PGIMER

Management Protocols in
Pediatric Emergency Medicine
Advanced Pediatrics Centre – Postgraduate Institute of Medical Education and Research

Published By
Indian Journal of Pediatrics, New Delhi, India
www.ijppediatricsindia.in
2015
CONTENTS
 Initial Assessment and Triage in ER
 Approach to a Child with Breathing Difficulty
 Acute Community Acquired Pneumonia in Emergency Room
 Acute Upper Airway Obstruction
 Acute Chest Pain
 Approach to a Child with Sore Throat
 Acute Bronchial Asthma
 Approach to a Child with Lower Airway Obstruction and Bronchiolitis
 Airway Foreign Body Aspiration
 Fainting Attacks in Children
 Non-Traumatic Coma and Altered Mental Status
 Approach to Headache in Emergency Department
 Management of Acute Seizure and Status Epilepticus in Pediatric Emergency
 Raised Intracranial Pressure (ICP): Management in Emergency Department
 Approach to a Child with Acute Flaccid Paralysis
 Tumor Lysis Syndrome
 Superior Mediastinal Syndrome: Emergency Management
 Febrile Neutropenia: Outline of Management
 Hyperleukocytosis: Emergency Management
 Management of a Child with Vomiting
 Management of Acute Diarrhea in Emergency Room
 Approach to a Child with Upper Gastrointestinal Bleeding
 Emergency Management of Lower Gastrointestinal Bleed in Children
 Approach to a Child with Bleeding in the Emergency Room
Indian J Pediatr (September 2011) 78(9):1100–1108
DOI 10.1007/s12098-011-0411-3
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Initial Assessment and Triage in ER
M. Jayashree & Sunit C. Singhi
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 8 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Triage refers to quick assessment of a patient in
the Emergency Room with a view to define urgency of care
and priorities in management. Triage evaluation can be
completed in an organized and systematic manner using
Pediatric Assessment Triangle (PAT), which refers to
immediate visual and auditory assessment of appearance,
breathing and circulation. At the end of PAT, patient’s
illness is categorized as either stable or unstable. Unstable
conditions are further classified into life threatening and
non life threatening. Patients in the former category include
those in need of immediate resuscitation e.g. cardiac arrest,
cardio-respiratory failure, decompensated shock, deep
coma, severe stridor etc. Once a child is on the way to
stabilization, the primary assessment (assessment penta-
gon),which takes 1–3 min follows. It involves the detailed
physical examination/assessment of airway (A), breathing
(B), circulation(C), neurologic abnormalities (D) and head
to- toe examination (Exposure). After the primary assess-
ment, patient’s illness severity is triaged into 5 levels of
acuity based on the physiological abnormalities: those in
need of Resuscitation, Emergent care, Urgent care, Less
urgent and Non-urgent care.
Keywords Pediatric triage . Pediatric assessment triangle .
PAT . Pediatric assessment pentagon
M. Jayashree : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
M. Jayashree
e-mail: mjshree@hotmail.com
Introduction
Quick recognition and timely intervention in seriously ill or
injured children is the key to prevent progression to life
threatening state. Triage refers to assessment of a patient in
the Emergency Room with a view to define urgency of care
and priorities in management, thus helping in the rational
allocation of limited resources when the demand exceeds
the availability. This would mean that patients, who need
acute care in the Emergency Department (ED), are first
taken up for care in order of priority while those needing
less acute care wait in the triage room. Thus, triage system
is basically a framework within which a patient is classified
according to the acuity and severity of illness. There are
many international triage systems devised for acute care in
emergency departments like Emergency triage and treat-
ment (ETAT) guidelines [1], Emergency Severity Index
(ESI) [2], Canadian Triage and Acuity System (CTAS) [3,
4] and the Australian Triage Scale [5].
Pediatric Triage
Pediatric triage assessment is a rapid 3–5 min evaluation of a
child that gathers pertinent subjective and objective data to
determine the severity of illness. Pediatric patients who seek
emergency care require timely assessment by experienced
emergency care providers. Also it is particularly important to
triage each child according to the age, symptomatology and
acuity of illness. What is assigned a high level of acuity differs
with age and associated symptoms and signs. e.g. abdominal
pain or fever <39°C in older child may be non urgent but an
emergency for a one- month- old infant. Once the patients
are triaged, they are classified into various levels of illness
acuity and prioritized accordingly.
Indian J Pediatr (September 2011) 78(9):1100–1108
Goals of Triage System [6]
As the patients present to the ED, the rule of “Rights” have
to be followed:
Get the right patient to the right provider, in the right
moment of time, to receive the right care, to achieve
the right outcome.
1. To rapidly assess and identify patients with life
threatening illness.(This initial screening and clas-
sification of the patient frequently determines how
quickly the child will receive medical and nursing
interventions)
2. To determine appropriate cause and initiate first aid
measures by experienced nurse or doctor and order
immediate investigations and procedures as per the
need.
3. Ongoing assessments are to be performed, as
pediatric patients may deteriorate rapidly
4. To provide safe and quality care to patients and to
utilize the limited resources in an efficient manner.
Triage Assessment
Triage evaluation can be completed in an organized and
systematic manner using the general assessment i.e. Pediatric
Assessment Triangle (PAT) and primary assessment (ABCDE
approach) (details are given in triage form). This assessment is
different than diagnostic evaluation. The objective here is to
identify anatomical or functional abnormality, its severity, to
plan and guide initial emergency treatment as summarized in
Fig. 1. In the authors’ emergency room, triage assessment and
management is done by a junior (trainee) resident, well trained
in Pediatric Advanced Life Support (PALS), supported and
supervised by the on duty senior resident (who is also trained
in PALS). The assessment and treatment go hand in hand.
General Assessment
PAT is the immediate visual and auditory assessment while the
patient is brought in, based on the triad of appearance,
breathing and circulation. This initial general impression of
the patient is to be completed in initial 30–40 s. This helps in
identifying the patients requiring rapid life saving decisions.
Appearance Breathing
Circulation
1101
Appearance Can be assessed while the child is in mother’s
lap. Look for posture/positioning (sniffing position, or
leaning forward on outstretched arm), muscle tone (active,
moving or limp and listless), alertness and interaction,
consolability, playful, agitated or crying, look/gaze or
speech/cry (normal weak, muffed, hoarse). A grossly
abnormal appearance suggests seriously ill child. It could
be due to underlying hypoxemia, poor cerebral perfusion,
infection, poisoning, brain injury, hypoglycemia or any
metabolic cause. Such patients should be started measure to
improve oxygenation and perfusion before continuing with
further assessment.
Work of Breathing Look for signs of increased work of
breathing (nasal flaring, lower chest wall retractions),
decreased or absent efforts, abnormal breath sounds
(wheeze, grunt, stridor).
A normal appearance and increased work of breathing
indicates a compensated state of respiratory distress, in
which oxygenation and ventilation are reasonably well
maintained. Abnormal appearance (agitation, restlessness,
lethargy or diminished responsiveness) with increased work
of breathing, on the other hand indicates a state of acute
hypoxemia and hypercapnia (respiratory failure).
Circulation Look for abnormal skin color (pale/mottled,
cyanosed) or bleeding all over the body. When cardiac
output is low there is constriction of blood vessels to the
skin and blood flow to the skin is minimal. Pallor and/or
mottling are usually the first signs of poor perfusion
(shock). Cyanosis is a sign of respiratory failure or late
shock. Abnormal circulation with normal appearance
suggests early or compensated shock, while abnormal
appearance and abnormal circulation indicate decompen-
sated or late shock.
At the end of PAT patient’s illness is categorized as
either stable or unstable (Table 1). Unstable conditions are
further classified into life threatening and non life threat-
ening. Patients in the former category e.g. cardiac arrest,
cardio-respiratory failure, decompensated shock, deep
coma, severe stridor etc. need immediate treatment/resusci-
tation before going to primary assessment.
Primary Assessment
Once a child is on the way to stabilization, the primary
assessment (assessment pentagon) follows. It involves the
detailed physical examination/assessment of airway (A),
breathing (B), circulation(C), neurologic abnormalities (D)
and head to- toe examination (Exposure). Primary assess-
ment should be completed in 1–3 min. This primary
assessment also involves additional recording of parameters
like SPO2, EKG and blood glucose.
1102 Indian J Pediatr (September 2011) 78(9):1100–1108

Sick child in ER

Pediatric
Assessment
Triangle

Pediatric
assessment
pentagon

No
Position, suction, oro- Is airway maintained?
pharyngeal airway

No Yes

Intubation or Tracheostomy Yes No Oxygen

Is Breathing appropriate? Assisted ventilation with bag/
in case of stridor, drooling,
mask

Yes No

No
Yes
IV access, Fluid bolus, Is Circulation appropriate? Endotracheal intubation
First dose of antibiotic

Yes
No

Cardiac compressions if Yes

Focused History
absent/feeble femoral pulse
Physical Examination

Five level Triage

Resuscitaion, Emergent, Urgent,
Less Urgent, Non Urgent

Fig. 1 Scheme for initial assessment and resuscitation in Emergency room

Airway obstruction. Feel—the movement of air at the nose and

It is essential to determine patency of the airway. To
assess upper airway. Look- for chest rise. Listen –for
breath sounds and air movement, audible abnormal airway
sounds—gurgling, stridor, and wheeze suggest airway
mouth.
Clinical signs of an airway obstruction include breathing
difficulty, inability to speak or breathe, a silent cough, or poor
air exchange. It is crucial to determine whether the airway is
maintainable by simple maneuvers, or not maintainable,
Indian J Pediatr (September 2011) 78(9):1100–1108 1103

Table 1 Interpretation of findings on PAT and immediate intervention

Appearance Work of Circulation Interpretation Stabilization

breathing

Normal Normal Normal Stable –

Abnormal Normal Normal Primary brain dysfunction Start O2, connect to pulse oximeter and cardiac monitor, obtain
or systemic disease vascular access, check dextrostix, start saline infusion at minimal rate.
Normal Abnormal Normal Respiratory distress Oxygen using face mark/nasal prongs at maximal flow; if airway
unstable insert oropharyngeal airway
Normal Normal Abnormal Compensated shock Start O2, connect to pulse oximeter and cardiac monitor, obtain
vascular access, start saline infusion 20 ml/kg, check dextrostix
Abnormal Abnormal Normal Respiratory failure If airway unstable, insert oropharynxial airway, start 100% oxygen
and perform endotracheal intubation
Abnormal Normal Abnormal Decompensated shock O2, Attach to a monitor—check for rhythm, obtain a vascular
access IV or intraosseus
Abnormal Abnormal Abnormal Cardiopulmonary failure/arrest Start CPR if absent or poor femoral/carotid/brachial pulse

Adapted and improvised from APLS Pediatric Emergency Manual, 4th edition, American Academy of Pediatrics: 2008: 34

necessitating advanced interventions. If head tilt-chin lift Breathing

positioning and suctioning do not relieve the signs of airway
obstruction, child needs direct laryngoscopy and endotracheal
intubation.
A B
E C
D excursion, and auscultation of air movement. Abnormal lung
The assessment of breathing includes an evaluation of the
respiratory rate and effort, lung sounds, and pulse oximetry.
Normal respiratory rates depend on the age of the patient.
However, there is some variation in normal rates defined by
different expert groups (Table 2). Tachypnea is defined as a
rate that is more rapid than normal for age, whereas bradypnea
is a rate that is slower than normal for age. WHO has
suggested age-specific threshold for tachypnea for children up
to 5 years of age to diagnose pneumonia. Apnea is defined as
a complete cessation of breathing for 20 s or more.
Auscultate for adequacy of air-entry and abnormal lung
sounds (crepitations, rhonchi, wheeze) over midaxillary line
on both sides.
Increased respiratory effort can manifest as nasal flaring,
retractions, accessory muscle use, or irregular respirations. Other
points for assessment include adequate and equal chest wall

Table 2 Expected respiratory rate (breath/min), according to age

Age range, years Neonate 0–1 1–2 2–3 3–4 4–5 5–6 6–12 12–13 13–18

APLS 30–40 30–40 25–35 25–30 25–30 25–30 20–25 20–25 15–20 15–20
PALSa 30–60 30–60 24–40 24–40 24–40 22–34 22–34 18–30 18–30 12–16
EPLSb 30–40 30–40 26–34 24–30 24–30 24–30 20–24 20–24 12–20 12–20
PHTLS 30–50 20–30 20–30 20–30 20–30 20–30 20–30 (12–20) (12–20) 12–20
ATLS <60 <40 <40 <35 <35 <35 >30 >30 <30
WHOc <60 <50d <40 <40 <40 <40 – – – –
a
PALS and EPLS provide separate ranges for infants up to 3 months, and for those between 3 months and 2 years of age
b
PALS and EPLS provide multiple ranges—ranges for awake children are tabulated
c
WHO has suggested age-specific threshold for tachypnea for children up to 5 years of age to diagnose pneumonia
d
PHTLS provides separate ranges for infants up to 6 weeks, and for those between 7 weeks and 1 year of age
PALS Pediatric Advanced Life Support; EPLS European Pediatric Life Support; APLS Advanced Pediatric Life Support; PHTLS PreHospital
Traumatic Life Support; ATLS Advanced Trauma Life Support; WHO World Health Organization
1104 Indian J Pediatr (September 2011) 78(9):1100–1108

sounds include stridor, grunting, gurgling, wheezing, and
crackles.
Retractions þ stridor ¼ Upper airway obstruction
Retractions þ wheeze ¼ Lower airway obstruction
Retraction þ Grunt=laboured breathing ¼ Parenchymal disease
O2 saturation ≥94% on pulse oximetry at room air suggests
adequate oxygenation. However, it should be interpreted
together with work of breathing. A child may be able to
maintain oxygenation by increasing respiratory rate and work
of breathing, but gets exhausted and deteriorates rapidly. Pulse
oximetry may show abnormally low SpO2 in presence of poor
peripheral perfusion (shock) or abnormally high SpO2 in a
distressed child may be seen in methemoglobinemia and CO
poisoning. Additional interventions are required if O2 satura-
tion is <92% in a child receiving 100% O2 by non-rebreathing
mask.
Circulation
The assessment of cardiovascular function includes heart
rate and rhythm, blood pressure, peripheral and central pulses,
capillary refill time, skin color and temperature. Heart rate
varies according to the child’s age, and includes a wide range
(Table 3). Typically, the rate will be much slower in a sleeping
or athletic child. Tachycardia is a heart rate faster than expected
for a child’s age, whereas bradycardia is slower than normal.
Similarly, blood pressures vary according to age (Table 4).
Hypotension is defined as a value below the fifth percentile of
expected blood pressures for age. Hypotension represents a
state of shock, either due to hemorrhage, sepsis, or cardiac
failure. An observed fall of 10 mm Hg in systolic BP from
baseline should prompt serial evaluations for additional signs of
shock.
If heart rate is too fast or too slow, immediately attach the
child to a monitor or obtain a three-lead ECG, especially the
one with signs of poor perfusion. Various rhythm disturbances,
or arrhythmias, can be recognized to initiate appropriate
interventions. The important dysrhythmias to recognize are
ventricular fibrillation, ventricular tachycardia, pulseless elec-
trical activity (PEA), asystole, and supraventricular tachycardia.
Disability Assessment
It involves quick evaluation of neurological status: mainly
cerebral cortex and the brain stem. Standard evaluation
includes level of consciousness using AVPU (awake, voice,
pain, unresponsive) scale, seizure, pupillary response to light
and posturing and motor activity (asymmetry/abnormal).
Level of consciousness could also be assessed by applying
modified Glasgow Coma Scale (GCS). A change of at least 2
points in the GCS score from one assessment to the next
indicates a clinically important change in neurological status.
Exposure
Examine whole body for evidence of trauma, unusual
markings of abuse, rashes, bleeds and core temperature, by
exposing entire body or one body area at a time.
After the primary assessment, patient’s physiological
status is classified as; stable, respiratory distress or
respiratory failure, shock compensated or decompensated,
primary brain/systemic dysfunction, cardiorespiratory fail-
ure or cardiorespiratory arrest and further triaged into 5
levels (Table 5).
Triage Classification [3]
Patients’ illness severity is triaged into 5 levels depending on
the physiological abnormalities as given in the Table 5. A
simple proforma used for triage in the authors’ emergency
department is shown in the Appendix.

Table 3 Expected heart rates, according to age (beats/minute)

Age, years Neonate 0–1 1–2 2–3 3–5 5–6 6–10 10–12 12–13 13–18

APLS 110–160 110–160 100–150 95–140 95–140 80–120 80–120 80–120 60–100 60–100
PALSa 85–205 100–190 100–190 60–140 60–140 60–140 60–140 60–100 60–100 60–100
EPLS 85–205 100–180 100–180 60–140 60–140 60–140 60–140 60–100 60–100 60–100
PHTLSb 120–160b 80–140 80–130 80–120 80–120 80–120 (60–80) (60–80) (60–80) 60–100c
>100 >100 100 <100
ATLS <160 <160 <150 <150 <140 <140 <120 <120 <100
a
PALS and EPLS provide separate ranges for infants up to 3 months, and for those between 3 months and 2 years of age
b
PALS and EPLS provide multiple ranges—ranges for awake children are tabulated
c
PHTLS does not provide ranges for adolescents over 16 years of age
PALS Pediatric Advanced Life Support; EPLS European Pediatric Life Support; APLS Advanced Pediatric Life Support; PHTLS PreHospital
Traumatic Life Support; ATLS Advanced Trauma Life Support; WHO World Health Organization
Indian J Pediatr (September 2011) 78(9):1100–1108 1105

Table 4 Expected systolic and diastolic blood pressures according to & Triage evaluation can be completed in an organized
age
and systematic manner using Pediatric Assessment
Age Systolic BP(mmHg) Diastolic BP(mmHg) Triangle (PAT), which refers to immediate visual and
auditory assessment of appearance, breathing and
0 day 60–76 30–45 circulation.
1–4 day 67–84 35–53 & At the end of PAT, patient’s illness is categorized as
1 month 73–94 36–56 either stable or unstable.
3 month 78–103 44–65 & Unstable conditions are further classified into life-
6 month 82–105 46–68 threatening and non life threatening.
1 year 67–104 20–60 & Patients in cardiac arrest, cardio-respiratory failure,
2 year 70–106 25–65 decompensated shock, deep coma, severe stridor etc.
7 year 79–115 38–78 are assessed as having life-threatening illness. They are
15 year 93–131 45–85 in need of immediate resuscitation
& The primary assessment (assessment pentagon), which
Females have slightly lower systolic blood pressures, and higher
diastolic blood pressures than males of the same age.
takes 1–3 min, follows once stabilization measures are
in place. It involves the detailed physical assessment
Adapted from Fourth Report on the diagnosis, evaluation and treatment
of high blood pressure in children and adolescents: NHLBI; May 2004 of airway (A), breathing (B), circulation(C), neuro-
logic abnormalities (D) and head to- toe examination
(Exposure).
Key Points & After the primary assessment, patient’s illness severity
is triaged into 5 levels of acuity based on the
& Triage refers to quick assessment of a patient in the physiological abnormalities: those in need of Resusci-
Emergency Room with a view to define urgency of care tation, Emergent care, Urgent care, Less urgent and
and priorities in management. Non-urgent care.

Table 5 Five levels of triage depending on the physiological abnormalities

Triage Acuity Description Target time to Examples Remarks

level treatment and
reassessment

Level 1 Resuscitation Patient with life- Immediate Cardiac arrest, severe respiratory distress/ Need continuous assessment
threatening disease or and failure, shock,seizure, unresponsive, airway and intervention to maintain
injury requiring continuous obstruction, hypothermia, coma, GCS<10, physiological stability
immediate treatment (1–5 min) major burns, severe trauma,
Level 2 Emergent Patient with significant 15 min Moderate respiratory distress, stridor, GCS< Any infant/child who requires
health problems that 13, Severe dehydration, fever: <3 months multiple interventions to
could become life age: and temp >38°C, inhalation or prevent further deterioration
threatening or ingestion of toxic substance, acute bleeding,
disabling purpuric rash, burns >10%, abdominal pain
with vomiting/diarrhea or abnormal vitals
Level3 Urgent Patient with significant 30 min Alert, oriented, with minor alteration in Level 3 patients need carefully
health problems that vitals. Febrile child >3 months old with planned reassessments while
are not immediately temperature >38.5°C, minor head injury awaiting care, since critical
life threatening or illness may present with
disabling common symptoms and may
evolve rapidly
Level4 Less urgent Patient with stable 1h Diarrhea with no dehydration, lacerations,
conditions; to be pain, sore throat
evaluated in the ED
Level 5 Non urgent Patient with stable health 2 h Afebrile, alert, well oriented, euhydrated, These patients may be referred
conditions; to be normal vitals. to other areas of hospital for
evaluated in ED/OPD management.

Adapted from Canadian pediatric triage and acuity scale [3, 4]

1106 Indian J Pediatr (September 2011) 78(9):1100–1108

Conflict of Interest None.

Role of Funding Source None.

Appendix
Indian J Pediatr (September 2011) 78(9):1100–1108 1107
1108
References
1. Emergency Triage Assessment and Treatment (ETAT) course:
WHO manual for participants 2005.
2. Shelton R. The emergency severity index 5-level triage system.
Dimens Crit Care Nurs. 2009;28:9–12.
3. Canadian Association of Emergency Physicians. Canadian
Pediatric triage and acuity scale: implementation guidelines
for emergency departments. Can J Emerg Med. 2001;3:1–
40.
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4. Beveridge R, Clark B, Janes L, et al. Canadian emergency
department triage and acuity scale: implementation guidelines.
Can J Emerg Med. 1999;1:S2–28.
5. Australasian College of Emergency Medicine. Policies & guide-
lines. G 24 guidelines for implementation of The Australasian
Triage Scale in Emergency Departments, Revised 05 August 2005.
http://www.acem.org.au/media/policies_and_guidelines/
G24_Implementation__ATS.pdf (last accessed 19th Feb 2011).
6. Fuchs S, Gausche-Hill M, Yamamoto L. The Pediatric Emergency
Medicine Resource, Advanced Pediatric Life Support (APLS)
manual 2004, American College of Emergency Physicians. 4th
ed. Dallas: Jones & Bartlett; 2004. p. 2–19.
Indian J Pediatr (September 2011) 78(9):1118–1126
DOI 10.1007/s12098-011-0424-y
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Approach to a Child with Breathing Difficulty
Joseph L. Mathew & Sunit C. Singhi
Received: 27 January 2011 / Accepted: 8 April 2011 / Published online: 1 June 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Breathing difficulty and respiratory distress is the
most common cause of admission to the Pediatric Emergen-
cy. Respiratory distress presents as altered breathing pattern,
forced breathing efforts or obstructed breathing, and chest
indrawing; respiratory failure is defined as paCO2 >50 mmHg
(inadequate ventilation) and/or a paO2 <60mmHg (inade-
quate oxygenation). Rapid assessment is aimed to ascertain
adequacy of airway patency, breathing, and circulation.
Immediate care is directed at (a) restoration of airway
patency- by positioning (head tilt –chin lift), cleaning the
oropharynx, and/or insertion of oropharyngeal airway; (b)
supporting breathing- with high flow oxygen and assisted
ventilation (with bag and mask or endotracheal intubation
and ventilation), and (c) restoration of circulation- using fluid
boluses and inotropes, if necessary. Immediate specific
management may require endotracheal intubation/tracheos-
tomy for upper airway obstruction; needle thoracotomy and
drainage of pneumothorax; and first dose of antibiotic for
febrile children. Thereafter meticulous history, focused
physical examination, and specific laboratory/radiological
investigations are undertaken to identify the underlying
cause. At the end of this, one should be able to categorize
the child to one of the following: (a) upper airway
obstruction, (b) pneumonia (syndrome of cough, fever and
breathing difficulty), (c) lower airway obstruction, (d) slow
or irregular breathing without pulmonary signs, and (e)
respiratory distress with cardiac findings, to initiate specific
treatment. Further respiratory support by Continuous Posi-
tive Airways Pressure (CPAP) and mechanical ventilation
may be required in some cases. All children with respiratory
distress must be monitored for early detection of worsening/
J. L. Mathew : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
complications, assessment of response to therapy and rapid
documentation of clinical state.
Keywords Respiratory distress . Breathing difficulty .
Respiratory failure . Upper airway obstruction . Lower
airway obstruction
Introduction
Breathing difficulty accounts for a significant proportion of
childhood visits to the Emergency department. It is one of four
cardinal manifestations presenting to the Emergency; the others
being altered consciousness, seizure, and shock [1]. In the
authors’ emergency, respiratory distress is second only to
fever as the most common presenting symptom in the
Emergency [2]. Acute respiratory infection (ARI) is the most
common diagnosis in secondary and tertiary level health-care
facilities [3, 4]. Early recognition of children at risk of
respiratory failure and timely initiation of appropriate sup-
portive and specific management can dramatically improve
the outcome.
Definitions
Respiratory Distress
Respiratory distress refers to any kind of subjective
difficulty in breathing. Objectively, it manifests as one or
more of the following: altered breathing pattern (fast, slow,
feeble or absent), forced breathing efforts or obstructed
breathing, and chest indrawing. Respiratory distress is
defined as a clinical state characterized by increased
respiratory rate (tachypnea) and respiratory efforts (in-
creased work of breathing) [5]. In this state the child tries to
Indian J Pediatr (September 2011) 78(9):1118–1126
maintain adequate gas exchange despite a respiratory
pathology. If the child tires or respiratory function
deteriorates further and adequate gas exchange cannot be
maintained, the child progresses to respiratory failure.
Respiratory distress can range from mild to severe.
When severe, it is often associated with respiratory failure.
Table 1 presents the grading of acute respiratory distress.
Respiratory Failure
Respiratory failure occurs when pulmonary function is
inadequate to deliver sufficient oxygen to meet demands of
the body and/or there is inability to eliminate carbon dioxide.
Arterial blood gas analysis shows paCO2 >50 mmHg
(inadequate ventilation) and/or paO2 <60mmHg (inadequate
oxygenation) while breathing 40% oxygen. Clinically respi-
ratory failure may manifest with central nervous system
(CNS) changes caused by hypoxemia (somnolence or
depressed consciousness, seizures and coma), or hypoxic
cardiovascular manifestations such as marked tachycardia or
bradycardia and hypotension (Table 1).
Pathophysiology
The unique anatomic and physiologic characteristics of the
respiratory tract in infants and children make them
especially vulnerable to respiratory distress and failure;
hence a systematic approach is vital to improve outcomes.
Table 1 Grading of acute respiratory distress
Mild
• Tachypnea
• Dyspnea or shortness of breath
Moderate
• Tachypnea
• Minimal chest wall retractions
• Flaring of alae nasi
Severe
• Marked Tachypnea (> 70 breaths/min)
• Apneic episodes/bradypnea/irregular breathing
• Lower chest wall retractions
• Head bobbing (use of sternocleidomastoid muscles)
• Cyanosis
Respiratory failure
• Respiratory distress + cyanosis or CNS* and/or cardiovascular**
signs of hypoxemia
*CNS signs of hypoxemia: restlessness, obtunded sensorium, somnolence,
seizures, coma
** Cardiovascular signs of hypoxemia: marked tachycardia, bradycardia,
hypotension, and cardiac arrest
1119
Normal respiration depends on intact function and coordi-
nation among (a) contraction of intercostal muscles and
diaphragm and generation of negative intrapleural pressure,
(b) expansion of lungs, (c) alveolar gas exchange through
diffusion, and (d) transport of oxygen through blood. A
pathophysiologic approach to causes of respiratory distress is
outlined in Table 2.
Approach to a Child with Respiratory Distress
Rapidly assess the child, identify the presence of a functional
derangement, and quantify its severity. This assessment
determines the urgency with which interventions need to be
instituted. The exact etiology of breathlessness is less
important at this time. Specific treatment based on etiology
is considered only after initial stabilization.
Initial General Assessment
The goal is to rapidly assess for (a) airway patency, (b)
adequacy of gas exchange, (c) circulatory status.
Assessment begins with a quick visual and auditory
evaluation using Pediatric Assessment Triangle [6] and includes
the following (see protocol on Initial assessment and Triage):
Appearance—interaction, muscle tone, consolability,
look/gaze or speech/cry.
Work of breathing—use of accessory muscles of
respiration (increased work of breathing) or absent
respiratory effort, abnormal breath sounds.
Circulation—abnormal skin color (pallor, cyanosis),
bleeding.
Primary Assessment
This is done using the Assessment Pentagon, which
includes Airway, Breathing, Circulation, Disability and
Exposure [6].
Airway
Assessment is aimed at deciding whether the airway is:
Clear—open and unobstructed.
Maintainable—maintained by simple measures like
position, suction etc.
Not maintainable—needs advanced measures like
intubation
Any audible sound during breathing is suggestive of
airway obstruction [7].
Stridor is a coarse high pitched sound typically heard on
inspiration. It is a sign of (extrathoracic) upper airway
obstruction.
1120 Indian J Pediatr (September 2011) 78(9):1118–1126

Table 2 Pathophysiologic approach to Clinical conditions causing respiratory distress

Etiology Pathophysiology Clinical conditions

Interference with air flow (entry or exit)
Interference with alveolar gas exchange
Cardiovascular problems
Nervous system disturbance
Other
Upper airway obstruction
Lower airway obstruction
Mechanical compression
Thoracic wall injuries
Failure of alveolar ventilation
Failure of diffusion
Mechanical or inadequate function
Depression of respiratory centre
Stimulation of respiratory center
Neuromuscular impairment of respiration
Insufficient oxygen supply to tissues
and/or increased oxygen demands
Compensation for metabolic acidosis.
Acute laryngitis, laryngotracheitis, diphtheria,
foreign body aspiration.
Bronchiolitis, asthma
Large pleural effusion, pneumothorax, tumors
and elevated dome(s) of diaphragm
Hemopneumothorax and flail chest.
Pneumonia, pulmonary edema, pulmonary
hemorrhage, pulmonary fibrosis.
Pneumonia, pulmonary edema, pulmonary
fibrosis, pulmonary embolism, interstitial
lung disease
Congestive cardiac failure, arrhythmias,
myocarditis, pericarditis, Right-to-left shunts
Impaired consciousness, raised intracranial
pressure, intracranial bleeding,poisoning
Acidosis, salicylate intoxication.
Acute paralytic poliomyelitis, Guillain-Barre
syndrome, organophosphate poisoning,
snake bite, diaphragmatic paralysis.
Sepsis, severe anemia, high altitude, carbon
monoxide exposure, smoke inhalation,
meth-hemoglobinemia
Diabetic ketoacidosis, acute renal failure.

Wheezing is a whistling sound heard most often
during expiration, indicating lower (intrathoracic) airway
obstruction.
Grunting is typically a short, low pitched sound heard
during expiration, produced by forced expiration against a
partially closed glottis. It is an attempt to keep small
airways and alveoli open to maintain oxygenation and
ventilation. It is typically a sign of severe respiratory
distress progressing to respiratory failure. At times, grunt-
ing may accompany high fever or severe pain (often
abdominal pain), even in the absence of significant
respiratory pathology.
Breathing
which is inappropriate for the clinical situation (relative
bradypnea) indicates advanced respiratory failure. In
cardiorespiratory disorders, tachypnea is accompanied by
increased work of breathing. Accessory muscles of
respiration are recruited, which manifests as supraclavicular,
suprasternal, intercostal, or subcostal retractions, nasal
flaring and sometimes head bobbing. See-saw respirations
(abdominal breathing), is seen in neuromuscular weakness,
but can also occur in the late stages of severe respiratory
pathology.
CNS disorders may result in respiratory failure
through hypoventilation. Respiration in these patients
could be too slow (bradypnea) or absent (apnea). and is
always ominous.

Normal spontaneous ventilation is quiet and effortless, and
maintains a steady tidal volume and rate. Adequacy of tidal
volume is assessed clinically by observation of chest wall
excursion and auscultation of the lungs. In pathological
states, one of the first compensatory mechanisms is increased
respiratory rate (tachypnea) to maintain oxygenation/CO2
removal. Thus, respiratory rate is also a good predictor of
hypoxemia [8]. When the body is unable to sustain increased
respiratory rate, respiratory muscle fatigue sets in, and tidal
volume starts falling. The respiratory rate may fall at this
stage; therefore an apparently ‘normal’ respiratory rate
Pulse Oximetry After evaluation for triage, all children with
signs of respiratory illness should have a pulse oximetry. It
measures percentage of hemoglobin saturated with oxygen
and is the best non-invasive method for early detection of
hypoxemia. Hypoxemia occurs frequently and is strongly
associated with mortality. It is not a sine qua non of
pneumonia (and occurs in many lower airway diseases, and
some upper airway problems) and may not be predictable
clinically [9]. Low oxygen saturation (hypoxemia) may be
detected much before the appearance of cyanosis. Oximetry
is unreliable in states of poor distal perfusion, abnormal
Indian J Pediatr (September 2011) 78(9):1118–1126
hemoglobin, and when the heart rate displayed by the
monitor does not correlate with the clinical heart rate.
Circulation
Assessment of circulation includes evaluation of cardio-
vascular function (pulse, heart rate and blood pressure)
and end organ perfusion. Heart rate should be appropriate
for the child’s age, level of activity, and clinical condition.
Tachycardia is a common, nonspecific response to a variety
of underlying conditions, but it could be the first sign of
compensated shock. Bradycardia, when associated with
other signs of decreased perfusion, most commonly indi-
cates hypoxia, and is an ominous sign demanding urgent
action.
Pulse Feeble peripheral pulse is first sign of compromised
perfusion; the skin over hands and feet becomes cold, pale,
dusky or mottled. Hypotension follows; finally the central
pulses become feeble.
Capillary refill time (CRT) is a more objective way to
assess skin perfusion. It is clinically measured as the time
taken for skin of palm/soles to become pink after it has
been blanched by gentle pressure of thumb. Normal CRT is
<2 s. A prolonged CRT indicates poor perfusion.
Disability
Reduced oxygen supply to brain because of hypoxemia or
poor perfusion affects consciousness, muscle tone and
pupillary responses. Early manifestations are anxious look,
irritability and agitation, followed by somnolescence and
decreased responsiveness, which can be rapidly assessed by
the AVPU scale (Alert, responsive to Voice, responsive to
Pain, Unresponsive).
Exposure
It includes undressing the child for a focused physical
examination, looking for evidence of trauma, petechiae/
purpura and warming if indicated.
Categorization of Severity of the Clinical Condition
Life Threatening Conditions
If at any point during the assessment, a life threatening
condition is identified (Table 3), appropriate interventions are
instituted, before proceeding with the rest of the assessment.
1121
In a sick child, irrespective of the original underlying
illness, life is endangered because of respiratory or cardio-
vascular dysfunction. Therefore, at the end of initial assess-
ment, one should be able to categorize the child’s functional
derangement into a primarily respiratory or a primarily
circulatory problem or both; with further categorization of
the severity of the derangement. Such a categorization helps to
decide the urgency with which intervention is required.
Assessment Severity
Respiratory problem Respiratory distress
Respiratory failure
Circulatory problem Compensated shock
Hypotensive shock
Immediate Care
The goal is to relieve hypoxemia and support respiratory
functions until specific therapy becomes effective. This is
done by (a) Ensuring an open airway and breathing. (b)
Delivering oxygen without causing agitation, and (c)
Ensuring adequacy of circulation, normal temperature and
hydration [10].
Airway patency can be achieved with
(a) Proper positioning (extend the neck, pull the mandible
forward, to lift the tongue),
(b) Cleaning the oropharynx of any secretions (manually
if necessary), and
(c) Insertion of an oropharyngeal airway.
In the presence of stridor, dysphagia and drooling, which
suggest upper airway obstruction, emergency endotracheal
intubation or tracheostomy may be needed. If this is not
feasible, insertion of a wide bore cannula or needle into trachea
through cricothyroid membrane (needle cricothyrotomy) can
be tried as a temporary measure.
Ensure Breathing/Respiration if spontaneous normal
breathing is absent/inadequate by:
(a) Assisted ventilation by bag and mask ventilation, (b)
Endotracheal intubation as soon as adequate expertise and
equipment are available, (c) Providing oxygen. Never delay
resuscitation for lack of equipment or trained personnel.
Oxygen can be effectively provided to children of all
ages by nasal prongs of appropriate size. A flow rate of
0.5–1.0 l/min is used for infants and 1-2 l/min for older
children. This will provide 30–35% oxygen if the source in
unblended 100% oxygen.
1122
Table 3 Signs of Life-threatening
illness in a child with respiratory Airway Complete or severe airway obstruction
distress Breathing Apnea/bradypnea, markedly increased work of breathing
Circulation Absence of detectable pulse, poor perfusion, hypotension, bradycardia
Disability Unresponsiveness,
Exposure Significant hypothermia or bleeding, petechiae/purpura consistent with septic shock
Oxygen can also be delivered by intranasal catheter at a
flow rate of 1-3 l/min; it should be inserted to half the
distance between the tip of nose and the tip of ear. Oxygen
tent, face mask, or head-box can deliver higher concentra-
tion of oxygen. Humidification of inspired air/oxygen can
be achieved using humidifier, heated water bath, or by
nebulization. However, there is no evidence supporting
need for routine humidification of O2 at flows ≤4 l/min
Nasal prongs are the recommended way of providing
oxygen to most children. However, There is no significant
difference in oxygen administration by nasal prongs or
nasopharyngeal catheters [11]; in fact all low-flow methods
are effective [12]. For older children, oxygen is best given
by a face-mask. The ventury masks usually provide 25–
40% oxygen. Some masks may provide upto 50% oxygen
in inspired air at a flow rate of 8–10 l/min, while >80%
oxygen concentration can be achieved in a head-box.
Table 4 shows common oxygen delivery devices and
delivered oxygen concentration at given flow rates.
Endotracheal Intubation is indicated in severe respiratory
distress, cyanosis or impending respiratory failure. Table 5
shows approximate size of endotracheal tube—length and
diameter—for different ages.
Ensure Circulation
If the patient is in shock, or has signs of severe sepsis, initiate
septic shock protocol [13]. Establish intravenous access and
initiate infusion of a saline bolus (20 ml/kg). If venous access
is not feasible, consider intraosseous infusion in young
children [10]. The first dose of an appropriate antibiotic for
severe infections, including severe respiratory infections,
must be administered without delay [13]. It is advisable to
obtain a blood sample for culture prior to administering
Table 4 Common Oxygen delivery devices and delivered oxygen
concentration (FiO2) at given flow rates
FiO2 Device (Flow rate/min)
25–50% Nasal cannula (1–6 L)
35–65% Simple Face mask (6–12 L)
24–60% Graded Ventury mask (graded 4–12 L)
60–80% Oxyhood (10–15 L)
>90% Non rebreathing masks (10–12 L)
Indian J Pediatr (September 2011) 78(9):1118–1126
antibiotic [13]. Appropriate choice of antibiotic for suspected
severe pneumonia includes Ampicillin (100 mg/kg) and
Gentamicin (7.5 mg/kg/d single dose) for young infants;
and Ceftriaxone (100 mg/kg/day in two divided doses) for
older children/adolescents. If Staphylococcus aureus infection
is suspected (retropharyngeal abscess, bacterial tracheitis,
severe malnourished state, post-measles state, suspected
immuno-compromised state, or multiple pustules/furuncles),
Cloxacillin (100 mg/kg) should be added [14].
Subsequent Management
If pneumothorax is suspected/detected, proceed with
needle thoracotomy in the second intercostal space under
water seal (using a syringe with saline), followed by
intercostal drainage.
Figure 1 outlines the management steps in a child with
acute respiratory distress. Once a clinical diagnosis is
evident, specific protocols are described later for managing
each clinical condition.
Diagnostic Evaluation
Once life-saving and life-supportive therapeutic interventions
have been instituted, establish the diagnosis for further
specific therapy. The goal is to identify the cause of respiratory
distress. Evaluation consists of meticulous history-taking;
including Signs and symptoms, Allergies, Medications, Past
medical history, Last meal, and Events leading to the present
illness (mnemonic SAMPLE from PALS Guidelines). This
should be followed by focused physical examination.
Thereafter, laboratory and radiological support may be
required. Table 6 highlights the essential components of
Diagnostic evaluation.
Common Causes
Children who present with breathlessness are likely to be
suffering from respiratory, cardiac or metabolic conditions.
Common respiratory causes include lower airway problems
including pneumonia, parapneumonic effusions/empyema,
bronchial asthma; and upper airway conditions such as
croup, airway obstruction, and congenital airway anoma-
lies. Conditions outside the respiratory tract such as
congestive cardiac failure, neuro-muscular weakness,
Indian J Pediatr (September 2011) 78(9):1118–1126 1123

Table 5 Guidelines to approximate size of endotracheal tube (ETT)- length and diameter, laryngoscope, and suction catheter sizes required at
different ages

Age of the Laryngoscope Internal Diameter Distance from midtrachea Suction

Patient Blade size of ETT (mm) to lips or gums (cm) Catheter (F)
>40 wks gestational age: 3x ETT size 2 x ETT size

Preterm infant Miller 0+ 2.5,3.0 uncuffed 8 5-6

Term infant Miller 0-1+ 3.0,3.5 uncuffed 9-10 6-8
6 months Miller 0-1+ 3.5,4.0 uncuffed 10.5–12 8
1 year Miller 1 4.0,4.5 uncuffed 12.13.5 8
2 years Miller 2 4.5 uncuffed 13.5 8
MacIntosh 2 4.0 cuffed
4 years Miller 2 5.0,5.5 uncuffed 15 10
MacIntosh 2 4.5 cuffed
6 years Miller 2 5.5 uncuffed 16.5 10
MacIntosh 2 5.0 cuffed
8 years Miller 2 6.0 cuffed 18 12
MacIntosh 2
10 years MacIntosh 2 6.5 cuffed 19.5 12
12 years MacIntosh 3 7.0 cuffed 21 12
Adolescent MacIntosh 3 7.0,8.0 cuffed 21 12
Miller 3

severe anemia, severe metabolic acidosis etc. can also
result in clinical features of respiratory distress [15, 16].
Behavioural problems (psychological problems, drugs
addiction, multiple trauma) among adolescents are also
significant causes [17].
Neurological Illnesses
Though neurological illnesses can lead to ‘breathlessness’,
it is unlikely to be the only or chief complaint. Whether the
neurological illness is acute (head injury, encephalitis,
meningitis), subacute or chronic (Guillian Barre syndrome,
spinal muscular atrophy) there is usually a prominent
history of the initiating/primary events which suggest the
possible cause. Hypo- or hyperventilation could be the end
result of progressive cardio-respiratory pathology as well.
Similarly, though see-saw respiration is classically seen in
neuromuscular weakness, it could be seen as a preterminal
event in any severe respiratory pathology.
Cardiac Causes
Detection of cardiac failure, shock, or cyanosis may
suggest a cardiac cause of breathlessness. Usually, when
cardiac failure presents as breathlessness, the complaint is
subacute/chronic and progressive. There could be a history
of diagnosed heart disease, or a history of feeding difficulty
(suck-rest-suck cycle). Less commonly, cardiac failure may
present as acute onset breathlessness as in myocarditis
(viral or acute rheumatic carditis). In either situation, other
physical findings, like disproportionate tachycardia, soft
muffled heart sounds, cardiac murmurs, cardiomegaly,
hepatomegaly, raised JVP, basal crackles and occasionally,
the presence of edema may provide valuable clues.
When a breathless infant or child is found to be in shock,
breathlessness could be due to hypoxia or metabolic acidosis,
whatever the etiology of shock. However, when the clinical
features suggest cardiogenic or obstructive shock, especially
in a young neonate, duct dependent lesions like critical
coarctation or critical stenosis should be suspected (besides
other cardiac causes) and rapidly investigated. Such patients
may appear mottled, ashen and gray.
When a breathless patient is cyanosed, the first step is to
differentiate central from peripheral cyanosis. The latter is
simply an indicator of poor peripheral perfusion. Central
cyanosis could be either respiratory or cardiac in origin. A
past history of cyanotic spells is useful. Deep cyanosis is
usually cardiac or due to methemoglobinemia. Respiratory
pathologies usually present with milder cynosis. However,
mild cyanosis could also be cardiac in origin; helpful clues
to a cardiac cause are findings suggestive of cardiac failure.
The presence and severity of respiratory distress may not
help in differentiating respiratory from cardiac causes.
Metabolic Causes
When children manifest with tachypnea that is not
accompanied by increased work of breathing and clear
1124 Indian J Pediatr (September 2011) 78(9):1118–1126

Child with Respiratory distress

Pediatric
Assessment
Triangle

Pediatric
assessment
pentagon

Secure airway
Start oxygen
Ensure breathing
Restore circulation

Intubation or Tracheostomy Yes

Is there stridor or drooling?

No

Needle thoracotomy Yes Is pneumothorax

Intercostal drainage suspected?

No

First dose of antibiotic Yes Is there fever?

No

Detailed clinical examination

for specific cause

UAO Pneumonia Wheezing Cardiac CNS Metabolic

Specific Investigations
Specific Management

Fig. 1 Approach to a child with breathing difficulty. (UAO = upper airway obstruction, CNS = Central Nervous System)

chest on auscultation, a metabolic cause should be Sometimes inborn errors of metabolism could present in
suspected. The common cause of such ‘breathlessness’ are a similar fashion, but other equally prominent accompa-
metabolic acidosis accompanying poor perfusion states nying symptoms such as vomiting, convulsion etc. are
(shock); or chronic renal disease or diabetic ketoacidosis. common.
Indian J Pediatr (September 2011) 78(9):1118–1126
Table 6 Diagnostic evaluation of respiratory distress
A. History
• Acute, recurrent or chronic and nature of progression.
• Associated symptoms: cough, fever, rash, chest pain
• Preceeding events:choking,foreign body inhalation, trauma/
accident, and exposure to chemical or environmental irritants.
• Family history: exposure to infections, tuberculosis, atopy.
B. Physical Examination
• Assess stability of the airways, and ventilatory status.
⋄ Respiratory rate (counted for a full minute), rhythm, depth and
work of breathing.
⋄ Color, level of activity and playfulness.
⋄ Chest movements, indrawing of chest wall
⋄ Stridor (suggests upper airway obstruction)
⋄ Wheezing (suggests lower airway obstruction)
⋄ Grunting (suggests alveolar disease causing loss of functional
residual capacity)
• Tracheal position
• Segmental percussion
• Auscultation:
Air entry, type of breath sounds, wheeze, rhonchi, crepitations
• Clubbing, lymphadenopathy
• Assessment of CVS and CNS
C. Diagnostic Work-up
• Direct laryngoscopy, if upper airway obstruction is detected/
suspected
• X-rays: chest, lateral neck, and decubitus views
• Arterial blood gas analysis for hypoxemia (paO2 <60 mm Hg),
hypercarbia (paCO2 >40 mm Hg), (acidosis pH<7.3), alkalosis
(pH>7.5, and SaO2 monitoring
• Sepsis work-up; Blood counts and culture studies
Indications for Urgent X-ray
In general, management of respiratory distress does not
require an immediate chest radiograph; most conditions are
apparent clinically and waiting for radiography to initiate
treatment can waste precious time [18, 19]. However, in
cases of suspected pneumothorax, pleural effusion, media-
stinitis/pneumomediastinum [20] and traumatic chest-wall
injuries, radiography may guide appropriate management.
Upper airway obstruction by foreign body aspiration,
epiglottitis, retropharyngeal abscess may also require
radiographic confirmation prior to invasive interventions
[21].
Differential Diagnosis
Following the detailed clinical evaluation described above,
it would be possible to categorize respiratory distress into
the following groups for further specific management:
1125
1. Upper airway obstruction-(a child with stridor)—needs
urgent endotracheal intubation or tracheostomy
2. Cough, fever and breathing difficulty/(Pneumonia)
3. Lower airway obstruction-(Wheezing child)—Anti-in-
flammatory therapy (corticosteroids) and β2 agonists.
4. Slow or irregular breathing without any pulmonary
signs—Needs mechanical ventilation
5. Respiratory distress with cardiac findings.
Each of these clinical profiles is detailed separately in
later sections.
Specific Respiratory Support
If adequate oxygenation is not achieved after establishing
airway patency, administration of supplemental oxygen and
specific bronchodilator therapy, wherever applicable, consider
using CPAP and mechanical ventilation
Continuous Positive Airways Pressure (CPAP)
CPAP mechanically prevents airway closure and maintains
alveolar patency at the end of expiration in a spontaneously
breathing child. With CPAP a continuous flow of warmed,
humidified oxygen or mixed oxygen/air is provided via
nasal prongs. The continuous flow creates a positive
pressure when the child breathes out. This helps to prevent
alveolar collapse and reduces work of breathing. CPAP is
given via nasal prongs with a special CPAP circuit. CPAP
facility can be established in the emergency room after
naso-pharyngeal intubation, or endotracheal tube with T-
piece. A bubble CPAP circuit is used with an underwater
pipe coming off the oxygen supply line to the nasal prongs
or a special nose piece is used (a flow driver). Face masks
may be ineffective in providing CPAP due to inadequate
Table 7 Monitoring protocol
• Rate, rhythm and depth of respiration.
• Heart rate
• Blood pressure
• Temperature
• Presence/absence of cyanosis
• Use of accessory muscles, flaring of alae nasi and chest wall
retractions, and the degree of distress.
• Air entry in both lungs. In case an endotracheal tube has been
passed, check its position and patency and need for suction.
• Signs of exhaustion such as somnolence, confusion, and seizures.
• Non-invasive monitoring: Oxygen saturation (pulse oximetery) and
if available End tidal CO2 (EtCO2).
• Arterial blood gas (ABG). This must be interpreted together with the
clinical data of the patient.
1126
sealing and additional risk of pressure necrosis of eyes and
face. CPAP (usually between 5–10 cm H2O) must be
applied by an experienced person trained in using the
circuit. At higher CPAP (>10 cm H2O) cardiac output may
get compromised.
Mechanical Ventilation
This should be considered in serious respiratory depression or
paralysis, apnea and any severely distressed, cyanosed child
with hypoxemia (paO2 <60 mmHg) despite maximal oxygen
therapy. Manual ventilation can continue till in the child
reaches a PICU. Volume-limited ventilator delivers a preset
tidal volume even when the compliance of the lung is
decreased. This can lead to high pressures and create air-
leaks in some situations. Pressure-limited ventilator delivers
a tidal volume till preset pressure limit is reached. The tidal
volume is, therefore, variable. Any decrease in the compli-
ance may decrease the tidal volume and hence alveolar
ventilation. Generally, it is more convenient to utilize
pressure preset ventilators with variable flow rate in infants
and young children (<10 kg), whereas volume preset
ventilators are used most commonly in older children
(>10 kg).
Further details of specific treatment are discussed
elsewhere.
Monitoring
The goals of monitoring are:
(a) Early detection of worsening/complications
(b) Assessment of response to therapy
(c) Rapid documentation of clinical state
Table 7 highlights important components of the Moni-
toring protocol after initial stabilization and starting specific
therapy.
Key Points in Management of Acute Respiratory
Distress
& Initial Assessment: Appearance, Work of breathing,
Circulation
& Manage/Restore Airway, Breathing, Circulation
& Provide high flow oxygen
& Immediate management for specific clinical conditions
(intubation/tracheostomy for upper airway obstruction;
needle thoracotomy and drainage of pneumothorax, first
dose of antibiotic for febrile children).
& Detailed clinical assessment to localize illness to respira-
tory system (upper airway obstruction, pneumonia,
Indian J Pediatr (September 2011) 78(9):1118–1126
wheezing illness) or cardiovascular system or central
nervous system.
& Chest x-ray is not mandatory in the initial stage for the
most cases.
& Specific investigations and treatment should be based
on the likely cause identified on clinical evaluation.
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Indian J Pediatr (September 2011) 78(9):1127–1135
DOI 10.1007/s12098-011-0412-2
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Acute Community Acquired Pneumonia in Emergency Room
Parag S. Dekate & Joseph L. Mathew & M. Jayashree &
Sunit C. Singhi
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 4 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Community acquired pneumonia is the leading
killer of children under the age of 5 years. In ER, a
diagnosis of pneumonia may be made and the severity
graded on basis of WHO’s classification for pneumonia in
children up to 5 years of age. It relies on age-specific
respiratory rate, presence of lower chest indrawing and
signs of severe illness. A diagnosis of pneumonia is made if
a febrile child has history of cough and difficult or rapid
breathing and a respiratory rate above age specific
threshold; however, signs of airway obstruction should be
ruled out. Severe pneumonia is diagnosed if with the above
features lower chest wall retraction is present; nonetheless,
all infants below 2 months and children with moderate to
severe malnutrition with pneumonia are categorized as
having severe pneumonia. A chest radiograph is indicated
only if the diagnosis is in doubt; complications are
suspected and there is severe/very severe or recurrent
pneumonia. Non-severe pneumonia is treated at home with
oral amoxicillin for 3–5 days. If there is no improvement in
48 h it is changed to amoxicillin-clavulanate. Azithromycin
is added for atypical pneumonia. Indications for hospital-
ization include age <2 months, treatment failure on oral
antibiotics, severe/very severe or recurrent pneumonia,
shock, hypoxemia, severe malnutrition, immunocompro-
mised state. Severe pneumonia is treated with injectable
ampicillin; Cloxacillin is added if clinical/radiographic
features suggest Staphylococcal infection. On review after
48 h, if improved, the child may be sent home on oral
P. S. Dekate : J. L. Mathew : M. Jayashree : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
amoxicillin for 5 more days; if not, it is treated as very
severe pneumonia. Very severe pneumonia is treated with
injectable Ampicillin plus gentamicin. If improved after
48 h, oral amoxicillin and gentamicin are continued for
10 days. If not, respiratory support is enhanced, antibiotics
are changed to intravenous ceftriaxone and amikacin and
further work up is planned. Children with chronic diseases
and recurrent pneumonia require specific antibiotics
depending on the underlying cause.
Keywords Community acquired pneumonia . Children .
Severe pneumonia . Very severe pneumonia . Antibiotic
therapy
Introduction
Pneumonia is the leading killer of children, causing an
estimated 1.9 million deaths worldwide under the age of
5 years. About 90% of these deaths occur in the developing
world [1]. Pneumonia is an inflammation of the parenchyma
of the lungs. Although most cases of pneumonia are caused
by micro-organisms, noninfectious causes include aspiration
of food or gastric acid, foreign bodies, hydrocarbons, and
lipoid substances, hypersensitivity reactions, and drug or
radiation-induced pneumonitis.
In developed countries, the diagnosis is usually made on
the basis of radiographic findings. The World Health
Organization (WHO) has defined pneumonia solely on the
basis of clinical findings obtained by visual inspection and
counting the respiratory rate, for developing countries.
Table 1 shows the age-specific criteria used to define
pneumonia. The clinical features of pneumonia include
cough, increased respiratory rate, chest indrawing, stridor
and altered sensorium.
1128 Indian J Pediatr (September 2011) 78(9):1127–1135

Table 1 WHO age specific criteria for tachypnea [1] & Nonspecific complaints, such as irritability or poor
Age Approximate normal respiratory Tachypnea threshold feeding may be the presenting symptoms
rate (breaths/min) (breaths/min) & Cyanosis may be present in severe cases
& Chlamydia trachomatis pneumonia should be consid-
2–12 months 25–40 50 ered in infants aged 2–4 wks and is often associated
1–5 years 20–30 40 with conjunctivitis.
>5 years 15–25 30

Infants

The etiology of infective pneumonia in children, based on a
series of research studies in India [2–6] is given in Table 2.
Approach to a Child with Pneumonia
Presentation
Any patient presenting with cough and difficult or rapid
breathing should be considered as a case of pneumonia [1].
Table 1 summarizes the normal respiratory rates and
tachypnea thresholds in children of different age groups.
Other symptoms may be present along with respiratory
symptoms. However, this should be differentiated from other
common respiratory illnesses such as asthma, bronchiolitis
and upper airway infections. In children, the etiologic agent,
age of the patient, and underlying illnesses/clinical state, all
affect the clinical features of the illness.
Neonates
& Neonates present with tachypnea, and signs of respira-
tory distress such as grunting, flaring and retractions.
& Fever and cough may be absent; however hypothermia
and temperature instability may be observed.
& After the first month of life, cough is the most common
presenting symptom.
& Infants may have a history of antecedent upper
respiratory symptoms.
& Depending upon the degree of illness, tachypnea,
grunting, and retractions may be noted.
& Vomiting, poor feeding, and irritability are also common.
& Infants with bacterial pneumonia often are febrile, but
those with viral or atypical pneumonia may have low-
grade fever or could be afebrile.
& Wheezing or noisy breathing. Wheeze suggests a viral
cause.
Toddlers and Preschool Children
& A history of antecedent upper respiratory illness is
common.
& Cough is the most common presenting symptom.
& The presence and degree of fever is dependent upon the
organism involved.
& Vomiting, particularly post-tussive, may be present.
& Chest pain may be observed with inflammation of or
near the pleura.
& Abdominal pain or tenderness is often seen in children
with lower lobe pneumonia.

