacial anomalies, reliably predict the presence or severity of upper airway obstruction
neuromuscular disease, and trisomy 21), the incidence may be as high when the child is supine and asleep
as 13–80%. ™ A lateral soft tissue radiograph of the neck can identify tonsillar and
adenoid tissue
Predisposing Factors and High-risk Groups ™ MRI, CT scan of the airway and craniofacial anatomy, airway
OSAHS can be caused by anything that interferes with neural control fluoroscopy or endoscopy and cephalometric radiographs can
of the upper airway, abnormal upper airway dilator muscle function, display airway dimensions, dynamics and abnormal structural
structural factors that affect airway dimensions and muscle function, or relationships
increased resistance upstream from the collapsible segment (e.g. nasal
obstruction, enlarged adenoids, tonsils). Screening studies including home audio-taping, home video-taping,
overnight oximetry and sleep sonography have been used but have
Fig. 13.2 above depicts the factors involved in producing dynamic insufficient sensitivity and specificity for the diagnosis of OSAHS. Also,
upper-airway obstruction. these tests are limited because they give no information about sleep
disruption, cannot distinguish between central and obstructive apnoea,
Consequences of Childhood OSAHS and fail to detect obstructive hypoventilation or hypercapnia, or to
The consequences on longstanding untreated OSAHS include: establish the cause of hypoxemia.
™ Death
™ Cor pulmonale Nap studies have been done in some centres and have been shown to
™ Pulmonary hypertension have almost a 100% positive predictive value but only a 17% negative
™ Systemic hypertension predictive value, thus making it a poor screening test. Nocturnal
™ Enuresis polysomnography remains the diagnostic modality of choice and is the
™ FTT gold standard for diagnosis of OSAHS.
™ Increased Gastro-oesophageal Reflux Disease (GORD)
™ Developmental delay
486 The Baby Bear Book Respiratory 487

Is the history or Findings associated with OSAS include: Management

physical examination ™ History Tonsillectomy and Adenoidectomy (T&A)
suggestive of OSAS? Š habitual snoring with labored
™ Mainstay of treatment of childhood OSAHS
breathing
™ Relatively simple procedure that usually results in cure
Š observed apnea
Š restless sleep
™ Outpatient surgery is not recommended as post-operative
Yes No Š daytime neurobehavioural respiratory complications may occur
abnormalities or sleepiness ™ Children at increased risk of complications include those who are
™ Physical Examination severely obese, those < three years old, those with severe OSAHS
Š growth abnormalities complicated by cor pulmonale or FTT, and those with underlying
Š signs of nasal obstruction, adenoidal abnormalities e.g. neuromuscular disorders, cerebral palsy, Trisomy 21,
Continue screening facies, enlarged tonsils
craniofacial disorders, or achondroplasia. These same children are at
Š increased pulmonic component of
second heart sound risk for incomplete resolution of OSAHS after adenotonsillectomy and
Š patient may have no abnormalities on persistent or recurring symptoms should be re-evaluated and treated
examination
Other Surgical Techniques
™ Used in selected cases
Resuscitate if necessary, arrange urgent ™ Include uvulopharyngopalatoplasty, tongue wedge resection,
Is there evidence of cardiac or referral to appropriate physician depending epiglottoplasty, mandibular advancement, other craniofacial surgery
Yes
respiratory failure? on underlying cause, e.g. paediatrics, ENT, or tracheostomy
CICU, respiratory medicine or cardiologist.
Nasal Continuous Positive Airway Pressure (CPAP)
No Complex high-risk patients include: ™ Generally well-tolerated and effective
™ infants ™ Indications for CPAP include transient OSAHS in the peri-operative
™ patients with:
period after T&A, residual OSAHS after T&A, pre-operative
Š cranofacial Š Sickle cell stabilisation of severe OSAHS prior to T&A, long-term management
disorders disease of OSAHS in the child without adentonsillar hypertrophy and OSAHS
Is this a complex or high-risk patient? Š Down syndrome central
associated with morbid obesity
Š cerebral palsy hypoventialation
™ Pressure requirements change with growth. Thus it is necessary to
Š neuromuscular syndromes
No re-evaluate patients on a regular basis
disorders genetic /
Š chronic lung metabolic / ™ Side-effects of CPAP are minor and include nasal symptoms and skin
disease storage disease breakdown
Treat co-morbid conditions e.g.
allergic rhinitis, obesity and Yes Supplemental Oxygen
re-evaluate for OSAS ™ Results in improved arterial oxygen saturation
™ Does not address many of the pathophysiologic features associated
with the symptoms of OSAHS
™ May blunt the hypoxic drive and should not be used as a first-line
Refer to physician treatment
Needs
Persistent symptoms with expertise in
Polysomnography
sleep disorders Intraoral Appliances
™ Have not been studied in children, and their effect on facial growth
Fig. 13.3: Evaluation of obstructive sleep apnoea syndrome (OSAS). has not yet been determined
488 The Baby Bear Book
™ Nasal valve dilators have been marketed to improve snoring in adults
and have no role in the treatment of OSAHS in children
Weight Loss
™ Recommended for all obese patients; clearly desirable but difficult to
achieve
Pharmacological Agents
™ Limited role
™ Nasal decongestants and topical steroids may be helpful in snoring
and mild OSAHS
™ Medroxyprogesterone acetate augments ventilatory drive and
has been used in the management of day-time hypoventilation
associated with obesity hypoventilation syndrome
™ Protriptyline and other REM sleep suppressants have been used in
adults to reduce the number and severity of obstructive apnoeas by
reducing the time spent in REM sleep and is not recommended for
use in children
Follow Up
Most children with OSAHS have complete relief of symptoms with
adenotonsillectomy. A post-operative polysomnogram is indicated in
children with residual symptoms after surgical management, those
with severe OSAHS (> 20 events/hr) and in patients with increased
risk of surgical failure (CNS disease, Down Syndrome, etc.). Long-term
monitoring in high-risk children is appropriate as recurrence of OSAHS is
not uncommon.
BIBLIOGRAPHY
1. 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.
2. 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.
3. 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.
4. 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.
Respiratory 489
UPPER RESPIRATORY TRACT INFECTIONS
Children < five years experience between three and eight episodes of
URTI per year. Most are minor, of short duration and are self-limiting.
Over 90% are caused by viruses for which antibiotics are not necessary.
COMMON COLD (ACUTE INFECTIVE RHINITIS)
™ Usually viral in aetiology — Rhinovirus most common
™ Presentation — Nasal congestion, sneezing and mucoid discharge
with the absence of pharyngitis. Mild conjunctivitis, throat irritation
and low-grade fever can also be present
™ Symptomatic relief of the nasal congestion and secretions is
sufficient. Antibiotics are not indicated
™ Mucopurulent nasal discharge is a common feature of
uncomplicated viral rhinitis and is not an indication for antibiotics
™ Must be differentiated from conditions such as allergic and
vasomotor rhinitis which have a more chronic course
™ In very young children, a nasal foreign body should be excluded
PHARYNGITIS
Patients who present with a sore throat may have pharyngitis, tonsillitis
or tonsillopharyngitis. The presence of rhinorrhoea, laryngitis, cough
and discrete mouth ulcers is more likely with a viral infection. Main
concern — untreated Group A Bhaemolytic Streptococcus (GABHS) may
cause rheumatic fever. May be difficult to differentiate viral pharyngitis
from GABHS in a clinical setting.
™ Predictive model — Presence of moderate to severe tonsillar
swelling, moderate to severe tenderness and enlargement of cervical
lymph nodes, and the absence of coryza yields a 65% probability for
GABHS. When present, a scarlatiniform rash increases the probability
to 95%. A probability of < 15% was observed when all the above
features were absent, and coryza was present
™ Rapid antigen detection assays for GABHS are diagnostic if positive,
with 98–99% specificity. With only 70% sensitivity, follow-up cultures
for negative tests are necessary
™ Recommended treatment for group A streptococcus infection —
Penicillin V (50mg/kg/day, six hourly) for ten days or amoxycillin
(50mg/kg/day, eight hourly) for six days. Antibiotic therapy should
be instituted within nine days of infection
490 The Baby Bear Book
SINUSITIS
Acute sinusitis is a difficult diagnosis to make in children as characteristic
symptoms are often absent.
™ Maxillary or ethmoid sinusitis usually follows a viral URTI
™ Symptoms — Fever, mucopurulent nasal discharge, cough and facial
pain
™ Diagnosis is considered only after seven days of symptoms as prior to
this the presentation is very similar to acute rhinitis
™ It can be considered in a child with severe URTI symptoms with nasal
discharge and high fever of > 39˚C
™ Diagnosis supported by radiological imaging, though generally not
necessary in those < six years old. The best modality is a limited CT
scan, especially when surgical drainage is being considered
The majority of cases of acute sinusitis are caused by bacteria.
™ Common organisms — S. pneumoniae, H. influenzae and Moraxella
catarrhalis
™ Treatment:
Š Amoxycillin or cotrimoxazole for ten days
Š Amoxycillin/sulbactam combination can be used if there is poor
response with first-line drugs
Š Adjunctive therapy such as nasal decongestants and
antihistamines may be useful
™ Complications — Intracranial infection such as meningitis or brain
abscess
™ Refer to Ear, Nose and Throat specialist if pre-septal cellulitis occurs
or if symptoms persist after three weeks despite adequate antibiotic
treatment
LOWER RESPIRATORY TRACT INFECTIONS (LRTI)
LRTI such as croup (acute laryngotracheobronchitis), bronchiolitis,
bronchitis and pneumonia account for a large proportion of infants and
children admitted to hospital.
Croup (Acute Laryngotracheobronchitis)
™ Peak age of susceptibility is six months to two years
™ Presentation — Few days of an URTI, followed by a gradual onset
of stridor and a harsh barking cough. Usually not toxic. The illness
gradually resolves spontaneously over a few days
™ The most common aetiological agent is parainfluenza virus;
antibiotics are not indicated
Respiratory 491
™ Therapy includes:
Š Humidified oxygen
Š Dexamethasone (either 0.6mg/kg/day as a single dose IM or
0.2mg/kg 12 hourly for three doses orally)
Š Inhaled adrenaline (1:1,000) 0.5ml/kg (max 5ml)
Š Admission for monitoring and further treatment may be
necessary for moderate to severe cases
™ Differential diagnoses of stridor in children include acute epiglottitis,
bacterial tracheitis and retropharyngeal abscess. These require an
urgent referral to hospital. In young children with a sudden onset of
stridor, foreign body aspiration must be excluded.
Bronchiolitis
Acute bronchiolitis affects about 1–2% of infants. It occurs below the
age of two years with a peak age between two to ten months. The main
aetiological agent is RSV. Children present with upper tract symptoms
progressing on to develop tachypnoea, crepitations and rhonchi.
Therapy is primarily supportive with maintenance of adequate
oxygenation and appropriate hydration and nutrition.
™ Antibiotics are not indicated unless bacterial co-infection is
suspected
™ Bronchodilators not routinely given. Trial of bronchodilators can be
used, continuing therapy only if there is a definite clinical response
™ No clinical benefit from the nebulised or systemic corticosteroids in
the acute phase of bronchiolitis
Bronchitis
Acute bronchitis is an inflammatory condition involving the airways.
™ It occurs in older children, as opposed to viral bronchiolitis
™ It is usually precipitated by a viral infection and is self-limiting
™ Occasionally Mycoplasma pneumoniae can be a causative agent
™ Presentation — Symptoms of an URTI associated with tachypnoea,
crepitations and rhonchi
™ The appearance of the sputum is not predictive of a bacterial process
Pneumonia
Community-acquired pneumonia remains a serious cause of morbidity
and mortality in children. It is diagnosed in approximately 2% of infants
younger than one year and in 4% of children aged one to five years. The
responsible pathogen is determined in 40–60% of cases.
492 The Baby Bear Book Respiratory 493

LRTI? ™ Majority of pneumonias are viral in aetiology, the main organism

Respiratory distress, tachypnoea, crepitations, rhonchi, breath sounds being RSV
™ Clinical, laboratory and radiographic findings are not specific in
CXR differentiating bacterial and viral etiologies
™ In managing bacterial pneumonia, the choice of antibiotic is based
Normal or hyperinflated or Bronchopneumonia, on the frequency of the pathogens in various age groups, local
perihilar streakiness lobar consolidation antibiotic resistance patterns, clinical presentation and host factors
™ Main bacterial aetiological agent causing severe pneumonia is S.
Reconsider
Toxic? Yes No Toxic? pneumoniae
diagnosis
™ Risk factors for acquiring drug-resistant S. pneumoniae include:
No Yes
Š Young children
Š Recent or prophylactic use of antibiotics
Symptomatic treatment Age?
< three Š Co-existing illness or underlying disease
months Š Immunodeficiency syndromes
Age > two years? Š Daycare centre attendance
No Yes
Three Š Recent hospitalisation or institutionalised patients
to 24 ™ If pneumonia develops in these high-risk groups, higher doses of
months amoxycillin should be used for treatment
Bronchiolitis Bronchitis
™ Oral antibiotics are sufficient for the majority of patients except for
Two to
those with severe infection associated with respiratory insufficiency,
Trial of five years
septicaemia, empyema or lung abscesses
bronchodilators
> five ™ Switching from parenteral to oral therapy can be done in the
No improvement years absence of complications such as empyema or lung abscess if the
after one week
child is afebrile for 24–48 hours
Toxic? Mycoplasma pneumoniae S. pneumoniae
Erythromycin x ten days Amoxycillin x seven days BIBLIOGRAPHY
No Yes 1. Selwyn BJ. The epidemiology of acute respiratory tract infection in young children:
comparison of findings from several developing countries. Coordinated Data Group of
S. pneumoniae BOSTID Researchers. Rev Infect Dis. 1990;12 Suppl 8:S870–S888.
Secondary bacterial infection, H. influenzae
2. Denny FW, Clyde WA Jr. Acute lower respiratory tract infections in nonhospitalized
S. pneumoniae or children. J Pediatr. 1986;108(5 Pt 1):635–646.
Amoxycillin x seven days 3. Attia MW, Zaoutis T, Klein JD, Meier FA. Performance of a predictive model for
H. influenzae streptococcal pharyngitis in children. Arch Pediatr Adolesc Med. 2001;155(6):687–691.
Amoxycillin x seven days 4. Yun BY, Kim MR, Park JY, Choi EH, Lee HJ, Yun CK. Viral etiology and epidemiology of acute
S. pneumoniae lower respiratory tract infections in Korean children. Pediatr Infect Dis J. 1995;14(12):1054–
H. influenzae 1059.
Chlamydia trachomatis 5. Tan TQ, Mason EO Jr, Barson WJ, Wald ER, Schutze GE, Bradley JS, et al., Clinical
S. aureus characteristics and outcome of children with pneumonia attributable to penicillin-
Bordetella pertussis
Amoxycillin ± Cloxacillin susceptible and penicillin-nonsusceptible streptococcus pneumoniae. Pediatrics.
Moraxella catarrhalis 1998;102(6):1369–1375.
Erythromycin x ten to 14 days
GBS, E. coli,
N. meningitidis
L. monocytogenes
IV Ampicillin and Gentamicin
Duration of treatment indicated is the minimum for uncomplicated cases.
Fig. 13-4: Algorithm for the management of LRTI.
494 Rheumatology, Immunology and Allergy 495

™ Infection-related e.g. reactive arthritis, septic arthritis and rheumatic

RHEUMATOLOGY, IMMUNOLOGY & ALLERGY fever

™ Connective tissue disease e.g. Juvenile Idiopathic Arthritis (JIA),
Lupus, Juvenile Dermotomyositis and vasculitis
™ Metabolic conditions such as rickets and mucopolysaccharidoses e.g.
APPROACH TO LIMB ACHES Scheie’s Syndrome
AND JOINT PAINS ™ Perthe’s Disease
™ Ehlers-Danlos Syndrome
When a child complains of limb or joint pain, it is important to ™ Drugs, especially steroids (compression fractures or avascular
determine the: necrosis)
™ Anatomical source of pain
™ Cause Musculoskeletal pain syndromes of childhood include:
™ Any contributing emotional and social factors ™ Reflex Sympathetic Dystrophy (RSD)
™ 'Growing pains', which may be associated with hypermobility
Sources of limb pain include:
™ Muscle e.g. viral myositis, Juvenile Dermatomyositis (JDM) A large psychological component and secondary gain (attention,
™ Bone e.g. from fracture, tumour, infection escape, insurance) may play a key role in:
™ Ligament or tendon e.g. from overuse, sprain, enthesitis ™ Psychosomatic (conversion) disorders
™ Skin and soft tissue e.g. cellulitis, abrasion, foreign body ™ Malingerers
™ Neurovascular e.g. compartment syndrome, reflex sympathetic ™ Munchausen’s Syndrome and Munchausen’s Syndrome by Proxy
dystrophy
™ Joint pain (such as from synovitis, loose body, hemarthrosis In these conditions, the child may complain of severe pain, yet have no
™ Referred pain (such as from a proximal joint or nerve objective evidence of physical illness and be otherwise quite well.
™ Psychologically related ('head' and 'heart' involved)
The aetiology of pain is elicited by the time-honoured techniques of
Causes of pain include: careful history, physical examination and selected tests, with special
™ Trauma attention to:
™ Tumour ™ Excluding serious systemic illness (pallor, lassitude, weight loss,
™ Infection hepatosplenomegaly, lymphadenopathy, abdominal masses, fever,
™ Inflammation rashes)
™ Immunological reaction ™ Observing the psyche and social makeup of child and family as well
™ Hematologic and vascular disease as informal observation of the child’s behaviour
™ Metabolic disease ™ Inflamed joints are usually painful, warm, erythematous, swollen and
™ Musculoskeletal limited in range of motion. By contrast, cool, dusky limbs are found
™ Degenerative disease and in vasculitis and RSD. Lack of use from pain may result in secondary
™ Hypermobility stiffness, contractures, atrophy and weakness
™ Investigations that are helpful include markers of inflammation
In children, special conditions to be aware of include: and connective tissue disease, as well as imaging. Joint aspirates to
™ Non-accidental injury exclude infection or bleeding biopsies, peripheral blood film and
™ Leukemia bone marrow aspirate (for malignancy), coagulation screen (for
™ Haemophilia bleeding dyscrasias), immunoglobulins (for immunodeficiency)
496 The Baby Bear Book
and metabolic screen (e.g. for rickets, Marfan’s syndrome, storage
disease) are done if the specific disorders are considered likely
Some important causes of limb aches and pains include growing pains,
reactive arthritis, JIA, Enthesitis Related Arthritis (ERA) and malignancy.
In growing pains, the pain typically occurs in the legs at night, and can
be very severe. It lasts for < one hour, and is relieved by mummy’s loving
caress and massage (any ointment will do). There is no swelling, redness
or limping. The child is between four to 12 years old, and is totally well
the next day, running around and jumping as usual with no evidence of
synovitis; investigations are normal. There may be mild hypermobility of
the joints. The child outgrows this with time.
Malignancy may be in the form of leukemia (check for
hepatosplenomegaly, lymph nodes, loss of appetite and weight, pallor,
and blasts in the PBF), lymphoma, neuroblastoma or primary bone or
muscle tumours.
Reactive arthritis can occur within four to six weeks of an URTI,
gastroenteritis or vaccination. It can give rise to elevated ESR, swelling,
and limp and restricted movement. Paracetamol or NSAIDS and rest
during the acute phase, followed by physical stretching and activity,
helps relieve pain and hastens recovery to full range of movement and
normal muscle strength.
JIA occurs in children below the age of 16 years, lasts at least six weeks,
has no known underlying cause and has definite evidence of arthritis,
manifested by swollen, painful joints and limited range of movement.
™ The commonest form of JIA is pauci-articular onset (four joints or
less) which responds to NSAIDs/intra-articular steroid injection, and
has the highest risk of silent uveitis (regular eye review necessary)
™ Polyarticular disease (five joints or more) may need methotrexate/
steroids. Etanercept and Infliximab (anti-Tumour Necrosis Factor
(TNF) drugs) are used for resistant cases
™ Systemic disease with fever, rash and hepatosplenomegaly is treated
in the systemic phase with NSAIDs and steroids. Arthritis may need
methotrexate and joint injections. Note that the rash appears during
a spike in temperature and the arthritis may be delayed by weeks to
months. Fever must show a quotidian pattern and be continuous for
at least two weeks
Rheumatology, Immunology and Allergy 497
™ ERA often starts in young boys around the age of nine to ten years.
They might complain of backache, peripheral arthritis (knee, ankle,
Metatarsophalangeal (MTP) joints), enthesitis (especially Achilles
tendon) and plantar fasciitis. They may be Human Leukocyte
Antigens (HLA)-B27-positive. There may be a family history of HLA-
B27-positive arthritis
™ In all cases, take care to exclude presence of psoriasis
INITIAL INVESTIGATIONS FOR SUSPECTED
RHEUMATOLOGICAL DISORDERS
WHEN TO SUSPECT RHEUMATIC DISEASE
™ Prolonged fever
™ Rash
™ Musculoskeletal complaints (limb or joint pain, swelling, disuse)
™ Multisystemic disease
™ Loss of weight
CONDITIONS WHICH MAY HAVE A RHEUMATIC COMPONENT
Inflammatory Rheumatological Disorders ('Autoimmune
Disorders')
™ SLE, JDM, Scleroderma, Mixed Connective Tissue Disease (MCTD),
Undifferentiated Connective Tissue Disease (UCTD)
™ JIA
™ Vasculitides
Non-inflammatory Musculoskeletal Pain Syndromes
™ Hypermobility
™ Overuse/trauma/osteochondroses
™ Musculoskeletal pain syndromes — Growing pains, reflex
sympathetic dystrophy
™ Psychosomatic/malingering
Musculoskeletal Manifestations of Systemic Disease
™ Infection — Infectious, reactive, rheumatic fever
™ Malignancy — Leukemia, lymphoma, neuroblastoma, bone/
cartilaginous tumour
498 The Baby Bear Book Rheumatology, Immunology and Allergy 499

Table 14-1: Tests to order to assess the particular rheumatic disease.

