Paediatric Pharmacy Services Guideline PDF

Pharmaceutical Services Division
Ministry of Health Malaysia

Lot 36, Jalan University,

46350 Petaling Jaya,
Selangor Darul Ehsan.
Tel : +603 7841 3200 Fax : +603 7968 2222
Website : www.pharmacy.gov.my
First Edition 2015
Ministry of Health, Malaysia
©ALL RIGHTS RESERVED
This is a publication of the Pharmaceutical Services Division, Ministry of Health

Malaysia. Enquiries are to be directed to the address below. Permission is
hereby granted to reproduce information contained herein provided that such
reproduction be given due acknowledgement and shall not modify the text.

Lot 36, Jalan Universiti,
Selangor, Malaysia
Tel: 603 - 7841 3200 | Fax: 603 - 7968 2222
Website: www.pharmacy.gov.my
2 Paediatric Pharmacy Services Guideline

Message
MESSAGE
Paediatric pharmacists are in prime position to maximize the safe and effective
use of medicines and influence the management of medicines for children and
adolescents. Children are a special population which require detailed attention on
the management and medications as their physiological function is still developing
and yet to mature.
Paediatric pharmacy is a specialized clinical pharmacy service that is currently

increasing in significance in Malaysia. We aim to have paediatric pharmacy
service in all major hospitals and at least one paediatric pharmacist in secondary
hospitals.
Therefore Clinical Pharmacy Working Committee ( Paediatric subspecialty )

Pharmaceutical Services Division, Ministry of Health has initiated to produce this
guideline. I am optimistic that this guideline will assist paediatric pharmacist in
their practices especially for those who will set up paediatric pharmacy services
in their setting.
I would like to commend the Clinical Pharmacy Working Committee (Paediatric

subspecialty) Pharmaceutical Services Division, Ministry of Health for their
contribution and commitment to the development of this guideline.
Thank you.
Puan Abida Haq bt Syed M. Haq

Director of Pharmacy Practice and Development Division
Paediatric Pharmacy Services Guideline 3

Advisors
ADVISORS
Madam Abida Haq Syed M.Haq

Director of Pharmacy Practice & Development Division
Pharmaceutical Services Division, Ministry of Health, Malaysia
Madam Rosminah Mohd Din
Deputy Director (Clinical Pharmacy & Technical)
Madam Noraini Mohamad
Senior Principal Assistant Director Pharmacy
Main Editorial Committees
Noor Haslina Othman Stella Chuo Sing Hong

Senior Clinical Pharmacist Senior Pharmacist
Hospital Raja Perempuan Zainab II Hospital Sibu
Subasyini Sivasupramaniam Won Zi Yun
Senior Clinical Pharmacist Pharmacist
Hospital Kuala Lumpur Hospital Putrajaya
Khoo Sze Ni Wong Pui Mun
Senior Clinical Pharmacist Senior Pharmacist
Hospital Raja Permaisuri Bainun Hospital Serdang
Ng Boon Yah Nurul Hidayah Salleh
Senior Pharmacist Pharmacist
Hospital Pulau Pinang Hospital Tengku Ampuan Afzan
Ng See Yee Khairunnisa Mohamad
Senior Clinical Pharmacist Pharmacist
Hospital Sultanah Bahiyah Hospital Kemaman

Advisors
Wong Shien Woan Low Yong Chia
Pharmacist Pharmacist
Hospital Melaka Hospital Wanita dan Kanak-kanak
Likas
Sharini Sha’ari
Senior Pharmacist Tan Jing Wen
Hospital Tuanku Ja’afar Pharmacist
Hospital Kuala Lumpur
Tea Ming Hui
Pharmacist Angeline Tan Meng Wah
Hospital Sultanah Nora Ismail Principal Assistant Director
Pharmaceutical Services Division,
Irwinder Kaur Chhabra MOH
Pharmacist
Hospital Wanita dan Kanak - kanak
Likas

Table of Content
1.0 Introduction To The Guideline 8

2.0 Job Description Of A Paediatric Pharmacist 9
3.0 General Pediatrics 11
Respiratory Illness 12
Viral Bronchiolitis 12
Asthma 14
Neurology 24
Status Epilepticus 24
Epilepsy 28
Infantile Spasm 37
Nephrology 43
Acute Glomerulonephritis 43
Nephrotic Syndrome 45
Acute Renal Failure 49
Infectious diseases 52
Tuberculosis 52
Malaria 60
Meningitis 71
Urinary Tract Infection 77
Viral Croup 80
Pneumonia 84
Cardiovascular 92
Kawasaki Disease 92
Rheumatic Heart Disease 95

4.0 Paediatric ICU 98
Fluid & Electrolyte Management 99
Nutrition In Critically Ill Patients 107
Shock Management 113
Neuromuscular Blockade 119
Stress Ulcer Prophylaxis 127
Sedation & Pain Management 131
5.0 Neonatal ICU 141
Neonatal Jaundice (NNJ) 142
Sedation & Pain Management 147
Total Parenteral Nutrition In Neonates 161
Fluid & Electrolyte Management 168
Necrotizing Enterocolitis 170
6.0 Dosing Considerations in Special Populations 181
7.0 Appendix 189
Corticosteroid Equipotency Chart 189
Nutrition Reference 190
Immediate-release Opioid Analgesics Comparison Chart 191
TDM Sampling Time 192
Growth Charts 193
Stability and Storage of Oral Medications 203
Drugs To Avoid In G6PD Deficiency 211

1.0 Introduction To The Guideline
Neonates and paediatrics are vulnerable groups who require extra careful
handling, and hence the role of paediatric pharmacists is crucial to ensure
medication safety. With this insight, paediatric pharmacy service was introduced
under the pharmacy program of Ministry of Health (MOH), Malaysia in 2006,
and subsequently the first paediatric pharmacists working group committee was
formed in 2009.
The role of paediatric pharmacists has gained recognition throughout the years.
Despite the increasing demand for paediatric pharmacists, this remains as one
of the most challenging clinical pharmacy field to venture in. The lack of evidence
and standardized dosing in paediatrics and neonates can be a hurdle to practice
evidence based medicine in this field. Also, the lack of standardized guidelines
on the conduct of paediatric pharmacy services under facilities of MOH, Malaysia
may lead to great differences in the expected roles and responsibilities as a
paediatric pharmacist.
The aim of this service guideline is to serve as a baseline reference and information
for paediatric pharmacists who are new to this field on the conduct and practice
of paediatric pharmacy. It can also be a basic reference for provisionally registered
pharmacists (PRP) who will be doing paediatric clinical clerkship during clinical
attachment.
It is of great hope that with the introduction of this service guideline, paediatric
pharmacy services under MOH, Malaysia can be further expanded and
established.

2.0 Job Description of a Paediatric Pharmacist
Paediatric pharmacy consists of general paediatric, paediatric intensive care

2.0 Job Description Of A Paediatric Pharmacist
and neonatal intensive care. The ultimate goal of paediatric pharmacy service
is to assist
Paediatric in the consists
pharmacy best possibleof generalway to achieve
paediatric, safeintensive
paediatric and effective
care andtreatment.
neonatal
Hence, evidence-based
intensive care. The ultimate practice should be
goal of paediatric the mainstay
pharmacy service in
is the management
to assist in the bestof
possible way to achieve
all patients at all time. safe and effective treatment. Hence, evidence-based practice
should be the mainstay in the management of all patients at all time.
Table 2.1: Job Description of Paediatric Pharmacist

Job Scope Description
Admission • Medication history clerking, which includes non-prescription

clerking drugs e.g. herbal remedies and over the counter drugs (OTC)
• Compliance assessment (CP1 form) – if applicable
• Medication reconciliation
Pharmacotherapy • Active participation in ward rounds with doctors

Rounds • Collaborate with other healthcare providers in developing
pharmaceutical care plans for the patients
• Provide medication therapy evaluations and
recommendations to healthcare providers supported by
evidence-based medicines
Monitor and • Case clerking and review (CP2 form)

review patients’ • Checking patient’s medication chart
medication • Ensure medications are served
• Ensure prescription is completely filled
• Ensure safe and rational drug use
• Ensure approppriate dilution and administration of injectable
drugs
• Ascertain proper extemporaneous preparation
• Therapeutic Drug Monitoring (TDM) / Total Parenteral
Nutrition (TPN) services
Identify • Dosing adjustment based on patient’s body weight, age

Pharmaceutical group, body surface area, renal and liver function.
Care Issues • Medication errors e.g. drug, dose, frequency, duration,
administration, etc
• Drug- drug interactions
• Drug incompatibilities and contraindications
• Polypharmacy

2
Adverse Drug • Identifies and report any suspected adverse drug reaction
Reaction Report (ADR) or drug allergy
• Provision of allergy card
Provision of Drug • Drug availability

Information • Safety and toxicology
• Cost-effectiveness of medications
• Maintains current drug references
Education • Continuous Professional Development

• Continuous Nursing Education
• Provides drug therapy related to team members
Patient /caregiver • Bedside/Discharge counselling

counselling • Specialised drug delivery devices e.g. Insulin pen, inhalers,
spacers
• Oral drug preparation (e.g. freshly prepared syrup, drug
reconstitution)
Research and • Participate in research work/project pertaining to paediatric

Development pharmacy practice
• Contributes to the pharmacy and medical literature for
examples case reports, pharmacokinetics and
pharmacoeconomics reports

General Pediatrics
3.0
3.0 General
Paediatric

General Pediatrics
Respiratory Illness
3.0
Viral Bronchiolitis
Introduction
Viral bronchiolitits is a common respiratory illness especially in infants aged 1
to 6 months old. Respiratory Syncytial Virus (RSV) remains the commonest
cause of acute bronchiolitis in Malaysia. Although it is endemic throughout the
year, cyclical periodicity with annual peaks occuring in the months of November
December and January1. It is characterized by acute inflammation, edema and
necrosis of epithelial cells lining small airways, increased mucus production, and
bronchospasm2.
Clinical Features
Patients typically presents with a mild coryza, low grade fever and cough.
Tachypnoea, chest wall recession, wheeze and respiratory distress subsequently
develop. The chest may be hyperinflated and auscultation usually reveals fine
crepitations and sometimes rhonchi. A majority of children with viral bronchiolitis
has mild illness and about 1% of these children require hospital admission1.
Management
Pharmacotherapy
• 3% saline solution via nebulizer
Shown to increase mucus clearance and significantly reduce hospital stay
among non-severe acute bronchiolits. It improves clinical severity score in both
outpatients and inpatients populations1.
• Inhaled ß2-agonists
Pooled data have indicated a modest clinical improvement with the use of ß2 -
agonist. A trial of nebulised ß2-agonist, given in oxygen, may be considered in
infants with viral bronchiolitis. Vigilant and regular assessment of the child should
be carried out1.Parameters to measure its effectiveness include improvements
in wheezing, respiratory rate, respiratory effort, and oxygen saturation1.

General Pediatrics
3.0
• Inhaled steroids
Randomised controlled trials of the use of inhaled or oral steroids for treatment
of viral bronchiolitis show no meaningful benefit1.
• Antibiotics
Recommended for all infants with recurrent apnoea and circulatory impairment,
possibility of septicaemia, acute clinical deterioration, high white cell count.,
progressive infiltrative changes on chest radiograph1.
Supportive Management
Arterial oxygenation by pulse oximetry (SPO2) should be performed at presentation
and maintained above 93%. Administer supplemental humidified oxygen if
necessary. Routine full blood count and bacteriological testing (of blood and
urine) is not indicated in the assessment and management of infants with typical
acute bronchiolitis1.
Special consideration
• Palivizumab Injection
Clinicians may administer palivizumab prophylaxis to selected infants and
children with chronic lung disease or a history of prematurity ( less than 35
weeks’ gestation ) or with congenital heart disease2. When given, prophylaxis
should be given monthly for a total of 5 doses at a dose of 15mg/kg/dose
administered intramuscularly2.
References:
1. Muhammad Ismail HI, Ng HP, Thomas T, et.al. Paediatric Protocols for Malaysian
Hospitals, 3rd Edition. Malaysia: Kementerian Kesihatan Malaysia; 2013.
Chapter 31, Viral Bronchiolitis; p.161-2.
2. Lieberthal AS, Bauchner H, Hall CB, Johnson DW, Kotagal U,Light MJ, et
al. Diagnosis and Management of bronchiolitis. American Academy of
Pediatrics 2006;118:1774-1793.

General Pediatrics
Respiratory Illness
3.0
ASTHMA
Introduction
Asthma is defined as a chronic airway inflammation leading to increase airway

responsiveness that leads to recurrent episodes of wheezing, breathlessness,
chest tightness and coughing particularly at night or early morning. It is often
associated with widespread but variable airflow obstruction that is often reversible
either spontaneously or with treatment. There is reversible and variable airflow
limitation as evidenced by >15% improvement in PEFR (Peak Expiratory Flow
Rate), in response to administration of a bronchodilator1.
Pre-school wheezing can be divided into two main categories, episodic (viral
wheeze) and multiple trigger wheeze. Children who only wheeze with viral
infections and are well between episodes can be classified as viral wheeze.
Multiple trigger wheezers are children who have discrete exacerbations and
symptoms in between these episodes. Triggers are smoke, allergens, crying,
laughing and exercise1. The presence of atopy (eczema, allergic rhinitis and
conjunctivitis) in the child or family supports the diagnosis of asthma. However,
the absence of these conditions does not exclude the diagnosis1.
Management of Chronic Asthma
The management of chronic asthma can be based on either the severity

of asthma or the degree of asthma control. Newly diagnosed patients will be
categorized into different degrees of asthma severity by the physicians as in Table
11. Patients who are already on treatment should be assessed at every clinic visit
on their control of asthma as in Table 22.

episodes can be classified as viral wheeze. Multiple trigger wheezers are children who have
General Pediatrics
discrete exacerbations and symptoms in between these episodes. Triggers are smoke,
allergens, crying, laughing and exercise1. The presence of atopy (eczema, allergic rhinitis and
conjunctivitis) in the child or family supports the diagnosis of asthma. However, the absence of
these conditions does not exclude the diagnosis1.
Management of Chronic Asthma
The management of chronic asthma can be based on either the severity of asthma or the
3.0
degree of asthma control. Newly diagnosed patients will be categorized into different degrees of
asthma severity by the physicians as in Table 11. Patients who are already on treatment should
be assessed at every clinic visit on their control of asthma as in Table 22.
Table 1: Evaluation of Newly Diagnosed Asthma
Category
Clinical
Persistent
Parameters Intermittent
Mild Moderate Severe
Daytime symptoms Less than once a week More than once a week Daily Daily
More than twice a

Nocturnal symptoms Less than once a month More than once a week Daily
month
Exercise induced
No Yes Yes Daily
symptoms
Brief exacerbations not

> 1x/month affecting > 2x/month affecting Frequent >2x/month
Exacerbations affecting sleep and
sleep, activity sleep, activity affecting sleep,activity
activity
Lung function Normal PEFR / FEV1:> 80% PEFR / FEV1: PEFR / FEV1: < 60
60 - 80%
• This division is arbitrary and the groupings may merge. An individual patient’s classification may change from
time to time.
• There are a few patients who have very infrequent but severe or life threatening attacks with completely normal
lung function and no symptoms between episodes. This type of patient remains very difficult to manage.
• PEFR = Peak Expiratory Flow Rate; FEV1 = Forced Expiratory Volume in One Second.
Source: Adapted from Paediatric Protocols For Malaysian Hospitals 3rd edition
6

Table 2: Evaluation of Asthma Control
Partly Controlled
Controlled
Characteristics Any measure present in Uncontrolled
All of the following:
any week
Daytime Symptoms None >2 per week

Limitations of activities None Any ≥ 3 features of
Nocturnal symptoms or partly controlled
None Any
awakenings
Need for reliever None >2 per week asthma present
< 80% predicted or in any week

Lung function test Normal personal best
One in any week

Exacerbations None ≥ 1 per year
Pharmacotherapy
The treatment of asthma consists of 2 components which consist of preventor therapy for
reducing airway inflammation and reliever therapy for relieving the respiratory symptoms.
Patients who have persistent asthma should be started onPharmacy
daily preventor medication. The initial
Paediatric Services Guideline
medication and dosages depends on the severity and necessity to attain quick control of
15
2
General Pediatrics
3.0
Pharmacotherapy
The treatment of asthma consists of 2 components which consist of preventor
therapy for reducing airway inflammation and reliever therapy for relieving the
respiratory symptoms. Patients who have persistent asthma should be started
on daily preventor medication. The initial medication and dosages depends on
the severity and necessity to attain quick control of asthma2. A comprehensive
treatment plan for asthma includes asthma education, avoidance of trigger
factors and strategies to optimize pharmacotherapy. The management plan for
each patient should be individualized because each patient has different trigger
factors, asthma phenotypes and different responses to the medication2. Asthma
management based on levels of control is a step up and step down approach
as shown in Table 4. Before progressing to the next step, pharmacists can assist
physicians in deciding the management of asthma by assessing the compliance
and inhaler technique as well as any exposure to trigger factors and relaying the
information to the physicians. It is important that the delivery system is appropriate
to the child’s age2. Metered dose inhaler therapy via spacer with facemask is as
efficacious as nebulizer therapy2.
Role of pharmacists:
• Provide medication education by providing information on the indication of the

medications, dose, frequency and duration of the medications.
• Suggest the most suitable inhaler devices based on the patient’s ability to
understand the instructions and ability to use the inhalers correctly
• Counseling of proper inhaler techniques (metered dose inhalers [MDI],
spacers with face mask, dry powder inhalers) and proper way of
administrating medications ( ie Montelukast Granules ) to patients, parents or
care givers
• Counsel patients on common side effects of each medications and how to
prevent them (eg: Gargle after using inhaled corticosteroids to avoid oral
thrush, sore throat and hoarse voice )
• Educate on the proper care of drug delivery devices for example spacers with
face mask (refer to individual product care) as a properly functioning delivery
device is essential to ensure optimum delivery of medication to patients.
• Encourage adherence to medications and find ways to overcome if any
issues of nonadherence (eg: noncompliance to inhaled corticosteroid due to
fear of dependence to steroids)

General Pediatrics
ensure optimum delivery of medication to patients.
• Encourage adherence to medications and find ways to overcome if any issues of
3.0
nonadherence (eg: noncompliance to inhaled corticosteroid due to fear of dependence
ensure
to optimum delivery of medication to patients.
steroids)
• Encourage adherence to medications and find ways to overcome if any issues of
nonadherence (eg: noncompliance to inhaled corticosteroid due to fear of dependence
to steroids)
Table 3: Inhaler Devices Recommended For Different Age
Children aged 0-6 years Metered dose inhaler + spacer with facemask
Table 3: Inhaler Devices Recommended For Different Age
Metered dose inhaler + spacer with facemask
Children aged 0-6 years Metered dose inhaler + spacer with facemask
Children aged > 6 years Metered dose inhaler + spacer with mouthpiece
Metered dose inhaler + spacer with facemask
Dry powder inhaler (may be suitable)
Children aged > 6 years Metered dose inhaler + spacer with mouthpiece
Source: Adapted from Clinical Practice Guidelines for the Management of Childhood Asthma 2014
Dryofpowder
Table 4: Management Asthmainhaler (may be suitable)
Source: Adapted from Clinical Practice Guidelines for the Management of Childhood Asthma 2014
REDUCE ←
Table 4: Management of Asthma
→ INCREASE
STEP 1 REDUCE STEP 2 ← STEP 3 → STEP 4 INCREASE STEP 5
Mild Moderate Severe Severe

Intermittent
STEP 1 STEP 2 STEP 3 STEP 4 STEP 5
Persistent Persistent Persistent Persistent
Mild Moderate Severe Severe

Intermittent As needed rapid acting β2-agonist
Persistent Persistent Persistent Persistent
Controller As needed rapid acting

Select one Select one β2-agonist
Add one / more Add one / more
Options
Controller Medium / High

Low doseone
ICS + Oral/ more
Options LowSelect one
dose inhaled Select Adddose
one ICS
/ more Add one
long acting β2- Glucocorticoids
steroids + long acting β2-
agonist Medium / High lowest dose
Low dose ICS + agonist Oral
Low dose inhaled dose ICS
long acting β2- Glucocorticoids
steroids + long acting β2-
Leukotriene agonist
Medium / High Leukotriene lowest dose
agonist Anti-IgE
receptor antagonist dose ICS receptor antagonist
Leukotriene Medium / High Leukotriene

Low dose ICS + Anti-IgE
receptor antagonist dose ICS receptor antagonist
SR Theophylline
Leukotriene
receptor antagonist
Low dose ICS +
Low dose ICS + SR Theophylline
Leukotriene
SR Theophylline
receptor antagonist
Low dose ICS +
ICS: Inhaled corticosteroid; SR: Sustained relase
SR Theophylline
ICS: Inhaled corticosteroid; SR: Sustained relase
8

8


General Pediatrics
3.0
Table 5: Drug Doses Of Common Medications Used in Asthma
1.2.3.4.5.6 4,5,7
Drug Formulation Dose Additional information
Oral 0.15 mg/kg/dose 6-8H/ PRN
100-200 mcg/dose 4-6H/

Metered dose inhaler
PRN
Dry powder inhaler

100-200 mcg/dose 6H/ PRN
For continuous intravenous

infusion,
Bolus:
5-10 mcg/kg over 10 min dilute to a concentration of
200 micrograms/mL
Salbutamol
Infusion:
Intravenous with Glucose 5%, Sodium
Start 0.5-1 mcg/kg/min,
Chloride 0.9% ; if fluid-
increase by 1 mcg/kg/min
every 15 min to a max of 20 restricted,can be
mcg/kg/min
given undiluted through
central venous catheter
0.15 mg/kg/dose (max 5 mg)

or
Nebuliser < 2 years old : 2.5 mg/dose
> 2 years old : 5.0 mg/dose
Continuous : 500 mcg/kg/hr
5-10mcg/kg
Terbutaline Subcutaneous
(Maximum 0.5mg/dose)
0.5-1mg/kg/day x 3-5 days
Prednisolone Oral
(Maximum: 60mg/day)
4 mg/kg/dose 6H (max
Hydrocortisone Intravenous
100mg/dose)
0.5-1 mg/kg 6H day 1, 12H
day 2, then 1mg/kg daily,
Methylprednisolone Intravenous
reducing to minimum
effective dose
Beclomethasone <400 mcg/day : low dose
Metered dose inhaler Dry
Diproprionate / 400-800 mcg/day : Moderate
powder inhaler
Budesonide 800- 1200 mcg/day: High
Fluticasone Metered dose inhaler Dry <200 mcg/day : Low

Propionate powder inhaler 200-400 mcg/day : Moderate
400-600 mcg/day : High
9


General Pediatrics
3.0
Ciclesonide Metered dose inhaler 160 microgram daily Licensed for children over 6
320 microgram daily years old
Children 4 years and older:
2 inhalations of
25mcg/50mcg BD
12 years and older: There are no data available

Metered dose inhaler
for use in children below 4
2 inhalations of years old
25mcg/50mcg BD or
Salmeterol +
Fluticasone 2 inhalations of
25mcg/125mcg BD
12 years and older:
1 inhalation of
50mcg/250mcg BD or
Dry powder inhaler
1 inhalation of
50mcg/500mcg BD
1-5 years old:

4 mg granules ON
6-14 years old:

Montelukast
Oral 5mg/tablet chewable ON
>14 years old:
10mg/tablet ON
Oral Syrup
Theophylline 5 mg/kg/dose TDS/QID
Slow Release
10 mg/kg/dose BD
Therapeutic drug monitoring:
6 mg/kg slow bolus (if not 10-20mg/L
Aminophylline previously on theophylline)
Intravenous (IV)
followed by infusion 0.5 -
1mg/kg/hr
Nebuliser solution < 5 years old : 250 mcg 4-6
Ipratropium bromide (250 mcg/ml) hourly
> 5 years old : 500 mcg 4-6
hourly
10


General Pediatrics
3.0
Prevention
Identifying and avoiding the following common triggers may be useful1
• Environmental allergens
These include house dust mites, animal dander, insects like cockroach,
mould and pollen. Useful measures include damp dusting, frequent laundering
of bedding with hot water, encasing pillow and mattresses with plastic / vinyl
covers, removal of carpets from bedrooms, frequent vacuuming and removal
of pets from the household
• Cigarette smoke
• Respiratory tract infections - commonest trigger in children
• Food allergy - uncommon trigger, occurring in 1-2% of children
• Exercise- Although it is a recognized trigger, activity should not be limited.
Taking short acting 2-agonist prior to strenuous exercise ( 10-20 minutes
before exercise )2 as well as optimizing treatment is usually helpful.
Asthma Action Plan
An asthma action plan is a written instruction by the physician for the

patient, parents or care giver on the daily management of asthma and how to
identify and manage asthma exacerbations. The asthma action plan may differ for
different institutions. An example of asthma action plan is available in the Clinical
Practice Guidelines for the Management of Childhood Asthma 2014, Malaysia.
Special Considerations :
Ciclesonide is the most recent inhaled corticosteroid available for use in children.
It is a prodrug activated locally in the lung by pulmonary esterase to des-
ciclesonide, which ensures high local concentration8.

General Pediatrics
3.0
Management Of Acute Asthma
The management of acute asthma depends on the severity at presentation, the

Management Of Acute Asthma
response to therapy, the availability of drugs and facilities at the particular clinic/
hospital and the experience
The management of acute asthma of the attending
depends doctor.atBefore
on the severity children
presentation, can receive
the response to
therapy, the availability of drugs and facilities at the particular clinic/ hospital and the experience
appropriate treatment for the acute asthma in any setting, it is essential to assess
of the attending doctor. Before children can receive appropriate treatment for the acute asthma
accurately theitseverity
in any setting, oftotheir
is essential attack
assess
2.
accurately the severity of their attack2.
Table 7: Assessment of Severity of Acute Asthma Exacerbation in Children
Parameters Mild Moderate Severe Life Threatening
When talking At rest

Breathless When walking Infant: When Infant: Stops
feeding Feeding
Talks in Sentences Phrases Words Unable to speak
Usually Usually Drowsy / confused/

Alertness Maybe agitated
agitated agitated coma
Normal to Mildly Markedly Poor Respiratory

Respiratory Rate Increased
increased increased Effort
Accessory Muscle Present – Present – Paradoxical thoraco-

Absent
Usage / retractions Moderate Severe abdominal movement
Moderate, often
Wheeze only end Loud Usually loud Silent chest
expiratory
SpO2 (on air) >95% 92-95% <92% Cyanosis & <92%
>120 (>5
yrs)
Pulse / min <100 100-120 Bradycardia
>160
(infants)
PEFR* >80% 60-80% <60% Unable to perform
*Peak Expiratory Flow Rate (PEFR) after initial bronchodilator, % predicted or of personal best

General Pediatrics
3.0
Algorithm 1: Management of Acute Exacerbation of Bronchial Asthma in

Children
Source: Adapted from Clinical Practice Guidelines for the Management of
Childhood Asthma 2014

General Pediatrics
3.0
References :
1. Muhammad Ismail HI, Ng HP, Thomas T, et.al. Paediatric Protocols for

Malaysian Hospitals, 3rd Edition. Malaysia: Kementerian Kesihatan Malaysia;
2013. Chapter 30, Asthma; p.149-60
2. Clinical Practice Guidelines for the Management of Childhood Asthma.
A Consensus statement prepared for the Academy of Medicine of Malaysia,
Malaysian Thoracic Society and Lung Foundation of Malaysia. 2014.
3. Shann F. Drug Doses.16th Edition. Australia:Royal Children’s Hospital
Parkville, Victoria; 2014.
4. BMA, Royal Pharmaceutical Society, Royal College and Pediatric of Child
Health. BNF for Children 2012-2013.
5. Seretide Evohaler [Package insert].Burgos, Spain: Glaxo Wellcome S.A;
2010
6. Seretide Accuhaler [Package insert].Ware,UK: Glaxo Wellcome Operations;
2010
7. Alvesco [Package insert].Leicester,England: Takeda GmbH; 2013
8. Rizzo MC, Solé D. Inhaled corticosteroids in the treatment of respiratory
allergy: safety vs. efficacy. J Pediatr (Rio J). 2006;82(5 Suppl):S198-205.

General Pediatrics
NEUROLOGY
3.0
Status Epilepticus
Introduction
Status epilepticus (SE) is defined as any seizure lasted > 30 minutes which
can be continuous or intermittent with incomplete recovery of consciousness in
between seizures. However, any seizure > 5 minutes warrants pharmacological
intervention as it is unlikely to terminate rapidly or spontaneously by itself. Based
on the electroclinical features, SE may be classified broadly as convulsive SE and
non-convulsive SE1, 2.
Convulsive SE is defined as convulsions associated with rhythmic jerking of

extremities and mental status impairment. It can be further classified as tonic-
clonic SE, tonic SE, clonic SE and myoclonic SE. Generalised tonic-clonic SE is
the most common form of SE1.
Non-Convulsive SE is defined as seizure activity seen on electroencephalogram

(EEG) without physical convulsions. It is characterized by abnormal mental status,
unresponsiveness, ocular motor abnormalities, persistent electrographic seizures
and possible response to anticonvulsants1.
Seizure which is continuous or repetitive lasting longer than 60 minutes despite

treatment with benzodiazepine and one standard anticonvulsant (usually
phenytoin or phenobartbitone) in adequate loading dose is defined as refractory
status epilepticus1.

General Pediatrics
Management
Pharmacotherapy
Refer to Algorithm 1.
3.0
Algorithm 1: Management of Status Epilepticus

General Pediatrics
3.0
Special Consideration
1. Benzodiazepine should be the agent of choice for emergent initial treatment

of SE3.
2. If the patient is currently treated with antiepileptic drugs, a drug level (TDM)
should be checked and history obtained regarding compliance3.
3. If < 2 years old, pyridoxine ( IV 100mg if available, oral dose up to 30mg /
kg / day ) will be helpful especially for suspected pyridoxine dependent
seizures2,4.
4. Avoid sodium valproate in metabolic encephalopathy ( patient with metabolic
or mitochondrial disease)2.
5. Be aware of the severe complication associated with propofol- ‘propofol
infusion syndrome’ especially on dose exceeds 5mg/kg/hr for more than 48
hours. It is a potentially fatal condition characterized by severe metabolic
acidosis, hyperlipidemia, rhabdomyolysis and cardiovascular collapsed1.
6. Phenobarbitone has no anticonvulsant ceiling effect, titrate to achieve burst
suppression pattern on EEG. High dose phenobarbitone up to 80mg/kg/
day, with serum level more than 1000 micromol/L (232 microgram/ml) has
been shown to be effective in achieving seizure control children with refractory
SE (eg. FIRES- Febrile Infection Related Epilepsy Syndrome). Major adverse
effects of high dose phenobarbitone are sedation and respiratory depression
which are usually subject to tolerance over a relatively short time1.
7. T herapeutic Drug Monitoring (TDM) sampling time and indication are
important; always relate TDM results with clinical condition of patient2.

General Pediatrics
3.0
References :
1. Cherian A, Thomas SV. Status Epilepticus. Annals of Indian Academy of

Neurology 2009 Jul-Sep; 12(3): 140-53.
Malaysian Hospitals, 3rd Edition. Malaysia: Kementerian Kesihatan
Malaysia;2013. Chapter 44, Status Epilepticus; p.207-12
3. Gretchen MB, Rodney B, Jan C, et al. Guideline for the Evaluation and
Management of Status Epilepticus. Neurocritical Society 2012 April 24.
4. Gospe SM. Pyridoxine- dependent Epilepsy. NCBI Bookshelf; 2001.
5. Pediatric Dosage Handbook (Lexi-comp) 16th Edition
6. Product Insert Parental Dilantin Pfizer
7. Drug Doses Frank Shann 15th Edition 2010
8. Abend NS, Gutierrez-Colina AM, Monk HM, et al. Levetiracetam for
Treatment of Neonatal Seizure. Child Neurol. 2011 April 26(4): 465-470.
9. University Collge London Hosputals NHS Fpundation Trust. Neonatal Unit
Drug Monography - Phenobarbital; 2012 [cited 4 Nov 2014]. Available from
www.uclhguide.com / fragr_image / media / phenobarbital
10.RPA Newborn Care Drug Database [cited 4 Nov 2014]. Available from
www.sswahs.nsw.gov.au / rpa / neonatal / html / listview.asp ? DrugID=35
11.Taylor LM, Farzam F, Cook AM, Lewis DA, Baumann RJ, Kuhn RJ. Clinical
Utility of a Continuous Intravenous Infusion of Valproic Acid in Pediatric
Patients. Pharmacotherapy. 2007;27(4):519-25.

General Pediatrics
NEUROLOGY
3.0
Epilepsy
Introduction
Epilepsy
Epilepsy is a neurological condition characterized by recurrent unprovoked
Introduction
epileptic seizures. According to The International League Against Epilepsy (ILAE)
Epilepsy is a neurological condition characterized by recurrent unprovoked epileptic seizures.
classification of seizure type revisedAgainst
According to The International League
in 2010, seizures are broadly classified as
Epilepsy (ILAE) classification of seizure type
1
generalized, focalseizures
revised in 2010, and unknown
are broadly. classified as generalized, focal and unknown1.
1. Generalised seizures
(arising within and rapidly engaging bilaterally
distributed networks- involves whole brain)
Tonic-clonic Absence Clonic Tonic Atonic Myoclonic

- myoclonic
- myclonic-atonic
- myclonic-tonic
Absence with special
features
- Myoclonic absence
Typical Atypical
- Eyelid myoclonia
2. Focal seizure 3. Unknown

Originating within networks limited Insufficient evidence to
to one hemisphere characterize as focal,
generalized or both)
Characterized according to one or

more features:
Aura
- Epileptic spasms
Motor
- Other
Autonomic
Awareness/ responsiveness:
Altered (dyscognitive) or retained
May evolve to
Bilateral convulsive seizure

(Old term: secondarily tonic clonic seizure)
Chart 1: Category of Seizures

19
General Pediatrics
3.0
Types of seizure Characteristic signs
Tonic clonic (grand-mal) Tonic stiffening (extension) followed by clonic flexion
motions (muscle jerking). Seizure followed by postictal
confusion
May produce labored respirations, cyanosis, incontinence,
involuntary tongue biting.
Absence (petit-mal) Staring, loss of expression, unresponsiveness, stopping

from ongoing activity
No convulsions or postictal symptoms
Usually recovers immediately and resumes previous
activity with no memory of the seizure.
Clonic Rapid, repetitive motor activity

Tonic Sudden, brief stiffening of the muscles of whole body
Atonic Sudden, brief loss of muscle tone of the body
Myoclonic Brief but intense muscle jerks
2
Pharmacotherapy
Pharmacotherapy2
• Treatment recommended
• Treatment recommendedifif ≥
≥ 22 episodes
episodes ( recurrent
(recurrent risk
risk up up to 80% ).
to 80%).
• Monotherapy
• Monotherapyisispreferred, choose
preferred, choose most
most appropriate
appropriate drug according
drug according to
to types of seizure
typesand
ofepileptic
seizuresyndromes. Increase
and epileptic dose gradually
syndromes. until seizure
Increase dosecontrolled
graduallyor maximum
until
dose reached or side effects occur.
seizure controlled or maximum dose reached or side effects occur.
nd
• Add
• Add on secondAED
on second AEDififthe
the first
first drug
drugfailed, then
failed, optimize
then 2 AED
optimize 2ndand try to
AED withdraw
and try to first
AED (alternative monotherapy).
withdraw first AED ( alternative monotherapy ).
• Rational combination therapy (usually 2 or maximum 3 drugs) i.e. combines drugs with
• Rational combination therapy (usually 2 or maximum 3 drugs) i.e. combines
different mechanism of action, and consider their spectrum of efficacy, drug interactions
drugs andwith different
adverse effectsmechanism of action, and consider their spectrum of
efficacy, drug interactions and adverse effects
• TDM monitoring is not routinely required (except for phenytoin) unless non-compliance,
• TDMtoxicity
monitoring
or drugisinteraction
not routinely required ( except for phenytoin ) unless non-
suspected.
compliance, toxicity or drug interaction suspected.
• When withdrawal of medication is planned (generally after being seizure free for 2
• When withdrawal
years), of medication
consideration is planned
should be given to (epilepsy
generally after being
syndrome, likelyseizure free and
prognosis
for 2individual
years ), circumstances
considerationbefore attempting
should be givenslow
to withdrawal of medicationlikely
epilepsy syndrome, over 3-
6months ( maybe longer for clonazepam and phenobarbitone). If seizures recur, the last
prognosis and individual circumstances before attempting
dose reduction is reversed and medical advice sought. slow withdrawal of
medication over 3-6months ( maybe longer for clonazepam and
phenobarbitone ). If seizures recur, the last dose reduction is reversed and
medical advice sought.
20

General Pediatrics
3.0
Table 2: Choice of Antiepileptics
Selecting antiepileptic drugs according to seizure type

Seizure type First line Second line
Focal Seizure
Carbamazepine Lamotrigine, Topiramate,
Valproate Lavetiracetam, Clobazam,
Phenytoin, Phenobarbitone
Generalised Seizure
Tonic-clonic/ clonic Valproate Lamotrigine, Topiramate,
Clonazepam, Carbamazepine1,
Phenytoin1, Phenobarbitone
Absence Valproate Lamotrigine, Levetiracetam

Atypical absences, Valproate Lamotrigine, Topiramate,
Atonic, Tonic Clonazepam, Phenytoin
Myoclonic Valproate Topiramate, Levetiracetam,
Clonazepam Clonazepam, Lamotrigine2,
Phenobarbitone
Infantile Spasm Prednisolone4 ,Vigabatrin3, Nitrazepam, Clonazepam,
ACTH Valproate, Topiramate
Footnote:
1. May aggravate myoclonus/ absence seizure in Idiopathic Generalized Epilepsy.
2. May cause seizure aggravation in Dravet syndrome and Juvenile Myoclonic Epilepsy
3. Especially for patient with Tuberous Sclerosis (TS).
4. United Kingdom Infantile Spasms Study (UKISS) protocol
Antiepileptic Drugs That Aggravate Selected Seizure Type

Phenobarbitone Absence seizure
Clonazepam Causes Tonic Status in Lennox-Gastaut syndrome
Lamotrigine Dravet syndrome
Myoclonic seizures in Juvenile Myoclonic Epilepsy
Phenytoin Absence, Myoclonic seizure
Vigabatrin Myclonic, Absence seizure
21
30
Paediatric Pharmacy Services Guideline
General Pediatrics
3.0
References :
1. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, Boas WE, Engel
J, French J, Glauser TA, Mathern GW, Moshe SL, Nordli D, Plouin P, Sheffer IE.
Revised Terminology and Concepts for Organization of Seizures and Epilepsies:
Reports of the ILAE Commision on Classification and Terminology, 2005-2009.
Epilepsia 2010, 51 (4):676-685.
2. Muhammad Ismail HI, Ng HP, Thomas T, et.al. Paediatric Protocols for Malaysian
Hospitals, 3rd Edition. Malaysia: Kementerian Kesihatan Malaysia; 2013.
Chapter 44, Epilepsy; p.207-12
3. Kammerman S, Wasserman L. Seizure disorders: Part 1. Classification and
Diagnosis. WJM 2001 August; 175.
4. Seizure SMART Classification of Seizures. Epilepsy Austria; March 2012.
Available from: http://www.epilepsy.org.au/sites/default/files/Seizure%20
Smart%20-%20Classification%20of%20Seizures%20%28focal%29_0.pdf

3.0 General Pediatrics
32
PHARMACOKINETICS AND SIDE EFFECTS OF COMMON ANTIEPILEPTIC DRUGS
DRUG PHARMACOKINETIC SUBSTRATE INDUCER / SIDE EFFECTS COMMENTS

OF CYP INHIBIT CYP
ADM: with food to decrease GI
Potentially fatal blood cell upset.
Induces
½ abnormalities (aplastic Do not crush CR tab.
t 8-14hrs 1A2 (strong)
anemia, agranulocytosis),
Metabolised by CYP 3A4 to 2B6 (strong)
severe dermatologic Advice pt to report if develops skin
1 CBZ-epoxide and others 2C8 (minor) 2C8 (strong)
Carbamazepine reaction: SJS, toxic rash or any sign/ symptom bone
3A4 (major) 2C9 (strong)
epidermal necrosis (higher marrow depression eg. Fever, sore
Protein binding CBZ 75-90%, 2C19 (strong)
risk with variant HLA- throat, easy bruising, infections.
epoxide 50% 3A4 (strong)
B*1502 allele), elevated Level decrease ~3 weeks after
liver enzyme, jaundice. initiation due to self-induced
metabolism.
½
4 t 36-42 hrs
Clobazam
Metabolised primarily via
Constipation (2-10%) ADM: with or without food
3A4 to active N-
Induce 3A4 Drooling (up to 14%) Tab can be crushed.
desmetylclobazam. 2C19
Inhibit 2D6

Excretion: renal 82% (94%
as metabolite)
Protein binding 80-90%
Hypotension, respiratory
½ depression, bronchial ADM: with food to decrease GI
t 22-33hrs
1 hypersecretion, distress
Clonazepam Metabolised in liver 3A4 -
hyperactivity and Withdraw gradually when
Protein binding 85%
aggression. discontinuing therapy.
Skin rash 10% (higher ADM: without regard to food

With enzyme-inducer incidence in children and Regular tab: Do not chew, as a
½
t 6-11hrs (age 10 mo-5.3 those receiving valproate, bitter taste may result.
yr) 7-31hrs high initial dose or with Dispersible/ chewable tab: Only
rapid dose increment). whole tablets should be
1 With VPA: 30-52hrs (10 mo- Severe skin rash eg.SJS administered; may swallow whole,
Lamotrigine - -
5.3 yr) 0.8% chew, or disperse in water or
50-74hrs (5-11yo) diluted fruit juice (~5ml).
Potential fatal
With both: 7-13 hrs hypersensitivity (watch for When discontinue therapy, tapper
Protein binding 55% early signs: dose by 50%/week over at least 2
lymphadenopathy, fever) weeks unless safety concerns.
22

Substrate of Inducer
Drug Pharmacokinetic Side effects Comments
CYP /Inhibit CYP
½
t 5hrs
Neuropsychiatric s/e:
enzymatic hydrolysis, not
behavioural symptoms 38%
cytochrome P450
(agitation, aggression, ADM: without regard to meals.
dependent. Excreted renally
anger), somnolence 23% , Swallow whole, do not break, crush
1 as unchanged drug 66% and
Levetiracetam - - dizziness 7%. headache or chew if possible.
inactive metabolites 27%.
GI: vomiting 15%, anorexia
Clearance decreased in
13%, diarrhea 8%
renal dysfunction.
Hematologic: decreased in
Protein binding < 10%
RBC, Hb, Hct, WBC, and
neutrophil.
CVS: hypotension,
ADM: oral with water, milk or juice
bradycardia
1 ½
Phenobarbitone t 20-133 hrs (infant), 37-73 CNS: drowsinwss, CNS
Induces Rapid IV administration may cause
hrs (children). depression, paradoxical
1A2 (strong) respiratory distress, apnea,
20-50% excreted unchanged 2C9 (minor) excitement, hyperkinetic
2A6 (strong) laryngospasm, or hypotension (do
in urine, clearance can be 2E1 (minor) activity
2B6 (strong) not inject faster than 1mg/kg/min).
increased with urine 2C19 (major)
2C8 (strong)
alkalization or oral multiple- DERM: skin eruption, rash,
2C9 (strong)
dose activated charcoal. exfoliative dermatitis
3A4 (strong)
Protein binding 35-50%
RESPI: depression, apnea
Hepatic: hepatitis
Ocular: nystagmus, ADM: May administer with food or

diplopia, blurred vision milk to reduce GI upset. High fat
½ CNS: slurred speech, meal reduces bioavailability of
t 14- 22hrs
dizziness generic products. Switching brand
Major metabolite (via Induces
Derm: hirsutism, may affect serum concentration.
oxidation) undergoes 2B6 (strong)
2C9 (major) coarsening of facial
1 enterohepatic recycling and 2C8 (strong)
Phenytoin 2C19 (major) features, rash SJS Bioavailability decrease with NG
eliminate in urine as 2C9 (strong)
3A4 (minor) GI: gingival hyperplasia, tube and antacid. Hold feedings/
glucuronides. 2C19 (strong)
gum tenderness, nausea, antacid for 2 hrs prior to and 2hrs
Protein binding 90-95% 3A4 (strong)
vomiting after phenytoin administration.