Table 2 Etiology of pneumonia in children in various age groups

Age group Frequent pathogens (in order of frequency)

Neonates Group B streptococcus, Escherichia coli, other gram-negative bacilli cytomegalo virus.
(<1 month) Streptococcus pneumoniae, Haemophilus influenzae (type b) are uncommon
1–3 months
Febrile Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H.
pneumonia influenzae (type b)
Afebrile Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, cytomegalovirus
pneumonia
3–12 months Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H.
influenzae (type b), C.trachomatis, Mycoplasma pneumoniae, Group A streptococcus, Staph. aureus
2–5 years Respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H. influenzae (type b), Staph. aureus
M. pneumoniae, C. pneumoniae, group A streptococcus
5–18 years M. pneumoniae, S. pneumoniae, C. pneumoniae, H. influenzae (type b), influenza viruses, adenoviruses, other respiratory viruses
Indian J Pediatr (September 2011) 78(9):1127–1135
Older Children and Adolescents
& Atypical organisms, such as Mycoplasma are common
in this age group.
& In addition to the symptoms observed in younger
children, adolescents may have other constitutional
symptoms, such as headache, pleuritic chest pain, and
vague abdominal pain. Headache, fever and myalgia are
associated with M. pneumoniae.
& Vomiting, diarrhea, pharyngitis, and otalgia/otitis are
also common symptoms.
Assess for Contributing Etiology
The following history and examination should try to elicit
important information about the etiology:
& Contact with person(s) having respiratory infection
& Possibility of foreign body aspiration
& Possibility of primary aspiration
& Stools consistent with malabsorption (may suggest
cystic fibrosis)
& Sinusitis
& Asthma
& Growth and nutritional status
& Dysmorphic syndromes
& Neuromuscular weakness
& Cardiac failure
Risk Factors
The risk factors for the development of community
acquired pneumonia [7, 8] include malnourished state,
young age (<6 months), post-measles state, absence of (or
inadequate) breastfeeding, and solid fuel use. The pointers
towards hospital acquired infection/pneumonia [9] include
hospitalization for ≥48 h, broad spectrum antibiotic therapy
for ≥7 days in the preceding 30 days, immunosuppressive
therapy including glucocorticoid therapy, neutropenia and
severe structural lung disease.
Severity Assessment
Any infant with age ≤2 months with symptoms suggestive
of pneumonia should be considered as having severe
pneumonia. Such a child needs immediate hospitalization
[1, 5]. Tachypnea (respiratory rate >60/min) in this age
group is often associated with hypoxemia [10] and it is
important to note severity of pneumonia in children from
2 months to 5 years. The WHO criteria for severity of
pneumonia in this age group are shown in Table 3. A child
with protein energy malnutrition or lower chest indrawing
1129
Table 3 WHO criteria for severity assessment child age 2 months to
5 years [1]
Severity classification Clinical features
Very severe pneumonia Not able to drink
Convulsion
Abnormally sleepy or difficult to awake
Severe malnutrition
Central cyanosis
Severe pneumonia Lower chest indrawing
Grunting
Cyanosis
Pneumonia (not severe) Fast breathing (>age specific threshold)
No chest in-drawings
Cough and cold (no No fast breathing
pneumonia) No chest in-drawings
with symptoms suggestive of pneumonia has severe
pneumonia, There is no validated criteria for severity
assessment in children >5 years. In this age group,
pneumonia is considered severe if the following features
(of severe respiratory distress) are present. It is subjective
and determined by same parameters as mentioned above.
& Respiratory rate >30/min
& Chest wall retraction
& Use of accessory muscles of respiration
& Altered sensorium
Investigations
i. Chest radiography (CXR): Chest radiographs are not
needed routinely in all children with suspected pneu-
monia. Specific indications include:
1. When the diagnosis is in doubt (bronchiolitis,
asthma, developmental malformation, foreign body
inhalation, aspiration pneumonia etc.)
2. Asymmetrical findings on chest examination
3. Suspected complications of pneumonia (pleural
effusion, empyema, lung abscess etc.)
4. Known case of recurrent chest infection (asthma,
cystic fibrosis, immunodeficiency etc.)
5. Severe and very severe pneumonia
Findings to be looked for in chest radiograph include:
& Parenchymal infiltrates (evidence of consolidation)
& Features of atypical pneumonia (bilateral streaky infiltrate)
& Presence of pneumatocele
& Any evidence of foreign body inhalation
& Pleural spaces for pneumothorax, effusion
Figure 1 shows some characteristic chest radiographs.
1130 Indian J Pediatr (September 2011) 78(9):1127–1135

Fig. 1 Antero-posterior chest ra-

diograph. a showing left lower A B
zone consolidation, b showing
diffuse streaky infiltrate of atypi-
cal pneumonia, c showing right
middle zone consolidation, d
showing left homogenous opacity
with blunting of costophrenic
angle suggestive of parapneu-
monic effusion/empyma

C D

ii. Arterial blood gas (ABG): The indications are:
1. Severe and very severe pneumonia
2. Hypoxemia on pulse oxymetry (SpO2 <94% on
40% oxygen), cyanosis
3. Shock
Baseline Stabilization
& A-Airway assessment
& B-Breathing
& C-Circulation
& Resuscitation if required as per the Pediatric Assess-
ment Triangle and Primary Assessment
& O2 inhalation by nasal prongs, at flow rate 1–5 l/min
(depending on age) if child has lower chest wall
indrawing or SpO2 ≤92%. Oxygen can be effectively
delivered by any low-flow delivery method [11];
therefore the specific delivery device (nasal prongs,
face mask, nasal catheters etc.) are more a matter of
personal/institutional choice. For more details, please
see the Protocol on Acute respiratory Distress.
& First dose of antibiotic as early as possible; preferably after
obtaining a sample for blood culture. However, adminis-
tration of the first dose should not be delayed for this.
& Hydration (intravenous or nasogastric tube feed)
i. If child is accepting orally well—allow orally (ad
libitum)
ii. If not accepting well orally (but feeding not
contraindicated)—Nasogastric or orogastric feed
can be started
iii. Start 0.45 Saline in 5% dextrose as 2/3rd to 3/4th
maintenance if there is respiratory distress (where
feed cannot be started) or underlying dehydration
or ongoing losses through vomiting etc.
& Treatment of other emergent co-morbidities
i. Hypoglycemia
ii. Electrolyte imbalance
Hospitalization
The indications for hospitalization are:
& Age <2 months
Indian J Pediatr (September 2011) 78(9):1127–1135
& Severe and very severe pneumonia (as per WHO
definition)
& Signs of shock
& Hypoxemia (requirement for supplemental oxygen)
& Moderate to severe malnutrition [12] because it
increases the risk of mortality
& Recurrent chest infection (cardiopulmonary disease,
anatomical defects in airway, neurological disease)
& Immunocompromised state
& Not accepting orally, dehydration, vomiting
& No response or increased severity (treatment failure) on
appropriate oral antibiotic therapy
& Family unable to provide appropriate care at home.
Other Investigations in Hospitalized Patients
& Hemogram with total and differential leukocyte count
& Serum electrolytes and renal function test
& Blood culture: These are positive in 10%–20% of
children with pneumonia
& Other diagnostic investigations:
In atypical pneumonia: Serology—RSV, Mycoplasma,
Chlamydia
CMV serology (if suspected like immune-compromised
and TORCH group of infection)
& Atypical H1N1 (swine flu) testing during epidemics
& CSF (if feasible) in case of
i. Newborns
ii. Infants presenting with altered sensorium
iii. Seizures
Antibiotic Treatment
Choice of Antibiotics
The choice of first-line antibiotic therapy [13] is guided by:
& Age of the child
& Severity of pneumonia
& Associated clinical features suggesting specific etiology
e.g. pustules suggesting Staphylococcal infection
& Immune-suppressed or immunocompromised state
(such as post-measles state)
& Underlying chronic lung disease e.g. cystic fibrosis
& Radiographic pointers towards a specific etiology (necro-
tizing pneumonia, pneumatoceles suggest Staphylococcal
infection, parahilar streaky infiltrates are more common in
atypical pneumonia.)
& Presence of complication such as pneumothorax/empyema.
1131
Treatment of Non-severe Pneumonia (at home) [14–17]
& Non-severe pneumonia can be treated at home with oral
antibiotics in most cases.
& Amoxicillin (50 mg/Kg/day) in 2 divided doses for 3–
5 days
& Advise to return immediately if the child develops
lower chest indrawing, is unable to drink/feed, is
excessively sleepy or sick looking.
& Follow-up after 2 days
○ Check the child for general danger signs such as
inability to suck/drink, impaired sensorium, convul-
sions, grunting, cyanosis.
○ Assess the child for cough and difficult breathing
○ Ask: Is the child breathing slower? Is there less
fever? Is the child eating better?
○ If the answer to above questions is Yes, complete 3–
5 days of amoxicillin
○ If the child has persistent raised respiratory rate but
no indication for admission, change to Amoxicillin-
clavulanic acid (80–90 mg/kg of amoxicillin) in 2
divided doses for 5 days or add Azithromycin 5 mg/kg
for 5 days if clinical and radiological features suggest
atypical pneumonia. Cloramphenicol is a less desirable
second line agent for non severe pneumonia because of
its potential for bone marrow toxicity.
○ If lower chest indrawing or a general danger sign
appears, hospitalize urgently for treatment as severe/
very severe pneumonia
Treatment Failure in Non-severe Pneumonia (Table 4)
A systematic assessment should be done for children who
have failed therapy for non-severe pneumonia. Treatment
failure is defined as follows:
○ Persistently raised respiratory rate at 72 h
○ Danger sign at any time during the illness, such as
inability to suck/drink, impaired sensorium, convul-
sions, grunting, cyanosis.
○ Development of lower chest-wall indrawing
○ Central cyanosis
Severe Pneumonia
& Hospitalize, continue oxygen.
& Injectable ampicillin (50 mg/kg/dose) IV 6 hourly.
& Add Cloxacillin (100–200 mg/kg/day in 4 four divided
doses) if clinical features (presence of pustules, post-
measles state, severe malnutrition, empyema) and
1132 Indian J Pediatr (September 2011) 78(9):1127–1135

Table 4 Potential reasons for

treatment failure for WHO de-
fined non-severe pneumonia and
possible solutions
Reasons for treatment failure Possible intervention
Common
Reactive airway disease/asthma Admission and bronchodilator therapy
Viral infection Observation in hospital
Malnutrition Hospitalization and nutritional rehabilitation
Malaria (in endemic region) Hospitalization, blood smear exam and antimalarials
Uncommon
Anemia Hospital assessment
Cardiac diseases Hospital assessment
Tuberculosis Hospital assessment and anti tuberculous drugs
Foreign body Hospital assessment, bronchoscopy
Empyema, abscess Hospital assessment, radiography and drainage
Pulmonary maldevelopment Hospital assessment
Non-susceptible organism Appropriate antibiotics
HIV/AIDS Hospital assessment, HIV testing and anti-retrovial therapy

radiographic features (pneumatoceles, necrotizing pneu-
monia) suggest Staphylococcal infection.
& Assess and monitor for oral intake/feeding, respiratory
rate, chest indrawing, and oxygenation (by pulse
oximetry) .
& If at any time danger signs of very severe pneumonia
develop treat as very severe pneumonia
& After 48 h—if improved: continue: on oral amoxicillin
for 5 more days, if not improved in 48 h/deteriorated:
treat as very severe pneumonia
Very Severe Pneumonia
Children with very severe pneumonia require immediate
hospitalization, oxygen, injectable ampicillin plus gentamicin,
and chest radiograph. The protocols for treatment of Very
severe pneumonia [18] and Pneumonia in infants ≤2 months
are shown in Figs. 2 and 3, respectively.
Special Situation
& Cystic fibrosis
○ Start Anti-staphylococcal and anti-Pseudomonal
antibiotics in combination
& Aspiration pneumonia
○ Start Crystalline Penicillin or Metronidazole
& Ampicillin: 100–200 mg/kg/day IV q 6 hourly (maxi-
mum dose 12 gm/day)
& Amoxicillin: Standard dose 50/kg/day oral in 2 divided
doses
▪ High dose 80–90 mg/kg/day oral in 2 divided doses
& Gentamicin: 7.5 mg/kg/doe IV q 24 hourly
& Ceftriaxone: 80–100 mg/kg/day IV q 12 hourly (max-
imum dose 4 g/day)
& Amikacin: 15 mg/kg/dose IV q 24 hourly (maximum
dose 1.5 g/day)
& Cefotaxime: 100–200 mg/kg/day IV q 8 hourly or 6
hourly (maximum dose 12 g/day)
& Cefoperazone + sulbactum: 100–150 mg/kg/day (of
cefoperazone) IV q 8 hourly (maximum dose 12 g/day)
& Cloxacillin: 100–200 mg/kg/day IV q 6 hourly (maxi-
mum dose 4 g/day)
& Vancomycin: 40–60 mg/kg/day IV q 6–8 hourly (max-
imum dose 2 g/day)
& Cefoperazone + sulbactum: 100–150 mg/kg/day (of
cefoperazone) IV q 8 hourly
& Piperacillin + tazobactum: 200–300 mg/kg/day (of
piperacillin) IV q 6–8 hourly
& Meropenem: 60–120 mg/kg/day IV q 8 hourly (maxi-
mum dose 6 g/day)
Work up Plan in Non-responders

& Repeat chest radiograph (look for non resolving

Doses of Drugs pneumonia or complications such as pleural effusion,
empyma, lung abscesses etc.)
& Crystalline Penicillin: 1,00,000–4,00,000 IU/kg/day IV & Consider underlying heart and lung diseases (congenital
q 6 hourly (maximum dose 24 million) heart disease, cystic fibrosis, chronic lung diseases etc.)
Indian J Pediatr (September 2011) 78(9):1127–1135 1133

Very severe pneumonia

Baseline stabilization, oxygen, iv fluids, chest radiograph

IV Ampicillin + Gentamicin
Add Cloxacillin if radiograph shows pneumatocele or pus in pleural fluid
Add only Azithromycin if radiograph suggests atypical pneumonia
Monitor RR, chest indrawing oral intake, SpO2

Improving# Assess after 48 hrs* Not-improving

Oral Amoxicillin (100 mg/kg/d Escalate Respiratory support

in 3 divided doses for 10 days) + IV Ceftriaxone + Amikacin
Inj Gentamicin 5.0-7.5mg/kg/d
Further work up
Change antibiotics as per cultures
Consider discharge$

Not-improving Monitor; Assess after 48hr*

Improving #

Further management based on

individual case scenario Complete 10-14 days of IV
antibiotics
Consider Pediatric Pulmonology
consultation Consider discharge $

#
Improvement involves (3, 4) $
Discharge criteria
* Assessment involves
1. Afebrile • Accepting orally well and normal
• RR 2. ↓ RR ≥10/min within 48h
• Retraction 3. ↓ Retraction within 72 h sensorium
• Saturation 4. Saturation >92%
• General well being • Afebrile for at least 48 h
5. Improved general well being
• Oral acceptance 6. Improved oral acceptance • No oxygen requirement for at least 48 h
• Completed IV antibiotics

Fig. 2 Protocol for very severe pneumonia

& Consider hospital acquired infection ○ Fungal culture and serology (in immuno-compromised
& Consider further work up children)
○ Pleural fluid examination
○ Tuberculosis work up
Indications for PICU Transfer
▪ Mantoux test
▪ Gastric aspirate for AFB
At any stage, the following should be considered for
▪ Family screening
transfer to ICU:
▪ Sputum examination if possible
○ Cystic fibrosis work up & Very severe pneumonia
○ GER scan (if suspected GERD) & Hypoxemia/Respiratory failure
1134 Indian J Pediatr (September 2011) 78(9):1127–1135

All to be hospitalized

Resuscitation
Baseline stabilization, oxygen, iv fluids, chest radiograph
IV Cefotaxime + Amikacin
Add Cloxacillin if CXR shows pneumatocele or pus in pleural fluid
Add Azithromycin if CXR shows atypical pneumonia

Improving # Assess after 48 h* Not-improving

Escalate Respiratory support

IV antibiotics for 10-14days
Antibiotics to be decided on the basis of individual
Consider discharge$ case scenario and antibiotic susceptibility profile £
Further work up
Change antibiotics as per cultures

Improving # Reassess after Not-improving

48 h*

IV antibiotics for 10-14days Escalate respiratory support

Consider discharge $ Change antibiotic as per culture report

Further plan to be decided as per individual

case scenario

#
* Assessment involves Improvement involves (3, 4) $
Discharge criteria £
Alternate antibiotic options
RR 1. Afebrile Accepting orally & normal Cloxacillin
Retraction 2. RR 10/min within sensorium Vancomycin
Saturation 48hours Afebrile for at least 48 hours + Meropenem
General well 3. Retraction within 72 hours No oxygen requirement for at Cefoperazone + sulbactum
being 4. Saturation >92% least 48 hours Piperacillin + tazobactum
Oral acceptance 5. Improved general well being Completed IV antibiotics Metronidazole
6. Improved oral acceptance

Fig. 3 Protocol for pneumonia in infants ≤2 months old

& Patients requiring intubation/ventilation
& Presence of shock
Key Points
& Pneumonia is diagnosed clinically in a child with cough
and difficult or rapid breathing.
& Age-specific respiratory rate and presence of chest indraw-
ing can be used to categorize severity. Infants ≤2 months
and children with moderate to severe malnutrition should
be considered as having severe pneumonia.
& Pneumonia should be differentiated from other respiratory
illnesses such as asthma, bronchiolitis and upper airway
infections.
& Chest radiograph is not needed routinely; specific
indications include doubtful diagnosis, asymmetrical
examination findings, suspected complications, recur-
rent chest infection, and severe/very severe pneumonia.
& Indications for hospitalization are: age <2 months,
severe/very severe pneumonia, signs of shock, hypox-
emia, moderate to severe malnutrition, recurrent chest
infection, immunocompromised state, poor oral accep-
tance, treatment failure on appropriate oral antibiotic
therapy, and inability to provide care at home.
& Choice of first-line antibiotic therapy is guided by: age,
severity, clinical features suggesting specific etiology,
immune status, underlying chronic lung disease, and
radiographic pointers towards specific etiology and/or
complication such as pneumothorax/empyema.
Indian J Pediatr (September 2011) 78(9):1127–1135
& Non-severe pneumonia can be treated at home with oral
amoxicillin (50 mg/kg/day in 2 divided doses for 3–
5 days); with advice to return immediately if the child
develops lower chest indrawing, is unable to drink/feed,
is excessively sleepy or sick looking.
& If the child has persistent tachpnea but no indication for
admission, change therapy to Amoxicillin-clavulanic
acid (80–90 mg/kg of amoxicillin in 2 divided doses for
5 days) or add Azithromycin (5 mg/kg for 5 days) if
clinical and radiological features suggest atypical
pneumonia. Follow protocol for severe/very severe
pneumonia if clinical signs of these appear.
& Severe pneumonia is treated in hospital with injectable
ampicillin (50 mg/kg/dose iv 6 hourly). Add Cloxacillin
(100–200 mg/kg/day in 4 four divided doses) if clinical
and/or radiographic features suggest Staphylococcal
infection. If danger signs of very severe pneumonia
develop, treat as very severe pneumonia. If improved
after 48 h, use oral amoxicillin for 5 more days.
& Very severe pneumonia is treated with injectable ampicillin
plus gentamicin. If improved after 48 h, continue oral
Amoxicillin (100 mg/kg/d in 3 divided doses for 10 days)
and Gentamicin (5.0–7.5 mg/kg/d iv). If not improved,
escalate respiratory support, change to IV Ceftriaxone and
Amikacin (or as per as per cultures), and plan further work
up. Total duration of antibiotic therapy is 10–14 days.
Conflict of Interest None.
Role of Funding Source None.
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Indian J Pediatr (October 2011) 78(10):1256–1261
DOI 10.1007/s12098-011-0414-0
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Acute Upper Airway Obstruction
K. Sasidaran & Arun Bansal & Sunit Singhi
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 11 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Upper airway obstruction is defined as blockage
of any portion of the airway above the thoracic inlet.
Stridor, suprasternal retractions, and change of voice are the
sentinel signs of upper airway obstruction. Most of the
common causes among children presenting to emergency
department are of acute infectious etiology. Among these,
croup is the commonest while diphteria remains the most
serious life-threatening cause. Recent reports indicate that
bacterial tracheitis has become increasingly common. In ER
evaluation the key clinical data in determining the cause
and the site of obstruction are the onset, presence of fever,
character of the stridor, retractions, the voice and the ability
to handle secretions. After assessment of the severity of
respiratory distress and resuscitative or supportive therapy
including oxygen and emergent airway, specific treatment is
directed at underlying etiology. All patients with audible
stridor require early endotracheal intubation/tracheostomy. In
croup the mainstay of treatment are cold humidified oxygen,
budesonide nebulization ( in mild cases), Dexamethasone
0.6 mg/kg iv or im (in moderate and severe cases), and
Adrenaline 5 ml 1:1000 (5 mg) solution as nebulization ( in
severe cases). In diphtheria, early tracheostomy, anti-
diphtheric serum and injectable penicillin are critical.
Bacterial Tracheitis and Retropharyngeal abscess need
early administration of injectable Cloxacillin, Amikacin
and Clindamycin. ENT consultation should be obtained
for early surgical drainage of retropharyngeal abscess.
Angioneurotic edema is treated with subcutaneous adren-
aline (1:1000, 0.01 ml/kg); hydrocortisone 10 mg/kg IV
and antihistamines. Patients with severe obstruction and
K. Sasidaran : A. Bansal : S. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre, PGIMER,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
those with endotracheal tube/ trachesotomy should be
transferred to PICU.
Keywords Children . Upper airway obstruction . Croup .
Diphtheria . Bacterial tracheitis . Retropharyngeal abscess .
Angioneurotic edema
Introduction
Acute airway obstruction in children is one of the most
common life-threatening emergencies in pediatric practice.
It usually generates a great deal of anxiety since there is
little time for deliberation, and it may lead to significant
morbidity and indeed mortality.
Upper airway obstruction is defined as blockage of any
portion of the airway above the thoracic inlet. Stridor,
suprasternal retractions, and change of voice are the
sentinel signs denoting upper airway obstruction.
Stridor is a harsh, vibratory sound of variable pitch
caused by partial obstruction of the respiratory passages
that result in turbulent airflow through the airway.
Inspiratory stridor is a harsh, high pitched sound produced
when child inspires through a spasmodically closed glottis.
Expiratory stridor is a singing sound due to semi-
approximated vocal cords offering resistance to exhalation
or to due to tracheobronchial obstruction.
Biphasic stridor is a harsh sound of vibratory quality
produced due to little change in airway size with respiration
caused by a fixed obstruction and, heard during both phases
of respiration. Pathophysiologic events leading to various
kinds of stridor in upper airway obstruction in children are
shown in Fig. 1.
If a child’s stridor becomes softer but the work of
breathing remains increased, the obstruction may be
getting worse; if the child is unable to sustain increased
work of breathing he is getting tired.
Indian J Pediatr (October 2011) 78(10):1256–1261 1257

Fig. 1 Pathophysiology of
Normal airway Laminar air flow pattern
upper airway obstruction
in children
Progressive airway inflammation Exposure to inciting agent

Narrowing of airway lumen

Venturi effect Turbulent airflow

Increased airflow velocity

Drop in pressure normally exerted against airway wall

Increase in intra luminal negative pressure

Airway collapse 1. Supraglottic level – Inspiratory stridor

2. Intra thoracic trachea or major bronchi – Expiratory stridor

3. Fixed obstruction at cricoids – Biphasic stridor

Causes of Upper Airway Obstruction & Pattern of fever, duration as well as the severity
& History of trauma to head or neck—Neurogenic stridor
Causes of upper airway obstruction can be classified & History of choking—to exclude foreign body aspiration
according to the age group, duration of symptoms (acute & Epidemiological conglomeration of similar cases—
or chronic) and whether it is of infectious origin or not as Diphtheria, Viral croup
shown in Table 1. Acute infectious cause is the commonest
among children presenting to emergency department with
upper airway obstruction. Table 1 Common causes of upper airway obstruction in children
Croup and bacterial tracheitis remain as the two common Infectious Non-infectious
causes of acute onset upper airway obstruction in children.
Recent reports indicate that bacterial tracheitis is becoming Acute
increasingly common [1]. Diphtheria remains as one of the Croup Airway burns
common causes in India. (Caustic or Thermal)
Diphtheria Upper airway foreign body
Bacterial tracheitis Angioneurotic edema of upper
Evaluation of a Child with Stridor airway
Retropharyngeal abscess Trauma
A prepared clinician can often make the diagnosis based Peritonsillar abscess Vocal cord paralysis
Acute severe tonsillitis
solely on the history and physical examination (Fig. 2);
Infectious mononucleosis
using radiographs and laboratory examinations to aid in
Epiglottitis
diagnosis when the clinical picture is unclear [2].
Chronic
Chronic tonsillitis Laryngomalacia
History (age specific—in infants)
Adenotonsillar hypertrophy Vascular ring
& Characteristics of the onset of illness, and the course of Neoplasms of upper airway
(Hemangioma, cystic hygroma
development of respiratory signs should be carefully cysts of larynx)
obtained Tracheal stenosis
& Characteristics of voice and voice change—if present
1258 Indian J Pediatr (October 2011) 78(10):1256–1261

Fig. 2 Diagnostic algorithm in

Stridor
a child with stridor

Is the child febrile ?

Yes No

History of trauma or
Severe distress or drooling ?
Foreign body ?

Yes No
Yes

Hoarseness of voice Muffled voice

Laryngeal problem +
Foreign body
No
Caustic/thermal injury
Pharyngeal problem +
Laryngotracheal trauma

Croup Severe tonsillitis

Angioneurotic edema
Bacterial tracheitis Peritonsillar abscess
Spasmodic croup
Retropharyngeal Parapharyngeal abscess
abscess

Diphtheria

Epiglottitis

Physical Examination Laboratory Testing and Imaging

Physical examination is important and should be performed
in a warm, well-lit room, preferably with the child in parent’s lap
and the child’s chest exposed. The key physical findings in
determining the site of obstruction involve the character of the
stridor, retractions, the voice and the ability to handle secretions
& General appearance and posture
& Cry or voice (pitch, aphonia, muffled, hoarse)
& Difficulty in a child’s ability to handle oral secretions.
& Nasal flaring
& Degree of dyspnea and respiratory pattern
& Use of accessory muscles of respiration (degree of
retractions)
& Look for craniofacial anomalies (maxillary hypoplasia,
nasal septal deviation, micrognathia, retrognathia, pla-
tybasia, or macroglossia)
& Throat examination: look for acute inflammation of
tonsils, faucial pillars, evident exudates and membrane.
& Neck examination: look for any extrinsic mass, evidence
of trauma and tracheal position
Laryngoscopy or any procedure that may agitate the patient
is postponed till the emergency airway is established.
No investigation is warranted before stabilizing the airway.
A physician who is competent in providing airway support
may accompany stable patients to the X-ray department.
Classic features of common disorders causing upper
airway obstruction are shown in Table 2
A diagnostic approach to child with stridor is shown in Fig. 2.
Specific Management Guidelines
Croup Syndrome Management
Assess the child for severity of respiratory distress and give
resuscitative or supportive therapy accordingly. Westley’s
clinical croup score (Table 3) may be used to aid in the
decision as to which children should be hospitalized and to
decide upon the treatment protocol.
The mainstay of treatment are cold humidified oxygen,
Budesonide nebulization (1,000 μg given 30 min apart in
mild cases) [4], Dexamethasone [4, 5] 0.6 mg/kg iv or im
(one dose in mild and moderate cases, otherwise 6 hourly),
and Adrenaline 5 ml 1:1000 (5 mg) solution as nebulization
( in severe cases). Avoid situations that may precipitate
Indian J Pediatr (October 2011) 78(10):1256–1261 1259

Table 2 Classic features of common upper airway disorders

Disease process Age group Mode of onset of respiratory distress

Viral croup
Bacterial tracheitis
Diphtheria
Retropharyngeal abscess
Peritonsillar abscess
Foreign body aspiration
3 month–3 years. Gradual onset of stridor and barking cough after mild URI
2–7 years. Acute onset high grade fever, toxic appearance, respiratory distress
Any age Gradual onset of stridor preceded by swelling over neck and URI in
an unimmunized child, membrane on throat examination
Infancy—3 years. Fever, toxicity, and distress after URI or pharyngitis
Usually >8 years Acute onset high grade fever, toxicity, distress with unilateral throat pain,
“hot potato speech”
Late infancy—4 years Choking episode resulting in immediate or delayed respiratory distress

distress and monitor for the response. Management guidelines Because prompt treatment is crucial, it is prudent to start
for croup based on Westley’s croup score are given in Table 4. therapy on the basis of clinical findings and microbial
culture would confirm the diagnosis later. Nevertheless,
Diphtheria Management send a throat swab for bacteriological studies (Albert’s
stain and culture) to confirm the diagnosis.
Laryngeal Diphtheria Membranous pharyngitis progress
over a period of 2 to 3 days to manifest with hoarseness & Give Oxygen. Try not to upset child and do not
of voice, dysphagia and minimal to severe inspiratory attempt to look inside the mouth as this may
stridor. The patient is usually nontoxic in appearance but precipitate airway obstruction. Send throat swab for
may have low grade fever. bacteriological studies (Albert’s stain and culture) to
confirm the diagnosis.
& Airway management: Endotracheal intubation should
be avoided, and early tracheostomy to establish emer-
Table 3 Westley’s clinical croup score [3] gency airway is advised.
& Give diphtheria antitoxin 80,000 to 120,000 units IV
Category Score
infused over 1 h.
Level of consciousness & Crystalline penicillin 40,000 U/kg/dose iv, q 6 hourly ×
Normal (including sleep) 0 14 days; Erythromycin 15 mg/kg/dose q 8 hourly (not
Disoriented 5 to exceed 2 g/day) × 14 days may be used in those
Cyanosis sensitive to penicillin.
None 0 & Patients should be isolated until three consecutive
Cyanosis with agitation 4 cultures at the completion of therapy have documented
Cyanosis at rest 5 elimination of the organism from oropharynx. Contacts
Stridor
should receive erythromycin15 mg/kg/dose q 8 hourly
None 0
for 7 days.
When agitated 1
At rest 2
Retropharyngeal Abscess Management
Air entry
Normal 0
& Start oxygen in nonthreatening manner. Try not to upset
Decreased 1
child
Markedly decreased 2
& Airway management: Endotracheal intubation should
Retractions
be done in any child with audible stridor at presentation.
None 0
Orotracheal intubation is preferred because of the risk
Mild 1
of rupture of abscess.
Moderate 2
& Start with Cloxacillin (50 mg/kg/dose q 6 hourly)
Severe 3
Amikacin (15 mg/kg/day in once a day dose) along with
Categories: Mild croup—Score 0–2; Moderate croup—Score 3–5; clindamycin (10 mg/kg/dose TID).
Severe croup—Score 6–11; Impending respiratory failure—Score 12–17. & Surgical drainage.
1260 Indian J Pediatr (October 2011) 78(10):1256–1261

Table 4 Management guidelines for croup based on Westley’s croup score

Score Category Management guidelines

0–2 Mild Budesonide nebulization therapy one dose [3] or Dexamethasone one dose of 0.6 mg/kg iv
or im [3]; If child is older than 6 months and parents are reliable, child can be discharged.
Advise cold mist therapy at home.
3–5 Moderate Dexamethasone 0.6 mg/kg im or iv stat [4]; Cold humidified oxygen; Minimize
situations that may precipitate distress in the child.
Monitor using Westley’s score at 30 min interval and re-classify. Child can be discharged
only if he improves to mild category at the end of 6 h, has age more than 6 months and
parents are reliable.
6–11 Severe Dexamethasone 0.6 mg/kg im or iv stat [4]; Cold humidified oxygen; Minimize situations
that may precipitate distress in the child; Administer Adrenaline 5 ml 1:1000 (5 mg)
solution as nebulization. Monitor using Westley’s score at 30 min interval and re-classify
according to score.
Responsive to initial therapy
Child can be observed in ER if the score improves to be classified as moderate category.
Recurrence of respiratory distress can be treated with repeat adrenaline nebulization,
Dexamethasone 0.6 mg/kg/dose q6 hourly × four doses
Poor response to initial therapy
Airway stabilization and ICU care are indicated in a child who remains in severe category
even after the above mentioned therapy
12–17 Acute life-threatening Proceed to Airway stabilization (Intubation/Tracheostomy) and ICU care

Bacterial Tracheitis & Send a blood culture. Start Cefotaxime 50 mg/kg/dose,

& Give oxygen in nonthreatening manner
& Active management of airways. Endotracheal intubation
should be done in any child with audible stridor at
presentation.
& It is recommended to start with Cloxacillin (100–200 mg/
kg in four divided doses per day), amikacin (15 mg/kg/day
in once a day dose) and clindamycin (10 mg/kg/dose
TID).
Acute Epiglottitis Management
& Give Oxygen: Start high flow oxygen through re-
breathing mask. Try not to upset the child and do not
attempt to look inside the mouth as this may precipitate
airway obstruction
& Call for anesthetist and/ or ENT specialist for help.
While waiting for help, give adrenaline nebulization
5 ml of 1:1000 (1 mg/ml) solution.
& Airway assessment. Try to answer following questions:
& Unsecure airway?
& Obstruction severe?
& Epiglottitis on direct laryngoscopy?
If answer to any of these questions is yes, child
should be intubated by a specialist preferably in
operation theatre under inhalational anesthesia.
IV q 6 hourly following a loading dose of 100 mg/kg.
Continue the supportive management and arrange for
PICU transfer. Prophylactic Rifampicin 20 mg/kg/dose
OD × 4 days to be given for all household contacts.
Angioneurotic Edema Management
& Give oxygen in nonthreatening manner
& Active management of airways. Endotracheal intubation
should be done in any child with audible stridor at
presentation.
& This condition is treated by administration of adrenaline
(1:1000), subcutaneously 0.01 ml/kg (maximum
0.3 ml); hydrocortisone 10 mg/kg IV and antihistamines
like chlorpheniramine.
Airway Burns Management
& Give oxygen in nonthreatening manner
& Early tracheostomy is indicated in any child with audible
stridor at presentation. Child with facial burns and
suspected smoke inhalation having soon to-be obstructed
airway should receive endotracheal intubation. Preferably
intubation should be done in a controlled atmosphere by a
specialist.
& Endotracheal intubation can later be converted to
tracheostomy after the management of surface burns.
Indian J Pediatr (October 2011) 78(10):1256–1261
Conflict of Interest None.
Role of Funding Source None.
References
1. Hopkins A, Lahiri T, Salerno R. Changing epidemiology of
Life-threatening upper airway infections: the reemergence of
bacterial tracheitis. Pediatrics. 2006;118:1418–21.
1261
2. Stroud RH, Friedman NR. An update on inflammatory disorders of
the pediatric airway: epiglottitis, croup, and tracheitis. Am J
Otolaryngol. 2001;22:268–75.
3. Westley CR, Cotton EK, Brooks JG. Nebulized racemic
epinephrine for the treatment of croup. Am J Dis Child.
1978;132:484–7.
4. Ausejo M, Saenz A, Kellner JD, et al. The effectiveness of
glucocorticoids in treating croup: meta—analysis. BMJ. 1999;3
19:595–600.
5. Russell KF, Liang Y, O’Gorman K. Glucocorticoids for croup.
Cochrane Database Syst Rev. 2011;1:CD001955.
Indian J Pediatr (October 2011) 78(10):1262–1267
DOI 10.1007/s12098-011-0413-1
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Acute Chest Pain
Atul Jindal & Sunit Singhi
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 4 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Chest pain is a worrisome symptom that often
causes parents to bring their child to emergency department
(ED) for evaluation. In the majority of cases, the etiology of
the chest pain is benign, but in one-fourth of the cases
symptoms are distressing enough to cause children to miss
school. The clinician’s primary goal in ED evaluation of
chest pain is to identify serious causes and rule out organic
pathology. The diagnostic evaluation includes a thorough
history and physical examination. Younger children are
more likely to have a cardiorespiratory source for their
chest pain, whereas an adolescent is more likely to have a
psychogenic cause. Children having an organic cause of
chest pain are more likely to have acute pain, sleep
disturbance due to pain and associated fever or abnormal
examination findings, whereas those with non-organic chest
pain are more likely to have pain for a longer duration. Chest
radiograph is required in some, especially in patients with
history of trauma . In children, myocardial ischemia is rare,
thus routine ECG is not required on every patient. However,
both pericarditis and myocarditis can present with chest pain
and fever. Musculoskeletal chest pain, such as caused by
costochondritis and trauma, is generally reproducible on
palpation and is exaggerated by physical activity or breathing.
Pneumonia with or without pleural effusion, usually presents
with fever and tachypnea; chest pain may be presenting
symptom sometimes. In asthmatic children bronchospasm and
persistent coughing can lead to excess use of chest wall
muscles and chest pain. Patients’ who report acute pain and
subsequent respiratory distress should raise suspicion of a
spontaneous pneumothorax or pneumomediastinum. ED
A. Jindal : S. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
management includes analgesics, specific treatment directed
at underlying etiology and appropriate referral.
Keywords Chest pain . Children . Osteochondritis .
Psychogenic chest pain
Introduction
Chest pain is a worrisome symptom that often causes
parents to bring their child to emergency department(ED)
for evaluation. No specific data from India on incidence
and causes of chest pain in children is available. In North
America, the incidence of pediatric patients presenting to
ED with a complaint of chest pain is 3–6 for every 1,000
patient visits [1, 2]. In the majority of cases, the etiology of
the chest pain is benign, but symptoms are distressing
enough to cause 27–30% of children to miss school [2, 3].
Causes
The clinician’s primary goal in evaluating the chest pain is
to identify serious causes and rule out organic pathology.
There are numerous causes for pediatric chest pain; these
are listed in Table 1.
In general, the most frequently reported cause is
musculoskeletal pain, followed by respiratory causes.
Despite extensive investigations, one may not find any
cause in as many as 20–61% of cases [3–7] (Table 2).
Clinical Presentation
The clinical presentation of the pediatric patient with chest pain
varies greatly. The average age at presentation is 10–12 years,
Indian J Pediatr (October 2011) 78(10):1262–1267 1263

Table 1 Differential diagnosis of pediatric chest pain

Idiopathic Abdominal and Gastrointestinal

Cardiovascular Esophagitis (gastroesophageal reflux disease, bulimia, pill esophagitis)
Structural (hypertrophic cardiomyopathy, valvular stenosis Esophageal foreign body
[pulmonary, aortic], mitral valve prolapse) Esophageal spasm/dysmotility
Myocarditis Musculoskeletal and Chest wall
Pericarditis Chest wall strain (exercise, overuse injury, forceful coughing)
Endocarditis Skeletal (chest wall or thoracic spine) anomaly
Coronary artery disease (anomalous coronary arteries, Trauma (contusion/rib fracture)
acute Kawasaki disease, premature atherosclerosis) Costochondritis/Tietze syndrome
Coronary artery vasospasm (toxicologic ingestion) Slipping rib
Arrhythmia Precordial catch (Texidor twinge)
Aortic aneurysm or dissection Breast tenderness
(Marfan, Turner, and Noonan syndromes) Cutaneous (e.g., herpes zoster)
Respiratory Psychiatric
Pneumonia Stress-related pain
Pleuritis/pleural effusion Hematologic and Oncologic
Pleurodynia (coxsackie virus) Sickle cell disease
Severe cough Chest wall, thoracic, or mediastinal tumor
Pneumothorax/pneumomediastinum Neurologic
Asthma Migraine
Pulmonary embolism Spinal nerve root compression

with an equal distribution between sexes [1–4]. Younger Evaluation

children are more likely to have a cardiorespiratory source for
their chest pain, whereas an adolescent is more likely to have The diagnostic evaluation of pediatric patients presenting
psychogenic cause [1, 3]. Children with non-organic chest with chest pain includes a thorough history and physical
pain are more likely to have pain for a longer duration and examination. Further diagnostic studies may be needed
more likely to have a family history of chest pain or heart (Fig. 1). Chest radiograph is not required in every child
disease [3]. On the other hand, children having an organic with chest pain, but should be ordered when there is
cause of chest pain are more likely to have acute pain, sleep suspicion of respiratory, cardiac or traumatic cause. In
disturbance due to pain and associated fever or abnormal children, myocardial ischemia is rare, thus routine ECG is
examination findings. Children often have difficulty in also not required on every patient. When a child presents
localising and qualifying their pain. In instances where the with chest pain, clinical features can provide a clue to the
child is able to localize chest pain (e.g. right sided, left sided diagnosis.
and sternal), no specific relationship to a particular diagnosis Take a careful history and focus on:
or diagnostic category has been found [1–3]. The description
History
of the pain (e.g. sharp, dull and aching) is also unrelated to
the actual diagnosis [3]. & Acute onset of pain—likely to have an organic etiology
& Pain wakes child from sleep—likely to have an organic
Table 2 Frequency of causes of chest pain in children [3–9] etiology
& Pain associated with exertion, syncope—more likely to
Cause Emergency department (%) Cardiology clinic (%)
be cardiac in nature, or exercise-induced asthma
Idiopathic 12–61 37–54 & Presence of Fever—Pneumonia; pleural effusion, Pleuritis
Musculoskeletal 7–69 1–89 consider myocarditis, pericarditis
Respiratory 13–24 1–12 & Midsternal burning pain (worsens when recumbent)—
Gastrointestinal 3–7 3–12 gastroesophageal reflux
Psychogenic 5–9 4–19 & History of heart disease—pain is sometimes related to
Cardiac 2–5 3–7 underlying condition (often just anxiety about the
underlying condition)
1264 Indian J Pediatr (October 2011) 78(10):1262–1267

Child presenting
with chest pain

Yes Is there history of No

trauma?

Chest X-Ray
Fever and
Yes respiratory
findings

Chest X-Ray
Consider Pulmonary
Causes: Pneumonia No
Asthma

EKG, Chest X-Ray

Abnormal Consider Structural
If risk factors If abnormal cardiac cardiac Exam Yes abnormality
present, consider D- exam, consider: arrhythmia
dimer & CT chest EKG, ECHO for Myocardial Ischemia
for pulmonary myocarditis and
embolism pericarditis

No
If concerns for
myocardial ischemia,
get troponins

Dysphagia, pain
associated with
food, or
epigastric pain
Yes Explore GI Causes,
Consider Chest X-Ray
for Foreign body

No

Consider
Reproducible Pain?
Yes musculoskeletal
Overuse?
causes

No

Consider Evaluation with

Recent Stressors? Yes Psychogenic child psychologist
Cause

No

Idiopathic Needs
close monitoring

Fig. 1 Chest pain diagnostic algorithm

& Serious associated conditions (Kawasaki disease, asthma,
Marfan syndrome, lupus)—these children are at risk for
serious complications like ischemia, pneumothorax, pleural
effusion
& Stressful life events that correlate with onset of pain—
consider psychogenic pain (anxiety)
Physical examination: Check for:
& Respiratory distress, abnormal vital signs
& Decreased breath sounds, palpable subcutaneous air—
consider pneumonia, pneumothorax, subcutaneous
emphysema.
Indian J Pediatr (October 2011) 78(10):1262–1267
& Wheezing—consider asthma and pain related to com-
plications like pneumomediastinum, pneumothorax
& Abnormal cardiac findings (pathologic murmur, rub,
arrhythmia)—consider pericarditis, myocarditis, supra-
ventricular tachycardia, structural heart disease
& Evidence of trauma—consider pneumothorax, chest
wall injury
& Reproducible pain—consider musculoskeletal pain,
costochondritis
& Drooling in a young child—consider foreign body
aspiration/inhalation (coin)
Always look for Red flag signs (Table 3).
In these patients chest pain could be a sign of serious
underlying illness.
When to Consider Chest X-Ray and ECG?
Chest-radiograph is needed in all the patients with history
of trauma. In others it is indicated on basis of clinical signs
given in Table 4.
Consider further testing:
& D-dimer, chest CT scan and if available radionuclide
scan—if patient has increased risk for pulmonary
embolism (coagulation disorder, trauma)
& Holter monitor—if arrhythmia suspected
& Exercise stress test, pulmonary function tests—if pain is
related to exercise
& Child psychology evaluation.
Differential Diagnosis
Cardiac
Pediatric chest pain is rarely due to cardiac pathology.
However, it is the second most common cause for referral
to a pediatric cardiologist. Careful history and physical
Table 3 Chest pain in children—Red flag signs indicating serious
underlying etiology
✓ Young age
✓ Acute onset
✓ Pain precipitated with exercise
✓ Pain associated with syncope
✓ Pain associated with palpitations
✓ Pain associated with respiratory distress
✓ Pain associated with abnormal cardiorespiratory examination
✓ Pain associated with trauma
1265
examination are generally sufficient to diagnose cardiac-
related chest pain. If not, they should at least be sufficient
to guide the use of chest x-ray, ECG, and echocardiograms.
Pericarditis and myocarditis both can present with chest
pain and fever. Pericarditis usually presents with sharp,
substernal pain, which is alleviated by leaning forward. On
physical examination, the patient classically has distant
heart sounds, a friction rub, and signs of congestive heart
failure. Myocarditis patients often have vague symptoms
including chest pain, dyspnoea, dizziness, nausea, vomiting
and fatigue. Physical examination usually reveals a gallop,
signs of congestive heart failure, and tachycardia unresponsive
to fluids.
Structural abnormalities of the heart and vessels can
cause chest pain. Hypertrophic cardiomyopathy patients
usually give a history of increased chest pain with exertion.
Aortic stenosis, pulmonary stenosis, abnormal coronary
arteries, and mitral valve prolapse, depending on the
severity, can lead to ischemia of the heart and papillary
muscles. History and physical examination of these patients
typically reveal a heart murmur associated with the lesion.
Arrhythmias can cause chest pain in the pediatric patient.
Premature ventricular tachycardia can present as a fleeting,
sharp pain, or palpitations. Supraventricular tachycardia
(SVT) is usually described as a rapid heartbeat. Physical
examination should cue the physician to the possibility of
SVT.
Myocardial infarction is rare in children, but has been
reported in literature in previously healthy adolescents
[10, 11]. These patients usually present with classic severe,
substernal chest pain with radiation to the left arm or jaw.
Patients are at greater risk for myocardial ischemia if they
have a history of congenital heart disease, acquired heart
disease (Kawasaki disease), or drug abuse (cocaine).
Respiratory
Pediatric chest pain attributed to a pulmonary etiology is usually
accompanied by other symptoms and signs of organic illness.
Pneumonia with or without pleural effusion, usually presents
with fever, tachypnea, and respiratory symptoms. Physical
examination may reveal decreased breath sounds or rales.
Patients presenting with a history of asthma or reactive
airway disease should prompt the physician to assess the
possibility of chest pain secondary to an asthma exacerbation.
Bronchospasm and persistent coughing can lead to excess use
of chest wall muscles and is a common cause of chest pain.
Patients’ who report acute pain and subsequent respiratory
distress should raise suspicion of a spontaneous pneumothorax
or pneumomediastinum. Patients with asthma, Marfan
syndrome or cystic fibrosis are at increased risk of developing
pneumothorax. Physical examination may reveal decreased
breath sound on the affected side and crepitus depending on
1266 Indian J Pediatr (October 2011) 78(10):1262–1267