™ Bone/connective tissue disorder — osteochondrodysplasia, Marfan’s
Syndrome, Ehlers-Danlos Syndrome First-line Second-line
™ Metabolic Disease e.g. mucopolysaccharidoses/ mucolipidoses Suspected SLE ANA, dsDNA, complements, PBF for haemolysis, reticulocyte
™ Haemophilia urinalysis, U/E/Cr count, Direct Coombs Test (if
™ Endocrine — Hypothyroidism, pancreatitis related anaemic), ENA (Ro, La, Smith,
™ Immunodeficiency-associated arthritis Ribonucleoproteins (RNP)), RF, APS
(PTT, Lupus Anticoagulant (LAC),
™ Periodic Fever syndromes (FMF†, Hyper IgD, PFAPA†, NOMID/CINCA†)
Anticardiolipin Antibody (ACA))
FCUS†, MWS†, TRAPS†
Suspected JDM Muscle enzymes (aldolase, MRI, Electromyography (EMG)
Creatine Phosphokinase (CK), muscle biopsy
PURPOSE OF INVESTIGATIONS LDH, AST, ALT) Exclude SLE, MCTD (dsDNA, rnp)
™ Diagnose rheumatic disease and major associated complications
Suspected JIA ANA Joint aspirate (exclude infection,
™ Exclude other conditions
RF (polyarticular disease) malignancy, haemarthrosis)
ASOT (reactive arthritis), RF,
Groups of Investigations HLA B27 (subtype of JIA)
™ Evidence of inflammation — ESR, CRP, FBC (prolonged inflammation X-ray (exclude cyst/tumour,
can result in anaemia, leucocytosis, thrombocytosis) infection)
™ Specific tests for autoimmune rheumatic diseases — Anti-nuclear Hepatosplenomegaly Cultures (blood, others as Serology (Hepatitis, Typhoid, EBV,
Antibody (ANA), Double-stranded DNA (dsDNA), Rheumatoid and fever — suspect relevant - for bacteria) PBF for CMV, Bartonella)
Factor (RF), Extractable Nuclear Antigen (ENA), complement, Still’s disease, blasts, consider bone marrow, CT Malaria (PBF), TB (Mantoux, CXR)
Anti-neutrophil Cytoplasmic Antibodies (ANCA), markers for malignancy, SLE, abdomen ANA, dsDNA Consider metabolic screen for
metabolic disorder, Mucopolysaccharidosis (MPS),
Antiphospholipid Syndrome (APS)
infection Metachromatic Leukodystrophy
™ Organ involvement — Renal function, urinalysis, liver function tests, (MLD), etc.
muscle enzymes
™ X-rays, aspirates, biopsy as appropriate
™ Specific tests for other diseases as suspected:
Š Infectious agents INTERPRETATION OF RESULTS
Š PBF for blasts, bone marrow aspirate, CT scan for malignant mass Hematological: FBC, PBF, reticulocyte
Š Immunoglobulins Haemoglobin: Anaemia
Š Coagulation screen, PTT ™ Normochromic, normocytic anemia of chronic disease (inflammatory
Š Thyroid function, amylase, urine for metabolic screen disorder)
™ Haemolytic anemia (SLE)
Which Tests to Order to Assess Particular Rheumatic Disease ™ Iron deficiency anaemia (blood loss e.g. from esophagitis
™ FBC, ESR, CRP for all — Useful to screen for inflammatory disease -scleroderma, NSAIDs, poor diet)
(autoimmune disease, infection, malignancy) ™ Megaloblastic anaemia (pernicious anemia associated with autoimmune
™ In general, RF, ANA synovial biopsy and plain radiographs are disease, Rheumatoid Arthritis, drugs like methotrexate, Azathioprine)
unsuitable for screening as they are neither sensitive nor specific
White Cells
™ Counts low in SLE (especially lymphocytes), immunosuppressive
†
drugs (Azathioprine, cyclophosphamide, methotrexate), infiltrative
FMF: Familial Mediterranean fever; PFAPA: Periodic fever, aphthous stomatitis, pharyngitis and adenitis;
NOMID/CINCA: Neonatal onset multisystem inflammatory disease / Chronic infantile neurologic cutaneous malignancy e.g. neuroblastoma
articular syndrome; FCUS: Familial Cold Urticaria Syndrome; MWS: Muckle Wells Syndrome; TRAPS: TNF ™ Counts elevated in infection, leukemia, inflammation (Still’s disease),
Receptor Associated Periodic Syndrome steroid use
500 The Baby Bear Book
Platelets
™ Thrombocytopenia (SLE, APS, immunosuppressive drugs
™ Thombocytosis (inflammation e.g. Still’s disease, reactive to anaemia)
Peripheral Blood Film
™ Evidence of haemolysis
™ Blasts
™ Malaria
Biochemical Tests
™ Acute Phase Reactants: At least 30 proteins produced by liver in
response to cytokines in acute and chronic inflammation
™ Commonly measure ESR and CRP
™ Elevated ESR, CRP indicative of inflammatory diseases (e.g.
'autoimmune' diseases, infection, malignancy)
™ Normal ESR, CRP more likely found in mechanical, psychogenic,
metabolic/endocrine disease or if inflammation is mild (e.g. pauci-
articular JIA)
ESR (mm/hr)
Affected by anaemia, immunoglobulins, sex, age, weight (higher in
anaemic, older, obese, females)
CRP
™ Responds more rapidly than ESR but may not rise in mild
inflammation
™ In active lupus: High ESR but normal CRP (unless infection, serositis,
respiratory disease)
™ Useful to monitor response of infection to antibiotic treatment
LFTs
™ Enzymes elevated in liver damage (autoimmune disease e.g.
SLE; drugs e.g. methotrexate, cyclophosphmide, sulphasalazine,
azathioprine), myositis (JDM, polymyositis)
™ Albumin low in chronic disease, nephrotic syndrome (SLE)
™ Total protein elevated in SLE (hypergammaglobinemia)
Renal Function Tests
™ Urinalysis for haematuria, proteinuria, casts
™ Proteinuria quantified by urine protein/Cr ratio, timed collection (to
achieve 24-hour UTP)
Rheumatology, Immunology and Allergy 501
™ Serum creatinine not sensitive (creatinine clearance must fall to
below 30ml/min — about a third of normal values) before it rises
™ Creatinine Clearance Test (24-hour CCT) and chromium-labeled EDTA
test more useful
™ Plasma urea influenced by hydration and protein metabolism
Immunological Investigations
Autoantibodies
™ Immunoglobulins that bind to self antigens
™ RF, ANA, dsDNA, ENA, APS, ANCA
Rheumatoid Factor (RF)
™ IgM to Fc portion of IgG
™ Significance related to your own lab’s normal values and clinical
correlation
™ Found in the rare JIA-Polyarticular-RF-positive subtype
™ Can be non-specific: Also found in SLE, Sjögren’s Syndrome, vasculitis
(Polyarteritis Nodosa (PAN)), chronic infection (EBV, Subacute
Bacterial Endocarditis (SBE), TB, leprosy, syphilis), chronic liver disease
Antinuclear Antibodies (ANA)
™ Immunoglobulins that bind to antigens on the cell nucleus
™ Detected by Immunofluorescence (IF)
™ Non-specific, can be found in:
Š Autoimmune disease (SLE > 95%, Sjögren's Syndrome 80%,
scleroderma 20%, Rheumatoid Arthritis (RA) 30%)
Š Infection (especially chronic infection like TB, leprosy) — Transient
Š Chronic active hepatitis
Š Malignancy
Š Old age (generally low-titre)
™ Pattern of immunofluorescence depends on which antigens are
recognised:
Š Homogenous — Lupus (DNA or histones)
Š Speckled — Smith, Ro, La, RNP (overlap or mixed disease, lupus,
Sjögren's Syndrome)
Š Nucleolar — Scleroderma
Š Centromere (in dividing cells) - CREST (restricted form of
scleroderma)
™ More accurately characterised by Enzyme-linked Immunosorbent
Assay (ELISA)
502 The Baby Bear Book
Antibodies to DNA (dsDNA)
™ Detected by ELISA, Farr assay (precipitation test)
™ In SLE: dsDNA antibodies diagnostic, vary with disease activity,
especially associated with renal disease
Antibodies to Extractable Nuclear Antigens (ENA)
™ Smith — SLE
™ Ro, La — Sjögren’s Syndrome, SLE
™ RNP — High titre found in MCTD
™ May have considerable overlap between expression of clinical
disease and particular antibodies
Antiphospholipid Antibodies (APS)
™ Bind chiefly to negatively charged phospholipids like cardiolipin
™ Three tests available which detect slightly different but overlapping
populations of antibodies:
Š VDRL false positive — Limited use
Š LAC — More sensitive, coagulation assay based on PTT
Š ACAs IgG and IgM ELISA — Simplest and cheapest
™ Fourth test: Antibody to co-factor protein (2 glycoprotein 1 — May
be better associated with clinical features now becoming available at
specialist centres)
™ Persistently raised levels especially of IgG associated with
thrombosis, recurrent foetal loss, thrombocytopenia, neurological
disorders
™ APS 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 IF:
Š cANCA (cytoplasmic diffuse staining) to serine proteinase III e.g.
Wegener’s Granulomatosis (80%)
Š pANCA (peripheral staining around edge of nucleus) to
myeloperoxidase e.g. PAN, vasculitis complicating SLE, Ulcerative
Colitis (UC), RA
Immunoglobulins
™ General polyclonal rise in total Ig seen in many rheumatic conditions
as non-specific reflection of an acute-phase response
™ Can also be markedly elevated in HIV infections, where some
manifestations may mimic rheumatic conditions
Rheumatology, Immunology and Allergy 503
™ Primary immunodeficiency (low concentration of one or more
immunoglobulin class or subclass) may present with lupus, joint
disease
Complement
™ Complement cascade plays central role in cell lysis, opsonisation of
bacteria, clearance of immune complexes
™ Elevated in inflammation as part of acute-phase response (RA,
seronegative arthropathies)
™ Fall with immune complex formation and consumption (especially
active lupus, nephritis)
™ Persistently low C4 in hereditary conditions which may be associated
with the development of SLE
Imaging
X-rays for Swollen Joint
™ To exclude bone tumour, osteomyelitis with lytic or reactive changes
™ In JIA: Bony changes are not useful as screening test
Š Relatively early change: Increased joint space, soft tissue swelling
Š Later: Narrowing of joint space, erosions, sclerosis
Š Osteopenia, osteoporosis, subluxations, collapse and destruction
of joints, ankylosis
MRI
™ To ascertain site of inflammation e.g. localise tendon sheath synovitis
for steroid injection, biopsy site for JDM
™ Exclude soft tissue tumour or Villonodular Synovitis (VNS)
Joint Aspirate/Synovial Biopsy
™ Synovial biopsy: To exclude TB or foreign body synovitis
In JIA: Non-specific, reveals only chronic inflammatory changes
™ Joint aspirate: Exclude infection (pyogenic bacteria, TB), blood
(haemophilia, VNS, trauma)
In JIA: Proteinaceous, cellular infiltrate
Levels of Significance
™ Depends on laboratory, technique used, local population norms and
clinical correlation
™ For the current laboratory results in KKH/Singapore General Hospital
(lab), significant values for:
Š ANA > 1/800
Š Anti-dsDNA > 70 IU/L (ELISA)
504 The Baby Bear Book Rheumatology, Immunology and Allergy 505

Table 14-2: The three classification systems.

Š ACA:
y ACA IgG > 20 IU/L ACR EULAR ILAR
y Moderate > 20 IU/L Term Juvenile Rheumatoid Juvenile Chronic Juvenile Idiopathic
y High > 80 IU/L Arthritis (JRA) 1976 Arthritis (JCA) 1977 Arthritis (JIA) 1997
Š Significant proteinuria for SLE > 2+ (1g/L) Duration of arthritis ≥ six weeks ≥ three months ≥ six weeks
Š Nephrotic range proteinuria > 40mg/m2/hr Onset types Three Six Seven
Š Urine protein/creatinine ratio > 20mg/mmol
Systemic Systemic Systemic

Polyarticular Polyarticular (RF- Polyarticular RF-

negative) negative
JUVENILE IDIOPATHIC ARTHRITIS (JIA) Juvenile Rheumatoid Polyarticular RF-
Arthritis (RF-positive) positive
™ Is an idiopathic chronic arthritis that begins in childhood
™ Different from adult rheumatoid arthritis Pauciarticular Pauciarticular Oligoarticular
™ Heterogenous clinically Persistent
™ Aetiology unknown. Genetic predisposition with environmental Extended
triggers leads to cytokine mediated inflammation (such as
Juvenile Psoriatic Psoriatic Arthritis
Interleukin 1 (IL1), Interleukin 6 (IL6) and TNF alpha). Possibly a
Arthritis
complex genetic trait associated with HLA genes and cytokine gene
polymorphisms (HLA B27, DR1, 4, 5, 8) Juvenile Ankylosing Enthesitis-related
™ The incidence ranges widely from 0.8–22/100,000 worldwide. In Spondylitis (JAS) Arthritis
Singapore, the incidence is much less — approximately 3.5/100,000
children at risk below the age of 16 years. Asian children lack the Other arthritis (fulfil
female predominance and uveitis described in the west criteria of > one type
or none)
* ACR system: Excludes seronegative spondyloarthropathies (JAS, psoriasis and related diseases)
DIAGNOSIS AND CLASSIFICATION * EULAR system includes spondyloarthropathy. JRA in EULAR refers only to IgM RF-positive disease
™ Clinical and by exclusion. Current recommended definition
and classification is by International League of Associations for
Rheumatology (ILAR):
Š Arthritis for ≥ six weeks SUBTYPES OF ARTHRITIS — ILAR CLASSIFICATION
Š Age onset < 16th birthday The onset subtype is decided by clinical features in the first six weeks of
Š Exclusion of secondary causes illness and is helpful for prognosis and treatment:
Š Arthritis: Joint swelling, or two out of three of pain, warmth, ™ Oligo-articular disease ( ≤ four joints at onset i.e. within the first six
restriction of movement months)
Š 'Dry synovitic' may have progressive contracture without effusion Š Persistent onset (after six months)
™ Different classification systems have been developed by the Š Extended onset ( ≥ five joints after six months) (Extended Onset
European League Against Rheumatism (EULAR) , the American Oligo-articular Juvenile Idiopathic Arthritis (EOPJIA))
College of Rheumatology (ACR) and ILAR (see Table 14-2 next ™ Polyarticular-RF-positive
page). ILAR is recommended for universal application. The three ™ Polyarticular-RF-negative
classification systems have some differences; important to be aware ™ Systemic disease
of this when interpreting literature ™ ERA
506 The Baby Bear Book Rheumatology, Immunology and Allergy 507

Table 14-3: Characteristics of JRA subtypes (adapted from Cassidy & Petty 2001).
™ Psoriatic
™ Other: Oligo or
Polyarthritis Systemic
Š Does not fulfill criteria for any of the other categories Pauciarticular
Š Fulfils criteria for > one category Frequency of cases 30% 60% 10%
Number of
≥ five ≤ four Variable
™ Each joint is counted separately except cervical spine, carpus, tarsus, joints involved
which are each counted as one joint Throughout childhood; Early childhood;
Throughout childhood;
™ Positive RF — Detected on two occasions three months apart Age at onset peak at one to three peak at one to two
no peak
years years
Systemic Disease Sex ratio (F:M) 3:1 5:1 1:1
™ Arthritis with or preceded by daily spiking fever for two weeks, Systemic involvement Moderate involvement Not present Prominent
(quotidian pattern documented for at least three days) and Occurrence of
™ One of the following: Typical rash (evanescent, erythematous), 5% 20% Rare
chronic uveitis
organomegaly, generalised lymphadenopathy, serositis Frequency of seropositivity
™ Rarest form, typically in very young but can occur at any age,
Rheumatoid factors 10% (increases Rare Rare
including adults
with age)
™ May be difficult to diagnose because earliest features often extra-
Antinuclear antibodies 40–50% 75–85%* 10%
articular. A third develops severe polyarthritis which is difficult to
Guarded to Excellent except
treat. May be complicated by pericarditis and macrophage activation Prognosis Moderate to poor
moderately good for eyesight
syndrom
* In girls with uveitis

Polyarticular Disease
™ Arthritis affecting ≥ five joints during the first six months of disease
™ Relatively rare. More common in females. Tends to be bilateral,
symmetrical, erosive disease requiring Disease-modifying Anti-
rheumatic Drugs (DMARDs) like methotrexate
™ Mostly girls, who develop arthritis in pre-school years (RF-negative)
™ RF-positive arthritis is rare (< 10%), usually in older girls/adolescents,
mimics adult RA i.e. it is more severe
™ A third develop bony erosions and active arthritis that persist into
adulthood
Oligo-articular Disease
™ Classically the little girl with the swollen knee. Most common
subtype, commonly ANA positive
™ Arthritis is usually easily treated with NSAIDs or intra-synovial
steroids, but iritis (20% reported) can lead to blindness if untreated.
A third develops extended disease i.e. > four joints after the first six
months
Enthesitis-related Arthritis (ERA)
™ Arthritis and enthesitis, or
™ Arthritis or enthesitis with at least two of the following:
Š Sacroiliac joint tenderness and/or inflammatory spinal pain
Š Presence of HLA-B27
Š Family history in > one first- or second-degree relative of
medically confirmed HLA-B27-associated disease
Š Anterior uveitis that is usually associated with pain, redness or
photophobia
Š Onset of arthritis in a boy after eight years of age
™ 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

For the characteristics of JRA subtypes, please see Table 14-3 next page.
508 The Baby Bear Book Rheumatology, Immunology and Allergy 509

Juvenile Psoriatic Arthritis Physical Findings

™ Arthritis and psoriasis, or ™ Growth, pubertal status — Any delay (chronic illness)
™ Arthritis and at least two of the following: Dactylitis (sausage digit), ™ Systemic features — Fever, Rash (salmon pink evanescent/psoriatic/
nail pitting or onycholysis, family history of psoriasis in a first-degree vasculitic), nail pitting, organomegaly, lymphadenopathy
relative ™ Musculoskeletal — Qasting, abnormal gait (e.g. waddling), kyphosis
™ Arthritis may predate onset of psoriasis by many years
Mark joint/tendon findings on the skeleton n in
COMPLICATIONS OF JIA Fig. 14.1 for easier visualisation and review
™ Limb pain, swelling, deformity ™ Joints — Peripheral (include
™ Loss of function, independence and ambulation temporomandibular /sacro-iliac)
™ Contracture, limb overgrowth, limb length discrepancy ™ Axial skeleton — Cervical, thoracic, lumbo- mbo-
™ Osteoporosis, fracture, avascular necrosis sacral (touch toes, measure distance from om
™ Growth and pubertal delay (short stature, FTT) the floor)
™ Uveitis, loss of vision, blindness ™ Tendonitis/enthesitis — Including
™ Macrophage activation syndrome (risk of DIC, death) plantar fascia, tendoarchilles
™ Social and financial cost — Loss of schooling, social development, ™ Synovial swelling over tendon
poor self-image, hospitalisation sheaths e.g. dorsum of hand, feet
™ Drug toxicity ™ Deformities (contractures, varus,
valgus, dropped wrists, swanneck or
CLINICAL EVALUATION OF A CHILD WITH SUSPECTED JIA Boutonniere)
Aims ™ Measure limb length discrepancy
™ Determine any evidence of synovitis/arthritis/enthesitis Fig. 14.1: Skeleton to mark joint/tendon findings.
™ Exclude secondary causes for limb symptoms (especially infection, INVESTIGATIONS
malignancy, reactive arthritis) No investigation is pathognomonic of JIA, but several are useful for
™ Assess subtype of arthritis, severity and complications differentials.

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)
At Onset
™ Any evidence of inflammation, send immune markers
™ Exclude secondary disease
Š FBC, ESR, CRP
Š ANA, RF, HLA-B27 (if suspicious), ASOT (recent URTI),
immunoglobulins (immunodeficiency)
Š PBF for blasts, bone marrow, CT abdomen if suspicious of
malignancy e.g. pale, hepatosplenomegaly, distension,
uncharacteristic joint aspirate like few cells
Š Aspirate joint (to exclude infection, blood)
JIA: Neutrophils predominate, gram stain and cultures negative,
long-standing effusions tend to be thick and viscid, recent
effusions more watery and clear
Infection: Turbid, proteinaceous, send for gram stain and culture.
TB or fungus if suspicious
Blood: Haemophilia, trauma, villonodular synovitis
510 The Baby Bear Book Rheumatology, Immunology and Allergy 511

Š Liver function, renal function (baseline if starting NSAIDS) ™ Surgical (orthopaedic)

Š Eye (ophthalmological screening) — For all JIA and especially ™ Patient education, support (social, financial, emotional) — Support
pauci/oligoarticular disease; every four months for the first two club, social worker
years for uveitis
Š Imaging Pain Relief
y X-rays — To exclude other diseases (infection, malignancy). ™ Rest during active inflammation (including splinting), but minimise
Bony changes in JIA are relatively late time spent immobilised
Early: Peri-articular osteopenia, ↑ joint space ™ Warm or cold pack (ice)
Late: Erosions, sclerosis, ↓ joint space/subluxation ™ Paracetamol, massage, Transcutaneous Electrical Nerve Stimulation
Very late: Abnormal bone shape, joint collapse, ankylosis, (TENS)
compression fracture, dislocations, avascular necrosis
y Bone densitometry (DEXA scan) for osteoporosis and bone Physiotherapy
age (for long-standing disease at referral, especially if on ™ Early mobilisation is key to good joint and limb function
steroids or growth failure) ™ Maintains range of motion, coordination, strength
y Others as necessary — Ultrasound (fluid), MRI (localised ™ Land and hydrotherapy (warm water relaxes muscles, provides
tendinitis), CT (tumour), bone scan support and resistance)
™ Posture, stretches, repetitions, weights
Investigations for Follow Up
™ FBC, ESR, CRP
™ Liver function, renal function (for medication side-effects) Table 14-4: Drugs.
™ X-rays for progression of disease (usually for polyarticular disease, Oligo/Pauci-articular Intrasynovial steroids → Repeat injection → Methotrexate/
ERA for sacroiliac disease) Arthritis or NSAIDs Try different NSAIDs hydroxychloroquine
Polyarticular Disease Start DMARD early (methotrexate) oral, IM or SC, increase dose if tolerated
TREATMENT OF ARTHRITIS + Bridging steroid (oral usually, IV pulse if ill)
Goal: Suppression of inflammation and prevention of deformity and + Intrasynovial steroid for troublesome joints
disability, with minimum toxicity Methotrexate, combination with sulphasalazine,
(Others: Cyclosporin, cyclophosphamide, azathioprine, IVIG)
Team approach: Patients, parents, medical, rehabilitative therapists, Biologicals (etanercept, infliximab, adalimumab)
Stem cell transplant
school, social support
Still’s Disease Fever NSAIDs/ steroids (IV pulse methylprednisolone if ill)
™ Correct diagnosis, exclusion of secondary disease
Arthritis NSAIDs/intrasynovial steroids for oligo-articular involvement
Methotrexate for polyarticular disease ‡ similar alternatives
™ Physical — Rest, pain relief, physiotherapy, occupational therapy
Thalidomide
™ Medical: Etanercept
Š Conventional (NSAIDS — Oral, gels, plasters, Cyclo-oxygenase Enthesitis-related NSAIDs/intrasynovial steroid for localised arthritis, tendinitis
(COX-2) inhibitors, steroids — oral, iv, intra-articular, methotrexate, Disease + Sulphasalasine/methotrexate for erosive or resistant disease
sulphasalazine, hydroxychloroquine, IVIG, immunosuppressants) + Bridging steroid
Š New therapies (biologicals against TNF, IL1, IL6, leflunomide, → Combination
thalidomide, combinations, bisphosphonates for osteoporosis) → Biologicals
Š Alternative and traditional (massage, acupuncture, herbs, etc.) For all screen and Eyes: Regular review for uveitis and drug toxicity
Š Regular eye review for uveitis and toxicity of medication (steroid- monitor Drug toxicity
induced cataracts, glaucoma) Growth and osteoporosis e.g. FBC, LFT, U/E/Cr, X-ray
Š Future — Stem cell transplant Bone age, density as necessary
512 The Baby Bear Book Rheumatology, Immunology and Allergy 513