Others: folic acid depletion,
blood dyscrasias
33
23

34
SUBSTRATE INDUCER
DRUG PHARMACOKINETIC SIDE EFFECTS COMMENTS
OF CYP /INHIBIT CYP
½
t 6-10hrs Somnolence, fatigue, gait
Inhibit 2E1
Extensively via disturbances, ataxia, ADM: take with food (increased
(weak)
2 carboxylesterase-mediated shortening of QT interval, absorption)
Rufinamide -
hydrolysis of the multiorgan hypersensitivity Tablet may be swallowed whole,
Induce 3A4
carboxylamide group reactions (including severe split in half, or crushed.
(weak)
Protein binding 34% hepatitis).
Monitor symptoms of metabolic

acidosis (hyperventilation, fatigue,
anorexia, stupor, cardiac
Hyperchloremic metabolic
arrhythmia) and potential
acidosis may occur (inhibits
complications of chronic acidosis
carbonic anhydrase,
(nephrolithiasis, rickets, reduced
increases renal bicarbonate
growth rate).
loss causing decreased
Counsel patients to report any
serum bicarbonate).
blurred vision and/or eye pain.

1 Ocular symptoms
Topiramate
(secondary acute angle
Counsel patients for preventive
closure glaucoma and
½ strategies (hydration before and
t 7.7-12.8hrs Inhibit 2C19 acute myopia).
during exercise or exposure to hot
Minor amount metabolized in (weak)
temperature).
liver. 70% excreted - Oligohydrosis (decreased
unchanged in urine Induce 3A4 sweating) and hyperthermia
Use with caution in patients with
Protein binding 15-41% (weak)
inborn metabolic errors of
metabolism or decreased hepatic
Concurrent use of valproic
mitochondrial activity.
acid may result in
hyperammonemia with or
ADM: without regards to food.
without encephalopathy
Tablet can be crushed; broken
tablets may have bitter taste.
Somnolence, fatigue
Sprinkle capsule can be opened
alopecia, rash,
and mix the content with small
paraesthesia, tremor etc.
amount of soft food (1 teaspoonful
of oatmeal, pudding, custard,
applesauce, yogurt or ice cream),
swallow whole and do not chew.
24

SUBSTRATE INDUCER
DRUG PHARMACOKINETIC SIDE EFFECTS COMMENTS
OF CYP /INHIBIT CYP
Monitor patient closely for

1,2 appearance of malaise, vomiting,
Valproic acid Severe: hepatitis failure,
jaundice, abdominal pain,
½ life-threatening pancreatitis
t 7-12 hrs, prolonged with Inhibit unexplained lethargy, or changed in
hyperammonemic
liver disease 2C9 (weak) mental status.
encephalopathy.
2A6 (minor) 2C19 (weak)
Metabolised extensively in 2B6 (minor) 2D6 (weak) Counsel patient to report if easy
Risk of thrombocytopenia
liver via glucuronide 2C19 (minor) 3A4 (weak) bruising, yellow skin, loss of
with higher dose.
conjugation 30 - 50% and 2C9 (minor) appetite, nausea, vomiting or
40% via mitochondrial beta- 2E1 (minor) Induce 2A6 unexplained lethargy occurs.
Drowsiness, irritability,
oxidation. (weak/
rash, erythema multiforme,
Protein binding 80-90% moderate) ADM: may take with food to reduce
transient liver enzyme
GI effects. Avoid carbohydrate
elevation etc.
drink and milk. Do not crush or
chew enteric coated tablet.
Ophthalmologic examination should

be performed at baseline, 3
monthly (on therapy) and 3-
½
t 5.7-9.5 hrs, prolonged Permanent bilateral 6months after discontinuation.
with renal impairment concentric visual field Use with caution in patients with
2
Vigabatrin constriction (tunnel vision), renal impairment; dosage
Minimal metabolism blurred vision, diplopia, adjustment if CrCl <80 mL/minute
Induce
80% excreted unchanged in nystagmus.
- 2C9 (weak/
urine ADM: without regard to food.
moderate)
Weight gain, somnolence, Film coated tablet: swallow whole
Do not bind to plasma fatigue, excitation/ agitation, or break into half, do not crush
protein nausea, abdominal pain (manufacturer’s recommendation).
etc. If tablet administration not feasible,
may crush tablet and mix with soft
food eg. yogurt, honey or jam,
3
swallow whole without chewing .

REFERENCES:
35
2. Online Lexicomp
3. Medicines for Children [Internet]. Information for career and parents:vigabatrin for preventing seizures; 2014
[updated Jan, 2014]. Available from www.medicinesforchildren.org.uk
4. Micromedex v1622 3.0 General Pediatrics
General Pediatrics
3.0
References:
2. Online Lexicomp
3. Medicines for Children [Internet]. Information for career and parents:vigabatrin
for preventing seizures; 2014 [updated Jan, 2014]. Available from www.
medicinesforchildren.org.uk
4. Micromedex v1622

General Pediatrics
3.0
NEUROLOGY
Infantile Spasm
Introduction
Infantile spasm (West syndrome) is a severe form of epilepsy of early infancy,

onset during the first year of life with peak age between 3 and 7 month1. The
3 main features are a history of epileptic spasms, hypsarrhythmia (or modified
hypsarrhythmia) on EEG and often development arrest or regression2.
Spasms maybe subtle, brief, and sudden, the most subtle being a head nod or
tonic eye rolling, shown great variability in frequency which may be easily missed.
Typically the spasms involve brief symmetrical contraction of musculature of neck,
trunk and extremities lasting up to 5 seconds and occurring in clusters, occur
before or on awaking or just before sleep. The number of spasms can vary from
a few to more than hundreds per cluster with every cluster lasted from less than a
minute to more than 10 minutes3. Early detection and prompt effective treatment
is important to improve neurodevelopmental outcomes.
Management
Pharmacotherapy
1. United Kingdom Infantile Spasm Study (UKISS) Protocol4
Hormone treatment: Prednisolone 10mg QID (not weight based) for 2 weeks,
increasing to 20mg TDS after 1 week if spasm continued. After 2 weeks of
treatment, tapper off Prednisolone slowly with reduction of 10mg every 5 days
(over 2-3 weeks).
Ranitidine, omeprazole or esomeprazole should be considered to help prevent

gastric ulcer that may be caused by high dose prednisolone3.

General Pediatrics 1. United Kingdom Infantile Spasm Study (UKISS) Protocol4
Hormone treatment: Prednisolone 10mg QID (not weight based) for 2 weeks, increasing to
20mg TDS after 1 week if spasm continued. After 2 weeks of treatment, tapper off Prednisolone
slowly with reduction of 10mg every 5 days (over 2-3 weeks).
Ranitidine, omeprazole or esomeprazole should be considered to help prevent gastric ulcer that
may be caused by high dose prednisolone3.
3.0
Day 1- Day 7 Tab Prednisolone 10mg QID With ranitidine, omeprazole or

esomeprazole.
Monitor side effects:
D7 Spasm continued? No Yes § Hypertension

§ Electrolytes
imbalance, particularly
hypoK+
§ Immunosuppression
Increase §
Continue Irritability, restlessness
Day 8 - Day 14 § Increased appetite
10mg QID 20mg TDS
§ Weight gain
§ Facial puffiness
§ Acne
§ Glucosuria
Tapper off Prednisolone with § UTI
Over 2-3 weeks
reduction of 10mg every 5 days
5
Special consideration 26

• Prednisolone should be tapered off slowly to avoid acute adrenocortical

insufficiency.
• Steroid may cause a level of immunosuppression, causing increased
susceptibility of infection. Parents should be counseled to avoid contact with
infectious person, in particular those with varicella infection.
• No live vaccines (e.g. MMR, MMR-V, varicella, BCG) should be given during
therapy, and for 1 month after cessation of therapy.
• Similar efficacy between IM Tetracosactide (adrenocorticotrophic hormone
ACTH) and oral prednisolone4. Oral prednisolone is easily available, cost
effective, and having fewer side effects. It is recommended as an alternative
to intramuscular ACTH in the treatment of non-TS infantile spasms8.
2. Vigabatrin
Vigabatrin is recommended as first line treatment for children with infantile spasm
associated with tuberous sclerosis (TS) and also as second line treatment after
2-4 weeks of no response to corticosteroid in non-TS settings2.
Start with 50mg / kg / day in 2 divided doses, may titrate upwards by 25 to 50
mg / kg / day increments every 3 days based on response and tolerability ( max
150 mg / kg / day )6.

General Pediatrics
Special considerations
3.0
• Side effects: hypotonia, somnolence or insomnia along with permanent
vision field constriction (tunnel vision)7.
• Vigabatrin has also been associated with reversible signal changes at brain
MRI localized at thalamus, basal ganglia, corpus callosum and mid brain7.
• Use with caution in patients with renal impairment; dosage modification may
be necessary if CrCl <80 mL/minute6.
Non Pharmacotherapy
3. Ketogenic diet
Ketogenic diet is a strict diet which is high in fat, with adequate protein and low in
carbohydrate used as a treatment in refractory seizure. It may be considered for
children with infantile spasm who do not respond to hormone treatment and/or
vigabatrin3. The exact mechanism still unknown, metabolic changes likely related
to the its anticonvulsant properties include - but are not limited to - ketosis,
reduced glucose, elevated fatty acid levels, and enhanced bioenergetic reserves9.
Pharmacist’s role in managing patient on ketogenic diet
Pharmacist plays important role in optimize patient’s treatment outcomes by

restricting the use of concurrent medications with high carbohydrate content. A
general rule of thumb is that carbohydrate content is the highest in suspensions
and solutions, lower in chewable and disintegrating tablets, and lowest in tablets
and capsules10.
General principles
• No syrup medications, change to tablet or IV formulation.

• Freshly prepared with water only.
• No dextrose in IV drip, including diluents used for IV infusion.
• Medications using saccharin as the sweetener are suitable.
• Medications in suppository form are suitable for use on the ketogenic diet.
• Medication labeled as ‘sugar free’ does not mean the product is carbohydrate
free. Hidden carbohydrate source can be contributed by excipients.

General Pediatrics
3.0
Excipients which are source of carbohydrate 11
• Sugar ( dextrose, fructose, glucose, lactose, sucrose, sugar )

• Starches ( cornstarch, pregelatinized starch, sodium starch glycolate, sodium
starch glycolate )
• Sorbitol
• Mannitol
• Xylitol
• Maltitol
• Isomalt
• Erythritol
• Alcohol
• Glycerin
• Hydrogenated Starch Hydrolysates (HSH)
• Ascorbic acid
Excipients which are not source of carbohydrate11
• Su Cellulose
• Carboxymethylcellulose
• Hydroxymethylcellulose
• Microcrystalline cellulose
• Polyethylene glycol
• Magnesium stearate
• Aspartame
• Saccharine
• Asulfamine potassium (K)

General Pediatrics
Information on carbohydrate content in medications :
3.0
• www.matthewsfriends.org/Keto_Friendly_Medicine_List.doc
• Denis Lebel et al. (2001) The Carbohydrate and Caloric Content
of Concomitant Medications for Children with Epilepsy on the Ketogenic Diet.
Can. J. Neurol. Sci. 2001; 28: 322-340.
• Contact pharmaceutical companies for generic products
4. Other treatment options for infantile spasm
• Sodium valproate
• Topiramate etc.
References:
1. Hrachovy RA, Frost JD. Severe encephalopathic epilepsy in infants: infantile

spasm (West syndrome). In Pediatric Epilepsy: Diagnosis and Therapy. Edited
by Pellock JM, Bourgeois BF, Dodson WE, Nordli DR Jr,Sankar R. New York,
NY: Demos Medical Publishing 2008:249–268.
2. Children’s Neuroscience Centre Management Guideline: Management of
Infantile spasm (IS)/ West syndrome final 14-6-07
3. James WW, Patricia AG, Kari LR, Maria H, Christine OD, Vicky W, John MP.
Infantile spasms (West syndrome): update and resource for pediatricians and
providers to share with parents. BMC Pediatrics. 2012, 12:108.
4. Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW,
Callaghan FJK, Verity CM, Osborne JP. The United Kingdom Infantile Spasm
Study comparing vigabatrin with prednisolone or tetracosactide st 14 days: a
multicentre, randomized controlled study. Lancet 2004 Nov 13: 364: 1773-
1778.
5. Guideline for Investigation and Management of Children with Infantile Spasms
and West Syndrome. Nottingham University Hospital Trust; 2008 [cited
2014 Nov 4]. Available from: https://www.nuh.nhs.uk/handlers/downloads.
ashx?id=52197
6. Lexicomp Online

General Pediatrics
7. Piero P, Pasquale S, Raffaele F, Lorenzo P, Martino R. Infantile spasm

3.0
syndrome, West syndrome and related phenotypes: what we know in 2013.

Brain & Development. 2014, 739-751.
8. BH Ching, JW Tan, HS Heng, S Terumalay, TB Khoo, AR Mohamed. Paper
presented at: Paediatric Neurology Update; 2013 Sept 28; Ipoh General
Hospital, Perak, Malaysia.
9. Masino SA, Rho JM. Mechanisms of Ketogenic Diet Action. Jasper’s Basic
Mechanisms of Epilepsies. 4th Edition. NCBI Bookshelf Online Book Version.
10. Runyon Am, So TY. Review Article The Useof Ketogenic Diet in Pediatric
Patients with Epilepsy. International Scholarly Research Network ISRN
Pediatrics volume 2012.
11. Minimising the carbohydrate content of medications on the ketogenic diet
[cited 2014Nov 4]. Available from: http://www.gosh.nhs.uk/EasySiteWeb/
GatewayLink.aspx?alId=105274.

General Pediatrics
NEPHROLOGY
3.0
Acute Glomerulonephritis
Introduction
Acute Glomerulonephritis (AGN) is an abrupt onset of one or more features of

an Acute Nephritic Syndrome.Glomerular lesions are the results of glomerular
deposition or insitu formation of immune complexes. Commonest cause of AGN
in children (6-10 years old) is post-streptococcal infection of upper respiratory
tract or skin1 due to group A Beta-Hemolytic Streptococcus2. Non-infectious
causes of AGN are Henoch-Schoenlein purpura, IgA nephropathy, hereditary
nephritis, systemic lupus erythematosus or systemic vasculitidis.
Clinical Features
The onset is usually abrupt and nephritis may follow 7–15 days after streptococcal
tonsillitis and 4–6 weeks after impetigo2.
• Oedema (peripheral or periorbital).
• Microscopic /macroscopic haematuria (urine: tea-coloured or smoky)
• Decreased urine output (oliguria).
• Hypertension.
• Azotemia
Management
Fluid intake, urine output, daily weight and blood pressure (nephrotic chart) must
be strictly monitor. Patient must be bed rested and put on salt-free diet. Fluid
restriction if necessary until child diuresis and blood pressure (BP) is controlled.
Pharmacotherapy
• Penicillin V :
Start oral Penicillin (7.5-15mg/kg 6 hourly) for 10 days to eliminate -
haemolytic streptococcal infection (may use Erythromycin if allergic to
Penicillin).

General Pediatrics
3.0
Management of Severe Complications1
Hypertension
• For the management of hypertension use the following antihypertensives: oral

Nifedipine 0.25 - 0.5 mg / kg up to 4 hourly if needed, Frusemide 1mg / kg
/ dose, Captopril 0.1-0.5mg / kg 8 hourly or Metoprolol 1-4mg / kg 12 hourly.
• Monitor closely for signs and symptoms of severe hypertension or
hypertensive emergency / encephalopathy such as headache, vomiting, loss
of vision, convulsions, papilloedema.
• Target of BP control is to reduce BP to <90th percentile of BP for age, gender
and height percentile. Reduce BP by 25% of target BP over 3 - 12 hours and
the next 75% reduction is achieved over 48 hours.
Total BP to be reduced = Observed mean BP - Desired mean BP
Pulmonary Oedema
• IV Frusemide 2 mg/kg/dose stat; double this dose 4 hours later if poor
response.
• Fluid restriction for 24 hours if possible.
• Consider dialysis if no response to diuretics.
Acute Kidney Injury
• Mild renal impairment is common.
References:

2013. Chapter 58, Post-Infectious Glomerulonephritis; p.275-78
2. Garabed E, Norbert L, Kai-Uwe E, et.al. KDIGO Clinical Practice Guideline for

Glomerulonephritis. Kidney International Supplements 2012 June; 2(2):200-8.

General Pediatrics
NEPHROLOGY
3.0
Nephrotic Syndrome
Introduction
Primary or idiopathic nephrotic syndrome (NS) is the commonest type of

nephrotic syndrome in children. Secondary NS include post-streptococcal
glomerulonephritis, systemic lupus nephritis1.
Definition2:
• Relapses: Urine protein to creatinine ratio (uPCR) ≥2000mg/g (≥200mg/

mmol) or ≥ 3+ protein on urine dipstick for 3 consecutive days.
• Frequent relapses: ≥ 2 relapses within 6 months of initial response, or ≥ 4
relapses within any 12 month period.
• Steroid dependent: ≥ 2 consecutive relapses occurring during steroid taper
or within 14 days of the cessation of steroids.
• Steroid resistant: failure to achieve response to an initial 4 weeks treatment
with prednisolone at 60mg/m2/day.
Clinical Features
• Edema
• Hypoalbuminaemia of < 25g/l
• Proteinuria > 40 mg/m²/hour (> 1g/m²/day) or an early morning urine protein
creatinine index of >200 mg/mmol (> 3.5 mg/mg)
• Hypercholesterolaemia

General Pediatrics
3.0
Management
Pharmacotheraphy
• Oral Penicillin V
For prevention of primary bacterial peritonitis, 125 mg Oral BD (1-5 years
age), 250 mg BD (6-12 years), 500 mg BD (> 12 years)
• In patient with reduced urine output Human Albumin (20-25%) at 0.5 - 1.0 g
/ kg may be use with IV Frusemide at 1-2 mg/kg to produce a diuresis.
• Corticosteroid therapy, cyclophosphamide (refer algorithm).
Management of Complications1
• Hypovolaemia.
Clinical features: abdominal pain, cold peripheries, poor pulse volume,
hypotension, and haemoconcentration. Treatment is to infuse Human
Albumin at 0.5 to 1.0 g/kg/dose fast. If human albumin is not available, other
volume expanders like human plasma can be used. Do not give Frusemide.
• Primary Peritonitis
Clinical features: fever, abdominal pain and tenderness in children with newly
diagnosed or relapse nephrotic syndrome. Peritonitis is treated with parenteral
penicillin and a third generation cephalosporin
• Thrombosis
Thorough investigation and adequate treatment with anticoagulation is usually
needed. Please consult a Paediatric Nephrologist.

• Thrombosis
Thorough investigation and adequate treatment with anticoagulation is usually needed.
General Pediatrics
Please consult a Paediatric Nephrologist.
1. INITIAL EPISODE OF NEPHROTIC SYNDROME

Prednisolone 60 mg/m²/day for 4 weeks
3.0

Response No Response

Prednisolone 40 mg/m²/alternate day for 4 weeks. then RENAL BIOPSY

taper at 25% monthly over 4 months

2. RELAPSE
• Prednisolone 60 mg/m²/day till remission

• 40 mg/m²/alternate day for 4 weeks then stop

3. FREQUENT RELAPSES
• Reinduce as (2), then taper and keep low dose alternate day Prednisolone
0.1 -‐ 0.5 mg/kg/dose for 6 months

4. RELAPSES WHILE ON PREDNISOLONE

• Treat as for (3) if not steroid toxic
• Consider cyclophosphamide if steroid toxic.

5. ORAL CYCLOPHOSPHAMIDE
• 2-‐3 mg/kg/day for 8-‐12 weeks

Cumulative dose 168 mg/kg

6. RELAPSES POST CYCLOPHOSPHAMIDE

• As for (2) and (3) if not steroid toxic

• If steroid toxic, refer paediatric nephrologist to consider therapy with
cyclosporin or levamisole

Algorithm 1: Management of Nephrotic Syndrome
34


General Pediatrics
3.0
• If exposed to chickenpox and measles during corticosteroid therapy, it should

be treated like any immunocompromised child who has come into contact
with these diseases.
• Live vaccines should be deferred until prednisolone dose is <20mg/day or
2 m g / k g o n a l t e r n a t e d a y s ( < 4 0 m g o n a l t e r n a t e d a y s ) a n d / o r
immunosuppressive agents have been stopped for at least 1-3 months2.
References:

2013. Chapter 59, Nephrotic Syndrome; p.279-84
2. Garabed E, Norbert L, Kai-Uwe E, et.al. KDIGO Clinical Practice Guideline for

Glomerulonephritis. Kidney International Supplements 2012 June; 2(2):156-76

General Pediatrics
3.0
NEPHROLOGY
Acute Renal Failure
Introduction
Acute renal failure (ARF) also known as acute kidney injury. It is an abrupt onset
of rising in serum creatinine (SCr) level and decreased glomerular filtration rate
(GFR) and inability of kidney to regulate electrolytes and fluid hemostasis. ARF
is divided into pre-renal injury, intrinsic renal disease, or post-renal obstruction.
ARF since childhood due to haemolytic-uremic syndrome, post-infectious acute
glomerulonephritis or dehydration are reversible, but a small percentage may
progress to chronic renal failure (CRF)1.
Clinical Features
• Oliguria (< 300 ml/m²/day in children; < 1 ml/kg/hour in neonates) or

• Non-oliguria (Nephrotoxic injury, Interstitial Nephritis, or Neonatal Asphyxia)
Management
Pharmacotherapy
Fluid Balance
In hypovolaemia, fluid resuscitation must be initiated regardless of oliguric / anuric
state by crystalloids e.g. isotonic 0.9% saline / Ringer’s lactate 20 ml/kg fast (in
< 20 minutes) after obtaining vascular access. Transfuse blood if haemorrhage is
the cause of shock. If urine output increases, continue fluid replacemen homever
if there is no urine output after 4 hours (confirm with urinary catheterization),
monitor central venous pressure to assess fluid status3.
In hypervolaemia / fluid if necessary to give fluid, restrict to insensible loss (400 ml/
m²/day or 30ml/kg in neonates depending on ambient conditions). Treat with IV
Frusemide 2 mg/kg/dose (over 10-15 minutes), maximum of 5 mg/kg/dose or IV
Frusemide infusion 0.5 mg/kg/hour. Dialysis if no response or if volume overload
is life-threatening. Once normal volume status is achieved, give insensible loss
plus obvious losses (urine / extrarenal) 3.

General Pediatrics
3.0
Hypertension
Usually related to fluid overload and/or alteration in vascular tone. Treatment with
anti-hypertensive drugs depends on degree of BP elevation, presence of central
nervous system symptoms of hypertension and cause of renal failure. A diuretic
is usually needed.
Metabolic acidosis
It is treated if pH < 7.2 or symptomatic or contributing to hyperkalaemia. Ensure
that patient’s serum calcium is > 1.8 mmol/L to prevent hypocalcaemic seizures
with Sodium bicarbonate therapy. Replace half the deficit with IV 8.4% Sodium
bicarbonate (1:1 dilution) if indicated.
Bicarbonate deficit = 0.3 x body weight (kg) x base excess (BE)
Electrolytes abnormalities
• Hyperkalemia
•
(K+> 6.0 mmol/l in neonates and > 5.5 mmol/l in children):
Electrolytes abnormalities
Hyperkalemia (K⁺> 6.0 mmol/l in neonates and > 5.5 mmol/l in children):
Table 1: Treatment of Hyperkalemia in Acute Kidney Injury
TREATMENT OF HYPERKALEMIA IN AKI PATIENTS

Do 12-‐lead ECG and look for hyperkalaemic changes
If ECG is abnormal or plasma K+ > 7 mmol/l, connect patient to a cardiac monitor and give the following
in sequence:
1 IV 10% Calcium gluconate 0.5 -‐ 1.0 ml/kg (1:1 dilution) over 5 -‐15 mins (Immediate onset of action)
2 IV Dextrose 0.5 g/kg (2 ml/kg of 25%) over 15 – 30 mins.
3 ± IV Insulin 0.1 unit/kg (onset of action 30 mins).
4 IV 8.4% sodium bicarbonate 1 ml/kg (1:1 dilution) over 10 -‐ 30 mins (Onset of action 15 -‐ 30 mins)
5 Nebulized 0.5% salbutamol 2.5 -‐ 5 mg (0.5 -‐ 1 ml : 3 ml 0.9% Saline) (Onset of action 30 mins)
6 Calcium polystyrene sulphonate 0.25g/kg oral or rectally 4 times/day (Max 10g/dose) (Calcium
Resonium / Kalimate) [Give rectally (NOT orally) in neonates 0.125 – 0.25g/kg 4 times/day]
OR
6 Sodium polystyrene sulphonate 1g/kg oral or rectally 4 times/day (Max15g/dose) (Resonium)
In patients with serum potassium between 5.5 -‐ 7 mmol/L without ECG changes, give calcium or
sodium polystyrene sulphonate
If insulin is given after dextrose, monitor RBS / Dextrostix for hypoglycaemia.
Dialyse if poor or no response to the above measures
Hyponatremia: fluid restriction if dilutional; if symptomatic or level Na+ <120 mmol/L give
•
Sodium Chloride.
[Sodium deficit: (desired sodium – actual sodium) x 0.6 x body weight]
Give 50% of sodium deficit then reassess, avoid rapid correction.1
• Hyperphosphatemia: oral phosphate binder.
50• Paediatric Pharmacy
Hypocalcemia: Treat ifServices Guideline
symptomatic (usually serum Ca²⁺ < 1.8 mmol/L), and if Sodium
bicarbonate is required for hyperkalaemia, with IV 10% Calcium gluconate 0.5 ml/kg,
General Pediatrics
3.0
• Hyponatremia: fluid restriction if dilutional; if symptomatic or level Na+ <120
mmol/L give Sodium Chloride. [Sodium deficit: (desired sodium – actual
sodium) x 0.6 x body weight] Give 50% of sodium deficit then reassess, avoid
rapid correction.1
• Hyperphosphatemia: oral phosphate binder.
• Hypocalcemia: Treat if symptomatic (usually serum Ca² < 1.8 mmol/L),
and if Sodium bicarbonate is required for hyperkalaemia, with IV 10% Calcium
gluconate 0.5 ml/kg, given over 10 - 20 minutes, with ECG monitoring3.
Dialysis
Indicated if there are severe complication.
• Medications: dose adjustment, avoidance of nephrotoxic agents, dilutions of

medications.3
References:
1. Chan, J.C.M, Williams, D.M., Roth, K.S. Pediarics in Review. Feb 2002;
23(2): 47-60.
2. Guideline on management and investigation of acute renal failure. Renal

Unit Royal Hospital for Sick Children. November 2005. [cited on: 2014 Oct
20 ] Available from: http://www.clinicalguidelines.scot.nhs.uk

2013. Chapter 60, Acute Renal Failure; p.285-91

General Pediatrics
INFECTIOUS DISEASES
3.0
Tuberculosis
Introduction
Tuberculosis (TB) is the most common cause of infection-related death
worldwide1.
TB occurs when individuals inhale bacteria aerosolized by infected persons. The
organism is slow growing and tolerates the intracellular environment, where it
may remain metabolically inert for years before reactivation and disease. The
main determinant of the pathogenicity of TB is its ability to escape host defense
mechanisms, including macrophages and delayed hypersensitivity responses2.
Disease may be pulmonary (PTB) or extrapulmonary (EPTB), (i.e. central nervous
system (CNS), disseminated (miliary), lymph node, bone & joint) or both2.
Clinical features
Common clinical features suggestive of TB in children are prolonged fever, failure

to thrive, unresolving pneumonia, loss of weight and persistent lymphadenopathy.
TB should be suspected in a symptomatic child having history of contact with
active TB2.
Any patient with pneumonia, pleural effusion, or a cavitary or mass lesion in
the lung that does not improve with standard antibacterial therapy should be
evaluated for TB2.
Management
Pharmacotherapy
Corticosteroids3
• Indicated for children with TB meningitis
• May be considered for children with pleural and pericardial effusion (to hasten
reabsorption of fluid), severe miliary disease (if hypoxic) and endobronchial
disease
• Steroids should be given only when accompanied by appropriate
antituberculous therapy
• Dosage: prednisolone 1-2mg/kg per day (max. 40 mg daily) for first 3-4 week,
then taper over 3-4 weeks

General Pediatrics
3.0
Table 1: Recommended Doses of AntiTB Drugs in Children2
DAILY DOSE INTERMITTENT DOSE

DOSE
DRUG MAXIMUM MAXIMUM SIDE EFFECTS4,5
(RANGE) IN MG/KG/DAY
DOSE (MG) DOSE (MG)
MG/KG/DAY
Skin rash,
jaundice,
hepatitis,
anorexia, nausea,
abdominal pain,
Isoniazid 10 (10-15) 300 10 900
burning,
numbness or
tingling sensation
in the hands or
feet
Skin rash,
jaundice,
hepatitis,
anorexia, nausea,
abdominal pain,
Rifampicin 15 (10-20) 600 10 600 orange or red
urine, flu
syndrome (fever,
chills, malaise,
headache, bone
pain)
Skin rash,
jaundice,
Pyrazinamide 35 (30-40) 2000 hepatitis,
- -
anorexia, nausea,
abdominal pain &
joint pains
Ethambutol 20 (15-25) 1000 30-50 2500 Visual impairment
Pyridoxine 5 - 10 mg daily needs to be added if isoniazid is prescribed

40


General Pediatrics
3.0
Table 2: Suggested second line AntiTB Drugs in Children, Dosages and Side effects2
DAILY DOSE
DRUG DOSE (RANGE) MAXIMUM SIDE EFFECTS4,5
FREQUENCY
IN MG/KG/DAY DOSE (MG)
Kanamycin 15-30 1000 Daily Nephrotoxicity,
peripheral neuropathy,
Amikacin 15-22.5 1000 Daily rash, auditory damage
Nephrotoxicity, tubular
Capreomycin 15-30 1000 dysfunction, azotaemia,
Daily
proteinuria, urticaria or
maculopapular rash
Neurological and
psychiatric disturbances
Including headaches,
irritability, sleep
disturbances,
aggression and tremors,
Cyloserine* 10-20 1000 Daily/Twice daily
gum inflammation, pale
skin, depression,
confusion, dizziness,
restlessness, anxiety,
nightmares, severe
headache, drowsiness
Severe gastrointestinal
intolerance, psychotic
Ethionamide 15-20 1000 Twice daily disturbances,
neurotoxicity,
gynecomastia
Gastrointestinal
p- intolerance, careful use
aminosalicylic 3-4 times equally in patients with glucose6-
200-300 12000
acid divided dose phosphate
(PAS) dehydrogenase
(G6PD) deficiency.
Chthyosis,dry skin; pink
to brownish-black
discolouration
Clofazimine Safety and efficacy not estalished
of skin, cornea, retina
and urine; anorexia,
abdominal pain
Ofloxacin Twice Gastrointestinal
15-20 800 daily intolerance, headache,
Levofloxacin Daily malaise, insomnia,
7.5-10 750 restlessness, dizziness,
allergic reactions,
Daily diarrhoea,
Moxifloxacin 7.5-10 400
photosensitivity
41


General Pediatrics
* All patients receiving cycloserine should be given 50 mg pyridoxine for every
3.0
250 mg of cycloserine.
Monitoring of Drug Toxicity2
• Indications for baseline and routine monitoring of serum transaminases and

bilirubin are recommended for:
* Severe TB disease.
* Clinical symptoms of hepatotoxicity.
* Underlying hepatic disease.
* Use of other hepatotoxic drugs (especially anticonvulsants).
* HIV infection.
• Routine testing of serum transaminases in healthy children with none of the

above risk factors is not necessary.
• Children on Ethambutol should be monitored for visual acuity and colour

discrimination.

General Pediatrics
3.0
Table 3: Recommended Treatment Regimens for Children in Different TB Diagnostic

Categories2
Regimen*
TB cases Intensive Continuation Remarks
phase phase
New smear
positive PTB Ethambutol can be added
in the intensive phase of
New smear 2HRZ 4HR suspected isoniazid-resistance
negative PTB or extensive pulmonary
disease cases
Less severe EPTB
Severe concomitant
2HRZE 4HR
HIV disease
Severe form of
EPTB
2HRZE 10HR
TB meningitis/
spine/bone
All attempt should be made to
Previously treated obtain culture and sensitivity
smear positive PTB result. In those highly
including relapse 3HRZE 5HRE suspicious of Multidrug resistant (MDR-
and treatment after TB), refer to
interruption paediatrician with experience
in TB management.
Treatment failure Refer to paediatrician with

TB experience in TB management.
MDR-TB Refer to paediatrician with

Individualised regimen
experience in TB management.
*Direct observation of drug ingestion is recommended especially during the initial phase of treatment and
whenever possible during the continuation phase.
H=isoniazid,
Source: AdaptedR=rifampicin, Z=pyrazinamide,
from Malaysian CPG- E=ethambutol
Management of Tuberculosis, 3rd Edition, MOH
Latent Tb Infection (LTBI)2
Source: Adapted
Young children living infrom
close Malaysian
contact with CPG-
a case ofManagement
smear-positive PTBof Tuberculosis,
are at risk of TB3rd
infection and
Edition, MOH disease. The Tb
Latent risk Infection
of developing(LTBI)2
disease after infection is much greater for infants
and young children under five years. Active TB usually develops within two years of infection but
the time-lag can be as short as a few weeks in infants.
42


General Pediatrics
Young children living in close contact with a case of smear-positive PTB are at
3.0
risk of TB infection and disease. The risk of developing disease after infection is
Source: Adapted from Malaysian CPG- Management of Tuberculosis, 3rd Edition, MOH
much greater for infants and young children under five years. Active TB usually
Latent Tb Infection (LTBI)2
develops within two years of infection but the time-lag can be as short as a few
weeks
Youngin children
infants. living in close contact with a case of smear-positive PTB are at risk
infection and disease. The risk of developing disease after infection is much greater for
and young
Children children
younger thanunder fiveof
5 years years. Active
age with TBhave
LTBI usually
a 10develops within
- 20% risk two years of infecti
of developing
the time-lag can be as short as a few weeks in infants.
TB disease
Children younger than 5 years of age with LTBI have a 10 - 20% risk of developing TB dis
Management
Management
Pharmacotherapy
Pharmacotherapy
Table 4: Anti-TB Regimens for LTBI in Children
Drug Duration Interval

Isoniazid 6 months Daily
Isoniazid + Rifampicin 3 months Daily
Non-HIV infected children with latent tuberculosis infection should be treated with 6-month
2
isoniazid
Non-HIV or 3-month
infected of isoniazid
children plustuberculosis
with latent rifampicin . infection should be treated with
2
6-month of isoniazid or 3-month of isoniazid plus rifampicin .
There is no retrievable evidence of treatment for LTBI in HIV-infected children. However,
WHO recommends 6-months isoniazid therapy2.
There is no retrievable evidence of treatment for LTBI in HIV-infected children.
However, WHO recommends 6-months isoniazid therapy2.
Congenital & Perinatal TB
Congenital TB is defined as a direct spread through the umbilical cord, by aspirat

swallowing of infected amniotic fluid, or by direct contact with maternal genital lesions
delivery. Perinatal TB includes early postnatal transmission of the disease and is a
inclusive term2.
After active TB is ruled out, babies at risk of infection from their mothers should be giv
months of isoniazid preventive therapy, followed by BCG vaccination2.
Alternatively, if three months of isoniazid is given, tuberculin skin test (TST) should be do
completion of treatment:-
•If TST is negative (<5 mm), BCG vaccine should be administered and treatment
stopped2
•If TST is positive (=5 mm), treatment should continue for six months, followed by the
BCG at the end of treatment2.
General Pediatrics
Congenital & Perinatal TB

3.0
Congenital TB is defined as a direct spread through the umbilical cord, by

aspiration or swallowing of infected amniotic fluid, or by direct contact with
maternal genital lesions during delivery. Perinatal TB includes early postnatal
transmission of the disease and is a more inclusive term2.
After active TB is ruled out, babies at risk of infection from their mothers should be
given six months of isoniazid preventive therapy, followed by BCG vaccination2.
Alternatively, if three months of isoniazid is given, tuberculin skin test (TST) should
be done on completion of treatment:-
• If TST is negative (<5 mm), BCG vaccine should be administered and treatment
stopped2
• If TST is positive (=5 mm), treatment should continue for six months, followed
by the BCG at the end of treatment2
Table 5: Prophylaxis for Infants with Maternal TB2
Active PTB diagnosed before delivery Active PTB diagnosed after delivery
>2 months before <2 months before <2 months after >2 months after
Smear
Smear
positive
negative just
just before - - -
before delivery
delivery
Give prophylaxis: Give prophylaxis: Isoniazid for six

No prophylaxis Isoniazid for six months months
for infant OR isoniazid for three OR isoniazid + rifampicin for three
months followed by TST months
Reimmunise
If BCG given at birth,
Defer BCG at birth, give with BCG after
no need to
BCG at birth after stopping isoniazid stopping
reimmunise
isoniazid
Source: Adapted from Malaysian CPG- Management of Tuberculosis, 3rd Edition, MOH
Breast-feeding and mother with PTB3

TB treatment in lactating mothers is safe as the amount of drug ingested by the baby is minimal.
General Pediatrics
3.0
Breast-feeding and mother with PTB3
TB treatment in lactating mothers is safe as the amount of drug ingested by the

baby is minimal. Hence if the mother is already on treatment and is non-infective,
the baby can be breastfed.
Women who are receiving isoniazid and are breastfeeding should receive
pyridoxine.
If the mother is diagnosed to have active PTB and is still infective:
• The newborn should be separated from the mother for at least 1 week while
the mother is being treated.
• Mother should wear a surgical mask subsequently while breast feeding until
she is asymptomatic and her sputum is AFB-smear negative.
• Breast feeding is best avoided during this period but expressed breast milk
can be given.
• The infant should be evaluated for congenital TB. If this is excluded, BCG is
deferred and the baby should receive isoniazid for 3 months and then
tuberculin tested. If tuberculin negative and mother has been adherent to
treatment and non-infectious, isoniazid can be discontinued and BCG given.
If tuberculin positive, the infant should be reassessed for TB disease and if
disease is not present, isoniazid is continued for total of 6 months and BCG
given at the end of treatment.
References
1. Pediatric Tuberculosis.Vandana Batra, MD; Chief Editor: Russell W Steele,

MD http://emedicine.medscape.com/article/969401-overview#aw2aab6b4
2. Malaysian CPG- Management of Tuberculosis, 3rd Edition, MOH, 2012.
2013. Chapter 80, Tuberculosis; p.419-24.
4. World Health Organization. Treatment of tuberculosis Guidelines Fourth
Edition. Geneva: WHO; 2010
5. World Health Organization. Guidelines for the programmatic management of
drug-resistant tuberculosis 2011 Update. Geneva: WHO; 2011

General Pediatrics
INFECTIOUS DISEASES
3.0
Malaria
Introduction
Malaria is a tropical infection caused by members of protozoan genus called

Plasmodium that parasitize human red blood cells and liver. It is transmitted by
anopheline mosquitoes and the most common Plasmodium species that caused
malaria infection in human included P. falciparum, P.vivax, P.ovale, P. malariae and
P.knowlesi1.
According to WHO world report 2013, endemic area in Malaysia included Sabah,
Sarawak and central Peninsular Malaysia, with majority infection caused by
P.vivax (24%) and P. falciparum (18%). P.falciparum is associated with highest
mortality and morbidity. Symptoms of malaria included fever, malaise, weakness,
gastrointestinal complaints (nausea, vomiting, diarrhea), neurologic complaints
(dizziness, confusion, disorientation, coma), headache, back pain, myalgia, chills,
and / or cough2.
Management
Pharmacotherapy

Disease management depends on the type of Plasmodium infection and the
severity of infection3-5.

myalgia, chills, and/or cough .
General Pediatrics
Management
Pharmacotherapy
Disease management depends on the type of Plasmodium infection and the severity of
infection3-5.
3
(i) Uncomplicated P. falciparum infection
3.0
3
(i) Uncomplicated P. falciparum infection
Table 1: First line treatment for uncomplicated P. falciparum infection
First line : Artemisinin-based Combination Therapy (ACT)

Preferred treatment Alternative treatment
Artesunate/Mefloquine (Artequine)* Artemether/Lumefantrine (Riamet)
Dosage: Dosage:
10-20kg: 5-14kg:
Artesunate 50mg OD x 3/7 D1: 1 tab stat then 1 tab again after 8 hours,
Mefloquine 125mg OD x 3/7 D2-D3: 1 tab BD
Artequine 50/125mg (fixed dose pellets)
OD x 3/7 15-24kg:
D1: 2 tabs stat then 2 tabs again after 8 hours
20-40kg: D2-D3: 2 tabs BD
Artesunate 100mg OD x 3/7
Mefloquine 250mg OD x 3/7 25-35kg:
(Artequine 300/750) D1: 3 tabs stat then 3 tabs again after 8 hours
D2-D3: 3 tabs BD
>40kg:
Artesunate 200mg OD x 3/7 >35kg:
Mefloquine 500mg OD x 3/7 D1: 4 tabs stat then 4 tabs again after 8 hours
(Artequine 600/1500) D2-D3: 4 tabs BD
Riamet should NOT be used in young infant less than 5kg or less than 4 months.
46
Treatment
recommendation for these group of patients :
D1: IM Artesunate 1.2mg / kg or IM Arthemether 1.6mg / kg

D2-D7: Oral Artesunate 2mg / kg / day
OR
D1-7: Oral Quinine 10mg/kg TDS for 4 days, then 15-20mg/kg TDS for 4 days.
(Ref: Malaria in children, Department of tropical Pediatrics, Faculty of Tropical