Table 4 Worrisome signs and

symptoms to prompt further
workup in pediatric patients
Work up History/symptom Sign
Chest radiograph Fever Tachypnea, rales and distress
Cough Ill appearing
Shortness of breath Tachycardia
Acute onset of pain Abnormal cardiac findings
Pain adversely affecting sleep Absent/decreased breath sounds
Associated with exercise Palpation of subcutaneous air
Associated with serious medical condition Drooling/gagging
History of foreign body ingestion
Electrocardiogram Pain precipitated exercise Abnormal cardiac findings
Syncope, palpitation Tachycardia (>180/min)
Drug use Ill appearing
Fever Fever
Underlying serious medical problems

the extent of pathology. A hemothorax should be considered
if there is a history of trauma.
Pulmonary embolism is rare in children but should be
considered in adolescents who complain of dyspnea,
pleuritic chest pain, hemoptysis and low grade fever. Risk
factors for pulmonary embolism are prolonged immobility,
hypercoagulable disorders, (including nephrotic syndrome)
indwelling central lines and major trauma particularly to the
lower extremities.
Chest wall deformities (pectus excavatum/pectus carina-
tum) in children are sometimes associated with chest pain.
They can lead to restricted lung function, and many are
related to psychologic problems in children because of the
associated cosmetic defects.
Gastrointestinal
Gastrointestinal causes for pediatric chest pain make up 3–7%
of ED visits. Gastroesophageal reflux disease often causes a
burning substernal type of pain because of resulting gastritis
and esophagitis. Epigastric tenderness on physical examina-
tion and association of pain with eating is suggestive of a
gastrointestinal origin of the chest pain and should be further
investigated. A trial of antacids is often diagnostic and
therapeutic.
Children that have ingested a foreign body that is lodged in
esophagus can have chest pain. Patients may have dysphagia
depending on the location of foreign body. A careful history
and chest radiograph usually reveals the diagnosis.
Musculoskeletal
Musculoskeletal chest pain is generally considered when pain
is reproducible on palpation or suggested by a history of muscle
strain or minor trauma. Reproducibility of chest wall pain is
generally a good marker for costochondritis. However, absence
does not always exclude a musculoskeletal cause. The
duration of musculoskeletal chest pain can be relatively long.
Trauma can cause fractures and contusions that may
result in chest pain. Overuse or overexertion of the chest
wall muscles may cause muscle strain.
Costochondritis is a common condition which is
recognised by eliciting pain while palpating the costochondral
joints. The etiology of costochondritis is unknown but it is
considered to be a benign inflammatory condition. It usually
involves 4th to 6th costochondral junctions and produces
localised tenderness. The pain is exaggerated by physical
activity or breathing. A similar disease Tietze’s syndrome also
occurs at costochondral junction but has the associated findings
of swelling, redness and warmth. Like costochondritis, Tietze’s
syndrome is thought to be a self limited inflammatory condition.
Slipping rib syndrome usually occurs at the false or
floating ribs. The patient describes a sharp intermittent pain
that lasts a few minutes and settles to a dull ache. There
may be a history of trauma and aggravation with movement.
The pain is thought to result from the anterior end of ribs
slipping out of place and aggravating the adjacent intercostal
nerves. The hooking manoeuvre can be used to help diagnose
this condition. The patient is instructed to lie down on the
unaffected side and the examiner reaches under the lower
coastal margin and pulls the rib anteriorly. A positive test results
in the reproduction of the patient’s pain and click sensation.
Precordial catch syndrome or Texidor’s twinge syndrome
is a benign condition that causes a brief sharp pain to the left
chest without radiation. The pain may occur with exercise or
when the patient is at rest in a slouched position. The etiology
is unclear but is thought to occur from the parietal pleura,
intercostals nerves or from the stretching ligaments of the heart.
Intense chest wall pain that follows a dermatome should
raise the physician’s suspicion for a herpes zoster infection.
Diagnostic studies usually do not help identify muscu-
loskeletal chest pain. If musculoskeletal pain is identified,
Indian J Pediatr (October 2011) 78(10):1262–1267
analgesics (ibuprofen or paracetamol) should be offered.
The slipping rib syndrome can be treated with education
and avoidance of the offending movements. An orthopedic
opinion is helpful as local nerve blocks and corticosteroid
injections are sometimes needed. A surgical alternative is to
have the anterior end of the rib and costal cartilage
removed, but this is usually done after failure of medical
management. Precordial catch syndrome is a self limiting
condition that requires only education and supportive care.
Psychogenic
A psychogenic source for chest pain accounts for 5–9% of
ED visits. Pediatric patients experiencing anxiety, depression
or stress can have symptoms manifesting as chest pain. The
history usually reveals a recent stressful event in the child or
adolescents’ life. This could be school failure, recent death or
illness in family, recent loss of friend from moving to a new city
or school or school phobia. The family history may be positive
for angina, and the child may imitate the pain as an attention
seeking mechanism. The symptoms usually do not fit into any
specific pattern. Play periods are not interrupted. Hyperventi-
lation may be associated with psychogenic chest pain.
Psychogenic chest pain should not be a diagnosis of exclusion.
If significant stress is temporally related to the pain it is a
reasonable diagnosis. However, a concomitant cause for the
chest pain should also be explored.
Idiopathic
Idiopathic chest pain is diagnosed in 12–61% of cases of
children with chest pain. A thorough history and physical
examination is essential to look for a possible etiology
before this diagnosis is made.
For patients with idiopathic or undiagnosed pain,
analgesics and close follow-up are appropriate.
Management
Begin treatment directed at specific underlying etiology
& Bronchodilators for asthma-related pain
1267
& Antibiotics for suspected pneumonia
& H2 blocker or proton pump inhibitor for midsternal
burning pain
& Analgesics for musculoskeletal pain
& Management of traumatic chest/chest wall injuries
Treat idiopathic or undiagnosed pain
& Analgesics for all (paracetamol or ibuprofen unless
contraindicated)
& Consider H2 blocker or proton pump inhibitor as a
therapeutic trial.
Conflict of Interest None.
Role of Funding Source None.
References
1. Massin MM, Bourguinont A, Coremans C, et al. Chest pain in
pediatric patients presenting to an emergency department or to a
cardiac clinic. Clin Pediatr. 2004;43:231–8.
2. Rowe BH, Dulberg CS, Peterson RG, et al. Characteristics of
children presenting with chest pain to a pediatric emergency
department. Can Med Assoc J. 1990;143:388–94.
3. Selbst SM, Ruddy RM, Clark BJ, et al. Pediatric chest pain: a
prospective study. Pediatr. 1998;82:319–23.
4. Lin CH, Lin WC, Ho YJ, et al. Children with chest pain visiting
the emergency department. Pediatr neonatol. 2008;49:26–9.
5. Driscoll DJ, Glicklich LB, Callen WJ. Chest pain in children: a
prospective study. Pediatrics. 1976;57:648–51.
6. Zavaras-Angelidou KA, Weinhouse E, Nelson DB. Review of 180
episodes of chest pain in 134 children. Pediatr Emerg Care.
1992;8:189–93.
7. Freedman JT. Evaluation of chest pain in pediatric patient. Med
Clin N Am. 2010;94:327–47.
8. Evangelista JA, Parsons M, Renneburg AK. Chest pain in
children: diagnosis through history and physical examination. J
Pediatr Health Care. 2000;14:3–8.
9. Yildirim A, Karakurt C, Karademir S, et al. Chest pain in children.
Int Pediatr. 2004;19:175–9.
10. Lane JR, Ben-Shachar G. Myocardial infarction in healthy
adolescents. Pediatrics. 2007;120:e938–43.
11. Gokhale J, Selbst SM. Chest pain and chest wall deformity.
Pediatr Clin N Am. 2009;56:49–65.
Indian J Pediatr (October 2011) 78(10):1268–1272
DOI 10.1007/s12098-011-0467-0
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Approach to a Child with Sore Throat
Ravi Shah & Arun Bansal & Sunit C. Singhi
Received: 6 April 2011 / Accepted: 4 May 2011 / Published online: 10 June 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Sore throat is one of the common reasons for
outpatient and emergency visits among children. It could be
because of several etiologies; of these bacterial pharyngitis
is the most important. Major challenge for the clinician is to
diagnose group A beta hemolytic streptococcus (GABHS)
pharyngitis and diphtheria, which are associated with
serious complications. Throat swab smear with culture
and rapid antigen tests are useful for making the diagnosis
but the later may not be available in resource poor settings.
Many clinical scores have been devised to diagnose
GABHS with variable success but usually clinical features,
epidemiological criteria and expert clinical judgment with
or without supportive investigations indicate need for
antibiotics. A child with sore throat and toxic look may
have diphtheria or parapharyngeal/retropharyngeal abscess,
and therefore should be hospitalized.
Keywords Children . Group A beta-hemolytic streptococcus .
Sore throat . Diphtheria . Pharyngitis . Throat swab
Introduction
Upper Respiratory tract infections are seen with great
frequency in both children and adults and have remarkable
economic impact, related to the frequent prescription by
physicians of antibiotics, even when the causative agents of
infection are not bacteria. About one-fourth of children with
sore throat have bacterial pharyngitis and about half of the
families with index case have a secondary case [1].
R. Shah : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Identification and adequate antibiotic treatment of group A
streptococcal sore throat is important for primary prevention
of acute rheumatic fever, as it carries approximately 3% risk
of development of acute rheumatic fever.
Definition
Soreness is generally described by the patient as pain in the
throat without the effort of swallowing and also a painful
swallow [2]. Sore throat is primary symptom of pharyngi-
tis. The terms “sore throat” and “pharyngitis or pharyngo-
tonsillitis” are often used interchangeably. Pharyngitis
refers to objective evidence of inflammation of the pharynx,
such as exudates, ulceration, or definite erythema. Redness
of the throat may occur as part of the general redness of all
mucous membranes in a patient with fever. A diagnosis of
pharyngitis is justified only when the pharynx is redder
than the rest of the oral mucosa.
Etiology
Most sore throats are caused by viruses. Less often, sore
throats are due to bacterial infections.
Viral Infections
& Corona virus, rhinovirus, adeno virus, influenza and
parainfluenza are the commonest etiological agents and
usually presents as common cold.
& Other viral infections that can present with sore throat
are Ebstein Barr (EB) virus and HIV which can present
as a sore throat in initial course of illness.
& Recurrent sore throat can occur due to cytomegalovirus
or fungal infections in immunosuppresed patients.
Indian J Pediatr (October 2011) 78(10):1268–1272 1269

Bacterial Infections Approach to the Patient

& Group A beta-hemolytic streptococcus (GABHS) is the
most common cause of bacterial sore throat. It accounts
for 15–36% of cases of acute pharyngitis in children in
west [1], and 13.4% of cases in India, according to one
study done at PGIMER [3].
& Streptococcus type C and G
& Diphtheria—is an important cause in India and many
developing countries.
& H influenza, Staphylococcus aureus, Mycoplasma,
Chlamydia pneumoniae, Moraxella catarrhalis and
Yersinia are some uncommon bacterial causes.
& Fusobacterium necrophorum infection. This uncommon
infection which starts as fever and sore throat, can
complicate into Lemierre’s syndrome. (Positive blood
culture, clinical or radiographic evidence of internal
jugular vein thrombosis, and at least one metastatic focus.)
Other Causes
& Peritonsillar, Retropharyngeal and Lateral Pharyngeal
abscesses—usually due to spread of infection from
local site like bacterial tonsillitis. Along with fever and
sore throat, other features like painful swallowing,
drooling, trismus, visible swelling below mandible and
deviation of uvula to opposite side may be present.
& Allergies—especially when complicated by postnasal
drip.
& Irritants—Dust, tobacco smoke (in teenagers) or chem-
icals (occupational hazard for children/adolescents
working in factories). Sore throat in such patients is
usually chronic.
& Muscle strain—talking in loud noise without rest for
long period.
& GastroEsophageal Reflux Disease (GERD)
& Psychogenic
Majority of the times, history and clinical examination
gives clue to etiology (Table 1). The major challenge is to
diagnose GABHS infection, because the signs and
symptoms of GABHS pharyngitis overlap with other
infections and untreated GABHS can cause serious
complications. No single element of the history or
physical examination reliably confirms or excludes
GABHS pharyngitis.
Several scoring systems have been developed to
predict which patients will have GABHS. Use of these
does improve quality of care but none of these systems,
however, is totally reliable in identifying children who
need treatment [4]. A clinical scoring system has been
designed in India but it has to be validated for local use.
This scoring system uses variables such as age, season,
fever, erythema of pharynx, size of tonsil, pharyngeal
exudates; lymphadenopathy and pain in throat, and scores
are assigned according to throat culture positivity in
association with the same. Cut off value of 15 predicts
GAS infection with 91% sensitivity and 98% specificity
[3].
The evaluation of patient should include the following:
History
& Onset and duration
& Fever—degree (doesn’t help much to differentiate)
& Associated cough, coryza, conjunctivitis (more with
viral); headache, myalgia (more with GABHS)
& Any breathing difficulty especially new onset snoring at
night or stridor (a likely sign of developing abscess)
& History of rash, diarrhea, allergy
& History of regurgitation, epigastric or retrosternal pain
usually indicates GERD
& History of sore throat in family in past 2 wks.
& Similar complaints in past, with vaccination history

Table 1 Clues towards etiological diagnosis of sore throat

Enterovirus Summer, pharyngeal vesicle/ulcer, rash, diarrhea

EBV(infectious Teenagers, tender posterior cervical lymphadenopathy, tender hepatomegaly, splenomegaly, petechial rash, edema of
mononucleosis) eyelids, supported by thrombocytopenia, >10% atypical lymphocytes on peripheral smear and positive monospot
test or IgM antibody against Viral Capsular Antigen (VCA).
Adenovirus Preschoolers, conjunctivitis, follicular hyperplasia of tonsils
Diphtheria Unvaccinated child, shallow ulceration of upper lips and external nares, neck swelling, characteristic
pseudomembrane
GastroEsophageal Reflux Retrosternal burning/epigastric pain, lump in throat, no fever
Disease
Fungal Oral thrush, common in neonates and infants <9 months. Immunocomromised/HIV
1270 Indian J Pediatr (October 2011) 78(10):1268–1272

Examination or cervical and/or generalized lymphadenopathy favours

Look oral cavity with a good light for-
& Exudates: White/gray scum on the surface of the tonsils
or pharynx, readily wiped off without producing
bleeding is more likely with bacterial pharyngitis.
& Ulcer
& Membrane: Exudates of bacterial pharyngitis may
organize as gray-white layer of materials that can be
peeled from the pharynx.
○ A membrane is seen with infectious mononucleosis,
diphtheria and sometimes streptococcal infection.
Arcanobacterium hemolyticum and tularemia are rare
causes of membranous pharyngitis.
○ Gray to black adherent membrane, with extension
beyond the faucial area (esp. soft palate and uvula),
dysphagia, and relative lack of fever suggest a
diagnosis of diphtheria.
○ Oral thrush seen in neonates and infants which can
have pseudomembrane (curd like plaques), removal
of which may cause mild punctuate bleeding.
& Bulging of oropharynx or uvula displacement are
suggestive of parapharyngeal or peritonsillar abscess.
& Painful vesicular lesions on pharynx and tonsils are
characteristic of herpangina. Herpes simplex produces
painful vesicles confined to anterior mouth which may
sometimes extend to anterior tonsillar pillars.
& Lymphadenopathy: Look for anterior (tonsillar) and
posterior cervical lymph nodes. Tender anterior lymph-
adenopathy favors bacterial sore throat. Tender posteri-
Ebstein Barr (EB) virus infection.
& Examine for neck swelling, conjunctivitis, auscultatory
abnormalities and hepatosplenomegaly.
& Vital signs, including blood pressure, should be recorded.
Poor quality of the heart sounds raises the possibility of
diphtheritic myocarditis. Absence of a heart murmur or
dependent edema should be noted for their relevance to
rheumatic fever and glomerulonephritis.
Common signs and symptoms of streptococcal pharyngitis
include sore throat, temperature ≥38.3°C, tonsillar or
pharyngeal exudates and cervical lymphadenopathy.
Cough, coryza and diarrhea are more common with viral
pharyngitis. Differentiating features between streptococcal
pharyngitis and viral pharyngitis are given in Table 2.
Investigations
A major concern in emergency room for a child with sore throat
is not to miss diagnosis of diphtheria and GABHS pharyngitis.
& Obtain throat swab for bacterial smear and culture
including Albert stains for diphtheria. A provisional
diagnosis of diphtheria is suggested if typical drum
stick organisms are seen in the smear. However, a
definitive diagnosis requires growth of C. diphtherium
in culture as diphtheroids are commensals in throat.
& Rapid Antigen Diagnostic Tests (RADTs) for GABHS
[5, 6]: It is based on nitrous acid extraction of group A
carbohydrate antigen from organisms obtained by throat

Table 2 Clinical clues to differ-

entiate viral infection from those GABHS Viruses
of Group A beta-hemolytic
streptococcus (GABHS) Age 5–11 years All ages
Season Late winter/early spring All
Symptoms Sudden onset Onset varies
Severe sore throat Mild sore throat
Absent cougha Present
Fever≥38.3°Ca/b Varies
Absent coryza Present
Headache, myalgia +/−
Throat pain –
Signs Severe pharyngeal erythema Mild
Pharyngeal exudatesb No exudate
Palatal petechieb Enanthem
Anterior cervical nodesa, tender Varies
Tonsillar exudate Absent
a
High sensitivity for Tonsil enlargement large/moderate Normal
GABHS [1] Scarlentiform rashb Exanthem
b
High specificity for H/o streptococcus exposure in past 2 wks Presentb Absent
GABHS [1]
Indian J Pediatr (October 2011) 78(10):1268–1272 1271

Note: antibiotics are indicated in any child who is looking sick and/or suspected to have complications.

Fig. 1 Clinical decision guideline for suspected streptococcal pharyngitis

swab. It is highly specific (>95%), and provides ○ Complete blood count

immediate results, but has variable sensitivity. Throat
culture confirmation of a negative RADT is recommended
to increase sensitivity. Confirmation of positive test is not
recommended because of very high specificity.
& Other investigations to be done according to clinical
possibility.
○ Peripheral blood smears-for atypical lymphocytes.
○ EB virus serology (IgM antibody against VCA(viral
capsular antigen))
○ Streptococcal antibody titre is not useful for
diagnosis of streptococcal pharyngitis and is not
routinely recommended.

Table 3 Antibiotic choice for

streptococcal pharyngitis Drug Route Dosage Duration

Penicillin V Oral <27 kg–250 mg 2–3/day 10 days

≥27 kg–250 mg 3–4/day or 500 mg 2/day
a
Amoxicillin is equally effective Amoxicillina Oral 40 mg/kg/day in 3 divided doses 10 days
as penicillin V and is more Penicillin G benzathine IM <27 kg–6 lac unit Single dose
palatable ≥27 kg–12 lac unit
The following medications are Options for patients allergic to penicillin
FDA (U.S. Food and Drug Admin- Erythromycin ethylsuccinate Oral 30–50 mg/kg/day in 2–4 divided doses 10 days
istration) approved, but are not
recommended by guidelines for Erythromycin estolate oral 20–40 mg/kg/day in 2–4 divided doses 10 days
primary GABHS therapy: azithro- Cefadroxil Oral 30 mg/kg/day in 2 divided doses 10 days
mycin, clarithromycin, cefpodox- Cephalexin Oral 25–50 mg/kg/day in 2 divided doses 10 days
ime, ceftibuten, and cefdinir
1272
○ X ray soft tissue neck (lateral view) for retrophar-
yngeal abscess.
○ CT scan of neck including base of skull for abscess.
Throat Swab Sampling Technique
Samples should be obtained by vigorous swabbing of both
tonsillar surfaces or fossae and the posterior pharynx [6, 7].
Correctly sampled and plated, throat swab culture has 90–
95% sensitivity. Swabbing the soft palate and uvula should
be avoided, because it dilutes the inoculums.
Management
GABHS pharyngitis is self-limiting illness. Antibiotic treat-
ment provides acute symptom relief, prevent suppurative
(otitis media, sinusitis, quinsy) and non suppurative compli-
cations, and reduce communicability. Antibiotics reduce
incidence of rheumatic fever by more than two third [8].
Clinical decision guideline for sore throat is given in Fig. 1.
Clinical features, epidemiological criteria and expert
clinician judgment with or without supportive investigation
usually indicate need for antibiotics. Currently used score for
decision making in pharyngitis has been adapted by adding
age to four components of original Centor score (absence of
cough, swollen and tender anterior cervical nodes, temper-
ature >38°C and tonsillar exudates or swelling) [9]. Each
component is given 1 point; age of 3–14 years carries 1 point
while that of 14–44 years, zero. Patients with a score of zero
or 1 do not require testing or antibiotic therapy. Patients with
score of 2 or 3 should be tested and prescribed antibiotics if
found positive while patients with score of 4 or higher, are at
high risk of streptococcal pharyngitis and should be given
empiric treatment [10].
Antibiotics
Based on cost, narrow spectrum of activity, safety, and
effectiveness, penicillin is the drug of choice [10, 11]. Shorter
duration of treatment increases risk of bacteriological
recurrence [12] Inappropriate use of macrolides for treatment
of GABHS pharyngitis has been the main cause of resistant
strains in western countries [13]. The various alternatives to
penicillin and the dosage of antibiotics are given in Table 3.
Diphtheria Management
& Stabilize child (ABC…) (For details refer to section on
upper airway obstruction).
& Diphtheria antitoxin: 50,000–120,000 U IV depending
on extent of involvement.
Indian J Pediatr (October 2011) 78(10):1268–1272
& Antibiotics: Aqueous crystalline penicillin G 40,000 U/
kg/dose 6 hourly IV or erythromycin 15 mg/kg 8 hourly
(not to exceed 2 g/day) oral/IV for 14 days.
For prophylaxis to contacts same dose of erythromycin for
7 days or a single injection of benzathine penicillin G
(600,000 U IM for <30 kg, 1,200,000 U IM for ≥30 kg.) is
recommended.
Indication for Hospitalization
& Toxic looking child
& Not accepting orally well
& Suspected to having associated complications or diphtheria.
Conflict of Interest None.
Role of Funding Source None.
References
1. Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational
clinical examination. Does this patient have strep throat? JAMA.
2000;284:2912–8.
2. Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic
treatment of children with sore throat. JAMA. 2005;294:2315–
22.
3. Nandi S, Kumar R, Ray P, Vohra H, Ganguly NK. Clinical score
card for diagnosis of Group A Streptococcal sore throat. Indian J
Pediatr. 2002;69:471–5.
4. Wigton RS, Connor JL, Centor RM. Transportability of a decision
rule for the diagnosis of streptococcal pharyngitis. Arch Intern
Med. 1986;146:81–3.
5. Schwartz B, Marcy SM, Phillips WR, Gerber MA, Dowell SF.
Pharyngitis-principles of judicious use of antimicrobial agents.
Pediatrics. 1998;101:171–4.
6. Van der Veen EL, Sanders EAM, Videler WJM, van Staaij BK,
van Benthem PPG, Schilder AGM. Optimal site for throat culture:
tonsillar surface versus posterior pharyngeal wall. Eur Arch
Otorhinolaryngol. 2006;263:750–3.
7. American Academy of Pediatrics, Committee on Infectious
Diseases. Red Book, 26th edn. Elk Grove Village, Ill.: American
Academy of Pediatrics; 2003. pp. 578–80.
8. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat.
Cochrane Database Syst Rev. 2006;4:CD000023.
9. McIsaac WJ, Goel V, To T, Low DE. The validity of a sore throat
score in family practice. CMAJ. 2000;163:811–5.
10. McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score
to reduce unnecessary antibiotic use in patients with sore throat.
CMAJ. 1998;158:75–83.
11. Rimoin AW, Hamza HS, Vince A, et al. Evaluation of the WHO
clinical decision rule for streptococcal pharyngitis. Arch Dis
Child. 2005;90:1066–70.
12. Zwart S, Sachs APE, Ruis GJHM, Gubbels JW, Hoes AW, de
Melker RA. Penicillin for acute sore throat: randomised double
blind trial of 7 days versus 3 days treatment or placebo in adults.
BMJ. 2000;320:150–4.
13. Hasenbein ME, Warner JE, Lambert KG, Cole SE, Onderdonk
AB, McAdam AJ. Detection of multiple macrolide- and
lincosamide-resistant strains of Streptococcus pyogenes from
patients in the Boston area. J Clin Microbiol. 2004;42:1559–63.
Indian J Pediatr (November 2011) 78(11):1388–1395
DOI 10.1007/s12098-011-0524-8
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Acute Bronchial Asthma
Sudhanshu Grover & Atul Jindal & Arun Bansal &
Sunit C. Singhi
Received: 20 April 2011 / Accepted: 30 May 2011 / Published online: 16 July 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Acute asthma is the third commonest cause of
pediatric emergency visits at PGIMER. Typically, it presents
with acute onset respiratory distress and wheeze in a patient
with past or family history of similar episodes. The severity of
the acute episode of asthma is judged clinically and catego-
rized as mild, moderate and severe. The initial therapy consists
of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline),
inhaled budesonide (three doses over 1 h, at 20 min interval)
in all and ipratropium bromide and systemic steroids
(hydrocortisone or methylprednisolone) in acute severe
asthma. Other causes of acute onset wheeze and breathing
difficulty such as pneumonia, foreign body, cardiac failure etc.
should be ruled out with help of chest radiography and
appropriate laboratory investigations in first time wheezers
and those not responding to 1 h of inhaled therapy. In case of
inadequate response or worsening, intravenous infusion of
magnesium sulphate, terbutaline or aminophylline may be
used. Magnesium sulphate is the safest and most effective
alternative among these. Severe cases may need ICU care and
rarely, ventilatory support.
Keywords Acute asthma . Children . Inhaled salbutamol .
Inhaled budesonide . Magnesium sulphate . Terbutaline
infusion
Introduction
Global prevalence of asthma in childhood ranges between
10% and 30% and is on the rise [1]. At PGIMER, acute
S. Grover : A. Jindal : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
exacerbation of asthma is the 3rd commonest diagnosis
after acute diarrhea and seizures among the patients
attending pediatric emergency service [2]. Despite advanc-
ing knowledge of the pathophysiology and treatment,
asthma related morbidity and mortality is on the rise.
Definition
Acute exacerbation of asthma can be defined as episodes of
coughing (particularly at night/early morning), wheezing,
breathlessness or chest tightness associated with widespread,
but variable, airflow obstruction within the lung that is often
reversible either spontaneously or with treatment [3, 4].
The term ‘status asthmaticus’ relates severity to the
outcome and has been used to define a severe asthmatic
exacerbation that does not respond to repetitive or continuous
administration of inhaled short-acting β2-adrenergic receptor
agonists (SABAs) in the emergency setting [5].
Pathophysiology
Small airway obstruction within lungs leads to increased
airway resistance, reduced expiratory flow, air trapping with
each breath and lung hyperinflation. The expiration
becomes an active process. Diaphragmatic flattening from
hyperinflation causes additional mechanical disadvantages.
Both forced expiratory volume and forced vital capacity are
decreased and total lung volumes are increased.
Gas exchange abnormalities occur because of V/Q
mismatch, increased intrapulmonary shunt, and increased
dead space (airway over-distension).
Dynamic hyperinflation (air trapping with each breath)
in severe asthma can stretch the pulmonary vasculature,
Indian J Pediatr (November 2011) 78(11):1388–1395 1389

increasing pulmonary vascular resistance and right ventric- Table 1 Differential diagnosis of wheezing in childhood
ular afterload. Due to large negative intrathoracic pressure 1. Infection
during inspiration, left ventricular afterload is increased, A. Viral
and systolic blood pressure decreases. Exaggerated varia- • Respiratory syncytial virus/bronchiolitis
tion in systolic blood pressure during inspiration is termed • Parainfluenza, Influenza, Adenovirus, Rhinovirus, Human
as pulsus paradoxus. metapneumovirus
B. Bacterial pneumonia
C. Chlamydia
Principles of Management 2. Asthmaa
3. Aspiration syndromesa
Emergency room management of acute asthma includes the • Gastro-esophageal reflux disease (GERD)
following: 4. Heart diseasea
& Rapid diagnosis and assessment of the severity based 5. Anatomic abnormalitiesa
on clinical evaluation A. Extrinsic airway anomalies
& Appropriate interventions to relieve breathing difficulty • Vascular ring/sling
and airway obstruction B. Intrinsic airway anomalies
& Assessment of response to the therapy (using clinical • Airway hemangioma
asthma severity scores) [6] and • Cystic adenomatoid malformation
& Stepping up the therapy to overcome unresponsiveness • Bronchial lung cyst
• Congenital lobar emphysema
• Sequestration of lung
• Mediastinal lymph node/tumor/TB lymphadenitis
Clinical Evaluation and Assessment of Severity
C. Malacia of larynx, trachea, or bronchi
6. Foreign body
A child with acute exacerbation of asthma presents with
7. Anaphylaxis
cough and wheezing, and exhibits signs of dyspnea,
increased work of breathing, and anxiety. The sick 8. Inhalational injuries (burns)
asthmatic child may also present in respiratory failure or 9. Mucociliary clearance disordersa
even frank cardiopulmonary arrest. Ominous signs include • Cystic fibrosis
distant or absent breath sounds (“silent chest”) in the face of • Primary ciliary dyskinesia
increased respiratory effort. While there is no diagnostic • Bronchiectasis
test for asthma, a family history of reactive airway disease, Entities marked a
are causes of recurrent wheeze
a history of recurrent symptoms, and a good response to
therapy support the diagnosis.
Peak flow measures obstruction in larger airways, spirometry
The diagnosis can be difficult in the “first time wheezer”
assesses the more peripheral airways.
or in a child with atypical symptoms (Table 1). In such
Based on history and clinical examination, the severity of
patients, pneumonia, bronchiolitis, airway foreign body and
acute asthma may be regarded as mild, moderate and severe
congestive heart failure must be rapidly differentiated from
(Tables 2 and 3). The same parameters can be used to assess
asthma.
the initial severity and also to monitor the response to therapy.
Clinical history should include history of cough, fever,
Presence of disturbed level of consciousness (drowsy,
respiratory distress, noisy breathing, whistling sounds,
confused), inability to speak, markedly diminished or
cyanosis and lethargy, past history of asthma, details of
absent breath sounds, central cyanosis, diaphoresis, pulsus
treatment, whether on regular treatment, previous hospital-
paradoxus >20 mm Hg, PEFR <25% of predicted or
ization and if yes, details of treatment, and pointers to rule
patient’s best, abdominal paradox, SpO2 <90% often
out foreign body inhalation and pneumonia.
indicate respiratory failure and imminent respiratory arrest.
In clinical examination, note the respiratory rate, temper-
One should always remember:
ature, heart rate, peripheral pulses, blood pressure, pulsus
paradoxus, air entry, nasal flaring, retractions, accessory – A calm patient usually denotes, at the most, mild
muscle usage, wheeze (phase and length of wheeze), oxygen distress
saturation (off and on oxygen) by pulse oximetry and any – An anxious asthmatic child indicates severe obstruction
abnormality in other systems’ examination. and probably hypoxia
Peak flow and spirometry are useful in older than 5 years and – “Silent chest” indicates inadequate air exchange and
co-operative children (especially if baseline values are known). severe airway obstruction
1390 Indian J Pediatr (November 2011) 78(11):1388–1395

Table 2 Clinical asthma severity scorea [6]

Score RR Room air saturationb Auscultation (wheeze) Retractionsc Dyspnea

0 <30 97–100 None None None

1 31–45 94–96 End expiration +/− Full sentences
2 46–60 91–93 All expiration ++ Partial sentences
3 >60 <91 Inspiration and Expiration without stethoscope +++ Single word/grunt
a
Maximum score is 15. This score should be used for the initial assessment and to monitor the response to therapy. Generally, the severe cases will
have a high score (i.e. >7)
b
Off oxygen for 5 min or until saturation drops less than 91%
c
Subjective assessment

– Unilateral diminished breath sounds (in a case of asthma)
indicates severe obstructive atelectasis or a pneumotho-
rax, and needs urgent attention.
Chest Radiography and Other Laboratory Studies
Laboratory studies are generally not indicated in a routine
acute exacerbation. However if the child is unusually ill or
there is doubt of an infection, blood samples should be
taken for the following:
1. White blood cell count
2. Serum electrolytes
3. Blood culture
Chest radiographs are not routinely indicated in the
unintubated asthmatic child, as unexpected radiographic
abnormalities are very rare [7]. A chest radiograph is
indicated if clinical examination suggests the possibility of
pneumothorax or pneumonia, or when there is doubt about
other cause of wheeze such as airway foreign body,
anatomic abnormality etc.
Arterial blood gas measurement yields quantitative infor-
mation on pulmonary gas exchange and is used in severely
distressed or ventilated patients. Typical findings during the
early phase of severe asthma are hypoxemia and hypocarbia.
With increasing airflow obstruction, hypercarbia develops.
PaO2 <60 mm Hg and PaCO2 >45 mm Hg often indicate
respiratory failure and imminent respiratory arrest.
Treatment of Acute Asthma
Goals
– Correction of hypoxemia with oxygen

Table 3 Assessment of severity [3]

Parametera Mild Moderate Severe Imminent respiratory

arrest

Breathlessness Walking Talking (infant—shorter At rest (infant will stop feeding)

cry/difficult feeding);
Can lie down Prefers sitting Hunched forward
Talks in Sentences Phrases Words
Alertness May be agitated Usually agitated Usually agitated Drowsy/confused
Respiratory rate Increased Increased Increased
Accessory muscles and Usually not Usually Usually Paradoxical movement
suprasternal retractions
Wheeze Moderate Loud Usually loud Absence of wheeze
(end expiration)
Pulse/min <100 100–120 >120 Bradycardia
Pulsus paradoxus (mm Hg) Absent (<10) 10–25 >25 Absence suggests
respiratory muscle
fatigue
PEFR (after bronchodilator) >80% 60–80% <60%
PaO2 on room air and/or Normal >60 <60
PaCO2 (mm Hg) (need not be tested) <45 >45
Saturation >95% 91–95% 90% or less
a
The presence of several parameters, but not necessarily all, indicate the severity of the attack
Indian J Pediatr (November 2011) 78(11):1388–1395
– Rapid reversal of airflow obstruction using inhaled
bronchodilators and corticosteroids
– Close monitoring of the clinical response and titration
and escalation of therapies (including parenteral
bronchodilators) to achieve rapid reversal of airflow
obstruction.
– To establish a future plan of management
The flowchart illustrates the treatment plan to
achieve above goals (Fig. 1). All children with acute
exacerbation of asthma should be cared in a comfortable
and supportive environment, ideally with a parent or in
the presence of a family member. Although hypoxemia
and anxiety may lead to agitation and restlessness,
sedatives are contraindicated in the nonintubated asth-
matic patient. Cardiorespiratory monitoring should be
established.
Oxygen
High-flow humidified oxygen should be delivered to all
the patients with acute asthma exacerbation to maintain a
SpO2 >92%; they are at risk of hypoxemia caused by
ventilation/perfusion mismatch. Oxygen is best delivered
via a partial or nonrebreathing mask. There is no evidence
that oxygen will suppress the respiratory drive in the
absence of preexisting chronic pulmonary disease.
Beta-2 Receptor Agonists
β2-receptor agonists remain the mainstay of therapy in
acute exacerbation of asthma. These agents mediate
bronchodilatation via stimulation of β2-receptors on
airway smooth muscle, which in turn mediates smooth-
muscle relaxation. All patients with acute asthma should
receive nebulized salbutamol in a dose of 0.15 mg/kg
every 20 min, three doses over 1 h. Tidal volume,
breathing pattern, and nebulizer gas flow vary the amount
of drug delivery, hence some experts recommend higher
doses of nebulized β-agonists. Presently, there is no
recommendation regarding the use of the much more
expensive (R)-albuterol in children with acute exacerba-
tion of asthma [8].
The nebulization device should be driven by oxygen.
Care must be taken to utilize the correct flow rate. Each
nebulizer device has a different flow-particle size
relationship, but most devices require 6–12 L/min in
order to deliver particles in the 1- to 3 μm range.
Although a Cochrane meta-analysis showed no overall
difference between the effects of albuterol delivered by
metered dose inhaler (MDI) spacer or nebulizer, MDI-
spacer administration can be difficult in patients in severe
distress [9].
1391
For children who need more frequent doses of β-
agonist, continuous nebulization appears to be superior to
intermittent doses. Use of continuous nebulization with
salbutamol may lead to more rapid improvement,
improved sleep, and may also be more cost-effective in
patients with severe exacerbation of asthma [10]. Orally
administered β-agonists are ineffective in severe asthma.
Subcutaneous epinephrine is indicated only in extreme
circumstances where inhaled β2-agonists are unavailable
or undeliverable (no aeration, intubated patient without
proper delivery device), when there are other systemic
signs of anaphylaxis, and when intravenous access has
not been established in a patient with impending
respiratory failure.
Major adverse effects of β-agonists include tachycardia,
prolonged QTc interval, hypokalemia and tremors. Cardio-
vascular adverse effects and tremors show tachyphylaxis,
whereas bronchodilator response usually does not.
Corticosteroids (Inhaled and Systemic)
Early use of anti-inflammatory therapy with systemic
steroids is effective in the emergency room treatment of
acute, moderate and severe exacerbations of asthma.
Inhaled glucocorticosteroids have a potential benefit in the
acute setting because they are delivered directly into the
airways, have few systemic side effects and induce a
reduction in the airway hyperreactivity [11].
Studies from the authors’ centre have shown a signifi-
cant reduction in the number of patients requiring hospital-
ization, total duration of oxygen treatment, and the number
of patients requiring intravenous infusion and steroids
among patients receiving inhaled budesonide therapy early
in the emergency room treatment of acute moderately
severe exacerbations of asthma [12, 13]. A 2003 Cochrane
Database review also supports improved outcomes for
children who receive corticosteroids early in their emer-
gency department course [14].
Systemic steroids should be started at the outset in the
following situations:
1. A child with a very severe attack of asthma.
2. Previous history of life-threatening attack or severe
attacks not responding to bronchodilators.
3. Child on regular oral steroids or high dose inhaled
steroids.
Studies suggest that a substantially increased dose of
inhaled steroid may be as effective as systemic steroids for
all but the most severe exacerbations.
Dose of inhaled steroids for the management of acute
severe asthma is 800 μg/dose. An oral dose of 1–2 mg/kg
of prednisolone may be as effective as an equivalent dose
of hydrocortisone (10 mg/kg) given intravenously, be-
1392 Indian J Pediatr (November 2011) 78(11):1388–1395
 Indian J Pediatr (November 2011) 78(11):1388–1395
ƒFig. 1 Flowchart for management of acute asthma
cause the time for onset of action is same. Cortico-
steroids may be continued as 0.25–0.5 mg/kg/dose of
prednisolone or 2.5–5 mg/kg/dose of hydrocortisone
every 6 hourly. Duration of steroid therapy depends on
severity of the attack and on chronicity of underlying
inflammation. The total duration of therapy may be 3–
7 days depending upon the response.
Anticholinergics: Ipratropium Bromide
Ipratropium bromide is preferred in the emergency setting
because of its selective muscarinic action on airway smooth
muscle receptors (through which bronchodilation is mediated)
and absence of systemic anticholinergic adverse effects.
Three doses of nebulized ipratropium bromide (250–500 μg),
combined with salbutamol, at 20 min intervals are recom-
mended in acute severe asthma. It produces additional
bronchodilation, resulting in fewer hospital admissions,
in patients who have acute severe or life-threatening asthma
or those with a poor initial response to β-agonist therapy.
Subsequently, the recommended dose is 250–500 μg at a
dosing interval of 6 h [15].
Magnesium Sulphate
A study at the authors’ centre in 1997 had clearly
shown that administration of intravenous Magnesium sulfate
(i.v. MgSO4) in children with acute severe asthma not
responding to conventional therapy (oxygen, nebulized
salbutamol, and corticosteroids) resulted in earlier improve-
ment in clinical signs and symptoms of asthma and PEFR
[16]. A Cochrane meta-analysis of seven studies supports
these early observations and concluded that IV magne-
sium sulphate improves pulmonary function and reduces
hospital admissions, particularly for the patients with the
most severe exacerbations of asthma [16, 17]. It acts by
bronchodilating effects on smooth muscle cells, reduction
of the neutrophilic burst associated with inflammation, and
by decreasing uptake of calcium by bronchial smooth
muscles.
Recommended dose is 50 mg/kg (range 25–75 mg/kg)
administered IV over 20–30 min; the maximum dose
allowed is 2 g. The onset of action is within 2–5 min. Its
main adverse effects are skin reddening and nausea, usually
during infusion.
In a recently completed randomized trial at the present
centre, magnesium sulphate infusion was found to be
superior to terbutaline and aminophylline infusion in
children who had failed to respond to 1 h treatment with
salbutamol, ipratropium and inhaled and systemic cortico-
steroids [18].
1393
Intravenous β2-Agonists
Intravenous infusion of β-agonists can be considered in
patients unresponsive to treatment with continuous nebu-
lisation. Accepted indications for β2-agonist infusion
includes progressive retention of CO2 (hypoventilation)
and signs of imminent respiratory fatigue. Intravenous
salbutamol affected a rapid drop in PaCO2 levels and
averted the need for ventilation in over two-thirds of
patients [19]. In authors’ experience, children with asthma
who failed to respond to nebulized bronchodilators and
intravenous steroids, terbutaline was similar to aminophyl-
line, but had lesser side effects [18].
The doses of intravenous salbutamol and terbutaline are
as follows:
Salbutamol—10 μg/kg loading dose. Maintenance dose
5–10 μg/kg/min for 1 h followed by 1–2 μg/kg/min.
Terbutaline—10 μg/kg loading dose, followed by
0.1–10 μg/kg/min.
Terbutaline is the intravenous beta agonist being used in
authors’ set up. It is generally started at a minimal dose, and
can be subsequently titrated up every 15–20 min to desired
clinical response. Serious side effects include hypokalemia,
arrhythmia, hypotension and myocardial ischemia.
Methylxanthines: Aminophylline
Aminophylline acts as phosphodiesterase inhibitor, stim-
ulates endogenous catecholamine release, augments dia-
phragmatic contractility, increases binding of cAMP, acts as
prostaglandin antagonist, and has other unspecified anti-
inflammatory effects.
The role of the Aminophylline in the treatment of children
with severe asthma has been debated. Several recent studies,
however, suggest that aminophylline may offer some benefit.
In a recently completed study from authors’ centre, intravenous
aminophylline was found to be equally efficacious intravenous
terbutaline but had more side effects [17]. To avoid the side
effects, the dosage needs to be adapted to age groups and
individual patient’s serum levels (goal 10–20 μg/mL). A
reasonable starting point is a 5 mg/kg loading dose, followed
by a 0.9 mg/kg/h infusion. The narrow therapeutic range of
theophylline overlaps with its toxicity range. Toxicity
includes nausea and vomiting, tachycardia, and agitation.
Severe and life-threatening toxicity has been reported in the
form of cardiac arrhythmias, hypotension, seizures, and death
with high theophylline serum concentrations [20, 21].
Ketamine
Ketamine acts as a sympathomimetic by inhibiting neuronal
norepinephrine reuptake, and blocking airway N-methyl-D-
1394
aspartate receptors linked to the mediation of increased airway
tone. Because of its anesthetic and bronchodilatory properties,
ketamine can be very useful as an induction agent for
intubation in children with severe asthma going on mechan-
ical ventilation. The usual dose is IV bolus of 2 mg/kg
followed by a continuous infusion of 0.5–2 mg/kg/h, but
higher doses have been used for asthmatic children. Unwant-
ed effects of ketamine include increase of bronchial secretions
(atropine or glycopyrrolate should be co-administered), and
postanesthesia emergence reaction in older children.
Antibiotics
Asthma attacks triggered by infection mostly involve viral
pathogens; therefore, antibiotics are not indicated as a
routine measure. Antibiotics are indicated when more than
one of following is present:
1. High grade fever
2. Purulent sputum with presence of polymorphs and not
eosinophils and
3. Chest radiograph showing a consolidation
Supportive Treatment
Overall care of the child should also be given due
consideration, with maintenance of good hydration status,
control of temperature and strict fluid and electrolyte
balance. Poor fluid intake, increased loss of insensible
fluids and vomiting may cause dehydration in the asthmatic
child. Euvolemia should be maintained. In a normally
hydrated child, fluid should be restricted to 65% of
maintenance volume as the syndrome of inappropriate
antidiuretic hormone has been described in severe asthma.
Overhydration may lead to pulmonary edema. Fluid
balance should be monitored carefully.
Potassium level should be monitored frequently; hypoka-
lemia could occur because of beta-agonist therapy (causing
potassium to move into the intracellular compartment), and
due to increased losses caused by the use of steroids and
theophylline induced diuresis.
Endotracheal Intubation
Absolute indications for intubation in Emergency department
include:
– Cardiopulmonary arrest
– Severe hypoxemia
– Rapid deterioration in the child’s mental state
Note: Many hypercarbic patients can be managed
without invasive support while other patients with mild
hypercarbia may need emergent airway support.
Indian J Pediatr (November 2011) 78(11):1388–1395
Before intubation, the child must be preoxygenated with
100% oxygen. Rapid sequence intubation should proceed
with atropine (if indicated), a sedative or anesthetic,
followed by a rapid-acting muscle relaxant. Ketamine, is
the preferred induction agent in patients with severe
asthma. A cuffed or sufficiently large endotracheal tube is
recommended to minimize air leak with the anticipated
high inspiratory pressures.
Indications for Transfer to an Intensive Care Unit
1. Any child with signs of life-threatening attack
2. If the child has been receiving therapy in emergency
department for a few hours and has shown poor
response.
3. Development of clinical signs of respiratory failure
such as persisting hypoxemia, exhaustion or change in
the level of consciousness.
Treatments that are not Recommended in the
Emergency Care [3]
– Antibiotics (except as needed for co-morbid conditions)
– Aggressive hydration
– Chest physical therapy
– Mucolytics
– Sedation
Discharge Advice
– MDI with spacer (ensure proper technique)
– A course of oral steroids (1–2 mg/kg) if steroids
have been used during the treatment of acute episode
(total duration 5 days).
– Health education/councelling.
Key Messages
& Acute asthma is a condition of acute progressive worsen-
ing of bronchospasm, lower airway obstruction and
respiratory dysfunction, unresponsive to standard therapy.
& In a child with first episode of suspected acute asthma,
other causes of wheeze namely, pneumonia, bronchio-
litis, heart failure and foreign body should be ruled out.
& Clinical interventions should be based primarily on the
physical examination, clinical assessment of severity of
asthma, and not on blood gas examination.
& Nebulized short acting bronchodilators, salbutamol
along with inhaled budesonide and anticholinergics
Indian J Pediatr (November 2011) 78(11):1388–1395
every 20 min in three doses, and systemic steroids are
the mainstay of therapy.
& Magnesium sulphate infusion (50 mg/kg) should be
used in patients failing to respond to beta-agonists,
inhaled and systemic steroids and inhaled ipratropium.
& IV and subcutaneous administration of β2-agonists is
most beneficial for patients with severe status asthma-
ticus and limited airflow, in whom distribution of
inhaled medications may be significantly reduced.
& Endotracheal intubation is indicated for patients with
cardiorespiratory arrest, refractory hypoxemia, or those
who have significant respiratory acidosis unresponsive
to pharmacotherapy.
& When maximal medical therapy is failing, mechanical
ventilation should be considered.
Conflict of Interest None.
Role of Funding Source None.
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Indian J Pediatr (November 2011) 78(11):1396–1400
DOI 10.1007/s12098-011-0492-z
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Approach to a Child with Lower Airway Obstruction
and Bronchiolitis
Sudhanshu Grover & J. Mathew & Arun Bansal &
Sunit C. Singhi
Received: 25 April 2011 / Accepted: 16 May 2011 / Published online: 28 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Lower airway obstruction can occur at the level of
trachea, bronchi or bronchioles. It is characterized clinically
by wheeze and hyperinflated chest, apart from other signs of
respiratory distress. Common causes include bronchiolitis,
asthma, pneumonia, laryngotracheo-bronchitis, congenital
malformations and foreign body inhalation. Bronchiolitis
usually occurs in children aged 2 months to 2 years. It is
most commonly caused by respiratory syncytial virus infec-
tion. The diagnosis is mainly clinical, and investigations have
a very limited role. Humidified oxygen and supportive therapy
are the mainstays of treatment. A trial of inhaled epinephrine
or parenteral steroids may be considered for non-responders. It
is usually associated with good outcome.
Keywords Children . Lower airway obstruction . Wheeze .
Bronchiolitis
Lower Airway Obstruction
Obstruction in the lower airways (i.e. airways within the
thorax) may occur in the trachea, bronchi or bronchioles.
The general symptoms/signs of respiratory tract disease
include cough, tachypnea, and increased respiratory effort.
The most characteristic symptom and sign of lower airway
obstruction is wheezing. Wheeze is a high pitched whistling
sound usually heard during expiration (sometimes heard
with stethoscope only). It is caused by vibrations of airways
during passage of air through narrow lumen. Other relatively
S. Grover : J. Mathew : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
specific clinical pointers are prolonged expiration and
hyperinflated chest. Wheeze is most often expiratory, but it
may also be inspiratory or biphasic. Expiration becomes an
active rather than a passive process in such cases. There are
many causes of wheezing in infancy and childhood. These are
summarized in Table 1. The most common among these,
presenting with an acute illness in authors’ emergency
department are bronchiolitis, acute asthma, pneumonia,
congestive cardiac failure, laryngotracheo-bronchitis, airway
foreign bodies and congenital malformations. In a study
published in 2002 from a teaching hospital in north
India, the common causes of wheezing in children aged
2 months to 1 year were bronchopneumonia(50%),
bronchiolitis(34%), bronchial asthma(16%) after exclud-
ing foreign body inhalation, congestive cardiac failure,
and anatomical malformations [1]. In Singapore, 22.7%
children had at least one episode of wheeze by the second
year of life [2], while in the West one-third children had at
least one lower respiratory tract infection with wheeze in
the first 3 years of life [3].
Older patients with lower airway obstruction tend to
breathe at a slower rate; however infants breathe faster. This
is because of a highly compliant chest wall; wherein slower
breathing would lead to subatmospheric intrapleural pres-
sure and collapse of the chest wall.
Approach to a Wheezing Child
In pediatric emergency, important points in history and
examination are as follows:
History
& Age of onset: Onset in neonatal period/early infancy sug-
gests CCF, anatomic malformation, or immunodeficiency.
Indian J Pediatr (November 2011) 78(11):1396–1400 1397

Table 1 Differential diagnosis of acute wheezing in infants & Signs of allergy or atopy like rhinitis, conjunctivitis,
1. Infection eczema suggest asthma/allergic bronchitis.
• Viral: Respiratory syncytial virus bronchiolitis, Parainfluenza, & Look for the signs of CCF like hepatomegaly, neck
Influenza, Adenovirus, Rhinovirus, Human metapneumovirus veins, dependent edema, and growth pattern.
• Bacterial pneumonia Remember
• Chlamydia pneumonia
2. Asthmaa & In a child with acute onset wheezing, with history of
3. Aspiration syndromesa preceding fever and abdominal pain, and presence of
4. Heart diseasea temperature >38°C at presentation, pneumonia is the
• Congestive cardiac failure
likely diagnosis [4].
• Myocarditis
& All infants/children with bilateral wheezing do not have
• Cardiomyopathy
bronchial asthma [4]
& Foreign body aspiration can present with non-
5. Anatomic abnormalitiesa
lateralization of findings; it should be suspected in non-
• Extrinsic airway compression
responders to inhaled bronchodilators and corticosteroids
- Vascular ring/sling
[4].
- Mediastinal lymph node/mass
& Asthma and congenital heart disease can coexist [4].
• Intrinsic airway anomalies
& In a young infant (2 to 6 months) with mild to moderate
- Airway hemangioma
grade fever and wheeze along with respiratory distress,
- Cystic adenomatoid malformation
bronchiolitis is the most likely diagnosis.
- Bronchial lung cyst
- Congenital lobar emphysema
- Sequestration of lung
Bronchiolitis
- Mediastinal lymph node/tumor/TB lymphadenitis
• Central airway obstruction: laryngotracheo-malacia
“Bronchiolitis” refers to inflammation of peripheral air-
6. Foreign body
ways. It is the most common cause of wheezing in young
7. Anaphylaxis
infants.
8. Inhalational injuries (burns)
9. Mucociliary clearance disordersa
Etiology
• Cystic fibrosis
• Primary ciliary dyskinesia
Respiratory syncytial virus (RSV) is responsible for more
• Bronchiectasis than 50% cases. Other etiologic agents include Para-
10. Gastro-esophageal reflux influenza, Adenovirus, Mycoplasma, and Human Meta-
11. Immunodeficiencies – HIV, IgA deficiency, B-cell deficiency pneumovirus. Human Metapneumovirus is an important
a
These conditions can be associated with recurrent wheezing
primary cause or it can occur as a co-infection. There is no
evidence for a bacterial cause of bronchiolitis.
& Frequency: Recurrent or persistent symptoms point to-
wards asthma, cardiac cause, or anatomical malformation. Clinical Features
& A positive family history or a personal history of atopy
indicates asthma. & Age—Bronchiolitis generally occurs in young infants
& Other specific symptoms like fever, cardiac symptoms, 2 to 6 months of age. It may occur up to 2 years of
GERD may suggest the definitive cause of wheeze. age.
& Previous treatment and response to the treatment is also & History—Fever (mild to moderate grade), refusal to
important in making a diagnosis. feed, breathing difficulty, wheeze, lethargy
& On examination: wheeze, hyperinflation, hyper- reso-
Examination
nant percussion note, obliteration of liver and cardiac
& Clubbing is an indicator of chronic disease (e.g. dullness.
bronchiectasis)
& Chest shape: Barrel shaped chest is seen in asthma/ Differential Diagnoses
chronic lung disease; precordial pulsation/bulge is seen
in congenital heart disease. The differential diagnoses of wheezing in infants/children
& Lateralization of findings suggests foreign body, ana- are presented in Table 1. First episode of asthma,
tomical malformations, mediastinal lymph nodes/mass. pneumonia, and congestive cardiac failure are the most
1398
important diagnoses that should be ruled out. The following
points should be kept in mind.
& First episode of bronchial asthma—often has a family
history and shows good response to bronchodilators
& Pneumonia—usually a sick looking child, with moder-
ate to high grade fever; signs of obstruction are less
pronounced; and crackles are audible on auscultation.
& Cardiac failure due to myocarditis or congenital heart
disease—is associated with tachycardia, tender hepato-
megaly, basal crackles, murmur and cardiomegaly on
chest radiography.
Investigations
Indications for investigations: possible alternate diagnosis,
severe distress, worsening, and absence of clinical improvement.
The following investigations may be required:
& Chest radiograph
& Viral studies (nasopharyngeal swab): Nasopharyngeal
swab may be positive for RSV.
& Blood gas analysis
Chest radiograph provides information about the base-
line lung condition for any infant with respiratory distress
and helps to rule out other differential diagnoses such as
foreign body and pneumonia, and to look at chronic lung
conditions e.g. bronchiectasis. In bronchiolitis, it typically
shows hyperinflation and patchy atelectasis.
Figure 1 shows a typical chest radiograph of bronchio-
litis. This one and a half month infant was brought with
fever and paroxysmal cough for 4 days. Long bouts of
cough were associated with apnea. He had family history of
asthma. On examination: respiratory rate was 65/min with
chest wall retractions, decreased air entry and wheeze and
scattered crepts all over chest. Nasophryngeal swab was
positive for Respiratory Syncitial Virus.
Fig. 1 Chest radiograph of a two and a half month infant, with
bronchiolitis showing bilateral hyperinflation (hyperaerated lungs,
widening of intercostals space, straightening of ribs).
Indian J Pediatr (November 2011) 78(11):1396–1400
Treatment
An outline of treatment plan for suspected cases of
bronchiolitis is given in Fig. 2.
1. Humidified oxygen is the mainstay of treatment in
bronchiolitis.
2. Careful attention to fluid therapy is necessary; liberal
fluid therapy may lead to water intoxication [5].
Bronchiolitis of infancy is characterized by water
retention which is caused by impaired renal water
excretion.
Other modalities of treatment have been studied exten-
sively. These include inhaled epinephrine, parenteral ste-
roids (dexamethasone), inhaled salbutamol, inhaled
hypertonic saline etc. Their role is unproven; none of them
is supported by robust evidence of significant clinical
efficacy.
Nebulized Epinephrine
Epinephrine has been aptly described as the “least
ineffective” intervention [6, 7]. There is no benefit in terms
of admission rate or duration of hospitalization; however
subgroup analysis suggests that epinephrine has some
benefit among outpatients. Similarly, there is no difference
for surrogate outcomes including change in oxygen
saturation, heart rate and respiratory rate, although epi-
nephrine results in more favourable clinical score change
from baseline. A meta-analysis of the treatment effects of
nebulized epinephrine suggested a decrease in clinical
symptoms as compared with either placebo or salbutamol
[8].Nebulized epinephrine has been shown to improve
symptoms better than oral or nebulized salbutamol [9–11].
Some infants may experience worsening of symptoms
with nebulized epinephrine. Therefore, a trial should be
considered but treatment should be stopped if there is no
response.
Nebulized Salbutamol
There is no benefit of inhaled salbutamol on admission rate
or duration of hospitalization [12]. A meta-analysis of the
treatment effects of nebulized selective beta-agonists failed
to show any consistent benefits [13].
Nebulized Hypertonic Saline
It has been suggested that hypertonic saline nebulization
may be useful in making secretions less viscous and
promoting their excretion, thereby resulting in clinical
improvement. However, nebulized hypertonic saline has a
limited role in bronchiolitis [14].
Indian J Pediatr (November 2011) 78(11):1396–1400 1399

Fig. 2 Flowchart showing out- Humidified oxygen

line of management in suspected
case of bronchiolitis IV fluids (70%)/ supportive therapy