Occupational Therapy
™ Splints and casts to maintain position after stretching (e.g. sleep), for
function (wrist paddles)
Table 14-5: Criteria for the classification of SLE (ACR 1997).
™ Aids (thick pencil, handles), ambulation if really necessary (crutch,
rollator, stroller, wheelchair) Criteria Features/explanations
™ Home adaptations (ramps, rails, height of table, chair, fittings) Malar (butterfly) rash Fixed erythema, sparing nasolabial folds
™ School (ramps, lifts, locker, class location) 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
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Nephritis‡ Persistent proteinuria > 0.5g/dL or 3+
cellular casts (red cell, Hb, granular, tubular,
™ SLE is a multi-systemic disease of immune dysregulation mixed)
characterised by circulating antibodies to nuclear and other
Encephalopathy‡ In the absence of offending drugs or metabolic
tissue antigens (99% positive ANA). Autoantibodies and immune derangements e.g. uremia, ketoacidosis,
complexes mediate tissue injury electrolyte imbalances
™ Wide variety of clinical features, can evolve with time, affecting Seizures
different organ systems; renal, neurological, cardiac disease and Psychosis
infection are major causes of mortality Serositis‡ Pleuritis (pain, rub, effusion)
™ Aetiology unknown, probably an interplay between genetic factors Pericarditis (ECG, rub, effusion)
and environmental triggers Cytopenia‡ In the absence of offending drugs
™ More common in females overall, possible due to hormonal Haemolytic anemia with reticulocytosis
differences. In adults five to ten times more in females, local ratio of Leucopenia (< 4,000/mm3)
9:1. Equal sex distribution below the age of five years Lymphopenia (< 1,500/mm3)
™ Sometimes familial Thrombocytopenia (< 100,000/mm3)
™ Rare in children. In Singapore, analysis of KKH figures (1997–2003) Positive antinuclear antibody test In the absence of drugs associated with 'drug-
indicate the incidence is at least about 1.5/100,000 children at risk induced lupus'
per year, which is about three times the reported western incidence, Positive immunoserology‡ Antibodies to dsDNA
and the overall sex ratio is 3:1 (female predominance). In KKH, we see Antibodies to Smith nuclear antigen
about ten new SLE cases per year
Positive finding of antiphospholipid antibodies
™ IgG or IgM ACA
EVALUATION AND DIAGNOSIS ™ LAC
™ Definite diagnosis of SLE is made when four out of 11 of ACR ™ False positive serologic test for syphilis
classification criteria are present (at any time) and no alternative for at least six months (false positive
explanation exists VDRL) confirmed by Treponema Pallidum
™ However, lupus should be considered when characteristic features Immobilisation (TPI) or Fluorescent
occur in combination or evolve over time. Treatment should be Treponemal Antibody (FTA) absorption test
‡
started if clinical disease is significant even if less than four criteria Any one of the features on the right-side column will do
are met
™ High ESR and normal CRP, low complement levels (especially C3) are
suggestive of active SLE
514 The Baby Bear Book
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, hyperlipidemia)
™ 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
™ Anaemia 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
™ Evaluation of lupus nephritis:
Š Urinalysis — Chemical and microscopic; culture if white blood
cells present
Š Measurement of glomerular function:
y Plasma creatinine, urea nitrogen
y Creatinine clearance; 24-hour protein excretion
y Radionuclide Glomerular Filtration Rate (GFR)
Š Disease — Anti-dsDNA antibody level, complement assay
Š Renal ultrasonography and biopsy — Light Microscopy (LM),
Electron Microscopy (EM), IF
Rheumatology, Immunology and Allergy 515
™ 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
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
™ Activity and chronicity index
Š High activity indicates need for aggressive treatment and
immunosuppression
Š High chronicity and low activity indicates that the damage may
not be reversible. Heavy immunosuppression at this stage is not
recommended because toxicity outweighs benefit
Antiphospholipid Syndrome (APS)
™ At least one of the following: Recurrent foetal loss, vascular
thrombosis (arterial and venous)
™ Plus ACA IgG or Ig M > two standard deviations (probable APS), > five
standard deviations (definite APS) or LAC on two or more occasions
in the last six weeks
™ Other features not included in the classification criteria include leg
ulcer, livedo recticularis, hemolytic anaemia and thrombocytopenia
Neurolupus
™ Clinical features may be due to leucostasis, vasculitis, APS with
thrombosis, infarct, haemorrhage
™ May be overt (seizures, stroke) or subtle (mood changes,
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:
Š CNS: Cerebrovascular disease (stroke/Transient Ischemic 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
516 The Baby Bear Book
Š Peripheral nervous system: Acute inflammatory demyelinating
polyradiculoneuropathy (Guillain-Barré Syndrome), autonomic
disorder, mononeuropathy, single/multiplex, myasthenia gravis,
cranial neuropathy, plexopathy, polyneuropathy
Investigations (Baseline)
For diagnosis of disease, major organ involvement:
™ FBC, ESR, CRP, U/E/Cr, LFTs
™ ANA, dsDNA, Complements C3 C4
™ Urinalysis (UFEME, proteinuria)
™ Other ENA (Ro, La, Smith, RNP), antiphospholipid markers (PT, PTT,
LAC, ACA, VDRL — subject to clinical features, availability, cost) —
Distinguish subsets at risk of different complications
™ Eye review (retinitis, baseline before starting steroid,
hydroxychloroquine)
Investigations (Follow-up)
™ FBC, ESR, C3 C4, dsDNA — For disease activity
™ Urinalysis, U/E/Cr, ± timed UTP, CCT, renal biopsy
™ Others pending organ system involvement
™ Eye review
™ X-ray, bone age, bone densitometry (if at risk for osteoporosis and
growth delay e.g. active disease, prolonged steroid use envisaged)
Clinical Review at Each Visit
Disease activity, disease damage, any new organ involvement, drug
toxicity
™ Growth, pubertal development, general health
™ Clinical — Pallor, rash, ulceration, serositis, hepatosplenomegaly,
arthritis, oedema, neurological deficit, Cushingoid
™ BP
THERAPY
™ Is not curative. Aim to prevent progressive tissue damage and
incapacitating symptoms
™ Individualised
™ Combined care: Medical assessment by rheumatologist,
nephrologist, ophthalmologist, endocrinologist, others as necessary.
Family doctor important in support and coordination
™ Treat flares, hypertension, infection early and appropriately
Rheumatology, Immunology and Allergy 517
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
™ Rest and avoidance of triggering factors (sun or fluorescent-light
exposure, fatigue, intercurrent infection) which provoke exacerbations.
Use Ultraviolet A and B sunscreen SPF >15, hats, long sleeves
™ Raynaud’s Phenomenon: Avoid cold exposure, cigarettes, caffeine,
reduce stress
™ Support groups — JLC (Juvenile Lupus Club), Club Rainbow
Medical Drugs
Use the lowest effective dose
™ Steroids
Š Mainstay of treatment for flares and maintenance treatment (low
dose)
Š Oral steroids for fever, rash, arthritis, serositis, nephritis,
haemolytic anemia, cerebritis
Dose 0.5–2mg/kg/day. Taper slowly as inflammation is controlled
to alternate day dosing
Š IV pulsed steroids (methylprednisolone) associated with faster
clinical improvement especially for rapidly progressive CNS
or renal disease. Dose 10–30mg/kg/dose for one to three
consecutive days (0.5–1g)
Š Topical steroids for localised skin rash
Š Monitor for toxicity especially BP, eye, osteoporosis and growth
failure
™ Hydroxychloroquine
Š Useful for rash, arthritis, serositis and malaise, protects against
APS and prolongs remission. Not effective for CNS, renal,
haematological disease
Š Dose 3–6mg/kg/day
Š Monitor for liver and retinal toxicity
™ Methotrexate
Š For arthritis and rash. Up to 15mg/m2/week
Š Monitor liver function and FBC
™ Azathioprine
Š For nephritis and moderate lupus rash
Š Oral 1–3mg/kg/day
518 The Baby Bear Book Rheumatology, Immunology and Allergy 519

™ Cyclophosphamide Differentiating Between Lupus Flare and Infection

Š For nephritis Class IV (diffuse proliferative GN), neurolupus ™ Both can present with fever and ill health
Š Oral for three-month course or IV pulse 0.5–1g/m2/monthly x ™ Infection can precipitate a flare
seven then three monthly ™ Infection important cause of mortality, so have high index of suspicion
For CNS, up to a year; for Class IV nephritis, up to three years ™ Often infection will have high CRP, but active lupus has normal CRP
™ Mycophenolate (Mofetil) despite high ESR
Š If unable to tolerate cyclophosphamide, or failed azathioprine, ™ Look for sources of infection including respiratory, meningitis, skin
cyclophosphamide, cyclosporin A in class III, IV, V nephritis infection, TB; culture as necessary
Š Dose 600mg/m2 BD oral/IV (0.5–2.0g/day max) ™ Look for evidence of active lupus: rash, arthritis, serositis, low C3,
™ Cyclosporin A high dsDNA titre
Š For nephritis ™ If uncertain, may need to cover for both infection and active disease
Š Dose 3–5mg/kg/day, keep trough level < 200ng/ml flare until investigations return
™ Enalapril
Š For proteinuria, hypertension PROGNOSIS OF SLE
Š Dose 0.2–1.0mg/kg/dose (max 40mg) once a day ™ Vast improvement over the last ten years
™ Others: Antihypertensives, antibiotics, anticonvulsants, splenectomy as ™ Early studies: < 5% survive five years
necessary ™ Now 85–90% survive five years, 75–85% survive ten years. Most
patients have near-normal life span
For APS ™ Worst in Afro-carribeans, Asians, males, patients at extremes of age,
™ Acute phase — Aspirin, heparin, low-molecular-weight heparin like non-compliance with treatment, family history of severe lupus
fraxiparine, prostacyclin ™ Infections, renal disease, CNS complications are major causes of
™ Prophylaxis if major vessel thrombosis — Warfarin, keep INR 3–4 death
(arterial), 2.5–3 (venous) ™ Late in disease — Fracture, cardiovascular complications, infection
are major causes of morbidity
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
JUVENILE DERMATOMYOSITIS (JDM)
Other therapeutic options include renal dialysis, organ transplant, and
stem cell transplant. ™ Characterised by a diffuse microangiitis involving skin, skeletal
muscle, gastrointestinal tract, CNS
In General for Active Nephritis ™ Relatively rare connective tissue disease, locally about two new
Class II Steroids suffice cases/year seen in KKH
Class III Steroids + immunosuppressant e.g. azathioprine ™ Aetiology unknown. Seems to develop after an acute viral infection
Class IV Usually needs aggressive treatment with in many children
cyclophosphamide
Class V Usually nephrotic, may not respond to steroids or CLINICAL EVALUATION
immunosuppressants, use cyclosporin ™ Commonly presents with muscle tenderness and weakness, rash on
ACE inhibitors like enalapril help decrease proteinuria or face and extensor surface, constitutional symptoms
Angiotensin receptor antagonist like losartan ™ Calcinosis, arthritis, muscle atrophy, alopecia common
™ Gastrointestinal vasculitis and CNS disease potentially fatal
520 The Baby Bear Book
™ Palatal and respiratory disease can result in aspiration pneumonia
and respiratory failure
™ Unique characteristics of JDM (as opposed to adults):
Š Vasculitis and calcinosis: Frequent and often severe, indicate
active disease
Š Malignancy: Not associated
™ Range of clinical features of JDM:
Š Constitutional: Fever, malaise, loss of appetite, loss of weight
Š Skin/mucosa: Heliotrope rash and periorbital edema, 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
Š Muscle: Proximal muscle weakness, truncal weakness, speech
(nasal), swallowing, breathing difficulty (shortness of breath,
exertional dyspnea)
Š Joints: Arthritis, arthralgia, contractures
Š Gastrointestinal tract: Gut vasculitis (potentially life-threatening),
pancreatitis, hepatitis
Š CNS: Vasculitis with seizures, stroke, chorea
Š Lung: Interstitial lung disease, pneumothorax, abnormal lung
function
Š Cardiac: Pericarditis, myocarditis, arrhythmia, sinus tachycardia
Š Infection: Prone to infections of skin (calcinotic lesions, S. aureus
abscess), lung (suppurative, TB, Pneumocystis carinii pneumonia
(PCP))
Š 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
14-6 next page for the five 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)
Rheumatology, Immunology and Allergy 521
Table 14-6: 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 of skeletal muscle enzymes — CK, AST, LDH, aldolase
™ EMG — Myopathy and denervation
™ Muscle biopsy — Necrosis and inflammation
™ 'Dermatomyositis sine myositis' — 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
™ Important to exclude other connective tissue disease (e.g. SLE, MCTD
- check ANA, dsDNA, u1 RNP), eczema, infective rash. Usually no
positive immune markers in JDM
MEDICAL TREATMENT
™ Glucocorticoids
Initial:
Oral prednisolone 2mg/kg/day x one month/until better; or
IV methylprednisolone 30mg/kg/day x one to three days (for severe disease — more
rapid improvement);
Then:
Oral prednisone 1mg/kg/day followed by a gradual taper in dose over approximately
two years
™ Hydroxychloroquine
3–6mg/kg/day in addition to prednisolone for control of skin disease
™ Immunosuppressives
Methotrexate: 0.35–0.65mg/kg/week or 10–20mg/m2/week (oral, IM or SC); max
20mg/week
Cyclosporin: 3–5mg/kg/day
Cyclophosphamide: 1mg/kg/day orally or 500–750mg/m2/month
Azathioprine: 1–3mg/kg/day
™ Intravenous immunoglobulin
2g/kg/month
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
522 The Baby Bear Book Rheumatology, Immunology and Allergy 523

Review Other modalities of treatment include:

At each visit, assess: ™ Plasmpheresis — Anecdotal use in severe SLE, in combination with
™ Growth, pubertal development, general health and activity immunosuppression
™ Rash — Increasing calcinosis or vasculitis ulcers, infection ™ Bone marrow/stem cell transplant — Limited number of successful
Š Muscle power — Limbs (proximal and distal), trunk, neck, speech, reports for SLE, JIA other rheumatic disease refractory to other treatment
swallowing, breathing ™ B cell immunio suppresion Rituximab for refractory SLE
Š Functional status — Activities of daily living, feeding, getting out
of bed, stairs, school NSAIDS
Š Childhood Myositis Assessment Scale (CMAS) — Every visit ™ First-line of treatment for arthritis (together with intra-synovial steroids)
™ Other organ disease — CNS, gut, respiratory ™ Symptomatic relief of pain and reduction of inflammation, but do
™ Toxicity of medication — Cushingoid, BP not arrest joint damage or erosive x-ray changes
™ Muscle enzymes need only be checked initially for improvement. ™ Similar efficacy — Choice based on cost, ease of administration and
When clinically better; not routine. Review dates for eye assessment, toxicity
LFT. For Methotrexate (MTX) — FBC, LFT ™ Different people may have different responses - If one doesn’t work
after two to three weeks at therapeutic dose, try another, or review
Investigations at Baseline diagnosis or class of medication required
™ FBC, ESR
™ Muscle enzymes (CK, aldolase, AST, LDH), LFT Aspirin (Acetylsalicylic Acid)
™ ANA, dsDNA, RNP (as appropriate) ™ Traditional drug, but frequent dosing (qid), and toxicity have led to
™ EMG, MRI, muscle biopsy — Only if myositis is uncertain increased use of other drugs
™ Eye (ophthalmologist ) — Baseline for steroids, hydroxychloroquine ™ Dose: 80mg/kg/day (max 3.6g/day), adjust to keep levels 20–30mg/
dl, given with food
Investigations at Follow Up ™ Side-effects/limitations: Reye’s Syndrome, gastrointestinal, hepatic,
™ FBC, muscle enzymes irreversible platelet inactivation, salicylism
™ For drug toxicity (LFT for MTX, azathioprine, cyclophosphamide),
renal function (cyclosporin A) Traditional NSAIDs
™ Eye (steroids) ™ Anti-inflammatory drugs that suppress both COX-1 enzyme (which is
™ BP (steroids) constitutively produced for homeostatic function in gastric mucosa,
endothelium, platelets and kidney), as well as COX-2 enzyme (which
is increased during inflammation, producing inflammatory cytokines)
™ Similar toxicity so optimal dose of one drug is better than different
NSAIDs simultaneously
DRUGS IN RHEUMATOLOGY ™ Well-absorbed (gastrointestinal), excretion is renal
™ Recommended Daily Allowance (RDA)-approved for children — see
A wide array of drugs are available for symptomatic, anti-inflammatory Table 14-7 overleaf
and immunomodulation of rheumatic disease, to control pain, damage ™ Side-effects/limitations — Many, especially gastrointestinal, platelets,
and progression: are due to COX-1 inhibition
™ NSAIDs Gastric — Dyspepsia, nausea, gastritis, diarrhoea, ulceration. Less
™ Steroids with food
™ DMARDs Hepatic — Elevated liver enzymes, usually mild and reversible
™ Cytotoxics Renal — Fluid retention, block diuretics. ARF if GFR poor. Nephrotic,
™ Biologics: Anti-TNF, anti-IL1 agents interstitial nephritis
524 The Baby Bear Book Rheumatology, Immunology and Allergy 525

Table 14-7: Traditional NSAIDs that have been RDA-approved for children.
STEROIDS
NSAID Dosage Comments Among the most potent anti-inflammatory drugs. Mainstay of treatment
Well-tolerated, approved for many severe rheumatic diseases such as SLE, JDM, vasculitis and rarely,
Ibuprofen 30–40mg/kg/day (tds, qds)
for children arthritis. Dramatic effects but prolonged administration at high dose gives
Approved for children unacceptable toxicity, therefore limit the dose and duration of treatment.
Tolmetin 20–40mg/kg/day (tds, qds)
> two years old
Approved for children Routes of Administration
Naproxen 10–20mg/kg/day (bd)
> two years old ™ Intrasynovial For severe inflammation of a few joints, effects
Diclofenac (Voltaren) 1–3mg/kg/day (tds) last days to months
For children > 14 years old; ™ Oral SLE, JDM, vasculitis, JIA — Polyarthritis (bridge)
Indomethacin 1–2.5mg/kg/day (tds, qds) higher CNS and gastric for severe disease
toxicity Systemic arthritis — For severe systemic features
(fever, serositis, Multiple Autoimmune Syndrome
(MAS))
Platelet — Reversible platelet inactivation (improves on discontinuation) ™ Intravenous pulse For severe disease — Faster onset
Skin — Rashes and oral ulceration at high dose. Photosensitive ™ Intra-ocular For chronic anterior uveitis
scarring in fair, blue-eyed
CNS — Headache, drowsiness, dysphoria Doses
Hypersensitivity/allergy — Especially if allergic to aspirin ™ Intrasynovial: Triamcinolone acetonide/hexacetonide — 1mg/kg/
large joint
New Cyclo-oxygenase-2 (COX-2) Selective Inhibitors ™ Oral: 1–2mg/kg/day, taper once better to EOD dose
™ New generation of NSAIDs that selectively inhibit COX- 2 enzyme with More frequent daily dosing more potent but associated with more
minimal effect on COX-1 enzyme at recommended doses, thus safer toxicity. Daily OM dose → EOD dose, less toxic, recommended if it
(gastrointestinal) and as effective for a cute and chronic pain relief does not compromise disease control
™ Not yet approved for children <12 years, though under trial. Holds ™ IV methylprednisolone pulse: 10–30mg/kg/day for three days
promise for the future, and already in use in many centres worldwide With IV frusemide to lessen risk of hypertension
™ Potentially useful in patients with: Pulse has profound immediate anti-inflammatory effects leading to
Š Poor gastrointestinal tolerance of traditional NSAIDs rapid clinical improvement lasting about three weeks. Alternate days
Š Sensitivity to traditional NSAIDs (e.g. Monday, Wednesday, Friday) for quick control, then one to three
™ Adult doses used (with or without food) monthly pulses as maintenance

OA RA Acute pain Toxicity Risks

™ Intrasynovial steroids — Infection, transient crystal synovitis, if
Celebrex (celecoxib) 200mg OD 200mg BD
repeated cartilage damage, most common are atrophic skin changes,
asymptomatic calcifications
™ Limitations ™ Intra-ocular — Glaucoma
Š Not yet approved for children ™ IV pulse — Long-term side-effects like growth retardation decreased,
Š Gastrointestinal toxicity (though much less than traditional NSAIDs) but acute toxicity like hypertension, hyperglycemia, arrhythmia, CNS
Š No effect on platelets. Can cause fluid retention and hypertension psychosis/fits limiting factor in predisposed patient
Š Cost ™ Oral steroids especially longer, high dose
Š Formulation: Capsule (celebrex), ideally liquid or smaller-dose ™ Suppression of hypothalamic-pituitary axis
tablet for children Š Can cause hypoadrenalism as steroids are tapered
526 The Baby Bear Book Rheumatology, Immunology and Allergy 527

Š Stress doses if febrile or for surgery ™ Methotrexate

Š Do not suddenly stop steroids (Addisonian Crisis, shock, advise Š Effective and generally well-tolerated in children
importance of compliance) Š Dose 0.3–1mg/kg once a week oral/SC (better absorption and
Š Medical alert card/bracelet (Medik Awas) efficacy)
™ Immune suppression Š Give with folic acid daily, avoid sulphur drugs and alcohol
Š More susceptible to infection (e.g. TB, Herpes virus) Š Monitor carefully because of potential for toxicity
Š Avoid crowded places, seek treatment early if febrile, contact with y Bone marrow suppression (megaloblastic anaemia,
chickenpox, measles lymphopenia)
Š Signs of infection may be masked, so have high level of suspicion y Hepatic (enzyme elevation)
™ Physical appearance changes y Gastrointestinal including nausea, oral ulcers
Š Cushingoid, weight gain, rounded face, buffalo hump, acne, ™ Sulphasalazine
striae, hirsutism can be very disturbing Š 40–70mg/kg/day (BD or TDS)
Š Advise regarding controlled-calorie, low-fat, low-sugar diet Š Side-effects include rash, gastritis, liver dysfunction, renal
Š Easy bruising, poor wound healing — physical care to avoid injury dysfunction and bone marrow suppression
™ Metabolic ™ Hydroxychloroquine
Š Hyperglycemia, hypercholesterolemia, sodium and water Š Anti-malarial drug with moderate anti-inflammatory properties
retention, hypokalemia Š Used for arthritis and SLE (skin, joint, serositis, malaise, prolong
Š Hypertension remission, APS prevention)
™ Neurological Š 3–6mg/kg/day (max 400mg/day)
Š Euphoria, depression, mood lability, psychosis, pseudotumour Š Side-effects:
cerebri y G6PD deficiency — Relative contraindication
Š May be difficult to distinguish from neuropsychiatric y Regular eye review — Macular degeneration, corneal deposit
manifestations of SLE (must stop)
™ Musculoskeletal y Gastric irritation
Š Osteopenia, proximal myopathy, avascular necrosis y Skin rash — Reversible
Š Advice regarding diet, calcium supplement, exercise, consider
bisphosphonates IMMUNOSUPPRESSIVES AND CYTOTOXICS
Š Growth suppression on doses as low as 3mg/day — risk higher at Cyclophosphamide
higher dose ™ Alkylating agent with potent anti-inflammatory action, use limited
™ Eye review regularly — Cataract, glaucoma by toxicity
™ Risks of steroid withdrawal — Adrenal crisis, flare of disease, ™ Used for lupus nephritis (Class IV), CNS lupus, vasculitis
headache (benign raised intracranial hypertension) ™ Dose IV 0.5–1g/m2 monthly for six months then three monthly for
one year (CNS lupus), up to three years ( for Class IV nephritis)
™ Daily oral dosing may give higher cumulative doses and long-term
toxicity
™ Side-effects:
DISEASE MODIFYING Š Nausea and vomiting
ANTI-RHEUMATIC DRUGS (DMARDS) Š Myelo- and immunosuppression greatest in second week post IV
pulse (fall in total white)
™ Slow or even reverse bony erosion and cartilage loss, thus affect Š Liver toxicity
natural course of RA
™ Act slowly over weeks or months
528 The Baby Bear Book
Š Haemorrhagic cystitis — Ensure adequate hydration (> 2L/
m2/24hr) with diuresis and Mesna (2-mercaptothanesulfonic acid)
360mg/m2 if at higher dose/or prone to it
Š Long-term risk of secondary malignancies (myeloproliferative,
bladder and skin cancer)
Š Gonadal damage with hormonal deficiency and sterility, least risk
in prepubertal children, greatest risk in gonadally mature males
Mycophenolate Mofeteil
™ New immunodulating drug — Prodrug (rapidly hydrolysed to
mycophenolic acid)
™ Inhibits purine synthesis in T and B cells (selective non-competitive
inhibitor)
Š Useful in SLE nephritis intolerant of cyclophosphamide, and JIA
uveitis
Š Awaits controlled studies in children
™ Dose oral 600mg/m2 BD (max 0.5–2.0g/day)
Azathioprine ™ Purine analogue. Traditional drug treatment for SLE,
JDM, PAN, systemic sclerosis — Nephritis, thrombocytopenia, haemolytic
anemia
™ Dose 0.5–2.5mg/kg OD
™ Start low and gradually increase, watching for side-effects
™ Side-effects:
Š Oral ulcers, gastrointestinal, bone marrow suppression, liver
Š 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
™ 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:
Š U/E/Cr, BP, urinalysis, FBC, LFT
Š Trough levels (125–175μg/ml, but do not correlate well clinically)
Š Grapefruit juice can increase levels of cyclosporin significantly
Rheumatology, Immunology and Allergy 529
BIOLOGICALS
IVIG
For KD, systemic onset JIA, JDM, SLE (especially thrombocytopenia)
Etanercept
™ 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
DMARDS, uveitis
™ Combination MTX and Etanercept increases efficacy with acceptable
toxicity
™ Dose 0.4mg/kg/dose up to max 25mg/dose SC twice a week (can be
combined into one dose)
™ Well-tolerated
™ Side-effects: Injection site reactions, headache, URTI
™ No increased rate of infection, but try to complete immunisation
before starting etanercept; if contact with chickenpox, give VZIG
Infliximab
™ Chimeric TNF receptor blocker (monoclonal antibody)
™ For JIA (especially uveitis, ankylosing spondylitis), Crohn’s and
rheumatoid arthritis; not yet FDA-approved for JIA
™ Dose infusion 5mg/kg over two hours at time zero, two weeks, six
weeks, eight weeks after initial infusion
™ Risk of anaphylaxis, reactivation of tuberculosis
™ Contraindicated in tuberculosis, heart failure and during intercurrent
infection
Adalimumab
™ Humanised monoclonal antibody against tumour necrosis factor
™ Dose 24/mg/m2 two weekly
™ Side-effects similar to Etanercept
530 The Baby Bear Book Rheumatology, Immunology and Allergy 531