Medicine, Mahidol University)

General Pediatrics
Riamet should NOT be used in young infant less than 5kg or less than 4 months. Treatment
recommendation for these group of patients :
D1: IM Artesunate 1.2mg/kg or IM Arthemether 1.6mg/kg

D2-D7: Oral Artesunate 2mg/kg/day
3.0
3
(ii) Second line P. falciparum infection OR
D1-7: Oral Quinine 10mg/kg TDS for 4 days, then 15-20mg/kg TDS for 4 days.
• An alternative ACT is used (if Riamet was used in the first regimen, use Artequine
(Ref:
for Malaria infailure
treatment children,
andDepartment of tropical Pediatrics, Faculty of Tropical Medicine,
vice-versa).
Mahidol University)
• Artesunate 4mg/kg OD plus Clindamycin
3
10mg/kg/dose bd for a total of 7 days.
(ii) Second line P. falciparum infection
• Quinine 10mg salt/kg 8 hourly plus Clindamycin 10mg/kg/dose bd for a total of
• An alternative ACT is used (if Riamet was used in the first regimen, use Artequine for
7 days.treatment failure and vice-versa).
• Artesunate 4mg/kg OD plus Clindamycin 10mg/kg/dose bd for a total of 7 days.
• Quinine 10mg
‘Add primaquine salt/kg 8
0.75mg hourly plus
base/kg Clindamycin
single dose 10mg/kg/dose bd for a is
OD if gametocyte total of 7 days.
present at any
time during treatment.
Add primaquine 0.75mg base/kg single dose OD if gametocyte is present at any time during
treatment.
(iii)(iii) Severe P.
Severe falciparum infection
3 3
P. falciparum infection
Table 2: Treatment for severe P. falciparum infection
Preferred Treatment Alternative treatment
IV Artesunate: IV Quinine loading 7mg salt/kg over 1 hour

2.4mg/kg at 0,12 and 24 hours, then daily until followed by 10mg salt/kg over 4 hours then
patient is able to tolerate orally. 10mg salt/kg every 8 hour
The use of IV Artesunate should continue for OR

minimum of 24 hours or as soon as patient
can tolerate orally. IV Quinine loading 20mg salt/kg over 4 hours,
then 10mg salt/kg every 8 hour, for 7 days.
PLUS
Children > 8 yrs old:

Doxycycline 3.5mg/kg OD x 7 days
OR
Children < 8 yrs old:
Clindamycin 10mg/kg BD x 7 days.
47


General Pediatrics
(iv)(iv)
Treatment P.vivax*,
ofP.vivax*,
Treatment of malariae
malariae or knowlesi
or knowlesi 3 3
3.0
Table 3: Treatment for P.vivax, malariae or knowlesi
Preferred Treatment
Chloroquine sensitive: Primaquine (7.5mg base/tab)
Chloroquine (150mg base/tab) § Add on Primaquine 0.5mg base/kg

D1: 10mg base/kg stat then 5mg base/kg 6 daily for 14 days to ensure radical
hours later cure of hypnozoites for P.vivax
D2: 5mg base/kg OD infection.
D3: 5mg base/kg OD
§ Check G6PD before giving
* Calculation of chloroquine dose should be Primaquine.
based on the base, not salt form.
PLUS § For mild to moderate G6PD
deficiency, an intermittent
Chloroquine resistant: S Primaquine regimen of 0.75mg
base/kg weekly for 8 weeks can be
§ To use ACT in relapse or chloroquine given under medical supervision.
resistant P.vivax, OR
§ Quinine 10mg salt/kg three times a day for § In severe G6PD deficiency
7 days OR Primaquine is contraindicated.
§ Mefloquine 15mg/kg single dose
Severe and complicated P.vivax, malariae and knowlesi should be managed as severe
Severe and complicated P.vivax, malariae and knowlesi should be managed as
falciparum malaria.
severe falciparum malaria.
48


General Pediatrics
(v) Chemoprophylaxis6-7
3.0
(v) Chemoprophylaxis6-7
Table 4: Chemoprophylaxis for travelling to malaria endemic areas
Drug Duration of Prophylaxis Dosage

Atovaquone/Proguanil Start 2 days before journey, Pediatric tablet of 62.5mg
(Malarone) continue daily during Atovaquone and 25mg Proguanil:
Pediatric tablet: exposure and up to 7 days 5-8kg: ½ tablet daily
(Atovaquone thereafter. >8-10kg: ¾ tablets daily
62.5mg/Proguanil 25mg) >10-20kg: 1 tablet daily
>20-30kg: 2 tablets daily
Adult tablet: >30-40kg: 3 tablets daily
(Atovaquone >40kg: 1 adult tablet daily
250mg/Proguanil 100mg)
Mefloquine (250mg base, Start 2-3 weeks before, <15kg: 5mg salt/kg
275mg salt per tablet) continue weekly during 15-19kg: ¼ tab/week
exposure and for 4 weeks 20-30kg: ½ tab/week
thereafter 31-45kg: ¾ tab/week
>45kg: 1 tab/week
Doxycycline Start 2 days before journey, 2.2mg base/kg once daily (max
continue daily during 100mg) (ref: Lexi comp)
exposure and for 4 weeks <25kg or < 8 years old: Do not use
thereafter. 25-35kg or 8-10 yrs old: 50mg
Maximum duration of 36-50kg or 11-13 yrs old: 75mg
prophylaxis: 4 months >50kg or >14 yrs old: 100mg
Chloroquine phosphate Begin 1–2 weeks before 5mg/kg base orally once/week, up to
250mg (equivalent to travel to malarious areas. maximum of 300mg base
Chloroquine base 155mg) Take weekly on the same
day of the week while in the
malarious area and for 4
weeks after leaving such
areas.
Primaquine (i) Prophylaxis for short- (i) 0.5mg/kg base up to 30mg base
duration travel to areas with (adult dose) orally, daily
principally P.vivax
(ii) Used for presumptive (ii) 0.5 mg/kg base up to adult dose
antirelapse therapy orally, daily for 14 days after
(terminal prophylaxis) to departure from the malarious area
decrease the risk for
relapses of P. vivax and P.
ovale
49

Special Consideration6-9
Table 6: Special considerations in anti-malarials
No Antimalarial Administration Precaution/Contraindications Side Effects/Remarks
1 Artesunate/ Pediatric pellets can be administered -Not to be used in children <10kg. - Dizziness
Mefloquine directly on patient’s tongue, or placed on - Avoid in children with epilepsy as it - Disturbed sense of balance
(Artequine) the spoon and mixed with little amount of may increase the risk of seizure (it may - Neuro- psychiatric reactions
liquid. Then rinse the mouth with small lower the plasma concentration of -Abdominal pain
amount of liquid to ensure all remaining Valproic acid, Carbamazepine, -Nausea
pellets are swallowed. Phenobarbital or Phenytoin). - Vomiting
If patient vomited within 1 hour of -No dosage adjustment for liver and - Diarrhoea
administration, one replacement dose is renal impairment. -Asthenia
required -Do not administer Halofantrine with - Anorexia
Artequine as it may cause potentially -Hypokalaemia
fatal prolongation of QT interval.
2 Artemether/Lum Administer with high fat diet. -Do not give Riamet for children less -QT inverval prolongation
efantrine In young children, Riamet can be than 5kg or less than 4 months of life -Fatigue
(Riamet) crushed and mixed with liquids. -No dosage adjustment for liver and -Dizziness
renal impairment.

3 Chloroquine Administer with meal to decrease GI -Renal adjustment dose needed. -May exacerbate psoriasis and
sulphate upset. May mix with chocolate syrup or -Use with caution in patients with liver porphyria.
banana to mask the bitter taste. disease, G6PD deficiency, seizure -Irreversible retinal damange
If the child vomits within first 30 minutes, disorder, severe blood disorder and was reported in patients with
full dose to be repeated, half dose if pre-existing auditory damage. long term or high dose
vomited between -Use in pregnancy should be avoided therapy.
30 minutes and 1 hour) unless benefit outweighs the risk to the - Agranulocytosis, neutropenia,
fetus. pancytopenia,
thrombocytopenia
- Myopathy

-Alopecia, blue gray skin
pigmentation
65
66

4 Primaquine Administer with meals to decrease GI - Screen for G6PD status before - Anemia
1 Artesunate/ effects; pellets
Pediatricdrug hascan be administered
a bitter taste. -Not
initiating used in children <10kg.
to betreatment Methemoglobinemia ( in
-- Dizziness
Mefloquine directly on patient’s
Extemporaneous tongue, or placed
preparations formulaon Cannotinbe
-- Avoid children
used by with
pregnant as it
epilepsywomen Disturbed sense of balance
-NADH-methemoglobin
(Artequine) the spoon
available. and mixed with little amount of may increase
- Cannot be used the risk of seizure
by women may
who(itare Neuro- psychiatric
-reductase reactions
deficient individuals)
liquid. Then rinse the mouth with small lower the plasma
breastfeeding concentration
unless the infant has
of also -Abdominal
- Leukopeniapain
amount of liquid to ensure all remaining Valproic acid, Carbamazepine,
been tested for G6PD deficiency -Nausea
pellets are swallowed. Phenobarbital or Phenytoin). - Vomiting
If patient vomited within 1 hour of -No dosage adjustment for liver and - Diarrhoea
5 Quinine Infusion rate should be <5 mg salt /kg/hr -May prolong QT interval or cause -May cause significant
required -Do not administer Halofantrine with - Anorexia
Maximum Quinine per dose = 600mg cardiac arrhythmias hypoglycaemia in pregnancy.
-reduce dose in patients with impaired -Stevens Johnson syndrome
liver function. and toxic epidermal necrolysis
-Contraindicated in patients with pre- has been reported.
existing QT prolongation, myasthenia - Agranulocytosis, aplastic

2 Artemether/Lum Administer with high fat diet. -Do notoptic
gravis, Riamet for
give neuritis, children
G6PD less
deficiency. -QT inverval
anemia, ITP, prolongation
hemolytic anemia
efantrine In young children, Riamet can be than
-Use 5kgof Quinine than
or less in pregnancy
4 monthsatof life -Fatigue
- Colour vision disturbance,
(Riamet) crushed and mixed with liquids. -No dosage adjustment
therapeutic dose is generally for liver and -Dizziness
diminished visual fields, optic
renal impairment.
considered safe. (Lexi Comp) neuritis

3
6. Chloroquine
Artesunate Administer
-Inject (1ml)with
5% meal
NaHCO to decrease GI -Renal adjustment
-Animal experiments dose
haveneeded.
shown some -May exacerbate
-Transient psoriasis and
reticulocytopenia
3 solution
sulphate upset.
providedMay mix
into thewith chocolate
Artesunate syrup
vial, or
shake -Use
embryowith caution
toxic effect.
in Should
patientsbe with liver
used porphyria.
may occur when >3.75mg/kg is
banana
2-3 to mask
minutes until the bitter
clear solution
taste.is disease, G6PD
with extreme deficiency,
caution seizure
in pregnancy -Irreversible
used. retinal damange
If the child
obtained. vomits within first 30 minutes, disorder, severe blood
within first three months. disorder and was reported in patients with
full dose
-For to be repeated,
IV injection, add 5mlhalf dose
of NS if
or D5% No dosageauditory
-pre-existing damage.
adjustment for liver and long term or high dose
to make final concentration of 10mg/ml of renal impairment.
30 minutes
Artesunate. and 1 hour) unless benefit outweighs the risk to the - Agranulocytosis, neutropenia,
Administer at the rate of 3-4ml/min. fetus. pancytopenia,
-For IM injection, add 2ml NS or D5% to thrombocytopenia
make final concentration of 20mg/ml - Myopathy
(total 3ml) -Alopecia, blue gray skin
-Inject immediately after reconstitution. pigmentation

7 Atovaquone/Pro Tablets are not palatable due to bitter -Contraindicated in people with severe - Transaminase increases
1 Artesunate/
guanil Pediatric
taste. Maypellets
crushcanthe be administered
tablets and mix with -Not
renaltoimpairment children
be used in(CrCl <30<10kg.
ml/min) Muscle weakness
-- Dizziness
Mefloquine
(Malarone) directly
condensedon patient’s
milk in children
tongue,withor placed on
difficulty - Avoid
-Not in children with
recommended epilepsy as it
for children Dizziness sense
-- Disturbed of balance
and headache
(Artequine) the spoon and
swallowing tablets. mixed with little amount of may increase the risk of
weighing <5 kg, pregnant women, seizure may
(it and psychiatric
Abdominal
-- Neuro- reactions
pain, anorexia,
Take Then
liquid.with foodrinse
or the mouth
a milky drinkwith small
(increase lower
women the plasma concentration
breastfeeding of
infants weighing -Abdominal
diarrhoea, nausea,
pain vomiting.
amount
the rate of
and liquid to ensure
extend all remaining
of absorption). Valproic
<5 kg acid, Carbamazepine, -Nausea
pelletsdaily
Take are atswallowed.
the same time each day Phenobarbital
-Absorption of or Phenytoin).
Atovaquone may be -GoodVomiting
for last-minute travelers
If patient
while vomited
in the within
malarious 1 hour
area andof for 7 -No dosageinadjustment
decreased patients who liver and
for have Diarrhoea
-because the drug is started 1-2
administration,
days after leaving one replacement
such areas. dose is renal impairment.
diarrhoea or vomiting. -Asthenia
days before traveling to an
required -Do not administer Halofantrine with -area Anorexia
where malaria
transmission occurs
8 Mefloquine Administer with food. - Cannot be used in : -Dizziness, vertigo, tinnitus,
Bitter taste. • areas with mefloquine loss of balance
2 Artemether/Lum Administer
Tablets canwith high fat diet.
be crushed and mixed with -Do not give Riamet for children less -QT inverval
-Anxiety, prolongation
depression,
resistance
efantrine In young
small children,
amount Riamet
of water, can
milk, be
applesauce, than 5kg or less than 4 months of life -Fatigue
restlessness, confusion
• patients with certain psychiatric
(Riamet) crushed and mixed with liquids.
chocolate syrup, jelly or food. -No dosage adjustment for liver and -Dizziness
-Agranulocytosis, aplastic
conditions
Repeat full dose if vomiting occurs within renal impairment. anemia
• patients with a seizure disorder
30 minutes after administration. • patients with cardiac conduction -Sinus bradycardia, sinus
Repeat additional half dose if vomiting arrhythmia, fist degree AV
Chloroquine Administer with to decrease abnormalities
-Renal adjustment dose needed. -May
3 occurs within 30-60
mealminutes after GI block,exacerbate
QT-intervalpsoriasis and
sulphate upset. May mix with chocolate syrup or -Use be used
- Canwith in pregnancy
caution in patients with liver porphyria.
administration. -Avoid concurrent use of drugs known prolongation, abnormal T
waves
If the child vomits within first 30 minutes, to cause QT-interval
disorder, severe blood prolongation
disorder and (eg. was reported in patients with
full dose to be repeated, half dose if halofantrine, quinine, quinidine)
pre-existing auditory damage. or long term or high dose
CYP3A4 inhibitors (eg. ketoconazole) Due to limited clinical
experience and dosage form
30 minutes and 1 hour) -Concurrent
unless benefituse with chloroquine
outweighs may
the risk to the Agranulocytosis,
-availability, neutropenia,
increase risk of seizure. WHO guidelines
exclude patients weighing
- Not a good choice for last-minute thrombocytopenia
travelers because drug needs to be <5kg from antimalarial dosage
Myopathy
-recommendations but CDC
started at least 2 weeks prior to travel

-Alopecia, blue
guidelines gray
do not skin
exclude
pigmentation
these patients.
67
9 Doxycycline Administer with liquids, avoid antacids, - Cannot be used by pregnant women -Photosensitivity
infant formula, milk, dairy products, and and children <8 years old. - Vaginal thrush
iron 1 hour before or 2 hours after - Use with caution in patients with renal - Pseudo-membranous colitis
administration of doxycycline. impairment. - Neutropenia 3.0 General Pediatrics
halofantrine, quinine, quinidine) or 3.0 General Pediatrics
CYP3A4 inhibitors (eg. ketoconazole) Due to limited clinical
-Concurrent use with chloroquine may experience and dosage form
increase risk of seizure. availability, WHO guidelines
Special Consideration6-9 - Not a good choice for last-minute exclude patients weighing
68
travelers because drug needs to be <5kg from antimalarial dosage
Table 6: Special considerations anti-malarials
started atinleast 2 weeks prior to travel recommendations but CDC
guidelines do not exclude
these patients.
9 Doxycycline Administer with liquids, avoid antacids, - Cannot be used by pregnant women -Photosensitivity
1 Artesunate/ infant formula,
Pediatric pelletsmilk,
candairy products, and
be administered and
-Not children
to be used years
<8 in children
old. <10kg. Vaginal thrush
- Dizziness
Mefloquine iron 1 hour
directly on patient’s
before ortongue,
2 hoursorafter
placed on Use with
- Avoid caution in
in children patients
with with
epilepsy asrenal
it Pseudo-membranous
- Disturbed colitis
sense of balance
(Artequine) administration
the spoon and of doxycycline.
mixed with little amount of impairment.
may increase the risk of seizure (it may Neutropenia
- Neuro- psychiatric reactions
May be administered with food
liquid. Then rinse the mouth with tosmall lower the plasma concentration of Thrombocytopenia
--Abdominal pain
decrease
amount ofGI upset.
liquid to ensure all remaining Valproic acid, Carbamazepine, -Nausea
May mix
pellets with
are milk, chocolate pudding,
swallowed. Phenobarbital or Phenytoin). - Vomiting
apple juice
If patient to increase
vomited withinpalatability.
1 hour of -No dosage adjustment for liver and - Diarrhoea
required -Do not administer Halofantrine with - Anorexia 52

2 Artemether/Lum Administer with high fat diet. -Do not give Riamet for children less -QT inverval prolongation
efantrine In young children, Riamet can be than 5kg or less than 4 months of life -Fatigue
(Riamet) crushed and mixed with liquids. -No dosage adjustment for liver and -Dizziness
renal impairment.

3 Chloroquine Administer with meal to decrease GI -Renal adjustment dose needed. -May exacerbate psoriasis and
sulphate upset. May mix with chocolate syrup or -Use with caution in patients with liver porphyria.
If the child vomits within first 30 minutes, disorder, severe blood disorder and was reported in patients with
full dose to be repeated, half dose if pre-existing auditory damage. long term or high dose
30 minutes and 1 hour) unless benefit outweighs the risk to the - Agranulocytosis, neutropenia,
thrombocytopenia
- Myopathy
-Alopecia, blue gray skin
pigmentation
General Pediatrics
Non Pharmacotherapy
3.0
Malaria Protective Measures10-11
Mosquito avoidance methods:
• Minimize outdoors activities during its feeding time from dusk to dawn,
and protect living quarters from mosquitoes to reduce exposure to the female
Anopheles mosquito
• Avoid dark clothing, aftershaves, perfumes which can attract mosquitoes
• Covering exposed skin areas with long sleeve clothes and long pants
• Use mosquito repellents, eg. diethyltoluamide (DEET)-containing repellents
(use DEET <35% in children) indoor and outdoor.
• Use mosquito nets, insecticidal (Deltamethrin, Permethrin, Alpha-
cypermethrin) impregnated clothes and nets.
Mosquito repellents:
CDC recommends the use of products containing DEET, picaridin, IR3535, and
some oil of lemon eucalyptus and para-menthane-diol products that provide
longer-lasting protection. Most products can be used on children. The American
Academy of Pediatrics recommended that insect repellents containing DEET
should not be used on children under 2 months of age and ≤30% DEET should
be used on children aged >2 months. Products containing oil of lemon eucalyptus
should not to be used on children under the age of three years. (CDC, FDA)
References:
1. Centers for Disease Control and Prevention (CDC). CDC Health Information
for International Travel. New York: Oxford University Press; 2014; Chapter
3. Available from http://wwwnc.cdc.gov/travel/page/yellowbook-
home-2014. Accessed 26 Oct 2014.
2. World Health Organization. World Malaria Report 2013; 2013:147.ISBN:

9789241564694. Available from http://www.who.int/malaria/publications/
world_malaria_report_2013/en/. Accessed 26 Oct 2014.
3. Muhammad Ismail HI, Ng HP, Thomas T. Paediatric Protocols for Malaysian

Hospitals. 3rd Ed. Ministry of Health;2013

General Pediatrics
4. Stauffer W, Fischer PR. Diagnosis and treatment of malaria in children.

3.0
Clinical Infectious Diseases. 2003;37:1340-1348.
5. Centers for Disease Control and Prevention (CDC). Treatment of Malaria

(Guidelines For Clinicians). July 2013. Available from http://www.cdc.gov/
malaria/resources/pdf/clinicalguidance.pdf. Accessed 26 Oct 2014.
6. Centers for Disease Control and Prevention (CDC). Choosing a drug to

prevent Malaria. Updated November 9, 2012. Available from http://www.
cdc.gov/malaria/travelers/drugs.html. Accessed 26 Oct 2014.\
7. World Health Organization. Guidelines for the treatment of malaria, 2nd

e d i t i o n . M a r c h 2 0 1 0 . Av a i l a b l e f r o m h t t p : / / w h q l i b d o c . w h o . i n t /
publications/2010/9789241547925_eng.pdf?ua=1. Accessed
16 Oct 2014.
8. Lexi-Comp Inc. Pediatric & Neonatal Lexi-Drugs. Lexi-Comp Inc.; Version
2.2.1 26 Oct 2014.
9. World Health Organization. Status report on artemisinin resistance.

September 2014. Available from http://www.who.int/malaria/publications/
atoz/status-rep-artemisinin-resistance-sep2014.pdf?ua=1. Accessed
26 Oct 2014.
10. World Health Organization. WHO recommended long lasting insecticidal

nets. February 2014. Available from http://www.who.int/whopes/Long_
lasting_insecticidal_nets_Jul_2012.pdf. Accessed 26 Oct 2014.
11. Centers for Disease Control and Prevention (CDC). Fight the bite for
protection from malaria. Guidelines for DEET insect repellent use.
Department of health and human services centers for disease control
and prevention. Available from http://www.cdc.gov/malaria/toolkit/DEET.
pdf. Accessed 26 Oct 2014.

General Pediatrics
INFECTIOUS DISEASES
3.0
Meningitis
Introduction
Meningitis is still a major and sometimes fatal problem in Paediatrics1.
Bacterial meningitis, an inflammation of the meninges affecting the pia, arachnoid,

and subarachnoid space that happens in response to bacteria and bacterial
products, continues to be an important cause of mortality and morbidity in
neonates and children2.
Morbidity is also high. A third of survivors have sequelae of their disease. However,
these complications can be reduced if meningitis is treated early1.
Management
Approach to a Child With Fever and Signs/symptoms of Miningitis
Fever & Symptoms/Signs

of Bacterial Meningitis
When NOT to do a Lumbar Puncture
• Glasgow coma Scale < 8

Lumbar Puncture (LP) • Abnormal ‘dolls eye’ reflex or unequal pupils
Contra indicated • Lateralized signs or abnormal posturing
No Yes
• Immediately after a recent seizure
Do LP With Hold LP • Papilloedema
• Do Blood, urline C&S

• Start Anitibiotics +- Dexamethasone
Abnormal CSF Normal CSF, wait for

CSF cuture and Latex agglutination
Continue antibiotics
Positive Negetive
Improvement No improvement
Re-evaluate, Consider discontinue Antibiotics
Complate Treatment ( See Next Page ) Persistent Fever > 72 Hours and
Neurological deficit
(rule out various causes)
Consider Ultrasound / CT Brain

Repeat LP if no evidence of
raised ICP
Change antibiotics
Consider TB, Fungus or Encephalitis Complate course of antibiotics

General Pediatrics
Table 1.0 Investigation of Cerebrospinal fluid (CSF) values in neurological disorders

with fever1:
3.0
Cerebrospinal fluid (CSF) values in neurological disorders with fever
Leukocytes Glucose
Comments
Condition (mm³) Protein (g/l) (mmol/l)
Acute Bacterial Gram stain may

Meningitis 100 - >50,000 Usually 1- 5 <0.5 - 1.5 be positive
1 - 10,000 CSF may be

Partially-treated Usually high sterile in
Bacterial PMN, Pneumococcal,
>1 low
Meningitis but may have Meningococcal
lymphocytes meningitis
Smear for acid

fast bacilli (AFB),
10 - 500 TB Polymerase
Tuberculous
Early PMN, later chain reaction
(TB)
high 1- 5 0 - 2.0 (PCR) + in CSF;
Meningitis
lymphocytes High Erythrocyte
sedimentation rate
(ESR)
Fungal 50 – 500 Normal or CSF for

Meningitis Lymphocytes 0.5 - 2 low Cryptococcal Ag
Normal / CSF virology and

Encephalitis 10 - 1,000 0.5-1 Normal HSV DNA PCR
Table 2.0: Gram Stain results of common bacteria causing community acquired
bacteria meningitis3
ORGANISM CSF GRAM STAIN

Gram positive cocci resembling streptococci
Group B streptococcus
Gram positive diplococci or GPC resembling
Streptococcus pneumoniae streptococci
Gram negative diplococci or gram negative

Neisseria meningitidis cocci
Gram negative cocco-bacilli

Haemophilus influenzae
Gram negative rods
Enterobacteriaceae e.g. E coli
Gram positive or Gram variable rods
Listeria monocytogenes

General Pediatrics
Pharmacotherapy
3.0
Table 3.0: Recommended antibiotic therapy according to likely pathogen1
Initial Duration
Age Group Antibiotic Likely Organism (if uncomplicated)
C Penicillin + Grp B Streptococcus

Cefotaxime E. coli 21 days
< 1 month
Group B
Streptococcus
C Penicillin +
E. coli 10 – 21 days
1 - 3 months Cefotaxime
H. influenzae
Strep. pneumoniae
C Penicillin + H. influenzae 7 – 10 days

Cefotaxime, OR Strep. pneumoniae 10 – 14 days
> 3 months
Ceftriaxone N. meningitides 7 days
Note:
1. Review antibiotic choice when infective organism has been identified.
2. Ceftriaxone gives more rapid CSF sterilisation as compared to Cefotaxime or Cefuroxime.
3. Ceftazidime has poor activity against pneumococci and should not be substituted for
cefotaxime or ceftriaxone4.
4. If Streptococcal meningitis, request for MIC values of antibiotics
MIC level Drug of choice:

• MIC < 0.1 mg/L (sensitive strain) C Penicillin
• MIC 0.1-< 2 mg/L (relatively resistant) Ceftriaxone or Cefotaxime
• MIC > 2 mg/L (resistant strain) Vancomycin + Ceftriaxone or Cefotaxime
5.Extend duration of treatment if complications e.g. subdural empyema, brain abscess.
Table 4.0: Duration of therapy for uncomplicated cases of meningitis
Common organism Duration of therapy

Group B streptococcus 21 days1
Gram negative rods 21 days3
Listeria monocytogenes 21 days3
Neisseria meningitidis 7 days3
Haemophilus influenzae type b 10 days3
Streptococcus pneumoniae 14 days3
‘Culture negative’ but significant CSF pleocytosis present, minimum of 7 days
recommended3.

General Pediatrics
Table 5.0 Estimates of CSF penetration of antibiotics used for the treatment of
3.0
bacterial meningitis5-7
CSF CSF
penetration penetration
(Drug in (Drug in Comments on use of antibiotic class for
CSF:plasma) in CSF:plasma) meningitis treatment
Antibiotics uninflamed in inflamed
meninges meninges
ß-lactams Poor CSF penetration, but high systemic doses are
well tolerated and attain CSF concentrations that
Benzylpenicillin 0.02 0.1 greatly exceed the MIC of susceptible bacteria. 40%
Amoxicillin/ampicillin 0·01 0·05 of cefotaxime vs 90% of ceftriaxone is protein bound.
Cefotaxime 0.1 0.2 Avoid imipenem because it could lower the seizure
Ceftriaxone 0.007 0.1 threshold. Continuous infusions could enhance
Meropenem 0.1 0.3 bacterial killing.
Aminoglycosides Poor CSF penetration and toxicity limits increases in

systemic doses. Consider intraventricular/intrathecal
Gentamicin 0.01 0.1 delivery if needed
Amikacin No data 0.1
Glycopeptides Poor CSF penetration and toxicity limits increases in
systemic doses. Continuous infusions could enhance
Vancomycin 0.01 0.2 bacterial killing. Limited data for
Teicoplanin 0.01 0.1 intraventricular/intrathecal delivery
Fluoroquinolones Good CSF penetration.
Ciprofloxacin 0.3 0.4 Moxifloxacin is an alternative agent for the treatment

Moxifloxacin 0.5 0.8 of penicillin-resistant
Levofloxacin 0.7 0.8 pneumococcal meningitis
Others
Chloramphenicol 0.6 0.7 Excellent CSF penetration, although toxicity concerns

limit its use.
Rifampicin 0.2 0.3 80% protein bound; CSF concentrations greatly
exceed MIC of susceptible bacteria.
Newer agents
Cefepime 0.1 0.2 Effective against penicillin-resistant pneumococcal

meningitis
Linezolid 0.5 0.7 Case report/series suggest eff ectiveness for

pneumococcal, staphylococcal, and enterococcal
meningitis, although high interindividual variability in
CSF pharmacokinetics suggests therapeutic drug
measurements could be needed
Daptomycin No data 0.05 Poor penetration, but CSF concentrations exceed MIC
of susceptible bacteria; case reports/series suggest
efficacy in staphylococcal and enterococcal
meningitis
Tigecycline No data 0.5 Good CSF penetration, but concentrations achieved

at current standard doses could be insufficient to
ensure bacterial killing
58


General Pediatrics
Corticosteroids in meningitis:
3.0
Corticosteroids are drugs that can reduce the inflammation caused by infection8.
Dose: IV Dexamethasone 0.15 mg/kg 6 hly for 4 days or 0.4 mg/kg 12 hly for
2 days1
Do not use corticosteroids in children younger than 3 months with suspected or

confirmed bacterial meningitis9.
If dexamethasone was not given before or with the first dose of antibiotics, but
was indicated, try to administer the first dose within 4 hours of starting antibiotics,
but do not start dexamethasone more than 12 hours after starting antibiotics9.
The corticosteroid dexamethasone leads to a reduction in hearing loss and other

neurological sequelae in participants in high-income countries who have bacterial
meningitis, but is not effective in low-income countries8.
An analysis for different bacteria causing meningitis showed that patients with
meningitis due to Streptococcus pneumoniae treated with corticosteroids
had a lower death rate, while no effect on mortality was seen in patients with
Haemophilus influenzae and Neisseria meningitidis meningitis8.
Corticosteroids decreased the rate of hearing loss in children with meningitis due
to H. influenzae, but not in children with meningitis due to other bacteria8.
Dexamethasone increased the rate of recurrent fever but was not associated with
other adverse events8.

General Pediatrics
References:
3.0

2013. Chapter 46, Meningitis; p.215-8.
2. Kim KS. Acute bacterial meningitis in infants and children. The Lancet
infectious diseases. 2010;10(1):32-42.
3. NSW Health. Infants and Children: Acute Management of Bacterial Meningitis:

Clinical Practice Guideline. 2014
4. Muller ML. Pediatric bacteria meningitis treatment and management. [Online].

2014 Nov 03 [cited 2015 Aug 4]; Available from: http://emedicine.medscape.
com/article/961497-treatment#d10
5. Van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment
of bacterial meningitis. The Lancet. 2012;380(9854):1693-702.
6. Nau R, Sorgel F, Eiff ert H. Penetration of drugs through the blood-

cerebrospinal fluid/blood–brain barrier for treatment of central nervous
system infections. Clin Microbiol Rev 2010; 23: 858–83.
7. Andes DR, Craig WA. Pharmacokinetics and pharmacodynamics of

antibiotics in meningitis. Infect Dis Clin North Am 1999; 13: 595–618.
8. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute

bacterial meningitis. Cochrane Database Syst Rev. 2013;6.
9. NICE clinical guideline. Bacterial meningitis andmeningococcal septicaemia

Management of bacterial meningitis and meningococcal septicaemia in
children and young people younger than 16 years in primary and secondary
care. 2015

General Pediatrics
INFECTIOUS DISEASES
3.0
Urinary Tract Infection
Introduction
UTI comprises 5% of febrile ilnesses in childhood. Around 2% of children will

have had a UTI before the age of 2 years. UTI is an important risk factor for the
development of hypertension, renal failure and end-stage renal disease1.
Management1
Pharmacotherapy
All infants with febrile UTI should be admitted and IV antibiotics started as for
acute pyelonephritis. In patients with high risk of serious illness, it’s preferable to
obtain a urine sample first; however treatment should be started if urine sample
is unobtainable.
• Antibiotic Prophylaxis
Antibiotic prophylaxis should not be routinely recommended in infants
and children following first time UTI, as antimicrobial prophylaxis does not seem
to reduce significantly the rates of recurrence of pyelonephritis, regardless of
age or degree of reflux. However, antibiotic prophylaxis may be considered in
the following:
- Infants and children with recurrent symptomatic UTI.

- Infants and children with vesico-ureteric reflux grades of at least grade III.

General Pediatrics
Antibiotic treatment for UTI

Type of Infection Preferred Treatment Alternative Treatment
UTI (Acute cystitis)
3.0
E. coli PO Trimethoprim PO Trimethoprim/

4mg/kg/dose BD Sulphamethoxazole
(max 300mg daily) for 1 week 4mg/kg/dose (TMP) BD for 1
Proteus spp. week
• Cephalexin, cefuroxime can be ued especially in children who had prior antibiotics.
• Single dose of antibiotic therapy is not recommended.
Upper Tract UTI (Acute pyelonephritis)
E. coli IV Cefotaxime 100mg/kg/day IV Cefuroxime 100mg/kg/day

q8h for 10-14 days q8h
OR
Proteus spp. IV Gentamicin 5-7mg/kg/day
daily
• Repeat culture within 48 hours if poor response.

• Antibiotics may need to be changed according to sensivity.
Suggest to continue IV antibiotic until a child is afebrile for 2-3 days and then switch to
appropriate oral therapy after culture results. Eg. Cefuroxime for total 10-14 days.
Asymptomatic bacteriuria
No treatment recommended
Antibiotic prophylaxis for UTI
UTI prophylaxis PO Trimethoprim 1-2mg/kg PO Nitrofurantoin 1-2mg/kg ON

ON OR
PO Cephalexin 5mg/kg ON
• Antibiotic prophylaxus is not to be routinely recommended in children with UTI.

• Prophylactic antibiotics should be given for 3 days with MCUG done on second day.
• A child who develops an infection while on prophylactic medication, treatment should be
with a different antibiotic and not a higher dose of the same prophylactic antibiotic.
Normal Renal Tracts
• Prophylactic antibiotic not required.

• Urine culture during any febrile illness or if the child is unwell.
No vesicoureteric reflux but renal scarring present
• Repeat urine culture only if symptomatic. 61

• Assessment includes height, weight, blood pressure and routine tests for
proteinuria.

General Pediatrics
• Children with a minor, unilateral scarring do not need long-term follow up
unless recurrent UTI/family history/lifestyle risk factors for hypertension.
• Children with bilateral abnormalities, impaired renal function, raised blood
3.0
pressure and/or proteinuria should be managed by a nephrologist.
• Close follow up during pregnancy.
Vesicoureteric Reflux
Management
• Antibiotic prophylaxis
• Surgical management or endoscopic treatment is considered if the child has
recurrent breakthrough febrile UTI.
Non Pharmacotherapy1
Measures to reduce risk of infections
• Dysfunctional elimination syndrome (DES) or dysfunctional voiding is defined

a an abnormal pattern of voiding of unknown etiology characterised by fecal
and/or urinary incontinence and witholding of both urine and feces.
• Treatment of DES includes high fibre diet, use of laxatives, timed frequent
voiding, and regular bowel movement.
• If condition persists, referral to a pediatric urologist/nephrologist is needed.
Summary
• All children less than 2 years of age with unexplained fever should have urine
tested for UTI.
• Antibiotic prophylaxis should not be routinely recommended following first
time UTI.
Reference:
1. Hussain Imam MI, Ng HP, Thomas T. Urinary Tract Infection. Paediatric

Protocols For Malaysian Hospitals 3rd Edition. 63:305-312.

General Pediatrics
3.0
INFECTIOUS DISEASES
Viral Croup
Introduction
Viral Croup is a clinical syndrome that is characterized by barking cough,

inspiratory stridor, hoarse voice and respiratory distress of varying severity. It is
also known as laryngotracheobronchitis, as it involved the inflammation of larynx,
trachea and bronchi. Virus that commonly caused croup included Parainfluenza
1 and 2 and Respiratory Syncytial Virus (RSV), Adenovirus, Enterovirus, Influenza
virus type A & B, and it mostly affects children between 6 and 36 months of
age, although may occur on older children. Croup may cause various degrees of
airway obstruction. However, several structural and infective conditions may also
cause airway obstruction (eg. laryngomalacia, foreign body, epiglottitis, subglottic
hemangioma). Hence, other causes need to be ruled out as the management
may differ.
MANAGEMENT
Management of croup depends on the severity upon presentation. Mild croup

can be managed as outpatient but moderate and severe croup will warrant
hospital admission for further management (treatment algorithm as below-paeds
protocol).
Assessment of severity Clinical Assessment of Croup (Wagener)
• Mild : Stridor with excitement or at rest, with no respiratory distress.

• Moderate : Stridor at rest with intercostal, subcostal or sternal recession.
• Severe : Stridor at rest with marked recession, decreased air entry and altered
level of consciousness.

• Moderate: Stridor at rest with intercostal, subcostal or sternal recession.
• Severe: Stridor at rest with marked recession, decreased air entry and
General Pediatrics
altered level of consciousness.
3.0
Pharmacological treatment
• Corticosteroid2-6
The mechanism of action of systemic corticosteroid is believed to be due to
its rapid anti-inflammatory effects or rapid vasoconstriction actions on the63
upper
airways.
The use of systemic steroids is associated with significant reduction of
the number of adrenaline nebulization needed and reduced the average length of
stay in Emergency Department9,10.
Dexamethasone and prednisolone has been shown to have equivalent initial
7
clinical response but there is a higher representation rate with prednisolone8
is no superiority in the choice of route of administration for the steroids (IV, IM or
oral), however oral route maybe preferable if the child can tolerate orally as it is the
least expensive and least traumatic way for the child (Feyzullah 2004).The anti-
inflammatory effect of Dexamethasone can last for 2-4 days.
The use of inhaled corticosteroid (eg. inhaled Budesonide) is also effective in
treating moderate croup. The onset of action is within 30 minutes5, which is
comparable to the systemic steroid, which the onset of action is 1 hour1,2,6.
• Nebulised Adrenaline
Nebulised Adrenaline should be used if the patient present with severe croup,
or no improvement or stridor worsened after the use of corticosteroid. It has
been suggested that inhaled adrenaline reduce bronchial and tracheal epithelial
vascular permeability to help decrease airway edema, which results in increase
in airway radius and improved airflow1,2. The onset of action is clinically rapid (30
minutes), and the duration of effect is 2 hours3,4. However, in severe croup, the
dose maybe repeated every 15-20 minutes. if the child required repeated doses
of Adrenaline nebulization, it may indicate that the child required intubation4.

General Pediatrics
Non pharmacological treatment4

3.0
• Oxygen
Oxygen is considered as the standard treatment for any patient with severe
croup, SpO2 <93% or with any significant respiratory distress. It can be given
concurrently with other pharmacological treatment such as corticosteroid and
adrenaline nebulization.
• Steam
Cold mist, steam and humidified air was once the mainstay of treatment in croup
during the 19th and 20th century, but there is no evidence that this strategy can
speed recovery, yet it may be associated with burns and scalds, hence the use
is not recommended in most of the treatment guidelines.
• Heliox
Heliox is a mixture of Helium and Oxygen (with not less than 20% oxygen).
Despite the conflicting findings from several clinical trials on the efficacy of Heliox
compared to other conventional modalities, there is still insufficient evidence to
establish the beneficial effect of the role of Heliox in the management of croup
The use of adrenaline should be cautioned in patients with ventricular outflow

obstruction such as TOF.

General Pediatrics
References:
3.0
1. Klassen TP. Croup: A Current Perspective in Emergency Medicine.
Pediatric Clinic of North America. 1999;46(6):1167-1178
2. Fitzgerald DA, Mellis CM, Johnson M, Copper PC, Allen HA, Van Asperren
PP, Nebulised Budesonide as Effective as Nebulised Adrenaline in
moderately severe croup. Pediatrics. 1996;97:722-725.
3. Waissman Y, Klein BL, Boenning DA et al. Prospective randomised double

blind study comparing L-epinephrine and racemic epinephrine aerosols in
the treatment of laryngotracheitis (croup). Pediatrics.1992;89:302-306.
4. Fitzgerald DA, Mellis CM. Management of acute upper airways obstruction

in children. Mod. Med Aust. 1995; 38:80-88
5. Husby S, Agertoft L, Mortensen S, Pedersen S. Treatment of croup with

nebulised steroid (Budesonide): a double blind, placebo controlled study.
Arch Dis Child.1993;68:352-355.
6. Geelhoed GC, MacDonald WB. Oral and inhaled steroid in croup: A

randomized, placebo-controlled trial. Pediatr Pulmonol.1995; 20:362-368.
7. Fifoot and Ting. EMA 2007;19:51-58.
8. Sparrow and Geelhoed GC. Arch Dis Child 2006:91;580-583.
9. Cruz MN, Stewart G, Rosenberg N. Use of Dexamethasone in the outpatient

management of acute laryngotracheitis. Pediatrics. 1995; 96:220-223
10. Jaffe D. The treatment of croup with glucocorticoids. N Eng J Med. 1998;
339:498-503.
11. Super DM, Cartelli NA, Brooks LJ et al. A prospective randomised double
blind study to evaluate the effect of dexamethasone in acute laryngotracheitis.
J Pediatr .1989;115:323-329.
12. Cetinkaya F, Tufekci BS, Kutluk G. A comparison of nebulised budesonide,

and intramuscular, and oral dexamethasone for treatment of croup.
International Journal of Pediatric Otorhinolaryngology. 2004 April; 68(4):
453-456.