Assess response

Adequate response Inadequate response

Continue supportive therapy Trial of inhaled epinephrine

Adequate response Worsening/ no response

Stop epinephrine.
PICU transfer
Give Dexamethasone (0.6 mg/kg) 1 dose

Inadequate response

Steroids (Oral/Inhaled) Use of CPAP (Continuous Positive Airway Pressure)

Steroids are no different from placebo with respect to hard A recent randomized controlled trial (n=31) compared the
outcomes and several surrogate outcomes (clinical scores, use of nasal CPAP with standard treatment. CPAP im-
oxygenation parameters, respiratory rate, readmission rate). proved ventilation and hypercapnea [23].
One trial (n=174) showed that a single dose of intravenous
dexamethasone (0.6 mg/kg) results in (statistically but not Treatment Modalities That Should Be Avoided
clinically significant) shorter duration of hospitalization and
time for resolution of respiratory distress [15, 16]. & Chest physiotherapy should not be used routinely in the
Inhaled dexamethasone does not show any difference in management of bronchiolitis.
clinical score and oxygenation compared to saline [17]. & No antibiotics should be given routinely [19].
A recent randomized controlled trial studied 800 patients
divided in 4 intervention groups: 1) Epinephrine–dexa-
Indications for Hospitalization
methasone group, 2) Epinephrine group 3) Dexamethasone
group 4) Placebo group. The doses used were:- Epineph-
Indications for hospitalization are mentioned in Table 2.
rine: 3 ml of generic epinephrine in a 1:1000 solution;
Dexamethasone: 1.0 mg/kg body weight (maximum dose,
Criteria for Discharge
10 mg) or placebo given after the first nebulized treatment
in the emergency department, followed by five once-daily
The following criteria are recommended for sending home
doses of dexamethasone (0.6 mg/kg; maximum daily dose,
an infant with bronchiolitis [24]:
10 mg). The study concluded that combined therapy with
dexamethasone and epinephrine may significantly reduce & Normal respiratory rate
hospital admissions [18]. & Oxygen concentration of at least 94%
& Adequate oral intake
Ribavirin (Aerosol) & Absence of respiratory distress

Ribavirin should not be used routinely in children with
bronchiolitis [19]. Indications for using ribavirin include
selected patients with life threatening RSV infection [20]:
such as prematurity, infants with congenital heart disease,
chronic lung disease and immunocompromised host.
One systematic review and two subsequent RCTs
found that, in children and infants admitted to hospital
with RSV bronchiolitis, ribavirin did not significantly
reduce mortality, respiratory deterioration, or duration of
hospital stay compared with placebo [21], but it signif-
icantly reduced the duration of ventilation compared with
placebo [22].
Table 2 Indications for hospitalization/markers for severe disease
• Age less than 3 months
• Gestational age at birth < 34 wks
• Cardiopulmonary disease/immunodeficiencies
• Anatomical defects of airways
• Neurological disease associated with hypotonia and pharyngeal
in-coordination
• Respiratory rate > 70/min
• Lethargic appearance
• Wheezing and respiratory distress associated with SpO2 <92%
• Atelectasis or consolidation on chest radiography
1400
Conflict of Interest None.
Role of Funding Source None.
References
1. Kumar N, Singh N, Locham KK, Garg R, Sarwal D. Clinical
evaluation of acute respiratory distress and chest wheezing in
infants. Indian Pediatr. 2002;39:478–83.
2. Tan TN, Lim DLC, Chong YS, Lee BW, Van Bever HP.
Prevalence of eczema symptoms in the second year of life. J
Allergy Clin Immunol. 1078;2004:113.
3. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M,
Morgan WJ. Asthma and wheezing in the first six years of life.
NEJM. 1995;332:133–8.
4. Singhi SC, Mathew JL, Jindal A. Clinical Pearls in Respiratory
Diseases. Indian J Pediatr. 2010 Dec 14.[Epub ahead of print]
doi:10.1007/s12098-010-0270-3.
5. Poddar U, Singhi S, Ganguli NK, Sialy R. Water electrolyte
homeotasis in acute bronchiolitis. Indian Pediatr. 1995;32:59–65.
6. Bush A, Thomson S. Acute bronchiolitis. BMJ. 2007;335:1037–41.
7. Mathew JL. What works in bronchiolitis? Indian Pediatr.
2009;46:154–8.
8. Hartling L, Wiebe N, Russell K, Patel H, Klassen TP. Arch Pediatr
Adolesc Med. 2003;157:957–64.
9. Ray MS, Singh V. Comparison of nebulised adrenaline versus
salbutamol in wheeze associated respiratory infections in infants.
Indian Pediatr. 2002;39:12–22.
10. Bertrand P, Aranibar H, Castro E, Sanchez I. Efficacy of nebulised
epinephrine versus salbutamol in hospitalized infants with
bronchiolitis. Pediatr Pulmonol. 2001;31:284–8.
11. Menon K, Sutcliffe T, Klassen TP. A randomized trial comparing
the efficacy of adrenaline with salbutamol in the treatment of
acute bronchiolitis. J Pediatr. 1995;126:1004–7.
Indian J Pediatr (November 2011) 78(11):1396–1400
12. Gadomski AM, Bhasale AL. Bronchodilators for bronchiolitis.
Cochrane Database Syst Rev. 2006;3:CD001266.
13. Flores G, Horwitz RI. Efficacy of b2 agonists in bronchiolitis: a
reppraisal and meta-analysis. Pediatrics. 1997;100:233–9.
14. Mathew JL. Hypertonic saline nebulization for bronchiolitis.
Indian Pediatr. 2008;45:987–9.
15. Teeratakulpisarn J, Limwattananon C, Tanupattarachai S, et al.
Efficacy of dexamethasone injection for acute bronchiolitis in
hospitalized children: a randomized, double-blind, placebo-
controlled trial. Pediatr Pulmonol. 2007;42:433–9.
16. Garrison MM, Christakis DA, Harvey E, et al. Systemic cortico-
steroids in infant bronchiolitis: a meta-analysis. Pediatrics.
2000;105:E44.
17. Bentur L, Shoseyov D, Feigenbaum D, et al. Dexamethasone
inhalations in RSV bronchiolitis: a double-blind, placebo-
controlled study. Acta Paediatr. 2005;94:866–71.
18. Plint AC, Johnson DW, Patel H, et al. Epinephrine and
dexamethasone in children with bronchiolitis. N Engl J Med.
2009;360:2079–89.
19. American Academy of Pediatrics. Subcommittee on diagnosis and
management of bronchiolitis. Diagnosis and management of
bronchiolitis. Pediatrics. 2006;118:1774–93.
20. American Academy of Pediatrics. Chapter on respiratory
syncytial virus. In: Pickering LK, editor. Red Book: 2009
Report of the Committee on Infectious Diseases. 28th ed.
Elk Grove Village: American Academy of Pediatrics; 2009.
p. 560–4.
21. Hartling L, Russell KF, Patel H, et al. Epinephrine for bronchio-
litis. Cochrane Database Syst Rev. 2004;1:CD003123.
22. Ventre K, Randolph AG. Ribavirin for respiratory syncytial virus
infection of the lower respiratory tract in infants and young
children. Cochrane Database Syst Rev. 2007;1:CD000181.
23. Thia LP, McKenzie SA, Blyth PB, et al. Randomised controlled
trial of nasal continuous positive airways pressure (CPAP) in
bronchiolitis. Arch Dis Child. 2008;93:45–7.
24. Basco WT. Predicting which pediatric bronchiolitis patients can be
safely discharged from the ED. Pediatrics. 2008;121:680–8.
Indian J Pediatr (November 2011) 78(11):1401–1403
DOI 10.1007/s12098-011-0488-8
SYMPOSIUM ON PGIMER PROTOCOLS ON RESPIRATORY EMERGENCIES
Airway Foreign Body Aspiration
Sudhanshu Grover & Arun Bansal & Sunit C. Singhi
Received: 23 April 2011 / Accepted: 11 May 2011 / Published online: 26 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Foreign body aspiration into the airway is one of
the dramatic pediatric emergencies. It is more common in
children aged 6 months to 5 years. Pea nuts and food items
account for most cases. Right main stem bronchus is the
most common site involved. The initial cough and choking
like episodes may be followed by a symptomless interval
before leading to further complications. Chest radiograph
findings may vary from normal to hyperinflation, obstruc-
tive emphysema or pneumothorax. Removal by rigid
bronchoscopy is the definitive treatment.
Keywords Foreign body . Choking . Bronchoscopy
Introduction
Foreign body aspiration is one of the common emergency
problems encountered in pediatric age group. At PGIMER,
it is responsible for approximately 0.6% of admissions in
pediatric emergency [1]. A male preponderance has been
noted. Delay in identification can lead to complications
including death. Most common age group affected is
6 months to 5 years. Most common objects inhaled are
pea nuts and food items. Organic objects may cause local
inflammation and swelling and convert partial obstruction
to complete obstruction. According to various studies, the
right main stem bronchus is the most common site of
obstruction [2, 3]. The larynx is the least common site.
S. Grover : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
The following factors make the children more prone to
foreign body aspiration:
1) Absence of molars—inadequate chewing
2) In-coordinated swallowing mechanism
3) Curiosity / carelessness
Pathophysiology
The pathophysiology (and clinical picture) depends upon
the type of foreign body and location in the airway. The
object itself may cause obstruction. Foreign body causing
total obstruction at trachea/larynx may cause respiratory
failure/arrest and death within minutes. Acute obstruction
of the level of carina or main bronchus may cause lung
collapse and hypoxemia. Overtime, pooled secretion
caused by partial obstruction may get infected and
present with pneumonia. A sharp foreign body (FB)
may lead to erosion, as is the case with battery cells.
Vegetable matter may swell over hours or days leading to
obstruction. Organic foreign bodies (nuts) may produce
inflammation and edema.
Clinical Features
There may be definite history of foreign body aspiration
in 40–70% cases [4, 5]. The initial symptoms may include
cough, gagging, choking, wheezing, dyspnea, cyanosis,
hoarseness, and drooling. Partial obstruction at larynx may
present with inspiratory stridor, drooling and voice
change.
Partial obstruction at trachea often presents with chok-
ing, cough, whereas partial obstruction at bronchus presents
1402 Indian J Pediatr (November 2011) 78(11):1401–1403

Fig. 1 Flowchart showing Man-

Evaluate and maintain ABC (Airway, Breathing, Circulation)
agement of suspected airway for-
eign body aspiration in children Examine throat for visible foreign body

Start oxygen (if distress) and antibiotics (if suspected infection)

X-ray chest

Definitive history
Doubtful history
Strong suspicion of foreign body

Foreign body removal by rigid Check bronchoscopy

bronchoscopy

Observe for 12-24 h after

bronchoscopy till respiratorydistress
settles*

*Note: Even after removing the foreign body, inflammatory changes and edema may persist for
some time leading to persistence of the symptoms.

with wheezing (localized/ generalized) cough and lateraliz- Investigations

ing finding.
Initial symptoms may resolve (symptomless interval)
due to adaptation of the surface sensory receptors to
pressure. After a few hours to weeks, it is followed by
complications such as airway obstruction and infection. In
up to one-third of cases, there may be no history of foreign
body inhalation.
Overall, cough is the most common symptom seen in
76%, followed by wheezing (50%), respiratory distress
(36%), and history of cyanosis (30%) [4, 5]. Classical
physical finding of unilateral decrease of air entry on the
affected side is seen in 61% cases.
Differential Diagnosis
In absence of typical history of choking, sometimes it may
be difficult to differentiate wheeze and respiratory distress
caused by airway foreign body from bronchial asthma and
pneumonia. In asthma, there is often a history of recurrent
symptoms with good response to bronchodilators and a
positive family history. The wheeze is generally audible all
over the chest. Patients with pneumonia have history of
fever and respiratory distress but no history of choking or
acute onset symptoms. Ausculation reveals crackles. How-
ever, sometimes it may be difficult to differentiate;
pneumonia may occur as a complication of a foreign body
inhalation.
All cases suspected of foreign body aspiration presenting to
the pediatric emergency should be thoroughly examined
and evaluated based on the clinical status (Fig. 1).
Blood Investigations
Total leukocyte count and blood cultures may be
required in cases of suspected infection/pneumonia.
Blood gas analysis may be required in patients with
respiratory distress.
Chest Radiograph
A chest radiograph must be obtained in all the cases of
suspected foreign body aspiration even in the absence of
clinical symptoms. Plain radiographs during inspiration and
expiration are useful to identify the hyperinflation or other
pathological findings (Fig. 2a and 2b).The following
findings may be noted [4]:
& Hyperinflation or loss of volume on the affected side
& Obstructive emphysema.
& In 8–10% cases, foreign bodies are visible on X-ray
(some foreign bodies being organic are radiolucent).
& Infiltrates
& Atelectasis
& Air leak or pneumothorax .
Indian J Pediatr (November 2011) 78(11):1401–1403
Fig. 2 a Chest radiograph of 1- year- old, showing loss of volume on
left side, caused by small pieces of pea-nut in left main bronchus. b
Chest radiograph of a one and half year old showing hyperinflation on
left side. Bronchoscopy reveled piece of groundnut just at the opening
of left main bronchus
The chest radiograph may be normal in about 30% of the
cases.
Bronchoscopy
For confirmation and removal of the foreign body, definitive
investigation is rigid bronchoscopy. In case of doubt, one can
consider a fibreoptic bronchoscopy to confirm the diagnosis.
Other Investigations
Fluoroscopy, lung scan or CT scan do not improve
diagnostic accuracy compared to history, physical
examination and chest radiograph.
CT virtual bronchoscopy may be helpful in cases of
large foreign body in main airways. It may not be
1403
useful if foreign body is small and lodged beyond main
stem bronchi [6].
Figure 2a shows chest radiograph of a 1- year- old boy
admitted with episodes of fever (mild/undocumented),
cough, noisy, fast breathing, last one being 3 months ago.
He was on oral and IV medications and nebulization. On
Initial Examination, respiratory rate was 62 /min, wheeze +
++, with moderate subcostal and intercostals retractions.
Initially he was managed as a case of acute asthma with
nebulized salbutamol, Budesonide, IV hydrocortisone,
MgSO4 infusion, but without significant responses. On
review there was differential air entry (Left side > Right
side), but no clear history of foreign body aspiration was
forthcoming. Chest radiograph showed loss of volume on
left side. A possibility of neglected foreign body was
considered. Rigid Bronchoscopy revealed small pieces of
pea nut in left main bronchus. Post- Bronchoscopy
respiratory distress settled.
Treatment
Pediatric surgeon or ENT surgeon should be consulted for
rigid bronchoscopy; bronchoscopic removal is the defini-
tive treatment.
Conflict of Interest None.
Role of Funding Source None.
References
1. Somanath BP, Singhi S. Airway foreign bodies in children. Indian
Pediatr. 1995;32:890–7.
2. Zhiiun C, Fugao Z, Niankai Z, Zingjing C. Therapeutic experience
from 1428 patients with pediatric tracheobronchial foreign body. J
Pediatr Surg. 2008;43:718–21.
3. Van Looij MA, Rood PP, Hoeve LJ, Borgstein JA. Aspirated
foreign bodies in children. Clin Otolaryngol Allied Sci.
2003;28:364–7.
4. Sehgal A, Singh V, Chandra J, Mathur N. Foreign body aspiration.
Indian Pediatr. 2002;39:1006–10.
5. Shivakumar AM, Naik AS, Prashanth KB, Shetty KD, Praveen DS.
Tracheobronchial foreign bodies. Indian J Pediatr. 2003;70:793–97.
6. Sodhi KS, Saxena AK, Singh M, Rao KL, Khandelwal N. CT
virtual bronchoscopy: a new non invasive tool in pediatric patients
with foreign body aspiration. Indian J Pediatr. 2008;75:511–3.
Indian J Pediatr (March 2012) 79(3):362–366
DOI 10.1007/s12098-011-0497-7

SYMPOSIUM ON PGIMER PROTOCOLS ON NEUROLOGICAL EMERGENCIES

Fainting Attacks in Children

Kirti M. Naranje & Arun Bansal & Sunit C. Singhi

Received: 12 May 2011 / Accepted: 1 June 2011 / Published online: 22 June 2011
# Dr. K C Chaudhuri Foundation 2011

Abstract Fainting attack or syncope in children is a Definition

common occurrence, with vasovagal syncope being the
commonest cause for majority of pediatric syncope. The
aim of emergency room evaluation is not to miss the rare
serious underlying disorder causing syncope. A complete
detailed history of the event followed by physical exami-
nation helps in categorising syncope into the three major
categories—neurally mediated, cardiovascular and non
cardiovascular syncope. Investigations will remain normal
in majority of the cases. A 12-lead ECG and standing test
should be done in all the cases which helps in establishing
the cause for syncope. Management varies depending upon
the cause and majority of them do not require hospital
admission.
Keywords Syncope . Standing test . Head up tilt test .
Vasovagal syncope
Syncope is defined as transient loss of consciousness
and postural tone caused by reduced cerebral perfusion.
It is characterized by sudden onset loss of consciousness
because of a lack of cerebral blood flow; falls of the
patient if he or she is not supported; and transient
attacks [2].
Etiology
Most children presenting to emergency department have a
benign cause for syncope; the commonest being vasovagal
syncope. Common causes of syncope can be broadly
divided into three major categories (Table 1).

Introduction
Fainting or syncope is a common clinical problem in
children and adolescents, with as many as 15% of children
experiencing at least one episode of syncope before the end
of adolescence. The overall incidence in children is 0.1–
0.5% and constitutes 1–3% of emergency visits [1]. The
vast majority of episodes of syncope are benign and only a
minority are caused by something potentially more serious
or even life threatening.
Evaluation
The aim of emergency evaluation is not to miss the rare
occurrence of serious underlying disorder in a child with
syncope and to differentiate syncope from seizures
(Table 2). A thorough clinical evaluation, including
history and physical examination is the first step in
identifying the three major categories of syncope (Tables 3
and 4).
Laboratory Investigations

K. M. Naranje : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh, India
e-mail: sunit.singhi@gmail.com
Laboratory investigations for syncope in childhood will
almost always be normal; the key to the diagnosis is a
detailed and careful history. A 12-lead ECG is required
in all children with syncope with special emphasis on the
Indian J Pediatr (March 2012) 79(3):362–366
Table 1 Common causes of pediatric syncope and their relative
incidence in children [2, 3]
Categories of syncope Causes
(Incidence %)
Neurally-mediated Vasovagal syncope
syncope (73) Reflex syncope
Orthostatic hypotension
Postural orthostatic tachycardia
syndrome
Cardiovascular
syncope (2.9)
Arrhythmias
Tachyarrhythmia Long QT syndrome
WPW syndrome
Bradyarrhythmia Heart block
Sick sinus syndrome
Structural Congenital heart diseases
Aortic stenosis
Cardiomyopathies
Non-cardiovascular
syncope (24)
Neurological (2.1) Seizures
Migraine
Psychogenic Conversion reaction
(pseudosyncope) (2.3) Depressive disorder
Generalised anxiety disorder
Hyperventilation
Metabolic (0.8) Hypoglycemia
Severe anemia
Drugs
Carbon monoxide
Electrolyte abnormalities
Unexplained syncope (18.9)
QT interval and T wave morphology for evidence of long
QT syndrome. In most cases, no further diagnostic tests
are needed when the history, physical examination and
ECG suggest neurally mediated syncope. A standing test
should be performed at this stage to identify neurally
Table 2 Key differences
between seizure and Features
syncope [4]
Precipitating factors
Prodromal symptoms
Posture at onset
Duration
Episode
Post event state
363
mediated syncope. Further diagnostic work up is required
if the following are present [2]:
& Exercise-induced syncope that occurs during exertion
& Chest pain that precedes an episode of fainting
& Seizure activity
& Recurrent syncope (three or more episodes)
& An abnormal cardiac examination
& Unexplained syncope
For Cardiovascular Syncope
& Chest radiograph
& Echocardiography
& Holter ECG
& Electrophysiological studies
For Non-cardiovascular Syncope
& Neurology referral for EEG, CT or MRI head
& Psychiatric referral
& Metabolic-blood glucose, complete blood count,
electrolytes, toxicological screen
For Unexplained Syncope
& Head up tilt test
Head Up Tilt Test (HUT)
The child is asked to rest supine for 15 min and is then
tilted to 60° head-up for a maximum of 45 min. During
this time the blood pressure and ECG are continuously
recorded. HUT is considered positive when syncope is
reproduced in association with hypotension (decrease in
systolic blood pressure >60% of the maximal value
observed in the upright position), bradycardia (decrease
>30% of the maximal value observed in the upright
position), or both. Three patterns of positive response
according to the changes in blood pressure and heart rate
are: (1) the cardioinhibitory pattern, which is character-
ized by a rapid decrease in heart rate, presenting as
bradycardia; (2) the vasodepressor pattern, with a rapid
decrease in blood pressure; and (3) the mixed pattern,
which is most common, in which both blood pressure
Seizures Syncope
Usually absent Usually present
May or may not be present Usually present
Any Usually standing
Few minutes Usually few seconds
Staring spells or atypical limb or facial Loss of consciousness and
movements prior to loss of tone tone at the onset
Drowsiness for minutes to hours Sleepiness for <5 min
364 Indian J Pediatr (March 2012) 79(3):362–366

Table 3 History taking in pediatric syncope

Key element History Significance

Detailed description Duration, posture, recovery Variable for each type

Precipitating factors
Prodromal features
Associated symptoms
Others
Emotional stress such as fear, anxiety or sudden Suggests neurally mediated/vasovagal syncope
change in posture, hunger, and a crowded or
poorly ventilated or warm and humid environment
Light-headedness, dizziness, nausea, shortness of Suggests neurally mediated/vasovagal syncope
breath, pallor, diaphoresis and visual changes
Chest pain, palpitations, breathlessness Suggests cardiovascular syncope
No prodrome
Prolonged loss of consciousness
Recurrent syncope
Exercise induced
Family history of similar episodes, sudden
unexplained death or cardiac illness
Seizure like activity, incontinence occurring in Suggests neurological syncope
infancy and recurrent syncope
Headache
Past and family history of seizures
History of recent medication Drugs (carbamazepine, tricyclic antidepressants,
astemizole, terfenadine, alcohol, cocaine)
Anemia, dehydration Anemia, electrolyte imbalance (hyponatremia)
Fall/injuries Significant underlying disease

and heart rate decrease during the tilting and is usually during the test. Figure 1 summarises approach to a child
seen with vasovagal syncope [5]. with syncope in emergency department.

Standing Test
Standing test is performed in a quiet and warm environ-
ment. Blood pressure and pulse are recorded after child had
rested in a supine position for at least 5 min. He is then
asked to stand for 10 min, and pulse and blood pressure are
measured immediately and after 1, 2, 3, 5 and 10 min [3].
Orthostatic hypotension is identified as persistent decrease
of more than 20 mmHg systolic blood pressure or decrease
of more than 10 mmHg diastolic blood pressure within
3 min after the start of HUT or standing test [6].
These tests should be done cautiously. Resuscitation
equipment should be available at hand on the bedside
Management
Syncope usually does not require hospital admission. The
indications for hospital admission include
& Syncope occurring several times a day
& Infants who have recurrent and severe episodes of
syncope
& Abnormal cardiac rhythm disturbances requiring acute
stabilisation
& Abnormal neurological/metabolic state requiring acute
stabilisation

Table 4 Clinical examination in pediatric syncope

Key element Examination finding Significance

Pulse Tachycardia/bradycardia, regular/ Tachycardia in postural orthostatic tachycardia syndrome

irregular Abnormal in cardiogenic syncope
Blood pressure Supine and standing variation with Suggests neurally mediated syncope (e.g., orthostatic hypotension)
posture
General physical Pallor, cyanosis, clubbing Anemia, cyanotic congenital heart disease
examination
Cardiac examination Murmurs, clicks, gallops Specific cardiac disease
Neurological Focal deficit, injuries, tongue bite Suggests neurological syncope (e.g., post ictal, transient ischemic attacks)
Indian J Pediatr (March 2012) 79(3):362–366 365

Child with history suggestive of syncope

• Baseline stabilisation –maintain airway, breathing, circulation

• Detailed history and focused clinical examination

• 12-lead ECG, blood glucose

• Standing test

ECG –Normal ECG – Abnormal ECG –Normal

Standing test -Positive Standing test -Negative Standing test -Negative

Neurally mediated syncope Cardiovascular syncope Non cardiovascular syncope

Vasovagal syncope Cardiology referral

Neurological Metabolic Psychogenic Unexplained
Orthostatic hypotension Chest radigraph

Reflex syncopes Echocardiography Neurology Electrolytes Observation HUT

referral
-Breath holding spells Holter ECG CBC Psychiatric
EEG consultation +ve -ve
- Micturation syncope Electrophysiological Toxicological
studies CT/MRI screen
Conversion
NMS
Reassurance Depression
Arrhythmias Seizures Hypoglycemia
Plenty of fluids Reappraisal
Structural heart lesions Migrane Hyponatremia Anxiety disorder
Salt intake Follow up
Long QT syndrome Anemia Hyperventilation
Postural maneuvers Specific
management Drugs
Specific management Specific drugs

Specific Behavioural
management therapy

Fig. 1 Approach to a child with syncope, Abbreviations: CBC Complete Blood Count, HUT Head Up Tilt Test, NMS Neurally Mediated Syncope

Neurally Mediated Syncope & Temporary pacemaker therapy for a sick sinus or heart block
& Disposition—Cardiology referral for definitive management
& Reassurance—especially that the episodes are not
caused by epilepsy or a cardiac problem
& Prevent triggering events Non-cardiovascular Syncope
& Plenty of fluids; older children and adolescents should & Neurological
be advised to drink around 2 L water or fluids per day
& Small amount of salty food – Antiepileptics for seizures
& Manoeuvres such as crossing the legs and folding the – Neurology consultation
arm, sitting or lying down at the onset of prodromal
symptoms & Metabolic
& Drugs are reserved for syncope not responding to above – Dextrose for hypoglycaemia
measures and frequent and recurrent episodes [7]. – Correction of electrolyte imbalance
– Fludrocortisone 100 μg/d – Iron supplements for anemia
– Specific management for drug overdose, carbon
– Beta-blockers
monoxide poisoning
& Disposition—Pediatric outpatient department follow up
& Psychogenic
Cardiovascular Syncope
– Psychiatric consultation
& Management of arrhythmias, wherever applicable – Anxiolytics, antidepressants and/or behavioral thera-
& Beta-blocker therapy in cases of long QT syndrome py after specialist consultation
366
– Disposition—neurology, psychiatric referral accord-
ingly. If none, pediatric outpatient department
follow up.
Key Points
& Fainting attack or syncope is a common occurrence in
pediatric population with 15% of children experiencing at
least one episode of syncope before the end of adolescence.
& Majority of the causes for syncope are benign, with
vasovagal syncope being the commonest one.
& Neurally mediated, cardiovascular and non-cardiovascular
syncope are the three major categories of causes for
pediatric syncope.
& Seizures remain the close differential diagnosis of
syncope in emergency room.
& A 12-lead ECG and standing test should be performed
in all children presenting with syncope.
& For unexplained syncope, a head up tilt test should be
done to diagnose neurally mediated syncope.
& Neurally mediated syncope is managed conservatively
with reassurance , plenty of fluids, salty food and certain
manoeuveres. Drugs are reserved only for refractory cases.
& Mainstay of cardiovascular syncope is management of
arrythmias and long QT syndrome.
Indian J Pediatr (March 2012) 79(3):362–366
& Management of non-cardiovascular causes of syncope
is according to the cause.
Conflict of Interest None.
Role of Funding Source None.
References
1. Singhi S, Singhi P. Syncope. In: Singhi S, Surpure J, editors.
Synopsis of Pediatric emergency care. 2nd ed. India: Peepee; 2010.
pp. 291–6.
2. Côté J-M. Syncope in children and adolescents: evaluation and
treatment. Paediatr Child Health. 2001;6:549–51.
3. Zhang Q, Du J, Wang C, Du Z, Wang L, Tang C. The diagnostic
protocol in children and adolescents with syncope: a multi-centre
prospective study. Acta Pediatr. 2009;98:879–84.
4. Singhi P. Non epileptic events: differential diagnosis of epilepsy. In:
Singhi P, editor. Seizures & epilepsy in children: a practical guide.
1st ed. India: Noble Vision; 2008. pp. 29–48.
5. Zhang Q, Du J, Jianjun C. Association of clinical characteristics of
unexplained syncope with the outcome of head-up tilt tests in
children. Pediatr Cardiol. 2004;25:360–4.
6. Stewart JM. Orthostatic intolerance in pediatrics. J Pediatr.
2002;140:404–11.
7. Benditt D, Fahy G, Lurie K, et al. Pharmacotherapy of neuro-
cardiogenic syncope. Circulation. 1999;100:1242–8.
Indian J Pediatr (March 2012) 79(3):367–375
DOI 10.1007/s12098-011-0555-1
SYMPOSIUM ON PGIMER PROTOCOLS OF NEUROLOGICAL EMERGENCIES
Non-Traumatic Coma and Altered Mental Status
Atul Jindal & Sunit C. Singhi & Pratibha Singhi
Received: 9 July 2011 / Accepted: 2 August 2011 / Published online: 26 August 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Non traumatic coma in childhood is an
important emergency. It can result from wide range of
etiologies. CNS infections are the most common cause of
non traumatic coma in children. However, multiple
interrelated factors may be present in one patient.
Management of a comatose child goes hand in hand
with clinical evaluation. It is an emergency that requires
simultaneous institution of immediate life support,
identification of the cause and institution of definite
therapy. The primary goal is to establish airway,
breathing and circulation and to identify and treat raised
intracranial pressure and seizures.
Keywords Coma . Encephalopathy . Impaired
consciousness . Intracranial pressure
Introduction
Non traumatic coma in childhood is a common pediatric
emergency. The incidence of non traumatic coma is 30/
100,000 children per year [1]. The diagnosis and manage-
ment of a comatose child in the emergency room is a
challenging task. Central nervous system (CNS) infections
are the most common cause of non traumatic coma in
children in the authors’ setting [2]. Regardless of the
A. Jindal : S. C. Singhi (*) : P. Singhi
Department of Pediatrics, and Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research
(PGIMER),
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
etiology, initial management of the comatose child in
emergency room involves immediate attention to sustain
life and prevent irreversible damage.
Definitions
Consciousness is a state of awareness of self and
surroundings which involves complex interaction of cere-
bral cortex and reticular activating system. This state is
determined by two separate functions:
& Awareness (content of consciousness), depends on an
intact cerebral cortex.
& Arousal (level of consciousness), depends on an intact
ascending reticular activating system (ARAS) and its
connections with diencephalic structures.
Coma is a state of altered consciousness with loss of
both wakefulness (arousal) and awareness of self and
surroundings characterized by a state of sustained, patho-
logic, unarousable unresponsiveness and absence of sleep-
wake cycles, which must last for at least 1 h [3].
Vegetative state describes a condition of complete
unawareness of the self and the environment accompanied
by sleep wake cycles with variable preservation of
brainstem functions [4].
Minimally conscious state is defined as a condition of
severely altered consciousness in which the patient dem-
onstrates minimal but definite behavioral evidence of self-
or environmental awareness [5].
Brain death is defined as the permanent absence of all
brain functions including those of the brainstem [6].
Descriptive terms such as somnolence, stupor, obtunda-
tion, and lethargy used to denote different levels of
368
wakefulness are best avoided, given the lack of uniformity
in the way these states are defined in the literature [7].
Etiopathogenesis
Common causes of non-traumatic coma seen in children in the
authors’ emergency department are central nervous system
infections, which includes tubercular meningitis (19%),
encephalitis (18%), and bacterial meningitis (16%),toxic-
metabolic encephalopathies (19%), status epilepticus (10%),
intracranial bleed (7%), and other (4%) [2]. Coma can be due
to a primary/direct insult to the cerebral cortex, diencephalic
structures, midbrain or rostral pons, or a secondary manifes-
tation of systemic derangements caused by toxins, metabolic
or endocrine disorders (Table 1). However, multiple interre-
lated factors may be present in one patient.
Coma can be precipitated by a critical hemispheric lesion
if there is bilateral diffuse involvement, or a large unilateral
lesion causing midline shift leading to central or tentorial
herniation with midbrain compression, compromising prox-
Table 1 Causes of
non-traumatic coma in Infections
children Tubercular meningitis
Viral meningoencephalitis
Bacterial meningitis
Cerebral malaria
Rickettsial meningoencephalitis
Rabies
Brain abscess
Subdural/epidural empyema
Toxic encephalopathy ( enteric fever, shigella
encephalopathy)
Severe systemic infections with shock
Post infectious
Acute demyelinating encephalomyelitis
Acute necrotising encephalopathy
Hemorrhagic shock encephalopathy syndrome
Post immunisation
Whole cell DPT
Semple rabies vaccine
Hypoxia-ischemia
Shock
Cardiac/pulmonary failure
Near drowning
Vascular
Arterial ischemic stroke
Sinus venous thrombosis
Intracranial bleed
Indian J Pediatr (March 2012) 79(3):367–375
imal elements of ARAS. However, comparatively small
brainstem and diencephalic lesions that disrupt or impair
the ARAS and its projections can cause coma.
Toxic and metabolic etiologies of coma have been linked
to an interruption in the delivery or utilization of oxygen or
substrate (hypoxia, hypoglycemia); alterations in neuronal
excitability and signalling (seizures, drug toxicity, acidosis)
or changes in brain volume (hyper/hyponatremia).
The degree of neurologic impairment is related to the
time course of the underlying cerebral pathology. An acute
lesion is usually associated with depressed consciousness
whereas a slowly developing lesion at identical location and
volume may be asymptomatic.
Evaluation of a Comatose Child
Management of a comatose child goes hand in hand with
clinical evaluation. It is an emergency that requires
simultaneous institution of immediate life support, identifi-
cation of the cause and definitive therapy.
Metabolic
Hypoglycemia
Diabetic ketoacidosis
Uremia
Hyperammonemia (hepatic encephalopathy, Reye
syndrome, disorders of fatty acid metabolism)
Mitochondrial encephalopathies
Dyselectrolytemia (hyponatremia, hypernatremia,
hypercalcemia, hypermagnesemia, hypophosphatemia)
Acute Porphyria
Acidosis/alkalosis
Toxic
Opioids
Barbiturates
Organophosphates and carbamates
Sedatives
Tricyclic antidepressants
Lead encephalopathy
Snake bite
Structural
Tumor
Hydrocephalus
Miscellaneous
Post ictal state
Status epilepticus (convulsive, non convulsive)
Hypertensive encephalopathy
Acute complicated migraine
Indian J Pediatr (March 2012) 79(3):367–375
Primary Assessment and Emergency Management
& The primary goal is to establish airway, breathing and
circulation and to identify and treat raised intracranial
pressure (ICP).
& Establish airway by jaw thrust/ oropharyngeal airway
and give high flow oxygen by mask.
& Perform endotracheal intubation by rapid sequence
induction and start bag ventilation if the patient has
modified Glasgow coma score≤8, impaired airway
reflexes, shock or evidence of herniation. Invasive
interventions can aggravate ICP; avoid trauma as far as
possible and try to keep oxygen saturation above 92%.
& If signs of compensated/ hypotensive shock are present,
establish a vascular access and resuscitate with isotonic
saline and inotropes. If there is high BP at contact, it could
be both cause and effect of coma; reduce it slowly.
& Assess level of consciousness using the modified
Glasgow coma scale (GCS) (Table 2). If in doubt on
scoring, record a lower score initially.
& Examine the fundi for papilledema (rarely seen in acute
encephalopathy; absence does not exclude intracranial
hypertension), retinal hemorrhage, and macular star
suggestive of hypertension.
& Look for tonic deviation of the eyes or nystagmus. If
there is tonic deviation of the eyes or nystagmus,
assume subtle status epilepticus and give benzodiaze-
pine (inj. Lorazepam 0.1 mg/kg or inj. diazepam
0.3 mg/kg) and load with inj. Phenytoin 20 mg/kg.
& Assess brain stem function (Table 3) and decide whether
the patient has evidence of herniation or raised ICP
Table 2 Modified Glasgow
coma scale [8] >5 y
Eye opening
4 Spontaneous
3 To voice
2 To pain
1 None
Verbal
5 Orientated
4 Confused
3 Inappropriate words
2 Incomprehensible sounds
1 No response to pain
Motor
6 Obeys commands
5 Localises to supraocular pain (>9 mo)
4 Withdraws from nailbed pressure
3 Flexion to supraocular pain
2 Extension to supraocular pain
1 No response to supraocular pain
369
(Table 4). If signs of raised ICP or impending herniation
are present, start manual hyperventilation with a bag
(PaCO2 30–35 mmHg) and give 20% mannitol (0.5 g/kg)
or hypertonic saline (preferred if patient in shock).
& Perform Dextrostix testing and send for simultaneous
venous blood sugar. Give dextrose 2 ml/kg of 25% dextrose
or 5 ml/kg of 10% dextrose if blood sugar is<60 mg/dl and
increase glucose infusion rate to 6–8 mg/kg/min.
& Take samples for serum electrolytes, arterial blood
gases, lactate, complete blood count, platelet count,
blood cultures, liver and kidney function tests, MP
smears, toxicology screen, urine sugar and ketones.
& Maintain normothermia—treat fever and hypothermia.
& In a febrile child give empiric first dose of ceftriaxone
(100 mg/kg i.v. in 2 divided doses) and acyclovir/
artesunate as indicated, obtain CT scan and decide about
further management.
– In a child with focal neurologic deficit, focal seizures,
behavioral changes, aphasia, neuroimaging suggestive
of fronto-temporal involvement or hemorrhagic CSF,
give first dose of Acyclovir (30 mg/kg i.v. in 3 divided
doses) and obtain MRI.
– If child is resident of P.falciparum endemic area, and
has hypoglycemia, anemia or absent meningeal signs
then give empiric IV Artesunate/Quinine.
Focussed History
A detailed history may not be available during initial
resuscitation phase of the comatose child but it should be
<5 y
5Alert, babbles, coos, words or sentences—normal
4 Less than usual ability, irritable cry
3 Cries to pain
2 Moans to pain
1 No response to pain
6 Normal spontaneous movements
5 Localises to supraocular pain
4 Withdraws from nailbed pressure
3 Flexion to supraocular pain
2 Extension to supraocular pain
1 No response to supraocular pain
370 Indian J Pediatr (March 2012) 79(3):367–375

Table 3 Focussed Clinical

Examination and Localisation Respiratory pattern Normal Brainstem intact
in Coma Cheyne-Stokes Diencephalic
Hyperventilation Midbrain/upper pontine
Ataxic, shallow Lower pontine
Gasping, slow, irregular Medullary
Posture Normal Brainstem intact
Hemiparesis Uncal herniation
Decorticate Diencephalic
Decerebrate Midbrain/upper pontine
Flaccid Lower pontine
Response to pain Flexion to supraocular pain Diencephalic
Extension to supraocular pain Midbrain/upper pontine
None Lower pontine
Tone/reflexes/plantars Normal Brainstem intact
Unilateral pyramidal Uncal herniation
Bilateral pyramidal Diencephalic
Flaccid/extensor plantars Lower pontine
Oculocephalic (doll’s eye) Saccadic eye movements Normal forebrain control
Exclude cord injury Full deviation eyes away Diencephalic
Turn head from side to side, watch eyes Minimal deviation eyes Midbrain/upper pontine
No movement eyes Lower pontine
Pupil size Normal midpoint Midbrain/upper pontine
Small Diencephalic
Unilaterally large Uncal herniation
Bilaterally large Lower pontine
Italics refers to clinical signs of Pupil response to light Brisk Brainstem intact
potentially reversible cerebral Bright torch Unresponsive Midbrain/upper pontine
herniation

Table 4 Clinical signs

suggestive of various herniation
syndromes
Italics refers to clinical signs of
potentially reversible cerebral
herniation
Uncal Unilateral fixed dilated pupil
Unilateral ptosis
Minimal deviation of eyes on oculocephalic/oculovestibular testing
Hemiparesis
Diencephalic Small or midpoint pupils reactive to light
Full deviation of eyes on oculocephalic/oculovestibular testing
Flexor response to pain and/or decorticate posturing
Hypertonia and/or hypereflexia with extensor plantars
Cheyne–Stokes respiration
Midbrain/upper pontine Midpoint pupils, fixed to light
Minimal deviation of eyes on oculocephalic/oculovestibular testing
Extensor response to pain and/or decerebrate posturing
Hyperventilation
Lower pontine Midpoint pupils, fixed to light
No response on oculocephalic/oculovestibular testing
No response to pain or flexion of legs only
Flaccidity with extensor plantars
Shallow or ataxic respiration
Medullary Pupils dilated and fixed to light
Slow, irregular, or gasping respiration
Respiratory arrest with adequate cardiac output
Indian J Pediatr (March 2012) 79(3):367–375
obtained as quickly as possible, as it may be crucial for
identification of the cause of coma. The history should
include details of events prior to coma, with special
attention to timing, exposures, and accompanying symp-
toms. Sudden onset of coma suggests spontaneous intra-
cranial hemorrhage or seizure. Slowly worsening state of
consciousness suggests hydrocephalus, an expanding mass
lesion, or indolent infection. Recent history of fever
suggests an infectious etiology but other disorders such as
Acute Demyelinating Encephalomyelitis (ADEM), Reye
syndrome or mitochondrial disorders must also be consid-
ered. Ask for history of seizures, rash, diabetes, trauma,
toxin exposure, snake bite, heat exposure, diarrhea, past
medical illness and family history. Suspect child abuse if an
infant/toddler develops sudden unexplained coma.
Focussed Examination
Look and record vitals. Fever is often a pointer to meningitis,
encephalitis, sepsis, pneumonia or brain abscess and some-
times of ADEM, Reye syndrome or heat stroke. Hypothermia
is seen in shock. Bradycardia is seen with raised ICP,
hypothermia, or hypoxia; tachycardia may be caused by
fever, raised ICP, shock states, myocarditis. Tachypnea may
be seen in sepsis, shock, pneumonia, and acidosis. Hypoten-
sion is seen in shock and may result in hypoxic ischemic
injury. Hypertension may be a feature of raised ICP or it may
be because of hypertensive encephalopathy. In hypertensive
encephalopathy there will be diastolic hypertension, with
associated findings of left ventricular hypertrophy (on ECG
and ECHO) and there may be changes in retina suggestive of
hypertensive retinopathy.
General Physical Examination
Presence of cyanosis, jaundice (hepatic encephalopathy,
complicated malaria, leptospirosis, enteric fever), pallor
(intracranial bleed, dengue, malaria), hyperpyrexia >40°C
(neuroleptic malignant syndrome, heat stroke), rash (den-
gue, measles, rickettsia, meningococcemia, mycoplasma,
viral exanthem), petechiae (dengue, DIC secondary to
severe sepsis, meningococcemia), edema (dengue, sepsis,
liver failure), dysmorphism, abnormal odour(sweet in
DKA, musty in hepatic and urine like in uremia), neuro-
cutaneous markers or any evidence of trauma could provide
important clue to the etiology.
Systemic Examination
Hepato-splenomegaly (malaria, enteric fever, viral hepatitis,
sepsis), murmurs (congenital heart disease, rheumatic fever,
infective endocarditis), signs of infective endocarditis, and
evidence of pneumonia may be helpful clues to the cause.
371
Neurological Examination
The neurologic examination is directed toward localising
brain dysfunction, identifying etiology, and determining
early indicators of prognosis. In a comatose child, exami-
nation requiring patient cooperation (mental status, sensory
testing) cannot be performed and hence examination is
directed towards assessing response to stimuli and brain-
stem and motor functions.
Level of consciousness Record level of consciousness
objectively by GCS score in children >5 y and modified
GCS score in children <5 y. GCS has several important
limitations. Subtle alterations in wakefulness and brainstem
findings may not be picked by GCS. It is difficult to
comment on the GCS of patients who are sedated or
intubated. It is always better to record detailed description
of clinical findings and detects changes over time in such a
situation.
Cranial nerves Cranial nerve evaluation helps in identifying
brainstem and cortical control of cranial nerve pathways.
Fundus examination gives information about retina and
optic nerve. Papilledema is seen in raised ICP, however its
absence does not rule out raised ICP as it takes hours to
days to develop papilledema. Retinal haemorrhages are
seen in inflicted child trauma and disorders of coagulation.
Soft and hard exudates with flame shaped hemorrhages are
seen in hypertensive encephalopathy.
Pupils should be examined for size, shape, symmetry,
and response to light. Pupillary size and reactivity are
controlled by centres in the brainstem which are adjacent
to those that maintain consciousness, and hence, brain
stem lesions commonly lead to abnormality of pupillary
reactivity and size. These pupillary changes are a valuable
guide to the presence and location of brain lesions and
also help in differentiating between metabolic encephalo-
pathies and structural lesions; these signs appear late in
metabolic encephalopathies. Unilateral pupillary dilatation
in a comatose patient is a sign of oculomotor nerve
compression from ipsilateral uncal herniation until proved
otherwise. (Table 5 for pupillary abnormalities in different
conditions.)
Brainstem function The details are given in Table 3.
Meningeal signs Seen in meningitis, subarachnoid
hemorrhage.
Herniation syndromes The details are given in Table 4.
Also look for focal deficits which may suggest presence
of intracranial space occupying lesion (abscess, tuber-
culoma, infarcts).
372
Table 5 Pupil abnormalities in
coma Etiology/localization
Pontine
Opiate/ Organophosphate poisonings
Hypothalamic
Metabolic
Midbrain
Oculomotor nerve, uncal herniation
Hypoxic ischemic encephalopathy
Tectal
Anticholinergic, sympathomimetic, antidepressant poisoning
Investigations
First Line Investigations
The first line investigations that should be performed in all
children with non-traumatic coma are already listed under
section ‘Primary assessment and Emergency management’.
In febrile coma: Perform malaria card test, send smear for
malarial parasite, and blood for serological tests—JE virus,
dengue, widal, herpes simplex virus, leptospira, rickettsia,
and mycoplasma.
Perform a lumbar puncture in every febrile patient with
coma unless contraindicated. The contraindications include
clinical features of raised ICP, focal signs, thrombocytope-
nia, local infection, shock. CSF should be tested for cell
count, glucose, protein, gram stain, culture, latex aggluti-
nation, Ziehl-Neelsen stain and AFB culture(if symptom-
atology for more than 1 wk), Herpes PCR and serology, JE
PCR and serology, and additional tests as guided by clinical
suspicion.
CT scan should be performed in all children with coma
except those with a known cause of coma such as
hypoglycemia and post-ictal state. CT will readily identify
intracranial bleed, hydrocephalus, cerebral edema, compart-
mental shifts, stroke, abscess or ICSOL. Initial normal CT
does not rule out an evolving lesion of an infection or
metabolic disorder as well as raised intracranial pressure. In
herpes simplex encephalitis CT head is abnormal in
approximately 50% of cases but may be normal in the first
4–5 d [9]. CT should be done only after stabilization of the
child and one should weigh the information generated from
CT against risk of transporting a critically ill child.
Second Line Investigations
Electroencephalography (EEG) Serial EEG’s are more
useful than single isolated EEG. EEG helps in detection
of non convulsive status epilepticus as a cause of coma. It is
relatively specific in herpes simplex encephalitis (periodic
Indian J Pediatr (March 2012) 79(3):367–375
Pupil appearance
Pinpoint
Pinpoint
Small reactive
Small reactive
Mid position, fixed
Ipsilateral pupil fixed and dilated
Bilateral fixed dilated
Large, nonreactive, hippus
Dilated and fixed
lateralised epileptiform discharges). Triphasic waves may
be seen in hepatic or uremic or other metabolic encepha-
lopathies. Diffuse theta and delta activity, absence of faster
frequencies are seen in severe encephalopathies. It also
assists in prognosis of later neurologic outcome (poor with
low amplitude EEG, generalised burst suppression or loss
of reactivity to external stimuli).
Magnetic Resonance Imaging (MRI) MRI should be done
in patients with unexplained coma and normal or equivocal
CT findings. MRI is useful in diagnosing many conditions
including stroke and encephalitis. It is abnormal in around
70–80% of herpes simplex encephalitis. In herpes simplex
encephalitis, asymmetrical hyperintensities in T2 weighted
images are seen in fronto-temporal lobe, insular cortex and
cingulated gyrus. Basal ganglia and thalamic involvement
may be seen in Japanese B encephalitis. Patchy demyelin-
ation in the brain and spinal cord is seen in ADEM.
Meningeal and gyral enhancement may be seen in
meningitis. Certain inborn errors of metabolism also
have specific MRI features. Severity of the MR changes
also helps in prognostication. MRI should be done only
after stabilization of the child. The procedure may take
an hour to do and one should weigh the information
generated from it against the risk of transporting a
critical child.
Metabolic testing Blood ammonia, TMS, GCMS, thyroid
function tests, ANA, ANCA.
Treatment
Once the child is stabilised with emergency management as
described above, next comes:
1. Specific management according to etiology
2. Prevention and treatment of secondary complications
(Fig. 1).
Indian J Pediatr (March 2012) 79(3):367–375 373

Fig. 1 Flow chart showing

Stepwise approach to child with
non-traumatic coma ADEM;
Acute demyelinating encephalo-
myelitis, EEG; Electroencepha-
lography, ICP; Intracranial
Pressure, GCMS; Gas Chroma-
tography Mass Spectrometry,
NCSE ; Non convulsive Status
epilepticus, TMS; Tandem Mass
Spectrometry
Coma
Assess and optimise the airway (A), breathing (B) and circulation (C) to ensure that brain is being adequately
perfused and maintain cerebral oxygenation.
1. Obtain immediate blood glucose and correct if it is low.
2. Identify and treat seizures.
Features of raised ICP Measures to reduce ICP
e.g. Head end elevation,
Identify signs of impending herniation
Yes adequate sedation and
analgesia, hyperventilation,
mannitol/hypertonic saline

*
Focussed history and neurological examination
* Assess the level of consciousness (table 2) *Focussed neurological examination (table 3,4,5)

First line investigations in all patients

Fever
No Yes
Afebrile encephalopathy Features of CNS infections

No Yes
Sepsis – broad spectrum antibiotics Refer to protocol for Febrile
DKA – Insulin, fluid and other supportive encephalopathy
therapy.
Hepatic encephalopathy – refer to
protocol for acute liver failure.
Uremia – refer to protocol for acute renal
failure.
Heat stroke- specific treatment

Focal signs with or without raised Raised ICP without Normal ICP and
ICP focal signs No Focal Signs

Dyselectrolytemia
Urgent CT Scan Toxins – naloxone, flumazenil
Metabolic
Abnormal
Snake Bite - ASV
Normal Hypoxic
Stroke – refer to protocol for stroke. Diabetic ketoacidosis DKA
Todd’s paresis ICSOL Acute hydrocephalus Postictal
Stroke Intracranial bleed Reye’s syndrome
Brain abscess

Urgent neurosurgery
evaluation and MRI
if possible

If no improvement or no cause is ascertained, do second line investigations

MRI EEG TMS, GCMS, Ammonia
ADEM – Steroids NCSE – Antiepileptics Metabolic causes – Drug levels
Stroke treat as per protocol Thyroid function test
ESR & autoimmune screen

Specific Management dose. Atropine and pralidoxime in organophosphorus

1. Treatment of neuroinfections—Start with inj. Ceftriax-
one 100 mg/kg/d in 2 divided doses and inj Acyclovir
30 mg/kg/d in 3 divided doses.
2. Start antimalarials (quinine/artesunate) if there is
clinical suspicion of malaria.
3. Try antidotes: Naloxone (0.1 mg/kg) in suspected
opioid poisoning, Flumazenil in benzodiazepine over-
poisoning.
4. Try Antisnake venom in snake bite.
5. Corticoteroids (Methyl prednisolone, hydrocortisone)
are useful in ADEM, enteric encephalopathy, and
TBM.
6. Treatment of metabolic coma- DKA, Hepatic, uremic
and other metabolic encephalopathies according to
specific protocols.
374 Indian J Pediatr (March 2012) 79(3):367–375

Prevention and Treatment of Secondary Complications Prognosis

All comatose children should be transferred to PICU. Till Prognosis largely depends on the underlying etiology and
then following measures should continue: severity of brain injury. A patient with delayed initiation of
treatment also will have poor prognosis. In a study of 100
1. Maintain ABC, correction of hypoglycemia.
consecutive patients in the authors’ Unit , survival rate was
2. Treatment of seizures.
65%. Among those who died, deep coma (GCS<6),
3. Maintain normothermia and euglycemia.
abnormal respiration patterns, abnormalities of vitals like
4. Correct electrolyte and acid base abnormalities.
hypothermia, hypotensive shock, abnormal tone (flaccidity)
5. Ensure adequate intravascular volume by use of N/2 or
were suggestive of poor prognosis. Among acute CNS
normal saline with added glucose in full maintenance
infections, rabies, herpes encephalitis, severe stages of
doses. Restriction of fluids does not improve the
TBM had poor prognosis. Among metabolic encephalopa-
outcome.
thies, children with hepatic coma had high mortality [2].
6. Measures to control raised ICP: Keep head in midline
with 30° elevation to promote cerebral venous drainage
(but may be kept flat if the child is in shock or if the
Key Messages
mean arterial blood pressure falls with change in
position).
& Urgent management is required in any child with coma.
7. Gentle suctioning and avoid vigorous physiotherapy,
& Stabilization of ABC in emergency room is most
catheterise the bladder to prevent urinary bladder
important to sustain life and prevent secondary brain
distension and surge in ICP, ensure deloading of colon
injury.
with use of laxatives, and early institution of nasogas-
& Secure airway, oxygenate, bag ventilate to keep CO2
tric feeds.
within low normal range.
8. General care: Minimal handling, care of eyes to prevent
& Identify the signs of impending brain herniation and
exposure keratitis, frequent change of position to
treat immediately.
prevent pressure sores, adequate analgesia (morphine)
& Identify and treat seizures.
and sedation (benzodiazepines).
& Identify and treat reversible and acute causes (e.g.,
9. Look for and treat nosocomial infections.
hypoglycemia) immediately.
& Diagnosis and specific treatment depends on the
etiology of coma.
Monitoring & Prognosis largely depends on the etiology and extent of
brain damage.
Monitor continuously for vital signs (at least hourly),
changing level of consciousness (GCS hourly), neurologi-
cal status, brainstem signs, ICP, Cerebral perfusion pressure,
SpO2 and EtCO2 or ABG, assess adequate sedation and Conflict of Interest None.
analgesia, input and output daily, weigh daily if possible
and if not contraindicated (raised ICP, ventilated), urine
Role of Funding Source None.
output, bowel sounds, blood counts, serum electrolytes,
blood sugar, serum and urine osmolality, EEG.
References