PRIMARY IMMUNODEFICIENCY (PID) Suspected

Clinical Findings Initial Tests
More Advanced
Abnormality Tests
Cell-mediated Pneumonia (pyogenic Total lymphocyte T-cell enumeration
Table 14-8: "Reg flags" for primary immunodeficiency. immunity bacteria, fungi, counts and subsets (CD3,
1 Family history Positive for early unexplained death, sepsis, recurrent e.g. DiGeorge Pneumocystis carinii, CD4, CD8, CD19,
infections, or specific immunodeficiency diagnoses Syndrome viruses) CD20, CD56)
2 Frequent infections Elevated frequency of documented infections including Gastroenteritis HIV, ELISA/Western In vitro T-cell
pneumonia, sepsis, osteomyelitis, meningitis (viruses, Giardia sp. blot proliferation to
3 Chronic infection Persistent sinusitis and otitis media, bronchiectasis, Cryptosporidium sp.) mitogens, antigens,
recurrent abscesses or allogeneic cells
4 Severe infection Sepsis or meningitis, especially if recurrent or severe Dermatitis/mucositis Delayed-type
(fungi) hypersensitivity
5 Complications of infection Present e.g. mastoiditis complicating otitis media skin test (Candida
6 Site of infection Unusual sites e.g. liver or brain abscess sp., tetanus toxoid,
7 Infecting organism Opportunistic, recurrent, or unusual pathogens e.g. mumps, Trichophyton
Aspergillus, Serratia, Nocardia, Burkholderia cepacia sp.)
8 Response to therapy Poor response or recurring infection after antimicrobial Antibody and cell- See above See above See above
discontinuation mediated immunity ADA assay
e.g. severe combined Alpha-fetoprotein
9 Other signs FTT, dermatitis, recurrent diarrhoea, history of immunodeficiency, Platelet count/size
autoimmune disease ataxia telangiectasia,
Wiskott-Aldrich
Syndrome,
Table 14-9: Evaluation of suspected immunodeficiency (adapted from Rosen, Cooper & common variable
Wedgewood 1995; and Shyur & Hill 1996). immunodeficiency,
hyper-IgM syndrome
Suspected More Advanced Spleen Bacteraemia or Peripheral Technetium-99
Clinical Findings Initial Tests
Abnormality Tests haematogenous blood smear for spleen scan
Antibody e.g. X-linked Sinopulmonary and Immunoglobulin B-cell enumeration infection Howell-Jolly bodies
agammaglobulinemia, systemic infections levels (IgG, IgM, IgA) (CD19, CD20) (pneumococcus, Haemoglobin
IgA deficiency (pyogenic bacteria) other streptococci, electrophoresis
Enteric infections Antibody titres to Immunofixation Neisseria sp.) (HbSS)
(enterovirus, other protein antigens Phagocytes Recurrent superficial Nitroblue Tetrazolium Quantitative
viruses, Giardia sp.) (diphtheria, tetanus) and deep-seated (NBT )Test phagocytosis and
Autoimmune Antibody titres IgG subclass levels infections with chemotaxis studies
disease (ITP, to polysaccharide Aspergillus, Nocardia
haemolytic anemia, antigens (> two and catalase-
Inflammatory Bowel years old) before and positive organisms.
Disease (IBD)) after immunisation Granuloma formation
(pneumococcal with obstructive
polysaccharide symptoms
vaccine)
532 The Baby Bear Book Rheumatology, Immunology and Allergy 533

Suspected
Clinical Findings Initial Tests
More Advanced Š Other: Nasal, ocular and palatal pruritus, sneezing, diaphoresis
Abnormality Tests and disorientation
Complement Bacterial sepsis, CH50 (total Alternative pathway ™ Laboratory evaluation: Some centres use serum tryptase levels (a
autoimmune haemolytic assays by-product of mast cells degranulation) to differentiate anaphylactic
disease (lupus, complement) Individual component reaction from other causes of shock and multiorgan failure
GN), angioedema, assays
pyogenic infection,
encapsulated MANAGEMENT
bacterial infections ™ A: Establish airway (A) if necessary
e.g. Neisseria sp. ™ B: Supply with 100% oxyen with respiratory support (B) as needed
™ C: Assess circulation and establish large-bore IV access. Place on
cardiac monitor
™ Adrenaline: 0.01ml/kg (1:1,000) IM (maximum dose 0.3ml). Repeat
every 15 minutes as needed
™ Salbutamol: 5mg in 3.5ml NS, by aerosol, every 15 minutes as
RECOGNITION AND TREATMENT OF needed
ALLERGIC EMERGENCY — ANAPHYLAXIS ™ Antihistamines: Diphenhydramine — 1–2mg/kg IM/IV/PO
(maximum dose 50mg); alternative promethazine — 0.2–0.5mg/kg
IV/PO (maximum dose 10mg)
DEFINITION Also, consider additional H2-receptor antagonist
Anaphylaxis is the clinical syndrome of immediate hypersensitivity. It is ™ Corticosteroids: Hydrocortisone 4mg/kg IV bolus, then 4mg/kg
characterised by cardiovascular collapse, respiratory compromise, and every six hourly; alternative methylprednisolone 2mg/kg IV bolus,
cutaneous and gastrointestinal symptoms. then 2mg/kg per day IV or IM divided every six hourly; or Prednisone
2mg/kg PO once daily
DIAGNOSIS ™ Support: Respiratory and cardiovascular functions as needed
™ The diagnosis is based on recognition of the clinical syndrome and ™ Observe: At least 24 hours for late-phase symptoms
the rapid involvement of multiple organ systems ™ Consider discharge with an EpiPen® (adrenaline 0.3mg) if weight
™ Initial signs and symptoms: Cutaneous erythema and pruritus, is > 30kg; EpiPen® Jr (adrenaline 0.15mg) if weight is < 30kg; or
sense of 'impending doom', 'light headedness' and cramping comparable injectable adrenaline product with specific instructions
abdominal pain on appropriate usage after an allergy consult
™ Associated manifestations (by system) ™ Discharge with an Allergy follow-up
Š Skin: Urticaria and angioedema (most frequent)
Š Respiratory: Hoarseness, dysphonia or globus, progresses
to stridor and total obstruction. The respiratory system is the
second most common system involved, and the leading cause of
mortality. Signs and symptoms of bronchoconstriction found on MANAGEMENT OF THE PATIENT WITH A
physical examination HISTORY OF DRUG HYPERSENSITIVITY
Š Gastrointestinal: Nausea, vomiting, abdominal pain and intense
diarrhoea (may be bloody)
Š Cardiovascular: Hypotension and vascular collapse (shock), INTRODUCTION
followed by possible complications of asphyxia, myocardial ™ True Allergic Drug Reactions (ADRs) are rare in children
infarction and cardiac arrhythmias ™ Nevertheless, ADRs may be life-threatening events
™ Patients at increased risk of developing an ADR are:
534 The Baby Bear Book Rheumatology, Immunology and Allergy 535

Š Immuno-compromised patients NORMAL RANGES FOR IMMUNOLOGY

Š Patients on multiple medications
Š Patients with a history of a prior ADR
Table 14-11: Blood leukocyte count (WBC) by age (adapted from Behrman 2003).
™ The history is the most important clinical tool available. Make sure
medical history concerning the drug allergy event is obtained from Age x109 cells/L
the best available source, in a language well understood by both Birth 9.0–30.0
medical and lay personnel 24 hours 9.4–34.0
™ If there is a reliable history of a severe drug associated reaction (i.e. One month 5.0–19.5
anaphylactic shock, toxic epidermal necrolysis, Steven Johnson’s
One to three years 6.0–17.5
Syndrome), avoid usage of involved medication at all costs
Four to seven years 5.5–15.5
™ For any other reaction, using the involved medication may be
feasible, if medically indicated, after desensitisation or a graduated Eight to 13 years 4.5–13.5
challenge procedure Adult 4.5–11.0
™ Beta-lactam antibiotics are involved in the majority of adverse drug
reactions in children
Table 14-12: Lymphocyte subset ranges by age (adapted from Behrman 2003).
Age
Table 14-10: Management of a child with a history of ADR to penicillins.
Lymphocyte Subsets W(E) Two to three Four to 12–23 24–59
Inpatient Outpatient Comments months eight months months
Urticaria and/or Cefuroxime Erythromycin, < 5% cross sensitivity months
Angioedema only Ceftriaxone Sulfamethoxazole with new generation Median lymphocytes, total 5.68 x 109 /L 5.99 x 109 /L 5.16 x 109 /L 4.06 x 109 /L
cephalosporins 5th–95th centiles 2.92–8.84 3.61–8.84 2.18–8.27 2.40–5.81
Anaphylaxis Macrolides, Erythromycin, If history unknown Median CD3 lymphocytes 4.03 x 109 /L 4.27 x 109 /L 3.33 x 109 /L 3.04 x 109 /L
Clindamycin, Clarithromy safest course 5th–95th centiles 2.07–6.54 2.28–6.45 1.46–5.44 1.61–4.23
Vancomycin Sulfamethoxazolecin, Median CD4 lymphocytes 2.83 x 109 /L 2.95 x 109 /L 2.07 x 109 /L 1.80 x 109 /L
Non-immediate Cefuroxime Cefuroxime Do not use implicated 5th–95th centiles 1.46–5.11 1.69–4.60 1.02–3.60 0.90–2.86
maculopapular only Ceftriaxone drug Median CD8 lymphocytes 1.41 x 109 /L 1.45 x 109 /L 1.32 x 109 /L 1.18 x 109 /L
Non-immediate severe Ceftriaxone Cefuroxime Do not use implicated 5th–95th centiles 0.65–2.45 0.72–2.49 0.57–2.23 0.63–1.91
(Steven Johnson's drug Median % lymphocytes 66 64 59 50
Syndrome, Toxic 5th–95th centiles 55–78 45–79 44–72 38–64
Epidermal Necrolysis
(TEN)) Median % CD3 lymphocytes 72 71 66 72
5th–95th centiles 60–87 57–84 53–81 62–80
Median % CD4 lymphocytes 52 49 43 42
5th–95th centiles 41–64 36–61 31–54 35–51
Median % CD8 lymphocytes 25 24 25 30
5th–95th centiles 16–35 16–34 16–38 22–38
536 The Baby Bear Book Rheumatology, Immunology and Allergy 537

Table 14-13: Complement component ranges (adapted from Behrman 2003).

FOOD ALLERGY
Total haemolytic complement activity (CH50) 75–160 IU/L
C3 mg/L
Cord blood 570–1,160 INTRODUCTION
One to three months 530–1,310 Food allergies are most prevalent during the first years of life, affecting
Three months to one year 620–1,800 about 6% of infants younger than three years. IgE-mediated food
One to ten years 770–1,950
reactions are characterised by a close temporal relationship between the
Adult 830–1,770
reaction and prior exposure to a specific food allergen. These reactions
C4 mg/L
can be sudden, unexpected, severe and life-threatening.
Cord blood 70–230
One to three months 70–270
Three months to ten years 70–400 The characteristic features are:
Adult 150–450 ™ The time from ingestion of the food to symptom onset is usually
rapid (usually within minutes but may be up to two hours)
Table 14-14: Immunoglobulin ranges (adapted from Behrman 2003).
™ Small amounts of food may elicit severe reactions, and
IgA mg/L ™ Reactions will usually continue to occur with re-exposure
Cord blood 14–36
One to three months 13–530 Anaphylaxis often occurs in the acute form, but although uncommon,
Four to six months 44–840
late-phase reaction or biphasic anaphylaxis (a second anaphylactic
Seven months to one year 110–1,060
Two to five years 140–1,590 reaction occurring up to eight hours after the first reaction) may occur.
Six to ten years 330–2,360 In the latter, there is higher risk of intractable hypotension resulting in
Adult 700–3,120 mortality. For this reason, patients with severe acute anaphylaxis should
IgD mg/L be observed in an appropriate medical facility for up to eight hours post
Newborn None detected reaction.
0–80
IgE kIU/L Patients with food-induced anaphylaxis should be referred to the
Male 0–230 Allergist for detailed evaluation, which would include diagnostic
Female 0–170 confirmation, assessment of cross-reacting foods (especially in nut
IgG g/L allergy), education on prevention of further episodes, such as avoiding
Cord blood 6.36–16.06 hidden sources of food allergens, and emergency treatment in case of
One month 2.51–9.06 accidental exposure.
Two to four months 1.76–6.01
Five to 12 months 1.72–10.69
Two broad groups of food allergy can be distinguished based on the
One to five years 3.45–12.36
Six to ten years 6.08–15.72 timing of the clinical reaction in relation to the food exposure. In some
cases there may be both immediate and delayed reactions to a food.
IgM mg/L
Cord blood 63–250 Although any food may provoke a reaction, relatively few foods are
One to four months 170–1,050 responsible for the vast majority of food allergic reactions in children,
Five to nine months 330–1,260 namely: eggs, milk, peanuts, shellfish, soy, fish, tree nuts, and wheat.
Ten months to one year 410–1,730 Regional exposures common to their local cuisines results in specific
Two to eight years 430–2,070 allergies in these regions e.g. bird’s nest allergy in Singaporean children.
Nine to ten years 520–2,420
Adult 560–3,520
538 The Baby Bear Book
The diagnosis of food allergy requires a careful detailed food history,
selective skin-prick tests, or in-vitro measurement of food-specific IgE
(Pharmacia Cap, Sweden); interpretation of the allergy tests and the
severity of previous food-related reactions will help determine the
individualised plan for either food elimination or oral food challenge for
that child.
DEFINITIONS
Adverse food reactions include any abnormal reaction resulting from
the ingestion of a food and might be the result of food intolerances
(non-allergic food hypersensitivities) or food hypersensitivity/allergy
(food allergy).
Food hypersensitivities/allergies are adverse immunologic reactions
that might be due to IgE- or non IgE-mediated immune mechanisms.
™ IgE-mediated: The clinical manifestations are usually generalised or
systemic and involve various specific organ systems:
Š Cutaneous — Flushing, urticaria and angioedema often with
pruritis
Š Upper and lower respiratory — Rhinoconjunctivitis, laryngeal
edema, and wheezing
Š Gastrointestinal — Vomiting, abdominal cramps and diarrhoea
Š Cardiovascular — Hypotension and shock
™ Mixed IgE- and cell-mediated:
Š Cutaneous: Atopic dermatitis
Š Gastrointestinal: Allergic eosinophilic esophagitis, allergic
eosinophilic gastroenteritis
Š Respiratory: Asthma
™ Cell-mediated:
Š Cutaneous: Contact dermatitis, dermatitis herpetiformis
Š Gastrointestinal: Food protein-induced enterocolitis, food
protein-induced proctocolitis, food protein-induced enteropathy
syndromes, celiac disease
Š Respiratory: Food-induced pulmonary hemosiderosis (Heiner’s
Syndrome)
Food intolerances (non-allergic food hypersensitivities) are adverse
responses caused by some unique physiologic characteristic of the
host, such as metabolic disorders (e.g. lactase deficiency, scamboid
poisoning).
Rheumatology, Immunology and Allergy 539
Food aversions also might mimic adverse food reactions but are not
reproducible when the patient ingests the food in a blinded fashion.
DIAGNOSIS
Medical History
™ The food responsible for provoking the reaction
™ The quantity of the suspected food ingested
™ The length of time between ingestion and development of
symptoms
™ Whether similar symptoms occurred when the food was eaten
previously
™ Whether other factors (e.g. exercise) are necessary to provoke the
reaction
™ How long since the last reaction to the food occurred
™ Dietary diaries may be a useful adjunct
Rationale for Skin-prick Testing and Specific IgE Testing
Skin-prick tests are highly reproducible and frequently used to screen
patients with suspected IgE-mediated food allergies. The criteria for
interpreting prick skin involves using glycerinated food extracts (1:10 or
1:20) and appropriate positive (histamine) and negative (saline) controls
are applied by the prick technique. Any food allergens eliciting a wheal
at least 3mm greater than the negative control is considered positive;
this denotes sensitisation to that particular food reagent but does not
confirm clinical allergy. For IgE-mediated food allergy, skin-prick testing
against particular food (overall positive predictive accuracy is < 50%),
whereas negative skin test results essentially confirms the absence of
IgE-mediated reactions (negative predictive accuracy >95%).
The use of a quantitative measurement of food-specific IgE antibodies
(CAP System FEIA; Pharmacia-Upjohn Diagnostics) has been shown
to be useful in predicting when to consider an oral food challenge in
childen (see Table 14-15 p. 542). Food-specific IgE levels exceeding the
'diagnostic values' indicate that the patient is > 95% likely to experience
an allergic reaction if he or she ingests the specific food. In addition, the
IgE levels can be monitored, and if they decrease to < 2kUA/L for eggs
or < 7kUA/L for milk, the patient can be re-challenged to determine
whether he or she has 'outgrown' the food allergy. There should be
facilities available for paediatric resuscitation.
540 The Baby Bear Book Rheumatology, Immunology and Allergy 541

MANAGEMENT
™ Diagnosis of the food allergy by a specialist for the advice of
appropriate elimination or re-introduction of the food in the diet Name:
™ Educate the family on reading of food labels Date of Birth:
Substance (allergens) to be avoided:
™ Recognise the early symptoms of an allergic reaction
™ In children at risk of anaphylaxis, a food allergy action plan (see Fig. Picture
14.2 next page) is recommended Family/carer name and contact:
™ Oral antihistamines for cutaneous reactions can be prescribed
™ Injectable adrenaline (EpiPen®) for cases of anaphylaxis
™ Inhaled ventolin with space chamber or nebulisation for airway
events Mild to Moderate Allergic Reaction Action
™ Itching and swelling of lips, face, eyes ™ Stay with the person and call for help
™ Patients with a history of anaphylaxis can be advised to wear a Medic
™ Hives or welts ™ Give medications (if any): ____________
Awas bracelet or Card. ™ Tingling mouth ___________________________
™ Vomiting, diarrhoea ™ Locate EpiPen® or EpiPen® Jr
Therapy for Anaphylaxis ™ Contact family/carer
™ Immediate action:
ŠAssessment
ŠCheck airway and secure if needed
ŠRapid assessment of level of consciousness Watch for
ŠVital signs
™ Treatment: any one of
Š Intramuscular epinephrine (0.01mL of 1:1:1,000 dilution/kg every the following
five to 15 minutes as needed; maximum 0.5mL per dose) or
intravenous epinephrine for severe hypotension (0.5–5μg/min to signs of
support BP) ANAPHYLAXIS
Š Supine position, legs elevated
Š Oxygen
™ Dependent on evaluation:
Š Start peripheral intravenous fluids
Š Oral, intramuscular or intravenous H1 antagonists
Š Oral prednisolone (1–2mg per kg body weight, up to 75mg) or Anaphylaxis (Severe Allergic Reaction) Action
™ Swelling of tongue ™ Give EpiPen® or EpiPen® Jr
intravenous methylprednisolone (2mg per kg bodyweight, up to
™ Swelling/tightness in throat ™ Give medications (if any): ____________
250mg) ™ Difficulty talking and/or hoarse voice ___________________________
Š Possible use of H2 antagonists (adults: 4–5mg of oral ranitidine ™ Wheeze or persistent hacking cough ™ Call Ambulance telephone # 995
per kg bodyweight up to 300mg; 50mg intramuscularly or ™ Difficult noisy breathing ™ Lay patient flat and elevate legs. If breathing
intravenously every six to eight hours; children: 1.5mg per kg ™ Loss of consciousness and/or collapse is difficult, allow to sit but do not stand
bodyweight intramuscularly or intravenously up to 50mg) ™ Pale and floppy (young children) ™ Contact family/carer
Š Inhaled via spacer device salbutamol (0.3 puffs per kg, max ™ Severe abdominal colic(older child/adults) ™ Further EpiPen® doses may be given if no

10 puffs) or nebulised salbutamol (1.25–2.5mg as needed or response after five minutes. If in doubt, give
EpiPen® or EpiPen® Jr
continually)
Š Transfer to hospital Fig 14.2: Food allergy action plan.
542 The Baby Bear Book Rheumatology, Immunology and Allergy 543

Table 14-15: Tests to assess the likelihood of obtaining a positive or negative Open Food
alternative in children who react or are intolerant of the EHF, especially
Challenge (OFC) in children.
in non-IgE-mediated cow’s milk allergy.
Serum Food-IgE (kIU/L) SPT Wheal (mm) There is no indication for partially hydrolysed formulae (hypoallergenic
Food
≈ 95% Positive ≈ 50% Negative* ≈ 95% Positive ≈ 50% Negative formulas) in children with true cow’s milk allergy as they have a risk of IgE-
≥ 15 ≤2 ≥8 — mediated reaction with these products.
Cow’s milk ≥ 5 if younger
— — — Special Precautions:
than one year
≥7 ≤2 ≥7 ≤3 Use of Alternate Milk Products — Alternate milk products are not
Egg white appropriate for feeding milk-allergic infants. For example, goat’s milk is
≥ 2 if younger
— — — an alternate milk product that is commonly recommended for infants
than two years
with cow’s milk allergy. Studies have shown that over 90% of children
≤ 2 with and ≤ 5
Peanut ≥ 14 without history of ≥8 ≤3 with confirmed cow’s milk allergy react to goat’s milk. Rice milk should
peanut reaction not be an alternative milk that is recommended for infants and children
with cow’s milk allergy. Enriched rice milk is a good source of calcium and
Fish ≥ 20 — — —
vitamin D; however, it lacks sufficient protein, fat and other nutrients.
A subset of patients with undetectable serum food-specific IgE antibody and negative skin-prick test has been
reported to have objective reactions confirmed by OFC.
* Children with about 50% chance of experiencing a negative challenge are the optimal candidates for a EGG ALLERGY
clinical-based OFC. However, serum levels of food-specific IgE antibodies and skin-prick test wheal sizes are Introduction
not absolute indications to performing an OFC. Laboratory test results have to be interpreted in the context
of clinical history.
Egg is the most common IgE-mediated food allergy in children. The yolk
is considered less allergenic than the white. Chicken egg white consists
of ovalbumin, ovomucoid, ovotransferrin. Ovomucoid in egg white is
responsible for clinical reactivity in the vast majority of egg-allergic
™ Hospital management: children. In addition, it has been shown that about half of children allergic
Š Continued therapy with above-noted agents and management of to eggs may be able to ingest small amounts of egg protein in extensively
complications heated (baked) products, such as breads, cakes and cookies. More than 80%
Š Oral H1 antagonists for three days of children would have outgrown their egg allergy by four years of age.
Š Oral Prednisolone (1mg per kg bodyweight per day, up to 75mg)
Š Follow up with appropriate specialist if not properly evaluated Special Precautions:
When to challenge a child with egg allergy — If there is a history of
COW’S MILK ALLERGY severe anaphylaxis, avoid egg and egg by-products. Send to Allergist
Introduction for advice. If the child’s skin-prick test is negative or the CAP fluorescent
Cow’s milk generally represents the first foreign proteins introduced into enzyme immunoassay (CAP-FIEA) for egg white +/- egg yolk is below the
an infant’s diet. It is a common food allergy in young children and has re-challenge levels, oral challenge can be recommended.
been implicated in a variety of hypersensitivity reactions. Peak incidence
of food allergy reaches 6–8% at one year of age. Prevalence plateaus to MEASLES, MUMPS AND RUBELLA (MMR) AND FLU
1–2%, which occurs during adulthood. Cow’s milk allergy is frequently VACCINATION AND EGG ALLERGY
'outgrown', with 85% of children with milk allergy able to tolerate Introduction
milk by three years of age. Up to 10% of these children may have soy A majority of children with cutaneous (non-anaphylactic) reactions
allergy. Extensively Hydrolysed Formula (EHF) (e.g. Alfare or Alimentum) to egg can be safely administered the MMR in an outpatient setting,
are usually supplements of first choice in milk-allergic children. An such as the polyclinic or private clinic. It is very rare for egg-allergic
amino-acid-derived elemental formula such as neocate may be a good individuals to have reactions to the egg MMR. Only patients who have a
history of anaphylaxis to egg should be referred to the Allergy Clinic for
544 The Baby Bear Book Rheumatology, Immunology and Allergy 545

Symptom
Take a detailed case history for symptoms, time of occurrence of
symptom after ingestion of food, age, nutrition, family history of
allergic disease, drug (NSAIDs, β-blockers, etc.)
evaluation of their food allergy and timely re-introduction of eggs and
egg by-products into the diet.
Patients with egg allergy who need the flu vaccine should be referred to
clinical facility experienced in the management of anaphylaxis. A split
two-dose protocol (e.g. a one-tenth dose followed by nine-tenths 30
minutes later) is considered in those with a history of anaphylaxis to egg.