General Pediatrics
INFECTIOUS DISEASES
3.0
Pneumonia
Introduction
There are two clinical definitions of pneumonia:
• Bronchopneumonia: a febrile illness with cough, respiratory distress with

evidence of localised or generalised patchy infiltrates1.
• Lobar pneumonia: similar to bronchopneumonia except that the physical
findings and radiographs indicate lobar consolidation1.
Clinical features
Criteria for Respiratory Distress in Children With Pneumonia2
Signs of Respiratory Distress
1. Tachypnea, respiratory rate, breaths/min

Age 0–2 months: > 60/min
Age 2–12 months: >50/min
Age 1–5 Years: >40/min
Age >5 Years: >20/min
2. Dyspnea
3. Retractions (suprasternal, intercostals, or subcostal)
4. Grunting
5. Nasal flaring
6. Apnea
7. Altered mental status
8. Pulse oximetry measurement ,90% on room air

3. Retractions (suprasternal, intercostals, or subcostal)
General Pediatrics
4. Grunting
5. Nasal flaring
6. Apnea
7. Altered mental status
8. Pulse oximetry measurement ,90% on room air
3.0
Table 1.0 Severity assessment3
Mild to moderate Severe

Infants Temperature <38.5˚C Temperature >38.5˚C
Respiratory rate <50 breaths/min Respiratory rate >70 breaths/min
Mild recession Moderate to severe recession
Taking full feeds Nasal flaring
Cyanosis
Intermittent apnoea
Grunting respiration
Not feeding
Tachycardia
Capillary refill time >2 s
Older Temperature <38.5˚C Temperature >38.5˚C
children Respiratory rate <50 breaths/min Respiratory rate >50 breaths/min
Mild breathlessness Severe difficulty in breathing
No vomiting Nasal flaring
Cyanosis
Grunting respiration
Signs of dehydration
Tachycardia
Capillary refill time >2 s
Criteria for hospitalization1
• Community acquired pneumonia can be treated at home 66

• Identify indicators of severity in children who need admission, as pneumonia
can be fatal. The following indicators can be used as a guide for admission:
• Children aged 3 months and below, whatever the severity of pneumonia.
• Fever ( more than 38.5 °C ), refusal to feed and vomiting
• Fast breathing with or without cyanosis
• Associated systemic manifestation
• Failure of previous antibiotic therapy
• Recurrent pneumonia
• Severe underlying disorder, e.g. Immunodeficiency

General Pediatrics
Criteria for hospitalization1

• Community acquired pneumonia can be treated at home
• Identify indicators of severity in children who need admission, as pneumonia
can be fatal. The following indicators can be used as a guide for admission:
• Children
Key features thataged 3 months
suggest and below,
a child whatever
requires the severity
transfer of pneumonia.
to intensive care3
3.0
• Fever ( more than 38.5 °C ), refusal to feed and vomiting

• Fast
• failure breathing with
to maintain or without
oxygen cyanosis
saturation >92% in fractional inspired oxygen of >0.6;
• Associated systemic manifestation
• shock;
• Failure of previous antibiotic therapy
• Recurrent pneumonia
• rising respiratory
• Severe anddisorder,
underlying pulse rate with clinical evidence of severe respiratory
e.g. Immunodeficiency
distress and exhaustion, with or without a raised arterial carbon dioxide tension;
Key features that suggest a child requires transfer to intensive care3
• recurrent apnoea or slow irregular breathing
• failure to maintain oxygen saturation >92% in fractional inspired oxygen of >0.6;
• shock;
• rising respiratory and pulse rate with clinical evidence of severe respiratory distress
Management
and exhaustion, with or without a raised arterial carbon dioxide tension;
• recurrent apnoea or slow irregular breathing
Pharmacotherapy
Management
Specific aetiological agents are not identified in 40% to 60% of cases1. It is often
difficult to distinguish viral from bacterial disease. The majority of lower respiratory
Pharmacotherapy
tract infections are viral in origin, e.g. Respiratory syncytial virus, Influenza A or B,
Specific aetiological agents are not identified in 40% to 60% of cases1.
Adenovirus, Parainfluenza
It is often difficult virus.
to distinguish viral from bacterial disease. The majority of lower respiratory
tract infections are viral in origin, e.g. Respiratory syncytial virus, Influenza A or B,
A helpful indicator
Adenovirus, in predicting
Parainfluenza virus. aetiological agents is the age group.
A helpful indicator in predicting aetiological agents is the age group.

Table 2.0 Predominant bacterial pathogens of pneumonia according to age group
Table 2.0 Predominant bacterial pathogens of pneumonia according to age group
Pathogens for Pneumonia

Age Bacterial Pathogens
Newborns Group B streptococcus, Escherichia coli,
Klebsiella species, Enterobacteriaceae
Infants 1- 3 months Chlamydia trachomatis
Preschool age Streptococcus pneumoniae, Haemophilus
influenzae type b,
Staphylococcal aureus
Less common: Group A Streptococcus,
Moraxella catarrhalis, Pseudomonas
aeruginosa
School age Mycoplasma pneumoniae, Chlamydia
pneumoniae
When treating pneumonia, consider clinical, laboratory, radiographic findings, as well as age
When
of thetreating pneumonia,
child, and consider of
the local epidemiology clinical, laboratory,
respiratory radiographic
pathogens findings, as
and resistance/sensitivity
well as age
patterns of the child,
to microbial agentsand
1
. the local epidemiology of respiratory pathogens and
1 1
Majority of infections are
resistance/sensitivity caused by
patterns toviruses and do
microbial not require
agents . antibiotics .
Majority of infections are caused by viruses and do not require antibiotics1.

67


General Pediatrics
Table 3.0 Bacterial pathogens and Recommended antimicrobial agents1
3.0
Pathogens Antimicrobial Agents
Beta-lactam susceptible
Streptococcus pneumonia Penicillin, cephalosporins
Haemophilus influenzae type b Ampicillin, chloramphenicol, cephalosporins
Staphylococcus aureus Cloxacillin
Group A Streptococcus Penicillin, cephalosporin
Mycoplasma pneumoniae Macrolides, e.g. erythromycin, azithromycin
Chlamydia pneumoniae Macrolides, e.g. erythromycin, azithromycin
Bordetella pertussis Macrolides, e.g. erythromycin, azithromycin
Table 4.0 Bacterial pathogens and recommended antimicrobial agents2.
Pathogen Parenteral therapy Oral therapy (step-down therapy

or mild infection)
Streptococcus Preferred: ampicillin (150–200 Preferred: amoxicillin (90 mg/kg/day
pneumoniae with mg/kg/day every 6 hours) or in 2 doses or 45 mg/kg/day in 3
MICs for penicillin penicillin (200 000–250 000 doses);
≤ 2.0 mcg/mL U/kg/day every 4–6 h);
Alternatives: second- or third-
Alternatives: ceftriaxone (50–100 generation cephalosporin
mg/kg/day every 12–24 hours) (cefpodoxime, cefuroxime,
(preferred for parenteral outpatient cefprozil); oral levofloxacin, if
therapy) or cefotaxime susceptible (16–20 mg/kg/day in 2
(150 mg/kg/day every 8 hours); may doses for children 6 months to 5
also be effective: clindamycin (40 years old and 8–10 mg/kg/day
mg/kg/day every 6–8 hours) or once daily for children 5 to 16 years
vancomycin (40–60 mg/kg/day old; maximum daily dose, 750 mg) or
every 6–8 hours) oral linezolid (30 mg/kg/day in 3
doses for children <12 years old and
20 mg/kg/day in 2 doses for children
≥12 years old)
S. pneumoniae Preferred: ceftriaxone Preferred: oral levofloxacin (16–20
resistant to (100mg/kg/day every 12–24 hours); mg/kg/day in 2 doses for children 6
penicillin, with MICs months to 5 years and 8–10
≥4.0 mcg/mL Alternatives: ampicillin mg/kg/day once daily for children 5–
(300–400 mg/kg/day every 6 hours), 16 years, maximum daily dose, 750
levofloxacin (16–20 mg/kg/day mg), if susceptible, or oral linezolid
every 12 hours for children 6 (30 mg/kg/day in 3 doses for children
months to 5 years old and 8–10 <12 years and 20 mg/kg/day in 2
mg/kg/day once daily for children 5– doses for children ≥12 years);
16 years old; maximum daily dose,
750 mg), or linezolid (30 mg/kg/day Alternative: oral clindamycin
every 8 hours for children <12 years (30–40 mg/kg/day in 3 doses)
old and 20 mg/kg/day every 12
hours for children >12 years old);
may also be effective: clindamycin
(40 mg/kg/day every 6–8 hours) or
vancomycin (40–60 mg/kg/day
every 6–8 hours)
68

General Pediatrics
Group A Preferred: intravenous penicillin Preferred: amoxicillin (50–75

3.0
Streptococcus (100 000–250 000 U/kg/day every mg/kg/day in 2 doses), or penicillin V

4–6 hours) or ampicillin (200 (50–75 mg/kg/day in 3 or 4 doses);
mg/kg/day every 6 hours);
Alternative: oral clindamycin
Alternatives: ceftriaxone (50–100 (40 mg/kg/day in 3 doses)
mg/kg/day every 12–24 hours) or
cefotaxime (150 mg/kg/day every
8 hours); may also be effective:
clindamycin, if susceptible (40
mg/kg/day every 6–8 hours) or
Vancomycin (40–60 mg/kg/day
every 6–8 hours)
Stapyhylococcus Preferred: cefazolin (150 mg/kg/day Preferred: oral cephalexin (75–100

aureus, every 8 hours) or semisynthetic mg/kg/day in 3 or 4 doses);
methicillin penicillin, eg oxacillin (150–200
susceptible mg/kg/day every 6–8 hours); Alternative: oral clindamycin
(combination therapy (30–40 mg/kg/day in 3 or 4 doses)
not well studied) Alternatives: clindamycin
(40 mg/kg/day every
6–8 hours) or vancomycin (40–60
mg/kg/day every 6–8 hours)
S. aureus, methicillin Preferred: vancomycin (40–60 Preferred: oral clindamycin (30–40

resistant, mg/kg/day every 6–8 hours or mg/kg/day in 3 or 4 doses);
susceptible to dosing to achieve an AUC/MIC ratio
clindamycin of >400) or clindamycin (40m Alternatives: oral linezolid
(combination therapy g/kg/day every 6–8 hours); (30 mg/kg/day in 3 doses for children
not well-studied) <12 years and 20 mg/kg/day in 2
Alternatives: linezolid (30 doses for children ≥12 years)
mg/kg/day every 8 hours for
children <12 years old and 20
children ≥12 years old)
S. aureus, methicillin Preferred: vancomycin (40–60 Preferred: oral linezolid (30

resistant,resistant to mg/kg/day every 6-8 hours or mg/kg/day in 3 doses for children <12
clindamycin dosing to achieve an AUC/MIC ratio years and 20 mg/kg/day in 2 doses
(combination therapy of >400); for children ≥12 years old);
not well studied)
Alternatives: linezolid (30 Alternatives: none; entire treatment
mg/kg/day every 8 hours for course with parenteral therapy may
children <12 years old and 20 be required
children ≥12 years old)
Haemophilus Preferred: intravenous ampicillin Preferred: amoxicillin (75-100

influenza, typeable (150-200 mg/kg/day every 6 hours) mg/kg/day in 3 doses) if b-lactamase
(A-F) or nontypeable if b-lactamase negative, ceftriaxone negative) or amoxicillin clavulanate
(50–100 mg/kg/day every 12-24 (amoxicillin component, 45
hours) if b-lactamase producing, or mg/kg/day in 3 doses or 90
cefotaxime (150 mg/kg/day every 8 mg/kg/day in 2 doses) if b-lactamase
hours); producing;
69

General Pediatrics
Alternatives: intravenous Alternatives: cefdinir, cefixime,
ciprofloxacin (30 mg/kg/day cefpodoxime, or ceftibuten
3.0
every 12 hours) or intravenous
levofloxacin (16-20 mg/kg/day every
12 hours for children 6 months to 5
years old and 8-10 mg/kg/day once
daily for children 5 to 16 years old;
maximum daily dose, 750 mg)
Mycoplasma Preferred: intravenous azithromycin Preferred: azithromycin (10 mg/kg

pneumoniae (10 mg/kg on days 1 and 2 of on day 1,followed by 5 mg/kg/day
therapy; transition to oral therapy if once daily on days 2–5);
possible);
Alternatives: clarithromycin
Alternatives: intravenous (15 mg/kg/day in 2 doses) or oral
erythromycin lactobionate erythromycin (40 mg/kg/day in 4
(20 mg/kg/day every 6 hours) or doses); for children >7 years old,
levofloxacin (16-20 mg/kg/day every doxycycline (2–4 mg/kg/day in 2
12 hours; maximum daily doses; for adolescents with skeletal
dose, 750 mg) maturity, levofloxacin
(500 mg once daily) or oxifloxacin
(400 mg once daily)
Chlamydia Preferred: intravenous azithromycin Preferred: azithromycin (10 mg/kg

trachomatis or (10 mg/kg on days 1 and 2 of on day 1,followed by 5 mg/kg/day
Chlamydophila therapy; transition to oral therapy if once daily days 2–5);
pneumoniae possible);
Alternatives: clarithromycin
Alternatives: intravenous (15 mg/kg/day in 2 doses) or oral
erythromycin lactobionate erythromycin (40 mg/kg/day in 4
(20 mg/kg/day every 6 hours) or doses); for children >7 years old,
levofloxacin (16-20 mg/kg/day in 2 doxycycline (2-4 mg/kg/day in 2
doses for children 6 months doses); for adolescents with skeletal
to 5 years old and 8-10 mg/kg/day maturity, levofloxacin
once daily for children 5 to 16 years (500 mg once daily) or oxifloxacin
old; maximum daily dose, (400 mg once daily)
750 mg)
Doses for oral therapy should not exceed adult doses.
Supportive treatment
1
1
Supportive treatment
i. Fluids
i. Fluids
• Withhold oral
• Withhold intake
oral whena child
intake when a child
is in is in severe
severe respiratory
respiratory distress. distress.
• In severe pneumonia, secretion of anti-diuretic hormone is increased as such
• In severe pneumonia,
dehydration secretion
is uncommon. of anti-diuretic
Avoid overhydrating the child.hormone is increased as
ii. such
Oxygen
dehydration is uncommon. Avoid overhydrating the child.
• Oxygen reduces mortality associated with severe pneumonia.
• It should be given especially to children who are restless, and tachypnoeic with
ii. Oxygen
severe chest indrawing, cyanosis, or is not tolerating feeds.
• Maintain
• Oxygen the SpO2
reduces > 95%. associated with severe pneumonia.
mortality
• It should be given especially to children who are restless, and tachypnoeic
with severe chest indrawing, cyanosis, or is not tolerating feeds. 70
• Maintain the SpO2 > 95%.

General Pediatrics
iii. Cough medication

• Not recommended as it causes suppression of cough and may interfere
3.0
with airway clearance. Adverse effects and overdosage have been

reported.
iv. Temperature control
• Reduces discomfort from symptoms, as paracetamol will not abolish fever
v. Chest physiotherapy
• This assists in the removal of tracheobronchial secretions: removes airway
obstruction, increase gas exchange and reduce the work of breathing.
• No evidence that chest physiotherapy should be routinely done.
Scientific basis of WHO recommendations for treatment of pneumonia4
• Children with fast breathing pneumonia with no chest indrawing or general

danger sign should be treated with oral amoxicillin: at least 40mg/kg/dose
twice daily (80mg/kg/day) for five days. In areas with low HIV prevalence, give
amoxicillin for three days.
• Children with fast-breathing pneumonia who fail on first-line treatment with
amoxicillin should have the option of referral to a facility where there is
appropriate second-line treatment.
• Children age 2–59 months with chest indrawing pneumonia should be treated
with oral amoxicillin: at least 40mg/kg/dose twice daily for five days.
• Children aged 2–59 months with severe pneumonia should be treated with
parenteral ampicillin (or penicillin) and gentamicin as a first-line treatment.
- Ampicillin: 50 mg/kg, or benzyl penicillin: 50 000 units per kg IM/IV every 6
hours for at least five days
- Gentamicin: 7.5 mg/kg IM/IV once a day for at least five days
• Ceftriaxone should be used as a second-line treatment in children with severe
pneumonia having failed on the first-line treatment.
• Ampicillin (or penicillin when ampicillin is not available) plus gentamicin or
ceftriaxone are recommended as a first-line antibiotic regimen for HIV-infected
and -exposed infants and for children under 5 years of age with chest
indrawing pneumonia or severe pneumonia.
• For HIV-infected and -exposed infants and for children with chest indrawing
pneumonia or severe pneumonia, who do not respond to treatment with
ampicillin or penicillin plus gentamicin, ceftriaxone alone is recommended for
use as second-line treatment.

General Pediatrics
• Empiric cotrimoxazole treatment for suspected Pneumocystis jirovecii
3.0
(previously Pneumocystis carinii) pneumonia (PCP) is recommended as an
additional treatment for HIV-infected and -exposed infants aged from 2
months up to 1 year with chest indrawing or severe pneumonia.
• Empirical cotrimoxazole treatment for Pneumocystis jirovecii pneumonia (PCP)
is not recommended for HIV-infected and - exposed children over 1 year of
age with chest indrawing or severe pneumonia.
References:

Malaysia; 2013. Chapter 33, Pneumonia; p.165-8.
2. Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et
al. The management of community-acquired pneumonia in infants and
children older than 3 months of age: clinical practice guidelines by the
Pediatric Infectious Diseases Society and the Infectious Diseases Society of
America. Clinical Infectious Diseases. 2011;53(7):e25-e76.
3. Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, et al.

British Thoracic Society guidelines for the management of community
acquired pneumonia in children: update 2011. Thorax. 2011;66(Suppl 2):ii1-ii23.
4. Organization WH. Revised WHO classification and treatment of pneumonia in

children at health facilities: evidence summaries. 2014.

General Pediatrics
CARDIOVASCULAR
3.0
Kawasaki Disease
Introduction
Kawasaki disease (KD) is an acute, self-limited febrile illness mainly affecting small-
to medium-sized vessels and occurs in early childhood. The etiology is currently
unknown, however it likely results from an immunologic response triggered by
microbial agents, with documented genetic susceptibility. KD typically presents in
children younger than 5 years as a febrile illness with mucocutaneous changes. If
untreated, KD can result in coronary aneurisms in 25% patients1,2.
In 1990 the American Heart Association(AHA) committee on rheumatic fever,
endocarditis, and Kawasaki disease gave the case definition that has been
generally accepted—ie, a febrile illness of at least five days with at least four of
the five following signs and no other reasonable cause for the findings1:
a) Bilateral conjunctival injection – (there is no corneal ulceration but there may

be a concomitant anterior uveitis on slit lamp examination)
b) Oral changes (erythema of lips or oropharynx, strawberry tongue due to

prominent papillae, or fissuring of the lips)
c) Peripheral extremity changes (oedema, erythema, or generalised or periungal

desquamation); erythema is seen in the first week whereas desquamation
begins about 14–21 days after the onset of the illness
d) Rash – this starts in the first few days; it is often diffuse and polymorphic
and lasts a week before fading. Vesicles are rarely seen; however, the rash
can appear macular, maculopapular, urticarial, scarlettina or even morbilliform
e) Cervical lymphadenopathy is found in about 50% of cases; most often there

is a painful solitary enlarged lymph gland, >1.5 cm in diameter

General Pediatrics
Fever is an essential feature; it is most often sudden in onset and swinging, going
above 40°C. It must last at least for five days but can persist for up to a month.
3.0
If coronary arterial aneurysms (CAA) are present, one of the most important
complications of Kawasaki disease, then only three of the clinical features are
required to clinch the diagnosis.
There are ‘incomplete cases’ when not all of the four (three with CAA) diagnostic
clinical features are present; some of these cases may evolve into complete
cases. Some incomplete cases are diagnosed by CAA on echocardiography or
at necropsy and the benefit of hindsight of the preceding clinical features.
For most children there is a subacute phase that lasts up to 30 days and a full
recovery by day 50 following the onset of the illness.
Management2
Management2
Pharmacotherapy
Pharmacotherapy
Table 1. Treatment dose for Kawasaki Disease
Drug Dose Suggested Additional information

monitoring
Primary treatment
If white blood cell
increases from the normal
2 Gm/kg infusion WBC (4500-11000 range 4500-11000 cell/µL
IV Immunoglobulins
over 10 - 12 hours cell/µL) then infusion rate has to be
slowed down until it falls
within the range
Bleeding
30 mg/kg/day for 2 Creatinine :
wks or until patient 0.2 to 1.0 mg/dL Lower the dose if aspirin
Oral Aspirin
is afebrile for 2-3 PT:10-13.5 Sec levels: >300 mcg/ml (toxic)
days APTT:26-42 Sec
INR:<1.5
Maintainence
3-5 mg/kg daily Bleeding
for 6 - 8 weeks Creatinine :
If coronary aneurysm
or 0.2 to 1.0 mg/dL
Aspirin present, then continue
until ESR and PT:10-13.5 Sec
aspirin until resolves
platelet count APTT:26-42 Sec
normalise. INR:<1.5
Dipyridamole
Blood Pressure
(Alternative for 3- 5 mg/kg daily.
Heart Rate
Aspirin)
Additional treatment
(Not responding to primary treatment. Persistent or recrudescent fever ≥ 36hrs after
completion of initial dose of IV Immunoglobulins)
IV Immunoglobulins 2 Gm/kg infusion over 10 - 12 hours
Special Consideration regarding vaccinations Paediatric Pharmacy

: The use may impair 93
Services Guideline
of Immunoglobulins
efficacy of live-attenuated virus vaccines. Delay these vaccinations for at least 11 months.
General Pediatrics
Special Consideration regarding vaccinations : The use of Immunoglobulins may

impair efficacy of live-attenuated virus vaccines. Delay these vaccinations for at
3.0
least 11 months.
References :
1. Best Practice - Kawasaki Disease, Ian K Maconochie, Arch Dis Child Educ
Pract Ed 2004;89:ep3–ep8. doi: 10.1136/adc.2004.053728
2. Paediatric Protocol for Malaysian Hospitals, 3rd Edition
3. Risk factors for refractory Kawasaki disease, Maria Cristina Maggio*,

Eugenia Prinzi, Giovanni Corsello, 21st European Pediatric Rheumatology
(PReS) Congress, Belgrade, Serbia Pediatric Rheumatology 2014, 12(Suppl
1):P359 http://www.ped-rheum.com/content/12/S1/P359

General Pediatrics
CARDIOVASCULAR
3.0
Rheumatic Heart Disease
Introduction
Acute Rheumatic Fever
• Acute Rheumatic Fever (ARF) is an illness caused by a reaction to a bacterial

infection with group A streptococcus (Streptococcus pyogenes)1.
• It causes an acute, generalised inflammatory response and an illness that
targets specific parts of the body, including the heart, joints, brain and skin2.
• Individuals with ARF are often unwell, have significant joint pain and require
hospitalisation. Despite the dramatic nature of the acute episode, ARF typically
leaves no lasting damage to the brain, joints or skin, but can cause persisting
heart damage, termed ‘rheumatic heart disease’ (RHD)2.
Rheumatic Heart Disease
• Rheumatic Heart Disease(RHD) is damage to the heart that remains after

the acute ARF episode has resolved. It is caused by an episode or recurrent
episodes of ARF, where the heart has become inflamed; the heart valves
remain stretched and/or scarred, and normal blood flow is interrupted.
• Recurrences of ARF may cause further valve damage, leading to worsening of RHD.
• Preventing recurrences of ARF by using prophylactic treatment with penicillin
is therefore of great importance in controlling RHD.
• Peak incidence 5 to 15 years old; more common in females1.

General Pediatrics
Management1
3.0
Aim to suppress inflammatory response so as to minimize cardiac damage,

provide symptomatic relief and eradicate pharyngeal streptococcal damage,
provide symptomatic relief and eradicate pharyngeal streptococcal infection.
• Bed rest. Restrict activity until acute phase reactants return to normal.
• Anti-streptococcal therapy:
IV C.Penicilline 50 000iu/kg/dose 6H or Oral Penicillin V 250mg 6H (<30kg),
500mg 6H (>30kg) x 10/7.
Oral Erythromycin x 10/7 if allergic to penicillin.
• Anti-inflammatory therapy:
Mild/no carditis:
Oral aspirin 80-100mg/kg/day in 4 doses fr 2-4 weeks, tapering over 4 weeks.
Pericarditis, or moderate to severe carditis :
Oral Prednisolone 2mg/kg/day in 2 divided doses for 2-4 weeks, taper with
addition of aspirin as above.
• Anti-failure medications:
Diuretics, ACE inhibitors, digoxin (to be used with caution).
Secondary Prophylaxis of Rheumatic Fever1

• IM Benzathine Penicillin 6 MU (<30 kg) or 1.2 MU (>30kg) every 3 to 4 weeks.
OR
• Oral Penicillin V 250mg BD
OR
• Oral Erythromycin 250mg BD if allergic to penicillin.
Duration of Prophylaxis1
• Until age 21 years or 5 years after last attack of ARF whichever was longer.
• Lifelong for patients with carditis and valvular involvement.

General Pediatrics
3.0
References:

2013. Chapter 38, Acute Rheumatic Failure; p.185-6.
2. RHDAustralia. Management of Rheumatic Heart Disease. Ch.5. 2nd Ed.

Paediatric Icu
4.0
4.0 Paediatric ICU

PAEDIATRIC ICU
FLUID & ELECTROLYTE MANAGEMENT
4.0
Fluid Management
Introduction
Fluid can be administered through parenteral or enteral (oral) route; however,

enteral route should be used wherever possible. Fluids are given through parenteral
route for resuscitation, maintenance of daily requirement, and replacement of fluid
deficit or abnormal losses such as severe dehydration due to excessive vomiting.
Resuscitation
Fluid boluses of 10-20ml/kg should be used during resuscitation to restore

circulation. Repeated fluid boluses may be necessary to correct the hypovolemia
after re-assessment. Crystalloids (normal saline, Ringer’s Lactate, Hartmann’s
solution) and colloids (albumin, gelatin, and blood) can be used during fluid
resuscitation. The volume and choice of fluid should be appropriate to patient’s
cause of circulatory collapse. If patient’s blood glucose is low, 2ml/kg of 10%
dextrose solution can be given1.
Maintenance
Maintenance fluid is the volume of fluid required daily to replace the ongoing
losses, including both sensible (urine and stool) and insensible losses (evaporative
and respiratory). Children experience greater fluid loss because children have
larger body surface area and higher metabolic and respiratory rate compared to
adult; thus requiring higher maintenance fluid2. Clinical conditions and illnesses
(eg. meningitis, pneumonia. fever, burn or diarrhea) may affect the fluid loss;
therefore the requirement should be individualized.
Holliday-Segar method is very commonly used for calculating maintenance fluid

requirement and estimating the infusion rate (ml/hour) in children. It is however,
only applicable to children above 2 weeks old3.

Children experience greater fluid loss because children have larger body surface area and
higher metabolic and respiratory rate compared to adult; thus requiring higher maintenance
fluid2. Clinical conditions and illnesses (eg. meningitis, pneumonia. fever, burn or diarrhea)
Paediatric Icu
may affect the fluid loss; therefore the requirement should be individualized.
Holliday-Segar method is very commonly used for calculating maintenance fluid requirement
and estimating the infusion rate (ml/hour) in children. It is however, only applicable to
children above 2 weeks old3.
4.0
Table 1: Calculation of maintenance fluid requirement and infusion rate, Holliday-

Segar method3.
Weight Total fluids requirement Infusion rate

First 10kg 100 ml/kg 4 ml/kg/hour
Subsequent 10kg 50 ml/kg 2 ml/kg/hour
All additional kg 20 ml/kg 1 ml/kg/hour
Ideal
Idealbody weightshould
body weight should be used
be used for calculating
for calculating maintenance
maintenance fluidforrequirement
fluid requirement obese or
foroverweight
obese orpatients.
overweight patients.
Deficit
Deficit
Deficit fluid is the volume of fluid that is loss before medical intervention, for instance the
fluid loss in patient with diarrhea, vomiting and significant blood loss. Deficit fluid is usually
administered
Deficit fluid isoverthea period
volume of time depending
of fluid that on
is clinical condition;
loss before however,intervention,
medical generally the
for
instance the fluid loss in patient with diarrhea, vomiting and significant blood loss.
Deficit fluid is usually administered over a period of time depending on clinical
77
condition;
however, generally the total volume is administered over the first 24
hours of hospitalization. Isotonic solution (eg. 0.9% normal saline) should be given
in replacement of deficit.
Total deficit volume to be replaced (ml) = Weight (kg) x degree of dehydration (%) x 10
Infusion rate/hour = Total deficit volume to be replaced / hour of infusion
Monitor daily electrolytes, fluid input and output and weight (if feasible) for all
children on IV fluids.

0.9% normal saline) should be given in replacement of deficit.
PAEDIATRIC ICU
Total deficit volume to be replaced (ml) = Weight (kg) x degree of dehydration (%) x 10
Infusion rate/hour = Total deficit volume to be replaced / hour of infusion
Monitor daily electrolytes, fluid input and output and weight (if feasible) for all children on IV
fluids.
4.0
Table 2: Commonly used intravenous fluids4,5
Tonicity
(with
Na+ Cl- Osmolality
Fluid kcal/l reference Uses
(mmol/l) (mmol/l) (mOsm/l)
to cell
membrane)
Dextrose 5% - - 200 278 Hypotonic Maintenance
Hypoglycemia
Dextrose 10% - - 400 555 Hypotonic
correction
Initial
resuscitation
Hartmann’s and used
131 111 0 278 Isotonic
solution intra- and
post-
operatively
0.45% NaCl 77 77 0 154 Hypotonic Maintenance
Initial
resuscitation
0.9% NaCl 150 150 0 308 Isotonic
and
maintenance
Sodium
3% NaCl 513 513 0 1026 Hypertonic
replacement
0.18% NaCl
with 4.23% 31 31 170 296 Hypotonic Maintenance
Glucose
0.18% NaCl
with 10% 30 30 400 615 Hypotonic Maintenance
Glucose
0.45% NaCl
with 5% 77 77 200 432 Hypotonic Maintenance
Glucose
0.9% NaCl
with 5% 150 150 200 585 Isotonic Maintenance
Glucose
Electrolyte Management
Table 3: Normal range and daily requirement of electrolytes6.
Electrolytes Normal range Daily requirement

Sodium 135-145 mmol/l 2-5 mmol/kg/day
Potassium 3.5-5.0 mmol/ l 2-4 mmol/kg/day
Calcium 2.1-2.6 mmol/l 0.25-2 mmol/kg/day
78


Paediatric Icu
Electrolyte Management
4.0
Table 3: Normal range and daily requirement of electrolytes6.
Electrolytes Normal range Daily requirement
Sodium 135-145 mmol/l 2-5 mmol/kg/day
Potassium 3.5-5.0 mmol/ l 2-4 mmol/kg/day
Calcium 2.1-2.6 mmol/l 0.25-2 mmol/kg/day
Magnesium 0.75-1.1 mmol/l 0.15-0.25 mmol/kg/day
Phosphate 1.3-2.3 mmol/l 0.5-2 mmol/kg/day
Management of Common Electrolyte Abnormalities
• Hyponatremia
Hyponatremia is defined as serum sodium < 135mmol/l, which can be due

to severe dehydration or dilutional from fluid overload. Signs and symptoms of
hyponatremia include headache, nausea/vomiting, lethargy, and neurological
involvement such as altered consciousness and seizure. Encephalopathy is a
very serious complication of hyponatremia, which can cause poor neurological
outcome and even death if not detected early and treated promptly and
adequately. A bolus of 4 ml/kg of 3% sodium chloride administered over 15-30
minutes will raise the serum sodium by 3 mmol/l and usually could cease the
hyponatremic seizure. Subsequent 3% saline boluses may be required if there
are ongoing seizures or persistent hyponatremia7. Thereafter, sodium should be
corrected gradually at a rate of not more than 8 mmol/l over 24 hours because
rapid correction may cause irreversible cerebral demyelination8.
Sodium required for correction in acute hyponatremia (mmol)9
= (Desired serum Na – present Na level) x 0.6 x weight(kg)
Depending on the hydration status of the child, 0.9% sodium chloride and 3%
sodium chloride solutions can be used for sodium correction. Hyponatremia
without symptom can be treated with enteral fluids or 0.9% sodium chloride.
Frequent serum sodium should be checked (every 1-2 hours) until patient is
stable, subsequently every 4-6 hours until serum sodium normalize.

PAEDIATRIC ICU
• Hypernatremia
4.0
Hypernatremia is defined as serum sodium > 145 mmol/l, which can be due to
water loss in excess of sodium, water deficit or excess sodium gain. Symptoms
usually occur when there is severe hypernatremia, that is when the serum
Na+ > 160 mmol/l. Signs and symptoms include nausea/vomiting, irritability,
restlessness, lethargy, anorexia, tremor, and may also lead to subarachnoid
hemorrhage and coma. Management will depend on severity and the cause of
hypernatremia. Lowering sodium slowly at a rate not more than 0.5 mmol/l/hr
because rapid correction can cause cerebral edema, convulsion, and death.
However, for patient in shock, resuscitation with 20ml/kg of 0.9% sodium chloride
boluses is required7. In contrast, if the hypernatremia is caused by water deficit
due to central diabetes insipidus, vasopressin can be used. Monitor the serum
sodium every 6 hours until patient stabilize.
• Hypokalemia
Hypokalemia is defined as serum potassium < 3.5mmol/l. Signs and symptoms

of hypokalemia include generalized muscle weakness, paralytic ileus, cardiac
arrhythmias, ECG changes, confusion, and impaired respiratory function. The
common causes of hypokalemia are excess loss from renal or gastrointestinal
tract; other causes include diabetic ketoacidosis, sepsis, and iatrogenic. Identify
and treat the underlying cause, and correct hypokalemia in patient with serum
potassium < 3.0mmol/l or clinically symptomatic patient with potassium < 3.4
mmol/l, either using potassium chloride (oral or IV infusion) or IV potassium
dihydrogen phosphate
Table 4: Potassium chloride administration10,11

Preferred Maximum
Concentration of 40mmol/l 60-80 mmol/l (peripheral)*
infusion 200mmol/l (central)*
< 0.2 mmol/kg/hr
Rate of infusion (peripheral) 1 mmol/kg/hr*
< 0.4 mmol/kg/hr (central)
Footnote - * Infusion at concentration and rate higher than the preferred range
should be used only after discussion with specialist / senior medical staff and in
intensive care setting

Paediatric Icu
4.0
• Hyperkalemia
Hyperkalemia is defined as serum potassium > 5.5mmol/l. Hyperkalemia may

be presented with muscles weakness, ileus, paresthesia or palpitation. Causes
are dehydration, acute renal failure, diabetic ketoacidosis, hypoaldosteronism,
tumour lysis syndrome and atrogenic. Underlying cause need to be identified and
treated accordingly.
Table 5: Drugs used in treatment of hyperkalemia1,7,12
Drugs Dosage Onset Duration

Nebulized ≤ 2.5 yrs : 2.5mg;
2.5-7.5 yrs: 5mg; 30 mins 2-3 hrs
salbutamol
>7.5 yrs: 10mg
IV calcium 0.5-1.0 ml/kg (max 20 ml)

(1:1 dilution) over 5-15 mins <3 mins ~30 mins
gluconate
IV dextrose 0.5g/kg (2mls/kg of 25%)

over 15-30 mins peak 60 mins,
15 mins 2-3 hrs
IV insulin short
0.1 unit/kg
action
IV 8.4% sodium 1ml/kg (1:1 dilution) over

10-30 mins 30-60 mins 2-3 hrs
bicarbonate
PO/PR calcium
0.25g/kg (max 10g/dose) 4 4-6 hrs (PO), variable
polystyrene
times /day 1hr (PR)
sulphonate

PAEDIATRIC ICU
Hyperkalemia (K+.5.5 mmol/l)
4.0
Stop all K+ Supplementation
Stop medications causing hyperkalemia
Cardiac monitoring
Exclude pseudo hyperkalemia
Recheck with venous sample
Child unstable Child stable Child stable

or symptomatic asymptomatic asymptomatic
Abnormal Normal ECG Normal ECG

+>
5.5, < 6 mmol/l
+ +
K > 7 mmol/l K > 6, < 7 mmol/l K
Discuss for dialysis Discuss for dialysis Discuss for dialysis
IV Calcium (0.1 mmol/kg) IV Insulin with glucose + Neb Salbutamol
Neb Salbutamol
+ IV Bicarbonate if acidosis + IV Bicarbonate if acidosis
( <2.5 yrs; 2.5-7.5 yrs:
5mg; >7.5yrs: 10mg)
IV Bicarbonate (1-2mmol/kg) + PR/PO Resonium + PR/PO Resonium
Algorithm 1: Hyperkalemia treatment1
References:

Malaysia; 2013. Chapter 3, Paediatric Fluid and Electrolyte Guidelines;
p.19-26.

Malaysia; 2013. Chapter 60, Acute Kidney Injury; p.285-291.
3. Meyers R. Pediatric fluid and electrolyte therapy. The Journal of Pediatric

Pharmacology and Therapeutics 2009 Oct-Dec; 14(4):204-211

Paediatric Icu
4. Holliday MA, Segar WE. The maintenance need for water in parenteral fluid
therapy. Pediatrics 1957;19:823-832
4.0
5. Terris M, Crean P. Fluid and electrolyte balance in children. Anaesthesia and

intensive care medicine. Elsevier. 2011; 13(1): 15-19
6. Product labels:
a) INFUSOL® D5. Ain Medicare Sdn. Bhd.
b) INFUSOL® D10. Ain Medicare Sdn. Bhd
c) INFUSOL® HM. Ain Medicare Sdn. Bhd.
d) INFUSOL® HS. Ain Medicare Sdn. Bhd.
e) INFUSOL® NS. Ain Medicare Sdn. Bhd.
f) INFUSOL® S3. Ain Medicare Sdn. Bhd.
g) INFUSOL® QSD10. Ain Medicare Sdn. Bhd.
h) INFUSOL® QSD10. Ain Medicare Sdn. Bhd.
i) 0.45% Sodium Chloride And 5% Glucose Intravenous Infusion
B.P. B. Braun Medical Industries S/B.
j) INFUSOL® NSD5. Ain Medicare Sdn. Bhd.
7. The ASPEN Nutrition Support Manual, 2nd Edition, American Society for
Parenteral and Enteral Nutrition; 2005.
8. Clinical practice guidelines: Intravenous fluids. The Royal Children’s Hospital

Melbourne, Australia.
9. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia.

Seminars in Nephrology. 2009; 29:282–299
10. Farrell C, Del Rio M. Hyponatremia. Pediatrics in Review. 2007; 28:426-428.
11. Micromedex Healthcare Series. DRUGDEX System. Truven Health

Analytics Inc. Vol. 163
12. Paediatric Formulary Committee. British National Formulary for Children

2011-2012. London and Chicago: BMJ Pub. Group, RPS Pub., RCPCH
Pub.; 2011.

PAEDIATRIC ICU
NUTRITION IN CRITICALLY ILL PATIENTS
4.0
Introduction
Critically ill children have a high risk of malnutrition because of stress-induced

changes in intermediary metabolism; these changes are characterized by an
increased basal metabolic rate and intensive protein catabolism. In general, the
development or perpetuation of malnutrition during hospitalization in the paediatric
intensive care unit (PICU) is due to illness, unknown nutrition condition, and an
inadequate supply of nutrients. In these patients, malnutrition is associated with
physiological instability. As a result, more intensive clinical care is required, and
the mortality rate is high4.
Nutrition therapy is indicated when a patient is unable to receive calories and

nutrients orally for a long period of time. Enteral nutrition (EN) is preferred because it
is more physiologic, promotes intestinal trophism, stimulates the immune system,
and reduces the incidence of bacterial translocation and sepsis. However, when
it is impossible to use the digestive tract, parenteral nutrition (PN) is the only
alternative for ensuring an adequate supply of nutrients during hospitalization.
The combination of EN and PN may be useful for the first 72 hours of intensive
clinical car or when EN alone is not sufficient to meet the nutrition demands of
the patient4.
Recommendation from ASPEN for nutrition support of the critically ill child is list in
Table 1. While Table 2 – 9 are the total daily requirement for paediatric.
Complications of PN
Complications may be considered in 3 groups: central venous catheter (CVC)

related stability of the PN solutions and interactions with added drugs, metabolic
or nutritional and other organ systems.
CVC related complications include infection, occlusion, central venous

thrombosis, pulmonary embolism and accidental removal or damage1.
Metabolic or nutritional complications include deficiency or excess of individual

PN components including electrolytes, mineral, glucose, essential fatty acids,
vitamin, trace element and the presence of contaminants1.

Paediatric Icu
4.0
Other organ systems may be affected by the PN solutions, the underlying disease
process or both. Complications include hepatobiliary disease, metabolic bone
disease and growth impairment, some of which may be life threatening and raise
the need for other therapeutic interventions such as non-transplant surgery or
small bowel and liver transplantation1.
Monitoring of PN
Severe investigations are required such as full blood count, renal profile, dextrostix,
liver function test and lipid profile to monitor the complications of PN.