Follow Up
These children should be followed up to ensure early
detection and development for long duration. They should
be looked for early development of -
& Neurologic sequelae like motor, visual and hearing
deficits.
& Developmental and intellectual disabilities.
& Learning and behaviour problems.
& Seizures
1. Wong CP, Forsyth RJ, Kelly TP, et al. Incidence, Aetiology, and
Outcome Of Non-Traumatic Coma: A Population Based Study.
Arch Dis Child. 2001;84:193–9.
2. Bansal A, Singhi S, Singhi P. Non Traumatic Coma. Indian J
Pediatr. 2005;72:467–73.
3. Medical Aspects of the Persistent Vegetative State (1): The Multi-
Society Task Force on PVS. N Engl J Med. 1994; 330:1499–1508.
4. Giacino J, Whyte J. The Vegetative and Minimally Conscious
States: Current Knowledge and Remaining Questions. J Head
Trauma Rehabil. 2005;20:30–50.
5. Giacino JT, Ashwal S, Childs N, et al. The Minimally Conscious State:
Definition and Diagnostic Criteria. Neurology. 2002;58:349–53.
Indian J Pediatr (March 2012) 79(3):367–375
6. Task Force for the Determination of Brain Death in Children.
Guidelines for the Determination of Brain Death in Children.
Pediatrics. 1987;80:298.
7. Laureys S, Owen AM, Schiff ND. Brain Function in Coma,
Vegetative State, and Related Disorders. Lancet Neurol.
2004;3:537–46.
375
8. Tatman A, Warren A, Williams A, et al. Development of a Modified
Paediatric Coma Scale in Intensive Care Practice. Arch Dis Child.
1997;77:519–21.
9. Baringer JR. Herpes Simplex Virus Encephalitis. In: Davis N,
Kennedy PGE, editors. Infectious Diseases of the Nervous System.
Oxford: Butterworth-Heinemann; 2000. p. 139–64.
Indian J Pediatr (March 2012) 79(3):376–380
DOI 10.1007/s12098-011-0570-2
SYMPOSIUM ON PGIMER PROTOCOLS IN NEUROLOGICAL EMERGENCIES
Approach to Headache in Emergency Department
Karthi Nallasamy & Sunit C. Singhi & Pratibha Singhi
Received: 21 July 2011 / Accepted: 27 September 2011 / Published online: 20 October 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Headache remains a frequently encountered
neurological symptom in Emergency department. Sec-
ondary causes of headache outnumber the primary
entities such as migraine. Most of the secondary
headaches have benign etiologies. The goal of emergent
evaluation is to detect those with serious or life
threatening causes. Identifying the pattern of headache
helps in narrowing down the possible etiological
diagnosis. A single episode of acute headache usually
results from an acute infection ranging from viral URI
to acute meningitis. Acute recurrent headaches are
typically a feature of migraine. Chronic progressive
headaches often indicate a serious underlying pathology
such as a brain tumor and warrant a detailed neurolog-
ical examination for signs of raised intracranial pressure
(ICP) and focal deficits. Children with abnormal
neurological findings require a neuroimaging. CT scan
usually detects most of the abnormalities. Initial stabi-
lization and management of raised ICP takes precedence
in sick children. While simple analgesics like para-
cetamol and ibuprofen are used for symptomatic
therapy, identification and appropriate treatment of
underlying conditions is necessary for complete resolu-
tion of headache.
Keywords Children . Headache . Migraine . Brain tumor .
Neuroimaging . Analgesics
K. Nallasamy : S. C. Singhi (*) : P. Singhi
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and
Research, (PGIMER),
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Introduction
Headache is one of the most frequent neurological
symptoms and about 60–70% children experience a
headache by the age of 7 to 9 y. However, headache as an
isolated symptom presenting to Emergency department
(ED) is less common; it is often accompanied by other
symptoms of an underlying illness. Children with acute or
acute on chronic headaches are the most frequent visitors to
emergency department while those with chronic headache
are usually seen in outpatient department.
Pathophysiology
Headache is a result of referred pain from parts of the head
and neck which include intracranial structures like the dura,
large arteries, venous sinuses and extracranial structures
like the periosteum, orbit, sinus, middle ear, teeth and facial
muscles. Pathology in the brain parenchyma alone cannot
cause headache as there are no pain receptors in it.
Common Causes
Headaches can be caused by primary entities as in migraine
or tension-type headaches or the pain may result from
secondary causes. Secondary headaches usually have
identifiable etiologies. Although the vast majority of
secondary headaches in children have benign underlying
cause (such as viral infections), the goal of the emergent
evaluation of children with headaches is to identify as a first
priority those with serious or life-threatening etiology
(brain tumors, CNS infections).
Indian J Pediatr (March 2012) 79(3):376–380
Objectives of Management in ED
Providing a diagnosis for every child who presents to ED
with a headache is challenging. The cornerstones of ED
management includes,
– Identifying the pattern of headache and possible etiology
– To exclude serious secondary causes
– To initiate appropriated therapy to relieve pain
– To give prompt referral for definitive management
Patterns and Possible Etiology
Classifying the headache symptoms into one of the
following five temporal patterns [1] often aids in reaching
the etiological diagnosis.
1. Acute headache: Single episode of head pain without
history of previous events
(i) Fever caused by infections is the most common cause
– Upper respiratory illness (sinusitis, otitis media)
– Acute meningitis, encephalitis
(ii) Other causes include
– Hypertension
– Trauma
– Venous sinus thrombosis
– Brain tumors with complications
– Acute Intracranial bleed (very acute and severe
like bolt from the blue)
2. Acute recurrent headache: Pattern of acute head pain
separated by symptom free intervals
– Migraine and its variants
– Tension headache
– Cluster headaches
3. Chronic progressive headache: Gradual increase in
frequency and severity
Often indicates serious underlying pathology
– Brain tumor
– Hydrocephalus
– Chronic meningitis (TB, fungal)
– Granulomas- Tuberculosis, Neurocysticercosis
– Brain abscess
– Subdural hematoma
– Benign intracranial hypertension
4. Chronic non-progressive headache: Frequent or con-
stant headache without change in frequency or severity
– Chronic sinusitis
– Refractory errors, glaucoma
377
– Post traumatic headache
– Stress related headache
5. Mixed headache: Migraine superimposed on chronic
daily headache
Evaluation
To determine the nature and cause of a child’s headache, the
evaluation begins with a thorough medical history, followed
by meticulous physical examination. A diagnostic algo-
rithm for a child with acute headache is shown in Fig. 1
History
This includes in particular the following details:
& Mode of onset, duration and frequency (recognizing
five patterns)
& Location of headache: Fronto temporal-migraine;
Periorbital-ocular causes; Facial-sinusitis, dental problems;
Generalized-meningoencephalitis, raised ICP, hypertension
& Character: Pulsating-Migraine; Band like-Tension type;
Thunderclap (worst ever)-subarachnoid hemorrhage
& Severity of pain: unable to carry out daily activities
(missing school etc.)-usually a secondary headache
& Time and circumstances: Early morning headache (that
awakens a child from sleep)-raised ICP due to intracra-
nial pathology
& Aggravating and relieving factors: Worsening
with coughing-raised ICP, Worsening on bending
over-sinusitis, worsening with noise and relief on
sleeping-migraine.
& Associated symptoms : Vomiting-intracranial pathology
(tumors, infections); fever, neck pain-meningitis; seiz-
ures, focal deficits Intracranial Space occupying lesion
(ICSOL); photophobia-meningitis, migraine; visual and
GI symptoms (aura)-migraine
& Recent or remote trauma: Intracranial bleed/hematoma
& Systemic illness-Hypertension, drugs causing benign
intracranial hypertension
& Social and emotional factors-Stress headaches, conver-
sion reaction
& Family history of Migraine, neurocutaneous syndromes
In any child presenting with headache, a change from
previous headache pattern, history of projectile vomiting or a
focal weakness indicates possible intracranial pathology [2]
Examination
& Airway, Breathing, Circulation
& Appearance: Sick looking-Meningitis, Intracranial
pathology
378 Indian J Pediatr (March 2012) 79(3):376–380

Fig. 1 Diagnostic algorithm for

Acute severe headache
a child with acute headache.
NCCT NonContrast Computer-
ized Tomogram, SDH Subdural
hematoma, ICH Intracranial H/o trauma NCCT
hemorrhage, LP Lumbar punc-
ture, NCC Neurocysticercosis, SDH / ICH
ICP Intracranial pressure,
CN Cranial nerves
No Abnormal Neurological Findings Yes

(CN palsy, focal deficits, papilledema)

MRI / CT scan

+ -

(Unless contraindicated) LP

Tumors Infections Others

Astrocytoma Tuberculosis / NCC Hydrocephalus

Medulloblastoma Brain abscess Shunt malfunction Meningitis

Spontaneous IC bleed

Idiopathic raised ICP

Fever

Yes No

Meningeal Signs Review History

+ -

Migraine

LP Sinusitis, Pharyngitis, Otitis Hypertension

Viral syndrome Stress headaches

Conversion

Meningitis

& Abnormal Vital signs-Fever, Hypertension – Meningeal signs-Meningitis, subarachnoid

& Eyes hemorrhage
– Tone, reflexes, gait- intracranial pathology
–Vision-Refractory errors
–Pupil (size, shape, reaction)- 3rd cranial nerve Investigations
palsy
– Ocular movements- 6th cranial nerve palsy Majority of patients with normal physical examination do
– Fundus examination- Papilledema not require investigation in the emergency department.
All of above signs indicate raised ICP or space occupying Blood—CBC and Blood culture in suspected infection;
lesion Radiograph—to look for sinusitis;
& Ear/Throat: Pharyngitis, Otitis media, Sinus tenderness - CSF—Lumbar puncture (LP) in suspected meningitis
Sinusitis (CT scan to be obtained prior to LP if there is raised ICP,
& Skull altered sensorium or focal findings).
Neuroimaging—CT scan vs. MRI
– Evidence of external trauma-IC bleed Indications for neuroimaging in a child with headache in
– VP shunt chamber/track-Shunt infection/mal- emergency department are shown in Table 1. Although CT
function scan detects most of the abnormalities that cause a headache,
Indian J Pediatr (March 2012) 79(3):376–380
Table 1 Indications for neuroimaging in a child with headache in
emergency department [1]
• Headache associated with abnormal neurological findings
(papilledema, cranial nerve and motor abnormalities)
• Early morning headache or the headache that awakens a
child from sleep
• Acute headache associated with episodes of confusion,
disorientation or signs of raised ICP
• Presence of ventriculo-peritoneal shunt
• History of recent trauma
• Age less than 3 y
• Severe parental anxiety
MRI is considered superior especially in detecting small
lesions, posterior fossa lesions and vascular malformations.
Management
1. Stabilization of Airway, Breathing, Circulation
2. Management of raised intracranial pressure
3. Identification and appropriate treatment of underlying
conditions will result in complete headache resolution
4. Symptomatic therapy: Analgesics
Paracetamol—15 mg/kg/dose P.O
Ibuprofen—10 mg/kg/dose P.O
Specific Conditions
Migraine
Migraine is one of the most common causes of acute and
recurrent headache in children. By 15 y of age, at least 5% to
10% of children have had a migraine headache. Migraine’s
incidence begins to peak in early adolescence and may be a
concern in children as young as 5 or 6 y of age.
Features
Classically the onset of pain is preceded by an aura (visual,
GI) and then an increasing severity of pulsatile pain often
felt unilaterally (frontal, temporal). However, children may
present with bilateral headache of shorter duration and
without the combination of photo and phonophobia.
Diagnostic criteria for migraine in children are given in
Table 2 [3].
Treatment of an Acute Attack [4]
First line
Analgesics:Paracetamol—15 mg/kg/dose P.O, Ibuprofen—
10 mg/kg/dose P.O
379
Table 2 Diagnostic criteria for migraine in children [3]
A. Five or more headache attacks that:
B. Last 1 to 48 h
C. Have at least two of the following features:
Bilateral or unilateral (frontal/temporal) location
Pulsating quality
Moderate to severe intensity
Aggravated by routine physical activities
D. Are accompanied by at least one of the following:
Nausea and/or vomiting
Photophobia and/or phonophobia
Antiemetics:Promethazine—0.25 to 0.5 mg/kg/dose P.O,
Prochlorperazine—0.25 to 0.5 mg/kg/dose P.O
Second line [5]
Sumatriptan nasal spray
Prochlorperazine 0.15 mg/kg i.v. (max 10 mg) for severe
acute attack
Removal of triggers such as sleep disturbance, stress and
caffeine
Disposition
& Observe for relief of an attack.
& Refer to a pediatric neurologist for further evaluation
and assessing the need for prophylactic therapy.
Intracranial Space Occupying Lesion
A wide variety of Childhood tumors and CNS infections
present with headache. The commonest among them include:
& Tumors (medulloblastoma, astrocytoma)
& Brain abscess
& Tuberculoma
& Neurocysticercosis
They often present with associated abnormal neurolog-
ical features (projectile vomiting, Cranial nerve palsy,
seizures, focal neurodeficits and papilledema) which alert
the physician towards the diagnosis of these conditions.
Neuroimaging (CECT/MRI) is mandatory.
Treatment
1. Stabilization of Airway, Breathing, Circulation
2. Management of seizures and raised intracranial pressure
3. Appropriate antibiotics (brain abscess)
4. Anti-edema measures: Dexamethasone i.v. 1 mg/kg
loading, then 1–1.5 mg/kg/d in 4 divided doses (max.
380
16 mg/d) or oral prednisolone 2 mg/kg/d in 3 divided
doses.
Disposition
Neurosurgery consultation and definitive management.
Key Points
& Acute headache is often accompanied by other symp-
toms of an underlying illness
& In addition to a complete neurological examination,
measurement of blood pressure and fundus examination
for papilledema are essential in the evaluation of a child
with headache.
& Acute attack of migraine and other acute headaches due
to benign etiologies are treated symptomatically with
NSAIDs (Paracetamol 15 mg/kg/dose; Ibuprofen
10 mg/kg/dose P.O)
& Children with history of trauma, chronic progressive
headache and/or abnormal neurological findings require
a CT scan to identify underlying intracranial pathology.
& Meningits and brain abscess are treated with appropriate
antibiotics. Children with brain tumor, brain abscess
Indian J Pediatr (March 2012) 79(3):376–380
and intracranial hemorrhage need i.v. dexamethasone
1 mg/kg loading, then 1–1.5 mg/kg/d in four divided
doses and further definitive neurosurgical management.
Conflict of Interest None.
Role of Funding Source None.
References
1. Lewis DW. Headaches in children and adolescents. Am Fam
Physician. 2002;65:625–32.
2. Rothner AD. The evaluation of headaches in children and
adolescents. Semin Pediatr Neurol. 1995;2:109–18.
3. Winner P, Wasiewski W, Gladstein J, Linder S. Multicenter
prospective evaluation of proposed pediatric migraine revisions to
the IHS criteria. Headache. 1997;37:545–8.
4. Lewis DW, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein
S. Practice parameter: pharmacological treatment of migraine
headache in children and adolescents. Neurology. 2004;63:2215–
24.
5. Damen L, Bruijn JKJ, Verhagen AP, Berger MY, Passchier J, Koes
BW. Symptomatic treatment of migraine in children: a system-
atic review of medication trials. Pediatrics. 2005;116:e295–
302.
Indian J Pediatr (April 2012) 79(4):510–517
DOI 10.1007/s12098-011-0604-9
SYMPOSIUM ON PGIMER PROTOCOLS IN NEUROLOGICAL EMERGENCIES
Management of Acute Seizure and Status Epilepticus
in Pediatric Emergency
K. Sasidaran & Sunit Singhi & Pratibha Singhi
Received: 4 August 2011 / Accepted: 20 October 2011 / Published online: 26 November 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Acute seizure and status epilepticus constitute one
of the major medical emergencies in children. Among
children, the incidence ranges from 4-38/100,000 children
per year respectively. The incidence in developing countries is
somewhat higher because of infections. Although, the
definition of status epilepticus is based on duration of seizures,
the operational definition is to treat any child who is brought
seizing to the emergency room, as status epilepticus. An
urgent time bound approach is of paramount importance when
managing a child in status epilepticus. Benzodiazepines
remain the first line antiepileptic drugs in the emergency
room; a long acting drug (Lorazepam) is preferred when
available. This is followed by Phenytoin (20 mg/kg) loading.
In patients refractory to above drugs, valproate (30 mg/kg)
loading is commonly used and if effective, followed by an
infusion (5 mg/kg/h) for seizure free period of 6 h. In non-
responders, a trial of Levetiracetam (40 mg/kg infused at
5 mg/kg/min) can be used before starting benzodiazepine or
thiopental coma (3–4 mg/kg loading dose, followed by
2 mg/kg/min infusion). When pharmacological coma is
initiated, the child needs to be shifted to pediatric intensive
care unit for proper monitoring and titration of medications.
Keywords Acute seizure . Children . Status epilepticus .
Febrile seizures . Refractory status epilepticus
Introduction
A seizure results from abnormal, excessive, paroxysmal
electrical discharge of neurons within the brain, primarily
K. Sasidaran : S. Singhi (*) : P. Singhi
Department of Pediatrics, Advanced Pediatric Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160 012, India
e-mail: sunit.singhi@gmail.com
within the cerebral cortex. These discharges occur in
various locations and may spread in different directions
and at different speeds, resulting in several types of
seizures, each with its own clinical manifestation.
Incidence
Incidence of seizures ranges from 40–70 per 100,000
population [1] in developed countries, and somewhat
higher, approximately, 60–124 in developing countries [2,
3]. Studies have shown that 4–6% of children will have
atleast one seizure in the first 16 y of life [4]. Among
children, the incidence of status epilepticus ranges from 4–
38 episodes per 100,000 children per year [5].
Definitions [6, 7]
Epileptic Seizure: It is a transient occurrence of signs and/
or symptoms due to abnormal or excessive synchronous
neuronal activity in the brain
Epilepsy: It is a disorder of brain characterized by an
enduring predisposition to generate epileptic seizures
and by the neurobiologic, cognitive, psychological and
social consequence of the condition. The definition of
epilepsy requires occurrence of atleast one epileptic
seizure; generally it includes two or more unprovoked
seizures
Convulsion: Attack of involuntary muscle contractions,
which may be sustained (tonic) or interrupted (clonic).
Status epilepticus: Operational definition: It is a condition
of prolonged seizure activity (more than 5 min) or
Indian J Pediatr (April 2012) 79(4):510–517 511

persistent, repetitive seizure activity without recovery of Table 1 Causes of refractory SE in children admitted to Pediatric
Intensive Care Unit, PGIMER, Chandigarh in 1995 and 2005
consciousness in between episodes. Any child who is
brought seizing to the emergency room should be treated Causes Number of Patients
as status epilepticus.
In 1995 (n=62) In 2005 (n=40)
Postictal period: It usually follows the seizure. During
Bacterial/ purulent meningitis 26 5
this time, the patient may be confused, lethargic,
Encephalitis 11 20
fatigued, or irritable; also, headache, vomiting, and
Idiopathic epilepsy 10 4
muscle soreness may occur. In general, the length of
Post-hypoxic encephalopathy 4 –
the postictal period is proportional to the length of the
Reye’s encephalopathy 2 –
seizure.
Shigella encephalopathy 2 –
Intracranial bleed – 2
Neuro metabolic disorders – 2
Pathophysiology
Others 5 7

Prolonged seizures cause an increased metabolic rate,

cerebral oxygen extraction and consumption and subse-
quently neuronal injury [8]. During the first 30 min of
seizures there is massive sympathetic and parasympathetic
over-activity, which may lead to tachycardia, hypertension,
hyperglycemia, hyperthermia, excessive sweating, and
salivary and tracheobronchial hypersecretion. If status
epilepticus persists for more than one hour, hypotension,
hyperkalemia, hypoglycemia, hypotension and respiratory
acidosis may ensue [8]. Treatment with benzodiazepines or
barbiturates may further worsen these complications. CSF
pleocytosis may occur [9].
Etiology
The important causes of status epilepticus may be broadly
divided into:
1) Acute: CNS infections (meningitis, meningoencephali-
tis), febrile convulsions, vascular episodes, trauma,
metabolic and poisonings.
2) Static: Status epilepticus as first manifestation of/or
during the course of epilepsy, with or without an
underlying neurologic disorder. In known epileptics,
non-compliance or withdrawal of anti-epileptic therapy,
intercurrent infections and stress may predispose to
status epilepticus.
In one study, more than 80% children younger than
2 y of age with status epilepticus had a febrile or
acute symptomatic origin, while among children older
than 2 y, 64% had a past history of seizures and 55%
were known to be previously neurologically abnormal.
In the authors’ emergency department, CNS infections
are the commonest cause of refractory status epilepti-
cus (RSE) [10, 11]. Causes of RSE in children admitted
to the authors’ unit in 1995 and 2005 are given in
Table 1
Diagnosis
Status epilepticus is generally hard to miss. Single seizures,
especially the first episode, can sometimes be confused
with the other paroxysmal disorders. The following key
features are helpful in differentiating common paroxysmal
non epileptic events from true seizure episodes:
& Syncopal episodes are usually preceded by blurred
vision, dizziness and pallor [12]
& Gastroesophageal reflux usually results in an arched
back position in a crying, conscious child, and is
associated with feeding
& Cyanotic breath holding spells usually occur after a
crying episode, and result in limpness and loss of
consciousness, occasionally with posturing [13]
& Child who is day dreaming maintains his or her posture
and head control, and can be interrupted by name
calling or touch [14]
& In pseudoseizure, the patient often keeps his or her eyes
tightly closed, resists eye opening, avoids painful stimuli,
limb movements are usually haphazard (not conforming
to any seizure type) and there is rapid return to normal
level of consciousness [15]
Figure 1 outlines the steps for confirming the diagnosis
and type of seizures
Febrile Seizures
Acute seizure in a febrile child needs to be differentiated
from simple febrile seizures. Simple febrile seizure would
fulfill all of the following characteristics:
& Patient age between 6 mo and 5 y
& Generalized tonic clonic convulsion
& Spontaneous cessation of convulsion within 15 min
& Return to alert mental status after convulsion
512 Indian J Pediatr (April 2012) 79(4):510–517

Paroxysmal Clinical Event

History of paroxysmal clinical event

Seizing child presenting to ER
Not seizing at presentation

Normal sensorium + Febrile child Afebrile child

Afebrile +
Simple febrile seizure Fever triggered seizure in a CNS infections
Normal on clinical examination
child with epilepsy
Complex febrile seizures

Witnessed event Event not witnessed Abort seizure activity

True seizure Paroxysmal Nonepileptic Event (PNE)

First episode seizure* or

Break through seizure in a
child with epilepsy

Refer to pediatric neurologist to

decide about further therapy/AED ER work up

* First episode seizure requiring antiepileptic therapy

Fig. 1 Steps for Confirming the diagnosis and type of Seizures. risk than generalized tonic clonic events), Positive family history of
* First episode seizure requiring antiepileptic therapy. epilepsy, Seizures associated with head injury/ Seizures in a predisposed
Symptomatic seizures due to underlying etiology (inflammatory child (developmental delay), Myoclonic seizures, Absence seizures,
granuloma, infarct, migration defect), Partial seizures (greater relapse seizure during sleep

& Documentation of fever (>38°C) outlines the team approach to a seizing child presenting to
& One convulsion within 24 h period the pediatric emergency.
& Absence of pre-existing neurological abnormality
Initial Stabilization (Supporting Vital Functions)

Attention to airway, breathing and circulation to ensure

Management of Seizing Child in Emergency Room
adequate cerebral perfusion oxygenation and glucose level
is the first priority in the management. This can be achieved
Management Goals
by maintaining optimal respiratory and hemodynamic
function using PALS guideline
& Supporting vital functions (stabilization of airway,
In actively seizing child with tightly shut clenched jaw,
breathing, circulation) to ensure adequate brain oxy-
abnormal breathing and poor air entry, the airway is not
genation and cardiorespiratory function
fully patent. Obstruction by tongue and mandibular block
& Terminate clinical and electrical seizure activity as
of tissue interferes with inspiratory air flow and imposes
expeditiously as possible
increased work of breathing resulting in ineffective venti-
& Identify and correct precipitating factors such as
lation and inadequate oxygenation. In such a patient,
hypoglycemia, electrolyte imbalance, infection, and
though, the patient clearly has central nervous system
fever to prevent seizure recurrence
(CNS) dysfunction the airway is the immediate concern.
& Diagnosis and initial therapy of life-threatening cause of
status epilepticus
& Ensure the airway patency by proper positioning of the
& Prevent and treat the systemic complications
head or by positioning the patient on the side and
The emergency team approaches a seizing child with the suctioning the nasopharyngeal secretions
objectives of initial stabilization, seizure termination and & Place a nasopharyngeal airway to open the airway.
evaluation and treatment of underlying cause. Figure 2 & Place patient on 100% oxygen by nonrebreathing mask.
Indian J Pediatr (April 2012) 79(4):510–517
Fig. 2 The team approach to a
seizing child presenting to the
pediatric emergency
Intravenous access
Proceed with seizure management algorithm
& Reassess the need for bag and mask ventilation (BMV).
Bag and mask ventilation should be started if there are
signs of inadequate ventilation and oxygenation such as
inadequate chest movements, poor air entry on auscul-
tation, tachypnea, poor respiratory efforts, central
cyanosis, or oxygen saturation <90%. If bag mask
ventilation is unsatisfactory, endotracheal intubation
should be done.
& Indications for endotracheal intubation (Rapid sequence
intubation):
– Severe hypoxia (bradycardia, hypotension, poor
perfusion)
– Failure or prolonged requirement of bag and mask
ventilation
– Children with features of raised intracranial pressure
– Refractory status epilepticus (seizure persists even
after adequate treatment with benzodiazepines and
Phenytoin)
& Obtaining a vascular access is the next important step.
This is needed for administration of fluids to stabilize
circulating volume and anticonvulsants therapy to abort
seizure. In a convulsing child, at times it may be
difficult to establish an intravenous access. In such a
situation one may use intraosseous (IO) route. In
children less than 6 y, all emergency anticonvulsants
and medications and fluids that are given by IV route
may be administered by IO infusions.
Termination of Seizure
& Administer lorazepam 0.1 mg/kg IV or diazepam 0.2–
0.3 mg/Kg IV.
513
Designate team member to proceed to achieve each objective
Pediatric Assessment triangle Focused history
Appearance
Physical examination
Breathing
Circulation
Assessment Pentagon
Appearance
Breathing
Circulation
Disability
Exposure
Stabilize Airway
Breathing
Circulation
& If vascular access cannot be quickly achieved, give
rectal diazepam or midazolam IM and continue to
establish vascular access.
& If the patient has no response to first dose of lorazepam/
diazepam, repeat the dose and
& Administer loading dose of phenytoin 20 mg/kg over
20 min (Phenobarbitone is preferred in neonates and in
SE associated with fever - loading dose of 20 mg/kg IV
at a rate of 1.5 mg/kg/h).
Drug Therapy to Terminate Seizure Activity
[10, 11, 16–18]
Intravenous Benzodiazepines
Intravenous administration of benzodiazepines stops
seizures most rapidly regardless of the etiology. Hence,
these are accepted as first-line treatment of convulsive
or non-convulsive SE. Midazolam 0.1–0.2 mg/kg (max-
imum 5 mg), or diazepam 0.3 mg/kg (maximum 10 mg)
at a rate no greater than 2 mg/min, or lorazepam 0.05–
0.1 mg/kg (maximum 4 mg) given over 2 min, can be
used as a first line treatment. The onset of action of
these drugs is within 1–3 min of administration.
However, the need to keep lorazepam refrigerated and
dilute it prior to administration makes diazepam use
easier in acute situations.
Rectal Diazepam
Rectal diazepam is as effective as intravenous diazepam
in aborting seizures if given within 15 min of seizure
onset. Diazepam parentral solution can be administered
514
per rectum at the dose of 0.5 mg/kg up to a maximum
of 10 mg. The anal opening should be strapped after
administration for about half an hour to prevent
spillage.
Intramuscular (IM) Midazolam
Midazolam being water soluble can be administered by IM
route The IM use of 0.2 mg/kg is as effective as intravenous
diazepam for the initial therapy of SE.
Phenytoin
Phenytoin is given intravenously, in a loading dose of
20 mg/kg, at a rate not exceeding 1 mg/kg/min (to avoid
hypotension and cardiac arrhythmias). An additional load-
ing dose up to 10 mg/kg may be used in young infants if SE
persists after 10 min. Phenytoin should be diluted only with
normal saline, and never with glucose containing solutions.
Fosphenytoin, a phenytoin prodrug, can be administered
IM with rapid and complete absorption. The dose of
Fosphenytoin is 15–20 mg/kg of phenytoin equivalents/
kg, infused at a rate of not more than 3 mg/kg/min. The cost
is however a limiting factor.
Phenobarbitone
Phenobarbitone is preferred over phenytoin in neonates and
in SE associated with fever. However, there is no evidence
to favor this preference. It is given in a loading dose of
20 mg/kg IV at a rate of 1.5 mg/kg/h. In neonates an
additional dose of 5–10 mg/kg may be given if seizure
persists (total of 30 mg/kg).
Treatment of Refractory Status Epilepticus (RSE)
If seizures persist even after the adequate treatment with
benzodiazepine, and phenytoin and/or phenobarbitone, it is
referred as RSE. About 10–15% of SE is refractory to
conventional therapies. The causes of RSE in the authors’
unit are given in Table 1.
Traditionally RSE is treated with barbiturate coma,
continuous benzodiazepine infusion or anesthetic agents.
At this point of time one has to consider intensive care unit
transfer, put patient on a ventilator and initiate continuous
EEG monitoring regardless of the drug used. In absence of
ready availability of ventilator, Sodium valproate can be
tried.
Sodium Valproate [17]
Sodium valproate is given as an initial loading bolus of
30 mg/kg diluted 1:1 in normal saline, over 2–5 min. This
Indian J Pediatr (April 2012) 79(4):510–517
is followed by infusion at a rate of 5 mg/kg/h, which can be
continued until a seizure free period of 6 h and then tapered
off over 6 h.
Diazepam or Midazolam Infusion
Diazepam or midazolam infusion could be considered if
there was an initial response to benzodiazepines. Both of
these drugs, when used in rapidly incremental doses
controlled RSE on an average within 15 min [10, 11].
Diazepam is diluted in normal saline, Ringer’s lactate or
dextrose water to give strength of 0.04 mg/ml. The starting
dose is 0.01 mg/kg/min. Most children require 0.02–
0.03 mg/kg/min. Midazolam infusion starting with 2μg/
kg/min up to 12 μg/kg/min may be used. In the authors’
experience midazolam was associated with about four times
higher risk of breakthrough seizures as compared to
diazepam [11].
Barbiturate Coma
Barbiturate coma using thiopental is highly effective for
treatment of refractory SE. Recommendations for the
choice of barbiturate have been solely based on theoretical
basis and there is no study directly comparing the efficacy
and safety of this drug. Thiopental is given in an initial dose
of 3–4 mg/kg IV over 2 min, followed by a continuous
infusion of 2.0 mg/kg/min. The rate is increased every 3–
5 min by 0.1 mg/kg/min until SE is controlled or a burst
suppression EEG recording is obtained. The major limita-
tion of the barbiturates is a need for mechanical ventilation,
hypotension requiring vasopressors support, delayed recov-
ery and pneumonia.
Other Drugs for RSE
Propofol The initial dose is 1–3 mg/kg I.V. followed by a
continuous infusion of 2–10 mg/kg/h as guided by EEG.
Lidocaine The initial loading dose is 1–2 mg/kg I.V. given
over 2 min. If seizures stop, continuous infusion of 2–4 mg/
kg/h is given under EEG monitoring. It may cause
hypotension, heart block and arrhythmia, and may exacer-
bate seizures at higher doses.
Ketamine Infusion Ketamine is an anesthetic agent shown
to be effective in control of refractory status epilepticus.
Borris et al. [18] found it to be more effective than
phenobarbital in prolonged status epilepticus. SE is a life-
threatening emergency that requires prompt and vigorous
treatment. Uncontrolled seizure activity results in progres-
sive neuronal damage. Hence, all treating units should
establish a time framed protocol. Table 2 outlines the
Indian J Pediatr (April 2012) 79(4):510–517 515

Table 2 Stepwise antiepileptic drug escalation protocol aiming at terminating the seizure activity

Drug Supportive treatment

0–3 min Initial stabilization and supporting vital functions as mentioned above
3–5 min Benzodiazepine first line therapy Start second IV line for simultaneous
Lorazepama 0.1 mg/kg over 2 min (max 4 mg) OR administration of second medication
Diazepam 0.3 mg/kg over 2 min (max 10 mg) and IV fluids
7–8 min Phenytoinb 20 mg/kg dilute in saline and infuse at a rate of not more than Thiamine 100 mg iv push; Pyridoxine
1 mg/kg/min 100 mg iv push in children <3 y of age
10 min Repeat Diazepam 0.3 mg/kg OR
Lorazepam 0.1 mg/kg
15 min Repeat Diazepam (same dose) OR
Lorazepam 0.1 mg/kg
25 min Phenytoin 10 mg/kg dilute in saline and infuse at a rate not more than
1 mg/kg/min
35 min IV Valproate 30 mg/kg diluted 1:1 in normal saline over 2–5 min. If the Transfer to PICU, prepare for intubation,
status is not controlled within 10 min of bolus, repeat 10 mg/kg bolus ventilation, get EEG
dose, followed by continuous infusion at the rate of 5 mg/kg/h [18]c OR
Midazolam OR Diazepam infusion [19]d Cardiorespiratory monitoring
Diazepam: 0.01 mg/kg/min, max 0.1 mg/kg/min
Midazolam: 2 mcg/kg/min upto 12 mcg/kg/min in increments of
2 mcg/kg/min every 5 min
Levetiracetam 40 mg/kg at 5 mg/kg/min can be infused after valproate before
initiating thiopental coma
45–50 min Thiopentale3–4 mg/kg iv over 2 min followed by an infusion at 2 mg/kg/h. Mechanical ventilation
a
Lorazepam must be refrigerated and diluted before administration
b
If the patient is already on Phenytoin, then administer 8 mg/kg of Phenytoin as the initial anticonvulsant
c
If the patient is already on Valproate, then 10 mg/kg is the loading dose. The infusion is continued until seizure free period of 6 h, then tapered
off @ of 1 mg/kg/h every 2 hourly
d
Midazolam or Diazepam infusion is preferred over Valproate in children less than 2 y. Benzodiazepine infusion is discontinued once thiopental
infusion is started
e
Infused in a separate IV line to avoid mixing with acidic drugs. Increase the infusion @ 1 mg/kg/h every 30 min to 6 mg/kg/h till seizure control
and burst suppression on EEG, The infusion is continued until seizure free period of 6 h, then tapered off

stepwise antiepileptic drug escalation protocol aiming at Physical Examination

terminating the seizure activity [19].
& The presence or absence of meningismus and photo-
phobia should be documented.
Diagnostic Evaluation
& The skin should be examined for petechiae, and
signs of neurocutaneous syndromes such as café’
History
au lait spots, ash leaf macules and adenoma
sebaceum.
Search for a cause should proceed side by side with
& A thorough neurological examination is performed.
therapeutic measures to terminate seizure. The evalua-
In some patients examination may reveal Todd’s
tion should include a brief history, physical examination
paresis, a transient paralysis that can follow seizure.
and selected investigations. If child was already on
It is usually unilateral and may involve both the face
antiepileptic medications, history regarding missing
and extremities.
dose, diarrhea, vomiting, fever, co-medication, under
dosage are necessary.
The focused brief history should include history of fever, Laboratory Evaluation (Table 3)
trauma, prior seizures, drug use or withdrawal, underlying
medical disorders, perinatal problems, developmental mile- & Bedside glucose check – to detect hypoglycemia in all
stones and family history of seizures. children.
516
Table 3 Suggested diagnostic
workup in a child in status Blood
epilepticus
Urine
CSF
Continuous EEG monitoring
Neuroimaging (CT scan, MRI)
& Serum electrolytes (Sodium, Calcium) in all infants and
young children with first episode seizures.
& Studies such as liver function tests, renal function tests,
lead level, urine amino acids, and organic acids should
be individualized.
& If there is a history of drug exposure, toxicology screen
needs to be considered.
& For febrile patients, etiology of fever needs to be
investigated, if not determined on physical examination.
& A lumbar puncture should be performed in any child
suspected of having a central nervous system infection.
However, if there are focal findings on physical
examination or suspicion of a mass lesion or increased
intracranial pressure, the lumbar puncture is delayed till
a CT scan of head is obtained [15].
& In infants younger than 6 mo with a first afebrile seizure,
with no etiology, and persistent decreased level of con-
sciousness, a lumbar puncture should be performed [15].
Radiologic Evaluation
Indications for Emergent Neuroimaging (Usually CT Scan)
& Child with focal onset seizures
& Child with features of raised ICP
& Suspected trauma – CT scan is preferred as an acute
hemorrhage can be detected, but MRI is preferred for
brain damage, old hemorrhage detection and postictal
focal deficit that doesn’t resolve in 12 h.
Electroencephalogram
& EEG is indicated in all children who remain in altered
sensorium even after complete control of clinical
convulsions
Table 4 Complications of status epilepticus
Cardiovascular Bradycardia, arrhythmia, cardiac failure or arrest, hypertension, hypotension, shock
Respiratory Hyperapnea, apnea, irregular or cheyne stokes breathing, respiratory acidosis, aspiration pneumonia, pulmonary edema
Renal Oliguria, acute renal failure, acute tubular necrosis, myoglobinuria(from rhabdomyolysis)
Autonomic Hyperpyrexia, excessive sweating, excessive secretions with airway obstruction
Metabolic Hyperglycemia, hypoglycemia, hyperkalemia, hyponatremia, metabolic and lactic acidosis
Indian J Pediatr (April 2012) 79(4):510–517
Hemogram, glucose, calcium, magnesium, urea, electrolytes, blood-gases
anti-epileptic drug levels, toxicology screen, culture if febrile
Routine analysis, myoglobinuria, toxicology
In suspected meningitis
In refractory SE and SE in neonates
In case of focal findings, raised ICP, suspected head injury, coma
& EEG evidence of persistent epileptiform discharges in a
clinically nonconvulsing child, would be helpful to
identify Non Convulsive Status Epilepticus (NCSE)
Guideline for diagnostic work-up in a child with statue
epilepticus is provided in Table 3
Complications of Status Epilepticus
Complications occur because of prolonged seizure activity
and sometimes due to the drug therapy. These should be
looked for and attended to. Table 4 outlines the common
complications of status epilepticus.
Disposition
Any child who has received Lorazepam or a long acting
anticonvulsant medication should be admitted to the hospital.
Intensive care admission is required in any child with
Refractory Status Epilepticus, requiring mechanical venti-
lation, or in whom the evaluation has revealed an etiology
requiring close monitoring.
Rescue medication: In children who are likely to get
recurrent seizures after status epilepticus, rescue medication
for prehospital use such as buccal or intranasal midazolam
is advised
In case of febrile children, the etiology of the fever should
be investigated and managed in the standard fashion.
In case of simple febrile seizures, parents or caregivers
need to be counseled emphasizing the following facts:
& Patients with a simple febrile seizure have a 32%
incidence of recurrence before their sixth birthday;
subsequent use of antipyretics at fever onset does not
lower the recurrence rate [20].
Indian J Pediatr (April 2012) 79(4):510–517
& A simple febrile seizure lasting less than 15 min is not
associated with any long-term effects on brain function
or intelligence [21].
& Whenever seizure recurs “Ensure that child is removed
from an area with sharp or dangerous surfaces; position
him to the side, and look at the clock at the onset to
note the exact duration of seizure”.
& “Swallowing of the tongue” is not a real concern, and
aggressive airway interventions such as bite-blocks
should be discouraged.
& If there are more than 3 episodes of simple febrile
seizure recurrence, it is advisable to review the child
with a pediatric neurologist.
& Advice to use rectal diazepam (Diazepam IV solution
per rectum 0.5 mg/kg up to a maximum of 10 mg) when
parental anxiety about febrile seizures is severe, this
may be effective in preventing recurrence [22].
& Intermittent prophylaxis may be advised in some
children with recurrent febrile seizures.
Key Points
& Acute seizure and status epilepticus constitute one of
the major medical emergencies in children.
& Any child who is brought seizing to the emergency
room to be treated as status epilepticus.
& Management is focused at stabilization of airway,
breathing, circulation and aborting the seizure activity.
Longer the status, it becomes more difficult to control
and results in poor outcome.
& Be watchful for hypoglycemia and hypocalcemia while
managing acute seizure.
& Search for precipitants (Missed antiepileptic drug dose,
Acute diarrhea, Toxins, Dyselectrolytemia (Mg/Na/Ca),
hypoglycemia) and treat if present.
& Benzodiazepines remain the first line antiepileptic drugs
in the emergency room; Lorazepam is preferred over
diazepam when available. This is followed by Phenytoin
(20 mg/kg) loading.
& Swift escalation of anti-epileptic without any delay is
the cornerstone of status epilepticus management.
& In SE refractory to above drugs, use Valproate (30 mg/kg
loading followed by an infusion 5 mg/kg/h for seizure free
period of 6 h) and if needed, a trial of Levetiracetam
(40 mg/kg infused @ 5 mg/kg/min) before starting
benzodiazepine or thiopental coma (3–4 mg/kg loading
dose, followed by 0.2 mg/kg/min infusion).
& Refractory status epilepticus can be best managed in
PICU settings.
& Uncontrolled seizure activity results in progressive
neuronal damage.
517
Conflict of Interest None.
Role of Funding Source None.
References
1. Commission on Epidemiology and Prognosis, International
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2. Bharucha NE. Epilepsy in India. In: Singhal BS, Nag ND, editors.
Indian epilepsy association Mumbai. 2000: 08-14.
3. Chowdry GVS, Murthy JMK, Vijay S, et al. Prevalence of seizure
disorders associated with neurocysticercosis: a community based
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(CRESSI) Presented at Asian and Oceanic congress of Neurology,
Singapore, 2005.
4. Hauser WA, Hersdorffer DC. Epilepsy, frequency, causes,
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5. Chin RF, Neville BG, Scott RC. A systematic review of the
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Neurology. 2002;59:S3–6.
9. Dunn DW. Status epilepticus in children: etiology, clinical
features and outcome. J Child Neurol. 1988;3:167.
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continuous diazepam infusion. J Child Neurol. 1998;13:23–261.
11. Singhi S, Murthi A, Singhi P, Jayashree M. Continuous
midazolam versus diazepam infusion for refractory convulsive
status epilepticus. J Child Neurol. 2002;17:106–10.
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variation. Pediatr Rev. 2007;28:363–71.
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BD, editors. UpToDate. Waltham, MA, 2007.
14. Tamer SK. Pediatric non-epileptic seizure. Indian J Pediatr.
1997;64:671–6.
15. Chapman K. Controversies in the treatment of epilepsy. Epilepsy
– making the diagnosis. San Francisco: American Academy of
Pediatrics, National Conference and Exhibition; 2007.
16. Louis CH, Louis AS. Evaluation and management of pediatric
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17. Mehta V, Singhi P, Singhi S. Intravenous sodium valproate versus
diazepam infusion for the control of refractory status epilepticus in
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status epilepticus. Epilepsy Res. 2000;42:117–22.
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management. Indian J Pediatr. 2003;70:S17–22.
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Indian J Pediatr (April 2012) 79(4):518–524
DOI 10.1007/s12098-011-0648-x

SYMPOSIUM ON PGIMER PROTOCOLS IN NEUROLOGICAL EMERGENCIES

Raised Intracranial Pressure (ICP): Management

in Emergency Department
Ramesh Kumar R. & Sunit C. Singhi & Pratibha Singhi

Received: 29 August 2011 / Accepted: 30 November 2011 / Published online: 6 January 2012
# Dr. K C Chaudhuri Foundation 2012

Abstract Raised intracranial pressure is a life threatening
condition; unless recognized and treated early, it may prog-
ress into herniation syndrome and death. Symptoms and
signs are neither sufficiently sensitive nor specific, hence a
high index of suspicion and vigilance are needed for early
recognition. Immediate goal of management is to prevent /
reverse herniation and to maintain good cerebral perfusion
pressure. The therapeutic measures include stabilization of
airway, breathing and circulation, along with neutral neck
position, head end elevation by 30°, adequate sedation and
analgesia, minimal stimulation, and hyperosmolar therapy
(mannitol or 3% saline). Short-term hyperventilation (to
achieve PCO2 ≈30 mm Hg) using bag ventilation can be
resorted to if signs of impending herniation are present.
Keywords Raised ICP . Cerebral perfusion pressure . Auto-
regulation . Herniation . Hyperventilation . Modified
Glasgow coma score . Mortality
reduced Cerebral perfusion pressure (CPP), and progress
into herniation syndrome and death.
Aim of management in a child with raised intracranial
pressure (ICP) is to break the vicious cycle of cerebral
edema and compromised cerebral blood flow (CBF) at the
earliest and to maintain adequate cerebral perfusion pressure
(CPP). The creation of standardized management protocol
has reduced variations in ICP, decreased duration of raised
ICP and improved outcome.
Pathophysiology
Monroe-Kellie Doctrine states that in a non-compliant skull
vault, ICP is the sum total of pressure exerted by the brain
(≈80%), blood (≈10%) and CSF (≈10%). The volume of
brain tissue increases without a significant change in ICP
because of adaptive reductions in CSF and CBV, but when
these adaptations have been exhausted, an inflection point is
reached beyond which ICP increases exponentially [2].

Introduction Normal Values

Raised ICP is a life threatening condition that is commonly The normal range for ICP varies with age. The normal
seen in emergency with both traumatic and non-traumatic values for ICP in children are not well established. The
neurological illnesses. Almost 93% of children with acute usual normal range is considered as 5 to 15 mmHg [2]. In
meningitis have signs of raised ICP at admission or develop new born term infants it is 1.5–6 mmHg, in young children
these within 48 h of admission [1–3]. Unless recognized and 3–7 mmHg and in older children 10–15 mmHg.
treated early it may cause secondary brain injury due to
ICP Threshold for Treatment
Ramesh
R. : S. C. Singhi
K. R. Kumar R. : S. C.
(*) : P. Singhi
Singhi (*) : P. Singhi
Department of Pediatrics, Advanced Pediatrics Centre, Current pediatric data support a definition of ICP more than
Postgraduate Institute of Medical Education
and Research (PGIMER),
20 mmHg as intracranial hypertension requiring treatment
Chandigarh 160012, India [3]. For all practical purposes, if symptoms and signs of
e-mail: sunit.singhi@gmail.com raised ICP are present, one should consider that ICP is more
Indian J Pediatr (April 2012) 79(4):518–524
than 20 mmHg and treat accordingly. Sustained ICP values
>40 mmHg indicate severe life threatening raised ICP.
Cerebral Perfusion Pressure (CPP)
CPP is the pressure at which brain is perfused. It provides an
indirect measure of adequacy of cerebral blood flow (CBF).
It is calculated as the difference between mean arterial
pressure (MAP) and ICP (CPP0MAP—ICP). Normal CPP
values for children are not clearly established, but the values
that are generally accepted as the minimal CPP necessary to
prevent ischemia are as follows: infants/toddlers: > 40–
50 mmHg; children: > 50–60 mmHg.
CPP<40 mmHg is a significant predictor of mortality in
children with traumatic brain injury (TBI). Autoregulation
that maintains a steady cerebral blood flow (CBF) within a
CPP range of 50–150 mmHg, despite fluctuations in sys-
temic blood pressure, is lost at CPP values <50 mmHg.
Once auto regulation is lost, CBF and cerebral blood vol-
ume (CBV) become dependent on changes in systemic
blood pressure.
Etiology
Common causes of raised ICP with respect to pathophysi-
ology are shown in Table 1.
Approach in an Emergency Department
Approach to a child presenting with raised ICP in an Emer-
gency department is shown in Fig. 1. All patients with an m-
Table 1 Common causes of raised ICP
A. Increase in Brain Volume
• Cerebral edema: Primary CNS illness: encephalitis, meningitis,
Head injury, Reye’s syndrome.
• Cerebral edema: Secondary to systemic illness: Hypoxic ischemic
injury (hypoventilation, shock), ischemic stroke/ infarct, metabolic
encephalopathy– hyperpyrexia, hepatic failure, lead intoxication.
• Space-occupying lesions: Hematomas, tumors, abscesses
B. Increase in Blood Volume
• Venous obstruction- Cerebral venous sinus thrombosis
• Hemorrhage
• Vasodilatation: Due to hypoxia, drugs or hypercapnia
• Status epilepticus
C. Increases in CSF Volume
• Obstructive hydrocephalus, Communicating hydrocephalus
• Impaired reabsorption: Subarachnoid hemorrhage.
• Increased production: Tumors
D. Idiopathic or Benign Intracranial Hypertension
519
GCS≤8 are likely candidates for raised ICP and in particular
the patients with following diagnosis:
1. Acute CNS infection with change in mentation/focal
signs.
2. Traumatic brain injury: Severe TBI (m-GCS≤8), mild
to moderate TBI with abnormal admission head CT scan
or hypotension, motor posturing
3. Acute hepatic encephalopathy Grade III or IV
4. Diabetic ketoacidosis with encephalopathy
5. Toxic encephalopathy, hypertensive encephalopathy
6. Hypoxemic encephalopathy- Gross ischemia—more
than 50% MCA territory infarction
Urgent neuro-imaging may be needed, after stabilization
of ABC and reversing potential or clinically manifest herni-
ation, to rule out surgically correctable causes of raised ICP.
Clinical Signs
Clinical symptoms and signs of raised ICP are highly vari-
able and depend on the nature of the primary brain insult,
the extent of compartmentalization, the presence and loca-
tion of a mass lesion, and the rate of increase in ICP.
In awake patients: irritability, headache, vomiting, con-
fusion and decreased alertness, and neck retraction may be
the presenting features. These are neither sufficiently sensi-
tive nor specific for timely recognition of raised ICP. Tense
fontanel on palpation and papilledema, are reliable signs of
raised ICP, but the later is usually absent in acute conditions,
even in patients with documented elevated ICP.
In unconscious/comatose patients, raised ICP should be
suspected in all patients with head injury, meningitis, en-
cephalitis, liver disease and diabetes mellitus. The clinical
features strongly favoring raised ICP are generally seen late,
when brain herniation is imminent or has already set in.
These are abnormal posturing (decerebration or decortica-
tion), abnormal pupillary dilatation, hypertension, bradycar-
dia, irregular breathing, sixth nerve palsy and papilledema.
Cushing reflex (hypertension, bradycardia, irregular
breathing) becomes evident only later in the course of ill-
ness, and may not occur in young children. Abnormal pu-
pillary dilatation and posturing can occur in the absence of
raised ICP.
CT scan signs of brain swelling are predictive of in-
creased ICP, but the CT scan may be normal even in the
presence of documented raised ICP.
Signs of Brain Herniation
Pressure gradient between various intracranial compartments
may lead to herniation of brain from one compartment to
520 Indian J Pediatr (April 2012) 79(4):518–524

Fig. 1 Approach to
Neurological Examination
Neurological examination
management of raised ICP
Si gns and
Signs andssymptoms
ym ptomsS/O
S/O raised
raised ICP
ICPorormm- GCS
- GCS≤ 8

If signs of impending herniation
present (unequal pupils, posturing )
Hyperventilation
-Double of the normal breathing rate
for the given child for 10 min only
-Look for reversal of unequal pupils and
posturing

If resectable mass/ bleed/

Care of A, B, C
hydrocephalous
General measures
Neuroimaging CT/MRI
NO Yes
Correct hypovolemia
Call neurosurgeon
Continue general measures
Resection/ Evacuation /CSF
diversion

Elevate head end Minimum stimulation Normocarbia(PaCo2≈35mmHg Maintain MABP >50th centile
to 30° Sedation analgesia Normoxia(PaO2>60mmHg,Sp2O by fluid and vasoactive agent
Midline (Midazolam/Morphine) >92%) Prevent or treat Fever and
Normovolemia seizures