Medical practitioners should be aware that anaphylaxis can happen

Anaphylaxis after any vaccination; therefore all vaccinations should be performed in
Yes No a setting equipped to deal with such emergencies.

Refer to specialist BIBLIOGRAPHY

General
1. Cassidy JT, Petty RE, editors. Textbook of Pediatric Rheumatology. 4th ed. Philadelphia: WB
Saunders; 2001.
2. Jacobs J. Paediatric Rheumatology for the Practitioner. New York: Springer Verlag; 1992.
IgE measurement of IgE measurement of 3. Snaith ML. ABC of Rheumatology. 2nd ed. London: BMJ Publishing Group; 1999.
4. Miller ML, Laxer RM, editors. Rheumatic Disease Clinics of North America. 2002;28(3):461–
suspected food allergen suspected food allergen 722.
(ImmunoCAP, skin-prick (ImmunoCAP, skin-prick 5. Graef JW, editor. Manual of Paediatric Therapeutics. 6th ed. Philadelphia: Lippincott-
test, etc.) test, etc.) Raven Publishers; 1997.
6. Ministry of Health. Health Facts Singapore 2002. Singapore: Ministry of Health; 2002.
7. See Y, Koh ET, Boey ML. One hundred and seventy cases of childhood-onset
rheumatological disease in Singapore. Ann Acad Med Singapore. 1998;27(4):496–502.
8. See Y. Paediatric Rheumatology in Singapore. Workshops in Rheumatology. Malaysia:
2000.

Positive IgE Negative IgE

Investigations for Suspected Rheumatic Disease
1. Hochberg MC. Updating the American College of Rheumatology revised criteria for the
classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
2. Schur PH, editor. The clinical management of systemic lupus erythematosus. 2nd ed.
Refer to specialist Food challenge test Philadelphia: Lippincott-Raven Publishers; 1996.
3. Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the
proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol.
1998;25(10):1991–1994.
4. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med.
1975;292(7):344–347.
Blood test or skin-prick test Positive Negative 5. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med.
Food challenge test 1975;292(8):403–407.

Consider re-evaluation
in the future
Elimination of diagnosed food
JIA
Re-introduce in diet 1. Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the
proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol.
1998;25(10):1991–1994.
2. Rosenberg AM, Petty RE. A syndrome of seronegative enthesopathy and arthropathy in
children. Arthritis Rheum. 1982;25(9):1041–1047.

Confirm tolerance, food challenge test* SLE

1. Hochberg MC. Updating the American College of Rheumatology revised criteria for the
* Generally, patients who demonstrate immediate type reaction in later childhood are less likely to acquire classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
tolerance. 2. Schur PH, editor. The clinical management of systemic lupus erythematosus. 2nd ed.
Fig 14.3: Procedure for diagnosis of IgE-mediated food allergy. Philadelphia: Lippincott-Raven Publishers; 1996.
546 The Baby Bear Book 547

3. American College of Rheumatology Ad Hoc Committee on Neuropsychiatric Lupus

Nomenclature. The American College of Rheumatology nomenclature and case
definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42(4):599–608.
4. West SG. Lupus and the central nervous system. Curr Opin Rheumatol. 1996;8(5):408–414.
5. Chao SM, See Y, Tan A. Clinical predictors of nephritis in childhood-onset SLE: A Singapore
APPENDIX I: GROWTH CHARTS
experience. Kandang Kerbau Women's and Children's Hospital Annual Scientific Meeting.
Singapore: 2001.
6. Feng PH, Boey ML. Systemic lupus erythematosus in Chinese: The Singapore experience.
Rheumatol Int. 1982;2(4):151–154.
7. Boey ML. Systemic lupus erythematosus in Singapore. Ann Acad Med Singapore.
1998;27(1):35–41.
8. Koh ET, Seow A, Leong KH, Chng HH. SLE mortality in an oriental population. Lupus. 1997;
6(1):27–31.

JDM
1. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med.
1975;292(7):344–347.
2. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med.
1975;292(8):403–407.
3. See Y, Giam YC, Chng HH. A retrospective study of 13 Oriental children with juvenile
dermatomyositis. Ann Acad Med Singapore. 1997;26(2):210–214.
4. See Y, Rooney M, Woo P. Palmer plantar hyperkeratosis: A previously undescribed skin
manifestation of juvenile dermatomyositis. Br J Rheumatol. 1997;36(8):917–919.
5. See Y, Martin K, Rooney M, Woo P. Severe juvenile dermatomyositis complicated by
pancreatitis. Br J Rheumatol. 1997;36(8):912–916.

PID
1. Rosen FS, Cooper MD, Wedgewood RJ. The primary immunodeficiencies. N Engl J Med
1995;333(7):431–440.
2. Shyur SD, Hill HR. Recent advances in the genetics of primary immunodeficiency
syndromes. J Pediatr. 1996;129(1):8–24.

Normal Ranges for Immunology

1. Behrman RE, Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics. 17th ed.
Philadelphia: WB Saunders; 2003.

Food Allergy
1. Chiang WC, Kidon MI, Liew WK, Goh A, Tang JP, Chay OM. The changing face of food
hypersensitivity in an Asian community. Clin Exp.Allergy 2007;37(7):1055–1061.
2. Chiang WC, Pons L, Kidon MI, Liew WK, Goh A, Wesley Burks A. Serological and clinical
characteristics of children with peanut sensitization in an Asian community. Pediatr
Allergy Immunol. 2009 [cited 26 November 2009]. Available from: Wiley Interscience.
http://www3.interscience.wiley.com/.
3. Pumphrey RS, Gowland MH. Further fatal allergic reactions to food in the United Kingdom,
1999–2006. J Allergy Clin Immunol. 2007;119(4):1018-1019.
4. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food
allergy. J Allergy Clin Immunol. 2001;107(5):891–896.
5. Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et
al. Second symposium on the definition and management of anaphylaxis: Summary
report — Second National Institute of Allergy and Infectious Disease/Food Allergy and
Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391–397.
6. Shek LP, Lee BW. Food allergy in Asia. Curr Opin Allergy Clin Immunol. 2006;6(3):197–201.
7. Erlewyn-Lajeunesse M, Brathwaite N, Lucas JS, Warner JO. Recommendations for the
administration of influenza vaccine in children allergic to egg. BMJ. 2009;339(b3680).
548 The Baby Bear Book Appendix I: Growth Charts 549
550 The Baby Bear Book Appendix I: Growth Charts 551
552 The Baby Bear Book Appendix I: Growth Charts 553
554 The Baby Bear Book Appendix I: Growth Charts 555
556 The Baby Bear Book Appendix I: Growth Charts 557
558 The Baby Bear Book Appendix I: Growth Charts 559
560 The Baby Bear Book 561

APPENDIX II: DRUGS

INFECTIONS

ANTIBIOTICS

Drug Preparation Route Dosage Remarks

Amikacin Inj 100mg IM Child: 15–22.5mg/kg/day q8–12hr Nephrotoxic and ototoxic.
250mg Adult: 15mg/kg/day q8–12hr; max Therapeutic level:
500mg/2ml vial IV 1.5g/day) For BD-TDS dosing:
Neonate: 15–30μg/ml (peak),
< 2kg (< 7 days): 7.5mg/kg/dose < 10μg/ml (trough),
q12–18hr For OD dosing: Trough at
(> 7 days): 7.5–10mg/kg/ 18 hrs < 3μg/ml.
dose q8–12hr Infuse over 30–60 mins.
> 2kg (< 7 days): 7.5–10mg/kg/ For infants, infuse over
dose q12hr 1–2 hrs.
(> 7 days): 10mg/kg/dose
q8hr
Amoxycillin Mixt 125mg/5ml Oral 30–50mg/kg/day q8hr Mixture stable for 14 days.
Mixt 250mg/5ml Otitis media due to resistant
Cap 250mg pneumococci: 80–90mg/kg/day
q8hr
Amoxycillin + Mixt 200mg + Oral Amoxycillin 30–50mg/kg/day Mixture stable for 7 days at
Clavulanic Acid 28.5mg/5ml q12hr (order as for Amoxycillin 4°C (store in refrigerator).
(Augmentin) Tab 500mg + 125mg dose) Not suitable for IM route.
Inj 500mg + 100mg Oral: Up to 80–90mg/kg/day for Use higher oral dose for
severe infections intermediate susceptibility/
IV IV Augmentin 30mg/kg/dose q8hr resistant pneumococcus.
(up to 40mg/kg/dose q8hr)
Ampicillin Inj 500mg/vial IM/IV IV: Mild/moderate: 100–150mg/ Allergic or anaphylactic
kg/day q6hr reactions may occur.
IV: Severe/meningitis:
200–400mg/kg/day q4 or 6hr
Neonate: Rubella-like rash common
< 2kg (< 7 days): 25mg/kg/dose with many viral infections;
q12hr does not equate to
(> 7 days): 25mg/kg/dose Ampicillin allergy.
q8hr
> 2kg (< 7 days): 25mg/kg/dose
q8hr
(> 7 days): 25mg/kg/dose
q6hr
Neonates with meningitis: Give
double dose i.e. 50mg/kg/dose
562 The Baby Bear Book Appendix II: Drugs 563

Drug Preparation Route Dosage Remarks Drug Preparation Route Dosage Remarks
Ampicillin\ For GBS meningitis: Cefotaxime Neonate:
(cont’d) ≤ 7 days: 200–300mg/kg/day (Claforan) < 2kg (< 7 days): 50mg/kg/dose
q8hr (cont’d) q12hr
> 7 days: 300mg/kg/day q4–6hr (> 7 days): 50mg/kg/dose
Ampicillin + Tab 375mg Oral Oral: < 30kg: 25–50mg/kg/day q8hr
Sulbactam (220mg + 147mg) IV/IM q12hr > 2kg (< 7 days): 50mg/kg/dose
(Unasyn) Syr 250mg/5ml > 30kg: 375–750mg/dose q8–12hr
Inj 750mg/vial, q12hr (> 7 days): 50mg/kg/dose
1.5g/vial IV: Mild/moderate: q6–8hr
100–150mg/kg/day q6–8hr Ceftazidime Inj 500mg IM Mild/moderate: 75–100mg/kg/day Third-generation
IV: Severe: 200–400mg/kg/day 1g/vial IV q8hr (adult 3g/day) cephalosporin.
q6hr (adult 6–12g/day — Severe/meningitis: 150mg/kg/day Activity against
Sulbactam 50mg/kg + (max 6g/day) Pseudomonas.
Ampicillin 100mg/kg) Neonate: Adjust dosing interval for
Neonates (especially premature) < 2kg (< 7 days): 50mg/kg/dose renal failure.
during Week 1 of life: IV 75mg/kg/ q12hr
day q12hr. Term IV 150mg/kg/day (> 7 days): 50mg/kg/dose
q12hr q8hr
Azithromycin Cap 250mg Oral 10mg/kg OM (max 500mg) on Dosage for respiratory tract > 2kg (< 7 days): 50mg/kg/dose
(Zithromax) Susp 200mg/5ml Day 1, then infections. q8–12hr
5mg/kg OM (max 250mg) on Avoid in known macrolide (> 7 days): 50mg/kg/dose
Days 2–5 allergy. q8hr
or Ceftibuten Cap 200mg, 400mg Oral 9mg/kg/day q12 or 24hr (max Oral third-generation
10mg/kg OM x 3 days (Cedax) Susp 180mg/5ml 400mg) cephalosporin.
Cefaclor Cap 125mg, 250mg Oral 20–40mg/kg/day q8–12hr Second-generation Ceftriaxone Inj 250mg IM 50–100mg/kg/day q12–24hr Third-generation
Susp 125mg/5ml Twice-daily regimen effective for cephalosporin. 500mg, 1–2g/vial IV Meningitis: 100mg/kg/day cephalosporin.
treatment of acute otitis media q12–24hr (max 2g q12hr)
Cefazolin Inj 1g/vial IM 20mg/kg/dose q8hr First-generation Neonate:
(Kefzol, Ancef) IV 70–150mg/kg/day q6–8hr (severe cephalosporin. < 2kg (< 7 days): 50mg/kg/dose
infections) q24hr
Neonate: Not indicated for initial (> 7 days): 50mg/kg/dose
< 2kg (< 7 days): 20mg/kg/dose therapy of neonatal bacterial q24hr
q12hr infections. > 2kg (< 7 days): 50mg/kg/dose
(> 7 days): 20mg/kg/dose q24hr
q12hr (> 7 days): 75mg/kg/dose
> 2kg (< 7 days): 20mg/kg/dose q24hr
q12hr Cefuroxime Inj 750mg/vial, IM Mild/moderate: 75–100mg/kg/day Second-generation
(> 7 days): 20mg/kg/dose (Zinacef) 1.5g/vial IV q8hr (adult 2–4g/day) cephalosporin.
q8hr Severe: 150–240mg/kg/day q8hr Good activity against
Cefepime Inj 1g/vial IM Mild/moderate: 100–150mg/kg/ (adult 4–6g/day) Haemophilus influenzae
IV day q8hr (adult 1–2g/day) (not recommended for
Severe: 150mg/kg/day q8hr (adult meningitis).
2–4g/day) Inactive against
Pseudomonas.
Cefotaxime Inj 500mg IM Mild/moderate: 75–100mg/kg/day Third-generation
(Claforan) 1g/vial IV q6–8hr cephalosporin. Cefuroxime Axetil Susp 125mg/5ml Oral 20–30mg/kg/day q12hr (adult
Severe: 150–200mg/kg/day Adjust dosing interval in (Zinnat) Tab 125mg, 250mg, 1g/day)
q6–8hr renal failure. 500mg Higher dose recommended for
Meningitis: Up to 300mg/kg/day treatment of otitis media
q6hr
564 The Baby Bear Book Appendix II: Drugs 565

Drug Preparation Route Dosage Remarks Drug Preparation Route Dosage Remarks
Cephalexin Cap 250mg, 500mg Oral 25–50mg/kg/day q6–8hr (max First-generation Doxycyline Tab 100mg Oral 2–4mg/kg/day q12–24hr (adult Not recommended for
(Keflex) Susp 125mg/5ml, 4g/day) cephalosporin. 100–200mg/day) children < 8 yrs.
250mg/5ml Otitis media: 75–100mg/kg/day Erythromycin Ethylsuccinate Oral Oral: 30–50mg/kg/day q6–8hr Drug of choice for pertussis
q6hr Syr 200mg/5ml (Erythromycin base) Adult and Mycoplasma.
Osteomyelitis: 100–150mg/kg/ (erythromycin base) 1–2g/day
day q6–8hr Tab 250mg (Base) Rheumatic fever prophylaxis: IV Infuse over 30–60 mins.
Chloramphenicol Tab 250mg Oral PO 50–100mg/kg/day q6hr (adult Aplastic anaemia. Tab 400mg (EES) 250mg BD
Susp 125mg/5ml. 1–2g/day) Grey baby syndrome. Inj 500mg/vial IV IV: 40–50mg/kg/day q6hr
Inj 1g/vial IV IV 50–100mg/kg/day q6hr (adult (Lactobionate) (adult 1–4g/day)
2–4g/day) Neonate (PO/IV):
Ciprofloxacin Tab 250mg Oral Oral: 20–30mg/kg/day q12hr Caution: Safety in children < 2kg (< 7 days): 10mg/kg/dose
Inj 100mg/5ml, (adult 0.5–1.5g/day) not established yet. q12hr
200mg/5ml IV IV: 20–30mg/kg/day q12hr (> 7 days): 10mg/kg/dose
(adult 400–800mg/day q8hr
q12hr) > 2kg (< 7 days): 10mg/kg/dose
q12hr
Clarithromycin Tab 250mg Oral 15mg/kg/day q12hr (adult 1g/day) Avoid in known macrolide (> 7 days): 10mg/kg/dose
(Klacid) Susp 125mg/5ml allergy. q6–8hr
Clindamycin Cap 150mg Oral Oral: 15–24mg/kg/day q6–8hr Diarrhoea is a common Ethambutol Tab 100mg, 400mg Oral 15–25mg/kg/day OM (max May cause optic neuritis.
Inj 300mg/2ml IV (adult 600–1800mg/day) side-effect. 2.5g/day)
IV: Mild/moderate: 5–25mg/ May cause
kg/day q6–8hr (adult pseudomenbraneous colitis. Fusidic Acid Susp 50mg/ml Oral Oral: 6.6–16.6mg/kg/dose q8hr Infuse over 2–4 hrs.
600mg–1.2g/day) Tab 250mg < 1 yr: 50mg/kg/day q8hr
IV: Severe: 25–40mg/kg/day Inj 500mg/vial IV 1–5 yrs: 250mg q8hr To be used in combination
q6–8hr (adult 1.2–2.7g/ > 6 yrs: 500mg q8hr therapy for MRSA infections.
day) IV: 20mg/kg/day q8hr (adult
Neonate: 500mg q8hr)
< 2kg (< 7 days): 5mg/kg/dose Gentamycin Inj 80mg/2ml IM 5–7.5mg/kg/day q8hr Nephrotoxic and ototoxic
q12hr IV UTI: 5mg/kg/day q24hr (not to be given by IV bolus
(> 7 days): 5mg/kg/dose (uncomplicated cases, > 1 mth old) injection but as 20-min
q8hr Neonate: infusion).
> 2kg (< 7 days): 5mg/kg/dose < 2kg (< 7 days): 2.5mg/kg/dose Therapeutic level:
q8hr q12–18hr For TDS dosing: 5–12μg/
(> 7 days): 5–7.5mg/kg/ (> 7 days): 2.5mg/kg/dose ml (peak), 0.5–2μg/ml
dose q6hr q8–12hr (trough).
Cloxacillin Cap 250mg Oral PO: 50–100mg/kg/day q6hr (adult Hypersensitivity reactions. > 2kg (< 7 days): 2.5mg/kg/dose For OD dosing: < 1μg/ml
Syr 125mg/5ml 2–4g/day) Diarrhoea. q12hr (trough at 18 hrs).
Inj 250mg/vial, IV/IM IV: 100mg/kg/day q6hr (severe (> 7 days): 2.5mg/kg/dose
500mg/vial infections) q8hr
IV: 200mg/kg/day q6hr Imipenem + Inj 500mg + 500mg IM 15–25mg/kg/dose q6hr (max Dosage based on imipenem
(meningitis) Cilastatin IV 2g/day) component of Tienam.
Co-trimoxazole TMP 20mg + SMZ Oral PO: 8–12mg TMP + 40–60mg Not to be used < 2 mths of (Tienam) Not recommended for
(Bactrim, 100mg (Paed. Tab), SMZ/kg/day q12hr age or in G6PD deficiency. meningitis.
Septrim) TMP 80mg + SMZ May cause convulsions.
400mg (Adult Tab) For PCP: Adjust dose in renal
TMP 40mg + SMZ IV/PO: 20mg TMP + 100mg dysfunction.
200mg/5ml (Syr) SMZ/kg/day q6hr Isoniazid Tab 100mg Oral 10–15mg/kg/day q24hr (max: Hepatitis.
TMP 80mg + SMZ IV (INH) 300mg 300mg/day) Hypersensitivity reactions.
400mg/5ml (Inj) Prophylaxis: 5–10mg/kg/day
q24hr
566 The Baby Bear Book Appendix II: Drugs 567

Drug Preparation Route Dosage Remarks Drug Preparation Route Dosage Remarks
Linezolid (Zyvox) Tab 400mg, 600mg Oral, IV 10mg/kg/dose q8hr (max 600mg Myelosuppression may occur. Penicillin For GBS meningitis:
Inj 600mg/vial q12hr) Crystalline G ≤ 1 wk of age: 250,000–450,000U/
Meropenem Inj 500mg,1g/vial IV 60mg/kg/day q8hr (adult 4g/day) (Benzylpenicillin) kg/day q8hr
Meningitis: 120mg/kg/day (adult (cont’d) > 1 wk of age: 450,000U/kg/day
6g/day) q6hr
Congenital Syphilis:
Metronidazole Inj 500mg/100ml IV PO: 15–35mg/kg/day q8hr For anaerobic infections. Neonate: IV 50,000U/kg/dose
(Flagyl) Tab 200mg Oral IV: 30mg/kg/day q6–8hr Peripheral neuropathy, q12hr during Day 1–7 of life,
Neonate: metallic taste. and q8hr thereafter for a total of
< 2kg (< 7 days): 7.5mg/kg/dose 10–14 days
q24hr
(> 7 days): 7.5mg/kg/dose Penicillin V Tab 250mg Oral 25–50mg/kg/day q6–8hr
q12hr Syr 250mg/5ml Rheumatic fever prophylaxis:
> 2kg (< 7 days): 7.5mg/kg/dose 250mg BD
q12hr Piperacillin Inj 2–4g/vial IM Mild/moderate: 100–150mg/kg/ For gram-negative bacteria,
(> 7 days): 15mg/kg/dose IV day q6hr (adult 6–8g/day) especially Pseudomonas.
q12hr Severe: 200–300mg/kg/day
Neomycin Tab 500mg Oral 50–100mg/kg/day q6hr (adult For suppression of intestinal q4–6hr (adult 12–18g/day)
Sulphate 1–2g q6hr) aerobic bacteria. Piperacillin/ Inj 4.5g/vial (4,000mg IM 200–300mg/kg/day of piperacillin For polymicrobial infections
In premature and newborn Tazoactam piperacillin + 500mg IV component q6–8hr including gram-negative
babies, 10% may be (Tazocin) tazobactam) bacteria, especially
absorbed. Pseudomonas, anaerobes
Nitrofurantoin Tab 500mg Oral 5–7mg/kg/day q6hr (adult Haemolytic anaemia in and Staphylococcus.
400mg/day) G6PD-deficient patients. Pyrazinamide Tab 500mg Oral 20–40mg/kg/day q12–24hr (max Hepatitis.
Prophylaxis: 1–2mg/kg/day q24hr Peripheral neuropathy. 2g/day)
Not recommended for Quinopristin- IV 7.5mg/kg/dose q8hr Not for Enterococcus faecalis.
neonates. Dalfopristin Preferably given by central
Penicillin Inj 2.4MU/vial IM Rheumatic fever prophylaxis: Long-acting penicillin. (Synercid) line due to thrombophlebitis.
Benzathine < 27.3kg: 0.6 million units once Arthralgia.
a mth Rifampicin Cap 150mg, 300mg Oral For TB: 10–20mg/kg/day q12–24hr Urine, faeces, saliva, tears
≥ 27.3kg: 1.2 million units once IV (max 600mg/day) and sweat stained red.
a mth N. meningitidis prophylaxis:
Congenital syphilis: 50,000U/ Neonate: 5mg/kg/dose q12hr x 2
kg/dose days
Penicillin Inj 1MU/vial, IM/ Mild/moderate: 25,000–50,000U/ > 1 mth: 10mg/kg/dose q12hr x 2
Crystalline G 5MU/vial IV kg/day q6hr days (max 600mg/dose)
(Benzylpenicillin) Severe: 250,000–400,000U/kg/day H. influenzae type B prophylaxis:
q4–6hr Neonate: 10mg/kg/day OM x 4
(max 24 million U/day) days
Neonate: > 1 mth: 20mg/kg/day OM x 4
< 2kg (< 7 days): 25,000U/kg/ days (max 600mg/dose)
dose q12hr Streptomycin Inj 5g/vial , Inj 1g/vial IM only 20–40mg/kg/day q12–24hr (max Nephrotoxic and ototoxic.
(> 7 days): 25,000U/kg/ 1g/day)
dose q8hr
> 2kg (< 7 days): 25,000U/kg/ Tetracycline Tab 250mg Oral 25–50mg/kg/day q6hr (adult Not recommended for
dose q8hr 1–2g/day) children below 8 yrs.
(> 7 days): 25,000U/kg/ Can cause permanent
dose q6hr discolouration and enamel
Double the dose for meningitis hypoplasia of the teeth.
568 The Baby Bear Book Appendix II: Drugs 569