PAEDIATRIC ICU
4.0
Table 1: ASPEN guidelines: Nutrition Support of the Critically Ill Child 20092.
Aspect Guideline recommendations Grade

Children admitted with critical illness should undergo nutrition
screening to identify those with existing malnutrition and those D
Nutrition who are nutritionally-at-risk
assessment A formal nutrition assessment with the development of a nutrition
care plan should be required, especially in those children with E
premorbid malnutrition
Energy expenditure should be assessed throughout the course
of illness to determine the energy needs of critically ill children.
D
Estimates of energy expenditure using available standard
equations are often unreliable.
IN a subgroup of patients with suspected metabolic alterations or
Energy
malnutrition, accurate measurement of energy expenditure using
requirement
indirect calorimetry (IC) is desirable. If IC is not feasible or not
available, initial energy provision may be based on published E
formulas or namograms. Attention to imbalance between energy
intake and expenditure will help to prevent overfeeding and
underfeeding in this population.
There are insufficient data o make evidence-based
recommendations for macronutrient intake in critically ill children.
Macronutrient
After determination of energy needs for critically ill child, the
intake during E
rational partitioning of the major substrates should be based
critical illness
upon understanding of protein metabolism and carbohydrate-
and lipid- handling during critical illness
In critically ill children with a functioning gastrointestinal tract,
enteral nutrition (EN) should be the preferred mode of nutrient C
provision, if tolerated.
A variety of barriers to EN exist in the paediatric intensive care
unit (PICU), clinicians must identify and prevent avoidable D
Route of nutrient
interruptions to EN in critically ill children.
intake (enteral
There are insufficient data to recommend the appropriate site
nutrition)
(gastric vs post-pyloric/transpyloric) for enteral feeding in
critically ill children. Post-pyloric or transpyloric feeding may
C
improve caloric intake when compared to gastric feeds. Post-
pyloric feeding may be considered in children at high risk of
aspiration or those who have failed a trail of gastric feeding.
Based on the available paediatric data, the routine use of
Immunonutrition
immunonutrition or immune-enhancing diets/nutrients in critically D
in the PICU
ill children is not recommended.
A specialized nutrition support team in the PICU and aggressive
Nutrition support
feeding protocols may enhance the overall delivery of nutrition,
team and
with shorter time to goal nutrition, increased delivery of EN, and E
feeding
decreased use of parenteral nutrition. The effect of these
protocols
strategies on patient outcomes has not been demonstrated.
Paediatric Pharmacy Services Guideline 85 109

Paediatric Icu
4.0
Table 2: Total Daily Fluid Requirement1,3.
Total daily fluid required (ml/kg/day)

Weight
ASPEN ESPEN
< 1.5kg 130 – 150
1.5-2kg 110 – 130 100
2-10kg 100
Subsequent 10kgs 50 50
All subsequent additional kgs 20 20
Table 3: Total Daily Energy Requirement1,3.
Total daily energy required (kcal/kg/day)

Age
ASPEN ESPEN
<6 months old 85 - 105
90 - 100
6-12 months old 80 - 100
1-7 years old 75 – 90 75 - 90
7-12 years old 50 – 75 60 - 75
> 12-18 years old 30 – 50 30 - 60
Table 4: Total Daily Protein Requirement1,3.
Total daily protein required (g/kg/day)

Age
ASPEN ESPEN
Infants 2–3
1 - 2.5
Child 1-3 years old
1–2
Child 3-10 years old
1-2
Adolescent 11-17 years old 0.8 - 1.5
Table 5: Total Daily Lipid Requirement1.
Total daily lipid required

Age (g/kg/day)
ESPEN
Infants 3
Child 1-10 years old 2–3
Child >10 years old 1 - 2.5
Table 6: Total Daily Carbohydrate Requirement1.
Total daily carbohydrate

Age required (mg/kg/min)
ESPEN
Infants 10 – 12
Child 1-10 years old 8 – 10
Child >10 years old 5–6
110 Paediatric Pharmacy Services Guideline 86

PAEDIATRIC ICU
4.0
Table 7: Total Daily Electrolyte and Mineral Requirement1,3.
ASPEN (mmol/kg/day) ESPEN (mmol/kg/day)

Electrolyte Adolescent / Child >1
Infants/children Infants
child >50kg years old
Sodium 2-5 1–2 2–3 1-3
Potassium 2-4 1–2 1–3 1-3
0-6 7-12
Calcium 0.25 - 2 5 - 10 months months 0.2
old: 0.8 old: 0.5
Phosphorus 0.5 - 2 10 - 40 0.5 0.2
Magnesium 0.15 - 0.25 5 - 15 0.2 0.1
As needed to maintain acid-base As needed to maintain acid-base
Acetate
balance balance
As needed to maintain acid-base As needed to maintain acid-base
Chloride
balance balance
Table 8: Total Daily Trace Elemental Requirement1,3.
ASPEN ESPEN
Adolescent
Trace
Infants Children or child Infants Children
elemental
(mcg/kg/day) (mcg/kg/day) >40kg (mcg/kg/day) (mcg/kg/day)
(per day)
<3 >3
50
months months
Zinc 50 - 250 50 - 125 2 - 5mg (maximum
old: old:
5mg/day)
250 100
200 -
Copper 20 5 - 20 20 20
500mcg
1
40 -
Manganese 1 1 1 (maximum
100mcg
50mcg/day)
0.2
Chromium 0.2 0.14 - 0.2 5 - 15mcg 0.2 (Maximum
5mcg/kg/day)
Selenium 2 1-2 40 - 60mcg 2–3 2-3
87

Paediatric Icu
Table 9: Total Daily Vitamin Requirement1,3.
ASPEN ESPEN
4.0
Vitamin Infants
1-3 kg > 3kg Children
(dose/body
(dose/day) (dose/day) (dose/day)
weight/day)
Vitamin A 450 690 150 – 300 150
(mcg)*
Vitamin D (IU) 260 (6.5mcg) 400 (10mcg) 32 (0.8mcg) 400 (10mcg)
Vitamin E 4.1 (4.5IU) 6.3 (7IU) 2.8 - 3.5 7 (7.7IU)
(mg) (3.1-3.9IU)
Vitamin K 130 200 10 200
(mcg)
Ascorbic acid 52 80 15 – 25 80
(mg)
Thiamine 0.78 1.2 0.35 - 0.5 1.2
(mg)
Riboflavin 0.91 1.4 0.15 - 0.2 1.4
(mg)
Niacin (mg) 11.05 17 4 - 6.8 17
Pantothenic 3.25 5 1–2 5
acid (mg)
Pyridoxine 0.65 1 0.15 – 2 1
(mg)
B12 mcg) 0.65 1 0.3 1
Biotin (mcg) 13 20 5–8 20
Folic acid 91 140 56 140
(mcg)
*1 mcg RE (retinol equivalent) = 1 mcg all-trans retinol =3.33 IU Vitamin A
References :
REFERENCES:
1) Koletzko
1) Koletzko B, B,Goulet
Goulet O, Hunt
O, Hunt J, Krohn
J, Krohn K, R.
K, Shamir Shamir R. on
Guideline Guideline
Paediatricon Paediatric
Parenteral
Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and
Parenteral Nutrition of the European Society of Paediatric Gastroenterology,
Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism
Hepatology and Nutrition
(ESPEN), Supported (ESPGHAN)
by the European and
Society of the European
Paediatric SocietyJ for
Research (ESPR). Clinical
Pediatr
Gastroenterol
Nutrition andNutr. 2005;41(2):S1-S87
Metabolism (ESPEN), Supported by the European Society of
2) Paediatric
Mehta NM, Research
Compher C,(ESPR).
A.S.P.E.NJ Board
Pediatr
of Gastroenterol Nutr.Clinical
Directors. A.S.P.E.N. 2005;41(2):S1-S87
Guidelines:
Nutrition Support of the Critically Ill Child. Journal of Parenteral and Enteral Nutrition.
2) Mehta NM, Compher C, A.S.P.E.N Board of Directors. A.S.P.E.N. Clinical
2009;33(3):260-276.
Guidelines: Nutrition Support of the Critically Ill Child. Journal of Parenteral
3) Mirtallo J, Canada T, Johnson D, Kumpf V, Petersen C, Sacks G, Seres D, Guenter P.
andSafeEnteral
PracticesNutrition. 2009;33(3):260-276.
for Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2004;28(6):S39-
S70.
3) Mirtallo J, Canada T, Johnson D, Kumpf V, Petersen C, Sacks G, Seres D,
Guenter
4) ZamberlanP.P,Safe Practices
Delgado AF, Leonefor C,
Parenteral
FeferbaumNutrition. JPEN
R, Okay TS. J Parenter
Nutrition Therapy Enteral
in a
Pedaitric Intensive Care Unit: Indications, Monitoring and Complications. Journal of
Nutr. 2004;28(6):S39-S70.
Parenteral and Enteral Nutrition. 2011;35(4):523-529
4) Zamberlan P, Delgado AF, Leone C, Feferbaum R, Okay TS. Nutrition Therapy88
in a Pedaitric Intensive Care Unit: Indications, Monitoring and Complications.
Journal of Parenteral and Enteral Nutrition. 2011;35(4):523-529

PAEDIATRIC ICU
Shock Management
4.0
Introduction
Shock is a physiologic state characterized by a significant, systemic reduction

in tissue perfusion; resulting in decreased tissue oxygen delivery and diminished
removal of harmful by-products of metabolism (eg, lactate). Children with
compromised circulation must be identified promptly. Successful management
requires rapid initiation of treatment (often before the cause of shock is apparent)
and careful assessment of the response to each intervention. Specific therapy
must be initiated as soon as the evaluation suggests a cause of shock. Most
children will improve with fluid resuscitation. Those who do not must quickly
receive more aggressive treatment. According to Paediatric Advanced Life
Support (PALS) course, shock is further classified into the following stages:
• Compensated shock – During compensated shock, the body’s homeostatic

mechanisms rapidly compensate for diminished perfusion and systolic blood
pressure is maintained within the normal range. Heart rate is initially increased.
Signs of peripheral vasoconstriction (such as cool skin, decreased peripheral
pulses, and oliguria) can be noted as perfusion becomes further compromised5.
• Decompensated shock – During this stage, compensatory mechanisms are

overwhelmed. Heart rate is markedly elevated and hypotension develops. Signs
and symptoms of organ dysfunction (such as altered mental status as the result
of poor brain perfusion) appear. Systolic blood pressure falls, although children
who have lost as much as 30 to 35 percent of circulating blood volume can
typically maintain normal systolic blood pressures. Once hypotension develops,
the child’s condition usually deteriorates rapidly to cardiovascular collapse and
cardiac arrest5.
• Irreversible shock – During this stage, progressive end-organ dysfunction

leads to irreversible organ damage and death. Tachycardia may be replaced
by bradycardia and blood pressure becomes very low. The process is often
irreversible, despite resuscitative efforts5.
In addition to these stages of shock, three broad mechanisms of shock are

recognized: hypovolemic, distributive, and cardiogenic. Each type is characterized

Paediatric Icu
by one primary physiologic derangement in table 1.

4.0
However, a patient may have more than one type of shock (such as an infant with
cardiogenic shock from supraventricular tachycardia who is also hypovolemic
because he has been unable to drink or a child with underlying cardiomyopathy
who is septic)5.
Table 1: Hemodynamic profiles of the types of shock5.
Physiologic Pump Tissue

Preload Afterload
variable function perfusion
Pulmonary
Systemic Mixed venous
Clinical capillary Cardiac Examples
vascular oxygen
measurement wedge Output
resistance saturation
pressure
haemorrhage,
gastrointestinal
Hypovolemic ↓ ↓ ↑ ↓ losses, insensible
losses (e.g., burns),
or third spacing
sepsis, anaphylaxis,
Cardiogenic ↑ ↓ ↑ ↓ or acute injury to the
spinal cord or brain
primary myocardial
injury, arrhythmias,
congenital heart
disease, or acquired
obstructive
Distributive ↓ or ↔ ↑ ↓ ↑
conditions (eg,
pneumothorax,
cardiac tamponade,
or pulmonary
embolism)
Disease management
Disease management
Initial management should focus on fluid resuscitation with isotonic crystalloid solution and
specific pharmacologic therapies as indicated once the aetiology of shock is identified. The
Initial management
following algorithm forshould
initiatingfocus on fluid resuscitation
and re-evaluating therapy once shockwithisisotonic
recognizedcrystalloid
has
solution and specific
been adapted pharmacologic
from consensus therapies
recommendations as management
for the indicated once theshock
of septic aetiology
in of
children which were based primarily upon evidence extrapolated from adult studies5.
shock is identified. The following algorithm for initiating and re-evaluating therapy
once shock agents
Vasoactive is recognized has for
may be useful been adapted
children from(other
with shock consensus recommendations
than hypovolemic shock)
for who have not improved
the management with initial
of septic shock fluid inresuscitation.
children whichThesewere
agents have primarily
based effects on upon
myocardial contractility, heart rate, and vasculature 5 that can improve cardiac output.
evidence
Initiation extrapolated fromprior
of vasoactive agents adult
to orstudies
in place of. adequately fluid resuscitating the patient,
regardless of the etiology of shock, may lead to end-organ ischemia. Furthermore, these
agents should be avoided in children with hypovolemic shock5.
Drugs that are typically used during the initial management of children with shock include
dopamine , epinephrine , norepinephrine, dobutamine , and phosphodiesterase enzyme
114
inhibitors. The choice
Paediatric of agent
Pharmacy depends
Services on the pathophysiologic parameters that must be
Guideline
manipulated5.
PAEDIATRIC ICU
Vasoactive agents may be useful for children with shock (other than hypovolemic
shock) who have not improved with initial fluid resuscitation. These agents have
effects on myocardial contractility, heart rate, and vasculature that can improve
4.0
cardiac output. Initiation of vasoactive agents prior to or in place of adequately
fluid resuscitating the patient, regardless of the etiology of shock, may lead to
end-organ ischemia. Furthermore, these agents should be avoided in children
with hypovolemic shock5.
Drugs that are typically used during the initial management of children with
shock include dopamine , epinephrine , norepinephrine, dobutamine , and
phosphodiesterase enzyme inhibitors. The choice of agent depends on the
pathophysiologic parameters that must be manipulated5.
FIGURE 1: Algorithm for time sensitive, goal-directed stepwise management of hemodynamic support
in infants and children. Proceed to next step if shock persists. 1) First hour goals—Restore and maintain
heart rate thresholds, capillary refill ≤ 2 sec, and normal blood pressure in the first hour/emergency
department. Support oxygenation and ventilation as appropriate. 2) Subsequent intensive care unit
goals—If shock is not reversed, intervene to restore and maintain normal perfusion pressure (mean
arterial pressure [MAP]-central venous pressure [CVP]) for age, central venous O2 saturation >70%, and
CI >3.3, <6.0 L/min/m2 in pediatric intensive care unit (PICU). Hgb, hemoglobin; PICCO, pulse contour
cardiac output; FATD, femoral arterial thermodilution; ECMO, extracorporeal membrane oxygenation;
CI, cardiac index; CRRT, continuous renal replacement therapy; IV, intravenous; IO, interosseous; IM,
intramuscular1.

4.0 Paediatric Icu
Table 2: Inotropes & Vasopressors3,5

Inotropes Dose MOA Heart rate Systolic Diastolic Myocardial O2 SVR PVR
function function demand
Dopamine 1-5mcg/kg/min Dopamingergic Increase Minimal No effect Minimal Minimal No effect
agonist effect increase increase
6-10mcg/kg/min β1 agonist Increase Increase No effect Increase Increase Minimal
increase
11-20mcg/kg/min α agonist Increase Increase No effect Increase Significant Minimal
increase increase
Notes: The effect of dopamine is dose-dependent. At low doses, it stimulates the heart and improves renal blood flow. At higher doses, it
causes vasoconstriction and increases systemic vascular resistance (SVR). In most situations, dopamine should be used first when vasoactive infusions
are required to treat shock that has not responded to fluid administration.
Dobutamine 1-10mcg/kg/min β1 agonist, Increase Increase No effect Increase Decrease Minimal
α anti-agonist decrease
Notes: Dobutamine increases myocardial contractility and heart rate. It also decreases systemic vascular resistance, which can cause
hypotension. It is useful for patients with decreased myocardial function who are normotensive.
Epinephrine 0.01-1mcg/kg/min β1 agonist > α Increase Significant No effect Significant Increase Minimal

agonist increase increase increase
Notes: Epinephrine stimulates the heart and is a potent vasoconstrictor. It also relaxes bronchial smooth muscle. It is typically used for
patients with anaphylaxis or those who do not respond to dopamine, particularly those with septic shock and increased SVR (cold
shock).
Norepinephrine 0.01-1mcg/kg/min β1 agonist < α Increase Some No effect Increase Significant Minimal
agonist increase increase increase
Notes: Like epinephrine, norepinephrine stimulates the heart and causes vasoconstriction. Vasoconstrictive effects are usually greater
than the effects on contractility and heart rate. It can be used for children who do not respond to dopamine and is preferred over
epinephrine by some experts for those patients with sepsis and decreased SVR (warm shock).
Milrinone 0.1-1mcg/kg/min Phosphodiesterase No change Increase Improves Minical Increase Decrease Decrease
inhibitor
Notes: Phosphodiesterase enzyme inhibitors (ie, milrinone ) improve cardiac contractility and reduce afterload. They may be used to treat
cardiogenic shock.
Vasopressors
Neosynephrine 0.1-2 mcg/kg/min Pure α agonist No effect No effect No effect No effect Significant No effect
increase
Vasopressin 0.0003-0.008 V receptor agonist No effect No effect No effect No effect Significant Effect
mcg/kg/min increase unknown
92

PAEDIATRIC ICU
Table 3: Shock & Inotropes3
4.0
Shock Infusions to consider Comments
Septic
• Dopamine • Decreased SVR
Early or warm
• Norepinephrine • Increase CO
• Increased SVR
• Dopamine
• Decrease CO
Late or cold • Epinephrine
• ? Decrease in
• Vasopressin
vasopressin levels
Cardiogenic
• Milrinone • Increased SVR
Normotensive
• Dobutamine • Decerase CO
• Epinehrine
• Increased SVR
Hypotensive • Slow addition of Milrinone
• Decrease CO
once BPs improved
• Dopamine • Increased SVR
Hypovolemic
• Epinephrine • Decreased CO
• Dopamine • Increased SVR
Obstructive • Epinephrine • Decreased CO
• Milrinone
• Decreased SVR
Distributive • Neosynephrine
• Normal CO
Children can effectively compensate for circulatory dysfunction (primarily by

increasing heart rate, systemic vascular resistance, and venous tone), maintaining
normal blood pressures despite significantly compromised tissue perfusion.
Consequently, hypotension is a very late and ominous finding. The challenge
for the clinician is to recognize children in shock early (before they develop
hypotension), when they are more likely to respond favorably to treatment5.
Paediatric inotropic therapy has been furnished with some new understanding of
older agents, and new ways of using them. Some agents are gaining an evidence
base, whilst even newer agents need such a base. Guidelines are emerging to
facilitate their use2.

Paediatric Icu
4.0
References:
1. Brierley J, Carcillo J.A., Choong K, Cornell T, DeCaen A, Deymann A, et al.

Clinical practice parameters for hemodynamic support of pediatric and
neonatal septic shock: 2007 update from the American College of Critical
Care Medicine. Crit Care Med, 2009: Vol. 37, No. 2: 666-688.
2. Clifford M. Inotropes in Children. Australasian Anaesthesia. 2005;pg 129-134
3. Kache S. Sanford PICU Rotation Guide. [Internet]. Stanford School of

Medicine.
Available from: http://peds.stanford.edu/Rotations/picu/pdfs/15_inotropes_
tables.pdf accessed 08/09/2014
4. Waltzman M. Initial management of shock in children. Up to date, 2013

[updated 2013 Apr 4]. Available from http://www.uptodate.com/contents/
initial-management-of-shock-in-children
5. Waltzman M. Initial evaluation of shock in children. Up to date, 2013 [updated:

2013 Jan 7]. Available from http://www.uptodate.com/contents/initial-
evaluation-of--shock-in-children.`

PAEDIATRIC ICU
Neuromuscular Blockade
4.0
Introduction
Neuromuscular blocking agents (NMBAs) are used in critically ill children for a
variety of reasons. The main indications for the use of NMBAs are based on the
optimization of immobility of the patient for procedures like:
• Short term (less than 6 hours)

1. Tracheal intubation
2. High-risk invasive procedures
• Long term (more than 6 hours)

1. Synchrony with mechanical ventilation (dyssynchrony, excessive
hyperventilation or hypoventilation, nonconventional ventilation)
2. Reduction of metabolic demand or work of breathing
3. Treatment of intense agitation unresponsive to higher doses of analgesia
and sedation
4. Therapeutic hypothermia (decreased shivering)
5. Protection of surgical repairs
It is important to remember that in all these indications, the use of NMBAs should
be considered in patients that deep sedation & analgesia have failed to reach
the desired effect1,2,5. The choice of the best NMBA becomes very difficult and
dependent on the degree and necessity of the muscular relaxation desired.
Neuromuscular blocking agents


Paediatric Icu
1) Depolarizing NMBAs
4.0
a. Succinylcholine
Succinylcholine is the only depolarizing NMBA in clinical use. It produces
the most rapid onset and ultra-short duration of neuromuscular block.
Succinylcholine can cause tachycardia, bradycardia, increase in intraocular
pressure, hyperkalaemia, myoglobinaemia, malignant hyperthermia, and even
fatal hyperkalaemia cardiac arrests. Therefore, succinylcholine is restricted to
emergency endotracheal intubation and instances where immediate securing
of the airway such as laryngospasm, difficult airway and full stomach1,2,4,5.
2) Non-depolarizing NMBAs
a. Benzylquinolium e.g. atracurium & cisatracurium

• Atracurium
Atracurium is a bisquaternary benzylquinolinium diester with an intermediate
duration of clinical action. The adverse effect associated with atracurium
relate mainly to histamine release such as macular rash, erythema,
hypotension, tachycardia or bronchospasm. Another adverse effect
of atracurium is dose-related cardiovascular changes. Long term infusions
have been associated with the development of tolerance, necessitating
dose increment1,2,5.
• Cisatracurium
Cisatracurium is an isomer of atracurium. Like atracurium, it is an
intermediate duration NMBAs. The potency of cisatracurium is about 3
times that of atracurium. Increase potency is associated with slower onset
of action which necessitates a relative high dose to achieve reliable
intubating conditions at 2 minutes. Cisatracurium has less propensity for
histamine release and provides greater cardiovascular stability compared
to atracurium2.

PAEDIATRIC ICU
4.0
b. Aminosteroidal compounds e.g. pancuronium, vecuronium & rocuronium
• Pancuronium
Pancuronium is a potent, long-acting, bisquaternary aminosteroid NMBAs
which has vagolytic effect (increase in heart rate of 30-40% and systolic blood
pressure of 10-15%). This vagolytic effect may be an advantage in infants,
in whom bradycardia is highly undesirable, or patients undergoing anaesthesia
with high-dose opiods, which tend to decrease heart rate and blood pressure.
Patients with renal and liver impairment will have prolonged neuromuscular
blockade due to accumulation of pancuronium and its active metabolite5.
• Vecuronium
Vecuronium is a monoquaternary derivative of pancuronium with greater
selectivity of pharmacological profile, a shorter duration of action, less vagolytic
effect and less cumulative properties compared to pancuronium. Same as
pancuronium, vecuronium will prolong the neuromuscular blockade in patients
with renal or liver impairment. Vecuronium is clearly a long-acting NMBA in
newborns and infants, in agreement with its increased residence time in
younger patients1,2.
• Rocuronium
Rocuronium is a desacetoxy analogue of vecuronium with a more rapid onset
of action. Rapid onset is the result of reduced potency, which necessitates
an increase in dose. Rocuronium has minimal cardiovascular effect
(tachycardia at high dose). Like vecuronium, rocuronium is longer
acting in infants than in children; however, rocuronium still retains the
characteristics of an intermediate-acting NMBA in infants. Same as
vecuronium, rocuronium will prolong the neuromuscular blockade in patients
with renal or liver impairment Rocuronium would be an acceptable alternative
to succinylcholine for rapid sequence induction2.
The pharmacological properties and drug-drug interaction of the NMBAs are

listed in Table 1 and Table 2.

4.0 Paediatric Icu
Table 1: Summary of Pharmacological properties of NMBAs1,2,5,6,7.
NMBA Succinylcholine Atracurium Cisatracurium Pancuronium Vecuronium Rocuronium

Infants Infants & child < 2 Infants & child < Infants Infants Rapid
IM: 3-4mg/kg/dose years old 2 years old IV: 0.1mg/kg/dose IV: sequence
IV: 0.3-0.4 IV: every 30-60 min as 0.1mg/kg/dose; intubation
IV: 2mg/kg/dose mg/kg/dose then 0.15mg/kg/dose needed repeat every Children &
then maintain by maintain by 0.3- hour as needed adolescents
0.3-0.6mg/kg/dose 0.4mg/kg/dose; Continuous Continuous infusion: 0.6-
every 5-10 min as repeat doses as infusion: 1- 0.4-0.6mcg/kg/min Continuous 1.2mg/kg/dose
needed needed 4mcg/kg/min infusion: 1-
Children 1.5mcg/kg/min Tracheal
Children > 1 year Continuous Child > 2 years IV: 0.15mg/kg/dose intubation,
old & adolescents infusion: 10- old & every 30-60 min as Child > 1 year surgical
IM: 3-4mg/kg/dose 20mcg/kg/min adolescents needed old & Infants, child,
IV: 0.1- adolescents adolescents
IV: 1mg/kg/dose Child > 2 years old 0.5mg/kg/dose Continuous infusion: IV: IV: 0.45-
then maintain by & adolescents 0.5-1.7mcg/kg/min 0.1mg/kg/dose; 0.6mg/kg/dose

Dose 0.3-0.6mg/kg/dose IV: 0.4- Continuous repeat every initially then
every 5-10 min as 0.5mg/kg/dose infusion: 1- Adolescents & adults hour as needed maintain by
needed then 0.08-0.1 4mcg/kg/min IV: 0.15mg/kg/dose 0.075-
mg/kg/dose 20-45 every 30-60 min Continuous 0.15mg/kg/dose;
min after initial infusion: 1.5- repeat as
dose; repeat as Continuous infusion: 2.5mcg/kg/min needed
needed at 15-25 0.4-0.6mcg/kg/min
minute intervals Continuous
infusion: 7-
Continuous 12mcg/kg/min,
infusion: Initial 9- use the lower
10mcg/kg/min then end of dosing
maintain by 5- range for infants
9mcg/kg/min and upper end
for children >2
years old.
Onset 30-60 sec 1-3 min 2-3 min 2-4 min 1-3 min 30-60 sec
98

NMBA Succinylcholine Atracurium Cisatracurium Pancuronium Vecuronium Rocuronium
Duration 4-6 min 25-35 min 35-45 min 90-100 min 35-45 min 25-40 min
Rapidly hydrolysed Hofmann Hofmann 30-40% metabolized 40-50% 50-60%
by plasma elimination (pH & elimination (pH & by liver into active metabolized by metabolized by
Metabolism cholinesterase temperature) into temperature) into metabolite 3- liver into 3 liver
laudanosine & laudanosine & hydroxypancuronium active
acrylate acrylate metabolites
10% excreted as <10% excreted as <10% excreted 40% excreted as 50% excreted 70% excreted in
unchanged drug in unchanged drug in as unchanged unchanged drug in in bile & 25% bile & up to 30%
Elimination urine urine drug in urine urine & 11% excreted excreted as excreted as
in bile unchanged unchanged drug
drug in urine in urine
Histamine No Yes Minimum No No No

release

123
99

4.0 PAEDIATRIC ICU
Paediatric Icu
4.0
Table 2: Drug Interactions affecting NMBAs.3,5,7.
Drug antagonising the action of

Drug potentiating the action of NMBAs
NMBAs
Aminoglycosides Frusemide (1-4mg/kg)B
N
Calcium channel blocker Carbamazepine
Clindamycin CorticosteroidN
Colistimethate sodium PhenytoinN
Corticosteroid (prolonged coadministration)N TheophyllineA
CyclophosphamideS
Cyclosporine
Frusemide (0.1-10mcg/kg)B
Lignocaine
Lithium carbonate
Magnesium
MetoclopramideS
Polymyxin B
Procainamide
Quinidine
Quinine
SpironolactoneN
Tetracycline
Vancomycin
S Succinylcholine
S only
Succinylcholine only
NN Non-depolarizing NMBAs
Non-depolarizing NMBAs onlyonly
A AAminosteroid NMBAs
Aminosteroid NMBAs onlyonly (eg rocuronium,
(eg rocuronium, pancuronium
pancuronium & vecuronium)
& vecuronium)
B
Succinylcholine & aminosteroid NMBAs only
B Succinylcholine & aminosteroid NMBAs only
Monitoring of NMBAs
Many factors can influence the depth of neuromuscular blockade such as acid-base
derangement, electrolytes imbalance and drug-drug interaction. Therefore, all patients
receiving NMBAs should be monitored both clinically and by train-of-four (TOF) monitoring to
assess the degree of neuromuscular blockade.
The use of TOF monitoring in attempts to optimise the degree of neuromuscular blockade
has been shown to reduce the total dose requirements of patients for NMBAs and allow
faster recovery of neuromuscular function and spontaneous ventilation and allow cost
savings5.
Complications of NMBAs
The major described complication is the prolonged muscle weakness after its
discontinuation. This complication is well documented in children, generally with the use
longer than 48 hours. This effect could last for up to 6 months. There are 2 patterns of
neuromuscular dysfunction: the persistent block of the NM junction (PBNMJ) and the acute
myopathy.
PBNMJ is probably due to accumulation of drugs or its active metabolites mainly in patients
with renal or hepatic failure. Co-administration of aminosteroid NMBA and corticosteroid is
significantly associated with PBNMJ. This drug-drug interaction is very important since one
124
of the Paediatric Pharmacy
major indications of Services
NMBAs inGuideline
paediatric is the child with status asthmaticus with
PAEDIATRIC ICU
Monitoring of NMBAs
4.0
Many factors can influence the depth of neuromuscular blockade such as acid-
base derangement, electrolytes imbalance and drug-drug interaction. Therefore,
all patients receiving NMBAs should be monitored both clinically and by train-of-
four (TOF) monitoring to assess the degree of neuromuscular blockade.
The use of TOF monitoring in attempts to optimise the degree of neuromuscular

blockade has been shown to reduce the total dose requirements of patients for
NMBAs and allow faster recovery of neuromuscular function and spontaneous
ventilation and allow cost savings5.
Complications of NMBAs

The major described complication is the prolonged muscle weakness after its
discontinuation. This complication is well documented in children, generally with
the use longer than 48 hours. This effect could last for up to 6 months. There are
2 patterns of neuromuscular dysfunction: the persistent block of the NM junction
(PBNMJ) and the acute myopathy.
PBNMJ is probably due to accumulation of drugs or its active metabolites

mainly in patients with renal or hepatic failure. Co-administration of aminosteroid
NMBA and corticosteroid is significantly associated with PBNMJ. This drug-
drug interaction is very important since one of the major indications of NMBAs in
paediatric is the child with status asthmaticus with dyssynchrony with mechanical
ventilation (and who uses short or long term corticosteroids). The acute myopathy
also leads to prolonged paralysis, but is not caused by delayed recuperation of
the neuromuscular junction1.
Muscular atrophy, joint contractures, thrombotic or embolic events, ulcers of the

skin, atelectasis, pneumonia and corneal drying are other possible complications.
Special attention should be given to the neurological assessment of patient with
status epilepticus and receiving NMBAs as NMBAs can completely obscure
many of the clinical manifestations of seizure activity1,5.

Paediatric Icu
Antagonism of NMBAs
4.0
Any residual neuromuscular block due to non-depolarizing NMBAs should be

antagonised by an anticholinesterase. This is especially important in neonates
and small infants because of their reduced respiratory reserve. The most
commonly used anticholinesterases are neostigmine and edrophonium5.
Sugammadex, a cyclodextrine which can reverse neuromuscular blockade that
induced by aminosteroid NMBAs and its mechanism of action is differently than
cholinesterase inhibitors4.
References :
1) Almeida JFL de, Filho WJK, Troster EJ. Neuromuscular Blockade in Children.
Rev. Hosp. Clin. Fac. Med. S. Paulo.2000;55(3):105-110
2) Meakin GH. Neuromuscular blocking drugs in infants andchildren. Continuing

Education in Anaesthesia. Critical Care & Pain. 2007;7(5):143-147
3) Micromedex® Healthcare Series. [Internet database]. Available from:

Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc ; 2011. [cited
20/11/2014]
4) Owczarek M, Bultowicz R, Kazmirczuk R, Owczarek KS, Paciorek P,

Jakubczyk M, Kupczyk K, Kusza K. Is suxamethonium still useful for
paediatric anaesthesia? Anestezjol Intents Ter. 2011;44(3):181-185.
5) Playfor S. Nueromuscular Blocking Agents in Critically Ill Children. Paediatric

and Perinatal Drug Therapy.2002; 5(1):35-46.
6) Shann F. Drug Doses, 16th Edition, Royal Children’s Hospital, Australia. 2014
7) Taketomo CK, Hodding JH, Kraus DM (Eds). Pediatric Dosage Handbook

with International Trade Names Index. 17th ed. Ohio. Lexi-Comp Inc; 2010

PAEDIATRIC ICU
Stress Ulcer Prophylaxis
4.0
Introduction
Stress-related mucosal damage (SRMD) is the board term used to describe the
spectrum of pathology attributed to the acute, erosive, inflammatory insult to
the upper gastrointestinal tract associated with critical illness. SRMD represents
a continuum from asymptomatic superficial lesions found incidentally during
endoscopy, occult gastrointestinal bleeding causing anemia, overt gastrointestinal
bleeding and clinically significant gastrointestinal bleeding.
Risk factors including:1,5
1) Coagulopathy
2) Shock
3) Surgery lasting for longer than 3 hours
4) Trauma
5) Pneumonia
6) Peadiatric Risk of Mortality Score ≥ 10
7) Thermal injury
Prophylaxis agent for SRMD
Prophylaxis is recommended for SRMD, but there is insufficient evidence to

recommend prophylaxis based on current trials on critically ill child1,5.
1) Sucralfate
Sucralfate acts by adhering to epithelial cells forming a physical cytoprotective
barrier at the ulcer site, thereby protecting the gastric mucosa from the
effects of acid and pepsin4.

Paediatric Icu
2) Histamine-2 receptor blockers (H2RBs)

4.0
H2RBs competitively inhibit histamine binding to its G-protein coupled

receptor on the basolateral membrane of gastric parietal cells, which results
in a reduction in acid production and an overall decrease in gastric
secretions4.
3) Proton Pump Inhibitors (PPIs)
PPIs inactivate the H+/K+ ATPase enzyme at the secretory surface of the
parietal cell, inhibiting the secretion of H+ ions and thereby increasing the pH
of the gastric contents4.
The pharmacological properties and drug-drug interaction of the prophylaxis

agents for SRMD are listed in Table 1.

Table 1: Summary of Pharmacological properties of prophylaxis agents for SRMD6,7.
Histamine-2
Proton Pump Inhibitors (PPIs)
Agent Sucralfate Receptor Blockers
Ranitidine Esomeprazole Lansoprazole Omeprazole Pantoprazole
PO: PO: 2-5mg/kg/dose PO: 0.4- PO: PO: 0.4- PO: 1mg/kg q12-
0-2 years old: q8-12h 0.8mg/kg/dose 1 years old – 0.8mg/kg/dose 24h
250mg q6h daily 30kg: 15mg daily q12-24h
Dose 3-12 years old: IV: 1mg/kg/dose q6-8h >30kg: 30mg daily IV: 1mg/kg q12-
500mg q6h IV: 0.4- 24h
>12 years old: 1g Continuous infusion: 0.8mg/kg/dose
q6h 2mcg/kg/min q24h
1-2 hr 1 hr - - PO: 1 hr PO: 2.5 hr
Onset IV: 15-30 min
Up to 6 hr PO: 4-12 hr - PO: ≥ 24 hr PO: 72 hr PO: 24 hr
Duration IV: 24 hr
Not metabolized Metabolized by liver Extensively by Extensively by Extensively by Extensively by
CYP2C19, CYP2C19 and CYP2C19 and CYP2C19 and
Metabolism
CYP3A3 & CYP3A4 CYP3A4 CYP3A4
CYP3A4
90% excreted in Excreted 30% (PO) & 80% excreted as 67% excreted in 77% excreted as 71% excreted as
stool 70% (IV) as inactive feces; 33% metabolite in urine metabolite in urine;
Elimination unchanged drug in metabolite in excreted in urine 18% excreted in
urine; feces as urine; 20% feces
metabolite excreted in feces
Digoxin, Cefuroxime Fluconazole Fluconazole Fluconazole Fluconazole
frusemide, Itraconazole Itraconazole Itraconazole Itraconazole Itraconazole
phosphate Ketoconazole Ketoconazole Ketoconazole Ketoconazole Ketoconazole
supplement, Protease inhibitor Methotrexate Methotrexate Methotrexate Methotrexate
Drug
quinidine, Protease Inhibitor Protease Inhibitor Protease Inhibitor Protease Inhibitor
Interaction
quinolone, Voriconazole Voriconazole Voriconazole Voriconazole

vitamin D
analogs, vitamin
K antagonists,
129
PAEDIATRIC ICU
4.0104
Paediatric Icu
Long-term and Serious Safety Concern with PPIs Use

4.0
Long-term inhibition of gastric acid secretion secretion leads to prolonged

hypergastrinemia and concerns for enterochromaffin-like cell hyperplasia,
carcinoid formation, vitamin B12 deficiency, hypomagnesemia, necrotizing
enterocolitis, osteoporosis, atrophic gastritis, and increased infections. These
concerns have been raised in adults, but paediatric studies are limited8.
Suppression of gastric acid secretion may predispose patients to certain

infections (Clostridium difficile infections, other enteric infections and respiratory
infections, including community-acquired pneumonias). The mechanism for this
may be that acid suppression eliminates a defense against pathogens2.
References:
1. ASHP Board of Directors. ASHP Therapeutic Guidelines on Stress Ulcer

Prophylaxis. America: Am J Health-Syst Pharm; 1999. 33 p.
2. Chen LL, Gao WY, Johnson AP, Niak A, Troiani J, Korvick J, Snow N, Estes
K, Taylor A, Griebel D. Proton Pump Inhibitors Use in Infants: FDA Reviewer
Experience. JPGN. 2012;54(1):8-14
3. M icro m edex® Heal thcar e S e r i e s. [ In t e r n e t da ta ba se ] . Ava i l a b l e

from:Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc ; 2011.
[cited 25/3/2015]
4. Pummer MP, Blaser AR, Deane AM. Stress Ulceration: Prevalence, Pathology
and Association with Adverse Outcomes. Critical Care. 2014;18:213
5. Reveiz L, Lozano RG, Camacho A, Yara L, Mosquera PA. Stress Ulcer,

Gastritis, and Gastrointestinal Bleeding Prophylaxis in Criticlly Ill Pediatric: A
Systematic Review. Pediatr Crit Care Med. 2010;11(1):124-132
6. Shann F. Drug Doses, 16th Edition, Royal Children’s Hospital, Australia. 2014
7. Taketomo CK, Hodding JH, Kraus DM (Eds). Pediatric Dosage Handbook

8. Ward RM, Kearns GL. Proton Pump Inhibitors in Pediatrics. Pediatr Drugs.
2013;15:119-131

PAEDIATRIC ICU
SEDATION & PAIN MANAGEMENT
4.0
Introduction
The indications for sedation in the paediatric intensive care unit (PICU) patient
are varied ranging from short term use for various procedures to prolonged
administration to provide comfort during mechanical ventilation11.
Due to diversity among patients and the varied indications for sedative and
analgesic drugs, it is not possible to provide a ‘cookbook’ of definite guidelines
for sedation and analgesia. Sedative and analgesia agents should not be
administered strictly on a per kilogram basis like other medications such as
antibiotics. Dosage recommendations are meant as guidelines for starting doses.
The actual amount administered should be titrated up or down to achieve the
desired level of sedation or analgesia11.
Undersedation and oversedation are both harmful. Agitation and inadequate

sedation have been correlated with adverse short- and longer-term outcomes.
Recent data have highlighted the intensive care and surgery are associated with
long-term dysregulation of nociceptive mechanisms, which may change behaviour
and responses to future sensory and pain stimuli. By contrast, oversedation
delays recovery promotes tolerance to the drugs and leads to distressing
symptoms on withdrawal (agitation, seizures, hallucinations, psychosis, fever and
tachycardia)12.
Opioids, in particular, are associated with dose-dependent immunosuppression

of both humoral and cell-mediated immunity, which acts on promote infection and
sepsis during a longer PICU stay12.

Sedative Agents
• Benzodiazepine
Mechanism of action of benzodiazepine is through the facilitations in
the CNS of the activity of the inhibitory neurotransmitter, Y-aminobutyric acid
(GABA).Midazolam are the most commonly used benzodiazepine in PICUs8.
Midazolam is a water-based acidic preparation; at plasma pH, it converts into
an un-ionised form that crosses the blood-brain barrier rapidly. It has the
shortest elimination half-life of the benzodiazepine group8.

Paediatric Icu
Generally, midazolam is a safe and effective sedative agent if given as short-

4.0
term infusion and it tends to accumulate if given as continuous infusion due to

its high volume distribution and high lipophilicity4. Dose reduction is
necessitating in patients with hepatic and/or renal dysfunction8,11.
The main adverse events associated with midazolam are tolerance,
dependence and withdrawal following discontinuation7.
• Dexmedetomidine
Dexmedetomidine is a selective 2-adrenergic agonist and is structurally
related to clonidine, but has a much greater affinity for æ2-receptors
over æ2-receptors. It is extensively metabolized through the cytochrome
P450 enzyme system, therefore dose reduction is recommended for patient
with hepatic dysfunction2.
The most significant adverse reasons are hypotension and bradycardia,
resulting from its sympatholytic activity. Both are rarely clinically significant
or required intervention to correct. Transient hypertension has been reported
with the administration of the loading dose due to initial vasoconstriction
caused by stimulation of peripheral postsynaptic 2-adrenergic receptors.
Management consists of slowing the infusion rate, but rarely is discontinuation
of treatment necessary. Dexmedetomidine is recommended to be used
with caution in patients with history of atrioventricular nodal block or
severe ventricular dysfunction, as well as in hypovolemic patients or
those with chronic hypertension2.
Although not well studied, abrupt cessation of dexmedetomidine may
produce withdrawal symptoms. Slowly taper off the dose of dexmedetomidine
may be useful to minimize the risk for withdrawal2.
• Ketamine
Ketamine is a dissociative anaesthetic agent, structurally similar to
phencyclidine, which produces a cataleptic trance-like state by apparently
producing an electrophysiological dissociation between the limbic and
thalamoneocortical systems7.

PAEDIATRIC ICU
Ketamine produces a dose-related acceleration of heart rate and blood
pressure thought to be caused by the release of endogenous catecholamines
4.0
through its stimulatory effect on the sympathetic nervous system. The indirect
sympathomometic effect of ketamine is assumed to dominate over its direct
negative inotropic properties, therefore resulting in reduced risk of
hypotension. In addition, respiratory function is well maintained with ketamine.
Functional residual capacity, minute ventilation and tidal volume are
unchanged, pulmonary compliance is improved and bronchospasms are
relieved due to release of catecholamines6.
Although ketamine generally preserves airway patency, rare cases of
pulmonary aspiration, apnea, arterial hypoxemia and laryngospasm have
been reported. Ketamine is a potent sialagogue. It increases salivary and
bronchial mucous gland secretions through stimulation of cholinergic
receptors. Ketamine also increases intracranial pressure (ICP) and pulmonary
vascular resistance. Therefore, is contraindicated for patients with pulmonary
hypertension or at risk for elevated intracranial pressure6.
Emergency phenomena are a hallmark event for ketamine and have been
described as vivid dream, hallucinations, floating sensations, delirium,
recovery agitation and dysphoria. Benzodiazepines have been co-
administrated with ketamine to reduce the frequency of emergency
phenomena, however, it is controversial3,6.
• Propofol
Propofol is a unique sedative-hypnotic agent with a rapid onset and offset of
action. Propofol also acts on the GABA receptor like benzodiazepine although
the side of action on this receptor is different4. It offers the advantages of
a quick onset of action, quick recovery once discontinued and lacks of active
metabolites11.
In addition to its sedative and amnesia effects, propofol also decreases
cerebral oxygen consumption and reduces intracranial pressure. It also
shows excellent antiepileptic activities with proven efficacy in treating patients
with refractory seizures11.
Propofol is a highly lipophilic compound and is essentially insoluble in water
or other aqueous medium. Therefore, it is formulated as an intravenous
emulsion with 10% lipid11. Propofol-related infusion syndrome is a rare
but frequently fatal complication characterised by acidosis, bradyarrhythmia
and rhabdomyolysis. It has been demonstrated that transient elevations in
malonylcarnitine and C5-acylcarnitine occur during propofol-related infusion
syndrome, suggesting that propofol impairs fatty acid oxidation and
mitochondrial activity at the subcellular level8.