No response

Mannitol / 3%saline Heavy sedation Mild hyperventilation

Call neurosurgeon Second tier therapy

No response
Decompressive Barbiturate coma
Craniectomy Shift to PICU once bed Hyperventilation-PaCo2<30mmHg

another . Early signs of herniation are mainly due to compres-
sion and ischemia rather than displacement of brain tissue.
Prompt recognition of the clinical signs of herniation is critical
to salvage life.
Central (or transtenorial) herniation syndrome occurs
when diffuse edema or a supratentorial mass causes down-
ward displacement of the brain through the tentorial notch.
It is characterized by progressive diencephalic dysfunction,
in a rostro -caudal direction. The earliest signs are nonspe-
cific: confusion and stupor, and small and sometimes poorly
reactive pupils. This is followed progressively by appear-
ance of decorticate (flexor) posturing, decerebrate (extensor)
posturing, obtundation and coma, and midposition, fixed
mid-size pupils. Cushing’s triad (hypertension, bradycardia,
and irregular respirations) is a late finding associated with
coma and impending death [4].
Lateral (or uncal) herniation syndrome occurs when a
lateral mass lesion causes displacement of the midbrain and
temporal lobe. The earliest signs are changes in mental
status and unilateral dilated pupil, most often on the same
side as the mass. This is followed progressively by an
ipsilateral hemiplegia (due to compression of the contra-
lateral corticospinal tract) and progressive diencephalic
dysfunction.
Herniation of cerebellar tonsils through the foramen
magnum can occur in patients with posterior fossa space
occupying lesions. It causes compression of the cerebellum,
and respiratory centers in the lower brain stem, resulting in
irregular breathing and respiratory arrest.
Goals and Principles of Therapy
The immediate goal is to prevent progression to herniation
or to reverse the herniation if present, and then to maintain a
CPP >60 mmHg and ICP <20 mmHg.
The principles of management include maintaining nor-
moxia and normocarbia; avoiding factors that aggravate or
precipitate raised ICP namely fever, hypoxia, hypoglyce-
mia, hypotension and any noxious stimulation; treatment
of underlying cause—whether intracranial or extracranial
including surgical intervention; maintain adequate MAP
(more than 50th centile for given age and gender) with help
of fluid and, if needed vasoactive therapy; and bringing
down ICP.
Therapeutic measures to bring down ICP, after surgi-
cal management of mass lesions, are divided into first-
tier and second-tier therapies (Table 2). First-tier
Indian J Pediatr (April 2012) 79(4):518–524
Table 2 Therapeutic modalities to reduce raised intracranial pressure
General measures and First tier therapy
• Head in neutral position, 30° elevation.
• Ensure oxygenation- Normoxia (PaO2 >60 mmHg, SpO2 >92%)
• Ensure adequate circulating volume- Normovolemia
• Maintain normal BP
• Ventilation to achieve PaCO2 035 mmHg
• Osmotic diuretic- Mannitol 0.25–0.50 /kg i.v. over 20 min,
repeat S.O.S or
Hypertonic (3%) saline infusion: 10 ml/kg bolus, followed by
0.1 ml−1.0 ml/kg h infusion
• Dexamethasone - 1–2 mg/kg i.v.q 6 h—cytotoxic cerebral
edema (brain abscess, granuloma, tumor)
• CSF drainage - Obstructive hydrocephalus
• Prevent all events that increase ICP
Fever / hypothermia, pain- adequate sedation–analgesia,
seizures- anticonvulsant, loud noise, invasive stimuli
Second tier therapy
• Hyperventilation (PaCO2 30–35 mmHg)
• Barbiturates coma- Thiopental or pentobarbital
• Moderate hypothermia(32–34°C)
Third tier therapy
• Decompressive craniectomy or temporal lobectomy
• Profound hyperventilation to PaCO2 <30 mmHg (use transiently)
therapies include elevation and positioning of head,
sedation and analgesia, hyperosmolar therapy, and mild
hyperventilation and placement of an ICP monitor. Sec-
ond and third tier therapies include lumbar drainage of
CSF, high-dose barbiturates, decompressive craniectomy,
and hypothermia; these treatments are reserved for increased
ICP that does not respond to first-tier therapies. Much of these
treatment principles and guidelines are extrapolated from
studies on adult patients and patients with traumatic brain
injury. Few studies have directly evaluated treatment of raised
intracranial pressure in children.
Airway, Breathing and Circulation
Airway
In unconscious patients airway patency should be ensured
by proper positioning of the head or by positioning the
patient on the side and suctioning of the oral secretion.
Oro- or naso- pharyngeal airways can be used.
Indications for endotracheal intubation [5]:
1. Modified Glasgow coma score (m-GCS)≤8
2. Patients with signs of respiratory distress
- Declining O2 saturation
- Increasing O2 requirement
521
3. Patients unable to protect airway
4. Signs of inadequate ventilation and oxygenation, such
as irregular respiratory effors, inadequate chest move-
ments, poor air entry, central cyanosis
Rapid sequence induction (RSI) accompanied by cricoid
pressure (Sellick maneuver) is preferred for emergency in-
tubation to prevent aspiration and sudden surge in intracra-
nial pressure (ICP). The medications that facilitate
intubation without increasing the ICP, should be used. [5].
Monitor heart rate, blood pressure, SpO2; provide 100%
oxygen and bag ventilation as tolerated by patient and if
no airway contraindications, administer sedation and neuro-
muscular blocking agents [5]: Midazolam (0.2–0.3 mg/kg
IV), Morphine (0.1 mg/kg IV) / Fentanyl (5–10 μg/kg IV),
and lidocaine (1–1.5 mg/kg IV) and short acting non-
depolarizing neuromuscular blocking agents (vecuronium
0.1 mg/kg IV/atracurium 0.5 mg/kg IV/ rocuronnium 0.6–
1.2 mg/kg IV). Ketamine and succinyl choline should be
avoided.
Breathing
Maintain normoxia and normocarbia. 100% oxygen should
be started with non re-breathing mask and if needed, bag
valve mask ventilation to ensure adequate oxygenation.
Mild short-term hyperventilation should be undertaken if
danger of impending herniation is present ((unequal pupils,
posturing; see above). To achieve this with manual ventila-
tion, administer double the normal breathing rate for given
age for 10 min duration. Monitor reversal of unequal pupils,
posturing and improvement in mentation. Target a PaCO2 ≈
30–32 mmHg. There is no role for prophylactic hyperven-
tilation Fig. 1.
Circulation
Maintain euvolemia. If there are signs of poor perfusion,
give a bolus of normal saline 20 ml/kg. Maintain MAP to
achieve desired CPP, if needed by using fluid and vasoactive
agents (dopamine, nor-epinephrine). Colloids are not rec-
ommended in acute brain injury (except in acute ischemic
stroke) due to their adverse effect on survival [7].
General Measures and First Tier Therapy
1. Head position
Elevate head end of bed by 30° and keep head in neutral
position to promote venous drainage via the external jugular
veins. Ensure adequate intravascular volume to prevent
orthostatic hypotension.
522
2. Sedation and Analgesia
Use midazolam 1–3 μg/kg/min, Morphine 0.1 mg/kg/
dose Q6h. Sedative doses have to be individualized, and
titrated to achieve Ramsay sedation scale score of 3–4. At
score 3 the patient responds to commands only and at score
of 4 the patient is asleep, but has brisk response to glabellar
tap or loud auditory stimulus.
3. Osmotherapy—Mannitol, 3% hypertonic saline (HS)
Mannitol (20%)
Early effect includes reduction of blood viscosity, with
improvement in microvascular CBF, cerebral oxygenation,
and CPP with reduction in cerebral blood volume (CBV),
and ultimately lowering of ICP. Late effect, that occurs
within 15–30 min and lasts upto 6 h, results from direct
osmotic effect on neural cells with reduction in total brain
water. Additional effects include reduced CSF production.
For optimal effect, serum osmolality should be maintained
below 320 mOsm [6].
Standard dosage: 0.5 g/kg i.v bolus, if further dose is
required use 0.25 g/kg/dose. Do not repeat mannitol in less
than 4 h. Monitor the urine output and take care of hypo-
volemia. Mannitol is contraindicated in decompensated
shock, oliguria, anuria and heart failure.
Hypertonic Saline (3%HS)
Hypertonic saline creates an osmotic force to draw water
from the interstitial space of the brain parenchyma into the
intravascular space. It promotes rapid CSF absorption,
increases cardiac output, and expands intravascular volume
thereby augmenting the CPP with a positive inotropic effect
[7, 8].
Standard dosage: For continuous infusion, 3% HS is
preferred via central line. Usual dose is 10 ml/kg as a
loading followed by 0.1–1 ml/kg/h. In cerebral edema, the
initial serum sodium goal is commonly set at 145–155 mEq/
L and is intensified upto 160 mEq/L if clinically indicated.
In general it is well tolerated and complications are rare.
Monitor serum sodium and creatinine every 6 h. It is contra-
indicated if serum sodium is >150 mEq/l, and /or osmolality
>320mOsmol/L.
Therapy must be tapered after 24 h of continued infusion
to prevent rebound rise of ICP.
Mannitol vs. Hypertonic Saline
It is unclear which of these two therapies is superior for
reduction of ICP. Hypertonic saline is effective in reducing
raised ICP, but does not have clear survival or outcome
Indian J Pediatr (April 2012) 79(4):518–524
benefit. A recent systematic review found that HS appears
to achieve a greater reduction in ICP than other osmotic
agents in TBI and in one series of non traumatic encepha-
lopathies, there was less mortality with use of HS as com-
pared to mannitol [8].
4. Temperature
Fever increases metabolic rate by 10% to 13% per degree
Celsius and is a potent cerebral vasodilator. Keep the tempera-
ture below 38°C (36–37°C axillary). If child is febrile, use
paracetamol 15 mg/kg/dose oral or IV Q4h and surface cooling.
5. Glucose control
Keep random blood sugar (RBS) around 150 mg/dl.
Hypogycemia (<60 mg/dl) and hyperglycemia (>180 mg/
dl) should be avoided.
6. Seizure prophylaxis
Consider seizure prophylaxis in patients at high risk of
seizures such as those with severe head injury, focal symp-
toms and signs and CNS infections (meningitis and enceph-
alitis). Use phenytoin—20 mg/kg IV loading, followed by
5 mg/kg/d for the first 7 d only.
Comatose children should also be considered for EEG
monitoring and seizure prophylaxis as non-convulsive seiz-
ures are not uncommon in them. These can cause sudden
surge in ICP.
7. Use Lidocaine 1 mg/kg/dose 5 min before endotracheal
suctioning and procedure (IV and ET). Do not repeat
within 2 h.
8. GI bleed prophylaxis
Use Antacid 1 ml/kg/dose Q 8 h or pantoprazole 1 mg/
kg/dose Q 12 h, (if G.I bleed is present use pantoprazole).
9. Anemia
Maintain Hb concentration around 10 g/dl, to help cerebral
oxygen delivery. In cases with severe anemia, a marked in-
crease in CBF occurs to maintain cerebral oxygen delivery.
10. Hypertension
Increase in blood pressure is common in response to
raised ICP. Characteristically rise in systolic-BP increase is
greater than diastolic-BP. When autoregulation is impaired,
hypertension may increase CBF and ICP, and may exacer-
bate cerebral edema and postoperative IC bleeds. Generally
it is left untouched in acute raised ICP unless underlying
cause is hypertensive encephalopathy. Treatment is also
reasonable in patients with impending congestive cardiac
failure, those with evidence of rapidly worsening brain
edema on CT scan, and those with a persistent extreme surge
in blood pressure. If it is decided to treat hypertension,
Indian J Pediatr (April 2012) 79(4):518–524
vasodilating drugs, such as nitroprusside, nitroglycerin and
nifedipine, should be avoided; these could increase ICP.
Sympathomimetic-blocking drugs (esmolol, labetalol) or
centrally acting alfa-receptor agonists (clonidine) are pre-
ferred because they reduce BP without affecting ICP.
11. Corticosteroids
Corticosteroids are commonly used for primary and sec-
ondary brain tumors, to decrease vasogenic edema. The
most commonly used regimen is IV dexamethasone
0.15 mg/kg/dose every 6 h (max.16 mg/d). Routine use in
TBI is not recommended.
12. Antibiotics/ Antiviral
In a febrile child give empiric first dose of ceftriaxone
(50 mg/kg IV q 12 h) and acyclovir 30 mg/kg iv in 3 divided
doses 8 h as infusion over 1–2 h for herpes encephalitis. If
child is a resident of P. falciparum endemic area, and has
hypoglycemia, anemia or absent meningeal signs then give
empiric IV Artesunate/Quinine.
13. Glycerol
It is not used for acute reduction of raised ICP. However,
oral glycerol (6 g/kg/d, 6 h for 2 d) has been shown to
improve outcome in children with acute meningitis.
Second Tier Therapy
These options may be considered in hemodynamically sta-
ble patients with raised ICP refractory to other measures, if
continuous cardiovascular and electroencephalogram moni-
toring, and mechanical ventilation are available.
1. Heavy sedation
Use morphine and midazolam and titrate the dose to achieve
the Ramsay sedation score 5, which corresponds to state where
child is asleep, and has sluggish response to glabellar tap.
2. Barbiturates coma- Thiopental or pentobarbital
Barbiturates can reduce the cerebral metabolic rate
and lower ICP. However, they can also cause significant
fall in systemic blood pressure. Pentobarbital is given in
a loading dose of 10 mg/kg followed by 5 mg/kg each
h for 3 doses. The maintenance dose is 1 to 2 mg/kg/h,
titrated to a achieve a burst suppression pattern on
electroencephalogram shows.
3. Moderate hypothermia (32–34°C)
Moderate hypothermia (32–34°C) is a controversial
second-tier therapy. Neuromuscular blocking agents and se-
dation must be used during hypothermia to prevent shivering.
523
Third Tier Therapy
Decompressive Craniectomy
Decompressive craniectomy may be a useful option for
control of increased ICP in children. Craniectomy per-
formed within the first 24 h after severe head injury, and
in refractory raised ICP due to CNS infections may improve
outcomes [9].
Investigations
Random blood sugar, i-Ca2+,serum electrolytes, Hemogram,
Blood culture and, febrile encephalopathy work-up should
be done.
Neuroimaging
Obtain neuroimaging (CT/MRI) in all patients with raised
ICP soon after stabilization. CT will readily identify intra-
cranial bleed, hydrocephalus, cerebral edema, compartmen-
tal shifts, infarct, abscess or ICSOL. Initial normal CT does
not rule out an evolving lesion of an infection or raised
intracranial pressure. In herpes simplex encephalitis, CT
head is abnormal in approximately 50% of cases but may
be normal in the first 4–5 d.
Monitoring
Monitor continuously for all vital parameters (temperature,
HR, RR, BP, MABP, CFT), and level of consciousness
(hourly), neurological status, brainstem signs, oxygenation
(SpO2) and EtCO2, ICP, cerebral perfusion pressure. Also
assess adequacy of sedation and analgesia, input and output
and bowel sounds. After a dose of mannitol, monitor the
urine output hourly. Random blood sugar should be moni-
tored at least every 6 h, and if hypoglycemia/hyperglycemia
monitor blood sugar every 1–2 h. Serum sodium should be
monitored every 4–6 h, if 3% saline is used. EEG should be
monitored to look for non-convulsive seizure if child is
comatose.
Disposition
All patients with raised ICP should be transferred to PICU
for continuous monitoring, including ICP monitoring, fur-
ther diagnostic evaluation and treatment.
524
Key Points
1. Immediate goal is to prevent progression to herniation or to
reverse herniation if present and to maintain CPP
>60 mmHg and ICP <20 mmHg.
2. Identify the signs of impending brain herniation and treat
immediately.
3. Keep the patient with head end elevated by 300 and
neutral neck position, under adequate sedation and anal-
gesia, and minimal stimulation.
4. Short term hyperventilation using bag ventilation is required
in patients with signs of impending herniation. Target
PaCO2 ≈30–35 mmHg while using hyperventilation.
5. Hyperosmolar therapy (mannitol or 3% saline) is useful
in achieving rapid fall in ICP. In general, 3% saline is
well tolerated and complications are rare.
6. Avoid factors that aggravate or precipitate elevated ICP.
7. Identify and treat reversible and acute causes.
8. Monitor the urine output and take care of hypovolemia if
mannitol is used.
9. Transfer to an ICU as soon as possible.
Indian J Pediatr (April 2012) 79(4):518–524
References
1. Singhi P, Singhi S, Baranwal AK. Bacterial meningitis in children:
critical care needs. Indian J Pediatr. 2001;68:737–47.
2. Singhi SC, Tiwari L. Management of intracranial hypertension.
Indian J Pediatr. 2009;76:519–29.
3. Bansal A, Singhi S, Singhi P, et al. Non traumatic coma. Indian
Pediatr. 2005;72:467–73.
4. Posner JB, Saper CB, Schiff ND, Plum F. Diagnosis of
stupor and coma. 4th ed. New York: Oxford University Press;
2007.
5. Thompson AE, Salonia R. Airway management. In: Fuhrman BP,
Zimmerman JJ, editors. Pediatric critical care. 4th ed. Philadelphia:
Elsevier Saunders; 2011.
6. Knapp JM. Hyperosmolar therapy in the treatment of severe head
injury in children. AACN Clinical Issues. 2005;16:199–211.
7. Mayer MJ, Megyesi J, Meythaler J, et al. Acute management of
acquired brain injury part II: an evidence-based review of pharma-
cological interventions. Brain Injury. 2010;24:706–21.
8. Gwer S, Gatakaa H, Mwai L, et al. The role for osmotic agents in
children with acute encephalopathies: a systematic review. BMC
Pediatrics. 2010;10:23–30.
9. Adamo MA, Deshaies EM. Emergency decompressive craniec-
tomy for fulminating infections encephalitis. J Neurosurg.
2008;108:174–6.
Indian J Pediatr (October 2012) 79(10):1351–1357
DOI 10.1007/s12098-012-0831-8
SYMPOSIUM ON PGIMER PROTOCOLS IN NEUROLOGICAL EMERGENCIES
Approach to a Child with Acute Flaccid Paralysis
Sunit C. Singhi & Naveen Sankhyan & Ravi Shah &
Pratibha Singhi
Received: 26 January 2012 / Accepted: 8 June 2012 / Published online: 12 July 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Acute flaccid paralysis (AFP) is a clinical syndrome
characterized by rapid onset weakness, that many times includes
respiratory and bulbar weakness. AFP is a broad clinical entity
with an array of diagnostic possibilities. An accurate and early
diagnosis of the cause has important bearing on the management
and prognosis. The immediate priorities in a child who presents
with acute progressive weakness are; to detect and manage
respiratory muscle weakness, to detect and manage bulbar
weakness, evaluate for cardiovascular instability, detect and
manage dyselectrolytemia or toxemia, and to detect and manage
a spinal compression (traumatic, intraspinal collections). Ur-
gent imaging of the spine is needed in settings where a spinal
cord involvement is suspected. Compressive or traumatic spinal
lesions may need early neurosurgical intervention. Anterior horn
cell injury is usually due to direct viral infection. More distal
pathologies are generally immune mediated and respond to
immunomodulation. Irrespective of the cause, generalized
weakness frequently affects respiratory and bulbar function.
Such children need careful monitoring and respiratory support.
Keywords Polio . Acute weakness . Paraparesis .
Transverse myelitis . Guillain Barre syndrome
S. C. Singhi (*) : N. Sankhyan : R. Shah : P. Singhi
Department of Pediatrics, Advanced Pediatrics Centre, Post
Graduate Institute of Medical Education and Research (PGIMER),
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Introduction
Acute flaccid paralysis (AFP) is a clinical syndrome
characterized by rapid onset weakness, that frequently
includes respiratory and bulbar weakness. The weakness
usually progresses to maximum within days to weeks.
The term “flaccid” indicates the absence of spasticity or
other signs of disordered central nervous system motor
tracts such as hyperreflexia, clonus or extensor plantars
[1]. AFP is broad clinical entity with an array of diag-
nostic possibilities. An accurate and early diagnosis of
the cause has important bearing on the management and
prognosis. If not managed appropriately, paralysis can
progress to respiratory failure and death. Another issue
of public health importance is the immediate reporting
of all cases of AFP to the polio surveillance team(Box
1). Any case meeting the AFP definition undergoes a
thorough investigation to determine if the paralysis is
caused by polio. Each case of AFP is to be reported
and 2 stool samples (≥24 h apart, each 8–10 g) are
collected within 14 d of paralysis onset and sent to
WHO accredited laboratory.
1352
Box 1 Acute flaccid paralysis (Epidemiological definition-WHO 2005)
This protocol focuses on the clinical evaluation of a
child presenting with AFP and provides a practical
clinical approach to diagnosis in the Emergency depart-
ment. For a detailed discussion on AFP the reader is
referred to other reviews on the subject [1]. The objec-
tives of this article are: to provide a practical approach
to diagnosis in an individual patient; to provide an
approach to rational use of diagnostic tests and discuss
the common causes of AFP in children.
Diagnostic Approach
Initial Assessment and Stabilization
Every child with AFP is a medical emergency requiring
systematic evaluation and management. Initial assess-
ment of any such acutely ill child should concentrate
on rapid cardiopulmonary assessment and resuscitation.
Following are the key areas on initial assessment;
& Detect and manage respiratory muscle weakness: Any
child with acute weakness should be evaluated for res-
piratory muscle weakness. Younger children with respi-
ratory muscle weakness may present with non-specific
irritability, sweating, poor feeding and shallow or para-
doxical respiratory efforts. Older children may complain
of respiratory difficulty, may have excessive sweating,
agitation, air hunger, reduced single breath count/chest
expansion or shallow/paradoxical respiratory efforts.
Careful serial examinations may be critical in such chil-
dren to pick up the weakness early. Early elective intu-
bation and respiratory support are critical to save these
affected children.
& Detect and manage bulbar weakness: Symptoms of
voice change, poor cry, pooling of secretions, gur-
gling sounds in throat, poor ability to swallow and
choking on feeds may be markers of bulbar dysfunc-
tion. Care should be taken to avoid oral feeding,
providing regular suction and ensuring entral nutri-
tion via nasogastric feeding.
Indian J Pediatr (October 2012) 79(10):1351–1357
& Evaluate for cardiovascular instability: Conditions
leading to AFP (Spine trauma, myelitis, Guillain
Barre syndrome) can also result in cardiac rhythm
abnormalities and cardiovascular insufficiency. These
issues will require a priority management. Hence,
attaching a quadriparetic child to an ECG/cardiac
monitor is an early step in the management.
& Rule out dyselectrolytemia or toxemia: Hypokalemia
and snake envenomation are important causes of flaccid
paralysis. These causes should be excluded in all chil-
dren with AFP by history and examination, early in
management course. A rapid assessment of electrolytes
and ECG should be sought in all such children.
& To rule out a spinal compression (traumatic, intraspinal
collections). : At the outset, patients with possible
spinal injury due to trauma or other lesions requiring
urgent neurosurgical intervention should be identified
on history and examination. Immediate spinal stabili-
zation and administration of corticosteroids in those
with trauma would be a priority, while neurosurgical
relief of spinal compression may be warranted to
prevent long term disability.
History
The first step is to determine if an unwell child actually has
muscle weakness. Many children with weakness present
with nonspecific symptoms of irritability, lethargy and
clumsy walk or refusal to walk. Children with abnormal
gait, limp or refusing to walk may present initially to ortho-
pedic or trauma clinics. Pseudoparalysis due to limb pain
may result from trauma, arthritis/arthralgia, myostis, joint or
periosteal bleeds or joint or periarticular infections or
inflammations.
It is useful to remember the possible causes of AFP
in children using a neuro-anatomical approach (Table 1).
Information is derived from the history and focused
neurological examination looking at pattern of tone,
tendon reflexes, sensory examination, signs and symp-
toms of bladder and/or bowel involvement. (Table 2).
Indian J Pediatr (October 2012) 79(10):1351–1357 1353

Investigations Table 2 Selected clues in history and examination while evaluating a

child with acute flaccid paralysis
The choice of the initial investigations would depend on
the information gained from history and examination. Points in history Remarks
and/or examination
Moreover, the urgency to arrive at the diagnosis would
also dictate the sequence and choice of investigations. A Fever at onset Polio or enteroviral myelitis, Transverse
step wise and judicious use of investigations would help myelitis, myositis, epidural abscess, and
reach the diagnosis with the minimum use of resources Koch spine (prolonged history)
(Fig. 1). Trauma: head/neck Trivial trauma may lead to spinal
compression in patients with cervical
1. MRI Spine: It is indicated when there is a suspicion of vertebral instability (Patients with
spinal cord compression or transverse myelitis. More Downs syndrome, congenital
cervicovertebral anomalies or juvenile
specifically, any child with history of neck or back trau- idiopathic arthritis)
ma, rapid onset flaccid profound quadreparesis, early or Exposure Toxins: lead, arsenic
persistent bladder or bowel involvement, sensory loss or Snake envenomation
sensory level on examination, spinal tenderness, neuro- Dog bite: Rabies
cutaneous markers, or appearance of UMN signs on ex-
Preceding infectious Guillain Barre syndrome or transverse
amination (e.g., up going plantars) should get an MRI of prodrome/vaccination myelitis
the spine. Sore throat, neck swelling, diphtheretic
2. CSF examination: This is helpful to narrow the diag- polyneuropathy (non/partly immunized)
nostic possibilities. A raised CSF cell count would be Precipitating factors Diarrhea: Hypokalemia, enteroviral
seen in patients with transverse myelitis, infective my- myelitis
elitis viz. polio or enteroviral myelitis, varicellas or Exertion or post parandial: Hypokalemic
herpes myelitis, rabies, etc. A raised CSF protein with periodic paralysis
normal cell count (albuminocytological dissociation) Intramuscular injection: Polio, traumatic
sciatic neuritis
suggests Guillain Barre syndrome, post diphtheritic
Sensory loss/level Compressive myelopathy, transverse
myelitis
Early bowel/bladder Compressive myelopathy, transverse
Table 1 A neuroanatomical differential diagnosis of acute flaccid involvement myelitis
paralysis in children Constipation in <1 y Botulism (H/o honey exposure)
Site Pathophysiology Disease Prominent autonomic Guillain Barre syndrome, Rabies, acute
signs/symptoms myelopathy
Spinal cord Compressive Traumatic spinal injury, epidural Ascending weakness Guillain Barre syndrome, Rabies,
abscess, hematoma, discitis Varicella zoster virus, ascending myelitis
Inflammatory Transverse myelitis Descending weakness Diphtheria, Botulism
Anterior horn Viral Poliomyelitis, vaccine associated Prominent and early Myasthenia Gravis, Botulism
cell poliomyelitis, Enteroviral ptosis
myelitis, Japanese encephalitis Facial weakness Guillain Barre syndrome, Myasthenia
Vascular Anterior spinal artery infarction Gravis, Botulism
Roots/nerves Immune mediated Guillain Barre syndrome, Fluctuating symptoms, Myasthenia Gravis
fatigability
Toxin Post diphtheritic, porphyria, Muscle tenderness Myositis, inflammatory myopathy,
arsenic (myalgias may be severe in Guillain
Viral Rabies Barre syndrome)
Trauma Injection related sciatic neuritis Muscle stretch reflexes Absent: Guillain Barre syndrome, Polio,
Neuromuscular Immune mediated Myasthenia Gravis Diphtheria, spinal shock, at level of
junction spinal cord damage
Drugs, toxins Organophosphates, snake venom,
drugs (aminoglycosides), Preserved : Myasthenia Gravis, periodic
Botulism paralysis, Botulism
Dyselectrolytemia Hypermagnesemia Exaggerated: Below level of spinal lesion,
Upper motor neuron lesion
Muscle Infection Viral myositis
Spinal tenderness, Spinal trauma, epidural abscess or other
Inflammation Inflammatory myopathy
painful spine extradural compression
(polymyositis)
movement
Channelopathy Hypokalemic periodic paralysis Neck stiffness Polio, enteroviral myelitis, Guillain Barre
Dyselectrolytemia Hypokalemia syndrome, transverse myelitis
1354 Indian J Pediatr (October 2012) 79(10):1351–1357

Fig. 1 Approach to child with Acute paraparesis/plegia

acute paraplegia or paraparesis

Features of spinal cord compression* / Sensory level on examination

Yes No

CEMRI spine as early as possible DTRs

/+

Compressive Noncompressive
Ocular/bulbar Symmetric?
myelopathy myelopathy
+ involvement?
+

Neurosurgery AcuteTM:Treat with high

Myasthenia, GBS#
consult+ steroids dose steroids and consult
Botulism CPK,K +,
DTR Deep tendon reflexes; CPK Urine myoglobin
Creatine phosphokinase; TM
Transverse myelitis; GBS Gul-
lain Barre Syndrome, NCV Polio, GBS,
Nerve conduction velocity; CSF Traumatic
Cerebrospinal fluid. *Bony ten- neuritis. Get
derness/deformity, root pains, NCV
girdle sensation /early bladder
Viral myositis,
or bowel involvement #other IVIG,Neuro
periodic paralysis,
possibilities according to clinical Rhabdomyolysis consult,NCV,
CSF
features as described in text

polyneuropathy or rarely may be seen in transverse
myelitis. The CSF can be normal early in the course of
these illnesses.
3. Nerve Conduction studies and Electro Myography
(EMG): These studies confirm the involvement of
nerves and help in diagnosis of anterior horn cell dis-
eases. These are particularly helpful to confirm Guillain
Barre syndrome. The repetitive nerve stimulation test
helps to diagnose myasthenia gravis and botulism.
Rarely, these may aid the diagnosis of an inflammatory
myopathy.
4. Creatine Kinase: Raised levels of muscle enzyme crea-
tine kinase reflects acute muscle fiber injury and may
point towards a muscle disease. In the setting of AFP
this may be seen in children with viral myositis or
inflammatory myopathy.
Differential Diagnosis of AFP (Table 3)
Some of the commonly encountered causes of AFP are
discussed below;
Guillain Barre Syndrome (GBS)
With the control of polio, GBS is the most common cause of
AFP in children. Worldwide its incidence is 0.6–4 cases per
100,000 per year [2]. It most commonly occurs after an
infection triggered immune mediated attack on the nerve axons
or myelin. Antecedant respiratory or gastrointestinal illnesses
are commonly found in the history [3]. The most common
underlying subtype of the syndrome is the acute inflammatory
demyelinating polyradiculoneuropathy (AIDP) but the other
common subtype of acute motor axonal neuropathy (AMAN)
may be equally common in Indian children [4]. In the typical
cases, the first symptoms are usually pain, paraesthesia, or
weakness in the limbs which spreads proximally. Weakness
may progress rapidly, and approximately 50 % of the children
will reach nadir by 2 wk, 80 % by 3 wk, and the rest by 4 wk.
Risk factors for children requiring ventilation are cranial nerve
involvement, increased CSF protein during first week of illness
and short period between antecedent illness and the onset of
symptoms [5]. Investigations required for confirming the diag-
nosis are; nerve conduction studies and lumbar puncture (to
document CSF albumin-cytological dissociation). A raised
CSF protein concentration is present in about 80 % of patients,
but CSF protein content is more likely to be normal during the
first days of the illness [3]. When a child presents in the acute
phase, the differentiation from polio or enetroviral myelitis can
be done based on CSF. Viral myeltis would show CSF pleocy-
tosis, which would be conspicuously absent in GBS. CSF
should be analyzed before treatment with intravenous immu-
noglobulin (IVIG) as IVIG can cause aseptic meningitis. Man-
agement of a child with GBS would involve a meticulous
observation for respiratory, bulbar muscle weakness. Early
elective intubation and ventilatory support are important in
the acute phase. During hospitalization, monitoring for
Indian J Pediatr (October 2012) 79(10):1351–1357 1355

Table 3 Characteristics to aid differential diagnosis of acute flaccid paralysis

Feature Transverse Poliomyelitis Guillain-Barre Traumatic neuritis

myelitis syndrome (following injection)

Development From hours to four days 24 to 48 h from onset From hours to 4 wk From hours to four days
of paralysis to full paralysis
Fever at onset May be present High, always present at Uncommon Present, if underlying
of weakness onset of flaccid paralysis infection being treated
with IM injections
Paralysis Symmetric Asymmetric, Symmetric, mostly ascending Affects only one limb
Progression Descending• Ascending
of paralysis
Muscle tone Reduced during Reduced Reduced Reduced
acute phase
Deep-tendon Absent in lower Decreased or absent Absent Decreased or absent
reflexes limbs(early);
hyperreflexia(late)
Sensation Anesthesia of lower Severe myalgia, backache, Cramps, tingling, hypoanesthesia Pain in gluteus
limbs with sensory no sensory changes of palms and soles
level
Cranial nerve Absent Only when bulbar Often present, affecting nerves VII, Absent
involvement involvement is present IX, X, XI, XII
Respiratory Sometimes Only when bulbar Occurs in severe cases Absent
insufficiency involvement is present
Autonomic signs Present Rare Frequent in severe cases (blood pressure Hypothermia in
and symptoms alterations, sweating, blushing, and affected limb
body temperature fluctuations)
Cerebrospinal Normal or Mild elevation of Albumin-cytologic dissociation (usually Normal
fluid Pleocytosis lymphocytes 10 <10 cells/ml, never >50cells/ml)
to 200/mL
Bladder dysfunction Present- early Rare Occasionally (Transient, at the Never
and persistent peak of weakness, 1–3 d (30 %))
Nerve conduction Normal Abnormal: anterior Abnormal: slowed conduction, Abnormal: s/o
velocity: third wk horn cell disease decreased motor-sensory
(normal during motor amplitudes axonal damage
first 2 wk)
Diagnostic test MRI–spine Stool viral detection Nerve conduction studies Nerve conduction studies,
Electromyography

Adapted and modified from Global Program for Vaccines and Immunization: Field Guide for Supplementary Activities Aimed at Achieving Polio
Eradication. Geneva, World Health Organization, 1996

autonomic instability and prevention of nosocomial complica-
tions are essential to optimize outcomes. IVIG is the
treatment of choice in the authors’ setting for GBS,
given the availability, ease of administration and the
safety compared with plasmapheresis. It is given in the
dose of 2 g/kg spread over 2–5 d.
Anterior Horn Cell Viral Myelitis
Poliomyelitis
Both the wild polio virus and the vaccine associated polio
virus cause anterior horn cell affliction to result in flaccid
paralysis. Children under 5 y are the most frequently affected.
However, older individuals and adults can also develop
poliomyelitis. The initial symptoms of polio are non-specific
and include fever, headache, vomiting, constipation, neck
stiffness and pain in limbs. The paralysis follows or accom-
panies these symptoms. The maximal weakness evolves
quickly over 1–2 d. A history of intramuscular injections
precedes paralytic poliomyelitis in about 50–60 % of patients,
patients may present initially with fever and paralysis (prov-
ocation paralysis). Clinical characteristics of poliomyelitis
include; 1. Fever at onset 2. Rapid progression of paralysis
within 24–48 h 3. Asymmetric, proximal more than distal
limb paralysis 4. Preservation of sensory function often with
severe myalgias 5. Residual paralysis at 60 d [6]. Most of the
children with paralytic polio die from complications of bulbar
paralysis and respiratory failure. Management is mainly fo-
cused on meticulous supportive care.
1356
Non Polio Enteroviral Myelitis
Non polio enteroviruses can cause a polio like paralytic
disease. Among all known nonpolio enteroviruses,
enterovirus-71 has been most strongly implicated in out-
breaks of central nervous system disease and AFP. The
clinical syndrome frequently is associated with aseptic men-
ingitis, hand, foot and mouth disease and hemorrhagic con-
junctivitis [7]. Weakness associated with enterovirus disease
can be severe and permanent.
Other Viruses Causing AFP
Rabies The common presentation of human rabies is with
fever, behavioral and autonomic instability and hydro/aero
phobia. However, a minority of the patients can present
primarily with paralytic disease. This type of presentation
follows a prodrome of paraesthesias in the bitten area,
ascending paralysis or paralysis progressing from the bitten
limb. Sphincter disturbances and autonomic instability is
common. Disease progression is slower in paralytic rabies
[8]. The disease can be easily missed if a history of animal
bite is not actively sought. Frequently the bite may not be
recent and the parents may not give the history, unless
specifically asked for.
Herpes group of viruses can lead to AFP by triggering GBS
or transverse myelitis, causing polyradiculoneuropathies in
immunocompromized hosts [9]. Japanese encephalitis virus
can also preferentially affect the anterior horn cell and cause
paralysis associated with encephalitis [10].
Transverse Myelitis
It is an acute demyelinating disorder of the spinal cord. It
may occur alone or in combination with demyelination in
other portions of the nervous system. It is believed com-
monly that previous infection or immunization triggers
transverse myelitis, but no evidence supports such a notion
[11].
The common presentation includes an acute phase of spinal
shock with flaccid paraparesis or quadreparesis, urinary reten-
tion or incontinence, absent reflexes and mute plantars, sen-
sory loss/level is frequently present. After a few weeks, the
signs of UMN dysfunction appear, in the form of spasticity,
and hypereflexia. This disorder should be suspected in any
child with rapid onset flaccid profound quadreparesis, early or
persistent bladder or bowel involvement, sensory loss or sen-
sory level on examination, with suggestion of UMN signs on
examination (e.g., up going plantars). In such a situation an
urgent spinal MRI is needed to establish the diagnosis. Other
causes of acute myelopathy like trauma, paraspinal/epidural
spinal abscess, hematoma or anterior spinal artery syndrome
need exclusion in this setting. The management of transverse
Indian J Pediatr (October 2012) 79(10):1351–1357
Table 4 Summary of approach to diagnosis in a child with acute
flaccid paralysis
1. ABCs
● Ensure protection of airway and adequate ventilation
(especially if there is respiratory muscle weakness,
shallow respiration, dysphagia, weak gag)
● Check and support: BP and Heart Rate
● Immobilize neck if history of neck/head trauma
● Send electrolytes and get an ECG- to look for hypokalemia
2. Examination and classification into pattern for example,
● Flaccid Paraparesis with sensory level (early bladder dysfunction)-
Transverse myelitis, compressive myelopathy
● Flaccid afebrile symmetric para/quadriparesis (+/− bulbar and
respiratory involvement) with areflexia
and minimal sensory loss (but often sensory symptoms) : Acute
neuropathy or polyradiculopathy (esp., Guillain Barre Syndrome)
● Flaccid, febrile, pure motor, asymmetric, paralysis (no bladder
involvement) often with meningismus: Enteroviral, polio, or vaccine
associated poliomyelitis
● Flaccid motor-sensory lower limb monoparesis after IM injection:
Injection neuritis
● Ophthalmoplegia, ptosis, bulbar weaknes with motor weakness:
Miller-Fischer variant of Guillain Barre
Syndrome, Botulism, Myasthenia Gravis
● Proximal muscle weakness, muscle tenderness without sensory
symptoms or signs and with preserved
reflexes: Viral myositis, Inflammatory myopathy (e.g.,
dermatomyositis)
3. Investigations (according to the suspected site of lesion and cause
of paralysis)
● Neuroimaging (spinal cord)
○ MRI indicated in all cases of myelopathy, suspected transverse
myelitis
○ X- ray spine: suspected atlantoaxial dislocation, vertebral
tuberculosis
● Electrophysiologic testing (NCV & electromyography):
Guillain Barre syndrome
● Lumbar puncture (CSF): Guillain Barre syndrome, suspicion
of viral myelitis
● Biochemistry: Creatine Kinase, Potassium, Magnesium, Phosphate
● ECG: Hypokalemia
● Urine for porpho-bilinogens in porphyria, toxins: arsenic
4. Management (depends on the underlying etiology identified)
● All children: meticulous supportive care, anticipate and identify
respiratory, bulbar weakness (except in
injection neuritis), shock due to reduced vascular tone (spinal cord
disease), Autonomic instability, complications of immobilization
and prevention of nosocomial infections.
● Specific therapy:
○ Guillain Barre syndrome: IVIG, 2 g/kg over 2–5 d
○ Transverse myelitis: IV methy-prednisolone 10–30 mg/kg, daily
(max-1 g) for 3–5 d
○ Compressive myelopathy: spinal immobilization, surgical
intervention, steroids (acute traumatic myelopathy)
○ Dermatomyositis, Myasthenia Gravis: Immunomodulation
○ Hypokalemia: Intravenous potassium correction
Indian J Pediatr (October 2012) 79(10):1351–1357
myelitis consists of immunosuppression and supportive care.
Attention is needed to maintain airway, breathing and circu-
lation, bladder catheterization and exclusion of compressive
myelopathy by imaging. High dose pulse corticosteroids are
the recommended form therapy [11]. Methylprednisolone is
given in a dose of 10–30 mg/kg/d (max:1 g/d) for 5 d followed
by oral prednisolone 1–2 mg/kg/d for 2 wk and then tapered
over subsequent 2–4 wk.
Traumatic Neuritis (Following Injection)
Traumatic neuritis is suspected in cases in which there is one
limb involvement and definite history of injection in that
limb (usually less than 24 h) before the onset of paralysis. It
is associated with pain and hypothermia of affected limbs. It
is sometimes difficult to distinguish it from polio. However,
sensory deficits and lack of CSF pleocytosis favor the diag-
nosis of traumatic neuritis. It is probable that some cases of
polio are misdiagnosed as traumatic neuritis. Residual sen-
sory deficits strongly favor the diagnosis of injection neuri-
tis. Management is entirely supportive.
Hypokalemic Paralysis
This is an important differential in any child particularly in a
younger child with AFP. An early recognition can prevent
potentially fatal cardiac complications. In the developing
countries, it most commonly results from diarrheal diseases.
However, rarer familial chanellopathies, underlying disorders,
such as renal tubular acidosis, primary/secondary hyperaldos-
teronism also need to be considered. Correction of potassium
levels rapidly reverses the paralysis in these children.
Conclusions
AFP is a broad clinical entity with an array of diagnostic
possibilities. Every case of AFP is a medical emergency. A
systematic anatomic/pathophysiological approach to diag-
nosis helps to narrow down the diagnostic possibilities in a
given child (Table 4). Accurate and early diagnosis of the
cause has important bearing on the management and prog-
nosis. The immediate priorities are to detect and manage
respiratory, bulbar muscle weakness, rapidly exclude causes
which are reversible like dyselectrolytemia or toxemia
1357
(snake bite). Evaluation of spine by imaging may be
needed urgently in patients with suggestive clinical fea-
tures. Once these causes are excluded, most distal pa-
thologies are generally immune mediated and respond to
immunomodulation. Irrespective of the cause, general-
ized weakness frequently affects respiratory and bulbar
function. Such children need to be carefully monitored
and treated.
Conflict of Interest None.
Role of Funding Source None.
References
1. Marx A, Glass JD, Sutter RW. Differential diagnosis of acute
flaccid paralysis and its role in poliomyelitis surveillance. Epide-
miol Rev. 2000;22:298–316.
2. Hughes RAC, Rees JH. Clinical and epidemiological features of
Guillain-Barré syndrome. J Infect Dis. 1997;176:S92–8.
3. Paradiso G, Tripoli J, Galicchio S, Fejerman N. Epidemiological,
clinical, and electrodiagnostic findings in childhood Guillain-Barré
syndrome: a reappraisal. Ann Neurol. 1999;46:701–7.
4. Kalra V, Sankhyan N, Sharma S, Gulati S, Choudhry R, Dhawan
B. Outcome in childhood Guillain-Barré syndrome. Indian J
Pediatr. 2009;76:795–9.
5. Rantala H, Uhari M, Cherry J, Shields WB. Risk factors of respi-
ratory failure in children with Guillain Barre syndrome. Pediatr
Neurol. 1995;13:289–92.
6. Melnick J. Enteroviruses: polioviruses, coxsackieviruses, echovi-
ruses, and newer enteroviruses. In: Field’s BN, Knipe DM,
Chanock RM, eds. Field’s virology. Philadelphia: Lippincott-
Raven Publishers; 1996. pp. 655–712.
7. Wadia NH, Wadia PN, Katrak SM, Misra VP. A study of the
neurologic disorder associated with acute hemorrhagic conjuncti-
vitis due to enterovirus 70. J Neurol Neurosurg Psychiatry.
1983;46:599–610.
8. Gadre G, Satishchandra P, Mahadevan A, et al. Rabies viral
encephalitis: clinical determinants in diagnosis with special
reference to paralytic form. J Neurol Neurosurg Psychiatry.
2010;81:812–20.
9. Tyler KL. Herpes simplex virus infections of the central nervous
system: encephalitis and meningitis, including Mollaret’s. Herpes.
2004;11:57A–64A.
10. Misra UK, Kalita J. Anterior horn cells are also involved in
Japanese encephalitis. Acta Neurol Scand. 1997;96:114–7.
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Indian J Pediatr (January 2013) 80(1):50–54
DOI 10.1007/s12098-012-0824-7

SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS ON ONCOLOGICAL EMERGENCIES

Tumor Lysis Syndrome

Aruna Rajendran & Deepak Bansal & R. K. Marwaha &
Sunit C. Singhi

Received: 10 March 2012 / Accepted: 4 June 2012 / Published online: 1 July 2012
# Dr. K C Chaudhuri Foundation 2012

Abstract Tumor lysis syndrome (TLS) refers to the constel-
lation of deranged metabolic state, characterized by hyper-
kalemia, hyperphosphatemia, hyperuricemia, hypocalcemia,
and/or azotemia, secondary to rapid breakdown of tumor
cells. It is a life threatening emergency that typically follows
administration of chemotherapy or may be spontaneous.
Malignancies which have a large tumor burden, rapid turn-
over, as well as speedy breakdown following chemotherapy
are susceptible. Acute lymphoblastic leukemia and non-
Hodgkins lymphoma (particularly Burkitt’s lymphoma) are
typically predisposed. TLS is best managed by early antici-
pation and preventive measures than the complicated task of
treating an established TLS. Vigorous intravenous hydration
is the cornerstone of prevention as well as treatment. Ras-
buricase has revolutionized the management. It is available in
India for past 1 1/2 y, although the cost is a limiting factor.
Children with acute leukemia in developing countries may
reach health facility late, with severe anemia and hyperleu-
kocytosis. Exchange transfusion may have to be restored to
in such patients to simultaneously correct anemia and hyper-
leukocytosis and enable safe administration of fluids. Dialy-
sis may be required when the metabolic ‘trash’ overwhelms
the renal excretion, resulting in renal failure. Chemothera-
peutic drugs are often administered in a phased manner in
A. Rajendran : D. Bansal : R. K. Marwaha
Hematology/Oncology Unit, Department of Pediatrics,
Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh, India
susceptible patients, in an attempt to prevent precipitous lysis
of tumor cells. Presentation and management of TLS in
relevance to the pediatric emergency room is outlined.
Keywords Alkalinization . Allopurinol . Furosemide .
Tetany . Urate oxidase
Introduction
Tumor lysis syndrome (TLS) refers to the constellation of
deranged metabolic state, characterized by hyperkalemia,
hyperphosphatemia, hyperuricemia, hypocalcemia, and/or
azotemia, secondary to rapid breakdown of tumor cells. It is
a life threatening oncological emergency which can be
encountered by physicians in emergency medicine, pediatri-
cians, oncologists or by a nephrologist, depending on the
presentation of the patient. Early identification of high risk
patients and initiation of preventive measures are more reward-
ing than the painstaking management of established TLS.
Pathophysiology
Rapid cell breakdown results in release of intracellular ions
(K+, PO4, uric acid), overwhelming the renal excretion
(Fig. 1). Delayed recognition of metabolic disturbances can
lead to acute renal failure, cardiac arrhythmia or seizures. Cell
lysis can be spontaneous, or typically follows chemotherapy.

S. C. Singhi (*)
Department of Pediatrics, Pediatric Emergency and Intensive Care, Etiology
Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India Lymphoproliferative disorders with rapidly multiplying
e-mail: sunit.singhi@gmail.com malignant cells, including acute lymphoblastic leukemia
Indian J Pediatr (January 2013) 80(1):50–54 51

DNA Purine Table 2 Definitions of laboratory and clinical tumor lysis syndrome [3]

Laboratory TLS
Hypoxanthine Two or more following metabolic abnormalities should be present
within 3 d before, or up to 7 d following initiation of therapy
Xanthine oxidase
Uric acid: >8 mg/dl in adults or above the upper limit of normal
Allopurinol
Xanthine range for age in children
Xanthine oxidase Phosphate: >4.5 mg/dl in adults and >6.5 mg/dl in children
Potassium: >6.0 mEq/L
Uric acid
(Insoluble) Calcium: Corrected calcium <7.0 mg/dl or ionized calcium <1.12
Urate oxidase not present in humans
(Rasburicase) Clinical TLS
Presence of Laboratory TLS + abnormalities in any one of the
Allantoin following end organs:
(Highly soluble)
Kidney: Acute Kidney Injury
• Increase in serum creatinine of 0.3 mg/dl
Fig. 1 Pathway of cell lysis in tumor lysis syndrome
• A single value >1.5 times the upper limit of normal for age, in the
absence of baseline value
(ALL) and Burkitt’s lymphoma are prone for TLS (Table 1). It • Oliguria (< 0.5 ml/kg/h), lasting for 6 h
is uncommon in solid tumors (e.g., wilms tumor, retinoblas- Cardiac: Arrhythmia, death
toma, and neuroblastoma) but not unknown, particularly Neurological: Seizures
with the usage of highly effective therapies [2]. Patients
with compromised baseline renal function are more prone
than those with normal kidney function. The mortality rate manifestations occur 12–72 h following the initiation of
in TLS is up to 20 %. chemotherapy. Rarely, the onset is spontaneous. Significant
hyperkalemia (>7 mEq/L) can lead to electrocardiogram
changes, including peaked T waves and QRS complex
Definition widening, which, when untreated, may result in ventric-
ular dysrhythmia and death. Hyperphosphatemia can
Classification of TLS, as laboratory and clinical TLS is manifest as cardiac arrhythmia as well. Tetany or seizures
enumerated in Table 2. can be features of hypocalcemia. The metabolic ‘trash’
can overwhelm the renal excretion, resulting in renal
failure. At this stage, patient may become oliguric or
Clinical Features anuric, an ominous sign. Rarely, renomegaly, hypertension
and acute renal failure are frontline presentation of acute
In the majority, TLS is asymptomatic to begin. This is leukemia. Unattended TLS rapidly progresses and can result
the opportunity to identify the high risk patient and in death.
initiate preventive measures to circumvent metabolic
compromise or end organ damage. Typical clinical
Management

Table 1 Risk stratification of tumors on the basis of potential for The components include:
tumor lysis syndrome [1]
1. Early identification of high risk patient
High risk 2. Hyper-hydration
○ Burkitt’s lymphoma/leukemia 3. Management of specific electrolyte imbalances
○ Lymphoblastic lymphoma 4. Role of alkalinization
○ Acute lymphoblastic leukemia, with TLC >1,00,000/μL 5. Renal replacement therapy
○ Acute myeloid leukemia, with TLC >50,000/μL
Intermediate risk
○ Acute lymphoblastic leukemia, with TLC 50,000–1,00,000/μL Early Identification of High Risk Patient
○ Acute myeloid leukemia, with TLC 20,000–50,000/μL
○ Diffuse large B cell lymphoma
TLS is best managed by early anticipation and preventive
Low risk
measures than the herculean task of treating an estab-
○ Hepatoblastoma, Neuroblastoma, Wilm’s tumor, Germ cell tumor
lished TLS. In patients with underlying predisposing
factors (Table 3), monitoring urine output, electrolytes
52
Table 3 Predisposing factors for tumor lysis syndrome [4]
Tumor characteristics
• Malignancies prone for rapid lysis: High chemo sensitivity and rapid
growth rate
○ Acute Leukemia (ALL) and non-Hodgkin’s lymphoma
(esp. Burkitt’s)
• Large tumor volume
○ Massive intra-abdominal tumor
○ Bone marrow involvement ± hyperleucocytosis
○ Extramedullary disease (huge lymphadenopathy, massive
hepatosplenomegaly)
Host characteristics
• Small child with a large tumor
• Volume depleted state: Poor oral intake, GI loses (vomiting,
diarrhea)
Aggravating factors
• Co-administration of nephro-toxic drugs (vancomycin, amikacin,
amphotericin, contrast agents)
• Tumor infiltrating the kidneys (Leukemia, Lymphoma) or
obstructing the ureters
• Highly effective targeted therapies (e.g., Rituximab in non-Hodgkin
lymphoma)
(sodium, potassium, calcium, phosphorus, uric acid, and
creatinine) every 6–8 h during the initial 48–72 h of
chemotherapy, vigorous hydration and administration of
prophylactic allopurinol, play the key role in prevention.
Continuous ECG monitoring is useful, as electrolyte
imbalance can be rapid. In a high risk patient, the nephrologist
should be involved early in the course of management, with a
low threshold for dialysis.
Hyper-hydration
Vigorous intravenous hydration is the cornerstone of
prevention as well as treatment of TLS. The guidelines
are:
& Saline dextrose fluids at a rate 2–4 times the mainte-
nance [5]. Aim is to achieve a urine output that exceeds
2–3 ml/kg/h. Fluids should to be started 48 h prior, and
continued at least 48–72 h following the initiation of
chemotherapy. Fluids should be potassium and calcium
free.
& If the urine output is below 2 ml/kg/h, with a volume
replete state, furosemide can be added at 0.5 mg/kg/dose,
every 8–12 h [6]
& In the authors’ unit, prior to hyper hydration, the authors
ensure a ‘reasonable’ hemoglobin (Hb≥7 g/dl), to avoid
precipitating fluid overload. If Hb is low (<7 g/dl), with
no hyperleukocytosis, packed red cells are transfused
prior to hyper-hydration. If Hb is very low (<5 g/dl),
along with hyperleucocytosis, an exchange transfusion
is performed.
Indian J Pediatr (January 2013) 80(1):50–54
Management of Specific Electrolyte Imbalances
Hyperkalemia
Defined as serum potassium level >6 meq/L. Management is
similar to that of any other cause. Monitor ECG continuously.
Perform electrolytes every 4–6 h.
1. Cardiac membrane stabilization is achieved by infusing
2 ml/kg of 10 % calcium gluconate over 20 min
2. Intracellular shifting of K+ ions is achieved with 0.1 ml/
kg of Insulin and 2 ml/kg 25 % dextrose infused over
30 min, salbutamol nebulization and/or sodium bicar-
bonate infusion at 1–2 meq/kg I.V push (can aggravate
hypocalcemia!)
3. Furosemide along with hydration increases urinary
potassium excretion
4. Exchange resins (Kayexalate: 1 g/kg/dose q 6 h)
eliminates potassium through the bowel and gradually
decreases serum level
5. Emergence of hyperkalemia is itself an indication to
initiate dialysis, particularly if the above listed measures
fail to lower the level
Hyperphosphatemia and Hypocalcemia
Defined as serum phosphate concentration >6.5 mEq/L and
serum calcium <7 mEq/L (ionized calcium <1.12 mmol/L),
respectively. Hyperphosphatemia can result in cardiac
arrhythmia and nephrocalcinosis. Reduction in serum phos-
phate is achieved with:
1. Hydration, the most effective measure
2. Insulin with hypertonic dextrose, as above
3. Oral phosphate binders, such as aluminum hydroxide
(50–150 mg/kg/d, divided every 4–6 h) and sevelamer [7]
4. Dialysis, if the above measures fail
Increase in serum phosphate is accompanied by concom-
itant hypocalcemia due to calcium consumption. Hypocalce-
mia manifests as muscle cramps, tetany, seizures, prolonged
QT interval, or fatal dysrhythmias. Any measure to increase
the serum calcium will increase the calcium/phosphate prod-
uct to more than 60, leading to metastatic calcification. Cal-
cium supplementation is reserved only for the symptomatic
patient (tetany, cardiac arrhythmia, seizures) at the lowest
possible dose (50–100 mg/kg slow i.v infusion under cardiac
monitoring), to relieve the symptoms [6].
Hyperuricemia
It is defined as uric acid >8 mg/dl in adults, or above the upper
limit of normal range for age in children. Xanthine oxidase
inhibitors (Allopurinol) and hydration should be initiated 48 h
Indian J Pediatr (January 2013) 80(1):50–54 53