Drug Preparation Route Dosage Remarks ANTIMALARIALS

Tobramcin Inj 20mg/vial IM 3–7.5mg/kg/day q8hr or once daily Infuse over 30–60 minutes.
40mg/vial IV Neonate: Nephrotoxic and ototoxic. Drug Preparation Route Dosage Remarks
< 2kg (< 7 days): 2.5mg/kg/dose Good activity against Chloroquine Tab 250mg Oral Treatment: Treatment for all Plasmodia
q12–18hr Pseudomonas. Phosphate (150mg base) Phosphate (150mg base) 10mg except Chloroquine-resistant
(> 7 days): 2.5mg/kg/dose base/kg (max 600mg) followed by P. falciparum.
q8–12hr 5mg base/kg (max 300mg) 6 hrs
> 2kg (< 7 days) 2.5mg/kg/dose later. Then 5mg base/kg at 24 and
q12hr 48 hrs (total dose of 25mg base/
(> 7 days): 2.5mg/kg/dose kg over 3 days).
q8hr
Vancomycin Inj 500mg/vial IV Mild/moderate: 40mg/kg/day Nephrotoxic and ototoxic. Prophylaxis: Start 1 wk before entering
q6–8hr (adult 1–2g/day q6–12hr) Each dose to be infused over 5mg base/kg (max 300mg) endemic area and continue
Severe/meningitis: 60mg/kg/day a period of at least 60 mins. once wkly until 4 wks after leaving.
q6hr (adult 2–4g/day q6–12hr) Peak: 20–40μg/ml. Trough: Mefloquine Tab 250mg Oral Treatment: The combination of
Neonate: 5–15μg/ml. < 45kg: 15mg/kg followed by Mefloquine and Quinine is
< 2kg (< 7 days): 10–15mg/kg/ Meningitis: Peak levels of 10mg/kg 6–8 hrs later best avoided.
dose q12–18hr 30–40μg/ml. (the paediatric dosage
(> 7 days): 10–15mg/kg/ Adjust dosing interval in has not been approved
dose q8–12hr renal failure. by the FDA)
> 2kg (< 7 days): 10–15mg/kg/ Adults: 750mg followed by
dose q8–12hr 500mg 6–8 hrs later
(> 7 days): 10–15mg/kg/
dose q6–8hr Prophylaxis: Start 1 wk before entering
< 15kg: 5mg/kg, once a wk endemic area and continue
15–19kg: 1/4 tab, once a wk until 4 wks after leaving.
20–30kg: 1/2 tab, once a wk
ANTIHELMINTHICS 31–45kg: 3/4 tab, once a wk
45kg/adult: 1 tab, once a wk
Drug Preparation Route Dosage Remarks Primaquine Base 15mg tab Oral 0.3mg base/kg daily for 14 days. Drug induced haemolysis
Phosphate 21 days for infection in SEA or may occur in G6PD
Albendazole Tab 200mg, 400mg Oral 1–2 yrs < 10kg: 200mg Drug of choice for Western Pacific (prevention of deficiency.
(Zentel) Susp 400mg/10ml > 2 yrs > 10kg: 400mg as a roundworm, whipworm, P. vivax and P. ovale relapses).
single dose hookworm. Should be Avoid primaquine
™ Roundworm, whipworm, avoided during pregnancy 0.75mg base/kg wkly for 8 wks (if in the presence of
hookworm: Wingle dose and lactation, and in G6PD deficiency). haemoglobinuria.
™ Pinworm: Repeat dose 2 wks children < 6 mths
later Quinine Inj 600mg/2ml IV IV Quinine 20mg salt/kg over 4 Beware hypotension and
™ Strongyloides: OM x 3 days Dihydrochloride (492mg base) hrs in 5% Dextrose (loading dose) hypoglycaemia (for ECG, BP,
followed by 10mg salt/kg over glucose monitoring).
2–4 hrs q8hr (max 1800mg/day),
until oral therapy can commence. Loading doses should not
be given to patients who
If > 48 hrs of parenteral treatment have received Quinine,
needed, the quinine dose should Quinidine or Mefloquine
be reduced by 1/3 to ½. within the previous 24 hrs.
Avoid Quinine in presence of
haemoglobinuria.
570 The Baby Bear Book Appendix II: Drugs 571

Drug Preparation Route Dosage Remarks Drug Route Dose Comments Side-effects
Quinine Sulphate Tab 300mg Oral 30mg salt/kg/day q8hr for 3–10 Use only for suspected Fluconazole PO 50mg, 3–12mg/kg PO 3–6mg/kg/day Rash, GI symptoms,
(250mg base) days (adult 600mg salt/dose q8hr) chloroquine resistance. 100mg, for oropharyngeal, hepatotoxicity.
(Infections acquired in SEA: Give 150mg cap; esophageal candidiasis. Anaphylaxis.
10 days of Quinine; 3–7 days For Chloroquine-resistant P. IV 100mg/ IV 10–12mg/kg/day
treatment for infections acquired falciparum (found in SEA) 5ml if invasive Candida/
elsewhere). add — Either Fansidar Cryptococcus. Not for
or Tetracycline 20mg/kg/day Aspergillus sp., Candida
q6hr for 7 days krusei or glabrata.
or Doxycycline 2mg/kg/day Itraconazole PO 5–10mg/kg/day OD or For Aspergillus, GI symptoms, rash,
for 7 days 10mg/ml BD. Solution best taken in mucocutanous Candida, oedema, headache, ↓K,
or Clindamycin 20–40mg/ solution fasting state Penicillium marneffei, hepatotoxicity, ↓plt,
kg/day q8hr for 5 days (150ml) Sporotrichosis, ↓WBC.
(Tetracycline/Doxycycline/ Scedosporium.
Clindamycin begin 2–3
days after treatment with Flucytosine PO 500mg IV/PO: 50–150mg/kg/day Used as adjunctive Bone marrow suppression
Quinine). (5-fluro-cytosine, IV 2,500mg/ div 6 hr therapy with AmB for (especially if renal failure),
5FC) 250ml vial Candidal/Cryptococcal renal dysfunction, GI
meningitis, neonatal symptoms, transaminitis,
invasive candidiasis. rash, neuropathy,
Unable to do 5 FC levels confusion, hallucinations.
ANTIFUNGALS locally, use 50–75mg/
kg/day to avoid marrow
Drug Route Dose Comments Side-effects suppression.
Amphotercin B IV 50mg/vial 0.25–0.5mg/kg initially, Use higher dose Fever, chills, phlebitis, Nystatin PO 100,000U/ Neonate: Oropharyngeal GI symptoms, rash.
(AmB, Fungizone) increase to 0.5–1mg/kg, 1–1.5mg/kg for nephrotoxicity, ↓K, ml solution Prem: 100,000U QDS, candidiasis.
infuse over 2–4 hrs. Aspergillus, 0.5–0.6mg/ ↓Ca, ↓Mg, headache, Term: 200,000U QDS
Dilute in electrolyte-free kg for C. albicans, hepatotoxicity, anemia. Infant: 200,000U QDS
5% Dextrose at 0.1mg/ml. 0.7–1.0mg/kg for Rare: Neurotoxicity, Child: 400,000U TDS
non-albicans Candida. Not anaphylaxis. Cream Adult: 600,000U TDS
effective against Fusarium Pre-treatment for infusion
or Scedosporium spp. reactions: Paracetamol, Apply cream QDS until 3
diphenhydramine or days after resolution.
hydrocortisone. Taper
hydrocortisone over time
as tolerance develops
to AmB.
Amphotercin B IV100mg/ 5mg/kg/day infused over * See guidelines for Fever, chills, other
Lipid Complex 20ml vial 2 hrs at 2.5mg/kg/hr. Do use of liposomal reactions as with AmB,
(ABLC, Abelcet) * not dilute with saline Amphotericin B. but less nephrotoxicity
* Guidelines for use of liposomal preparations of Amphotericin in place of standard formulation Amphotericin B
and hepatotoxicity.
Indications:
Liposomal 3mg/kg/day for empiric * See guidelines for Fever, chills, other ™ Pre-existing renal impairment
amphotericin therapy . the use of liposomal reactions as with AmB, ™ Development of Amphotericin B nephrotoxicity whilst on therapy
(L-Amb, 5mg/kg/day for probable Amphotericin B. but less nephrotoxicity ™ Patients where renal failure is expected to compromise underlying condition e.g. renal transplant, haematopoietic stem cell
Ambisome)* or proven invasive fungal and hepatotoxicity. 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
infection. 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/day as first-line:
Š Fusarium sp. or zygomycetes
Š For Scedosporium species, Voriconazole should be considered first-line treatment
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.
572 The Baby Bear Book Appendix II: Drugs 573

Drug Route Dose Comments Side-effects Drug Preparation Dosage Indications/Comments Side-effects
Caspofungin IV 50mg Load 70mg/m2/dose OD Second-line agent for May need adjustment Acyclovir (ACV) HSV keratitis/ Trifluridine: Local
(CANCIDAS) vial or (max 70mg), then invasive candidiasis in patients receiving a (cont’d) conjunctivits: PO ACV irritation, pruritus, ocular
70mg vial 50mg/m2/dose OD (max or aspergillosis concomitant liver enzyme 20mg/kg TDS x 10 days oedema.
50mg) or for empiric therapy inducer and/or with + gutt 1% Trifluridine 1
or treatment of sensitive moerate or severe hepatic drop 2 hrly (when awake,
fungal infection impairment. max 9 drops/day/eye)
not responding to Fever, rash, pruritus, GI till healing, then 1 drop
Amphotericin therapy. symptoms, headache, 4 hrly (max 5 drops/day/
anemia, phlebitis. eye) x 7 days.
Voriconazole PO 50, 200mg IV 7mg/kg/dose BD Invasive aspergillosis. GI symptoms,
(Vfend) tab PO Load 10mg/kg/dose Scedosporium species and photosensitivity rash Varicella (complicated) or
IV 200mg vial q12hr x 1 day, then second-line antifungal especially with prolonged HSV encephalitis or HSV
10mg/ml 7mg/kg/dose q12hr agent for invasive fungal therapy. in immunosuppressed:
disease failing to respond Visual disturbance < 1 yr old: IV 10mg/kg
Adult: IV 6mg/kg/dose to Amphotericin as first- (common, usually mild 8 hrly
q12hr x 1 day, then line therapy and reversible). > 1 yr old: IV 500mg/m2
4mg/kg/dose q12hr Caution in hepatic 8 hrly
PO > 40kg: 400mg BD x 1 impairment.
day, then Neonatal HSV:
200mg BD Skin/mucocutaneous
disease: IV 20mg/kg
8 hrly x 14 days
CNS/disseminated
disease: IV 20mg/kg
ANTIVIRALS 8 hrly x 21 days
Ganciclovir Cap 250mg IV induction: 5mg/kg Infuse over 1–2 hrs ↓WBC, ↓plt, headache,
Doses are per dose, OD = once daily, BD = twice daily, TDS = three times daily IV 500mg/vial 12 hrly x 2–3 wks (3–6 CMV pneumonitis in seizures, hypertension,
wks if colitis), then transplant pats: Add nausea, rash, renal/liver
Drug Preparation Dosage Indications/Comments Side-effects
maintenance 5mg/kg IVIG 500mg/kg EOD x 10 toxicity.
Acyclovir (ACV) Susp 200mg/5ml Varicella (uncomplicated) ACV indications for IV: Crystalline once daily or 6mg/kg five doses, then 500mg/kg
Tab 200mg PO 20mg/kg 6 hrly x uncomplicated VZ: nephropathy. times per wk. twice per wk x 8 doses.
IV 250mg/vial 5 days (max 800mg Second-degree Rare encephalopathy.
Valganciclovir Tab 450mg CMV maintenance Oral formulation of
5x/day) household contact, Headache, dizziness,
(Valcyte) therapy given three times gangciclovir with better
chronic lung/skin disease, rash, ↓WBC, GI side-
per wk bioavailability. Toxicity
HSV genital/labial (first steroids, salicylate effects.
Dose = 7 x BSA x CrCl same as for ganciclovir.
episode): therapy.
or
PO 20mg/kg TDS or VZ in immunosupressed:
CrCl > 70ml/min:
400mg TDS x 5–10 days IV x 7–10 days.
520mg x BSA
or IV 5mg/kg 8hrly x HSV encephalitis: For
50–70ml/min:
5–7 days 14–21 days
260mg x BSA
IV: slow infusion with
< 50ml/min:
HSV genital/labial adequate hydration as
130mg x BSA
(recurrent): PO 400mg ACV crystallises in renal
or 16mg/kg/dose BD
TDS x 5 days tubules.

Herpetic whitlow: PO
400mg TDS x 10 days
574 The Baby Bear Book Appendix II: Drugs 575

Drug Preparation Dosage Indications/Comments Side-effects Drug Preparation Dosage Indications/Comments Side-effects
Foscarnet 6gm/vial CMV: IV induction: 60mg/ Hydrate with N/S first. Renal: ↓K, ↓Ca, ↓Mg, Zidovudine Syrup 10mg/ml PO 160mg/m2 8 hrly HIV treatment and Anaemia, ↓WBC,
kg/dose 8 hr or 90mg/ For CMV resistant to GCV ↑Cr, nephrogenic DI, (ZDV, AZT) Cap 100mg (range 90–180mg/m2 prevention. nausea, vomiting, nail
kg/dose 12 hr x 2–3 or HSV resistant to ACV proteinuria, fever, Intravenous 6–8 hrly). pigmentation, headache.
wks, then maintenance nausea, ↓WBC, ↑LFT, solution 10mg/ml Neonate: PO 2mg/kg 6 Rare: Myopathy, myositis,
90–120mg/kg/dose OD. ↑BP, seizures, dizziness, hrly, IV: 1.5mg/kg 6 hrly. hepatotoxicity.
bronchospasm, GI Premature ≤ 2 wk: PO/
HSV: 60mg/kg 12 hrly till side-effects IV1.5mg/kg 12 hrly, > 2
infection resolved. wk: PO/IV 2mg/kg 8 hrly.
Ribavirin Inhalation 2gm in 100ml sterile H2O Only for RSV in Bronchospasm, Adolescent: 200mg TDS
6gm powder over 2 hrs q8hr or 6gm immunosuppressed conjunctivits, teratogenic, or 300mg BD.
in 300ml sterile H20 over patient*. Treat for 3–7 ↓BP, rash, haemolytic Lamivudine Susp 10mg/ml PO 4mg/kg BD. HIV treatment and Well-tolerated. Nausea,
Intravenous 12–18 hrs/day in mist days. anemia (both IV/PO) (3TC) Tab 150mg Neonate: 2mg/kg BD . prevention, Hepatitis B rash, vomiting, diarrhoea,
solution available tent by SPAG generator. reversible with drug Adolescent: 150mg BD. treatment. headache.
Hepatitis C treatment. withdrawal. Stavudine (d4T) Capsule 30mg < 30kg: 1mg/kg/dose HIV treatment. Can be given with food.
For intravenous usage: BD. Adjust dose with renal
Please consult with 30–60kg: 30mg/dose BD. impairment.
Infectious Diseases Team > 60kg: 40mg/dose BD. Do not use with ZDV
and Pharmacy. due to antagonistic drug
Zanamivir Aerosol 5mg/ Treatment: 2x 5mg puffs Influenza A, B treatment. Bronchospasm. Approved effect.
inhalation BD x 5 days . ≥ 7 yrs old. Didanosine Delayed-release Adolescent < 60kg: HIV treatment. Take on empty stomach
(ddI, Videx EC) (enteric coated EC) 250mg EC OD. (0.5 hr before meal or
Prophylaxis: 2x 5mg puffs 250mg, 400mg Adolescent/adult > 60kg: 2 hrs after). Diarrhoea,
OD x 10 days. 400mg EC OD. abdominal pain, nausea
Oseltamivir Tab 75mg Treatment 2mg/kg/dose Influenza A, B treatment Nausea, vomiting. and vomiting (more
BD (max 75mg BD) x and prophylaxis. common).
5 days Can cause peripheral
or neuropathy, pancreatitis
Children ≥ 12 mths old and renal impairment.
up to adult: Monitor amylase/lipase.
≤ 15kg: 30mg BD Efavirenz (EFV) Cap 200mg 10–15mg/kg/day ON. HIV treatment. Use only if age > 3
> 15–23kg: 45mg BD Adolescent > 40kg/ yrs old.
> 23–40kg: 60mg BD Adult: 600mg ON. Skin rash, CNS effects
> 40kg or adult: (abnormal dreams,
75mg BD insomnia, confusion,
Children < 12 mths old: agitation, hallucinations).
(2mg/kg/dose BD) Take on empty stomach,
< 3 mths: 12mg BD best given at bedtime.
3–5 mths: 20mg BD
6–11 mths: 25mg BD

Prophylaxis: Dose as
above OD x 10 days.

* 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.
576 The Baby Bear Book Appendix II: Drugs 577

Drug Preparation Dosage Indications/Comments Side-effects CARDIOVASCULAR SYSTEM

Nevirapine Susp 10mg/ml Treatment: Dose in HIV treatment and Warn family to observe
stepwise manner. perinatal prevention of for rash. Occurs within
Tab 200mg 2 mths–8 yrs old: 4mg/ HIV transmission. the first 6 wks of therapy.
kg/day OD x 2 wks, then PRESSORS
7mg/kg/day OD. Fever, nausea, headache
8–16 yrs old: 4mg/kg/ and abnormal LFTs. Drug Preparation Route Dosage Remarks
day OD x 2 wks, then Severe hepatitis and Adrenaline Inj 1:10,000 IV Bradycardia/hypotension: 0.1ml/ May be given via ETT in
8mg/kg/day q12h. hypersensitivity reaction 1mg/10ml kg IV/IO 1: 10,000 or 0.1ml/kg ET higher doses (0.1ml/kg
Adolescent/adult: (less common). 1:1,000 1mg/ml vial 1:1,000, and subsequently 0.1ml/ 1:1,000 diluted with 2–5mls
200mg OD x2 wks, then kg 1:10,000 IV/IO every 3–5 mins. N/S).
200mg BD. Infusion: 0.1–2μg/kg/min titrated For asystole/pulseless arrest,
Prevention: 2mg/kg/dose to effect. increased dosage no longer
within 72 hrs of birth. routinely recommended.
Lopinavir/ Solution If no concurrent NVP HIV treatment. Take with food. Dobutamine 250mg/5ml vial IV 5–20μg/kg/min. Contraindicated
ritonavir (LPV/ 80mg LPV/20mg or EFV: Diarrhoea, headache, infusion in hypertrophic
RTV) ‘Kaletra’ RTV per ml 7–15kg: 12mg/kg/dose nausea and vomiting, cardiomyopathy.
Cap 133mg LPV BD. rash (more common). Half-life 2 mins.
LPV/33mg RTV 15–40kg: 10mg/kg/dose ↑glucose, ↑triglycerides,
Tab 200mg LPVBD. ↑cholesterol (less Dopamine 200mg/5ml vial IV Low dose: 2–5μg/kg/min. Increases renal blood flow.
LPV/50mg RTV > 40kg: 400mg common). infusion Minimal effect on HR and
LPV/100mg RTV (2 cardiac output.
tab) BD. Intermediate dose: 5–15μg/ Increases renal blood flow,
kg/min. HR, cardiac output and
If on concurrent NVP contractility.
or EFV: High dose > 20μg/kg/min. Decreases renal perfusion,
7–15kg: 13mg/kg/dose prominent alpha adrenergic
LPV BD. effects.
15–40kg: 11mg/kg/dose Isoprenaline 0.2mg/ml IV 0.1–2.0μg/kg/min. Use with care in CHF,
LPV BD. infusion Start with low dose, increasing ischaemia, or aortic stenosis.
> 40kg: 533mg every 5 mins until desired effects Monitor for arrhythmias,
LPV/133mg RTV (2 or arrhythmias or HR > 180/min. hypertension and myocardial
tab) BD. ischaemia. Not used in
Nelfinavir Tab 250mg PO 30mg/kg TDS or HIV treatment and Diarrhoea, rash, cardiac arrests unless
(NFV) > 6 yrs old: 55mg/kg prevention. ↑glucose, ↑triglycerides, bradycardia due to heart
dose BD. ↑cholesterol. block
Adolescent: 750mg TDS. Milrinone 10mg/10ml IV 50μg/kg over 10 min (loading),
infusion 0.25–0.75μg/kg/min
(maintenance), max 1.13mg/
kg/day.
Noradrenaline Inj 4mg/4ml IV 0.05–0.5μg/kg/min.
infusion
Vasopressin Inj 20U/ml IV 0.0003U/kg/min for
infusion augmentation of vasopressor
response.
578 The Baby Bear Book Appendix II: Drugs 579