4.0 Paediatric Icu
Table 1: Summary of pharmacological properties of sedative agents5,9,10.
Agent Midazolam Dexmedetomidine Ketamine Propofol

Anaesthesia:
ICU:
IV: 1-2mg/kg/dose Anaesthesia:
Sedation: Infusion: 0.4mcg/kg/hr
IM: 5-10mg/kg/dose IV: 2.5-3.5mg/kg stat, then
IV bolus / IM: 0.1-
Infusion: 10-40mcg/kg/min 7.5-15mg/kg/hr
Dose 0.2mg/kg/dose Procedure:
Analgesia:
(maximum dose: 0.5mg/kg) Infusion: 0.5-1mcg/kg/min
IV: 1-1.5mg/kg Sedation:
Infusion: 1-4mcg/kg/min over 10-20 min, then 0.6
IM: 3-4mg/kg IV: 1-3mg/kg/hr
mcg/kg/hr
Infusion: 2-6mcg/kg/min
Anaesthesia:
IV: <30 sec
IV: 1-5 min
Onset IV: 30 min IM: 3-4 min IV: 10-50 sec
IM: <5 min
Analgesia:
IM: 10-15 min
Maximum IV: 5-7 min
- IM: 15-30 min -
effect IM: 15-30 min
Anaesthesia:
IV: 5-10 min

IV: 20-30 min IV: 4 hr
Duration IM: 12-25 min IV: 3-10 min
IM: 2-6 hr IM: 2.5 hr
Analgesia:
IM: 15-30 min
Full IV: 1-2 hr
May take >24 hours - -
recovery IM: 3-4 hr
Metabolize in liver via
Extensive metabolize in liver
CYP2B6, CYP2C9 & CYP3A4
via CYP3A4. Metabolize in liver via
into norketamine (active Extensive in liver via CYP2B6
Metabolism Primary metabolite (á- CYP2A6 into inactive
metabolite) and its potency is into inactive metabolites
hydroxy-midazolam) is active metabolites
one third of the parent
and equipotent to midazolam
compound.
Urine:
Urine:
63-80% excreted as á- Urine:
Urine: Majority excreted as inactive
hydroxy-midazolam; 88% excreted as metabolites;
95% metabolite; 4% excreted as
<1% excreted as unchanged <3% excred as unchanged
unchanged drug or
Elimination drug drug
Feces: norketamine
4%
Feces: Feces:
Feces:
2-10% as unchanged drug <2%
<5%
110

Agent Midazolam Dexmedetomidine Ketamine Propofol
Amnesia Yes Yes Yes Yes
Analgesia No Yes Yes No
Contraindicated:
Efavirenz; Protease
inhibitors;
Increased effect / toxicity

Midazolam may increase the
levels/effects of:
Clozapine, CNS depressant;
methotrimeprazine; Increased effect / toxicity
phenytoin; propofol Midazolam may increase the
Increased effect / toxicity
levels/effects of:
Increased effect / toxicity Propofol may increase the
The levels/effects of Hypotensive agents
The levels/effects of ketamine levels/effects of:
midazolam increased by:
increased by: Midazolam; ropivacaine
Antifungal agents (Azole The levels/effects of
CYP2B6 inhibitors; CYP2C9
derivatives, systemic); midazolam increased by:
inhibitors; CYP3A4 inhibitors; The levels/effects of propofol
Aprepitant; atorvastatin; Beta-blockeers; CYP2A6
Drug desatinib; quazepam increased by:
CCB (non-dihydropyridine); inhibitors; MAO inhibitors
interaction Alfentanil; CYP2B6 inhibitors;
cimetidine; contraceptives
Decreased effect midazolam; quazepam
(estrogens & progestins); Decreased effect
The levels/effects of ketamine
CYP3A4 inhibitors; The levels/effects of
may be decreased by: Decreased effect
Efavirenz; Isoniazid; midazolam may be decreased
CYP2C9 inducers; The levels/effects of propofol
Macrolide antibiotics; by:
Peginterferon α-2b may be decreased by:
Propofol; Protease inhibitors; Antidepressants (α2-
Peginterferon α -2b
PPI; SSRI antagonist); SSRI; tricyclic
antidepressants
Decreased effect
The levels/effects of
midazolam may be
decreased by:
Carbamazepine; CYP3A4
inducers; deferasirox,
rifampicin derivatives;
theophylline derivatives

135
111

4.0 PAEDIATRIC ICU
Paediatric Icu
Analgesic Agents
4.0
Opioids produce analgesia via a variety of central and peripheral opioids

receptors, particularly μ- and k-receptors. To varying degrees the opioids tend to
produce hypotension and respiratory depression7.
• Morphine
Morphine has the lowest lipid solubility of all the opioids, which accounts for
its delayed onset of clinical effect. Dose reduction of morphine is necessity for
patients with hepatic and/or renal dysfunction. Morphine stimulates the
release of significant amounts of histamine and inhibits compensatory
sympathetic responses; the resultant vasodilatation may result in hypotension.
Discontinuation of morphine is associated with withdrawal syndrome7.
• Fentanyl
Fentanyl is a potent synthetic opioid with a rapid onset of action, which is
associated with less histamine release than morphine, and therefore,
produces less hypotension; although it may reduce cardiac output by
decreasing the heart rate. Fentanyl is 100 times more potent compared to
morphine. When given intravenously there is rapid redistribution to peripheral
compartments, giving fentanyl a relatively short half-life of 30-60 minutes7.
An infrequenct adverse effect is chest wall rigidity, which is related to the dose
used, rate of infusion and age < 6 months1. Prolonged administration of
fentanyl is associated with tolerance7.
• Remifentanil
Remifentanil is a synthetic opioid with cardio-respiratiory effects similar
to other opioids and which is equipotent to fentanyl. Remifentanil has a
half-life of 3 minutes in all age groups because it is metabolised by plasma
and tissue esterases. No dosage adjustment is needed for patients with liver
and/or renal dysfunction. Prolonged administration of remifentanil is associated
with tolerance7.

Table 2: Summary of pharmacological properties of analgesic agents.5,9,10
Agent Morphine Fentanyl Remifentanil
Ventilated patient: Ventilated patient: Ventilated patient:

Dose IV: 0.1-0.2mg/kg/dose IV: 5-10mcg/kg/dose Infusion: 0.5-1mcg/kg/min
Infusion: 20-801mcg/kg/hr Infusion: 5-10mcg/kg/hr
IV: 5 min IV: Almost immediate IV: 1-3 min

Onset IM: 10-30 min IM: 7-15 min
Maximum IV: 20 min IV: 3-5 min

-
effect IM: 30-60 min
IV/IM: 3-5 hr IV: 30-60 min IV: 3-10 min

Duration
IM: 1-2 hr
Metabolize in liver via glucuronide Metabolize in liver via CYP3A4 into Metabolized rapidly by blood and
conjugation to morphine-6-glucuronide inactive metabolites tissue esterases into inactive
Metabolism
(active) & morphine-3-glucuronide metabolites
(inactive)
Urine: Urine: Urine:

90% excreted in urine; 2-12% excreted 75% excreted as metabolites; 90% excreted as inactive metabolites
as unchanged drug 7-10% excreted as unchanged drug
Elimination
Feces: Feces:
7-10% 1-9% as metabolites
Histamine Yes No No

release
137
115

4.0 PAEDIATRIC ICU
4.0 Paediatric Icu
Agent Morphine Fentanyl Remifentanil

Increased effect / toxicity Contraindicated: Contraindicated:
Morphine may increase the Protease inhibitors, MAO inhibitors MAO inhibitors
levels/effects of:
CNS depressant; desmopressin; Increased effect / toxicity Increased effect / toxicity
SSRI; thiazide diuretics Fentanyl may increase the Remifentanil may increase the
levels/effects of: levels/effects of:
The levels/effects of morphine may be Beta-blockers; CCB (non- Beta-blockers; CCB (non-
increased by: dihydropyridine); CNS depressant; dihydropyridine); CNS depressant;
Amphetamines; antipsychotic agents; desmopressin; MAO inhibitors; SSRI; desmopressin; MAO inhibitors; SSRI;
succinylcholine thiazide duiretics thiazide duiretics
Drug
Decreased effect The levels/effects of fentanyl may be The levels/effects of remifentanil may
interaction
The levels/effects of morphine may be increased by: be increased by:
decreased by: Amphetamine, antipsychotic agents; Amphetamines; antipsychotic agents;
Ammonium chloride; mixed agoinist / CYP3A4 inhibitors; MAO inhibitors; succinylcholine
antagonist opioids; peginterferon α - succinylcholine
2b; rifampicin derivatives Decreased effect

Decreased effect The levels/effects of remifentanil may
The levels/effects of fentanyl may be be decreased by:
decreased by: Ammonium chloride; mixed agoinist /
Ammonium chloride; mixed agoinist / antagonist opioids
antagonist opioids; rifampicin
derivatives
116

PAEDIATRIC ICU
Withdrawal syndrome
4.0
Withdrawal syndrome may occur following the discontinuation of sedative agents,
particularly benzodiazepines and opioids, and is thought to be related to the total
drug doses received. The withdrawal syndrome occurs in 50% of the cases with
a cumulative fentanyl dose greater than 1.5mg/kg or administration longer than 5
days, rising to 100% when the cumulative dose is greater than 2.5mg/kg or with
an administration longer than 9 days. The incidence of this syndrome increases
significantly with an cumulative midazolam dose greater than 60mg/kg1.
Different methods are used to prevent the development of the withdrawal

syndrome, such as gradual reduction in doses, enteral sedative agents and
subcutaneous use of fentanyl and midazolam and avoidance of continuous
intravenous sedation1.
References:
1) Bartolomé SM, Cid JLH, Freddi N. Analgesia and Sedation in Children:

Practical Approach for the Most Frequent Situations. Jornal de Pediatria.
2007;83(2):S71-S82.
2) Buck ML. Dexmedetomidine Use in Pediatric Intensive Care and Procedural

Sedation. J Pediatr Pharmacol Ther. 2010;15(1):17-29
3) Dolansky G, Shah A, Mosdossy G, Rieder MJ. What is the Evidence for

the Safety and Efficacy of Using Ketamine in Children? Paediatr Child Health.
2008;13(4):307-308
4) Gommers D, Bakker J. Medications for Analgesia and Sedation in the

Intensive Care Unit: An Overview. Critical Care. 2008;12(3):S1-S5.
5) Micromedex® Healthcare Series. [Internet database]. Available from:

Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc; 2011. [cited
20/11/2014]
6) Mistry RB, Nahata MC. Ketamine for Conscious Sedation in Pediatric

Emergency Care. Pharmacotherapy. 2005;25(8):1104-1111
7) Playfor SD. Analgesia and Sedation in Critically Ill Children. Arch. Dis. Child
Ed. Pract. 2008;93:87-92.

Paediatric Icu
8) Playfor S, Jenkins I, Boyles C, Choonara I, Davies G, Haywood T et al.

Consensus Guidelines on Sedation and Analgesia in Critically Ill Children.
4.0
Intensive Care Med. 2006;32:1125-1136
9) Shann F. Drug Doses. 16th ed. Victoria. Royal Children’s Hospital; 2014
10) Taketomo CK, Hodding JH, Kraus DM (Eds). Pediatric Dosage Handbook
11) Tobias JD. Sedation and Analgesia in Paediatric Intensive Care Units Paediatr
Drugs. 1999;1(2):109-126
12) Wolf AR. Analgesia and Sedation in Pediatric Intensive Care. South Afr J
Anaesth Analg. 2012;18(5):258-261

Neonatal Icu
5.0
5.0 Neonatal ICU

Neonatal Icu
NEONATAL JAUNDICE (NNJ)

5.0
Introduction
Neonatal Jaundice (NNJ) is one of the most common medical conditions

in newborns. All newborn babies have a transient rise in serum bilirubin but
only about 75% are visibly jaundiced. There are other risk factors that may be
associated with significant hyperbilirubinemia including prematurity, G6PD
deficiency and ABO incompatibility.
Jaundice or hyperbilirubinaemia is either unconjugated or conjugated. Without
treatment, high levels of unconjugated bilirubin may lead to acute and chronic
bilirubin encephalopathy. This causes neurodevelopmental problems including
athetoid cerebral palsy, hearing loss and, visual and dental problems.
Risk factors for severe NNJ:
• Prematurity • Low birth weight

• Jaundice in the • Mother with Blood
first 24 hours of life Group O or Rhesus Negative
• G6PD deficiency • Sepsis
• Rapid rise of total serum bilirubin • Exclusive breastfeeding
• Excessive weight loss • High predischarge bilirubin level
• Cephalhaematoma or bruises • Family history of severe NNJ in
• Baby of diabetic mothers siblings
Pharmacotherapy
There is limited good evidence on pharmacotherapy in NNJ and no conclusive
evidence to support the use of IVIG, human albumin and phenobarbitone in the
management of NNJ.
Non-Pharmacotherapy
• Phototherapy
Phototherapy is the mainstay of treatment in NNJ. There are many types of
devices that can be used to provide phototherapy such as fluorescent
tubes, Light Emitting Diode (LED), fibreoptic and halogen bulbs

Phototherapy is the mainstay of treatment in NNJ. There are many types of devices that can be
used to provide phototherapy such as fluorescent tubes, Light Emitting Diode (LED), fibreoptic
Neonatal Icu
and halogen bulbs.
Care of babies during phototherapy
• Babies should be regularly monitored for vital signs including temperature and hydration
status.
5.0
• Babies should be adequately exposed.
• Babies’ eyes should be covered to prevent retinal damage.
• Breastfeeding should be continued.
• Exchange Transfusion
-> Exchange transfusion (ET) should be considered when total serum 119

bilirubin reaches the threshold levels in neonatal jaundice (NNJ).
-> ET procedure should follow a standardized protocol and supervised by
experienced personnel. Babies undergoing ET should be closely monitored.
• Exchange Transfusion
• Exchange transfusion (ET) should be considered when total serum bilirubin
-> Reconstituted blood
reaches products
the threshold levelsmay be used
in neonatal if (NNJ).
jaundice citrated fresh whole blood
is not •available for ETshould
ET procedure in NNJ.
follow a standardized protocol and supervised by
experienced personnel. Babies undergoing ET should be closely monitored.
-> Blood• product used
Reconstituted most
blood commonly
products may be usedfor ET isfresh
if citrated citrated freshis whole
whole blood not
available for ET in NNJ.
blood.However,
• Blood product some used centres
most commonlyuse forreconstituted blood
ET is citrated fresh products
whole blood.
when it is not available.Both
However, some centrescitrated fresh whole
use reconstituted blood and
blood products whenreconstituted
it is not
available. Both citrated fresh whole blood and reconstituted blood products
blood products are comparable
are comparable in terms
in terms of efficacy of efficacy and safety
and safety.
TABLE 1: TSB levels for phototherapy & ET in babies ≥35 weeks gestation
Age LOW RISK MEDIUM RISK HIGH RISK

>38 weeks & well >38 weeks with risk factors 35 - 37 weeks + 6 days
or with risk factors
35 - 37 weeks + 6 days &
well
Hours Conventional ET - Conventional ET - Conventional ET -
of life Phototherapy TSB in Phototherapy - TSB in Phototherapy TSB in
- mg/dL TSB in mg/dL mg/dL - mg/dL
TSB in mg/dL (µmol/L) (µmol/L) (µmol/L) TSB in mg/dL (µmol/L)
(µmol/L) (µmol/L)
<24*
24 9 (154) 19 (325) 7 (120) 17 (291) 5 (86) 15 (257)
48 12 (205) 22 (376) 10 (171) 19 (325) 8 (137) 17 (291)
72 15 (257) 24 (410) 12 (205) 21 (359) 10 (171) 18.5
(316)
96 17 (291) 25 (428) 14 (239) 22.5 (385) 11 (188) 19 (325)
>96 18 (308) 25 (428) 15 (257) 22.5 (385) 12 (205) 19 (325)
a. Start intensive phototherapy at TSB 3 mg/dL (51 µmol/L) above the level for conventional
phototherapy or when TSB increasing at >0.5 mg/dL (8.5 µmol/L) per hour
b. Risk factors are isoimmune haemolytic disease, G6PD deficiency, neonatal encephalopathy
& sepsis.
*Jaundice appearing
*Jaundice within
appearing within 24of life
24 hours hours of life
is abnormal is further
& needs abnormal & needs further
evaluation.
evaluation.
• Complementary/Alternative Medicine/Practices
There is no good quality evidence

• Complementary/Alternative to support the use of
Medicine/Practices complementary/alternative
medicine/practices in the management of babies with NNJ.
There isofno
Impact good quality evidence to support the use of complementary/
Breastfeeding
alternative medicine/practices in the management of babies with NNJ.
• Breastfeeding, because of its benefits, should be continued in the jaundiced babies.
• Adequate lactation/breastfeeding support should be provided to all mothers, particularly
those with preterm babies. In breastfed babies with jaundice associated with
inadequate intake, excessive weightPaediatric Pharmacy
loss or dehydration, Services Guideline
supplementation with 143
expressed breast milk or formula may be considered
Neonatal Icu
Impact of Breastfeeding
• Breastfeeding, because of its benefits, should be continued in the
5.0
jaundiced babies.
• Adequate lactation/breastfeeding support should be provided to all
mothers, particularly those with preterm babies. In breastfed babies
with jaundice associated with inadequate intake, excessive weight loss or
dehydration, supplementation with expressed breast milk or formula may
be considered
121


Neonatal Icu
References:
5.0
1. Clinical Practice Guidelines Management of Neonatal Jaundice 2nd Edition
December 2014 Ministro of Health Malaysia
2. Huang MS, Lin MC, Chen HH, et al. Risk factor analysis for late-onset
neonatal hyperbilirubinemia in Taiwanese infants. Pediatr Neonatol 2009
Dec;50(6):261-265.
3. Jangaard KA, Fell DB, Dodds L, et al. Outcomes in a population of healthy
term and near-term infants with serum bilirubin levels of >or=325 micromol/L
(>or=19 mg/dL) who were born in Nova Scotia, Canada, between 1994
and 2000. Pediatrics. 2008 Jul;122(1):119-124.
4. Kuzniewicz MW, Escobar GJ, W i S, et al. Risk factors for severe
hyperbilirubinemia among infants with borderline bilirubin levels: a nested
case-control study. J Pediatr. 2008 Aug;153(2):234-240.
5. National Collaborating Centre for Women’s and Children’s Health. Neonatal
jaundice. London: NCC-WCH; 2010.
6. Maisels MJ, Bhutani VK, Bogen D, et al. Hyperbilirubinemia in the newborn
infant > or =35 weeks’ gestation: an update with clarifications. Pediatrics.
2009 Oct;124(4 ):1193-1198.
7. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia.
Management of hyperbilirubinemia in the newborn infant 35 or more weeks
of gestation. Pediatrics. 2004 Jul;114(1):297-316.
8. Boo NY, Gan CY, Gian YW, et al. Malaysian mothers’ knowledge & practices
on care of neonatal jaundice. Med J Malaysia. 2011 Aug;66(3):239-243.
9. Salas AA, Mazzi E. Exchange transfusion in infants with extreme
hyperbilirubinemia: an experience from a developing country. Acta Paediatr.
2008 Jun;97(6):754-758.
10.Weng YH, Chiu YW. Comparison of efficacy and safety of exchange
transfusion through different catheterizations: Femoral vein versus umbilical
vein versus umbilical artery/vein. Pediatr Crit Care Med. 2011 Jan;12(1):6 64.
11. Chen HN, Lee ML, Tsao LY. Exchange transfusion using peripheral vessels
is safe and effective in newborn infants. Pediatrics. 2008
Oct;122(4):e905-910.
12. Gharehbaghi MM, Hosseinpour SS. Exchange transfusion in neonatal
hyperbilirubinaemia: a comparison between citrated whole blood and
reconstituted blood. Singapore Med J. 2010 Aug;51(8):641-644.

Neonatal Icu
13. amidi M, Zamanzad B, Mesripour A. Comparing the effect of clofibrate

5.0
and phenobarbital on the newborns with hyperbilirubinemia. EXCLI Journal.

2013;12:75-78.
14. Xiong T, Chen D, Duan Z, et al. Clofibrate for unconjugated hyperbilirubinemia
in neonates: a systematic review. Indian Pediatr. 2012 Jan;49(1):35-41.
15. Ashkan MM, Narges P. The effect of low and moderate doses of clofibrate
on serum bilirubin level in jaundiced term neonates. Paediatric and Perinatal
Drug Therapy. 2007;8(2):51-54.
16. Louis D, More K, Oberoi S, et al. Intravenous immunoglobulin in isoimmune
haemolytic disease of newborn: an updated systematic review and meta-
analysis. Arch Dis Child Fetal Neonatal Ed. 2014 Jul;99(4):F325-331.
17. Ismael AS, Alrabaty AA. Role of Intravenous Human Albumin in Management
of Neonatal Hyperbilirubinemia. JSMC. 2013;3(1).
18. Shahian M, Moslehi MA. Effect of albumin administration prior to exchange
transfusion in term neonates with hyperbilirubinemia-a randomized controlled
trial. Indian Pediatr. 2010 Mar;47(3):241-244.
19. Suresh G, Martin CL, Soll R. Metalloporphyrins for treatment of unconjugated
hyperbilirubinemia in neonates. Cochrane Database of Systematic Reviews.
2003;Issue 1. Art. No.: CD004207.
20. Chawla D, Parmar V. Phenobarbitone for prevention and treatment of
unconjugated hyperbilirubinemia in preterm neonates: a systematic review
and meta-analysis. Indian Pediatr. 2010 May;47(5):401-407.
21. Hussain Imam MI, Ng HP, Thomas T, et al. Malaysian Paediatric Protocol for
Malaysian Hospitals 3rd Edition. Putrajaya: MoH; c2012.

Neonatal Icu
SEDATION & PAIN MANAGEMENT
5.0
Sedation & Pain Management
Table 1: Responses of Neonates to Pain
Physiological Behavioral Hormonal Autonomic Body

changes changes changes changes movements
Increase in: Grimacing Increased Mydriasis Finger clenching
Heart rate Pain release of: Sweating Trashing of
Blood pressure Cortisol Flushing limbs
Respiratory Definition Catecholamine Pallor Writhing
rate An unpleasant Glucagon Arching of back
Oxygen sensory and Growth hormone Head hanging
consumption emotional Renin
Mean airway experience Aldosterone
pressure associated with Antidiuretic
Muscle tone actual or potential hormone
Intracranial tissue damage or
pressure described in terms Decreased
of such damage 8 secretion of:
Insulin
Responses of
Neonates to Pain
Prolonged or
severe pain may
cause short- or
long term
physiological,
behavioral,
hormonal and
metabolic changes.
These changes
may result in
higher morbidity
and mortality as
well as alter
subsequent
responses to pain 4
Screwing up eyes
Nasal flaring
Curving of the
tongue
Quivering of the
chin
125


Neonatal Icu
Pain Assessment
5.0
Pain assessment in neonatal patients is mainly via self-reporting by staffs and

indirect measurement including behavioral, physiological and hormonal changes 10.
Pain Assessment
Pain assessment in neonatal patients is mainly via self-reporting by staffs and indirect
measurement including behavioral, physiological and hormonal changes 10.
Table 2: Commonly used Pain Assessment Tools in Neonatal Patients
Premature Neonatal Facial Neonatal

Assessment
Infant Pain Coding Scale Infant Pain CRIES Score
Tools
Profile (PIPP) (NFCS) Scale (NIPS)
Gestational age Brow bulge Facial Crying
Behavioural Eye squeeze expression Requires increase
state Nasolabial furrow Cry Oxygen
Heart Rate Open lips Breathing administration
Variables Oxygen Stretch mouth patterns Increased vital
assessed saturation Lip purse Arms signs
Brow bulge Taut tongue Legs Expression
Eye squeeze Chin quiver State of Sleeplessness
Nasolabial Tongue protrusion arousal
furrow
Sedation
Sedation
Definition
Definition
Sedation means reduced state of awareness but does not relieve pain. Procedural sedation and
analgesia is defined as the use of anxiolytic, sedative, analgesic or dissociative drugs to
attenuatemeans
Sedation pain, anxiety and motion
reduced to facilitate
state the performance
of awareness of adoes
but necessary
notdiagnostic
relieveor pain.
therapeutic procedure, provide an appropriate degree of amnesia or decreased awareness, and
Procedural sedation
ensure patient safety 2.and analgesia is defined as the use of anxiolytic, sedative,
analgesic or dissociative drugs to attenuate pain, anxiety and motion to facilitate
Level of Sedation / Depth of Sedation
the performance
Depth of sedation of a necessary
is defined diagnostic
as a continuum, or from
progressing therapeutic
mild throughprocedure,
moderate to deepprovide
sedation and to general anesthesia. Shown below are the definitions of levels of sedation as
an appropriate
defined and
degree
adopted by
of amnesia
American Society
or
of
decreased awareness,
Anesthesiologists 1
.
and ensure patient
safety2.
Table 3: Continuum of Depth of Sedation adopted by American Society of
Anaesthesiologists
Moderate
Minimal
Level of sedation/ General
sedation /
Depth of sedation is
Sedation
Anxiolysis
a continuum,Deep
defined asConscious sedation
progressing from mild through
anaesthesia
moderate to deep sedation Normal
and sedation
to general anesthesia. Purposeful
Shown below are the
Purposeful Unarousable
definitions of levels of
Responsiveness sedation
response to as defined
response to verbaland adopted by American
response following Society of
even with painful
1 verbal repeated or painful
Anesthesiologists . stimulation or tactile stimulation
stimulation
stimulus
No intervention Intervention may be Intervention often

Airway Unaffected
required required required
126


therapeutic procedure, provide an appropriate degree of amnesia or decreased awareness, and
ensure patient safety 2.
Neonatal Icu
Depth of sedation is defined as a continuum, progressing from mild through moderate to deep
sedation and to general anesthesia. Shown below are the definitions of levels of sedation as
defined and adopted by American Society of Anesthesiologists1.
Table 3: Continuum of Depth of Sedation adopted by American Society of
5.0
Anaesthesiologists
Moderate
Minimal
Level of sedation/ General
sedation / Deep sedation
Sedation Conscious anaesthesia
Anxiolysis
sedation
Normal Purposeful
Purposeful Unarousable
response to response following
Responsiveness response to verbal even with painful
verbal repeated or painful
or tactile stimulation stimulus
stimulation stimulation
No intervention Intervention may be Intervention often
Airway Unaffected
required required required
Spontaneous Frequently
Unaffected Adequate May be inadequate
ventilation inadequate 126
Cardiovascular
Unaffected Usually maintained Usually maintained Maybe impaired
function
General Principles of Pain Management & Sedation
General
• Principles
In both pretermof Pain
and term Management & Sedation
neonates, neuroanatomical components and neuroendocrine
10
systems are developed sufficiently to allow transmission of painful stimuli .
• Newborns may be more sensitive to pain and may be more susceptible to long term
• In both preterm and term neonates, neuroanatomical components and
effects of pain. However, pain in newborns are often not recognized and undertreated10
neuroendocrine
• Sedation does systems are relief
not provide pain developed sufficiently
and may mask
10
to response
the patient’s allow transmission
to pain of
• Approach to
painful stimuli10.pain prevention and management:
- Avoiding and limiting noxious stimuli
- Minimizing
• Newborns may be painful
moreprocedure
sensitive to pain and may be more susceptible to
Eg: placement of peripheral lines to reduce repeated IV punctures
long term effects
- Applying of pain. measurement
non-invasive However, pain in newborns are often not recognized
10
Eg: oximeter
and undertreated
- Assessment of neonatal pain
• Sedation does notmethods
- Behavioral provide pain relief and may
/ non-pharmacological mask the patient’s response to pain
therapy
Eg: sucrose, swaddling, non-nutritive sucking, skin10
to skin contact
• Approach to pain prevention
- Pharmacological therapy as and management:
pre-emptive analgesic
- Pharmacological therapy for on-going pain
- Avoiding and limiting noxious stimuli 4,9
Pain & Sedation Management in Ventilated Patient .
- Minimizing painful procedure
Analgesia/sedation should be used in neonates receiving continued ventilation.
••Eg:Morphine
placement of peripheral lines to reduce repeated IV punctures
- Applying non-invasive
Continuous measurement
morphine infusion may improve neurological outcome and reduce adverse
responses during endotracheal suctioning. Titrate up the morphine infusion according to
Eg:response.
oximeterIf a patient is ventilated for ≥ 1 week and on full enteral feed without needing
the intravenous access, switching to oral morphine can be considered.
- A•ssessment
Midazolam
of neonatal pain
Intermittent
- Behavioral during intubation
methods and continuous infusion
/ non-pharmacological of midazolam can be used as
therapy
sedation
Eg: sucrose, swaddling, non-nutritive sucking, skin to skin contact
Pain & Sedation Management in Procedures 6,11
- Pharmacological
• Behavioral methods therapy as pre-emptive
/ Non-pharmacological therapyanalgesic
- Hypnosis & distraction
- Pharmacological
- Music
therapy for on-going pain
- Non-nutritive sucking
- Breast-feeding during procedure
- Sucrose
Sucrose can be used for short term pain prior to minor procedures eg:
venipuncture, cannulation, heel prick, IM/SC injection, dressing change and eye
examination. It is not for continuing pain.

Neonatal Icu
Pain & Sedation Management in Ventilated Patient4,9.

5.0
• Analgesia/sedation should be used in neonates receiving continued

ventilation.
• Morphine
Continuous morphine infusion may improve neurological outcome and reduce
adverse responses during endotracheal suctioning. Titrate up the morphine
infusion according to response. If a patient is ventilated for ≥ 1 week and on
full enteral feed without needing the intravenous access, switching to oral
morphine can be considered.
• Midazolam
Intermittent during intubation and continuous infusion of midazolam can be
used as sedation
Pain & Sedation Management in Procedures 6,11

• Behavioral methods / Non-pharmacological therapy
- Hypnosis & distraction
- Music
- Non-nutritive sucking
- Breast-feeding during procedure
- Sucrose
Sucrose can be used for short term pain prior to minor procedures eg:
venipuncture, cannulation, heel prick, IM/SC injection, dressing change
and eye examination. It is not for continuing pain.

Neonatal Icu
Table 4: Mechanism of action, Dosing, Age group, Administration, Adverse Effects,
Cautions and Contraindications of Sucrose
5.0
Mechanism of action Elusive, maybe behavioral effect 13
Age group 1st month – 18months of life 11
Dosing 11 Maximum volume sucrose Maximum volume sucrose
Gestational Age / 24-33% solution per 24-33% solution within
Birthweight procedure 24hours
Nil orally 0.2ml 1ml
< 1500gm 0.5ml 2.5mls
< 1 month of age 1ml 5mls
1-18months of age 2mls 5mls
Administration I) Prepare the total amount of sucrose to be given for a
method 11,13 procedure using a syringe
Ii) Give a quarter of the total amount of sucrose 2minutes prior
to procedure
Iii) Administer on to the anterior of the tongue / by dip of
pacifier (0.2ml per dip)
Iv) Give the rest of the sucrose incrementally throughout the
procedure
Adverse effects5 Safe for one-off use
Repeated and frequent use in preterm neonate may cause
possible adverse neurobiological effect
Caution13 Coughing, choking and desaturation with oral administration
Contraindications4 Necrotizing enterocolitis, paralysed, absent of gag reflex
Pharmacological Therapy
Pharmacological Therapy
Topical anesthesia
Topical anesthesia
Methods that provide topical anesthesia including:
Methods that provide topical anesthesia 7,13
including:
• Local Anesthesia Lubricant Gel
• Local Anesthesia
Examples Lubricant
of local anesthesia Gel 7,13
lubricant gel include Lidocaine 1% and 2%( not available in
MOH formulary). They can be used prior to urinary catheterization, nasogastric tube
Examples of local anesthesia lubricant gel include Lidocaine 1% and 2%( not
insertion and circumcision.
available in MOH formulary). They can be used prior to urinary catheterization,
• Vapo-coolant Sprays 7,13
nasogastric
Examples oftube insertion
vapo-coolant and
sprays circumcision.
include Ethyl Chloride Spray which is available in MOH
formulary. Vapo-coolant sprays cause evaporative cooling thus provide transient numbness.
• Vapo-coolant
It is suitable forSprays
procedures lasting ≤ 60 seconds eg: venipuncture and immunisations. Ethyl
7,13
Chloride Spray should be sprayed at a distance of about 30cm until a fine white film is
Examples
produced. of vapo-coolant sprays include Ethyl Chloride Spray which is
available in MOH formulary. Vapo-coolant sprays cause evaporative cooling
thus provide transient numbness. It is suitable for procedures lasting ≤ 60
seconds eg: venipuncture and immunisations. Ethyl Chloride Spray should be
sprayed at a distance of about 30cm until a fine white film is produced.
• Topical Local Anesthesia Cream 128

Topical anesthesia is obtained by passive diffusion of cream through skin
surface to inhibit sensory neurons transmission in the dermis and epidermis.
Examples of topical anesthesia cream include EMLA Cream and Ametop Gel
(Tetracaine 4% Gel). Ametop Cream is not available in MOH formulary as well
as not in Malaysia market.

• Topical Local Anesthesia Cream
Neonatal Icu
Topical anesthesia is obtained by passive diffusion of cream through skin surface to inhibit
sensory neurons transmission in the dermis and epidermis. Examples of topical anesthesia
cream include EMLA Cream and Ametop Gel (Tetracaine 4% Gel). Ametop Cream is not
available in MOH formulary as well as not in Malaysia market.
Table 5: Mechanism of action, Age Limit, Dosing, Adverse Effects, Cautions and
Contraindications of EMLA cream
5.0
Lignocaine 2.5% and Prilocaine 2.5%

Active ingredients
Decrease the neuronal membrane’s permeability to sodium ions,
resulting in inhibition of depolarization, blocking the initiation and
Mechanism of action 9
conduction of nerve impulses, thus cause local anesthesia action
Onset of action for 60minutes

dermal analgesia 9
Duration of action after 1-2hours
removal 9
3 Not licensed for < 1 year old
Age limit
Hypotension, angioedema
Shock
9
Adverse effects Burning, erythema, itching, rash
Bronchospasm
G6PD deficiency (EMLA cream will predispose the patient to

methaemoglobinemia)
9
Caution Anemia
Methaemoglobinemia
Open wound
Mucous membrane
Contraindications 9
Atopic dermatitis
Dosing 9
Age and weight Max total dose Max application area Max application time
GA < 37weeks 0.5g No data 1 hour
GA ≥ 37weeks 1g 10cm2 1 hour
1 to <3mo or <5kg 1g 10cm2 1 hour
3 to <12mo and >5kg 2g 20cm2 4hour
1-6yo and >10kg 10g 100cm2 4hour
Non-opioid Analgesics
129
Non-opioid
analgesics do not cause respiratory depression, do not impair
gastrointestinal motility and do not cause dependence. Insufficient analgesic
potency for procedural analgesia, thus mainly used for the relief of post-operative
pain3,13

Non-opioid Analgesics
Non-opioid analgesics do not cause respiratory depression, do not impair gastrointestinal motility and do not cause dependence.
Insufficient analgesic potency for procedural analgesia, thus mainly used for the relief of post-operative pain 3 &13
Table 6: Mechanism of action, indications, routes available, time of onset, duration, dosage, adverse effects and contraindication of non-
opioid analgesics 3, 9, 12 &13
Non-opioid Paracetamol Non-steroidal Anti-inflammatory Drugs

Analgesics Diclofenac Ibuprofen
Inhibit the synthesis of prostaglandin in Inhibit prostaglandin synthesis by
Mechanism of Inhibit prostaglandin synthesis by decreasing
CNS and peripherally block pain decreasing the activity of
action the activity of cyclooxygenase
impulse generation cyclooxygenase
Indication
1) Mild-Moderate Pain
approved in 1) Pain And Inflammation In Rheumatic 1) Pain And Inflammation In Rheumatic
2) Post-Operative Pain
MOH Disease & Juvenile Arthritis Disease
3) Pain
formulary
1) Mild-Moderate Pain 1) Pain
FDA-approved 1) Mild-Moderate Pain
2) Moderate-Severe Pain (Adjunct) 2) Rheumatoid Arthritis
indication
3) Fever 3) Fever
Route of
PO , IV, PR PO , IV, PR PO
administration
PO: < 1hour
PO: 1 hour 30-60minutes
Time of onset IV: 5-10minutes
PR: ≤ 1hour
PR: absorption is variable & prolonged
Analgesic
PO; IV: 4-6hours No data 4-6 hour
duration
12
Dosage for PO & PR :
ROA LD MD Freq. Dosage for mild-moderate pain, for
20-25 12-15 Term: ≥6mo, PO or PR:
PO
mg/kg mg/kg QID 3
0.3-1mg/kg (Max: 50mg) TDS
Prem PMA ≥
30 12-18 32week: TDS
Dosage for infants:
PR Dosage for post-op pain for ≥6yo, PR: 4-10mg/kg/dose TDS-QID
Dosage mg/kg mg/kg Prem PMA < 9
32week: BD 1-2mg/kg/day in BD-TDS (Max: Max: 40mg/kg/day
3
150mg/day, 4days)
Dosage for IV :
Neonate: Limited data Dosage for post-op pain for ≥2yo, IM:
3
Infant/Children < 2yo: 0.3-1mg/kg OD-BD, (Max: 2days)
9
7.5-15mg/kg QID (Max: 60mg/kg/day )

131

153
5.0 Neonatal Icu
5.0 Neonatal Icu
Non-opioid Non-steroidal Anti-inflammatory Drugs

Paracetamol
Analgesics Diclofenac Ibuprofen
Liver toxicity (excessive dose or Nausea (7%) Rash (3-9%)
prolonged use/ > 48hours of Diarrhea (6%) Nausea (3-9%)
therapeutic dose) LFT raised (15%) Vomiting (1-3%)
Adverse Rash Constipation (8%) GIT haemorrhage (<1%)
effects Fever URTI (8%) GIT perforation (<1%)
Thrombocyopenia, leukopenia, Acute renal failure Hepatitis (<1%)
12
neutropenia GIT haemorrhage Acute renal failure (rare)
GIT perforation
Hypersensitivity Hypersensitivity Hypersensitivity
Contraindi-
Severe hepatic impairment Asthma Asthma
cation
History of allergic-reaction to aspirin History of allergic-reaction to aspirin
Products 1.Paracetamol syrup 125mg/5ml 1.Diclofenac tablet 50mg 1.Ibuprofen tablet 200mg
available in 2.Paracetamol suppository 125mg; 2.Diclofenac suppository 12.5mg; 25mg
MOH 250mg & 50mg
formulary 3.Diclofenac injection 75mg

Opioids Analgesics
Opioid analgesics had been used for analgesia and sedation. Eg: Morphine, tramadol, fentanyl.
Tramadol is not licensed for the use in children < 12yo.
Table 7: Mechanism of action, routes available, time of onset, duration, dosage and adverse effects of opioid analgesics3,9, 2 &13
Opioid
Morphine Fentanyl
Analgesics
Analgesic: Act on opioid mu receptor in CNS
Bind to opioid receptors in CNS causing inhibition of
descending pain pathway
Mechanism of
Sedation:
action
Bind to opioid receptors in CNS, causing generalized
CNS depression
1) analgesic 1) analgesic
Properties 2) sedative 2) sedative
3) anesthesia
132
Neonatal Icu
Opioids Analgesics
Opioid analgesics had been used for analgesia and sedation. Eg: Morphine,
5.0
tramadol, fentanyl. Tramadol is not licensed for the use in children < 12yo.
Table 7: Mechanism of action, routes available, time of onset, duration,

dosage and adverse effects of opioid analgesics3,9, 2 &13
Opioid Analgesics Morphine Fentanyl
Mechanism of action Analgesic: Act on opioid mu receptor in CNS

Bind to opioid receptors in CNS causing inhibition
of descending pain pathway
Sedation:
Bind to opioid receptors in CNS, causing
generalized CNS depression
Properties 1) analgesic 1) analgesic

2) sedative 2) sedative
3) anesthesia
Uses 1) Pain 1) Pain

2) Post-Op Pain 2) Intra-Op Pain
3) Immediate Post-Op Pain
4) Adjunct In Maintenance Of
General/Regional Anesthesia
Route of administration PO IV
IV; IM; SC (IV is preferred) IM (for> 1yo)
Time of onset IV: 5-10mins IV: almost immediate

PO: 30mins IM: 8mins
Duration of action 4 hours IV: 0.5-1 hour
IM: 1-2 hours
Dosage PO: Sedation/analgesia (IV slow push):

0.08mg/kg Q4-6hr 0.5-4mcg/kg, repeat PRN (Q2-4hr)
IV over 5mins, IM, SC: Sedation/analgesia (IVI):

0.05-0.2mg/kg/dose, repeat PRN (Q4hr) 1-5mcg/kg/hour
IVI: Anesthesia (IV):

LD 0.1-0.15mg/kg then 5-50mcg/k/dose 12
MD 10-30mcg/kg/hour
(Max: 30mcg/kg/hour) 9 & 12
Adverse effects 1) Respiratory depression Sedation/analgesia (IV slow push):

2) Sedation 0.5-4mcg/kg, repeat PRN (Q2-4hr)
3) Nausea & vomiting
4) Reduced GIT motility: constipation, ileus Sedation/analgesia (IVI):
5) Urinary retention 1-5mcg/kg/hour
6) Tolerance
7) Withdrawal symptoms Anesthesia (IV):
8) Hypotension, bradycardia 5-50mcg/k/dose 12
Notes • reliable & predictable effects • synthetic opioid analgesic

•easily reversed by naloxone • 50-100times more potent than
morphine
• < hypotensive effect & safer in
hyperactive airway disease
• easily reversed by naloxone

Neonatal Icu
Benzodiazepine
• Benzodiazepine have anxiolytic, amnestic and skeletal muscle relaxant
5.0
properties, but not analgesic effects. (Eg: Midazolam, diazepam, lorazepam.)