Obtain serum Potassium, Calcium, Phosphorus, Uric acid, Creatinine levels

and a baseline ECG. Monitor urine output

≥ 2 abnormal laboratory parameters

End organ damage

• Acute Kidney Injury
• Seizures
• Arrhythmia

NO YES

Laboratory TLS Clinical TLS

• Hyperhydration ± Furosemide
• Nephrology consultation
• Allopurinol
• Rasburicase for hyperuricemia
• Maintain Urine output ≥ 2ml/kg/h
• Electrolytes + renal function monitoring
• Specific measures for Hyperkalemia, if present

Renal replacement
Reassess at 6 h
therapy + supportive
treatment

No
Improving electrolytes and urine
output maintained

YES

Fig. 2 Approach to a child with tumor lysis syndrome

prior, and continued for at least 72 h, post initiation of chemo-
therapy. Allopurinol (available as 100 and 300 mg tablets) is
administered in a dose of 10 mg/kg/d in three divided doses;
maximum dose: 800 mg/d. The dose is reduced to 50 % or
more in renal failure. Allopurinol prevents formation of addi-
tional uric acid; it however does not lower the level of preexist-
ing raised uric acid.
Established or High Propensity to Develop Clinical TLS
Rasburicase, a recombinant urate oxidase can be used both
for prevention and treatment of hyperuricemia. The dose is
0.05–0.2 mg/kg/d I.V infusion, over 30 min. It acts by
converting uric acid to inactive, soluble allantoin. Rapid
reduction in uric acid levels without accumulation of pre-
cursor products is possible. The availability of Rasburicase
has significantly reduced the need for dialysis. It is contra-
indicated in patients with G-6PD deficiency. The drug is
expensive; a single dose often suffices in clinical practice. It
can be repeated after 24 h, if required (Inj Rasburicase
1.2 mg; ≈Rs 12,000)
54
Role of Alkalinization
Uric acid is soluble at physiological pH. In the past, systemic
alkalinization was performed with addition of 25–50 mEq
sodium bicarbonate to 500 ml maintenance fluids, to achieve
a urine pH in a narrow range, between 6.5 and 7.5 [8]. Urinary
alkalinization increases uric acid solubility. However, the
potential problems are:
& Aggravation of symptomatic hypocalcemia
& Obstructive uropathy due to intratubular calcium phos-
phate precipitation in alkalinized urine
& Crystallization of uric acid precursors, hypoxanthine and
xanthine at alkaline pH
Therefore, alkalinization has pros and cons and is a sub-
ject of controversy [6]. In the authors’ unit, alkalinization is
not performed routinely. It may be considered in a patient
with hyperuricemia when Rasburicase cannot be adminis-
tered for financial constraints.
Renal Replacement Therapy
Despite above measures for prevention and treatment of
TLS, few children do develop renal failure (6 %) or refrac-
tory metabolic abnormalities [4]. Dialysis effectively and
rapidly reduces the load of metabolic products and maintains
euvolemia in anuric children. Continuous renal replacement
therapy is the preferred modality in patients with hypoten-
sion, large metabolic burden and volume overloaded state
[1]. In a resource constraint setting, a peritoneal dialysis may
be better than no dialysis. Prognosis for complete recovery is
excellent if renal replacement therapy is initiated early and is
of prime importance than in choosing a specific dialysis
modality [4]. However, it must be emphasized that dialysis
is a suboptimal option as compared to prevention of acute
kidney injury. The management of TLS is outlined in Fig. 2.
Indian J Pediatr (January 2013) 80(1):50–54
Chemotherapy
In patients who are at risk of TLS, chemotherapeutic
drugs are often administered in a phased manner (e.g.,
prednisolone monotherapy in ALL), so as to prevent
massive tumor lysis.
Conflict of Interest None.
Role of Funding Source None.
References
1. Abu-Alfa Ali K, Younes A. Tumor lysis syndrome and acute kidney
injury: evaluation, prevention, and management. Am J Kidney Dis.
2010;55:S 1–S 13.
2. Gemici C. Tumor lysis syndrome in solid tumors. J Clin Oncol.
2009;27:2738–9.
3. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J
Med. 2011;364:1844–54.
4. Mughal TI, Ejaz AA, Foringer JR, Coiffier B. An integrated
clinical approach for the identification, prevention, and treat-
ment of tumor lysis syndrome. Cancer Treat Rev. 2010;36:164–
76.
5. Fisher MJ, Rheingold SR. Oncologic emergencies. In: Pizzo
PA, Poplack DG, eds. Principles and practice of pediatric
oncology. 6th ed. Philadelphia: Williams & Wilkins; 2011.
pp. 1143–5.
6. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guide-
lines for the management of pediatric and adult tumor lysis
syndrome: an evidence-based review. J Clin Oncol. 2008;26:2767–
78.
7. Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients
with kidney failure. N Engl J Med. 2010;362:1312–24.
8. Cairo MS, Bishop M. Tumor lysis syndrome: new therapeutic
strategies and classification. Br J Haematol. 2004;127:3–11.
Indian J Pediatr (January 2013) 80(1):55–59
DOI 10.1007/s12098-012-0884-8

SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS ON ONCOLOGICAL EMERGENCIES

Superior Mediastinal Syndrome: Emergency Management

Richa Jain & Deepak Bansal & R. K. Marwaha &
Sunit Singhi

Received: 10 March 2012 / Accepted: 23 August 2012 / Published online: 10 October 2012
# Dr. K C Chaudhuri Foundation 2012

Abstract Superior Vena Cava Syndrome (SVCS) refers to Introduction

signs and symptoms caused by obstruction of the superior vena
cava. Superior mediastinal syndrome (SMS) is the term used
when SVCS coexists with obstruction of trachea. In children, a
mediastinal pathology causing SVCS generally results in SMS
as well, due to the limited chest volume. Hence, the two terms
are often used interchangeably in children. SMS is a medical
emergency that can be challenging, albeit often rewarding to
manage. The common causes in a patient presenting to pediat-
ric emergency room include non-Hodgkin lymphoma and acute
lymphoblastic leukemia. Patients with SMS are at a very high
risk for adverse cardio-respiratory events in case they are
administered any kind of anesthetic agents, anxiolytics or sed-
atives. Investigations, including tissue diagnosis are desirable,
though not mandatory, before initiating emergency manage-
ment. The patient’s clinical condition should dictate the speed,
requirement and sequence of investigations and the specific
treatment. The least invasive procedure should be performed
to confirm the diagnosis. As the most common cause of SMS in
children is lymphoma/leukemia, the administration of systemic
steroids is often the front line therapy. Diagnosis, monitoring
and management of SMS in relevance to the pediatric emer-
gency room are outlined.
Keywords Chemotherapy . FNAC . Hydration .
Mediastinal mass . Tumor lysis syndrome
S. Singhi (*)
Department of Pediatrics, Pediatric Emergency and Intensive Care,
Advanced Pediatrics Centre, Post Graduate Institute of Medical
Education and Research, Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
R. Jain : D. Bansal : R. K. Marwaha
Department of Pediatrics, Pediatric Hematology Oncology Unit,
Advanced Pediatrics Centre, Post Graduate Institute of Medical
Education and Research, Chandigarh 160012, India
Superior Vena Cava Syndrome (SVCS) refers to the con-
stellation of signs and symptoms caused by obstruction of
the superior vena cava. Superior mediastinal syndrome
(SMS) is the term used when SVCS coexists with obstruc-
tion of trachea. In children, a mediastinal pathology causing
SVCS generally results in SMS as well, due to the limited
chest volume. Hence, the two terms are often used inter-
changeably in children [1].
Pathophysiology
The SVC drains blood from upper part of the body, accounting
for approximately 35 % of venous return to the heart. Any
pathology in the mediastinum causing compression of the SVC
impedes the venous return. Similarly, any thrombosis or ob-
struction of SVC directly causes impedance to the venous
return.
Clinical Features
SVCS is suspected in a patient with engorgement of
veins of upper part of the body with resultant edema
and suffusion in the head, face and neck. There may be
orthopnea and elevation of Jugular Venous Pressure
(JVP). Respiratory compromise results from compres-
sion of the tracheobronchial tree. In addition, the ve-
nous engorgement leads to edema of the trachea and
bronchi. In infants and younger children, this is espe-
cially worrisome, as the tracheobronchial diameter is
narrow. An associated pericardial and pleural effusion
may be present [e.g., in Non-Hodgkin lymphoma
(NHL)], that may worsen the cardiorespiratory insuffi-
ciency. CNS symptoms are caused by impeded venous
56
return and resultant cerebral edema; the patient may
have lethargy, confusion, headache, irritability, blurred
vision or syncope.
Clinically, the important parameters of severity of
SMS include the degree, as well as rapidity of obstruc-
tion [2]. In patients with NHL involving the mediastinal
nodes, there may be rapid enlargement in size of the
nodes. A very rapidly progressive obstruction does not
provide adequate duration for development of collateral
channels for venous drainage. These patients tend to be
more symptomatic than those with a similar degree of
obstruction that has developed gradually, with sufficient-
period for formation of collaterals.
Etiology
The common causes of SMS in children are listed in Table 1.
The primary cause of SMS in children is compression by
malignant mediastinal mass [3, 4].
Investigations
The point of utmost importance to remember while investi-
gating patients with SMS is that they are at a very high risk
for adverse cardio-respiratory events in case they are admin-
istered any kind of anesthetic, anxiolytics or sedatives. The
need to avoid these medications cannot be stressed more as
they result in reduced respiratory drive, poor respiratory
muscle tone, relaxation of bronchial muscles and diminution
of lung volume. Their use may precipitate the requirement
for resuscitation and cardiorespiratory support. Once intu-
bated, it is difficult to wean off mechanical ventilation and
extubate, till the resolution of SMS [1].At times, the
Table 1 Common causes of superior mediastinal syndrome [2–4]
Malignant
• Non-Hodgkin lymphoma
• Acute lymphoblastic leukemia
• Hodgkin disease
• Neuroblastoma
• Germ cell tumor
• Sarcomas:including Ewings sarcoma
• Thymic tumors
• Acute myeloid leukemia (rarely)
Non malignant
• Infections: Tuberculosis, fungal infections, histoplasmosis,
thymic infections, infected cysts in mediastinum.
• Venous thrombosis caused by cardiac surgery or presence
of a central line
Indian J Pediatr (January 2013) 80(1):55–59
obstruction may be present beyond the trachea, resulting in
compression of the main bronchi; in such cases, intubation
and mechanical ventilation may not be effective. These
children often have orthopnea; it may be treacherous to
perform investigations, including CT scan, bone marrow
examination, lumbar puncture, etc. The children with a
low PEFR (<50 % expected) and a decreased cross-
sectional tracheal area (<50 % expected) form the highest
anesthetic risk group [5].
The investigations which would help in reaching an early
diagnosis include:
Imaging
1. Chest radiograph (PA and lateral view) is required
to confirm the presence of the mediastinal mass.
Location is an important indicator of underlying
etiology (Table 2). Other findings that may coexist
include pleural effusion, cardiomegaly suggesting
pericardial effusion, and compression of the tra-
cheobronchial tree.
2. CT chest (contrast enhanced): CT is a very useful
(though not mandatory) investigation in patients with
SMS. Ensure normal renal function and do not ad-
minister sedatives while performing the imaging. It
provides information regarding the exact location and
size of mass, infiltration into surrounding structures
and vascularity. It aids in planning tissue diagnosis.
3. Ultrasonography (USG) chest: This may be useful
when a CT scan cannot be performed due to logistic
issues, concerns of transporting a sick patient, in
younger children who are not cooperative for a CT
scan in absence of sedation, or if the patient cannot lie
supine. A reasonable knowledge on the site, size and
nature (cystic versus solid) of mass can be determined.
4. Echocardiography may be required if there is a
suspicion of pericardial effusion or infiltration by
the mass into the pericardial cavity, e.g., in NHL.
Blood Investigations
1. Complete blood count with differential count (re-
quest the pathologist to look for any immature/blast
cells). Presence of blasts in the peripheral blood film
would confirm the diagnosis of acute leukemia with-
out any invasive investigations. In addition, presence
of any cytopenia or leukoerythroblastic picture would
indicate plausible bone marrow involvement and pro-
vide an opportunity to confirm the diagnosis by bone
marrow examination. NHL may be suspected clini-
cally and the peripheral blood examination may be
unremarkable. In such a situation,if a tissue diagnosis
from the mediastinal mass is considered challenging
due to constraints of resources or expertise, a bone
marrow examination may be an option,as it may
Indian J Pediatr (January 2013) 80(1):55–59
Table 2 Etiology of mediastinal mass according to location [6]
Location Neoplastic masses
Anterior mediastinum Lymphoma/Leukemia, germ cell tumors, thymoma
Middle mediastinum Lymphoma/Leukemia
Posterior mediastinum Neuroblastoma, ganglioneuroblastoma
indicate a diagnosis, if the marrow is involved. Plate-
let count should be noted; it should be optimal prior to
any planned invasive procedure. A bone marrow
examination can be performed safely with underlying
thrombocytopenia.
2. Metabolic profile, including uric acid levels to de-
termine co-existing complications of tumor lysis
syndrome and renal dysfunction.
3. Serum α feto-protein and β-HCG levels: If there is a
suspicion of germ cell tumor in a patient with an
anterior mediastinal mass.
4. Coagulation profile (Prothrombin time and activat-
ed partial thromboplastin time): Prior to Fine needle
aspiration cytology (FNAC)/biopsy.
Fig. 1 Flow sheet for
management of Superior
mediastinal syndrome
57
Non- neoplastic masses
Thymic infections, thyroid tumors, parathyroid adenoma,
infectious lymphadenopathy
Thyroid tumors, bronchogenic cyst, cystic hygroma,
infectious lymphadenopathy
Neuroenteric cysts
Tissue Diagnosis
Investigations, including tissue diagnosis are desirable,
though not mandatory, before initiating emergency manage-
ment. The patient’s clinical condition should dictate the speed,
requirement and sequence of investigations and the specific
treatment. The least invasive procedure should be performed to
confirm the diagnosis, to reduce the possibility of an adverse
cardio-respiratory event.
1. A peripheral pathological lesion, e.g., enlarged cervi-
cal lymph node, or skin nodule, is the preferred site for
FNAC/biopsy. In expert hands, a FNAC can be per-
formed easily without sedation, and has the advantage
of a rapid tissue diagnosis often within a few hours.
58
2. In presence of pleural or pericardial effusion, a tap
may be performed which may be diagnostic, as well as
therapeutic. The fluid should be submitted for malig-
nant cytology, besides the routine investigations, in-
cluding work up for tuberculosis, if clinically relevant.
Flowcytometry and immunocytochemistry can be per-
formed and may yield a definitive diagnosis.
3. An image (CT/USG) guided FNAC/biopsy may be
cautiously attempted from the mass.
If the above studies are not diagnostic, and the patient is a
high risk candidate for anesthesia, it is preferable to post-
pone diagnostic studies, and treat the patient for SMS.
Therapy
Supportive Care
The patient should have head end elevated, to assist the venous
drainage and decrease the edema [4]. Intravenous fluids, free of
potassium and calcium (N/2 or N/4 with 5 % dextrose) should
be administered at a rate of 1500 mL/m2/d. A higher fluid
intake (up to 3000 ml/m2) may be required in case a diagnosis
of ALL or NHL is suspected, to prevent tumor lysis syndrome.
Allopurinol and recombinant urate oxidase (rasburicase) may
be indicated for prevention of tumor lysis syndrome in children
with hyperuricemia. All intravenous lines should be placed in
the lower limbs. This will prevent raised hydrostatic pressure
in the superior vena cava and resultant increased edema.
Definitive Therapy
Steroids As the most frequent cause of SMS in children is
lymphoma/leukemia, the administration of systemic steroids
is the frontline therapy [1, 2, 7]. Steroids work by decreasing
the tumor burden and reducing the airway edema. In the
authors’ unit, either dexamethasone (4–6 mg/m2/d) or hy-
drocortisone (5 mg/kg/dose, q6H) is administered intrave-
nously. At times, a single dose of steroid may stabilize the
patient, and diagnostic procedures can be performed subse-
quently. There is a possibility that prolonged use of steroids
(beyond 24–48 h) in emergency, without a prior tissue
diagnosis may render subsequent tissue diagnosis is difficult
to interpret in upto 20–25 % cases. However, it is better to treat
the patient for a life threatening emergency, than to undertake
a risky diagnostic procedure and delay therapy, even in the
face of potential failure of accurate tissue diagnosis.
Chemotherapy A combination of chemotherapy including ste-
roids, vincristine, an alkylating agent and/or anthracycline may
be used in a life threatening situation, when steroids alone may
not provide a rapid enough relief [1]. The most commonly used
Indian J Pediatr (January 2013) 80(1):55–59
combination includes cyclophosphamide (200 mg/m2) with
dexamethasone and vincristine (1–1.5 mg/m2). Both drugs
should be used as a single dose, and steroids should be given
round the clock. The likelihood of precipitating tumor lysis
syndrome with steroids/chemotherapy has to be borne in mind
and managed.
The role of radiation is largely obsolete as leukemias and
lymphomas are highly chemosensitive. In addition, in children,
radiation may lead to a post-radiation respiratory deterioration
due to airway edema, necessitating emergency steroids. It
frequently renders the subsequent tissue sample difficult to
interpret [8].
In case of symptomatic SVCS secondary to central venous
line associated thrombosis, line removal in conjunction with
thrombolysis should be considered, especially if symptoms
have been present for less than 5 d. The patient should be
placed on anticoagulation with low molecular weight heparin
at a dose of 1 mg/kg BD, for a minimum period of 3 mo.
An outline for management of SMS is illustrated in Fig. 1.
Monitoring
Clinical Monitoring The child should be continuously
monitored for vitals including respiratory rate, saturation,
heart rate, blood pressure (look for pulsus paradoxus),
sensorium, JVP, and signs of airway obstruction (stridor,
air entry), frequently. Urine output should be monitored as
well.
Laboratory Monitoring should include complete blood
counts and evaluation for tumor lysis syndrome in patients
with a large tumor burden, every 6–12 hourly. It should
include electrolytes (Sodium, potassium, calcium, phospho-
rous) and renal function tests (urea, creatinine) and uric acid.
Conflict of Interest None.
Role of Funding Source None.
References
1. Fischer MJ, Rheingold SR. Oncologic emergencies. In: Pizzo PA, Poplack
DG, eds. Principles and Practices of Pediatric Oncology. 6th ed. Philadel-
phia: Lippencott Williams and Wilkins; 2011. pp. 1125–51.
2. Wilson LD, Detterbeck FC, Yahalom J. Superior vena cava syn-
drome with malignant causes. N Engl J Med. 2007;356:1862–9.
3. Ingram L, Rivera GK, Shapiro DN. Superior vena cava syndrome
associated with childhood malignancy: analysis of 24 cases. Med
Pediatr Oncol. 1990;18:476–81.
Indian J Pediatr (January 2013) 80(1):55–59
4. Cheng S. Superior Vena Cava Syndrome: A contemporary review of
a historic disease. Cardiol Rev. 2009;17:16–23.
5. Ricketts RR. Clinical management of anterior mediastinal tumors in
children. Semin Pediatr Surg. 2001;10:161–8.
6. Chapman S, Nakielny R. Respiratory tract. In: Chapman S,
Nakielny R, eds. Aids to Radiological Differential Diagnosis. 4th
ed. London: Saunders; 2003. pp. 180–7.
59
7. Borenstein SH, Grestle T, Malkin D, Thorner P, Filler RM. The
effects of prebiopsy corticosteroid treatment on the diagnosis of
mediastinal lymphoma. J Pediatr Surg. 2000;35:973–6.
8. Loeffler JS, Leopold KA, Recht A, Weinstein HJ, Tarbell NJ.
Emergency prebiopsy radiation for mediastinal masses. Impact on
subsequent pathological diagnosis and outcome. J Clin Oncol.
1986;4:716–21.
Indian J Pediatr (February 2013) 80(2):138–143
DOI 10.1007/s12098-012-0901-y
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS ON ONCOLOGICAL EMERGENCIES
Febrile Neutropenia: Outline of Management
Sapna Oberoi & Renu Suthar & Deepak Bansal & R. K. Marwaha
Received: 9 March 2012 / Accepted: 18 September 2012 / Published online: 22 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Febrile neutropenia is a common emergency en-
countered in children receiving chemotherapy for a malignan-
cy. Left untreated, it can lead to serious morbidity and
mortality. Febrile neutropenia is suspected in any patient on
chemotherapy who presents with fever. Prompt evaluation and
management by the primary contact pediatrician is essential
for a successful outcome. A detailed history and physical
examination is warranted to identify source of infection, al-
though two thirds of them may not have localizing symptoms
or signs. Risk stratification is valuable in categorizing the
severity and guiding therapy. Initial stabilization, prompt ini-
tiation of appropriate antibiotics and adequate supportive care
are the cornerstone of treatment. Knowledge of the locally
prevailing bacteriological profile and antimicrobial suscepti-
bility data is crucial for each hospital/unit to frame and peri-
odically modify guidelines for the choice of antimicrobials.
Delay in initiating antimicrobials significantly worsens the
outcome. Education of the family as well as the members of
the treating unit is important in this regard. Pro-active steps
must be taken to reduce incidence of hospital acquired sepsis.
Diagnosis and management in relevance to the emergency
room is reviewed and institutional practice is shared.
Keywords Absolute neutrophil count . Acute lymphoblastic
leukemia . ALL . Cancer . Culture . Growth-factors
Introduction
Febrile neutropenia is the most common emergency encoun-
tered in children on treatment for a malignancy and remains
S. Oberoi : R. Suthar : D. Bansal (*) : R. K. Marwaha
Hematology-Oncology unit, Department of Pediatrics,
Advanced Pediatric Center, Post Graduate Institute of Medical
Education and Research, Chandigarh 160012, India
e-mail: deepakritu@yahoo.com
a significant cause of morbidity and mortality. It commonly
occurs in children diagnosed to have acute leukemia, lym-
phoma, solid tumor or aplastic anemia [1]. It may result
from the underlying malignancy per se or typically due
to the effect of chemotherapy. Fever may be the sole
manifestation of a serious infection in neutropenic chil-
dren as other signs of systemic inflammation might be
attenuated. Therefore, all children with febrile neutrope-
nia should undergo a systematic evaluation, including a
history and physical examination, appropriate diagnostic
tests, and prompt initiation of empirical antimicrobial
therapy.
Definitions
Febrile neutropenia A single oral temperature of ≥38.3 °C
(101 °F) or a temperature of ≥38.0 °C (100.4 °F) for ≥1 h,
with an absolute neutrophil count [Absolute neutrophil count
(ANC) 0 mature granulocytes + neutrophil band or stab cells]
of <500/mm3, or an ANC that is expected to decrease to <500
cells/mm3 during the next 48 h [2].
Profound neutropenia ANC<100 cells/mm3
Prolonged neutropenia Neutropenia lasting >7 d
Evaluation
History
A relevant history should include the following points:
& Fever onset, duration and severity
& Associated localizing symptoms: Ear, nose, throat, res-
piratory, gastrointestinal tract, musculoskeletal and uri-
nary system
Indian J Pediatr (February 2013) 80(2):138–143 139

& Phase of chemotherapy (intensive vs. non intensive)
& Duration since the last chemotherapy
& Recent hospitalization and antibiotics received, if any
Examination
Vitals (temperature, heart rate, respiratory rate, capillary refill
time, blood pressure, saturation) should be checked in every
patient of suspected febrile neutropenia who walks in to the
emergency room. The patient may appear well despite being
in a state of hemodynamic compromise. A detailed physical
examination focusing on possible sites of infection must be
undertaken. Sites that deserve attention and are commonly
overlooked include oral cavity, ear, sinuses, skin, nails, peria-
nal area, intravascular catheter insertion site and the site of
bone marrow aspiration. The potential causes of infection in
patients with febrile neutropenia are listed in Table 1.
Indicators in history and examination can provide valuable
clues to the etiology of fever. For e.g., a child with respiratory
distress and hypoxemia with bilateral diffuse infiltrates on
chest radiograph may have infection with Pneumocystis jir-
oveci or respiratory syncytial virus. Fungal infection should be
suspected in the presence of skin lesions (necrotic eschars,
nodules or target lesions), sinusitis, orbital cellulitis or pleu-
ritic pain. Fever, headache, seizures, encephalopathy or focal
deficits may occur due to encephalitis, encephalomyelitis,
bacterial meningitis or brain abscess. Cytomegalovirus, Vari-
cella zoster virus, Epstein-Barr virus, mumps and Human
herpesvirus-6 are the common viruses responsible for enceph-
alitis. Brain abscess typically results from invasive infections
due to aerobic and anaerobic bacteria or fungi.
1. Complete blood count, including differential leukocyte
count and ANC
2. Serum electrolytes, urea and creatinine
3. Blood culture: Obtain as early as possible and always
before the administration of antibiotics. Two sets of blood
cultures from separate venipuncture sites should ideally
be drawn. In the presence of a central venous catheter, a
blood culture should be obtained from each lumen of the
catheter and another from a peripheral vein.
4. Chest radiograph: In patients with respiratory symptoms
and signs
5. Cultures from any other site, as clinically relevant. This
includes stool, urine, cerebrospinal fluid, skin, respira-
tory secretions or pus.
Second line investigations. These are dictated by the
clinical course:
1. Serum Galactomannan test, CT scan of chest/paranasal
sinuses may be indicated in patients with suspected
fungal infection.
2. Bronchoalveolar lavage: If pneumonia is non-resolving/
non-responding.
3. Skin biopsy, from skin nodules, if any.
Risk Stratification
Assessment of risk is crucial in determining the appropriate
choice of antimicrobials, the route of administration (intra-
venous vs. oral), setting (inpatient vs. outpatient) and dura-
tion. The patients can be classified as low or high risk [2, 3].
Low Risk Patients

Patients at low risk of a serious infection include children

Investigations
who fulfill the following criteria [2, 4]:
First line investigations to be performed in every case & Clinically stable and ‘well’ looking
include: & Temperature <39 °C

Table 1 Potential causes of infection in patients with febrile neutropenia

System Cause of infection

Eyes Conjunctivitis, orbital cellulitis

Ear, nose, throat Otitis media, sinusitis, tonsillitis, pharyngitis, oral candidiasis
Teeth Dental caries/abscess
Chest Pneumonia
Abdomen Diarrhea, dysentery, neutropenic enterocolitis, pseudomembranous colitis
Perineum Perianal candidiasis, perianal abscess
Skin Cellulitis, abscess, nodular or target lesions suggestive of fungal infections, varicella rash, purpura fulminans
CNS Meningitis, meningoencephalitis, cavernous sinus thrombosis
Urinary tract Urinary tract infection
Intravascular catheters Exit site infection, tunnel infection
140
& Non-intensive phase of chemotherapy, e.g., maintenance
phase of chemotherapy
& Malignancy in remission
& Lack of any focus of infection e.g., pneumonia, abscess,
sinusitis or diarrhea etc.
& Lack of medical co-morbidities
& ANC≥100/mm3 and likely to rise within the next 7 d.
& Absolute monocyte count >100/mm3
& Not fulfilling any criteria for the high risk category
If a close follow-up can be ensured, such episodes can
often be managed with oral antibiotics [5]. The choice
includes cefixime, amoxicillin-clavulanate or levofloxacin
[2]. If there is a doubt regarding the clinical condition or
reliability of follow-up, the patient should be admitted and
administered intravenous antibiotics, as in the high risk
group.
High-Risk Patients
Any of the following indicators categorize a patient as
‘high-risk’ [2, 4]:
& Recent intensive chemotherapy
& Profound neutropenia (ANC<100 cells/mm3), anticipat-
ed to extend for >7 d. It is typically observed during or
following the intensive phases of therapy, e.g., induc-
tion, consolidation or intensification blocks of chemo-
therapy in patients with acute lymphoblastic leukemia
& Any focus of infection, e.g., cellulitis, abscess, pneumo-
nia, diarrhea, etc.
& Evidence of hypotension, respiratory distress or
hypoxemia
& Mucositis interfering with oral intake or resulting in
diarrhea
Management
‘High-risk’ patients are to be hospitalized and adminis-
tered broad-spectrum intravenous antibiotics (Fig. 1).
Knowledge of the locally prevailing bacteriological pro-
file and antimicrobial susceptibility data is crucial for
the choice of antimicrobials. Each hospital/unit must
review the prevalance of common pathogens and their
antimicrobial susceptibility data periodically to frame
and modify the choice of antimicrobials in their setting.
Majority of infections in febrile neutropenia are caused
by gram negative organisms e.g., Pseudomonas aerugi-
nosa, E. coli, Klebsiella pneumonia and Acinetobacter
species [5, 6]. Staphylococcus aureus, coagulase nega-
tive Staphylococcus and Enterococcus are the common
gram positive organisms [6–8]. Fungal infections with
Candida, Aspergillus or Mucor are usually encountered
Indian J Pediatr (February 2013) 80(2):138–143
in patients with prolonged febrile neutropenia who are
receiving broad spectrum antibiotics [1, 2].
Antibiotics
It is important that patients are administered the first dose of
antibiotics without any delay. The patients in the authors
unit who are receiving intensive blocks of chemotherapy are
instructed to reside in the vicinity of the hospital, so that
antibiotics can be started promptly at the onset of fever.
Delay in initiating antimicrobials significantly increases
the morbidity and mortality. Education of the family as well
as the members of the treating unit is important in this
regard. Care-takers are advised not to administer paraceta-
mol at home as it may mask fever and can lead to delay in
seeking medical care.
& Anti-pseudomonal β-lactam agents: Monotherapy with
anti-pseudomonal β-lactam agents such as anti-
pseudomonas penicillin (piperacillin-tazobactum), anti-
pseudomonal cephalosporin (cefoperazone-sulbactum) or
carbepenems (meropenem or imipenem-cilastatin) or
cefepime is recommended as first line by Infectious Dis-
ease Society of America [2]. However, no significant
differences in treatment failure, including antibiotic mod-
ification, infection-related mortality, or adverse events
were observed while comparing anti-pseudomonas peni-
cillin±aminoglycoside regimen with carbapenem mono-
therapy in a recent metaanalysis [9]. Hence, carbapenems
can be reserved as second line antibiotics to prevent the
emergence of drug resistant organisms. Cefoperazone-
sulbactum along with Amikacin are the current first line
choice in authors unit. Therapy is switched to second line
drugs: Vancomycin and Carbepenems (meropenem or
imipenem-cilastatin) after 48–72 h, if fever is unrelenting
and there is no improvement in the clinical condition.
Colistin is reserved as a third line drug.
& In a hemodynamically unstable patient, an adequate
coverage for drug-resistant gram-negative and gram-
positive organisms, as well as for anaerobes should be
given. Hence, second line antibiotics should be admin-
istered upfront. A combination of an anti-pseudomonal
carbapenem, such as imipenem or meropenem, as well
as addition of an aminoglycoside, together with vanco-
mycin (three antibiotics) provides this cover [2].
& Specific gram positive cover is not a standard part of
initial empiric antibiotic therapy [2]. It should be added
in initial therapy, if patient has evidence of any of the
following:
– Hemodynamic instability
– Severe sepsis
– Radiographically confirmed pneumonia
– Clinically suspected catheter related infection
Indian J Pediatr (February 2013) 80(2):138–143 141

Fever (>38.3OC) and neutropenia (Absolute neutrophil count <500/mm3)

LOW RISK HIGH RISK

Non intensive phase of chemotherapy Intensive phase of chemotherapy

Clinically stable with no co-morbidity Clinically unstable patient
No focus of infection Any medical co-morbidity
Absolute neutrophil count ≥100/mm3 Any focus of infection
Anticipated neutropenia <7 d Absolute neutrophil count <100/mm3
Anticipated neutropenia >7d

INITIAL STABILIZATION and INVESTIGATIONS

Take care of airway, breathing and

INPATIENT IV ANTIBIOTICS circulation
OUT PATIENT ANTIBIOTICS
Gastrointestinal intolerance Obtain CBC, blood culture, electrolytes
Good oral intake Concern for compliance or Chest X-Ray and other cultures if indicated
Assured follow-up follow-up

Cefexime, or Defervescence INPATIENT IV ANTIBIOTICS

Amoxicillin/clavulanate, or
Levofloxacillin
If fever persists >48 h
hospitalize & start IV antibiotics
Continue IV or oral
antibiotic till ANC is rising
and ≥500/mm3
As per locally prevailing bacteriological
profile and antimicrobial susceptibility data
Cefoperazone/sulbactum or
Piperacillin/tazobactum ± Amikacin
Vancomycin + Carbapenem if
hemodynamically unstable

Adjust antimicrobials based on clinical

course, counts, radiology & cultures

Fig. 1 Initial management of patient with febrile neutropenia

– Skin or soft tissue infection
– Known colonization with methicillin-resistant Staphy-
lococcus aureus (MRSA), Vancomycin-resistant En-
terococcus (VRE), or Penicillin-resistant Streptococcus
– Severe mucositis, if fluoroquinolone prophylaxis
has been given and ceftazidime is employed as
empirical therapy
& Empirical or presumptive anti-malarial therapy is not
recommended [10].
General Considerations and Supportive Care
& Pro-active steps must be taken to reduce incidence of
hospital acquired sepsis, an increasingly common and
challenging complication in hospitalized patients.
– Frequent hand washing is often not practical in busy
units. However, the use of alcohol based hand rub in
between patients must be ensured by each medical
and nursing personnel.
– Use of IV fluids, central lines, foley’s catheter etc. must
be restricted, if possible. Administration of IV fluids
for minor reasons should be avoided. Nasogastric
feeding should be encouraged in patients with anorexia
or mucositis.
– Rectal enemas, suppositories, and rectal examinations
are contraindicated in neutropenic patients [2, 11]
& Patients with severe sepsis and septic shock should
be managed as per the survival sepsis guidelines
[12]. Non-invasive intermittent positive pressure
ventilation should be attempted in case of acute
respiratory failure, before restoring to mechanical
142
ventilation, except in those with severe hemodynam-
ic compromise [13, 14].
& Hemoglobin<8 g/dl is generally an indication for blood
transfusion in a stable patient.
& Indication for platelet transfusion: These vary with the
clinical condition of the patient. In a stable patient with-
out any co-morbidities and bleeds, prophylactic trans-
fusions are recommended at a count below 10×109/
mm3. Few studies have suggested that this threshold
can be further lowered to 5×109/mm3 [1, 15, 16]. Trans-
fusion threshold of 20×109/mm3and 100×109/mm3 is
recommended in patients with minor (mucosal, epistax-
is) and major bleeds (hemoptysis, GI or CNS bleed),
respectively [1]. The practice may often be varied in
different units, depending on physician preferences and
extent of availability of blood products.
& Growth factors: Administration of G-CSF has no role in
the management of children with uncomplicated febrile
neutropenia [12]. However, they might be useful in
reducing the duration of neutropenia and length of hos-
pital stay in children with complicated febrile neutrope-
nia (pneumonia, hypotension, invasive fungal infection
or multi organ dysfunction) [17, 18].
Subsequent Management
It depends upon response to initial antibiotics, clinical status
of the patient, culture results and ANC. The patient should
be transferred under the care of a Pediatric Oncologist at this
point.
& Patient who is without a focus of infection, afebrile
within 2–3 d after first line antibiotics, along with a
rising ANC, with negative cultures, may be discharged
after 24–48 h or may be shifted to oral antibiotics, till
ANC exceeds 500/cumm.
& In case of documented infections, including soft tissue
infection, pneumonia, or bacteremia, appropriate anti-
biotics should be given for 10–14 d.
& Persistent fever beyond 3 d, despite antibiotic therapy
should prompt a thorough search for source of infection:
– Relevant investigations include repeat blood/urine
cultures, stool for clostridium difficile, fungus and
atypical organisms in case of diarrhea, and CT scan
of chest/sinuses
– Antibacterials should be upgraded in high risk
patients with persistent fever after 48–72 h, or ear-
lier in case of any hemodynamic instability.
– Empirical antifungal therapy (Amphotericin) and
investigations for invasive fungal infections should
be considered for patients with persistent or recurrent
Indian J Pediatr (February 2013) 80(2):138–143
fever after 4–7 d of antibiotics and whose overall
duration of neutropenia is expected to exceed 7 d.
Conflict of Interest None.
Role of Funding Source None.
References
1. Walsh TJ. Infectious complications in pediatric cancer patients.
In: Pizzo PA, Poplack DG, eds. Principles and practice of
pediatric oncology. 5th ed; Philadelphia: Williams and Wilkins;
2006. pp. 1269–329.
2. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Infectious Diseases
Society of America. Clinical practice guideline for the use of
antimicrobial agents in neutropenic patients with cancer: 2010
Update by the Infectious Diseases Society of America. Clin Infect
Dis. 2011;52:427–31.
3. Badiei Z, Khalesi M, Alami MH, et al. Risk factors associated with
life-threatening infections in children with febrile neutropenia: a
data mining approach. J Pediatr Hematol Oncol. 2011;33:e9–e12.
4. Härtel C, Deuster M, Lehrnbecher T, Schultz C. Current
approaches for risk stratification of infectious complications in
pediatric oncology. Pediatr Blood Cancer. 2007;49:767–73.
5. Vidal L, Paul M, Ben-Dor I, Pokroy E, Soares-Weiser K, Leibovici
L. Oral versus intravenous antibiotic treatment for febrile neutro-
penia in cancer patients. Cochrane Database Syst Rev. 2004;4:
CD003992.
6. Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood acute
lymphoblastic leukemia: an analysis of 222 febrile neutropenic
episodes. Pediatr Hematol Oncol. 2008;25:385–92.
7. Kanafani ZA, Dakdouki GK, El-Chammas KI, Eid S, Araj GF,
Kanj SS. Bloodstream infections in febrile neutropenic patients at a
tertiary care center in Lebanon: a view of the past decade. Int J
Infect Dis. 2007;11:450–3.
8. Mathur P, Chaudhry R, Kumar L, Kapil A, Dhawan B. A study of
bacteremia in febrile neutropenic patients at a tertiary-care hospital
with special reference to anaerobes. Med Oncol. 2002;19:267–72.
9. Manji A, Lehrnbecher T, Dupuis LL, Beyene J, Sung L. A sys-
tematic review and meta-analysis of anti-pseudomonal penicillins
and carbapenems in pediatric febrile neutropenia. Support Care
Cancer. 2012;20:2295–304.
10. Bansal D, Gautam P, Dubey ML, Marwaha RK. Presumptive
treatment for malaria is not justified in children receiving cancer
chemotherapy. Pediatr Blood Cancer. 2010;55:1108–10.
11. Centers for Disease Control and Prevention; Infectious Disease
Society of America; American Society of Blood and Marrow
Transplantation. Guidelines for preventing opportunistic infections
among hematopoietic stem cell transplant recipients. MMWR
Recomm Rep. 2000;49:1–125.
12. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign:
international guidelines for management of severe sepsis and septic
shock: 2008. Crit Care Med. 2008;36:296–327.
13. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in
immunosuppressed patients with pulmonary infiltrates, fever, and
acute respiratory failure. N Engl J Med. 2001;344:481–7.
14. Pancera CF, Hayashi M, Fregnani JH, Negri EM, Deheinzelin D,
de Camargo B. Noninvasive ventilation in immunocompromised
pediatric patients: eight years of experience in a pediatric oncology
intensive care unit. J Pediatr Hematol Oncol. 2008;30:533–8.
Indian J Pediatr (February 2013) 80(2):138–143
15. Slichter SJ. Evidence-based platelet transfusion guidelines. Hem-
atol Am Soc Hematol Educ. 2007;2007:172–8.
16. Blajchman MA, Slichter SJ, Heddle NM, Murphy MF. New strat-
egies for the optimal use of platelet transfusions. Hematol Am Soc
Hematol Educ Progr. 2008:198–204.
17. Smith T, Khatcheressian J, Lyman G, et al. 2006 update of recom-
mendations for the use of white blood cell growth factors: an
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evidence based clinical practice guideline. J Clin Oncol.
2006;24:3187–205.
18. Ozkaynak MF, Krailo M, Chen Z, Feusner J. Randomized com-
parison of antibiotics with and without granulocyte colony-
stimulating factor in children with chemotherapy-induced febrile
neutropenia: a report from the Children’s Oncology Group. Pediatr
Blood Cancer. 2005;45:274–80.
Indian J Pediatr (February 2013) 80(2):144–148
DOI 10.1007/s12098-012-0917-3
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS ON ONCOLOGICAL EMERGENCIES
Hyperleukocytosis: Emergency Management
Richa Jain & Deepak Bansal & R. K. Marwaha
Received: 9 March 2012 / Accepted: 26 October 2012 / Published online: 24 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Hyperleukocytosis is defined as peripheral blood
leukocyte count exceeding 100,000/mm3. Acute leukemia is
the most common etiology in pediatric practice. Hyperleu-
kocytosis is a medical emergency. The increased blood
viscosity, secondary to high white cell count and leukocyte
aggregates, results in stasis in the smaller blood vessels.
This predisposes to neurological, pulmonary or gastrointes-
tinal complications. In addition, patients are at risk for tumor
lysis syndrome due to the increased tumor burden. Initial
management includes aggressive hydration, prevention of
tumor lysis syndrome, and correction of metabolic abnor-
malities. A red cell transfusion is not indicated in a hemo-
dynamically stable child, as it adversely affects the blood
viscosity. Leukapheresis is the treatment of choice for a very
high count, or in patients with symptomatic hyperleukocy-
tosis. The technical expertise required, a relative difficult
venous access in younger children, risk of anticoagulation
and possible non-availability of the procedure in emergency
hours are limitations of leukapheresis. However, it is a
rewarding procedure and performed with relative ease in
centers that perform the procedure frequently. An exchange
transfusion is often a practical option when hyperleukocy-
tosis is complicated with severe anemia. The partial ex-
change aids in correcting both, without the risk of volume
overload or hyperviscosity, which are the limitations of
hydration and blood transfusion, respectively. Etiology and
management of hyperleukocytosis in relevance to the pedi-
atric emergency room is outlined.
R. Jain : D. Bansal (*) : R. K. Marwaha
Hematology/Oncology Unit, Department of Pediatrics,
Advanced Pediatrics Center,
Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: deepakritu@yahoo.com
Keywords Acute lymphoblastic leukemia . ALL . CML .
Hydration . India . Leukostasis . Priapism
Introduction
Hyperleukocytosis is defined as peripheral blood leukocyte
count exceeding 100,000/mm3 [1]. It typically occurs in
hematological malignancies, including acute lymphoblastic
leukemia(ALL), particularly T-cell ALL, infant ALL or
hypodiploid ALL, and acute myeloid leukemia (AML).
Chronic myeloid leukemia, especially in blast crisis may
present with hyperleukocytosis [2]. Hyperleukocytosis com-
plicates the course of leukemia in 5–22 % children [3, 4].
Differential Diagnosis
Hyperleukocytosis should be differentiated from leukemoid
reaction, when a high total leukocyte count (TLC) (typically
>50,000/mm3) occurs in the presence of non-malignant dis-
orders. It is observed in certain infections, including pertus-
sis, staphylococcus aureus, Pneumococcus, tuberculosis and
varied inflammatory conditions [5, 6]. Generally, the counts
do not exceed 100,000/mm3. The predominant cells are
mature lymphocytes and granulocytes. Differentiation can
be done through history, examination and peripheral smear
examination. A high number of nucleated RBCs (nRBC) in
blood can also raise the TLC erroneously, especially when a
counter is used. This is commonly observed in patients with
thalassemia major and in neonates. The counter generates a
raised value of TLC, as the nRBC’s are spuriously counted
as leucocytes. The TLC generally is less than 100,000/mm3.
Here again, the examination of peripheral smear will con-
firm the presence of nRBC’s, and a corrected TLC can be
calculated.
Indian J Pediatr (February 2013) 80(2):144–148
Complications of Hyperleukocytosis
Hyperleukocytosis is an emergency as it may cause several
complications, resulting in morbidity or mortality. Vascular
obstruction can occur, leading to organ damage from tissue
hypoxia, thrombosis or hemorrhage. Metabolic derange-
ments are common due to high blast count. The most com-
monly affected organs are central nervous system (CNS)
and the lungs [2, 7, 8]. A CNS bleed, leukostasis or throm-
bosis, either independently or in combination, can cause
CNS symptoms. Manifestations include irritability, altered
sensorium, seizures, focal neurological deficits and raised
intracranial pressure. Pulmonary leukostasis may result in
hypoxia, respiratory distress and can require respiratory
support. Chest radiograph may show presence of diffuse
infiltrates. Other organ systems can also be involved. Gas-
trointestinal hemorrhage may occur, resulting in bleed, hem-
atemesis or pain abdomen. Priapism, clitoral engorgement
and dactylitis are the rarer manifestations of leukostasis.
An important complication relating to the high tumor
burden in patients with hyperleukocytosis is the tumor lysis
syndrome (TLS). TLS may present with isolated lab de-
rangement, including hyperuricemia, hyperkalemia, hyper-
phosphatemia, hypocalcemia or with associated clinical
symptoms, including oliguria or anuria, seizures, altered
sensorium ranging from irritability and confusion to frank
coma [9]. The most common time for TLS to occur is within
2–3 d following the initiation of chemotherapy, however
spontaneous TLS may occur in the absence of any therapy.
Pathophysiology
Two potential mechanisms have been suggested to explain
the complications caused by hyperleukocytosis. According
to the traditional explanation, there is an increase in blood
viscosity, secondary to high TLC and leukocyte aggregates,
resulting in stasis in the smaller blood vessels. The second
proposed mechanism is of adhesive interactions between the
damaged endothelium of the vessel and leukemic blasts,
precipitating leukostasis. The toxins and cytokines released
by the vascular endothelium exacerbate the situation [1, 2].
Clinically significant hyperleukocytosis usually occurs in
the presence of a TLC exceeding 300,000/mm3 in ALL, and
more than 200,000/mm3 in AML. However, several factors
may result in symptoms at a lower TLC. These include
severe anemia, thrombocytopenia, renal dysfunction, super-
imposed infection, dehydration and acidosis. The CNS
events and pulmonary leukostasis are more common in
children with AML, while TLS is observed with a higher
frequency in ALL [9–11]. In an analysis of 234 children
with hyperleukocytosis from St Jude hospital, 19 % of
children with AML had hemorrhagic complications,
145
including intracranial or pulmonary bleeds, vs. 2.5 % with
ALL [10]. Metabolic complications occurred more frequently
in patients with ALL than AML. The early mortality was
significantly higher in children with AML than ALL [10].
This difference is likely due to the larger size of blasts in
AML, along with increased adhesiveness. Larger myeloblasts
do not circulate freely in capillaries and small blood vessels,
leading to sequestration and vascular damage. The symptoms
may be more pronounced, and occur at lower TLC in children
with monocytic leukemia, where the blasts have a higher
propensity for adhesiveness and tissue invasion [12].
Investigations
Complete blood count with examination of peripheral smear
is the initial investigation in a patient with suspected leuke-
mia, and this would reveal the diagnosis of hyperleukocy-
tosis as well. It is a good practice to communicate directly
with the pathologist to ensure a timely and reliable report. It
is often possible for the pathologist to comment on the likely
possibility of AML vs. ALL from examination of the pe-
ripheral smear, including cytochemical stains.
All children, once diagnosed with hyperleukocytosis,
should be evaluated for the attendant complications. Most
importantly, they should be screened for TLS. Serum elec-
trolytes (including sodium, potassium, calcium, phosphate)
along with renal functions and uric acid should be requested
immediately. A coagulogram should be performed as dis-
seminated intravascular coagulation may be observed in
AML; association increases the chances of hemorrhage. A
blood gas analysis should be done to look for acidosis. A
chest radiograph may reveal a mediastinal mass suggesting
possibility of T cell-ALL, and pulmonary infiltrates in case
of leukostasis or infection. Blood samples for uric acid and
blood gas should be transported on ice, and analyzed early,
as the high TLC may result in false lowering of uric acid and
hypoxemia.
Management
Initial management is directed towards aggressive hydration,
use of allopurinol for prevention of TLS, and prevention or
correction of metabolic abnormalities. The definitive manage-
ment involves reduction of the tumor load by chemotherapy.
An outline of management is illustrated in Fig. 1.
Fluids
All patients should be initiated on continuous intravenous
hydration with potassium and calcium free fluids (N/2 or N/
4 5 % Dextrose is appropriate), 2–4 times of normal
146 Indian J Pediatr (February 2013) 80(2):144–148

Hyperleukocytosis

• Send tumor lysis work up, coagulogram, chest X-ray, blood gas
• Obtain EDTA sample for cross match
• Establish IV access; start potassium and calcium free fluids
• Start Allopurinol (250-500 mg/m2/d)

Asymptomatic Symptomatic leukostasis

No pulmonary or CNS stasis, no bleeds or
TLC > 200-300 x 10 3 /µ L

Hb >6-7g% Hb >6-7 g%
Severe anemia with impending
congestive cardiac failure (Hb <5-6g%)

• IVF: Two times maintenance • IVF: 70-100% maintenance • IVF: 3-4 times maintenance
• No red cell transfusion • Urgent leukapheresis or exchange transfusion • No red cell transfusion
• Treat coagulopathy (Platelets, FFP as needed)

• Monitor for TLS q 8-12 hourly; If present, manage as detailed elsewhere

• Vitals/sensorium/urine output monitoring 2-4 hourly
• Start definitive therapy as soon as diagnosis established