DIURETICS Drug Preparation Route Dosage Remarks

Lignocaine Inj 10mg/ml (1%) IV Anti-arrhythmic: 1mg/kg/dose For ventricular arrhythmias.
Drug Preparation Route Dosage Remarks Xylocaine) slow bolus. May cause hypotension,
Infusion 20–50μg/kg/min. seizure, cardiac or respiratory
Frusemide (Lasix) Tab 40mg Oral 0.5–1.0mg/kg/dose (max Potentiates ototoxicity
arrest.
Syr 5mg/5ml 20–40mg) 6–24 hr. and nephrotoxicity of
Inj 20mg/2ml IV 0.5–1.0mg/kg/dose (max aminoglycosides. Procainamide Tab SR 500mg Oral 15–50mg/kg/day QDS. For VT and flutter,
20–40mg) 6–24 hr. (Pronestyl) Inj 100mg/ml IV 2mg/kg/dose slowly over 5 mins. supraventricular arrhythmia
IV Infusion 0.1–1mg/kg/hr. Repeat 10–30 mins. unresponsive to digoxin.
QRS widening > 0.02 sec
Hydrochloro- Tab 25mg Oral 2–3mg/kg/day BD. K+ supplement needed.
suggests toxicity.
thiazide
Propranolol Tab 10mg, 40mg Oral 0.2–0.5mg/kg/dose (max For VT, digoxin-induced
Spironolactone Tab 25mg Oral 3mg/kg/day in divided doses. Contraindicated in renal
Inj 1mg/ml 10–25mg) 6–12 hr, slow increase arrhythmias and SVT not
Syr 5mg/ml failure.
to max 1mg/kg/dose 6–12 hr. responsive to digoxin.
May cause hyperkalaemia.
Contraindicated in asthma
IV 0.1mg/kg/dose over 15 mins. May and heart block. May
repeat 6–8 hrs later. Max single cause hypotension and
dose 1mg. bronchospasm.
ANTI-ARRHYTHMIC Tetralogy spells: 0.15–0.25mg/
kg/dose IV slowly. May repeat 15
Drug Preparation Route Dosage Remarks min x 1 (max single dose 5mg).
Adenosine Inj 6mg/2ml IV 0.1mg/kg/dose (max 6mg). For SVT. To be given rapidly Verapamil Inj 5mg/2ml IV 0.1–0.2mg/kg (max 5–10mg) For SVT, atrial fibrillation
0.2mg/kg/dose (max 12mg) if no via the largest IV cannula (Isoptin) Tab 40mg over 10 min under ECG and and flutter. If hypotension
response for subsequent second and flushed quickly with BP monitoring. May repeat 30 develops, give IV Ca
and third doses. 10–20ml N/S. mins later. Gluconate 10% 5ml/kg. If
bradycardia, give IV Atropine
Atropine Sulphate Inj 0.6mg/ml IV 0.02mg/kg/dose (min 0.1mg. Max For severe bradycardia. May Oral 1–3mg/kg/dose (max 0.01mg/kg.
0.5mg for children). be given through the ETT. 80–120mg) 8–12 hr. Contraindicated with beta-
Amiodarone Tab 200mg Oral 4mg/kg/dose (max 200mg) 8hr Decrease doses of digoxin, blockers.
(Cordarone) x 1 wk, then 12hr x 1 wk, then warfarin and flecainide.
12–24 hr. Prolongs QT.
Inj 150mg/3ml IV Taper IV infusion over few days Caution: Can cause severe
after starting oral. hypotension and/or
bradycardia. ANTI-HYPERTENSIVE
Loading 5mg/kg over 30 mins,
then 5–15μg/kg/min VT/VF 5mg/ Drug Preparation Route Dosage Remarks
kg over 10 mins.
Captopril Tab 12.5mg Oral 0.1–1mg/kg/dose 8 hrly (max Caution in renal failure.
Flecainide Tab 100mg Oral 2–3mg/kg/dose (max 100mg) For SVT including atrial Syr 1mg/ml 50mg).
(Tambocor) 12 hr. Can increase over 2 wks arrhythmias. Minor
to 7mg/kg/dose (max 200mg) negative inotropic effect Diazoxide Inj 300mg/2ml IV IV: 3mg/kg as a single dose Side-effects include
8–12 hr. — caution in heart failure rapidly. Repeat once after 5–15 hypotension and
or combination with mins if necessary. Max 4 doses hyperglycaemia.
beta–blockers. Increases in 24 hrs.
plasma digoxin level by 15%. PO: 1.7mg/kg/dose TDS.
Flecainide dose to be
reduced by 50% if used with For hyperinsulinaemic
amiodarone. hypoglycaemia: 10–15mg/kg/
day 8hr.
Enalapril Tab 5mg, 10mg Oral 0.2–1mg/kg/dose (max 40mg) Caution in renal failure.
once a day.
580 The Baby Bear Book Appendix II: Drugs 581

Drug Preparation Route Dosage Remarks RESPIRATORY SYSTEM

Hydralazine Tab 10mg, 50mg Oral 0.5–1mg/kg/dose BD-QDS (max Use with caution in cardiac
Inj 20mg/ml 50mg). disease.
IV 0.1–0.3mg/kg/dose 4–6 hrly .
May repeat after 30–90 mins. ANTI-ASTHMATIC DRUGS
Infuse at 4–6μg/kg/min
(continuous or intermittent Drug Preparation Route Dosage Remarks
infusions not recommended. Max Aminophylline Inj 500mg/2ml IV 4mg/kg/dose. Omit loading in patients
rate 5mg/min or 0.2mg/kg/min, (250mg/10ml) Slow infusion in 30 mins, then on theophylline therapy.
whichever is less). 16–20mg/kg/24hr, continuous Therapeutic level:
Nitroprusside Inj 50mg IV 0.5–8μg/kg/min (max 4μg/kg/ Must monitor with arterial infusion. 10–20μg/ml.
Sodium (Nipride) min if used > 24 hrs). line. In overdose, causes Beclomethasone Aerosol 50μg/puff Inhalation 1–2 puffs BD to QDS.
Dilute with D5% and protect hypotension, metabolic Dipropionate
from light. acidosis. Converted to (Becotide)
cyanide and thiocyanate.
Keep thiocyanate levels < Budesonide Aerosol 100μg/puff, Inhalation 1–4 puffs BD.
12mg/l. (Pulmicort) 200μg/puff 0.5–1mg BD reducing to
Respiratory solution Nebulised 0.25–0.5mg BD.
Glyceryl Trinitrate Inj 25mg/5ml IV 1–5μg/kg/min. 500μg/2ml
Increase at 20-min interval to
desired effects. Fluticasone Aerosol 50μg/puff or Inhalation > 4 yrs old: 50–100μg BD. Long-acting steroid
(Flixotide) 125μg/puff aerosol.
Amlodipine Tab 5mg Oral 0.05–0.2mg/kg once daily (max
(Norvasc) 10mg). Hydrocortisone Inj 100mg/vial IV 5mg/kg/dose 4–6 hrly.
Atenolol Tab 50mg, 100mg Oral 1–2mg/kg once daily. Contraindicated in cardiac Ipratropium Respiratory solution Inhalation 0.25–1ml 4–6 hrly.
failure, asthma. Bromide 250μg/ml
Adjust for renal failure. (Atrovent) Aerosol Inhalation 1–2 puffs 6–8 hrly.
Labetolol Inj 25mg/5ml IV Infusion 0.25–3mg/kg/hr. Contraindicated in cardiac Ketotifen 1mg/5ml Oral 6 mths–3 yrs old: 0.5mg BD.
failure, asthma. (Zaditen) > 3 yrs old: 1mg BD.
Nifedipine Cap 5mg, 10mg Oral 0.5mg/kg/dose 6–8 hrly (max Sublingual route not used Prednisolone Tab 1mg, 5mg Oral 2mg/kg/day.
(Adalat) Adalat LA 30mg 3mg/kg/day). in children — absorption Salbutamol Tab 2mg Oral 0.1–0.15mg/kg/dose TDS or QDS.
0.5–1mg/kg/dose 12 hrly. is erratic and no advantage (Ventolin) Syr 2mg/5ml 3–12 yrs old: 4mg BD.
over oral route. (Volmax) Respiratory solution Inhalation 0.01–0.03ml/kg 2–6 hrly. Controlled-release
Capsule can be broken 5mg/ml Salbutamol.
and the liquid consumed Aerosol 100μg/puff Inhalation 1–2 puffs TDS or QDS.
immediately. Inj 5mg/5ml IV 5μg/kg over 10 mins, then
Hypotension is an important 1–5μg/kg/min.
side-effect, especially the
Sodium Aerosol 5mg/puff Inhalation 1–2 puffs TDS to QDS. Trial of therapy for at
liquid form (after breaking
Cromoglycate least 3 mths.
the capsule).
(Intal 5)
Terbutaline Tab 2.5mg Oral 0.075mg/kg/dose TDS to QDS.
(Bricanyl) Syr 0.3mg/ml
Respiratory solution Inhalation 0.02–0.03ml/kg/dose TDS.
5mg/2ml
Aerosol 0.25mg/puff
(0.5mg/puff turbuhaler) Inhalation 1–2 puffs TDS or QDS.
Theophylline Syr 80mg/15ml Oral 15–20mg/kg/day TDS or QDS.
(Nuelin) Tab 250mg
(Nuelin Sr) 8–16mg/kg/day BD. Sustained-release.
(Austyn)
(Theo-Dur)
582 The Baby Bear Book Appendix II: Drugs 583

COUGH MIXTURES AND MUCOLYTICS Drug Preparation Route Dosage Remarks

Promethazine Syr 5mg/5ml, Oral < 6 mths old: Contraindcated. Not recommend for babies
Drug Preparation Route Dosage Remarks (Phenergan) Tab 25mg 6–24 mths old: Not with a past history of apnoea
recommended. and those with bronchiolitis.
Acetylcysteine Tab 600mg Oral < 1 yr old: 50mg BD.
> 24 mths old: 0.125–0.25mg/ For severe allergy: A single
(Flumucil) Sachet 100mg 1–2 yrs old: 50mg TDS.
Inj. 50mg/2ml IM/IV kg/dose TDS. dose of IM promethazine
2–6 yrs old: 100mg TDS.
0.5mg/kg..
6–10 yrs old: 200mg BD.
> 10 yrs old: 200mg TDS.
Actifed Compound/ Dextromethorphan Oral 2–5 yrs old: 2.5mls TDS. Not recommended for
Linctus Hydrobromide 6–12 yrs old: 5mls TDS. children < 2 yrs old because NEUROMUSCULAR SYSTEM
10mg of respiratory depression.
Pseudoephedrine
HCl 30mg
Tripolidine HCl ANTI-CONVULSANTS
1.25mg/5ml
Actifed Expectorant Guaiphenesin Oral 2–5 yrs old: 2.5mls TDS. Drug Preparation Route Dosage Remarks
100mg 6–12 yrs old: 5mls TDS. Carbamazepine Tab 200mg Oral Initiate at 10mg/kg/day BD-TDS Therapeutic levels:
Pseudoephedrine (Tegretol) CR Tab 200mg for 1 wk and gradually increase to 20–50umol/l.
HCl 30mg Susp 100mg/5ml 30mg/kg/day BD-TDS over 2–4 Monitor haematologic and
Tripolidine HCl wks (adult dose is 500mg TDS). hepatic toxicity.
1.25mg/5mls Look out for allergic reaction
Ambroxol HCl Syr 30mg/5ml Oral 1–2 yrs old: 2.5mls BD. up to 4–6 wks.
(Mucosolvan) Tab 30mg 2–4 yrs old: 3.75mls BD. Clonazepam Tab 0.5mg and 2mg Oral 0.05–0.1mg/kg/day BD or TDS Monitor haemtologic and
Benadryl Expectorant Syr 5mg/5ml Oral Children: (Rivotril) (adult dose 1.5mg/day TDS). hepatic toxicity.
(Diphenhydramine > 1 yr old: 2.5–5mls TDS. Diazepam Tab 2mg, 5mg, Oral 0.2–0.5mg/kg/day BD or TDS. Give undiluted at no faster
HCl and NH4Cl) > 12 yrs old: 5–10mls TDS. (Valium) 10mg than 2mg/min.
Bromhexine HCl Tab 8mg Oral < 2 yrs old: 1mg TDS. Inj 10mg/2ml IV 0.25mg/kg/dose. May repeat in 15 Use to abort acute seizures
(Bisolvon) Syr 4mg/5ml 2–5 yrs old: 4mg BD. (Stesolid) mins (not > 0.6mg/kg in 8 hrs). and prolonged seizures.
5–10 yrs old: 4mg TDS. Rectal solution Rectal < 10kg: 2.5mg (will not give
> 10 yrs old: 8mg TDS. 5mg/tube recommendation for <
Carbocysteine Syr 100mg/5ml Oral < 5 yrs old: 2.5ml BD. 10kg).
(Rhinathiol) Syr 250mg/5ml 5–15 yrs old: 5ml TDS. > 10kg: 0.4–0.5mg/kg (round up
Cap 375mg to 5mg). In most cases,
5–10mg is sufficient.
Cetirizine (Zyrtec) Syr 1mg/ml Oral 1–2 yrs old: 2.5mg BD.
2–5 yrs old: 2.5mg BD, or 5mg Nitrazepam Tab 5mg Oral 0.125–0.5mg/kg/dose BD for For infantile spasms,
daily. (Mogadon) epilepsy. myoclonic seizures.
> 6 yrs old: 10mg daily. 2.5–5mg on for hypnotic in child.
5mg on for adult (not
Chlorpheniramine Tab 4mg Oral 0.35mg/kg/day TDS or QDS. recommended for hypnosis).
Maleate (Piriton) Syr 2mg/5ml
Lamotrigine Tab 5mg, 50mg, Oral Dose without VPA 0.6mg/kg/day Steady state 3–15 days.
Desloratidine (Aerius) Syr 0.5mg/ml Oral 2–5 yrs old: 1.25mg daily. (lamictal) 100mg for 2 wks, then 1.2mg/kg/day for Adult starting dose:
6–11yrs old: 2.5mg daily. 2 wks, and increase fortnightly by 50mg/day BD (without VPA),
> 12 yrs old: 5mg daily. 0.6mg/kg/day to 5–15mg/kg/day and 25mg/day BD (with
Dexchlorpheniramine Tab 2mg Oral 6–12 yrs old: ½ Tab TDS to QDS. 12 hrly (maintenance). VPA).
Maleate (Polaramine) Dose with VPA 0.15mg/kg/day
for 2 wks, and increase fortnightly
Loratadine (Clarityne) Syr 5mg/5ml Oral < 30kg: 5mg daily.
by 0.15mg/kg/day to 1–5mg/kg/
Tab 10mg > 30kg: 10mg daily.
day 12hrly (maintenance).
584 The Baby Bear Book Appendix II: Drugs 585

Drug Preparation Route Dosage Remarks ANTI-EMETICS

Phenobarbitone Inj 20mg/0.5ml IV/IM IV loading: 20mg/kg over 30 mins. Therapeutic levels:
sodium Tab 10, 30mg Oral May repeat up to 60–80mg/kg 80–120Umol/l. Drug Preparation Route Dosage Remarks
Syr 15mg/5ml Oral (in CICU). Dilute in Normal saline.
Granisetron 3mg/vial IV > 30kg: 3mg/day OM.
Maintenance: 3–6mg/kg/day BD. May cause respiratory
(Kytril) < 30kg: 50μg/kg (round up to
Neonates: 3–4mg/kg/dose BD. depression, hypotension and
0.5mg or 1mg).
Steady state: 120–170 hrs. sedation. Monitor infants in
CICU. Metoclopramide Tab 10mg Oral 0.12mg/kg/dose 6 hrly. May cause oculogyric crisis.
(Maxolon) Syr 5mg/5ml Oral
Phenytoin Sodium Inj 250mg/5ml Slow IV Loading: 20mg/kg/dose over 20 Steady state: 23–140 hrs.
Inj 10mg/2ml IV, IM
Tab 30, 100mg Oral mins. May repeat 5mg/kg x 2 in To be diluted in normal
Syr 125mg/ml Oral status epilepticus. saline and run by syringe Ondansetron Tab 8mg Oral Prevention of chemotherapy- Maximum per dose: 8mg.
Load 10mg/kg/day BD or TDS driver. (Zofran) induced emesis: Children 4–11
for 3–5 days, then maintain at IV form may cause cardiac yrs old: 4mg 30 minutes before
3–10mg/kg/day BD or TDS. arrhythmias (monitor in chemotherapy; repeat 4 and 8 hrs
HD/CICU). after initial dose, then 4mg q8hr
for 1–2 days after chemotherapy
Pyridoxine Tab 5mg, 10mg, Oral 1–4mg/kg/day as maintenance. Consider in refractory
completed.
(Vit B6) 50mg neonatal seizures.
Inj 100mg/ml IV, IM 50mg IV or 100mg IM stat.
Inj 2mg/ml IV Prevention of chemotherapy-
Sodium Valproate Tab 200mg CR, Oral Initiate at 10mg/kg/day BD or TDS Therapeutic level: induced emesis: Children
(Epilim) 300mg, 500mg Oral for 1–2 wks, and maintain at max 40–100μg/ml. 6 mths–18 yrs old: IV 0.15mg/
(Convulex) Syr 200mg/5ml Oral 60mg/kg/day BD-QDS (adult dose: Steady state: 35–50 hrs. kg/dose administered 30 minutes
750–4,000mg/day BD-QDS). Monitor for hepatotoxicity prior to chemotherapy, 4 and 8 hrs
especially in children < 2 after the first dose or 0.45mg/kg/
yrs old and receiving many day as a single dose.
AEDs.
Lorazepam Inj 2mg/ml IV 0.1mg/kg (up to 4mg). May Use in status epilepticus. Prevention of postoperative
repeat in 5 mins same dose. Infuse at rate 1–2mg/min nausea and vomiting: Children
(slow bolus). 1 mth–12 yrs old:
Dilute in NS (equal volume). ≤ 40kg: 0.1mg/kg as a single dose
> 40kg: 4mg as a single dose
Topiramate Tab 50mg, 100mg Oral Initiate at 1–2mg/kg/day BD for Risk of renal stones, so
(Topomax) 1 wk, and increase by 1–2mg/kg/ ensure adequate fluid intake. Prochlorperazine Tab 5mg Oral 0.4mg/kg/day TDS or QDS. May cause oculogyric crisis.
day BD wkly until maintenance at New AEDs to start with Maleate Inj 12.5mg/ml IM 0.2mg/kg/day QDS (max 40mg/
1–9mg/kg/day BD. neurologist advice. (Stemetil) day).
Gabapentin Tab 300mg Oral 30–60mg/kg/day TDS. Careful in renal impairment.
(Neurontin) New AEDs to start with
neurologist advice.
Vigabatrin Tab 500mg Oral Initiate at 40mg/kg/day OM-BD New AEDs to start with ANTI-PYRETICS/ANALGESICS
for 2 wks, and increase slowly. neurologist advice.
Maintain at 80–100mg/kg/day Risk of visual field Drug Preparation Route Dosage Remarks
OM-BD. constriction. Acetysalicylic Acid Tab 100mg Oral Anti-inflammatory: 80–100mg/kg/day
Levetiracetam Tab 250mg, 500mg, Oral Initiate at 20mg/kg/day BD for 2 New AEDs to start with (Aspirin) Oral in divided doses.
1,000mg wks, and increase gradually every neurologist advice. Antiplatelet: 5mg/kg daily.
2–4 wks. Diclofenac Tab 25mg Oral 0.5–3mg/kg/day BD (max 50mg/dose). Not recommended for
Maintain at max 60mg/kg/day BD. (Voltaren) Supp 12.5mg, 50mg Oral children < 6 mths old.
Rectal
Ibuprofen Syr 100mg/5ml Oral 20–40mg/kg/day TDS or QDS. Higher dose for anti-
(Brufen) Tab 200 Oral inflammatory use.
Naproxen Tab 275mg Oral > 5 yrs old: 10–15mg/kg/day BD.
(Syn Flex)
586 The Baby Bear Book Appendix II: Drugs 587

Drug Preparation Route Dosage Remarks Drug Preparation Route Dosage Remarks
Paracetamol Tab 120, 500mg Oral 40–60mg/kg/day 4–6 hrly. Succinylcholine 100mg/2ml vial IV 1–2mg/kg/dose. Duration of action: 10 mins.
(Panadol) Syr 120mg/5ml Oral Side-effects include
Supp 125mg Oral hypotension, bradycardia,
Supp 250mg Rectal arrhythmias and muscle
Supp 325mg fasciculations.
Vecuronium 4mg/ml IV 0.1mg/kg/dose every 1–2 hrs.
1–10μg/kg/min.
SEDATIVES Edrophonium Inj 10mg/ml IV 0.02mg/kg/dose. Atropine: 0.01mg/kg/dose
(Tensilon) Repeat dose after 30 secs, if no (max 0.4mg) on standby.
Drug Preparation Route Dosage Remarks response.

Chloral Hydrate Syr 200mg/5ml Oral 30–50mg/kg/day TDS or QDS Contraindicated in hepatic or Neostigmine Inj 2.5mg/ml Oral Myasthenia Gravis: 2mg/kg/day
(max 1g). renal impairment. IM in 6–8 doses.
Relaxant reversal: 0.04mg/
Fentanyl 500μg/10ml IV 1–4μg/kg/dose. Give IV over 3–5 min. kg/dose.
100μg/2ml Infuse 2–4μg/kg/hr. Rapid infusion may cause
Ventilated 5–10μg/kg/hr. respiratory depression. Pyridostigmine Tab 10mg, 60mg Oral 7mg/kg/day in 5–6 doses.
(Mestinon) Increase dose and frequency
Lorazepam Tab 0.5mg Oral 0.02–0.06mg/kg/dose 8–24 hrly. according to response.
Tab 1mg
Methadone Tab 5mg PO 0.1–0.2mg/kg/dose 6–12 hrly
(Physeptone) (max 10mg/dose).
Midazolam Inj 15mg/3ml IM 0.1–0.2mg/kg/dose (up to Sedation. ENDOCRINE SYSTEM
(Dormicum) 0.5mg/kg/dose). Anaesthesia.
IV 0.5mg/kg, then 2μg/kg/min Antidote: Flumazenil. Drug Preparation Route Dosage Remarks
(3mg/kg in 50ml at 2ml/hr).
ACTH Synacthen 250μg/ IV First 6 mths: 36μg/kg. Short Synacthen test.
Morphine Inj 10mg/amp IV 0.1mg/kg/dose slow bolus (max Antidote: Naloxone. ml vial IM 6 mths–2 yrs old: 0.125mg
Sulphate Syr 5mg/5ml Oral 15mg). > 2 yrs old: 250μg
Infusion 0.5mg/kg in 50ml 5% 1mg ON x 3 days Long Synacthen test.
Dextrose.
Carbimazole Tab 5mg Oral 0.25mg/kg/dose TDS (max 15mg) Watch for neutropenia and
Rate: 1–4ml/hr (10–40μg/kg/hr).
x 2 wks, then 0.1mg/kg/dose myalgia.
0.2–0.5mg/kg/dose 4–6hrly.
8–12 hrly.
Pethidine Inj 10mg/ml IM 0.5–1.5mg/kg/dose 3–4hrly. Maximum dose: 75mg.
Desmopressin IN 100μg/ml sol Intranasal IN 5–10μg (0.05–0.1ml) per
Inj 50mg/ml Slow IV
Acetate (DDAVP) 12–24 hrly.

Tab 100μg, 200μg Oral Nocturnal enuresis: PO 100–400μg.

(Minirin) ON DI: 100–400(g/day in divided
MUSCLE RELAXANTS doses.