• Lorazepam has long duration of action, not used for procedural sedation.
Midazolam is commonly used due to its short half-life and fast onset. Diazepam
is used too but it has long half-life, active metabolites and erratic absorption.

dosage and adverse effects of benzodiazepines3,9, 2 &13
Benzodiazepine Midazolam Diazepam
Mechanism of action Bind receptor at several sites within CNS, Modulate postsynaptic effect of GABA-A
increase inhibitory effect of GABA transmission, resulting in increase in
presynaptic effect
Act on limbic system as well as thalamus
& hypothalamus, inducing a calming effect
Uses 1) procedural sedation 1) sedation/muscle relaxant (for children)

2) sedation
Route of administration PO; IV; IM PO

Intranasal (use 5mg/ml injection) IV/IM
Sublingual (5mg/ml injection, mixed with syrup)
Buccal (for ≥ 6mo)
PR (for ≥ 6mo)
Time of onset IV: 3-5mins IV: 2-3mins

IM: ≤ 5mins
Duration IV: 20-30mins IV: 30-90mins
IM: 2-6hours
Full recovery maybe ≥ 24hours
Dosage PO For procedures:

0.25mg/kg/dose PO:
0.2-0.3mg/kg (Max: 10mg) pre-procedure
Intranasal IV over 5mins:
0.2mg/kg/dose 0.05-0.1mg/kg, titrate slowly (Max:
0.25mg/kg total dose)
Sublingual
0.2mg/kg/dose For sedation/muscle relaxant:
PO:
IV (over 5mins); IM 0.12-0.8mg/kg/day in TDS-QID
0.05-0.15mg/kg, repeat PRN, Q2-4hr IV/IM:
0.04-0.3mg/kg/dose Q2-4hour (Max:
IVI 0.6mg/kg/within 8hour) 9
1-4mcg/kg/min 12
Adverse effects Decreased respiratory effect (23%) Common (frequency unknown):

Apnea (15%) Hypotension
Drowsiness (1-5%) Respiratory depression
Nausea-vomiting (3%) Fatigue
Cough (1%) Muscle weakness
Somnolence Urinary retention
Headache
Hiccoughs
Respiratory arrest
Hypotension

Neonatal Icu
Apnea (15%) Hypotension
Drowsiness (1-5%) Respiratory depression
Nausea-vomiting (3%) Fatigue
Barbiturates Cough (1%) Muscle weakness
Somnolence Urinary retention
Barbiturates Headache
act on GABA receptors and hyperpolarize the nerve cell
5.0
Hiccoughs
membrane via chloride channels. Barbiturates have sedation and
Respiratory arrest
amnesia properties
Hypotensionbut not analgesic effect. Barbiturates have neuro-
protective effect as they can lower intracranial pressure and they have
Barbiturates
anticonvulsant effect.
Barbiturates act on GABA receptors and hyperpolarize the nerve cell membrane via chloride ch
amnesia
Eg: properties but&not
Pentobarbital analgesic effect. Barbiturates have neuro-protective effect as they can l
Thiopental
anticonvulsant effect.
Pentobarbital is not available in MOH formulary.
Eg: Pentobarbital & Thiopental
Pentobarbital is not available in MOH formulary.
Table 9: Mechanismdosage and
of action, adverse
routes effects
available, timeofofthiopental
onset, duration, dosage and adverse e
Uses Induction of anesthesia (non-FDA approved for pediatric use)

Route of administration IV
Dosage 2-6mg/kg IV slow push
Adverse effects Respiratory depression
Tolerance, dependence, cardiovascular depression
(prolonged use)
Products available in Thiopental sodium injection 500mg
MoH formulary

5.0 Neonatal Icu
Miscellaneous agents
Eg: Ketamine, propofol, dexmedetomidine, nitrous oxide

dosage and adverse effects of miscellaneous agent. 3,9,12,13
Agent Ketamine Propofol Dexmedetomidine Nitrous oxide
Mechanism of Noncompetitive NMDA Act on GABA-A receptor Selective alpha-2 adrenergic

-
action receptor antagonist and block NMDA receptor agonist with sedative effects
1) Sedative 1) Anxiolytics
1) Sedative
Properties 2) Analgesic 1) Sedative 2) Amnestic
3) Amnestic 3) mild-moderate analgesic
1) sedation pre-procedure ( 1) sedation ( 1mo)
Uses in Safety and efficacy is not 1) maintenance of anesthesia
1mo) 2) Induction &
pediatric established in pediatric with other anesthestic agent
2) Induction & maintenance maintenance of anesthesia
patients patients 2) analgesia
of anesthesia ( 1mo)

IV
Route of
IM IV IV Inhalation
administration
Induction & maintenance of

anesthesia (short procedure)
IV over 1min:
Maintenance of anesthesia:
1-2mg/kg
50-6% in oxygen
3 IM
Dosage - -
4mg/kg
Analgesia
Up to 50% in oxygen
Induction & maintenance of
anesthesia (long procedure)
8-30mg/kg/min
1) Hypertension, tachycardia 1) hypoxia
Adverse effects 2) Pscychiatric sign & - - 2) megaloblastic anemia
symptoms 3) neurological toxic effect
Products
Ketamine Injection 10mg/ml; Propofol Injection Dexmedetomidine Injection
available in -
50mg/ml 10mg/ml; 20mg/ml 100mcg/ml
MoH formulary
Neonatal Icu
References:
5.0
1. American Society of Anesthesiologists Home of Delegates. Continuum of
Depth of Sedation: Definition of General Anesthesia and Levels of Sedation /
Analgesia, 2009 October
2. Bhatt M, Kennedy RM, Osmond MH, McAllister JD, Ansermino JM, Evered
LM, Roback MG. Consensus-Based Recommendations for Standardizing
Terminology and Reporting Adverse Events for Emergency Department
Procedural Sedation and Analgesia in Children. 2009 Apr; 53(4): 426-435.
3. BMA, Royal Pharmaceutical Society, Royal College and Pediatric of Child

Health. BNF for Children 2011-2012.
4. Brighton and Sussex University Hospital, NHS. Pain Management Guideline,

July 2010
5. Holsti L, Grunau RE. Considerations for Using Sucrose to Reduce Procedural

Pain in Preterm Infants. Pediatrics. 2010 April; 125(5): 1042-1047.
6. Lefrak L, Burch K, Caraventes R, Knoerlein Kim, DeNolf N, Duncan J,

Hampton F, Johnston C, Lockey D, Martin-Walters C, McLendon D, Porter
M, Richardson C , Robinson C, Toczylowski K. Sucrose Analgesia: Identifying
Potentially Better Practices. Pediatrics. 2006 Nov; 118 (S2): S197-S202.
7. My Pharmacist House. My Blue Book version 2.3.1
8. Pain Terms: A Current List with Definitions and Notes on Usage. International
Association for the Study of Pain Taxonomy Working Group; 2011. [cited
06 October 2014]. Available from: http://iasp.files.cms-plus.com/Content/
ContentFolders/Publications2/ClassificationofChronicPain/Part_III-
PainTerms.pdf
9. Pediatric & Neonatal Lexi Drugs, Lexicomp version 2.7.2
10. The Royal Australasian College of Physicians, Pediatrics & Child Health
Divisions. Guideline Statement: Management of Procedure- related Pain in
Neonates, 2005

Neonatal Icu
11. The Royal Children’s Hospital Melbourne. Sucrose (Oral) for Procedural Pain
5.0
Management in Infants, 14 Dec 2012.
12. Thomson Reuters. Neofax 24th edition 2011.
13. Wilson-Smith, EM. Procedural Pain Management in Neonates, Infants and

Children. Reviews in Pain. 2011 Sept; 5(3): 4-12.

Neonatal Icu
TOTAL PARENTERAL NUTRITION IN NEONATES
5.0
Indications for Total Perenteral Nutrition (TPN)
• Birth weight < 1000 gm

• Birth weight 1000-1500 gm and anticipated to be not on significant feeds for
3Total
or more days.
Parenteral Nutrition In Neonates
• Birth weight > 1500 gm and anticipated to be not on significant feeds for 5 or
Indications for Total Perenteral Nutrition (TPN)
more days.
• Birth weight < 1000 gm
• Surgical
• Birth conditions
weight 1000-1500in gm
neonates: necrotizing
and anticipated enterocolitis,
to be not on significant gastroschisis,
feeds for 3 or more
omphalocoele,
days. tracheo-esophageal fistula, intestinal atresia,
• Birth weight > 1500 gm and anticipated to be not on significant feeds for 5 or more days.
malrotation, short inbowel
• Surgical conditions syndrome,
neonates: meconium
necrotizing enterocolitis, ileus and
gastroschisis, diaphragmatic
omphalocoele,
hernia.tracheo-esophageal fistula, intestinal atresia, malrotation, short bowel syndrome,
meconium ileus and diaphragmatic hernia.
Energy Requirement
Energy Requirement
Table 1 : Parenteral Energy Requirement
Age (Year) Energy Requirements (Kcal/kg/day)

Pre-term 110 - 120
0-1 90 - 100
1-7 75 - 90
7-12 60 - 75
12-18 30 - 60
Components OfParenteral
Components Of Parenteral Nutrition
Nutrition
1. Macronutrients
1. Macronutrients
• Proteins
• Proteins
• Carbohydrates
• Carbohydrates
• Lipid
• 2.Lipid
Micronutrients
• Electrolytes
2. Micronutrients
• Trace elements
• Electrolytes
• Vitamins
• 3.Trace elements
Fluids
• Vitamins
• Water for injection
3. Fluids
• Water for injection

Neonatal Icu
1.Macronutrients
Proteins
• Multiple studies have demonstrated that earlier parenteral amino
5.0
acid administration at amounts of 1.0–3.5 g/(kg·day) can reverse a negative

nitrogen
1.
or stable isotope balance, which is indicative of protein accretion and
Macronutrients
thus growth, even at low caloric intake
Proteins
• It decreases frequency and severity of neonatal hyperglycaemia by stimulating
Multiple studies have demonstrated that earlier parenteral amino acid administration
•Macronutrients
1. endogenous
at amounts insulin
of 1.0–3.5 secretion
g/(kg·day) canand stimulates
reverse growth
a negative nitrogen by enhancing the
or stable
Proteins
secretion ofbalance,
isotope insulinwhich
and isinsulin-like growth
indicative of protein factors.
accretion and thus growth, even at low
caloric intake
• Reduction
• •Multiple in dosage
It decreases
studiesfrequency may be needed
and severity
have demonstrated of
that in critically
neonatal
earlier parenteralill,
hyperglycaemia significant
by stimulating
amino hypoxaemia,
acid administration
endogenous insulin secretion andcan
stimulates
suspected
at amounts orofproven
1.0–3.5 infection
g/(kg·day) and
insulin and insulin-like growth factors.
highgrowth
reverse dose by enhancing
steroids.
a negative nitrogen theorsecretion
stable of
isotope balance, which is indicative of protein accretion and thus growth, even at low
Reduction
•caloric intakein dosage may be needed in critically ill, significant hypoxaemia, suspected or
• Adverse effects of excess protein include a rise in urea and ammonia and high
proven infection and high dose steroids.
• It decreases
levels frequency and
of potentially severity of neonatal hyperglycaemia by stimulating
• Adverse effects of toxic
excessamino acids
protein include asuch as phenylalanine.
rise in urea and ammonia and high levels of
endogenous insulin
potentially toxic secretion
amino and as
acids such stimulates growth by enhancing the secretion of
phenylalanine.
insulin and insulin-like growth factors.
Proteins Requirement
• Reduction in dosage may be needed in critically ill, significant hypoxaemia, suspected or
Proteins requirement
proven infection and high dose steroids.
• Adverse effects of excess protein include a rise in urea and ammonia and high levels of
Table 2 : Parenteral amino acid supply
potentially toxic
Ageamino
(Year) acids such as phenylalanine.
Protein Requirement (g/kg/day)
Preterm Infants 1.5 - 4.0
Term Neonates 1.5 - 3.0
Proteins requirement
2nd Month to 3rd Year 1.0 - 2.5
3rd to 18th Year 1.0 - 2.0
Table 2 : Parenteral amino acid supply
(Critically ill patients may require upto 3.0)
Age (Year) Protein Requirement (g/kg/day)
1g amino
1g aminoacidsPreterm
acids provide
provideInfants
4kcal
4kcal energy
energy 1.5 - 4.0
Term Neonates 1.5 - 3.0
2nd nitrogen/
The preferred Month tonon-protein
3rd Year calorie is 1 g/100~200 kcal 1.0 - 2.5
The Product
preferred nitrogen/
used3rd
is Vaminolactnon-protein
6.53%
to 18th Year calorie is 1 g/100~200 1.0 -kcal
2.0 Product used is
Vaminolact 6.53% (Critically ill patients may require upto 3.0)
Lipids
1g amino acids provide 4kcal energy
Lipids • Lipids prevent essential fatty acid deficiency, provide energy substrates and improve
delivery of fat soluble vitamins.
The preferred
• Lipids
• LBW nitrogen/
prevent
infants maynon-protein
essential calorie
fatty
have immature is 1 g/100~200
acid
mechanisms deficiency, kcal provide
for fat metabolism. energy
Some substrates
conditions
Product used is lipid
inhibit Vaminolact 6.53%
clearance e.g. infection, stress, malnutrition.
and• improve delivery of
Avoid concentrations fat soluble
>2g/kg/day vitamins.
if infant has jaundice requiring phototherapy.
Lipids
• LBW infants may have immature mechanisms for fat metabolism. Some
Lipids requirement
conditions inhibitessential
• Lipids prevent lipid clearance
fatty e.g. Requirement
infection,
acid3 deficiency,
Table : Lipid provide stress, malnutrition.
energy substrates and improve
delivery of fat soluble vitamins.
• Avoid
• LBWAge
concentrationsInitiate,
infants may have g/kg/daymechanisms
>2g/kg/day
immature Increase
if infant forby,
has g/kg/day
fatjaundice Maximum,
requiring
metabolism. g/kg/day
phototherapy.
Some conditions
Preterm Neonates 0.5 - 1.0 0.5 - 1.0 3.0 - 4.0
inhibit lipid clearance e.g. infection, stress, malnutrition.
Term Neonates 1.0 0.5 - 1.0 3.0 - 4.0
• Avoid concentrations >2g/kg/day if infant has jaundice requiring phototherapy.
Lipids •Requirement
Lipid is crucial in avoiding essential fatty acids deficiency (EFAD). EFAD can be avoided
with as little as 0.5-1g/kg/day of fat emulsion.
Lipids requirement
• 1g of lipid provide 9 kcal of energy.
Table 20%
• Product available are lipofundin 3 : Lipid Requirement
and SMOFlipid. MCT/LCT lipid emulsions have an
advantage over LCT lipid emulsions.
Age Initiate, g/kg/day Increase by, g/kg/day Maximum, g/kg/day
Preterm Neonates 0.5 - 1.0 0.5 - 1.0 3.0 - 4.0
139
Term
Neonates 1.0 0.5 - 1.0 3.0 - 4.0
• Lipid is crucial in avoiding essential fatty acids deficiency (EFAD). EFAD can be avoided
with as little as 0.5-1g/kg/day of fat emulsion.
• Product available are lipofundin 20% and SMOFlipid. MCT/LCT lipid emulsions have an
advantage over LCT lipid emulsions.
Neonatal Icu
• Lipid is crucial in avoiding essential fatty acids deficiency (EFAD). EFAD can be
avoided with as little as 0.5-1g/kg/day of fat emulsion.
5.0
• Product available are lipofundin 20% and SMOFlipid. MCT/LCT lipid emulsions
have an advantage over LCT lipid emulsions.
Carbohydrate
• For ELBW neonates, continuous glucose infusion is needed to cater relatively

high energy requirement in maintaining cerebral function.
• Maximum
Carbohydraterate: 12 - 13 mg/kg/min (lower if lipid also administered) but in
practice
• For often
ELBW limited
neonates,by hyperglycaemia.
continuous glucose infusion is needed to cater relatively high
energy requirement in maintaining cerebral function.
• Hyperglycaemia
• Maximum rate: occurs in 20-80%
12 - 13 mg/kg/min (lowerof ELBW
if lipid also as a result but
administered) of decreased
in practice ofteninsulin
secretion and
limited by insulin resistance, presumably due to to glucagon,
hyperglycaemia.
catecholamine
• Hyperglycaemia and cortisol
occurs release.
in 20-80% Hyperglycaemia
of ELBW in theinsulin
as a result of decreased ELBW managed
secretion
by decreasing
and insulin glucose
resistance, administration,
presumably due toadministering intravenous
to glucagon, catecholamine andamino
cortisol acids
and/orrelease. Hyperglycaemia in the ELBW managed by decreasing glucose administration,
infusing exogenous insulin.
administering intravenous amino acids and/or infusing exogenous insulin.
Carbohydrate requirement
Carbohydrate requirement
Table 4 : Rate of administration of dextrose in pediatric patients on PN
Initiate, Increase by, Maximum rate,

Age
mg/kg/day mg/kg/day mg/kg/day
Preterm Neonates 4-6 1-2 12 - 13
Term Neonates 6-8 2-4 -
Infant 6-8 2-4 13 - 14
Children 6-8 2-4 6-9
• Source of
• Source of carbohydrate
carbohydrate is Dextrose 50%
is Dextrose 50%
• 1g of carbohydrate provides 4kcal energy.
• 1g of carbohydrate provides 4kcal energy.
*The use of early insulin therapy to prevent hyperglycemia is not recommended. The glucose
infusion rate should be reduced by 1-2 mg/kg/min and insulin should be administered (0.05
*TheIU/kg/h)
use of early
when insulin therapy
hyperglycemia to prevent
is uncontrollable hyperglycemia
with glucose is not
infusion rate being recommended.
4 mg/kg/min .
The Fluids
glucose infusion rate should be reduced by 1-2 mg/kg/min and insulin
should be administered (0.05 IU/kg/h) when hyperglycemia is uncontrollable with
• Fluids usually started at 60-80 ml/kg/day (if newborn), or at whatever stable fluid intake
glucose infusion rate being 4 mg/kg/min .
the baby is already receiving.
• Postnatal weight loss of 5 - 15 % per day in the ELBW is acceptable.
Fluids • Volumes are increased over the first 7 days in line with the aim to deliver 120-150
ml/kg/day by day 7.
• Fluids usually started at 60-80 ml/kg/day (if newborn), or at whatever stable
fluid
Fluidsintake the baby is already receiving.
requirements
• Postnatal weight Table loss of 5 - 15
5 : Parenteral fluid% per during
intake day infirst
thepostnatal
ELBW week
is acceptable.
• Volumes are increased over the Recommended first 7 daysfluidin line with
intake the aim to deliver 120-
Days After
150ml/kg/day
Birth by day 7. (ml/kg/day)
1st Day 2nd Day 3rd Day 4th Day 5th Day 6th Day
Term
60 -‐ 120 80 -‐ 120 100 -‐ 130 120 -‐ 150 140 -‐ 160 140 -‐ 180
Neonate
Preterm
60 -‐ 80 80 -‐ 100 100 -‐120 120 -‐150 140 -‐ 160 140 -‐ 160
Neonate
140
*The use of early insulin therapy to prevent hyperglycemia is not recommended. The glucose
infusion rate should be reduced by 1-2 mg/kg/min and insulin should be administered (0.05
IU/kg/h) when hyperglycemia is uncontrollable with glucose infusion rate being 4 mg/kg/min .
Neonatal Icu
Fluids Requirement
Table 5 : Parenteral fluid intake during first postnatal week
Recommended fluid intake

Days After
5.0
(ml/kg/day)
Birth
1st Day 2nd Day 3rd Day 4th Day 5th Day 6th Day
Term
60 -‐ 120 80 -‐ 120 100 -‐ 130 120 -‐ 150 140 -‐ 160 140 -‐ 180
Neonate
Preterm
Neonate 60 -‐ 80 80 -‐ 100 100 -‐120 120 -‐150 140 -‐ 160 140 -‐ 160
>1500g
>1500g
Preterm
Preterm
Neonate
Neonate 80
80 -‐ -‐9 90 0 100
100 -‐-‐ 1110
10 120
120 -‐130
-‐130 130
130 -‐150 140 140
-‐150 -‐ 160 -‐ 160 160 -‐ 160
180 -‐ 180
<1500g
<1500g
Factors affecting fluids requirement
140

2. Micronutrients
2. Micronutrients
Electrolytes
Electrolytes
• Sodium
• Sodiumsupplementation should
supplementation should be started
be started afterdiuresis
after initial initial (usually
diuresis (usually
after the 48 after
hours),
the 48 when serum
hours), whensodiumserum starts to drop or
sodium at least
starts toatdrop
5-6% weight
or at loss.
least at 5-6% weight
loss.
• Failure to provide sufficient sodium may be associated with poor weight gain.
• Potassium needs are 2-3 mEq/kg/day in both term and preterm infants. Start when urine
• Failure to provide sufficient sodium may be associated with poor weight gain.
output improves after the first 2-3 days of life.
• Potassium needsconditions,
• In extrauterine are 2-3 mEq/kg/day in both
intrauterine calcium termrates
accretion andispreterm
difficult toinfants.
attain. Start
whenConsidering
urine output improves
long-term after
appropriate the first 2-3
mineralization and days of that
the fact life.calcium retention
between 60 to 90 mg/kg/d suppresses the risk of fracture and clinical symptoms of
• In extrauterine
osteopenia, a conditions, intrauterine
mineral intake between 100 to calcium accretion
160 mg/kg/d rates is
of highly-absorbed difficult to
calcium
and 60 to 75 mg/kg/d of phosphorus could be recommended.
attain. Considering long-term appropriate mineralization and the fact that
• Monitoring for osteopaenia of prematurity is important especially if prolonged PN.
calcium retention between 60 to 90 mg/kg/d suppresses the risk of fracture
and• clinical
A normal symptoms
magnesium levelof isosteopenia,
a prerequisite a
formineral
a normal intake
calcaemia.between 100 to 160
In well balanced
formulations, however, magnesium level does not give rise to major problems.
mg/kg/d of highly-absorbed calcium and 60 to 75 mg/kg/d of phosphorus
could be recommended.
141
Neonatal Icu
• Monitoring for osteopaenia of prematurity is important especially if prolonged PN.
• A normal magnesium level is a prerequisite for a normal calcaemia. In well
balanced formulations, however, magnesium level does not give rise to major
problems.
5.0
Electrolytes Requirement
Electrolytes requirement
Table 6 : Daily electrolyte requirements for pediatric patients
Electrolytes Preterm Neonates Infants/Children

Sodium 2 - 5 mEq/kg 2 - 5 mEq/kg
Potassium 2 - 4 mEq/kg 2 - 4 mEq/kg
Calcium 2 - 4 mEq/kg 0.5 - 4 mEq/kg
Phosphorus 1 - 2 mmol/kg 0.5 - 2 mmol/kg
Magnesium 0.3 - 0.5 mEq/kg 0.3 - 0.5 mEq/kg
As needed to mantain acid As needed to mantain acid
Acetate
base balance base balance
Table 7 : Recommendations on the daily intake of Ca, P, Mg and vitamin D for preterm
VLBW infants issued by different bodies & authors
Current
Intake
ESPGAN ESPGHAN LSRO Atkinson & RIGO AAP authors
Reccomenda
1987 2010 2002 Tsang 2005 2007 2013 Proposal
tion
2013
Ca,
70 -140 120-140 150-220 120-200 100-160 150-220 120-200
mg/kg/day
P, mg/kg/day 50-90 60-90 100-130 70-120 60-90 75-140 60-140
Mg, 6.8-17mg/ Not Not
4.85-9.7 8-15 7.2-9.6 8-15
mg/kg/day 100kCal provided provided
Vitamin D, 800- 400-
800-1600 800-1000 90-225 200-1000 200-400
IU/day 1000 1000
142


5.0 Neonatal Icu

Table 8 : Acceptable range of vitamin intakes for VLBW & ELBW infants
Neonatal Icu
Table 8 : Acceptable range of vitamin intakes for VLBW & ELBW infants
Trace elements requirement
5.0
Trace elements requirement
Product Dosage
Peditrace
Neonates < 15kg : 1ml/kg/day
Trace Elements
Infants & Children >15kg : 15ml/day
Max : 15mL / day
Water soluble
Water vitamins
soluble vitamins requirement
requirement
Product Dosage
Soluvit N
Neonates < 10kg : 1ml/kg/day
Water Soluble Vitamin
Infants & Children >10kg : 10ml/day
Max : 10mL / day
References :
143

1. Guidelines on Paediatric Parenteral Nutrition of the European Society of
Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the
European Society for Clinical Nutrition and Metabolism (ESPEN), Supported
by the European Societyof Paediatric Research (ESPR) 2005; Berthold
Koletzko, Olivier Goulet, oanne Hunt, Kathrin Krohn, and Raanan Shamir
2. Paediatric Protocols For Malaysian Hospitals 3rd Edition ; Hussain Imam Hj

Muhammad Ismail; Ng Hoong Phak; Terrence Thomas
3. Koletzko B, Poindexter B, Uauy R (eds): Nutritional Care of Preterm Infants:

Scientific Basis and Practical Guidelines. World Rev Nutr Diet. Basel, Karger,
2014, vol 110, pp 49–63 ( DOI: 10.1159/000358458

Neonatal Icu
FLUID & ELECTROLYTE MANAGEMENT

5.0
Fluid, electrolyte, and nutrition management is important because most infants

in a neonatal intensive care unit (NICU) require intravenous fluids (IVFs) and have

shifts of fluids between intracellular, extracellular, and vascular compartments.
Therefore, careful attention to fluid and electrolyte balance is essential. If
Fluid & Electrolyte Management
inappropriate fluids are administered, serious morbidity may result from fluid and
electrolyte imbalances.
Fluid, electrolyte, Inadequate
and nutrition management attention to nutrition
is important becausein the
mostneonatal
infants in period
a neonatal
leads to growth
intensive failure,
care unit (NICU)osteopenia of prematurity,
require intravenous and other
fluids (IVFs) complications.
and have shifts of fluids between
intracellular, extracellular, and vascular compartments. Therefore, careful attention to fluid and
electrolyte
Total balance is essential.
fluid requirements If inappropriate fluids are administered, serious morbidity may
result from fluid and electrolyte imbalances. Inadequate attention to nutrition in the neonatal
period leads to growth failure, osteopenia of prematurity, and other complications.
Total fluid requirement includes the maintenance requirement to replace measure
losses (urine, stool) and insensible water loss (IWL) and the fluid requirement for
growth.
Fluid and Electrolyte Management
Total fluid
• Total requirements
fluids = Maintenance + Growth
Total Fluid requirement
• Maintenance = SWLincludes the maintenance
(sensible water lost)requirement to replacewater
+ IWL (Insensible measure
lost)losses
(urine, stool) and insensible water loss (IWL) and the fluid requirement for growth.
• Start with D10W (10% dextrose in water) Sodium and Potassium added on
• Total fluids = Maintenance + Growth
the second/third day
• Maintenance = SWL (sensible water lost) + IWL (Insensible water lost)
• Slower
• Startrates of increment
with D10W for preterm
(10% dextrose infants,
in water) Sodiumi.e.
andofPotassium
20 mls/kg/day.
added on the
second/third day
• More increments
• Slower may be needed
rates of increment for pretermif evidence
infants, i.e. of
of dehydration,
20 mls/kg/day.
i.e.
• excessive weight
More increments loss
may and hypernatraemia
be needed >145 mmol/l.
if evidence of dehydration,
i.e. excessive weight loss and hypernatraemia >145 mmol/l.
Table 1 : Empiric
Table Fluid
1: Empiric Therapy
Fluid forfor
Therapy Newborns
newborns
0-24 hours 60 ml/kg/day

> 72 hours 150 ml/kg/day
Fluid Issues Associated With Common Neonatal Conditions:
Issues requiring fluid restriction:
 RDS: Excessive fluid can lead to fluid overload and increased risk of BPD
 BPD: Excessive fluid can worsen therefore treated with diuretics to reduce
pulmonary edema
 PDA: Volume overload can open ductus and worsen respiratory status
 HIE: Associated with ATN and/or SIADH and can lead to subsequent volume
overload
Electrolyte Requirements
Neonatal Icu
Fluid Issues Associated With Common Neonatal Conditions:
Issues requiring fluid restriction:
5.0
• RDS: Excessive fluid can lead to fluid overload and increased risk of BPD
• BPD: Excessive fluid can worsen therefore treated with diuretics to reduce
pulmonary edema
• PDA: Volume overload can open ductus and worsen respiratory status
• HIE: Associated with ATN and/or SIADH and can lead to subsequent volume
overload
Electrolyte Requirements
First 24h of life: No electrolytes (except Ca)

• Ca especially important for preterm infants After 24h of life:
• Na : 2-3 mmol/kg/day
• K : 1-2 mmmol/kg/day
Supplemetation of elctrolytes will need to be fine-tuned according to measurement
of electrolytes and urine output and disease status.
* Extremely pre-term infants with metabolic acidosis (loss of bicarb in urine) may
benefit from sodium acetate
After the first week of life, during active groth the requirement of sodium and
potassium increases;
• Na: 3-5 mmol/kg/day
• K: 2-3 mmmol/kg/day
Many preterm may require 6-8mmol/kg/day of sodium and up to 12mmol/kg/
day. This is partly due to inability to retain sodium and secondary use of diuretics
References:
1. Hussain Imam Hj Muhammad Ismail, Ng Hoong Phak, Terrence Thomas.

Paediatric Protocols for Malaysian Hospitals, 3rd ed. : Kementerian Kesihatan
Malaysia; 2012
2. O’Brien, F., Walker, I. A. (2014), Fluid homeostasis in the neonate. Pediatric
Anesthesia, 24: 49–59. doi: 10.1111/pan.12326
3. B. Koletzko, C. Agostoni, P. Ball et al. ESPGHAN Guidelines on paediatric
parenteral nutrition.Journal of Pediatric Gastroenterology and Nutrition
2005;41:S1-S87

Neonatal Icu
NECROTIZING ENTEROCOLITIS
5.0
Introduction
As mentioned by Morgan JA et al, necrotising enterocolitis (NEC) is the commonest
neonatal gastrointestinal emergency.7 NEC is an inflammatory disease of the
intestine which is often associated with sepsis and frequently complicated by
perforation, peritonitis and death12
Spontaneous intestinal perforation (SIP) among preterm infants had been
categorized as necrotizing enterocolits. However it has different disease entity
and different pathogenesis. SIP usually occurs in the 1st several days after birth
and is not associated with enteral feeding. SIP is associated with minimal intestinal
inflammation and necrosis with low level of serum inflammatory markers8
Risk Factors7,9

(1) Prematurity (<28weeks)
(2) Enteral feeding
(3) Growth restricted neonate
(4) Maternal hypertensive disease of pregnancy
(5) Placental abruption
(6) Absent or reversed end diastolic flow velocity
(7) Use of umbilical catheters
(8) Low Apgar scores
(9) Packed cell transfusions
Pathogenesis6,8,9,12
The pathogenesis of NEC is not completely understood, it is considered to be

multifactorial. It is a combination of the following causes:
(1) Immature epithelial barrier
(2) Abnormal microbial colonization in the intestine
(3) Hypoxia-ischemia
(4) Genetic predisposition

Neonatal Icu
• Immature epithelial barrier 12
5.0
The intestinal mucosa presents a persistent equilibrium state between injury
and repair. Intestinal mucosa injury can be due to various factors including
hypoxia, infection, and starvation. In physiological conditions, healing of
epithelium starts with migration of matured enterocytes from health to the
injured area. Subsequently, new enterocytes will mature and migrate to the
surface epithelium. In NEC, there is a marked inhibition in both the enterocyte
migration and proliferation, resulting more intestinal mucosa injury.
Toll-like receptors (TLRs) are innate immunity components located on the
epithelial surface which play a major role in tissue repair. TLR type 4 (TLR4)
are crucial in NEC development. The activation of TLR4 inhibits the enterocyte
migration and maturation thus.
• Abnormal microbial colonization in the intestine9,12

Mechanism by which infection contribute to NEC remain unknown. The
suggested mechanism is the decreased microbial diversity and alteration in
the microbial species that may happen in prolonged antibiotic therapy,
which may reduce the colonization resistance. The usual rich diversity of
intestinal microflora which protect the host against hospital-acquired
pathogens is lacking. Studies suggest that NEC is not due to a single species
but is more likely from an undefined dysbiosis, that may cause TLR4 activation
and pathogens translocation across the epithelium.
• Hypoxia-ischemia8
Hypoxia and ischemia modulate the balance in microvascular tone related
to the production of vascular regulator eg nitric oxide and endothelin which
may cause NEC

dysbiosis, that may cause TLR4 activation and pathogens translocation across the epithelium.
• Hypoxia-ischemia 8
Neonatal Icu
Hypoxia and ischemia modulate the balance in microvascular tone related to the production of
vascular regulator eg nitric oxide and endothelin which may cause NEC
Fig 1: Pathogenesis of NEC (Adapted from Terrin G) 12

5.0
Table 1: Clinical presentation of NEC (Modified Bell Classification) (Adapted from Patel BK)9
148

Complications6,9
Complications
6,9
(1) higher incidence of nosocomial infection

(2) lower level of nutrient intake
(1) higher incidence
(3) slower of nosocomial infection
growth development
(2) lower level
(4) longer of nutrient
duration intake
of intensive care and hospital stay
(5) higher incidence of bronchopulmonary dysplasia
(3) slower growth
(6) higher incidence development
of retinopathy of prematurity
(4) longer duration
(7) growth restrictionofin intensive
long term care and hospital stay
(8) neurodisability
(9) adverse of bronchopulmonary
neurodevelopment in long term dysplasia
Management
of retinopathy of prematurity
(7) growth restriction in long term
Table 2: Management of NEC based on Modified Bell Classification (Adopted from Neu J)8
(8) neurodisability
(9) adverse neurodevelopment in long term
Modified Bell Classification Management
172 Paediatric Pharmacy Services

(1) Clinical observation of increased abdominal
Guideline
distension and feeding intolerance
(2) Brief discontinuation of feeding eg: 24hr-NBM
(5) higher incidence of bronchopulmonary dysplasia
(6) higher incidence of retinopathy of prematurity
(7) growth restriction in long term
Neonatal Icu
(8) neurodisability
(9) adverse neurodevelopment in long term
Management
Management
Table 2: Management of NEC based on Modified Bell Classification (Adopted from Neu J)8
5.0
Modified Bell Classification Management
(1) Clinical observation of increased abdominal

distension and feeding intolerance
(2) Brief discontinuation of feeding eg: 24hr-NBM
“Suspected” NEC (3) Abdominal radiograph (if have yet done)
(4) Monitor FBC
(5) Blood C&S
(6) Short course of IV antibiotics
(1) Enteral feeding discontinuation for 7-10days
(2) Monitor FBC
“Defined” NEC (3) Blood C&S
(4) IV antibiotics 7-10days
(5) Refer surgical team
“Advanced” NEC (1) Exploratory laparotomy with resection if necessary
(2) Primary peritoneal drainage without laparotomy
9 149
Indications for surgery 9
Indications fordeterioration
(1) clinical surgerydespite maximal medical intervention
(2) presence of pneumoperitoneum
(1) clinical deterioration
(3) abdominal mass with despite
intestinal maximal
obstruction medical intervention
(2) presence
(4) of pneumoperitoneum
development (2) Primary peritoneal drainage without laparotomy
of intestinal stricture
(3) abdominal
Indications
Prevention mass with
for surgery 9 intestinal obstruction
(1) clinical deterioration
Numerous approaches despite
have maximal
been medical
proposed intervention
to prevent NEC:
(4) development of intestinal
(2) presence of pneumoperitoneum
stricture
(3) abdominal mass
Table 3: with intestinal
Strategies Prevent NEC (Adapted from Neu J & Walker WA)8
toobstruction
(4) development of intestinal stricture
Prevention Evidence of Evidence of Efficacy Evidence of Efficacy Proposed Efficacy
Numerous approaches
Prevention
Efficacy & Safety have been proposed
but Questionable to Models
in Animal prevent NEC: but Lack of
Numerous approaches have been Safety but Not NEC:
proposed to prevent in Human Evidence
Breast-milk feeding Probiotics Growth factors Prebiotics
Non-aggressive Arginine
Table 3: Strategies Anticytokines
to Prevent NEC (Adapted from Neu JTLR4 WA)8
modulation
& Walker
enteral feeding
Evidence of Enteral antibiotics
Evidence of Efficacy Evidence of Efficacy Glutamine
Proposed Efficacy
Efficacy & Safety but Questionable
Glucocorticoids in Animal Models butfatty
n-3 Lackacids
of
Safety but Not in Human Evidence
Breast-milk
• Arginine feeding Probiotics Growth factors Prebiotics
Non-aggressive
Nitric Arginine role in mediating
oxide (NO) plays an important Anticytokines TLR4 modulation
intestinal vasomotor tone. It is an inhibitory
enteral feedingin the gastrointestinal system inducing gut smooth muscle relaxation, regulate
neurotransmitter
mucosal blood flow, maintainEnteralmucosal
antibiotics Glutamine
integrity and intestinal barrier function. Arginine is involved
in NO production. A Glucocorticoids
relative deficiency of arginine results in n-3 fatty acids NO, causing
inadequate
vasoconstriction, ischemic reperfusion injury and development of NEC. A systemic review included
• Arginine
2 studies ie. Amin et al 2002 and Polycarpou et al 2013 had been carried out.
• Arginine
Nitric oxide (NO) plays an important role in mediating intestinal vasomotor tone. It is an inhibitory
neurotransmitter
Table 4: A study in the gastrointestinal
of Arginine system inducing
Supplementation gut smooth
in Prevention muscle
of NEC relaxation,
in Preterm regulate
Infants
Nitricmucosal
oxide blood
(NO)flow,plays an important
maintain roleand
mucosal integrity in intestinal
mediating intestinal
barrier vasomotor
function. Arginine tone.
is involved
in
It is an NO production.
inhibitory
Study A relative
neurotransmitter
Population deficiency of arginine
Studyin the gastrointestinal
Resultsresults in inadequate
system
Conclusion NO, causinggut
inducing
design
smooth muscle
2 Mitchell
studies ie.
K etAminrelaxation,
et regulateetmucosal
al 2002 andSystematic
2 RCT Polycarpou al
59%2013 had blood
NEC flow,
been carried out. maintain
L-arginine can preventmucosal
integrity and 6intestinal barrierreview
al. (2014) function. Arginine
Table 4: A study of Arginine Supplementation
reduction inisL-involved
in Prevention
NEC ininpreterm
ofHowever
NO production.
NEC in Preterm
infants.
Infants
A
arginine group large RCTs are
relative deficiency of arginine results in inadequate NO, causing needed. vasoconstriction,
ischemicStudy reperfusionPopulation
injury and Study Results
development of NEC.Conclusion
A systemic review
• Epidermal Growth Factor design (EGF)
included
EGF 2 Kstudies
Mitchell
have 6
et
shown ie. Amin
2protective
RCT et al
Systematic
role in 2002
animal 59%
model.andNEC
EGF Polycarpou
in amniotic et inhibit
L-arginine
fluid can alcan2013
preventhad and
TLR4 signal been
al. (2014) enhance epithelial repair. As quoted by Patel BK & Shah JS, a infants.
review reduction in L- NEC in preterm
carried out.
subsequently
arginine group
small study by
However 9large RCTs are
Sullivan et al. in 2007 showed positive effect. Further investigation is needed
needed.
• Feeding Strategies
EGF
•- Epidermal
have shown
Growth Factor
Cautious Advancement
protective
(EGF) Paediatric Pharmacy Services Guideline
of Feeds
role that
in animal
173
Observational studies showed NEC model. EGFisinhigher
incidence amniotic
in fluid can inhibit
patients TLR4enteral
with early signal and
feed
subsequently enhance epithelial repair. As quoted by Patel BK & Shah JS, a small study by
neurotransmitter in the gastrointestinal system inducing gut smooth muscle relaxation, regulate
mucosal blood flow, maintain mucosal integrity and intestinal barrier function. Arginine is involved
in NO production. A relative deficiency of arginine results in inadequate NO, causing
Neonatal Icu
2 studies ie. Amin et al 2002 and Polycarpou et al 2013 had been carried out.
Table 4: A study of Arginine Supplementation in Prevention of NEC in Preterm Infants
Study Population Study Results Conclusion

5.0
design
Mitchell K et 2 RCT Systematic 59% NEC L-arginine can prevent
al. (2014)6 review reduction in L- NEC in preterm infants.
arginine group However large RCTs are
needed.
• Epidermal Growth Factor (EGF)

• Epidermal Growth Factor (EGF)
EGF have shown protective role in animal model. EGF in amniotic fluid can inhibit TLR4 signal and
subsequently enhance epithelial repair. As quoted by Patel BK & Shah JS, a small study by
- EGF haveet shown
Sullivan al. in 2007 protective role
showed positive in Further
effect. animal model.isEGF
investigation neededin9 amniotic fluid can
inhibit TLR4 signal and subsequently enhance epithelial repair. As quoted by
Patel -BKCautious
& Shah JS, a small
Advancement study by Sullivan et al. in 2007 showed positive
of Feeds
effect. Furtherstudies
Observational investigation is NEC
showed that needed9
incidence is higher in patients with early enteral feed
introduction and faster advancement. Nonetheless recent data are insufficient to determine which
6
specific feeding strategies have the highest risk of patients developing NEC
- Cautious Advancement of Feeds
Observational studies showed that NEC incidence is higher in patients150 with

early enteral feed introduction and faster advancement. Nonetheless recent
data are insufficient to determine which specific feeding strategies have the
highest risk of patients developing NEC6
- Trophic Feeding
As quoted by Patel BK & Shah JS, Cochrane review of 8 studies concluded
that trophic feeding has no significant effect on NEC9
• Gastric Acid Suppression
- As quoted by Morgan JA et al., Guillet R & colleagues showed that the use of
H2-blocker which suppress gastric acidity in preterm infants is associated
with higher risk of NEC. Gastic acid may play crucial role in preventing the
infection and inflammation that will cause NEC development. As quoted by
Morgan JA et al., Anderson P & Guillet R recommended that use of H2-
blocker should be restricted until further evidence that benefits outweigh the
7
harm is available
• Glutamine
- Experimental studies have shown that glutamine serve as fuel for enterocytes,
stimulate the mucosal cell proliferation and differentiation and maintain the
integrity of tight junctions thus reduce mucosal damage and lower the risk of
invasive infection7,9 However, as quoted by Morgan JA etal., a Cochrane
review of good quality randomized controlled trial, by Tubman TR published
in 2008 indicated that glutamine supplementation does not confer benefits for
preterm infants7

quoted by Morgan JA et al., Anderson P & Guillet R recommended that use of H2-blocker should
be restricted until further evidence that benefits outweigh the harm is available 7
Neonatal Icu
• Glutamine
Experimental studies have shown that glutamine serve as fuel for enterocytes, stimulate the
• Human milk
mucosal cell proliferation and differentiation and maintain the integrity of tight junctions thus reduce
mucosal damage and lower the risk of invasive infection7,9 However, as quoted by Morgan JA et
-al.,
It isa suggested thatof human milkrandomized
may reduce the risk
trial, of
by NEC by TR
reducing
5.0
Cochrane review good quality controlled Tubman published in
2008
pathogenic bacterial
indicated that glutamine colonization,
supplementationpromote
does not the
confergrowth
benefitsof preterm infants 7
fornon-pathogenic
microflora, enhance the maturation of gastrointestinal tract and regulate the
pro-inflammatory
• Human milk response in preterm neonates. The positive effects of
Ithuman milk may
is suggested be due
that human to may
milk several factors
reduce eg:
the risk of macrophages,
NEC by reducing lymphocytes,
pathogenic bacterial
colonization,
lysozyme,promote the growth of non-pathogenic microflora, enhance the maturation of
lactoferrin, oligosaccharides, nucleotides, cytokines, growth
gastrointestinal tract and regulate the pro-inflammatory response in preterm neonates. The positive
effects
factors and enzymes.
of human milk may be Studies
due to have
severaldemonstrated positive lymphocytes,
factors eg: macrophages, effect of humanlysozyme,
lactoferrin, oligosaccharides,
milk in lowering incidence of NEC8,9,12
nucleotides, cytokines, growth factors and enzymes. Studies have
8,9 & 12
demonstrated positive effect of human milk in lowering incidence of NEC
Table 5: Studies on Effect of Human Milk on NEC Development
Study Population/Subjects Study Results

Design
McGuire & 4 clinical trials Meta-analysis Infants on human milk were 4
Anthony, times less likely to have confirmed
20035 NEC
Sullivan et 207 preterm infants Randomized Exclusive human milk result in
al, 201010 Controlled lower incidence of NEC
Trial
• Judicious Restriction of Prolonged Empirical Antibiotics