Low Factor VIII V 0.3μg/kg/24 hrs

Drug Preparation Route Dosage Remarks Inj Minirin 4μg/ml IV in 1ml/kg saline over 1 hr every
Atracurium 25mg/2.5ml amp IV 0.3–0.6mg/kg bolus, followed Useful in patients with renal 12–24 hrs.
by IV injection 0.1–0.2mg/kg as dysfunction.
needed, or continuous infusion Diabetes insipidus: Start with
5–10μg/kg/min. IV/IM/SC 0.5–1μg 12–24 hrly.
Pancuronium 4mg/2ml IV 0.05–0.1mg/kg/dose 1–2 hrly. Vasopressin Inj 20U/ml (Soluble SC/IM Cerebral oedema: IV 0.5mg/kg For diabetes insipidus.
0.25–0.75μg/kg/min infusion. Pitressin) IV 0.5mU/kg/hr, double every 30 mins
if polyuria persists, to max 15mU/
kg/hr.
588 The Baby Bear Book Appendix II: Drugs 589

Drug Preparation Route Dosage Remarks ALIMENTARY SYSTEM

Dexamethasone Tab 0.5mg Oral Cerebral oedema: IV 0.5mg/kg Begin 24 hrs prior to
Tab 4mg IM/IV followed by 0.25mg/kg 6 hrly . elective extubation and
Inj 4mg/ml Airway oedema: IV 0.1–0.25mg/kg/ then for 4–6 doses.
dose 6 hrly. Indicated in Hib ANTACIDS AND ANTIULCERANTS
meningitis prior to
Meningitis: 0.15mg/kg/dose 6 hrly antibiotic treatment. Drug Preparation Route Dosage Remarks
x 4 days. Alginic Acid Na alginate 500mg Oral 1–12 yrs old: 5–10ml after meals. High sodium content.
Fludrocortisone Tab 100μg Oral 0.05–0.1mg/day. Babies with CAH may (Gaviscon) Na bicarbonate
initially need higher 267mg
doses of 200–400mg/ Ca Carbonate
m2 day plus NaCl 160mg per 10ml
supplementation. Cimetidine Tab 200mg Oral 20–40mg/kg/day q6hr (max Reduce dosage if renal
Glucagon 1mg freeze-dried IM 0.1–0.2mg/kg/dose. For hypoglycaemic coma. 200mg/dose). function impaired.
powder IV Max 1mg. Magnesium Mg Trisilicate Oral 1–2 yrs old: 2.5ml/dose 8hrly. To be given after meals.
Infusion 0.005–0.01μg/kg/hr. Trisilicate 500mg 2–5 yrs old: 5ml/dose 8 hrly.
Hydrocortisone Inj 100mg vial IV 4mg/kg stat and 4–6 hrly in status Triple the dose on Mg Carbonate 5–10 yrs old: 7.5ml/dose 8 hrly.
Sodium Succinate Tab 10mg asthmaticus. sick days orally or use 500mg > 10 yrs old: 10ml/dose 8 hrly.
IM/IV IM/IV 50–150mg pre-op or in parenteral route. Na Carbonate
adrenal crisis. 500mg/10ml
Oral Physiological replacement dose = Mylanta DS Mg (OH)2 400mg Oral 0.25ml/kg/dose q4–6hr.
10–20mg/m2/day in divided doses A1 (OH)2 400mg
8–12 hrly. Simethicone
Anti-inflammatory/ 40mg/5ml
immunosuppressive:
PO 2.5–10mg/kg/day 6–8 hrly. Omeprazole Cap 20mg Oral PO 0.4–0.8mg/kg/day (max
IV/IM 1–5mg/kg/day 12–24 hrly. (Losec) Tab 10mg 40mg).
Physiologic replacement therapy: Inj 40mg/10ml IV IV 500μg/kg/day-2mg/kg/day.
PO 0.5 to 0.75mg/kg/day 8 hrly. Ranitidine Syr 150mg/10ml Oral 2–6mg/kg/day q8–12hr. Excreted via the kidney.
IM 0.25 to 0.35mg/kg/day OD. Tab 150mg
L-Thyroxine Tab 50μg, 100μg Oral 100μg/m2/day Inj 50mg/2ml 1–3mg/kg/day q6–12hr slow IV.
(25μg/day in most newborns). Sucralfate Tab 1,000mg Oral 40–80mg/kg/day q6hr.
0–1 mth old: 10–15μg/kg OD.
1 mth– 2yrs old: 5–10μg/kg OD.
2–12 yrs old: 5μg/kg OD.
12–18 yrs old: 50–100μg OD. ANTI-DIARRHOEALS
Inj 500μg IV/IM: 50–75% of the oral dose.
Propylthiouracil Tab 50mg Oral 5mg/kg/day in 3 divided doses. Precautions as for Drug Preparation Route Dosage Remarks
carbimazole, but can
be tried in carbimazole Cholestyramine Powder 4g/sachet Oral 240mg/kg/day q8hr. For intractable diarrhoea.
allergy. Dioctahedral Powder 3g/sachet Oral < 1 yr old: 1 sachet/day q8–12hr. May interfere with
Smectite (Smecta) 1–2 yrs old: 1–2 sachets/day absorption of other drugs
q8–12hr. administered at the same
> 2 yrs old: 2–3 sachets/day time..
q8–12hr.
Kaolin mixture BP Susp Oral 1–2 yrs old: 2.5ml TDS.
2–5 yrs old: 5ml TDS.
5–10 yrs old: 7.5ml TDS.
>10 yrs old: 10ml TDS.
590 The Baby Bear Book Appendix II: Drugs 591

ANTI-SPASMODICS Drug Preparation Route Dosage Remarks

Monobasic Na Disposable Enema Rectal > 2 yrs old: 59ml. For children > 2 yrs old.
Drug Preparation Route Dosage Remarks Phosphate (Fleet 118ml (adult)
Enema) Disposable Enema
Hyoscine N Tab 10mg Oral 0.5mg/kg/dose (max 40mg)
59ml (Paediatric)
Butylbromide Inj 20mg/ml IM q6–8hr.
(Buscopan) IV Sodium Citrate Disposable enema Rectal 1 tube PRN (for < 3 yrs old, insert
Sodium Lauryl 5ml nozzle half way).
Propantheline Tab 15mg Oral 1.5mg/kg/day q6hr.
Sulfoacetate
Bromide
(Microlax)
Polyethylene Na Sulphate 5.685g Oral 25ml/kg/hr. For refractory encoperesis
Glycol Electrolyte Na Chloride 1.465g or colonic preparation for
Solution Na Bicarbonate colonoscopy. Administer
GIT REGULATORS 1.685g via nasogastric tube if child
Potassium Chloride unable to drink the required
Drug Preparation Route Dosage Remarks 0.7425g amount. May cause mild
Aspartame 0.0494g emesis. On rare occasions,
Domperidone Tab 10mg Oral 0.25mg/kg/dose TDS before Polyethylene glycol may require intravenous
(Motilium) Supp 10mg Rectal meals, and before bedtime if 59g fluid to prevent dehydration.
necessary.
Sennosides Tab 7.5mg Oral 2–6 yrs old: ½ tab ON.
Metoclopramide Syr 5mg/5ml Oral 0.1mg/kg/dose BD-TDS Can cause extra-pyramidal (Senokot) 6–12 yrs old: 1–2 tabs ON.
(Maxolon) Tab 10mg Children > 20kg: 0.5mg/kg/day reactions usually of the 12–18 yrs old: 2–4 tabs ON.
Inj 10mg/2ml IM /IV dystonic type.
Supp 20mg Suppository
Trimebutine Susp 72mg/15ml Oral < 6 mths old: 2.5ml BD-TDS.
Maleate Tab 100mg 6 mths–1 yr old: 5ml BD. IMMUNOSUPPRESSIVE DRUGS
(Debridat) 1–5 yrs old: 5ml TDS.
> 5 yrs old: 10ml TDS.
Drug Preparation Route Dosage Remarks
L-Asparaginase Inj 5,000IU IV Before use: Test dose 1–10U Stop administration if
Inj 10,000IU IM given S/C. allergic symptoms appear
SC Resuscitation trolley standby. e.g. hypotension, urticaria.
LAXATIVES Monitor BP closely for 1 hr.
Pre and post dose HC.
Drug Preparation Route Dosage Remarks First dose and test dose given
Bisacodyl — Tab 5mg Oral 0.3mg/kg/dose OD. in HD.
Enteric Coated Adult Supp 10mg Rectal < 1 yr old: 2.5mg. Bleomycin Inj 15mg/vial IV 10–20mg/m2 1–2 times a wk.
(Dulcolax) 1–5 yrs old: 5mg. IM
> 5 yrs old: 10mg. SC
Glycerine Supp (children) Rectal One suppository as needed. Busulphan Tab 2mg Oral 0.06–0.12mg/kg/24 hrs to
(Glycerol) maintain WBC ≥ 10,000/mm3.
Lactulose Liquid Oral 0.5ml/kg/dose q12–24hr. Cisplatinum Inj 10mg, 25mg IV Pre-hydrate for 6 hrs with D/S Monitor urea, electrolytes
Cisplatin 50mg/vial (R) or N/S. and creatinine, uric acid and
Hepatic coma 1ml/kg/dose hrly Post hydrate for 24 hrs. CaMg PO4.
until bowel cleared, then 6–8hr. Strict I/0 chart. Audiometry and renal
Liquid Paraffin Susp Oral 3–6 yrs old: 2.5–5ml ON. function should be
> 6 yrs old: 5–10ml ON. monitored.
592 The Baby Bear Book Appendix II: Drugs 593

Drug Preparation Route Dosage Remarks IMMUNOSUPPRESSIVE /

Cyclophos- Tab 50mg IV Give Mesna when dose is IMMUNOMODULATIVE DRUGS
phamide Inj 200m 1g/vial > 1,000mg/m2.
Mesna dose = 120%
cyclophosphamide.
50% given during infusion, and NSAIDS
50% over remaining 24 hrs..
Cytosine Inj 100mg/vial IV Severe mucositis and iritis Drug Preparation Route Dosage Remarks
with high dose Arabinoside Acetylsalicylic Tab 100mg Oral Anti-inflammatory: 80–100mg/ Risk of Reye’s Syndrome if
SC IT. Acid (Aspirin) kg/day 6–8 hrly. chickenpox, influenza, GI
Predsol eyedrops for Antiplatelet: 3–5mg/kg/day. irritation, hepatotoxicity,
prophylaxis. platelet inhibition
Dacarbazine 100mg/vial IV Rapid IV immediately after (irreversible).
dilution. Flush well. Aspirin sensitivity if nasal
polyps, asthma salicylism
Dactinomycin Inj 500μg/vial IV Observe for mucositis.
(tinnitus, dizziness,
0.5mg/ml
headache, sweating).
Doxorubicin Inj 10mg/vial IV Cardiotoxic-maximum cumulative Baseline 2D echo.
Diclofenac Tab 25mg Oral PO/Supp: 6 mths–18 yrs old: NSAIDs reduce inflammation
(Adriamycin) Inj 50mg/vial dose 350mg/m2
(Voltaren) Supp 12.5mg Rectal 0.3–1mg/kg tds (max 50mg/ and pain in arthritis but do
Inj 20mg/vial
Supp 50mg dose). not arrest joint damage. Also
(liposomal)
Gel 1% Topical relieve fever.
Etoposide (VP 16) Inj 100mg/via IV 100mg/m2. Can cause hypotension. Inj 75mg/3ml IM IM: 2–18 yrs old: 0.3–1mg/kg Toxicity: GI irritation,
Cap 25mg Usually over 3–4 hrs infusion. OD–BD (for max 2 days, total daily bleeding, ulcer.
Minimum dilution 0.5mg/ml NS. dose not to exceed 150mg). Hepatic transaminitis.
Lomustine (CCNU) Cap Tab 40mg Oral 100–150mg/m2 every 6–8 wks. Renal: Fluid retention,
nephrotic, interstitial
6-Mercaptopurine Tab 50mg Oral 75mg/m2 OM daily before food.
nephritis.
Vinblastine Inj 10mg/vial IV 0.1–0.2mg/kg single wkly dose. Platelet-reversible platelet
4–6mg/m2/wk. inactivation.
Vincristine Inj 1mg/vial IV 1.5–2mg/m2 wkly (max dose Look out for ileus/ CNS: Headache, drowsy,
Inj 5mg/vial 2mg). constipation. dysphoria.
Hypersensitivity.
Methotrexate Tab 2.5mg Oral High dose MTX 6–8gm/m2. Monitor strict I/0, U/E/Cr Photosensitive rashes
Inj 50mg/vial IT Prehydrate for 6 hrs and maintain and LFT. (especially naproxen).
Inj 1,000mg/vial IV 3l/m2 till rescue complete. Folinic acid rescue 24–36
IM Urine pH must be > 7.0 hrs later. Ibuprofen Tab 200mg, 400mg Oral 20–40mg/kg/day. FDA-approved for children.
Bactrim should be off 1 wk (Brufen) Syr 100mg/5ml
before HD MTX. Naproxen Tab 275mg Oral 10–20mg/kg/day. FDA-approved for children .
Mustine Inj 10mg/vial IV No single dose should exceed (Synflex)
Hydrochloride 8mg. Fast IV injection into running Indomethacin Cap 25mg Oral 1–2.5mg/kg/day. FDA-approved for children
infusion as it is very rapidly PDA Inj 1mg IV > 14 yrs old.
hydrolysed. Higher CNS and gastric
Procarbazine Cap 50mg Oral Commence with 25–50mg/m2 toxicity.
and gradually increase to 100mg/ Selective COX-2 Approved for > 16 yrs old.
m2/day. inhibitors Under trial in children.
Promising because of less
side-effects (especially GI)
but with similar efficacy.
Rofecoxib (Vioxx) Tab 12.5mg, 25mg Oral 25mg OD (adult RA).
Celecoxib Cap 200mg Oral 200mg bd (adult RA).
(Celebrex)
594 The Baby Bear Book Appendix II: Drugs 595

STEROIDS DMARDS

Drug Preparation Route Dosage Remarks Drug Preparation Route Dosage Remarks
Prednisolone Tab 1mg, 5mg, Oral 0.5–2mg/kg/day. Gradually tail to OD or Methotrexate Tab 2.5mg Oral 0.3–1mg/kg/wk. For polyarticular JIA, and
20mg EOD dose for less toxicity Inj 1,000mg/10ml IM 10–20mg/m2/wk. SLE, JDM.
Syr 10mg/5ml especially on growth. Inj 50mg/2ml SC (max 25mg/wk). Given once a wk. Folic acid
Toxicity: Cushingoid, IT supplement.
infection, IM and subcutaneous gives
immunosuppression, better absorption.
suppression of Risks: Bone marrow
hypothalamicpituitary suppression, liver toxicity,
axis, hypertension, nausea.
electrolyte, hyperglycaemia, Suphasalazine Tab 0.5g Oral 40–70mg/kg/day (max 3g/day). For Enthesitis-related
hyperlipidaemia, Syr 50mg/ml arthritis and IBD.
osteopenia, avascular May need to go up to 3g/
necrosis, myopathy, cataract, day in active disease in
glaucoma. adolescence.
Methylprednisolone Inj 1g/amp IV Anti-inflammatory or For rapid control of severe Risks: Hypersensitivity rash,
IM immunosuppressive: 0.5–1.7mg/ SLE (CNS, renal, serositis), liver, renal, bone marrow
kg/day in divided doses BD–QDS JDM, JIA (systemic, toxicity.
Pulse therapy: 15–30mg/kg/dose polyarticular disease). Hydroxychloroquine Tab 200mg Oral 3–6mg/kg/day (max 400mg/ Antimalarial drug with
OD for 3 days. Risk hypertension, day). moderate anti-inflammatory
hyperglycemia, arrhythmia, properties. For arthritis and
CNS toxicity (fits, psychosis). SLE (mild disease, skin, joint,
Dilute in 100ml of Dextrose serositis, malaise), not for
or NS and infuse slowly over renal and CNS.
2 hrs with BP monitoring. G6PD deficiency: Relative
Intrasynovial Inj 10mg/ml Intra- Injection: Long-acting steroid. For JIA. contraindication. Regular
Triamcinolone articular 500μg/kg for smaller joints (max Sterility important. eye review for macular
acetonide 20mg). Risk infection, transient degeneration, corneal
Finger and toe joints (max 10mg). crystal synovitis, skin deposit.
1mg/kg for larger joints (max atrophy, cartilage damage Gastric irritation. Reversible
40mg). May be repeated for (repeated), asymptomatic skin rash.
relapse. calcifications.
596 The Baby Bear Book Appendix II: Drugs 597

IMMUNOSUPPRESIVES VITAMINS AND IRON REQUIREMENTS

Drug Preparation Route Dosage Remarks Multivite Drops (Vidaylin) 1ml
Vitamin Daily Requirement Deficiency
Cyclophosphamide Tab 50mg Oral 0.5–1g/m2 1–3 mthly For lupus nephritis Class IV (i.e. 16 drops) Contains
Inj 1g/vial IV and CNS lupus: Mthly x 6 Vit A Infants: 1,500IU Latent deficient 5,000IU/day. 1,500IU
mths, then 3 mthly for 1 yr Older children: 2,000–4,500IU Xerophthalmia 5,000IU/kg/day
(CNS), up to 3 yrs (renal). x 5 days, then combined with IM
Toxicity: Bone marrow (max 25,000IU of Vit A per kg in oil daily
in second wk), nausea (give until recovery.
antiemetic like ganisetron), Vit B1 Infants: 0.5mg 10mg daily. 0.5mg
haemorrhagic cystitis (must Older children: 0.7–15mg Cardiac failure: 1mg IM or IV
hydrate and diurese, mesna shows dramatic improvement
if cyclophosphamide > within 24 hrs.
1g/m2 at dose of 0.66mg/
mg cyclophosphamide). Riboflavin Infants: 0.6mg 3–10mg daily. 0.6mg
Long-term risks: Secondary Children: 1–2mg
malignancy, gonadal Niacin Infants: 8mg 50–300mg daily. 8mg (Nicotinamide)
damage (post-pubertal Older children: 9–10mg
especially).
Pyridoxine Infant: 0.1–0.5mg Pyridoxine deficient convulsion 0.4mg
Azathioprine Tab 50mg Oral 0.5–2.5mg/kg/day. For SLE, JDM, PAN. Lupus Children: 0.5–1.5mg 100mg IM.
(Imuran) nephritis, thrombocytopenia, Pyridoxine dependent IM 2–10mg
haemolytic anaemia. daily, or
Risks: Oral ulcers, bone Orally 10–100mg daily.
marrow, liver toxicity.
Vit C Infant: 25–50mg 100–200mg daily. 35mg
Cyclosporin Cap 10mg, 25mg, Oral 2–3mg/kg/day. For Lupus nephritis, Children: 50mg
(Sandimmun 100mg refractory JIA, macrophage
Vit D 400IU 1,500–5,000IU daily will produce 400IU
Neoral) Syr 100mg/ml IV activation syndrome, JDM.
healing of rickets within 2–4 wks;
Inj 50mg/ml Risks: Renal toxicity,
to be followed by prophylactic
hypertension, hirsuitism,
doses 400IU/day.
gingival hyperplasia,
tremors, parasthesia,
nausea.

Drug Preparation Route Dosage Remarks

Alfacalcidiol 0.25μg tab Oral Neonatal: 0.1μg/kg/day. Indications: Rickets, renal
(One-Alpha/1- 1μg tab < 20kg: 0.05μg/kg/day. osteodystrophy, neonatal
BIOLOGICALS Hydroxy Vit D3) 2μg/ml drops > 20kg: 1μg daily. hypocalcaemia.
Drug Preparation Route Dosage Remarks Elemental Iron Ferrum drops: Oral 5–6mg elemental iron /kg/day in
50mg/ml divided doses for 3–4 mths.
Etanercept Vial 25mg S/C 0.4mg/kg twice a wk (max: 25mg Incredibly expensive, but Ferrous Fumarate
Box of 4 twice wkly). useful in severe polyarticular Tab: 200mg
JIA and systemic JIA
unresponsive to standard Calcitriol Cap 0.25μg Oral Start at 0.01μg/kg/day. For renal rickets,
therapy. More effective with (Rocaltrol/1,25 hypoparathyroidism.
methotrexate. Dihydroxy Vit D3) Ensure adequate calcium
Risks: Injection site intake.
reactions, headache, URTI.
Generally well-tolerated.
598 Appendix III: Useful Formulae 599

APPENDIX III: USEFUL FORMULAE

Estimated Weight Normal Ranges

Intubation — Sequence of Drugs [2 x (age in years + 4)] kg For Continuous Infusions
Age (yrs) Breaths/min HR beats/min 3mg/kg of X diluted in 50ml of Y
™ Pre-medication (Atropine) Expected Systolic Blood Pressure <1 30–40 110–160 gives a concentration where
™ Sedation/Anaesthesia/Analgedia [70 + (age in years x 2)] mmHg 2–5 20–30 95–140 1ml/hr of Y delivers 1μg/kg/min of X
(Etomidate/Midazolam/Morphine) ™ 0.3mg/kg in 50ml → 1ml/hr = 0.1μg/kg/
Bolus for volume resuscitation = 10–20ml/kg 5–12 15–20 80–120
™ Neuromuscular blockage min
(Succinylcholine) Use normal saline, 5% albumin, blood, FFP > 12 12–15 60–100 (e.g. Noradrenaline, Adernaline)
Total Body Blood Volume = 80ml/kg
Maintenance Fluid Requirements ™ 3mg/kg in 50ml → 1ml/hr = 1mμ/kg/
ETT size (internal diameter) = Fluids for neonates: min
[(age in years ÷ 4) + 4] Day of Life ml/kg/day (e.g. Midazolam)
ETT length (oral) = 1 60 ™ 30mg/kg in 50ml → 1ml/hr = 10μg/kg/
[(age in years ÷ 2) + 12] cm 2 90 min
ETT length (nasal) = 3 120 (e.g. Dopamine, Dobutamine)
Drugs Safe for Endotracheal Administration 4 to 1 yr 150
[(age in years ÷ 2) + 15] cm Naloxone
Atropine After the age of one year:
Estimated Size/Length of ETT Ventolin (Salbutamol) Neb 4ml/kg/hr for first 10kg Composition of Intravenous Fluids
Age Wt (kg) Size Oral (cm) Nasal Epinephrine (Adrenaline) 2ml/kg/hr for next 10kg
Neo 3 3.5 8.5 10 Lignocaine 1ml/kg/hr for every kg > 20kg Sodium mmol/l Dextrose g/ml
3
/12 5 3.5 10 12 Normal Saline 154 (0.9%) —
1 9 4.0 11 14 D/S(R) 77 (0.45%) 0.025 (2.5%)
2 12 4.5 12 15
4 16 5.0 14 17 D/S(M) 39 (0.23%) 0.0375 (3.75%)
8 24 6.0 16 20 Dextrose 50% 0.5
12 38 7.0 18 22 Burns Parkland Formula
Volume resuscitation in first 24 hrs Dextrose 10% 0.1
ETT size for neonates: = 4m/kg/% burnt BSA For admission to Children's ICU or to activate Dextrose 5% 0.05
< 1kg 2.5mm Give half in the first 8 hrs after the burn, the Children's Hospital Emergency Transport
half over the next 16 hrs. Service (CHETS), call direct +65-6394 1778/9. NB 20% Sodium Chloride has 3.4mmol/ml
1–2kg 3mm Continue to give normal maintenance fluid
> 2kg 3.5mm requirements.
Adult D/S = D/S(A) = 0.9% saline + 5% dextrose
D5/S(M) = 0.23% saline + 5% dextrose

Each 10ml of D50% added to 500ml increases

the dextrose concentration of the final solution
by 1%.
600 Appendix IV: Resuscitation Algorithm 601

BRADYCARDIA

APPENDIX IV: RESUSCITATION ALGORITHM

Assess ABCs
Secure airway
Hyperventilate with 100% oxygen
SUPRAVENTRICULAR TACHYCARDIA Obtain vascular access

If severe cardiopulmonary compromise

In shock Not in shock (poor perfusion, hypotension, respiratory distress)

Sync DC 0.5–1 J/kg Ice bag Chest compression if:

Vagal manoeuvres HR < 80/min in infant
Overdrive pacing HR < 60/min in child

Double the dose

Adenosine 0.1mg/kg
(max 6mg) Adrenaline every 3–5 mins
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
Adenosine 0.2mg/kg
(max 12mg)
May be repeated

Atropine 0.02mg/kg
May be repeated once
Consider cardioversion/
consider other
antiarythmics
Consider external pacing

ASYSTOLE

CPR: Check ABCs PULSELESS ELECTRICAL ACTIVITY / EMD

Secure airway
Hyperventilate with 100% oxygen
Obtain vascular access
Identify and treat causes
(severe hypoxemia, acidosis, hypovolaemia,
tension pneumothorax,
Adrenaline every 3–5 mins cardiac tamponade, hypothermia)
0.1ml/kg 1:10,000 adrenaline IV/IO (first dose)
0.1ml/kg 1:10,000 adrenaline ET or subsequent IV/IO
For second and subsequent doses, consider up to 0.1mg/kg Treat as for Asystole
602 The Baby Bear Book 603

VENTRICULAR FIBRILLATION OR PULSELESS VT Notes

Assess ABCs
Secure airway
Hyperventilate with 100% oxygen
Obtain vascular access
Correct apoxia, acidosis, hypothermia
Consider drug or metabolic causes

Defibrillate up to 3 times
(2J/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

Adrenaline every 3–5 mins

0.01–0.1ml/kg 1:1,000 adrenaline ET or subsequent IV/IO
604 605

Notes Notes
606 607

Notes Notes
608

Notes