• Judicious Restriction of Prolonged Empirical Antibiotics
Studies have shown that prolonged empirical antibiotics lead to higher NEC risk in premature
infants.have shown that prolonged empirical antibiotics lead to higher NEC risk
Studies
in premature infants.
Table 6: Studies on Prolonged Empirical Antibiotics Increase the Incidence of NEC or Death
Study Population Study design Results

Cotton MC et al. (1) N= 5693 Retrospective NEC or death is higher in the 151
1
(2009) (2) ≤ 1.0kg cohort study group of prolonged empirical
antibiotics (≥5days) (61%,
p<.001)
Kuppala V et al. (1) N= 365 Retrospective Late-onset-sepsis, NEC or
(2011) 3 (2) ≤ 32weeks cohort study death is significantly higher in
gestational age & the group of prolonged
≤1.5kg empirical antibiotics (≥5
days) (41% vs 18%,
p<.0001)
Based on the findings of these studies, Morgan JA et al reinforce that empirical antibiotics for
Based oninfants
preterm the findings
should be of these
started studies,
early Morgan
when sepsis JA et and
is suspected al reinforce that empirical
to be discontinued early
7
antibiotics
once sepsisfor preterm
is excluded infants should be started early when sepsis is suspected
7
and to be discontinued early once sepsis is excluded
• Lactoferrin
Lactoferrin is an antimicrobial glycoprotein which present in colostrum and breast milk. Lactoferrin
has broad activity against Gram-positive cocci, Gram-negative bacilli and Candida sp. There is low
level of Lactoferrin in VLBW infants and this is worsened by delay establishment of enteral
feeding7,9. An Italian randomized controlled Paediatric Pharmacy
trial showed Services
positive effect Guideline 175
of Lactoferrin
supplementation4
≤1.5kg empirical antibiotics (≥5
Neonatal Icu
days) (41% vs 18%,
p<.0001)
Based on the findings of these studies, Morgan JA et al reinforce that empirical antibiotics for
preterm infants should be started early when sepsis is suspected and to be discontinued early
•once
Lactoferrin
sepsis is excluded7
- Lactoferrin is an antimicrobial glycoprotein which present in colostrum and

5.0
•breast milk. Lactoferrin has broad activity against Gram-positive cocci, Gram-
Lactoferrin
Lactoferrin
negative is an antimicrobial
bacilli glycoprotein
and Candida sp. which
Therepresent
is lowinlevel
colostrum and breast milk.
of Lactoferrin Lactoferrin
in VLBW
has broad activity against Gram-positive cocci, Gram-negative bacilli and Candida sp. There is low
infants and this is worsened by delay establishment of enteral feeding7.9.
level of Lactoferrin in VLBW infants and this is worsened by delay establishment of enteral
An 7,9Italian
feeding . An randomized controlled
Italian randomized trial showed
controlled positive
trial showed effecteffect
positive of Lactoferrin
of Lactoferrin
4
supplementation4
supplementation
Table 7: RCT of Lactoferrin Supplementation in Prevention NEC in VLBW Infants
Study Population Study design Results

Manzoni P et al. 472 VLBW infants Multicenter, double Nil NEC in Lactoferrin +
(2009)4 blind, RCT probiotic group; 6%
NEC in control group
(p=.002)
• Modulation of TLR4
• Modulation of TLR4Signal
Signal
Only animal model has been tested, more human clinical trials are needed
- Only animal model has been tested, more human clinical trials are needed
• Oral Immunoglobulins (Ig)
• Oral Immunoglobulins (Ig)
Ig is a possible factors in human milk which is responsible for NEC protective effect. However, as
quoted
- Ig isbya Patel BK &factors
possible Shah JS,in Cochrane review
human milk published
which in 2004 showed
is responsible thatprotective
for NEC oral IgG as well
as combination of IgG with IgA did not result in significant reduction of NEC incidence9
effect. However, as quoted by Patel BK & Shah JS, Cochrane review published
in• 2004 showed that oral IgG as well as combination of IgG with IgA did not
Prebiotics
9
Prebiotics
result inaresignificant
non-digestible food components
reduction that beneficially
of NEC incidence affect the host by selectively
stimulating the growth and/or activity of one or a limited number of bacteria in the colon thereby
•improving
Prebiotics
host health9. Examples of prebiotics include oligosaccharides inulin, galactose, fructose
and lactulose. Oligosaccharides that are contained in human milk have been shown to enhance
- Prebiotics are non-digestible food components that beneficially affect the
host by selectively stimulating the growth and/or activity of one or a limited 152
9

number of bacteria in the colon thereby improving host health . Examples
of prebiotics include oligosaccharides inulin, galactose, fructose and lactulose.
Oligosaccharides that are contained in human milk have been shown to
enhance the proliferation of bifidobacteria and lactobacilli in the colon 9.
However, up to date, the evidence regarding the effectiveness of prebiotics
use in preterm infants is still limited.
• Probiotics
- Probiotics are live microorganisms such as lactobacilli and bifidobacteria
which when administered in adequate amount confer a health benefit on the
host. Potential benefits of probiotics including:
(1) inhibition of pathogenic colonization and produce anti-inflammatory effects
(2) s ecretion of lactic acid that lower local pH thus inhibit the growth of
pathogenic bacteria

• Probiotics
Probiotics are live microorganisms such as lactobacilli and bifidobacteria which when administered
Neonatal Icu
in adequate amount confer a health benefit on the host. Potential benefits of probiotics including:
(1) inhibition of pathogenic colonization and produce anti-inflammatory effects
(2) secretion of lactic acid that lower local pH thus inhibit the growth of
(3) communicate
pathogenic bacteriadirectly with pathogenic bacteria thus modulating their gene
(3) communicate directly with pathogenic bacteria thus modulating their gene
expression, reducing the binding to the host epithelial cells
expression, reducing the binding to the host epithelial cells
(4) stimulation of production of secretory immunoglobulins and cause positive effect to
5.0
immunity
(4) stimulation
response of production of secretory immunoglobulins and cause
positive effect to immunity response some clinical trials have demonstrated
Some clinical trials have demonstrated that supplementing the diet of preterm infants with
that supplementing the diet of preterm infants with probiotics is beneficial.
probiotics is beneficial.
Table 8: Clinical Trials of Probiotics Supplementation Decrease the Incidence of Neonatal

NEC
Study Population / Subjects Study Results

Design
Lin et al. Multicenter, 434 infants Masked 1.8% probiotics group developed NEC;
(quoted by randomized 6.5% non-probiotics group developed
Patel BK)9 controlled trial NEC
Deshpande 15 randomized Meta analysis 30% reduction in NEC (p<.00001)
et al.2 controlled trial
Wang et 20 randomized Meta analysis 3% probiotics group developed NEC;
al.13 controlled trial 7.4% placebo-group developed NEC
(p<.00001)
A recent commentary by Tarnow-Modi WO and colleagues also suggest the routine use of
11
probiotics
A However,
recent commentary bybyTarnow-Modi
a systematic review
WO and colleagues also suggest the
Milhatsch et al, published in 2012 concluded that there is still no
11
routine useevidence
conclusive of probiotics
to recommend routine use of probiotics in preterm infants.
In settings with high incidence of NEC, clinicians may consider off-label use of specific probiotics.
However,
There are a
stillsystematic reviewprobiotics
limitations of routine by Milhatsch
use14: et al, published in 2012 concluded
(1) unknown optimal strain and dosing
that there is still no conclusive evidence to recommend routine use of probiotics
(2) no evidence showing whether single or multiple strain are more effective
in preterm infants.
(3) safety and efficacy of each probiotic strain has to be studied
(4) non convincing data that probiotics prevent sepsis
In settings with high
(5) possibility incidence
of infections of by
caused NEC, clinicians may consider off-label use of
probiotics
specific (6) long term effects on fecal flora and immune system
probiotics.
There are still limitations of routine probiotics use14:
(1) unknown optimal strain and dosing
(2) no evidence showing whether single or multiple strain are more effective
(3) safety and efficacy of each probiotic strain has to be studied
(4) non convincing data that probiotics prevent sepsis 153
(5)
possibility of infections caused by probiotics
(6) long term effects on fecal flora and immune system
• Prophylatic Enteral Antibiotics
- As quoted by Patel BK & Shah JS and also Neu J & Walker WA, several small
studies suggest that oral antibiotics can reduce incidence of NEC8,9

• Prophylatic Enteral Antibiotics
Neonatal Icu
As quoted by Patel BK & Shah JS and also Neu J & Walker WA, several small studies suggest that
oral antibiotics can reduce incidence of NEC8,9
Table 9: Studies of Enteral Antibiotics Reduce the Incidence of NEC
Study Enteral antibiotics

5.0
Quoted by Patel BK & Shah JS 9

Egan et al. (1977) Kanamycin
Siu YK et al. (1998) Vancomycin
Bury RG (2000) Systemic review
Quoted by Neu J & Walker WA
Grylack LJ et al (1978) Gentamicin
Nonetheless, as being quoted by Patel BK, Cochrane review by Bury RG showed concern on
Nonetheless, asthus
resistant bacteria being quoted
routine by Patel BK,
use of prophylactic Cochrane
enteral review
antibiotics is by Bury RG
not recommended 9 showed
concern on resistant bacteria thus routine use of prophylactic enteral antibiotics
is not recommended9
• Polyunsaturated Fatty Acids (PUFA)
• Polyunsaturated Fattyto Acids
PUFA have been proposed modulate(PUFA)
inflammation and immunity. As quoted by Patel BK &
Shah JS, Carlson et al (1998) demonstrated lower incidence of NEC9
- PUFA have been proposed to modulate inflammation and immunity. As quoted
Synbiotics
by• Patel BK & Shah JS, Carlson et al (1998) demonstrated lower incidence of
Synbiotic is a product contain both probiotics and prebiotics. As quoted by Patel BK & Shah JS,
NEC9
RCT done by Underwood MA & friends in 2009 demonstrated positive result in synbiotics-group9
• Synbiotics
• Zinc
Zinc participates in many metabolic pathway. As quoted by Patel BK & Shah JS, Terrin R et al.
-demonstrated
Synbiotic is thata zinc
product
plays contain bothin probiotics
important role maintenance and prebiotics.
of epithelial barrier As quoted
function and by
induction
Patel of adequate immune response. Terrin R & colleagues (2013) showed that high dose zinc
BK & Shah JS, RCT done by
is also effective in reducing NEC in preterm infants 9 Underwood MA & friends in 2009
demonstrated positive result in synbiotics-group9
• Zinc
- Zinc participates in many metabolic pathway. As quoted by Patel BK & Shah
JS, Terrin R et al. demonstrated that zinc plays important role in maintenance
of epithelial barrier function and induction of adequate immune response. Terrin
R & colleagues (2013) showed that high dose zinc is also effective in reducing
NEC in preterm infants9
154


Neonatal Icu
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Moreno LA, Pohlandt F, Puntis J, Shamir R, Stadtmuller U, Szajewska H,
Turck D, Gondoever JB. Critical Systemic Review of the Level of
Evidence for Routine Use of Probiotics For Reduction of Mortality
a nd Prevention of Necrotising Enterocolitis and Sepsis in Preterm
Infants. Clinical Nutrition. 2012; 31: 6-15

Neonatal Icu
6.0 DOSING CONSIDERATIONS IN
SPECIAL POPULATIONS
5.0
Dosing considerations in underweight, overweight & obese children
When initiating drug therapy for children, the patient’s total body weight or
body surface area is used to calculate the dose required. However, special
consideration must be given to patients whose weight does not fall within the
accepted healthy weight range.
Definition of Healthy Weight: Children > 2 years or older : BMI-for-age is above

the 5th percentile and below the 85th percentile compared with children of the
same age and sex which reflects the desirable body weight for a particular age
and height that is optimal for nutrition status.
Dosing in Underweight Patients :

Definition of Underweight: Children > 2 years or older : BMI-for-age is below the
5th percentile compared with children of the same age and sex.
Dosing utilizes the actual total body weight while taking into consideration general
nutritional status and precautions regarding possible altered drug clearance e.g.
renal and hepatic function.
Dosing in overweight & obese children :

Definition of Overweight:
Children < 2 years of age: Normal BMI not available, hence weight-for-height
values above the 95th percentile in this age group can be categorized as
overweight.
Children >2 years or older : BMI-for-age at or above the 85th and below the 95th
percentile compared with children of the same age and sex

Neonatal Icu
Definition of Obese:
5.0
Children 2 years to adolescence: BMI-for-age at or above the 95th percentile on

the BMI for age charts compared with children of the same age and sex.
Adolescents: Obesity may be defined as BMI at or greater than the 95th percentile
OR 30kg/m2, whichever is lower.
There is limited data on the impact of obesity on the pharmacokinetics and

pharmacodynamics of drugs. Obese patients have significantly higher total
body water, body volume, lean mass, fat mass and bone mineral content. They
also have an increased hydration of lean mass, which is attributed to increased
extracellular water. The increases in fat mass are substantially more than that of
lean mass.1
Fat mass in the body will alter a drug’s volume of distribution whereby obese
patients will generally have a higher volume of distribution for lipophilic medications
due to its distribution into adipose tissue. Hydrophilic drugs will also have an
altered volume of distribution due to increased lean body mass, blood volume
& a decreased percentage of total body water. This may affect the loading
dose, dosing intervals, plasma half-life and the time to reach the steady-state
concentration. Obesity may also alter the metabolism and elimination of drugs.1-3
Loading doses are based on the volume of distribution (VD), body composition,
blood flow and plasma protein binding.
• Hydrophilic drugs are generally loaded based on ideal body weight (IBW)
• Partially lipophilic drugs are loaded based on an adjusted body metric with
consideration of the variability in distribution.
• Lipophilic drugs distribute freely into fat tissue resulting in greater distribution.
A larger dose may be needed for adequate response. Some recommend
dosing lipophilic medications on TBW. (However this should be assessed on
a case by case basis where the risks of toxicity are considered. For example,
propofol and thiopentone are lipophilic and are recommended for IBW
dosing).
Maintenance doses depend on the clearance rate for drugs, which is determined
by renal and hepatic function. The effect of obesity on metabolic activities in
children is not known and measures of renal function in children are not validated
in obesity.

Neonatal Icu
Utilizing an obese patient’s body weight or body surface area to calculate the
5.0
dose may result in doses exceeding the recommended adult doses, which
are used as a threshold for maximum doses in paediatric patients. Conversely,
using the maximum dose recommended may result in a sub therapeutic dose
as compared to the recommended weight-based dose if the drug is lipophilic.2
There is little evidence supporting the use of adjusted body weight to calculate
safe and efficacious doses in obese children as it assumes that the body
composition and functions are similar in obese and non obese children. Using
adjusted body weights may lead to subtherapeutic doses in obese children.1,2
Weight -based dosing should be utilized in patient’s <18 years of age who are
< 40kg.
For children who are >40kg, weight based dosing should be used, unless
the patient’s dose or dose per day exceeds the recommended adult dose. If
available, pharmacokinetics analysis for adjusting medications can be used to
ensure safe and effective regimen.
Consideration of other patient factors such as renal and hepatic function, drug
interactions and co-morbid states should also be considered when applying the
recommendations.1
References:
1. Johnson PN, Miller JL, Boucher EA, et al; PPAG Advocacy Committee.
Medication dosing in overweight and obese children. http://www.ppag.org/
obesedose/ Accessed April 30th, 2015.
2. Jessica C. Stovel. How Should Medications Be Dosed in Obese
Children? Medscape, Updates Sep 03, 2013. http://www.medscape.com/
viewarticle/81037/ Accessed May 2nd, 2015.
3. Mulla H, Johnson TN. Dosing dilemmas in obese children. Arch Dis Child
Educ Prac Ed. 2010;95:112-117

of drugs depend on glomerular filtration, renal tubular secretion/a
ecular size of the drug involved and the extent of protein binding
Neonatal Icu
tion is impaired, glomerular filtration becomes impaired and elimi

d, resulting in a prolonged plasma half-life of drugs.1
Children with renal impairment
5.0
elimination excreted by the kidneys is proportional to the glomer

quation,
RenalTraub Equation
excretion or aonnomogram
of drugs depend based
glomerular filtration, renalon serum
tubular creatini
secretion/
absorption mechanism, molecular size of the drug involved and the extent of
enerally
protein 1binding of the drug. When renal function is impaired, glomerular filtration Ra
accepted methods of estimating Glomerular Filtration
ars of becomes
age. impaired and elimination of drugs will be decreased, resulting in a
prolonged plasma half-life of drugs.1
ard forThecalculating endogenous creatinine clearance is still a timed
rate of drug elimination excreted by the kidneys is proportional to the
glomerular filtration rate. The Schwartz equation, Traub Equation or a nomogram
based on serum creatinine clearance and height are the generally accepted
Schwartz
age.1
Equation:1,2 Glomerular Filtration Rate(GFR) in children <18 years of
methods of estimating
The gold standard for calculating endogenous creatinine clearance is still a timed
collection of urine.
The Traditional Schwartz Equation:

mL/min/1.73m2
1,2
e clearance,
CrCl = Creatinine clearance, mL/min/1.73m2
eatinine expressed
Scr = as expressed
Serum Creatinine mg/dL (1 µmol/L
as mg/dL = 0.0113mg/dL).
(1 µmol/L = 0.0113mg/dL).
K = Constant proportionality that is age specific
oportionality that is age specific
Age K
Low birth weight 0.33
Full term ≤ 1 year old 0.45
1-12 years 0.55
13-21 years (Female) 0.55
13-21 years (Male) 0.70
rmula should not be used with SCr measurements calibrated to r

by IDMS(Isotope dilution mass spectroscopy). Using IDMS creatin
artz equation will result in an overestimation of GFR by 18%–39%
. The overestimation is highest in children younger than 3 years.
ation 184
wasPaediatric
updated to account for more modern creatinine calcula
Pharmacy Services Guideline
Neonatal Icu
However, this formula should not be used with SCr measurements calibrated
5.0
to reference measurements by IDMS(Isotope dilution mass spectroscopy).
Using IDMS creatinine values in the traditional Schwartz equation will result in
an overestimation of GFR by 18%–39%, depending on the patient’s age. The
overestimation is highest in children younger than 3 years.
In 2009, the equation was updated to account for more modern creatinine
calculations done by laboratories. The modified Schwartz no longer uses a
variable K value and instead uses a set K of 0.413.
The modified Schwartz equation :1,2

CrCl (mL/min/1.73m2) = 0.413 x L(cm) / SCr(mg/dL)*
*1 µmol/L = 0.0113mg/dL.
However, the Schwartz equation has its limitations. It can potentially overestimate
GFR, especially in moderate to severe renal insufficiency as serum creatinine is a
crude marker of GFR . Alternative methods based on additional factors such as
cystatin C or blood urea nitrogen have been proposed to estimate GFR in children
with renal insufficiency such as chronic kidney disease.2
The Paediatric Protocol for Malaysian Hospitals (3rd Edition) recommends the
following equation for estimating the GFR once the serum creatinine level remains
constant for at least 2 days :3
Creatinine Clearance (ml/min/1.73m2) =
References:
1. Michael E. Brier, PhD and George R. Aronoff, MD. Drug Prescribing in Renal
Failure, 5th Edition: American College of Physicians; 2007
2. Sandra Benavides, Milap C. Nahata,Michael Chicella, Michelle Condren, et
al. Paediatric Pharmacotherapy, 1st Edition. Kansas: American College of
Clinical Pharmacy; 2013. p. 23-25.
3. Hussain Imam B. Hj. Muhammad Ismail, Ng Hoong Phak, Terrence Thomas,
et.al. Paediatric Protocols for Malaysian Hospitals, 3rd Edition. Malaysia:
Kementerian Kesihatan Malaysia;p.290-1.

Neonatal Icu
Tpn In Special Populations

5.0
Total energy needs of a healthy individual are the sum of the basal metabolic
rate (BMR), diet induced thermogenesis (DIT), physical activity (PA) and growth.
Nutritional status, underlying diseases, energy intake, energy losses, age and
gender may affect the energy needs. Goran et al (1991) found that fat free mass,
gender and fat mass are important determinants of total energy expenditure
(TEE) in prepubertal children. On the other hand, gender, body composition and
season affects energy expenditure during puberty and adolescence.
Since body composition is an important factor in determining total energy

expenditure, patients who are obese or malnourished may have different energy
requirements. Prediction of energy needs should be based on fat free mass, to
account for differences in body composition.
Energy needs can be either measured or calculated based on acceptable

equations. The best way to assess energy needs in children is to measure total
energy expenditure or alternatively REE.1
TPN In Obese Paediatric Patients2
The American Academy of Pediatrics (AAP) defines obesity as children aged

between 2–20 years with a body mass index ≥ 95th percentile. Body mass index
is the preferred practical method to screen children for obesity.
(Grade D Evidence)
Pediatric obese inpatients may be at increased nutrition risk. Potential laboratory

abnormalities should be tested for safety reasons. Examples include fasting blood
sample, including lipid profile, glucose, phosphorus, and complete blood count.
This may aid in the development of a formal nutrition care plan as obese paediatric
patients are at risk for anemia, low concentrations of fat-soluble vitamin levels,
low vitamin B status, hyperlipidemia, insulin resistance and hyperglycemia.
(Grade E Evidence)
Whenever possible, energy requirements of obese hospitalized children should
be assessed using indirect calorimetry rather than predictive equations as the
Resting Energy Expenditure (REE) varies with obesity status. Using the excess
weight to estimate the ideal body weight using predictive equations leads to
imprecise estimations. This is because for every kilogram of weight above the
ideal weight, the percentage of lean body mass varies, which will result in varying
REE.

Neonatal Icu
Indirect calorimetry is considered the gold standard for determining energy
5.0
expenditure, enabling feeding to be adapted to the measured energy expenditure.
(Grade D Evidence)
Evidence is lacking regarding the clinical outcomes of the use of hypocaloric or

hypercaloric feeding during hospitalization in obese children. Therefore, until more
evidence is available, the goals for the provision of energy to pediatric obese
inpatients should be similar to the goals for their non obese counterparts.
(Grade E Evidence)
TPN in Malnourished Children1
During the first 2 years of life and later on during adolescence, changes in organ
maturation and higher growth velocity requires extra caloric needs as compared
to adults. The energy needed to maintain accelerated growth represents 30–35%
of the energy requirements in term neonates and is greater in preterm infants.
Children recovering from malnutrition need extra calories to correct their growth
deficits (weight, height). Thus, energy needs may be calculated based on the
50th percentile of weight and height for the actual age, rather than the present
weight. This difference will provide extra calories (above daily needs) to achieve
catch-up growth.
Alternatively, calculation may be based on the actual weight multiplied by 1.2–1.5,

or even by 1.5 to 2 times in severe cases of failure to thrive, to provide the extra
calories needed for catch up growth. Further caloric needs should be adjusted
according to weight and height gain.
ESPGHAN 2005 Guidelines for Paediatric Parenteral Nutrition quotes the Schofield
-WH equation to be the best predicting equation for calculating estimated daily
energy needs in cases of failure to thrive.
Schofield (WH) Equations for calculating REE and BMR (kcal/day) in children from
0-3 years
Male BMR = 0.167 x Wt(kg) + 1517.4 x Ht(m) - 617.6

Female BMR = 16.25 x Wt(kg) + 1023.2 x Ht(m) - 413.5

Neonatal Icu
Schofield-(WH) Equations for calculating REE and BMR (kcal/day) in children from
5.0
3–10 years
Male BMR = 19.6 x Wt(kg) + 130.3 x Ht(m) + 414.9

Female BMR = 16.97 x Wt(kg) + 161.8 x Ht(m) + 371.2
Schofield (WH) Equations for calculating REE and BMR (kcal/day) in children from
10-18 years
Male BMR = 16.25 x Wt(kg) + 137.2 x Ht(m) + 515.5

Female BMR = 8.365 x Wt(kg) + 465 x Ht(m) + 200
A caveat to refeeding the malnourished child is the risk of refeeding syndrome,

due to the sudden disruption to the adaptative state of semi-starvation. These
rapid changes in metabolic status can create life-threatening complications, so
the nutritional regimen must be chosen wisely and monitored closely. Kindly refer
to the ESPGHAN 2005 Guidelines on Paediatric Parenteral Nutrition for strategies
to reduce the risk of developing complications of refeeding syndrome.
References:
1. Berthold Koletzko, Olivier Goulet, Joanne Hunt, Kathrin Krohn,Raanan

Shamir . Guidelines on Paediatric Parenteral Nutrition of the European
Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)
and the European Society for Clinical Nutrition and Metabolism (ESPEN),
Supported by the European Society of Paediatric Research (ESPR). Journal
of Pediatric Gastroenterology and Nutrition 2005; Volume 41(Sup 2): p. S5-
8, S79.
2. Cheryl Jesuit, Cristin Dillon, Charlene Compher, Carine M. Lenders.

A.S.P.E.N. Clinical Guidelines: Nutrition Support of Hospitalized Pediatric
Patients With Obesity. Journal of Parenteral and Enteral Nutrition 2010; 34(1):
p.13-20.

Appendix
7.0 APPENDIX
Corticosteroid
Appendix Equipotency Chart
Corticosteroid Equipotency Chart
Potency relative to
Half-Life
Hydrocortisone
Corticosteroid Equivalent
Anti- Plasma Biological
Glucocorticoid Mineralocorticoid
Inflammatory (minutes) (hours)
Dose (mg)
Short Acting
Hydrocortisone 20 1 1 90 8-12
Cortisone Acetate 25 0.8 0.8 30 8-12
Intermediate Acting
Prednisone 5 4 0.8 60 12-36
Prednisolone 5 4 0.8 200 12-36
Triamcinolone 4 5 0 300 12-36
Methylprednisolone 4 5 0.5 180 12-36
Long Acting
Dexamethasone 0.75 30 0 200 36-54
Betamethasone 0.6 30 0 300 36-54
Mineralocorticoid
Fludrocortisone 0 15 150 240 24-36
Aldosterone 0 0 400+ 20 -
References:
REFERENCE:
1)1)Steven
Steven K.K. H. Adrenal
H. Adrenal cortical cortical
steroids. In:steroids. In: comparisons.
Drug facts and Drug facts5thand comparisons.
ed. St. Louis: Facts 5th
ed. St. Louis:Inc.;
and Comparisons, Facts and
122–128 Comparisons, Inc.; 122–128 (1997).
(1997).
163


Appendix
Nutrition Reference
Nutrition Reference
Supplement Nutrient Content Calories Indications And Contraindications
Carbohydrate Calorie supplemetation (lactose and

gluten free) Contains Na, K, Ca, Cl
Glucose polymers 3.8kcal/g powder;
Polycose and P (Limiting formula intake while
from hydrolyzed 2kcal/mL liquid
increasing calories may compromise
cornstarch
protein, vitamin, and mineral intake,
which may also lead to
hyperglycemia and diarrhea)
Infant rice
Rice 15 cal/tbsp
cereal Thickens feedings
Limit to 50% calories from fat to

Fat
prevent ketosis; may cause diarrhea;
do not use in bronchopulmonary
Medium-chain Lipid fraction of 8.3 kcal/g, 7.7
dysplasia (BPD) because risk of
triglyceride coconut oil cal/mL
aspiration pneumonia
To increase calories if fat absorption

Vegetable oil Soy, corn oil 9.0 cal/g (120
is normal
cal/tbsp)
Microlipid Safflower oil, Soy
To increase caloric density, fluid
lecithin, ascorbic 4.5 cal/mL, 5.9
restriction
acid, linoleic acid g/tbsp
4.1 cal/g (6 g of
protein/packet)
Calcium =
30mg/scoop
Sodium =
Protein
Whey protein 15mg/scoop Useful for protein and calorie
isolate/soy lecithin Potassium = supplementation
Beneprotein
35mg/scoop
Phosphorus =
15mg/scoop
Calories =
25/scoop
Adapted from: Gomella TL, Cunningham MD, Eyal FG, et al, editor. Neonatology
management, procedures, on-call problems, diseases and drugs. 6th ed. New York: Mc
Graw Hil
165


Appendix

Immediate-Release Opioid Analgesics Comparison Chart
IMMEDIATE-RELEASE OPIOID ANALGESICS COMPARISON CHART
Equianalgesic Usual starting IV doses Usual starting oral

doses and Intervals Parenteral doses and intervals
Drug
Child > / oral ratio Child Child >
Parenteral Oral Child <50kg
50kg <50kg 50kg
0.5-1
30-60 mg
Codeine 120mg 200mg - - 1:2 mg/kg q
q 3-4 hr
3-4 hr
Immediate
release:
Bolus: 0.1
Bolus: 5-8 15-20mg
mg/kg q 2-4 Immediate
30mg mg q 2-4 hr q 3-4 hr
hr release:
Morphine 10mg (long 1:3
0.3mg/kg
term) Infusion: Sustained
Infusion: 0.02- q 3-4 hr
1.5mg/kg/hr release:
0.03 mg/kg/hr
30-45 mg
q 8-12 hr
0.1-0.2
15-20 5-10 mg q
Oxycodone - - - - mg/kg q
mg 3-4 hr
3-4 hr
10- 5-8 mg q 4- 0.1mg/kg 2.5-10 mg
Methadone 10mg 0.1mg/kg 1:2
20mg 8 hr q 8-12 hr q 8-12 hr
Bolus: 0.5-1 Bolus: 25-

mcg/kg q 1-2 50 mcg q 1-
100mcg hr 2 hr
Fentanyl - - - -
(0.1mg) Infusion:
Infusion: 0.5- 25-100
2mcg/kg/hr mcg/hr
Bolus: 0.02 Bolus: 1 mg
mg q 2-4 hr q 2-4 hr 0.04-0.08
6-8 2-4 mg q
Hydromorphone 1.5-2 mg 1:4 mg/kg q
mg 3-4 hr
Infusion: Infusion: 3-4 hr
0.006mg/kg/hr 0.3 mg/hr
Bolus: 0.8-1 Bolus: 50- 100-150
Meperdine 300 2-3 mg/kg
75-100 mg mg/kg q 2-3 75mg q 2-3 1:4 mg q 3-4
(Pethidine) mg q 3-4 hr
hr hr hr
REFERENCE:
References:
1) Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Eng J Med.
1) Berde 2002;347:1094-1103
CB, Sethna NF. Analgesics for the treatment of pain in children. N Eng

J Med. 2002;347:1094-1103
166


Appendix
TDM Sampling Time

Appendix
Growth Charts
GROWTH CHARTS
168


Appendix
169


Appendix

170


Appendix
171


Appendix

172


Appendix
172


Appendix

173


Appendix
174


Appendix

175


Appendix
176


Appendix
Stability And Storage Of Oral Medications
The following information was adapted from Hospital Kuala Lumpur’s Pharmacy
Department Guidelines of Compilation of Medication Management (2013) :
DEFINITION
Stability
The extent to which a product retains, within specified limits, and throughout
its period of storage and use (i.e., shelf-life/BUD/etc), the same properties and
characteristics that it possessed at the time of its manufacture/compounding/
repackaging. There are five (5) types of stability which are generally recognized
i.e. Chemical, Physical, Microbiological, Therapeutic and Toxicological stability.
Stability studies conducted by the manufacturer are used determine shelf life and
thus the expiry date of a product.
Expiration Date
Expiration date is the identified time up to which the product is expected to meet
the requirements of the Pharmacopeial monograph, provided it is kept under the
prescribed storage conditions. Expiration date limits the time during which the
product may be dispensed or used. It is determined using stability studies and is
not the same as Beyond-Use Date (BUD)/ DiscardAfter Date.
In the event where stability studies are unavailable as in the case of extemporaneous
products, BUD will be assigned to the product.
Beyond-Use Date (BUD)/ Discard-After Date/ Shelf Life
Beyond-Use Date (BUD)/Discard-After Date/Shelf Life are equivalent and it is the

time/date after which a product (usually compounded/repackaged) must not be
used. It is assigned, using the criteria stated in the relevant sections below. In the
absence of appropriate stability studies to support expiration dates used and the
assigned BUD must be less than the expiration date of any of the initial product/
raw material/s.

Appendix
Extemporaneous/Compounded Preparation
A medicinal product (internal and external) where its use (prescribing, dispensing
and/or administration), involves some element of recipe or formula preparation.
This recipe or formulation must be present in at least one step in prescribing,
dispensing and/or administration but does not have to be present in all steps.
Repackaging/Pre-packing
An act of removing a preparation/drug from its original primary container and

placing it into another primary container (may be called secondary if Unit-Dose
packaging), usually of smaller size.
Storage
Procedures to maintain a proper storage environment for pharmaceutical products,

and to ensure product integrity, including its appearance, until it reaches the user.
Children >2 years or older : BMI-for-age at or above the 85th and below the 95th
percentile compared with children of the same age and sex

Procedures to maintain a proper storage environment for pharmaceutical products, and to
ensure product integrity, including its appearance, until it reaches the user.

205
Equivalent Container-Closure System
Refers to a container-closure system that yields the same, or better, moisture vapour Appendix
Appendix
Equivalent Container-Closure System
Refers to a container-closure system that yields the same, or better, moisture

vapour transmission rate (MVTR), oxygen and light transmission as the original
market container.
Multidose Packaging
Multidose packaging is the packaging of more than one single-dosage unit in a

reusable container.
Unit-Dose Packaging
Unit-dose packaging is the packaging of a single dose in a non-reusable

container. Medications in unit-dose packaging are easily identifiable and can be
returned to the pharmacy if the medication is discontinued/withhold.
Storage & Stability For Extemporaneous / Non-Sterile Compounded

Preparations
The assignment of stability, of an extemporaneous/non-sterile compounded
preparation should be done with prudent pharmaceutical judgment by attending
pharmacist based on literatures/ publications/ references on formulas with
stability data.
In the absence of stability information or if only anecdotal data is available; the

following maximum BUD are recommended for extemporaneous/non-sterile
compounded preparations, that are packed in tight, light resistant (if applicable)
containers and stored at Controlled-Room Temperature (CRT), unless otherwise
indicated:-

maximum BUD are recommended for extemporaneous/non-sterile compounded preparations,
that are packed in tight, light resistant (if applicable) containers and stored at Controlled-Room
Temperature (CRT), unless otherwise indicated:-

Internal
207
a) All extemporaneous/compounded preparation must utilize formulas with references whenever
possible. Preparations without such formulas or with anecdotal reference only, should be used
Appendix
Appendix
Internal
a) All extemporaneous/compounded preparation must utilize formulas with

references whenever possible. Preparations without such formulas or with
anecdotal reference only, should be used with prudent pharmaceutical
judgment by the attending pharmacist.
b) Stability of preparation should be labeled appropriately whereby, the term

‘Expiry Date’ should be used for formulas with stability studies and ‘BUD’
should be used for formulas without references on stability studies or for
formulas with only anecdotal references.
c) If a formula is not available, ‘freshly prepared’ (‘just prior to administration’) or

tablet dispersion method (stable for 24 hours) is recommended.
d) All preparations should be refrigerated (Cold temperatures [2°C to 8°C])

unless stated otherwise. Syrups, Suspensions, Solutions made from Powder;
are to be stored at Controlled-Room Temperature unless otherwise indicated.
e) However, Antibiotic suspension/solution (prepared from ingredients in solid

form) is stable for 14 days if stored in Cold Temperature, unless stated
otherwise on package.
f) All other formulations: once used, must be discarded upon completion of

therapy OR not more than 30 days, whichever is earlier.

Appendix
External
a) Refer Internal a) – b).

b) Material Safety Data Sheet (MSDS) should be readily available, for easy retrieval
and interpretation, in particular the safety hazard information; to all staff
preparing drug substances or bulk chemical on the compounding premise.
c) Stability of preparation should be assigned using the recommended expiry
date or BUD (refer above).
Repackaging/Prepacking Storage & Stability
Repackaging/prepacking operations should be conducted under conditions that

meet requirements; including specific storage temperature, i.e. maintenance of
CRT. Written procedures must be maintained for traceability of end product.
Repackaged/prepacked containers must be labeled with:
1. Generic name
2. Manufacturer name
3. Manufacturers batch number
4. Expiry date (new)/BUD
Package inserts (PI) or other appropriate literature of the item being repackaged/
prepacked should be readily available, for easy reference, in order to properly
select an equivalent container-closure system.
Manufacturer’s original expiration date may be used without additional stability
testing if the drug product is repackaged/prepacked into an equivalent container-
closure system.
If an equivalent container-closure system is not available, a stability data for

the new containerclosure system must be generated to justify the expiry date
assigned.
In the absence of stability information or only anecdotal data is available; the

following maximum BUD are recommended for repackaged/prepacked products
in an equivalent container-closure system and stored at Controlled-Room
Temperature (CRT) (if applicable), unless otherwise indicated:-

Appendix


Appendix

Drugs To Avoid In G6PD Deficiency
Drugs To Avoid In G6PD Deficiency
Definite Risk Of Hemolysis Possible Risk Of Hemolysis

Pharmacological Class Drugs Pharmacological Class Drugs
• ß-Naphthol • Acetylsalicylic acid
Anthelmintics • Niridazole (Aspirin)
• Stibophen • Acetanilide
• Nitrofurans • Paracetamol
- Nitrofurantoin (Acetaminophen)
- Nitrofurazone • Aminophenazone
Analgesics
• Quinolones (Aminopyrine)
- Ciprofloxacin • Dipyrone (Metamizole)
- Moxifloxacin • Phenacetin
- Nalidixic acid • Phenazone (Antipyrine)
- Norfloxacin • Phenylbutazone
- Ofloxacin • Tiaprofenic acid
• Chloramphenicol • Furazolidone
• Sulfonamides • Streptomycin
Antibiotics - Co-trimoxazole • Sulfonamides
(Sulfamethoxazole + Antibiotics • Sulfacytine
Trimethoprim) • Sulfaguanidine
- Sulfacetamide
• Sulfamerazine
- Sulfadiazine
• Sulfamethoxypyridazole
- Sulfadimidine
- Sulfamethoxazole Anticonvulsants • Phenytoin
- Sulfanilamide Antidiabetics • Glibenclamide
- Sulfapyridine Antidotes • Dimercaprol (BAL)
- Sulfasalazine • Antazoline (Antistine)
(Salazosulfapyridine) Antihistamines • Diphenhydramine
- Sulfisoxazole • Tripelennamine
(Sulfafurazole) • Hydralazine
• Mepacrine Antihypertensives
• Methyldopa
• Pamaquine • Chloroquine &
Antimalarials
• Pentaquine derivatives
• Primaquine • Proguanil
Antimethemoglobinaemic Antimalarials
• Methylene blue • Pyrimethamine
Agents • Quinidine
• Dapsone • Quinine
• Para-aminosalicylic Antimycobacterials • Isoniazid
acid • Trihexyphenidyl
• Sulfones Antiparkinsonism
Antimycobacterials (Benzhexol)
- Aldesulfone sodium • Dopamine (L-dopa)
(Sulfoxone) Cardiovascular Drugs • Procainamide
- Glucosulfone
• Quinidine
- Thiazosulfone
Diagnostic Agent for
• Doxorubicin • Toluidine blue
Antineoplastic Adjuncts Cancer Detection
• Rasburicase
• Colchicine
• Phenazopyridine Gout Preparations
Genitourinary Analgesics • Probenecid
(Pyridium)
Hormonal
• Acetylphenylhydrazine • Mestranol
Others Contraceptives
• Phenylhydrazine Nitrates • Isobutyl nitrite
Source : Adapted from MIIMS 2006
• Menadiol Na sulfate
For further • Menadione
For furtherinformation, Kindly
information, referrefer
Kindly : www.g6pd.org
: www.g6pd.org Vitamin K Substances
• Menadione Na bisulfite
• Phytomenadione
• Ascorbic acid (Vit C)
Vitamins
(rare)
• Arsine
• Berberine (in Coptis
chinensis)
Others • Fava beans
• Naphthalene (in
mothballs)
• Para-aminobenzoic acid

182
Lot 36, Jalan University,
Selangor Darul Ehsan.
Tel : +603 7841 3200 Fax : +603 7968 2222
Website : www.pharmacy.gov.my

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Pharmaceutical Services Division

Ministry of Health Malaysia

Lot 36, Jalan University,

©ALL RIGHTS RESERVED

This is a publication of the Pharmaceutical Services Division, Ministry of Health

Pharmaceutical Services Division

2 Paediatric Pharmacy Services Guideline

Paediatric pharmacy is a specialized clinical pharmacy service that is currently

Therefore Clinical Pharmacy Working Committee ( Paediatric subspecialty )

I would like to commend the Clinical Pharmacy Working Committee (Paediatric

Puan Abida Haq bt Syed M. Haq

Paediatric Pharmacy Services Guideline 3

Madam Abida Haq Syed M.Haq

Main Editorial Committees

Noor Haslina Othman Stella Chuo Sing Hong

4 Paediatric Pharmacy Services Guideline

Paediatric Pharmacy Services Guideline 5

1.0 Introduction To The Guideline 8

6 Paediatric Pharmacy Services Guideline

Paediatric Pharmacy Services Guideline 7

8 Paediatric Pharmacy Services Guideline

Paediatric pharmacy consists of general paediatric, paediatric intensive care

Table 2.1: Job Description of Paediatric Pharmacist

Admission • Medication history clerking, which includes non-prescription

Pharmacotherapy • Active participation in ward rounds with doctors

Monitor and • Case clerking and review (CP2 form)

Identify • Dosing adjustment based on patient’s body weight, age

Paediatric Pharmacy Services Guideline 9

Provision of Drug • Drug availability

Education • Continuous Professional Development

Patient /caregiver • Bedside/Discharge counselling

Research and • Participate in research work/project pertaining to paediatric

10 Paediatric Pharmacy Services Guideline

Paediatric Pharmacy Services Guideline 11

12 Paediatric Pharmacy Services Guideline

Paediatric Pharmacy Services Guideline 13

Asthma is defined as a chronic airway inflammation leading to increase airway

The management of chronic asthma can be based on either the severity

14 Paediatric Pharmacy Services Guideline

Management of Chronic Asthma

Table 1: Evaluation of Newly Diagnosed Asthma

More than twice a

Brief exacerbations not

Daytime Symptoms None >2 per week

< 80% predicted or in any week

One in any week

• Provide medication education by providing information on the indication of the

16 Paediatric Pharmacy Services Guideline

STEP 1 REDUCE STEP 2 ← STEP 3 → STEP 4 INCREASE STEP 5

Mild Moderate Severe Severe

Mild Moderate Severe Severe

Controller As needed rapid acting

Controller Medium / High

Leukotriene Medium / High Leukotriene

Paediatric Pharmacy Services Guideline 17

Table 5: Drug Doses Of Common Medications Used in Asthma

Oral 0.15 mg/kg/dose 6-8H/ PRN

100-200 mcg/dose 4-6H/

Dry powder inhaler

For continuous intravenous

0.15 mg/kg/dose (max 5 mg)

Fluticasone Metered dose inhaler Dry <200 mcg/day : Low

18 Paediatric Pharmacy Services Guideline