Fig. 1 Flow sheet detailing management of hyperleukocytosis

maintenance. Typically, the fluids may be initiated at a rate that
is twice the maintenance, and can be increased in a symptom-
atic patient who persists to have a high TLC. The fluid rate
depends on the tumor burden as well as the hemoglobin (Hb).
If the Hb is ‘reasonable’ (≈7–8 g/dL or more), higher fluid
volumes can be administered, while monitoring for fluid over-
load and urine output. If the Hb is very low (less than ≈6 g/dL),
less fluids should be given, as higher volumes may precipitate
congestive heart failure. There is no role of routine use of
diuretics in hyperleukocytosis, as the goal is hemodilution
and reduction of viscosity. Diuretics are however indicated if
there is co-existing TLS and fluid overload.
Transfusion of Blood Products
Platelets should be transfused at counts below 20,000/mm3
to prevent CNS bleed, or in the presence of any active
mucosal or visceral bleeds [1]. A platelet transfusion does
not increase the blood viscosity significantly. Packed red
blood cell transfusion is not indicated in a hemodynamically
stable child, as it increases the blood viscosity. In case of
severe anemia, with impending congestive cardiac failure,
leukapheresis or exchange transfusion are better options. Coa-
gulopathy may be observed in children with AML (particu-
larly promyelocytic variant). If present, it should be corrected
by transfusion of 10–15 mL/kg of fresh frozen plasma.
Prevention of Tumor Lysis
Aggressive hydration therapy administered for hyperleuko-
cytosis, aids in the prevention of TLS as well. The reader
may wish to read a recent review on TLS [13]. Briefly,
Allopurinol is started in all children, at a dose of 250–
500 mg/m2/d (maximum 800 mg/d) in three divided doses.
Tablet Zyloric is available in 100 and 300 mg strengths. In
case of established TLS with raised uric acid, the preferred
therapy is with recombinant urate oxidase, administered intra-
venously, at a dose of 0.05–0.2 mg/kg, to be repeated if
Indian J Pediatr (February 2013) 80(2):144–148
needed. It is more effective than allopurinol in preventing and
treating TLS, and decreasing the need for dialysis. A small case
series has shown its efficacy in preventing TLS in spite of a
very high TLC [3, 14]. (Inj Rasburicase1.5 mg; ≈ Rs 12,000).
Reduction of TLC is necessary to prevent morbidity and
mortality in symptomatic leukostasis and preventing tumor
lysis prior to initiating chemotherapy. It can be done by
leukapheresis or exchange transfusion.
Leukapheresis is the treatment of choice for a very high
TLC (>2–3 lakh), or in patients with symptomatic hyper-
leukocytosis [15]. It is the removal of circulating leukocytes
from the blood and re-infusion of the leukodepleted blood.
A single leukapheresis decreases the TLC by 20–50 %.
Most patients require a single procedure; rarely more than
two procedures are necessary [8, 16]. The difficult venous
access in younger children, technical difficulty of the pro-
cedure in small children, particularly those less than 15 kg,
risk of anticoagulation, inadequate experience and non-
availability of the procedure in emergency hours are the
limitations.
Exchange transfusion can be done with fresh whole blood or
with a mix of packed red blood cells and plasma (in a ratio of 2–
3:1), with platelet supplementation. Recommended volume
varies from 70 to 150 mL/kg, with an aim to reduce the blasts
by at least 50 % [17, 18]. It is a safe procedure even in neonates
or infants with hyperleukocytosis, and in neonates can be
performed through the umbilical catheterization [19]. It is par-
ticularly beneficial when hyperleukocytosis is accompanied
with severe anemia. The partial exchange aids in correcting
both, without the risk for volume overload or hyperviscosity,
which are the limitations of hydration and blood transfusion,
respectively. In the authors experience, a partial exchange with
~2 bags of whole or reconstituted blood in a child weighing 15–
25 kg, corrects the anemia safely, following which aggressive
hydration can be instituted. There has been no head to head
comparison between exchange transfusion and leukapheresis
on efficacy and safety. However, there is data to suggest that
both the procedures may be equally efficacious in reducing the
TLC, with a mean reduction in TLC of 50–60 % with either.
The choice between the two would depend on the clinical
scenario, with age, weight, ease of procedure and availability
of equipment being some of the deciding factors [18]. In the
authors’ institute, leukapheresis is increasingly preferred, in
parallel with the increasing expertise and experience of the
transfusion medicine services.
Chemotherapy It is important to remember that leukaphe-
resis or exchange transfusion is not the definitive therapy.
They are temporary measures, which aid in stabilizing the
patient, while establishing diagnosis and initiating chemother-
apy. Chemotherapy must be initiated as early as possible.
However, starting regular dose, multi-agent chemotherapy in
patients with hyperleukocytosis may result in life-threatening
metabolic derangements and TLS. This is particularly true for
147
children with ALL, who have a high risk of TLS, and may
develop renal shut down necessitating dialysis, with full dose
chemotherapy given upfront. In patients with AML, on the
other hand, regular chemotherapy can often be administered
even with a high TLC, as the metabolic complications are less
common. Lower doses of steroids alone may be given to
children with ALL, while continuing hyper-hydration and
other measures for control of hyperleukocytosis. In a study
of 15 children with ALL and hyperleukocytosis, intravenous
prednisone started at a low dose and gradually escalated over
5 d to full dose, led to significant reduction in TLC by day 3,
without developing severe metabolic complications [20]. In
authors experience, 2–3 d of steroids in patients with ALL as a
single agent chemotherapy along with aggressive fluid thera-
py, as against initiation of multi-agent chemotherapy, is often
successful in preventing TLS.
Monitoring forms an integral part of management of a
child with hyperleukocytosis. Clinical as well as lab parame-
ters should be recorded. Vitals should be monitored frequently
(q 3–4 hourly). Monitoring includes observation for respira-
tory distress and any hemodynamic instability which may
indicate a bleed or congestive cardiac failure. Sensorium
should be evaluated periodically as the earliest manifestations
of a CNS event are generally headache or persistent vomiting.
Adequate fluid intake and urine output (2–4 ml/kg/h) should
be ensured. Urinary catheterization is not recommended in a
conscious and hemodynamically stable child. It leads to un-
necessary discomfort and increases the risk of infection. Lab
monitoring includes daily or more frequent complete blood
counts, and evaluation for TLS (serum electrolytes including
K, Ca, iP, uric acid, urea and creatinine) every 8–12 hourly.
Coagulogram should be repeated if initially deranged.
Indian Experience
In a study from Delhi, Arya et al reported 38 % of patients
with T-cell ALL to have hyperleukocytosis; the survival of T-
cell ALL was equivalent to B-lineage ALL [21]. The inci-
dence of hyperleukocytosis was 11 % in children with ALL in
a study from Tata Memorial Hospital, Mumbai; leucocyte
count at diagnosis did not affect the incidence of off therapy
relapses [22]. Another study from the same center however
reported a high TLC (>60,000/mm3) to be a poor prognostic
marker in children with ALL [23]. From the authors center,
hyperleukocytosis was documented in 111 (14.6 %) of 762
patients [24]. Significant lymphadenopathy (45 %), mediasti-
nal adenopathy (26 %) and superior vena cava-obstruction
(9 %) were accompanying clinical features. TLS was observed
in 33 % and CNS complications (altered sensorium, raised
intracranial pressure, stroke or intracranial hemorrhage) in
19 %. The estimated mean survival for the entire cohort was
significantly inferior to that of other ALL patients [24]. With
148
improved supportive care and risk-stratified chemotherapy the
outcome is very likely to improve in the future.
Conflicts of Interest None.
Role of Funding Source None.
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15. Haase R, Merkel N, Diwan O, Elsner K, Kramm CM. Leukapheresis
and exchange transfusion in children with acute leukemia and hyper-
leukocytosis. A single center experience. Klin Padiatr. 2009;221:374–
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irradiation in patients with hyperleukocytic acute myeloid leuke-
mia: no impact on early mortality and intracranial hemorrhage. Am
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17. ALL-BFM 2000 Protocol, Version 12/2008, S99.
18. Bunin NJ, Kunkel K, Callihan TR. Cytoreductive procedures in
the early management in cases of leukemia and hyperleukocytosis
in children. Med Pediatr Oncol. 1987;15:232–5.
19. Warrier RP, Ravindranath Y, Emami A, Lusher J. Exchange trans-
fusion for hyperleukocytosis, anemia, and metabolic abnormalities
in leukemia. J Pediatr. 1981;98:338–9.
20. Ozdemir MA, Karakukcu M, Patiroglu T, Torun YA, Kose M.
Management of hyperleukocytosis and prevention of tumor lysis
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dren with acute lymphoblastic leukemia. Acta Haematol.
2009;121:56–62.
21. Arya LS, Padmanjali KS, Sazawal S, et al. Childhood T-
lineage acute lymphoblastic leukemia: management and out-
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2011;48:785–90.
22. Vaidya SJ, Advani SH, Pai SK, et al. Survival of childhood
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23. Advani S, Pai S, Venzon D, et al. Acute lymphoblastic leukemia in
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Indian J Pediatr (April 2013) 80(4):318–325
DOI 10.1007/s12098-012-0959-6
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN GASTROINTESTINAL EMERGENCIES
Management of a Child with Vomiting
Sunit C. Singhi & Ravi Shah & Arun Bansal &
M. Jayashree
Received: 10 August 2012 / Accepted: 28 December 2012 / Published online: 23 January 2013
# Dr. K C Chaudhuri Foundation 2013
Abstract Vomiting is a protective reflex that results in force-
ful ejection of stomach contents up to and out of the mouth. It
is a common complaint and may be the presenting symptom
of several life-threatening conditions. It can be caused by a
variety of organic and nonorganic disorders; gastrointestinal
(GI) or outside of GI. Acute gastritis and gastroenteritis (AGE)
are the leading cause of acute vomiting in children. Important
life threatening causes in infancy include congenital intestinal
obstruction, atresia, malrotation with volvulus, necrotizing
enterocolitis, pyloric stenosis, intussusception, shaken baby
syndrome, hydrocephalus, inborn errors of metabolism, con-
genital adrenal hypoplasia, obstructive uropathy, sepsis, men-
ingitis and encephalitis, and severe gastroenteritis, and in
older children appendicitis, intracranial mass lesion, diabetic
ketoacidosis, Reye’s syndrome, toxic ingestions, uremia, and
meningitis. Initial evaluation is directed at assessment of
airway, breathing and circulation, assessment of hydration
status and red flag signs (bilious or bloody vomiting, altered
sensorium, toxic/septic/apprehensive look, inconsolable cry
or excessive irritability, severe dehydration, concern for symp-
tomatic hypoglycemia, severe wasting, Bent-over posture).
The history and physical examination guides the approach in
an individual patient. The diverse nature of causes of vomiting
makes a “routine” laboratory or radiologic screen impossible.
Investigations (Serum electrolytes and blood gases,renal and
liver functions and radiological studies) are required in any
child with dehydration or red flag signs, to diagnose surgical
causes. Management priorities include treatment of dehydra-
tion, stoppage of oral fluids/feeds and decompression of the
stomach with nasogastric tube in patients with bilious vomit-
ing. Antiemetic ondansetron(0.2 mg/kg oral; parenteral
S. C. Singhi (*) : R. Shah : A. Bansal : M. Jayashree
Department of Pediatrics, Advanced Pediatrics Centre, PGIMER,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
0.15 mg/kg; maximum 4 mg) is indicated in children unable
to take orally due to persistent vomiting, post-operative vom-
iting, chemotherapy induced vomiting, cyclic vomiting syn-
drome and acute mountain sickness.
Keywords Children . Vomiting . Antiemetic
Introduction
Vomiting is a very common complaint in infants and chil-
dren who present to the emergency department (ED). A
large percentage of infants and children with vomiting have
a non-serious etiology for their symptoms and have a self-
limiting illness. However, vomiting may be the presenting
symptom in several life-threatening conditions. The ED
management is primarily tailored to identify and manage
those with a serious underlying cause, and provide symp-
tomatic relief to others.
Terminology
Vomiting is a complex behavior. It is usually composed of
three linked activities: nausea, retching and expulsion of
stomach contents.
Nausea is a sensation of impending emesis and is fre-
quently accompanied by autonomic changes, such as in-
creased heart rate and salivation. Vomiting can occur
without preceding nausea, for e.g., projectile vomiting in
individuals with increased intracranial pressure.
Retching is defined as strong, involuntary efforts to vomit
but without expelling material from the mouth, which may
be seen as preparatory manoeuvres to vomiting.
Vomiting is a protective reflex and is defined as forceful
ejection of stomach contents up to and out of the mouth [1].
Indian J Pediatr (April 2013) 80(4):318–325 319

It is caused by violent co-ordinated contraction of the dia-
phragm and abdominal muscles accompanied by pyloric con-
striction and gastroesophageal relaxation in response to
stimulation of the medullary vomiting centre. This stimulation
may occur from a variety of impulses -from pelvic and ab-
dominal viscera, the heart, the peritoneum, the inner ear, and
the chemoreceptor trigger zone (caused by circulating drugs,
toxins, and metabolic derangements). Vomiting is complete
emptying of the stomach as compared to regurgitation, which
is nearly effortless return of short amount of food during or
shortly after eating. When regurgitation occurs in a baby at or
after milk feed, it is known as posseting.
identify and often are viewed as diagnoses of exclusion.
Examples of non-organic causes are psychogenic vomiting,
cyclic vomiting syndrome, abdominal migraine, and bulim-
ia. Mnemonic ‘VOMITINGs’ can help to remember wide
ranging causes of vomiting:
& Vestibular: Otitis media
& Obstruction: Pyloric stenosis, malrotation, volvulus, in-
tussusception, incarcerated hernia
& Metabolic: Diabetic ketoacidosis, inborn errors of metab-
olism, congenital adrenal hyperplasia, Reye’s syndrome
& Infections:

– Gastrointestinal- Gastritis, gastroenteritis, necrotiz-

Causes
Vomiting does not always localize the problem to the GI
system. A variety of organic and non-organic disorders,
gastrointestinal (GI) or outside of GI, can be associated with
vomiting. Acute gastritis and gastroenteritis (AGE) are the
leading causes of acute vomiting in children. Although
vomiting is a fairly frequent occurrence in a younger child,
it tends to be less prevalent in older children [2]. The
differential diagnosis of isolated vomiting is broad and age
specific (Table 1). Non-organic causes are difficult to
ing enterocolitis, appendicitis, hepatitis, pancreati-
tis, cholecystitis.
– Other systems- Upper respiratory infections, phar-
yngitis, sinusitis, pneumonia, sepsis
& Toxins and drugs: Various poisons, chemotherapeutic
agents, iron, organophosphates, theophylline, salicy-
lates, alcohol, lead and other heavy metals.
& Increased intracranial pressure from any etiology.
& Nephrologic disease : Acute renal failure, chronic renal
failure, pyelonephritis, renal tubular acidosis, obstruc-
tive uropathy.

Table 1 Illnesses presenting with vomiting according to the age group

Neonate Infant Toddler/older child Adolescent

Common Reflux Food poisoning Gastroenteritis/Gastritis Gastroenteritis/Gastritis

Pyloric stenosis Gastroenteritis Nonspecific (Otitis, GERD
sore throat, sinusitis)
Sepsis GE Reflux Post tussive Appendicitis
UTI Post tussive UTI Ingestion (toxic, bacillus cereus)
Malrotation Overfeeding Meningitis Migraine
Esophageal atresia Feed intolerance Toxic/Poisoning/Drugs Inflammatory bowel disease
Inborn error of metabolism (IEM) UTI GERD Toxic/Poisoning/Drugs
Hydrocephalus Nonspecific (otitis Obstruction
Milk allergy media, pneumonia)
Uncommon Congenital Adrenal Hyperplasia IEM DKA Hepatitis
Incarcerated hernia Renal Tubular Acidosis IEM DKA
Ileus Obstruction Hepatitis Peptic ulcer
Hirschprung disease Malrotation Migraine Psychological
Intracranial bleed Intussusception Peptic ulcer Pancreatitis
Milk allergy Pancreatitis Cholelithiasis
Renal insufficiency Raised ICP (Brain Tumor) Renal colic
Raised ICP Reye’s syndrome Raised ICP (Brain tumor)
Cyclic vomiting syndrome Middle ear disease
Cyclic vomiting

IEM Inborn error of metabolism; DKA Diabetic Ketoacidosis ; GE Gastro esophagial; UTI Urinary tract infection; ICP Intracranial pressure; GERD
Gastroesophageal reflux diseases
320 Indian J Pediatr (April 2013) 80(4):318–325

& Gastrointestinal: Gastro -Esophagial reflux (GER), for- Initial Evaluation

mula intolerance, peptic ulcer disease, cyclic vomiting
syndrome.
& Genital system: Testicular torsion, epididymitis, dysmen-
orrhea, ovarian torsion, pelvic inflammatory disease.
Evaluation
Evaluation of a child with vomiting in ED comprises as-
sessment of severity (e.g., presence of dehydration, surgical
or other life-threatening disorders) and diagnostic search for
a cause. This is achieved through focussed history (includ-
ing characteristics of vomiting and associated symptoms)
and physical examination, and consideration of possibilities
according to the age (Fig. 1).
The initial diagnostic focus is on likely acute GI or
systemic infections and exclusion of surgical causes. In
infancy, the life threatening causes include congenital intes-
tinal obstruction, atresia, malrotation with volvulus, necro-
tizing enterocolitis, pyloric stenosis, intussusception, shaken
baby syndrome, hydrocephalus, inborn errors of metabo-
lism, congenital adrenal hyperplasia, obstructive uropathy,
sepsis, meningitis and encephalitis, and severe gastroenter-
itis. In older children, life threatening causes that need
attention are appendicitis, intracranial mass lesion, diabetic
ketoacidosis, Reye’s syndrome, toxic ingestions, uremia,
and meningitis.
Initial evaluation is directed at assessment of airway, breathing
and circulation i.e., checking the vitals (heart rate, respiratory
rate, blood pressure, capillary refill time and SpO2), assess-
ment of hydration status and Red flag signs (Table 2). If red
flag signs, seek gastroenterologist and surgical consult.
If vomiting is non-bloody and non-bilious, the important
diagnostic variables in history which help in making diag-
nosis are described below.
Age
Causes of vomiting vary with the age of the child (Table 1).
However, some overlap across the age groups can occur. For
e.g., congenital anomalies of the GI tract present commonly in
the neonatal period; yet webs and duplications can be discov-
ered throughout childhood. Malrotation or non-fixation of the
small intestine complicated by intermittent volvulus can cause
episodic vomiting at any age. Duodenal hematoma typically
follows accidental trauma to the abdomen in bicycling chil-
dren but can result from abuse of toddlers. [3]
Temporal Pattern of Vomiting (Table 3)
Acute vomiting episode, which is abrupt onset of vomiting
in previously well child, is the most common presentation in
children. Episodes separated by not more than 2 min are

Fig. 1 Algorithm for Patient having

evaluation of a child with dehydration?
vomiting in emergency room – Yes No
based on presence of other
symptoms, type of vomitus,
age, and physical signs Refer to protocol Characterization of
on diarrhea vomiting

Bloody Bilious Non bloody and non Regurgitant

bilious

Refer to protocol on Rule out

upper GI bleed obstruction
Neonate/ Child/
Infant Adolescent

Evidence of Lethargy/Altered
sepsis/meningitis? mental status?
No Yes No Yes

Evidence of Antibiotics, Diarrhea/Fever?

Metabolic,
obstruction? Evaluate Neurologic
No Yes
No Yes or
Peptic Endocrine
Metabolic/ Infectious
Surgical causes
disease/ causes
Endocrine
Toxins
Indian J Pediatr (April 2013) 80(4):318–325
Table 2 Red flag signs in a child presenting with vomiting
• Altered sensorium (cause or effect)
• Toxic/ septic /apprehensive look
• Bilious or bloody vomiting
• Presence of inconsolable cry or excessive irritability
(meningitis, intussusception)
• Signs of severe dehydration or concern for
symptomatic hypoglycemia
• Visible severe wasting
• Bent-over posture (drawing of legs up to the chest), and pained
avoidance of unnecessary movement typical of peritoneal
irritation (peritonitis, intussusception)
counted as a single episode. Recurrent vomiting is defined
as at least 3 episodes occurring over 3 mo period. Recurrent
vomiting is further subdivided into chronic vomiting, which
is low grade frequent (>2/wk) vomiting episodes, and epi-
sodic or cyclic vomiting, which is discrete episodes of high
intensity vomiting that occur sporadically in between
asymptomatic intervals. Cyclic vomiting syndrome is dis-
tinct clinical entity.It is important to elicit temporal pattern
of vomiting because any single attack of episode or cyclic
vomiting may resemble an acute vomiting attack.
Time of day vomiting occurs can give some clue to
diagnosis. Vomiting consistently in early morning is com-
mon with increased intracranial pressure from various
causes and cyclic vomiting syndrome.
Contents of Vomiting
Contents of vomiting gives important clue to diagnosis and
sometimes helps in identifying serious illness. These are
given in Table 4.
Relationship with Diet
Vomiting is aggravated by food in patients with gastritis,
cholecystitis, pancreatitis, protein allergy, and hereditary
Table 3 Temporal patterns of vomiting
Acute pattern
Epidemiology Most common
Etiology See Table 1
Vomiting severity Moderate to severe ± dehydration
Migraine family history
321
fructose intolerance. History of binge eating should be asked
when behavioral cause is suspected.
Associated Symptoms
GI Symptoms
& Diarrhea: Gastroenteritis (diagnosis is made if vomiting
and diarrhea both are present), bacterial colitis, inborn
error of metabolism and partial intestinal obstruction.
& Abdominal pain and its location
– Generalized : [peritonitis, abdominal migraine
(recurrent)]
– Substernal : Esophagitis
– Epigastric: Gastritis, pancreatitis
– Right upper quadrant : Cholelithiasis, pneumonia
– Right lower quadrant : Appendicitis (vomiting after
pain)
– Lower abdominal or suprapubic- UTI
Extra Intestinal Symptoms
& Sore throat, ear pain: Sinusitis, otitis media
& Urinary retention, dysuria: Urinary tract infection,
pyelonephritis
& Jaundice: Hepatitis, biliary disorders
& Headache: Allergy, chronic sinusitis, migraine
– Nocturnal or early morning worsened by coughing or
valsalva manoeuvre
& Vertigo: Migraine, Meniere disease
& Rash or urticaria: Food allergy, Henoch Schonlein purpura
& Back pain- Pyelonephritis
History of Toxic Ingestions: Food, iron, alcohol,
organophosphates
History of Drug Intake: digoxin (vomiting is first sign
of toxicity), theophylline, salicylates, chemotherapeutic
drugs, acetaminophen
Recurrent: chronic Recurrent: cyclic/episodic
2/3 of those with recurrent vomiting 1/3 of those with recurrent vomiting
Gastrointestinal (GI) more common Extra-intestinal causes outnumber
than extra-intestinal ones (7:1) GI ones (5:1)
Acid peptic disease, H. pylori Cyclic vomiting syndrome (88 %), DKA,
Addison disease, metabolic disorders,
malrotation, hydronephrosis
Mild (1–2 emeses/h at peak). Moderate to severe (6 emeses/h at peak),
Rarely dehydrated >50 % require IV hydration
Up to 14 % positive Up to 82 % positive
322 Indian J Pediatr (April 2013) 80(4):318–325

History of recent head trauma, similar symptoms in family
or neighbourhood (gastroenteritis, food poisoning,
hepatitis)
Physical Examination
The physical examination is directed towards evaluation of
degree of toxicity and dehydration and then focused according
to possible clinical etiology.
Abdominal Examination
& Look for signs of obstruction such as distension, tender-
ness, high-pitched bowel sounds (or absent sounds in
ileus), or visible peristalsis
& Look for organomegaly
& Genitalia and hernia sites for ovarian/testicular torsion,
strangulated hernia
& Per rectal examination: especially when intussusception
is suspected.
Clinical features of some common surgical causes of
vomiting are given in Table 5.
Extra Abdominal Examination
& Look for icterus (hepatitis, biliary disease), pallor (intra-
cranial bleed), rash or petechiae (CNS infection or bleed)
& Ear examination- Bulging red tympanic membrane (otitis
media)
& Abnormal muscle tone : Cerebral palsy (GER), metabolic
disorder, mitochondriopathy
& Abnormal fundoscopic exam or bulging fontanelle: In-
creased intracranial pressure, pseudotumorcerebri
& Neck stiffness, Kernig’s and Brudzinski’s sign: Meningitis
[Sensitivity and specificity of vomiting is 71 % and 62 %
respectively for diagnosis of meningitis in a child with
clinically suspected meningitis [4]].
Infant Regurgitation is defined as vomiting occurring two
or more times per day for 3 or more wk in the first 1–12 mo of
life (2–4 wk commonly) in an otherwise healthy infant [5].
Affected children may appear irritable during or after the
feedings and stereotypic opisthotonic movements with exten-
sion and stiffening of arms and legs and extension of the head
(Sandifer syndrome) occasionally may be observed. Infants
who have the classic history of recurrent emesis but who are
thriving and have normal physical examination findings do
not need specific treatment; up to 95 % of them have resolu-
tion of symptoms by 12 mo (majority by 6 mo). Thickening
the formula or human milk by adding cereal may help reduce
vomiting in such infants, but elevating the head in the supine
position has no proven beneficial effect [6].
Infants with severe GER can have recurrent microaspira-
tion into their lungs resulting in chronic wheezing, respira-
tory symptoms, and even failure to thrive. This is known as
GER Disease. Basic reflux precautions such as smaller,
more frequent feeds and allowing the infant to remain up-
right for 30 min after feeds can be helpful. Reassuring the
family that most children spontaneously outgrow GER by
the age of 1 usually helps alleviate parental anxiety.
Minor Head Injury Minor head injury can present as vomit-
ing in children, especially toddlers [7]. There is evidence to
suggest that vomiting after a minor head injury may be
related to intrinsic patient factors rather than the severity
of the injury [8]. Vomiting that is persistent or latent in onset
may more likely to signify head injury.
Rumination Syndrome Rumination syndrome, an under-
recognised condition, is characterised by effortless, often
repetitive, regurgitation of recently ingested food into the
mouth. It was originally described in children and in the
developmentally disabled but it is now well -recognised that
the condition occurs in patients of all ages and cognitive
abilities [9]. The pathophysiology is incompletely under-
stood, but involves a rise in intra-gastric pressure, generated
by a voluntary, but often unintentional, contraction of the
abdominal wall musculature, at a time of low pressure in the
lower oesophageal sphincter, causing retrograde movement

Table 4 Etiology and source of vomiting according to contents of vomitus

Material Source Examples

Undigested food Esophageal Esophageal stricture, achalasia

Bile: green/yellow Post-ampullary
Distal to ampulla of vater
Digested food, milk curds Stomach proximal to pylorus
Blood: red (fresh blood)/brown (old blood) Lesion above ligament of Treitz:
Stomach, esophagus
Clear large volume Increased gastric secretions
Malodorous/ feculent Distal or Colonic obstruction
Mucus Respiratory mucus, gastric
Small bowel obstruction (e.g., malrotation),
prolonged vomiting of any cause
Pyloric stenosis
Gastritis, esophagitis, bleeding diathesis
Peritonitis, Zollinger-Ellison syndrome
Malrotation, appendicitis, stasis syndrome
URI, sinusitis, eosinophilic esophagitis
Indian J Pediatr (April 2013) 80(4):318–325 323

Table 5 Typical clinical pre-

sentation of some surgical
illnesses which may present
with vomiting
Appendicitis Pre-adolescent child with periumbillical crampy pain and anorexia followed by
vomiting. Pain shifts to right lower quadrant and fever may develop. Abdominal
pain preceded by vomiting can be helpful in distinguishing appendicitis from
acute gastroenteritis
Intussusception 3 mo to 5 y-old (peak 6–11 mo) with intermittent colicky abdominal pain, vomiting,
and bloody mucous stools (triad in 20 % to 40 % of cases, and at least two findings
in 60 %), appears ill, quiet, or exhausted. Uncommonly classic tender sausage shaped
mass on right side of the abdomen and occult blood or frankly bloody, foul-smelling
“currant jelly” stool on rectal examination (absence of these does not rule out diagnosis).
Pyloric stenosis 3 wk-3 mo- old infant, with progressively worsening non-bilious vomiting, may
appear quite well early in the illness, but often seem frustrated and hungry. As the
obstruction increases, the vomiting becomes projectile.

of gastric contents into the oesophagus [9]. A typical history
can be highly suggestive but oesophageal manometry may
help to distinguish rumination syndrome from other belching/
regurgitation disorders [9].
Laboratory Investigations
The diverse nature of causes of vomiting makes a “routine”
laboratory or radiologic screen impossible. The history and
physical examination must guide the approach in individual
patients. Investigations are not required in following conditions
and a therapeutic trial of medications should be given if required.
& Well appearing infant with typical regurgitant reflex (no
diarrhea, fever, nausea and forceful abdominal contractions)
& Well child with suspected gastritis or gastroesophagial reflux.
& Brief episode of vomiting with no dehydration and clear
etiology like gastroenteritis
& Chronic vomiting where acid peptic disease is suspected
Selected tests can give useful clues to diagnosis.
Urinalysis
Presence of glucose and ketones suggest diabetic ketoaci-
dosis; red blood cells suggest a renal cause (nephritis, UTI,
renal calculi or trauma); and leukocytes or nitrites suggest a
urinary tract infection.
Blood Investigations
In any child with dehydration or red flag signs (Table 2),
total blood counts, blood sugar, serum electrolytes, blood
gases, Liver enzymes, and renal function tests should be
obtained according to the clinical possibility.
& Serum Electrolytes and Blood Gases: Typical abnormal-
ities occur in an infant with projectile vomiting from
pyloric stenosis (hypochloremic, hypokalemic metabolic
alkalosis), congenital adrenal hypoplasia (hyperkalemia
and hyponatremia), increased lactate production caused
by alcohols, salicylates, uremia, and metabolic defects
(acidosis with elevated anion gap), renal tubular acidosis
(metabolic acidosis with a normal anion gap) and renal
or prerenal failure (elevated creatinine).
Hepatic or pancreatic enzymes may be elevated in the
setting of liver or pancreatic disease.
Radiographic Tests
Radiographic tests are needed to differentiate surgical
causes from nonsurgical etiologies.
& Plain Radiograph Abdomen: Abdominal X ray (erect
preferably) should be done in any child with suspected
intestinal obstruction. Upright or cross-table lateral view
can reveal distended bowel loops and/or air-fluid levels
consistent with intestinal obstruction(in a child with
bilious vomiting, abdominal pain and distension); dilat-
ed stomach in pyloric stenosis; free air under diaphragm
in case of a hollow viscus perforation; abnormal calcifi-
cations like renal or biliary stones or fecoliths; and
basilar infiltrates caused by lower lobe pneumonias.
& Ultrasound: Uitrasonography of abdomen should be
obtained according to the clinical possibility. Abdominal
ultrasound can be helpful in diagnosis of appendicitis,
pyloric stenosis, and intussusceptions. Pelvic ultrasound
is the test of choice for renal, ovarian or uterine pathol-
ogy in children.
& An Upper GI Series best demonstrates malrotation and
upper gastrointestinal tract obstructions and may some-
times be needed for diagnosis of pyloric stenosis.
& CT Scan: A limited CT with rectal contrast can be
helpful in diagnosis of appendicitis. An abdominal CT
is most useful in imaging the liver and pancreas, and for
evaluating mass lesions in the abdomen.
Upper GI Endoscopy
Upper GI endoscopy is useful for defining upper GI muco-
sal pathology such as acute gastritis, gastric erosions, esoph-
agitis, acute duodenitis, duodenal ulcers, stricture, varices,
324
mass (polyp, lymphoma), and foreign body impaction. The
diagnostic yield of upper gastrointestinal endoscopy in chil-
dren up to 18 y of age with vomiting in one study from
Saudi Arabia was 67 %. [10]
Metabolic Work Up
In a child with episodic vomiting or suspected metabolic
disorders, blood and urine screening are positive only dur-
ing actual vomiting episode. Therefore, attempt should be
made to obtain samples (blood pH, ammonia, lactate,
ketones, urine ketones and electrolytes, porphyrins and re-
ducing substances) during acute episode only.
In chronic vomiting if therapeutic drug trial fails to im-
prove symptoms, screening laboratory tests (complete blood
count, ESR, celiac screening, liver enzymes) and abdominal
ultrasound can be obtained along with pediatric gastroenter-
ology consultation.
Emergency Management
& Treat dehydration (refer to protocol for diarrhea)
& If bilious vomiting, stop oral fluids/feeds (nil per oss –
NPO) and decompress the stomach with nasogastric
tube. Start intravenous fluids. Seek surgical consult.
& Antiemetics: Antimetics are not routinely indicated due to
concerns about side effects of earlier generation of antie-
metics (promethazine, prochlorperazine, and metoclopra-
mide) which cause somnolence, nervousness, irritability,
dystonic reactions and other extrapyramidal symptoms.
Newer antiemetics such as ondansetron have far fewer
side effects [11]. Evidence based on a limited number of
studies evaluating the role of ondansetron in the treatment
of acute gastroenteritis complicated by vomiting, favour
the use of ondansetron and metoclopramide to reduce the
number of episodes of vomiting. However, diarrhea
increases with both ondansetron and metoclopramide,
which is thought to be as a result of retention of fluids
and toxins that would otherwise have been eliminated
through the process of vomiting [12]. A recent RCT
concluded that administration of oral ondansetron in chil-
dren with acute gastroenteritis with vomiting who are
unable to tolerate oral intake decreases vomiting, ratio of
hospitalization as well as IV fluid requirement [13].
Use of antiemetics prior to evaluation for surgical abdomen
should be avoided. Following are acceptable indications for
antiemetics (Ondansetron) in children with vomiting:
1. Child not able to take orally due to persistent vomiting
2. Post-operative vomiting
3. Chemotherapy induced vomiting
4. Cyclic vomiting syndrome
Indian J Pediatr (April 2013) 80(4):318–325
5. Acute motion sickness
Dose of Ondansetron Oral: 0.2 mg/kg and Parenteral
0.15 mg/kg (maximum 4 mg); range 0.13–0.26 mg/kg. Higher
doses are not beneficial nor do they have more side effects [14].
While there are existing older studies evaluating domper-
idone, dexamethasone and promethazine, these studies have
small sample sizes, low methodological quality and reveal
inconsistent results and their use is not recommended, par-
ticularly in the light of increased concerns regarding the
safety of these medications for children.
& Drugs for acid peptic disease: can be given empirically
for 2 wk to 4 wk. H2 receptor antagonist or proton pump
inhibitor can be used.
& Cyclic vomiting syndrome is an idiopathic disorder that
usually begins in early childhood and is characterised by
repeated, discrete attacks of vomiting to the point of
dehydration, (on average 12 episodes/d, typically lasting
for 2–3 d) and intervening periods of normal health.
Relatively little is known about its’ pathogenesis or
cause [15]. Episodes usually occur in morning hours,
and may have associated prodrome of nausea, pallor and
headache. Treatment is supportive, focused on fluid
management in cases where dehydration and electrolyte
imbalance occur. Amitriptyline and propranolol have
been described as effective for prophylactic therapy
(antiemetics may be of benefit during an acute episode).
& The mainstay of treatment for rumination syndrome is
explanation and behavioral treatment which consists of
habit reversal techniques that compete with the urge to
regurgitate [9].
Conflict of Interest None.
Role of Funding Source Used available resources of Department of
Pediatrics
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Stanford: Appleton & Lange; 1999. pp. 586–96.
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DOI 10.1007/s12098-012-0909-3
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN GASTROINTESTINAL EMERGENCIES
Management of Acute Diarrhea in Emergency Room
Parag Dekate & M. Jayashree &
Sunit C. Singhi
Received: 3 July 2012 / Accepted: 8 October 2012 / Published online: 30 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Acute diarrhea is the second leading cause of
under-five mortality in India. It is defined as the passage
of frequent watery stools (>3/24 h). Recent change in con-
sistency of stools is more important than frequency. Acute
diarrhea is caused by variety of viral, bacterial and parasitic
agents. The common ones are: Rotavirus, E. coli, Shigella,
Cholera, and Salmonella. Campylobacter jejuni, Giardia
and E. histolytica are also not uncommon. The most impor-
tant concern in management of acute diarrhea in Emergency
room (ER) is fluid and electrolyte imbalances and treatment
of underlying infection, wherever applicable. It includes,
initial stabilization (identification and treatment of shock),
assessment of hydration and rehydration therapy, recogni-
tion and treatment of electrolyte imbalance, and use of
appropriate antimicrobials wherever indicated. For assess-
ment of hydration clinical signs are generally reliable; how-
ever, in severely malnourished children sunken eyes and
skin turgor are unreliable. Oral Rehydration Therapy is the
cornerstone of management of dehydration. Intravenous
fluids are not routinely recommended except in cases of
persistent vomiting and/or shock. Majority of cases can be
managed in ER and at home. Hospitalization is indicated in
infants <3 mo, children with severe dehydration, severe
malnutrition, toxic look, persistent vomiting and suspected
surgical abdomen. Supplementations with zinc and probiot-
ics have been shown to reduce severity and duration of
diarrhea; however evidence does not support the use of
antisecretary, antimotility and binding agents. Education of
parents about hand hygiene, safe weaning and safe drinking
water etc., can help in reducing incidence of this important
health problem in the country.
P. Dekate : M. Jayashree : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Keywords Children . Acute diarrhea . Oral rehydration
therapy . Severe dehydration
Introduction
Diarrhea remains second commonest cause of death in chil-
dren under 5 y in developing countries despite improving
trends in diarrhea mortality; it accounts for 15 % of all
deaths of children less than 5 y in developing countries
[1, 2]. On average, children < 5 y in developing countries,
suffer a median of 3.2 episodes of diarrhea/child/year and up
to 4.9 children/1000/year die because of diarrhea. Most of the
deaths are because of fluid and electrolytes imbalance. The
most common concern in Emergency management is acute
fluid and electrolytes imbalances and treatment of underlying
infection wherever indicated.
Definition
Diarrhea Diarrhea is defined as passage of unusually loose or
watery stools with an increase in the frequency, usually at least
three times in 24 h period. However, it is the consistency of the
stools rather than the number that is most important. Breast
fed babies may normally pass 5–7 stools a day. Diarrhea
lasting longer than 14 d is labeled as ‘persistent diarrhea’.
Dysentery Presence of gross blood in the stool is the hall-
mark of dysentery and may be accompanied by abdominal
cramps and fever.
What is Not Diarrhea?
& Passage of frequently formed stools.
& Passage of pasty stools in breast fed infants.
236
& Passage of stool during or immediately after feeding due
to gastrocolic reflex.
& Passage of frequent loose greenish yellow stools on the
3rd and 4th day of life called as transitional stools.
Etiology
Common organisms causing diarrhea, their incidence and
pathogenesis are given in Table 1.
Viral diarrhea infects small intestinal epithelium. The
onset is generally abrupt, patient is likely to be afebrile
and may have associated vomiting or respiratory symptoms.
Toxigenic bacteria also involves small bowels and causes
secretary diarrhea (Table 2)
Invasive bacterial and protozoal diarrhea involves colon.
Diarrhea is bloody or mucoid and may have associated col-
icky abdominal pain, fever and tenesmus. Food poisoning is
caused by preformed bacterial toxins. Onset is abrupt with
vomiting followed by diarrhea (Table 3).
Clinical Evaluation [2–4, 8–10]
The objectives of initial clinical evaluation of the patient in
emergency department are:
1. Assessment of the severity of the illness, grade of de-
hydration and rehydration needs.
2. Identification of likely causes on the basis of the history
and clinical findings.
A rapid assessment of airway, breathing and circulation
should be done in all children at presentation. Tachycardia,
prolonged capillary refill time, decreased urine output, al-
tered mental status and hypotension indicates presence of
shock and calls for oxygen, and fluid resuscitation with
20 ml/kg normal saline bolus.
History and Examination
Further history and examination [2–4, 8–10] should include
information as shown in Table 4.
Hydration status is assessed from stool frequency, heart
rate, pulse volume, capillary refill time, skin turgor, sunken
eyes or fontanelle and activity level, or change in weight
from the previous weight. Grading of hydration status based
on clinical signs is shown in Table 5 and that based on
change in weight in Table 6. Some of the typical signs of
dehydration may not be reliable in malnourished children.
Marasmic children may have sunken eyes, and diminished
skin turgor without dehydration. Skin turgor may be masked
by edema in children with Kwashiorkor; irritability and
Indian J Pediatr (March 2013) 80(3):235–246
apathy may be present in both the types of malnutrition. In
such children thirst, dry tongue and mouth (inner side of
cheek), and signs of hemodynamic compromise (fast thread
pulse, delayed capillary refill time and orthostatic
changes in BP, and hypotension) are most reliable indicators
of dehydration [4].
On abdominal examination children with uncomplicated
diarrhea generally tend to have diffuse abdominal tenderness
and loud bowel sounds. Presence of localized tenderness,
rebound tenderness to absent bowel sounds indicates a possi-
ble surgical cause. Palpation of a loop of bowel or a mass
suggests intussusception, enterocolitis or inflammatory bowel
disease.
Laboratory Investigations
Laboratory investigations are not required routinely in major-
ity of cases of acute diarrhea. Indications for selective use of
laboratory investigations are as summarized in Table 7.
Differential Diagnosis of Acute Diarrhea [3, 9]
Systemic Disease with Acute Diarrhea
Infants and young children with systemic disease can some-
times present with acute diarrhea. They generally have sys-
temic signs of sepsis and sick look, but not necessarily. In such
children following clinical diagnosis should be kept in mind.
& Otitis media, bacterial pharyngitis
& Urinary tract infection
& Pneumonia
& Meningitis
& Bacterial sepsis
Diarrhea with Surgical Acute Abdomen
When symptoms of colicky abdominal pain, vomiting and
lethargy accompany bloody diarrhea, and abdominal palpa-
tion reveals a mass, intussusception, malrotation, and sub-
acute intestinal obstruction should be ruled out.
Sometimes because of ingested food stools may appear
red (e.g., From beet, red candies, popsicles, cranberries etc.)
or tarry (bismuth containing anti-diarrhea, Iron-spinach,
chocolate etc.) mimicking blood in stools.
Management [2, 4]
Majority of the patients with diarrhea having mild or no
dehydration can be treated on ambulatory basis at home. Some
patients may need a brief period of observation while patients
Table 1 Etiological causes of diarrhea with incidence and pathogenesis [3–6]

Category Agent Incidence Pathogenesis

Indian J Pediatr (March 2013) 80(3):235–246

Viruses Rotavirus Causes 15–20 % of diarrhea Cytopathic to small intestinal epithelial cells
Responsible for upto 50 % of diarrhea associated with clinical
dehydration in children aged 6–24 mo.
Enterovirus Virus replication and cytopathic effect on small intestinal cells
Adenovirus 2–5 % Cytolysis, cytokine production, and induction of host inflammatory response
Bacteria Enterotoxigenic E. coli (ETEC) Causes up to 25 % diarrhea in all age groups Produces heat labile (LT) and/or heat stable (ST)
enterotoxins causing secretory diarrhea of small intestine
Shigella Causes upto 5–10 % of acute diarrhea in all age groups Dysentery syndrome by invasion of large bowel and enterotoxin
mediated small bowel diarrhea
Vibrio cholera Frequent cause of diarrhea in endemic areas in children 2–10 y Toxin mediated secretory diarrhea
of age. Accounts for 5–10 % hospitalization in non endemic areas.
Non typhoidal salmonella Causes 2–10 % of diarrhea in developing countries Intracellular invasion of ileal epithelium
Campylobacter jejuni Causes 5–15 % of all diarrhea. It is a zoonosis Invasive and toxigenic diarrhea
Protozoal Giardia duodenalis[5] Most common protozoal infection causing diarrhea Damage to the endothelial brush border, enterotoxins,
immunologic reactions, and altered gut motility and
fluid hypersecretion
Entamoeba histolytica [6] Annually 0.09 episodes/child of E. histolytica-associated diarrhea Excystation in the small bowel and invasion of the colon
and 0.03 episodes/child of E. histolytica-associated dysentery by the trophozoites
Cryptosporidium [7] Causes a self-limited diarrheal illness in healthy individuals Infects distal small intestine and proximal colon, no
and persistent diarrhea in immunocopromised children cytopathic effect. Causes villous atrophy, lymphocytic infiltration etc.
237
238 Indian J Pediatr (March 2013) 80(3):235–246

Table 2 Etiologic agents and and pattern of small vs. large bowel Table 4 History and clinical evaluation of diarrhea patient [2, 4, 8, 9]
diarrhea [3, 4]
History Assessment of dehydration
Site Organisms Characteristics
Onset, frequency, quantity General appearance, alertness
Small bowel Rotavirus, Salmonella, Frequent, large Character: bile, blood and mucus Temperature
diarrhea V. cholera, Giardia, quantity, watery,
Vomiting (color and frequency) Pulse rate, volume
Cryptosporidium greenish to white
stools Fever Respiratory rate (acidotic breathing)
Large bowel Shigella, Enteroviruses, Semi-loose, small Oral acceptance Blood pressure
diarrhea E. coli, C. jejuni, quantity, with or Abdominal distension Capillary refill time
E. histolytica without blood in Level of consciousness, Mucus membrane
the stool abnormal movements (tongue, inner cheek)
Urine output (passage Sunken fontanels, sunken eyes
of urine in last 6 h) Skin turgor
having severe dehydration and a selective group of very Perianal excoriation or redness Glasgow coma score (GCS)
young, malnourished, toxic-sick looking patients need hospi- Underlying medical condition Signs of malnutrition
talization as shown below. Past medical history Change in body weight
Epidemiological history (if previous body weight known)

Indications for Observation in Emergency Department

& Stable newborns and infants with diarrhea without fea-
tures of toxicity and dehydration.
& Patient with moderate dehydration accepting orally well.
& Malnourished children with mild dehydration.
& Patients with diarrhea without dehydration with de-
creased oral intake.
Indications for Hospitalization [2–4, 10]
& Severe dehydration requiring intravenous hydration.
& Newborns and infants <3 mo of age with dehydration.
& Malnourished children with dehydration.
& Toxic appearance, changing mental status (GCS<11) or
seizures.
& Fever >38.5 °C for infants > 3 mo or >39 °C for children
6–36 mo-old.
& Suspected surgical cause: localizing findings and entero-
colitis need surgical consult.
& High output diarrhea (>10 large volume stool/day).
& Persistent vomiting, or diminished or no oral intake .
& Suboptimal or no response to oral rehydration therapy
(ORT) or further deterioration.
& Inability of caregivers to administer ORT.
& History of premature birth, chronic medical conditions
or concurrent illness.
Table 3 Incubation period and likely causes of toxogenic diarrhea/
food poisoning [3, 4]
Incubation period Likely causes of diarrhea
<6 h Preformed toxins of B. cereus and S. aureus
6 – 24 h Preformed toxin of C. perfringes and B. cereus
16 – 72 h Vibrio, Salmonella, ETEC, Shigella,
Campylobacter, Yersinia, Shiga toxin
producing E.coli, Giardia, Cyclospora,
Cryptosporidium
Treatment of a Child with Diarrhea Presenting in Shock
It is difficult to distinguish between hypovolemic shock
caused by severe dehydration and septic shock initially. All
children in shock should be given 20 ml/kg of rapid fluid
bolus in first hour with continuous monitoring of pulse rate,
pulse volume, respiratory rate, capillary refill time and urine
output. If shock improves at the end of the bolus (reflected by
decrease in pulse rate, respiratory rate, improved pulse
volume, capillary refill time and urine output), a diagnosis
of hypovolemic shock (severe dehydration) should be con-
sidered and oral rehydration therapy should be started as
detailed later. If there is worsening or no improvement at
end of initial fluid bolus, septic shock should be considered
and appropriately managed as per the septic shock guidelines
(management of septic shock is beyond the scope of this
protocol, please refer to septic shock guidelines elsewhere).
Oral Rehydration Therapy (ORT)
Oral rehydration therapy (ORT) is the administration of
fluid by mouth to prevent or correct dehydration that
occurs as a consequence of diarrhea. ORT is the stan-
dard for efficacious and cost-effective management of
acute gastroenteritis, both in developing and developed
countries.
Oral rehydration solution (ORS) is the fluid specifically
developed for ORT. Composition of standard ORS is shown
in Table 8. A more effective, lower-osmolarity ORS (with
reduced concentrations of sodium and glucose, associated
with less vomiting, less stool output, and a reduced need for
intravenous infusions in comparison with standard ORS)
has been developed for global use [2, 8, 10].
Indian J Pediatr (March 2013) 80(3):235–246 239

Table 5 Assessment
of dehydration [2–4, 8, 9] Characteristics Mild Moderate dehydration Severe dehydration (>2signs)
dehydration (≥2 signs)

Watery stools < 4/d 4–10/d >10/d

Vomiting Some/none Some/none Very frequent
Condition Well alert Restless, irritable Lethargic, dry, floppy
Eyes Normal Sunken Very sunken and dry
Tears Present Absent Absent
Tongue Moist Dry Very dry
Thirst Drinks normally Thirsty, drinks eagerly Unable to drink
Skin turgor Normal Delayed (slow return) Very delayed (>2 s)
CRT Normal Prolonged Prolonged
Extremities Warm Cold Mottled, cynotic
Heart rate Normal Increased Increased or decreased in severe cases
Pulse quality Normal Normal to decreased Weak, thread, impalpable
Urine output Normal Decreased and high colored Very scanty/anuria for 6 h

ORT consists of
& Rehydration
& Maintenance therapy
& Prevention of ongoing losses
ORT may be contraindicated in children who are in hemo-
dynamic shock or with ileus. For children who are unable to
tolerate ORS via oral route (with persistent vomiting),
naso-gastric feeding can be used to administer ORS.
Treatment of Mild and Moderate Dehydration
1. Oral Rehydration Therapy (ORT) [2, 4, 10]
& Determine amount of ORS to be given during first
4 h (Table 9)
& Show the mother how to mix and give ORS solution.
Give frequent small sips from a cup. If the child vomits,
wait for 10 min. Then continue, but more slowly. Con-
tinue breastfeeding whenever the child wants.
& Give recommended amount of ORS over 4–h period as
mentioned in Table 9 according to the degree of
dehydration.
& Reassess for the degree of dehydration after 2–4 h and
select the appropriate plan for further rehydration.
2. Give Extra Fluids [2, 4, 11]
& If breast fed, breastfeed frequently and for longer at
each feed.
& If the child is not exclusively breastfed, give one or
more of the following home made food-based fluids
(such as soup, rice water, and yoghurt drinks), or
clean water.
& If the child wants more ORS than shown, give more.
& For infants less than 6 mo who are not breastfed, also
give 100–200 ml clean water during this period.
& Show the mother how much fluid to give in addition
to the usual:
Up to 2 y: 50 to 100 ml after each loose stool and in
between them.
2 y or more: 100 to 200 ml after each loose stool
and in between them.
3. Continue Feeding [2, 10]
Begin feeding the child in emergency itself with
whatever is appropriate for the age of the child. Avoid
high fiber and bulky food, very dilute soups and food
with lot of sugar.
Points to be Kept in Mind During Rehydration [4]
& Rehydration must be assessed by clinical examination
and not by fluid volume given.
& The volumes can be increased to achieve rehydration.
& Puffiness around the eyes suggests over hydration.

Table 6 Assessment of severity of dehydration as per body weight loss [2– 4]

Age Mild dehydration Moderate dehydration Severe dehydration

Infants (EWL) 0–5 % of body wt. loss 5–10 % of body wt. loss >10 % of body wt. loss
Children and adolescents(EWL) <3 % of body wt. loss 3–9 % of body wt. loss >9 % of body wt. loss

EWL Estimated weight loss

240 Indian J Pediatr (March 2013) 80(3):235–246

Table 7 Indications for various investigations in a patient with acute diarrhea and their importance [4, 10]

Investigations Indications Important points

Stool routine 1. Mucoid and bloody diarrhea Presence of leukocytes, protozoa, RBC’s and bacteria.
2. Suspected cholera (hanging drop preparation) Presence of polymorphs suggest infection by invasive bacteria
Stool culture 1. Toxic looking infants <1 y having Available after 2–3d
polymorphs in stool Start/change antibiotic as per sensitivity pattern
2. Suspected cholera
3. Immunocompromised children
4. Children with hemoglobinopathies
Blood counts, blood 1. Newborns with diarrhea Distinguishes Salmonella and Shigella infection -
culture, CRP 2. Toxic infants and children’s Shigella having a marked shift to left.
3. Infants <3 mo, with fever >38.5°C Start/change antibiotic as per sensitivity pattern
4. Older children with sepsis, fever, seizures Monitoring of systemic inflammation
and altered sensorium
Blood biochemistry (Na, K, 1. All those requiring hospitalization These parameters will guide the treatment plan and
urea, creatinine, glucose) 2. Seriously ill toxic patients guide the response to treatment. Some abnormalities
3. Severe dehydration/shock need urgent treatments (hypo kalemia, hypoglycemia,
hyponatremic seizures etc. )
4. Malnourished patients with dehydration
5. Newborns and infants <3 mo
6. Children with altered sensorium
Blood gas analysis 1. All seriously ill patients Will tell about metabolic acidosis, bicarbonate
2. Patients with acidotic breathing losses from the body, body compensation and
improvement with treatment
3. Patients with severe dehydration or shock
4. Malnourished patients with dehydration
ECG 1. Malnourished patients Will tell about the K+ status
2. Severely dehydrated patients
3. Patients with high output diarrhea
4. Patients having acidosis

Maintenance therapy should be started as soon as the signs of & Has sunken eyes
dehydration have gone, but not before it. A simplified algorithm & Has fever
for rehydration therapy of acute diarrhea is shown in Fig. 1. & Does not eat or drink normally
& Not passing urine for 6 h
When to Return & Having altered mentation
& Not getting better after 2 d
Mother/caretaker should be advised to return to health
care facility immediately if any of the following symp-
toms are noticed. Treatment of Severely Dehydrated Children
& Passes many stools (>10 times/d) (Replacement Therapy) [2, 4, 10]
& Is very thirsty
Start IV fluid immediately. If the child can drink, give
Table 8 Composition of WHO ORS [2] ORS by mouth while the drip is set up. Give 100 ml/kg
Components g/L Constituents Concentration Ringer’s Lactate Solution (or, if not available, normal
(ionic form) (mmol/L) saline) divided as follows: 20 ml/kg body weight intra-
venously till perfusion and mental status improve; then
Sodium chloride 2.6 Sodium 75 administer 100 ml/kg ORS over 4 h or 5 % dextrose ½
Anhydrous glucose 13.5 Chloride 65 saline IV at twice maintenance fluid rate (Table 9).
Potassium chloride 1.5 Glucose 75
Trisodium citrate, dihydrate 2.9 Potassium 20
& Reassess the child every 1–2 h. If hydration status is not
- - Citrate 10
improving; give IV drip more rapidly. Also give ORS
(about 5 ml/kg/h) as soon as the child can drink; usually
Total osmolality 245
after 3–4 h (infants) or 1–2 h (children).
Indian J Pediatr (March 2013) 80(3):235–246 241

Table 9 Guidelines for

rehydration therapy [2, 4, 10] Degree of dehydration Age group Type of fluid Volume of fluid Rate of administration

Mild All ORS 50 ml/kg Within 4 h

Moderate < 4 moa (< 6 kg) ORS 200 – 400 ml Within 4 h
4 –12 mo ORS 400 – 700 ml Within 4 h
(6 – 10 kg)
12 – 24 mo ORS 700 – 900 ml Within 4 h
a
Use the child’s age only when (10 – 12 kg)
the weight is not known. The 24 – 60 mo ORS 900 – 1400 ml Within 4 h
approximate amount of ORS re- (12 – 19 kg)
quired (in ml) in case of moder- Severe < 12 mo RL First 30 ml/kg Within 1 hb
ate dehydration can be
calculated as 50– 100 (75) ml/kg RL Then 70 ml/kg Within 5 h
of child’s body weight [2] 1–5y RL First 30 ml/kg Within 30 min
b
Repeat if radial pulse is still RL Then 70 ml/kg Within 2.5 h
very weak or not detectable and If signs of dehydration are still present follow by: ORS 20 ml/kg every hour
consider probable septic shock

& Reassess an infant after 6 h and a child after 3 h. Therapeutic End Points in Intravenous Rehydration Therapy
Classify dehydration. Then choose the plan to con-
tinue treatment 1. Adequate urine output
& If ORT is not possible or feasible, same amount of fluid 2. Urine specific gravity (1.010–1.015)
can be given intravenously. Type of fluid used is Ringer 3. Normal serum electrolytes
lactate or N/2 in 5 % dextrose (Fig. 1). 4. BUN decreased by one half every 15–20 h till normalized

Fig. 1 A simplified algorithm

for rehydration therapy
of acute diarrhea
242 Indian J Pediatr (March 2013) 80(3):235–246

5. Normal acid base status are signs of systemic infections, recognizable bloody
6. Urinary K+> 40 mEq/L diarrhea and in immunocompromised hosts as follows:

Antimicrobial Therapy [2, 3, 8, 10]
The decision to treat with antimicrobial therapy should
be made on a patient-by-patient basis, and may differ
according to the age group. Antimicrobials are not
needed for small bowel diarrhea and food poisoning
except cholera. Large bowel diarrhea is invasive. Sal-
monella can cause bacteremia in about 10–45 % of
infected infants and neonates, while shigella and inva-
sive E. coli can cause high fever and toxemia. In
shigellosis,therapy is required in severely ill children
or children with persistent symptoms. Yersinia needs
treatment when there is severe disease, bacteremia or
underlying illness. Timely antibiotic therapy in selected
cases of diarrhea may reduce the duration and severity
of diarrhea and prevent complications. While these
agents are important to use in specific cases, their
widespread and indiscriminate use leads to development
of anitmicrobial resistance. Use of antimicrobials is rec-
ommended in the treatment of acute diarrhea when there
1. Diarrhea with clinical signs of sepsis: (toxic look,
leukocytosis, fever > 38.5° C, septic shock): Ceftriaxone
50 –100 mg/kg/d IV/IM divided 12 hourly for 7–10 d.
2. Diarrhea in a child with severe malnutrition: Ampicillin
200 mg/kg/d IV/IM divided 6 hourly along with genta-
micin 5 mg/kg/d IV/IM 8 hourly for 7–10 d.
3. Neonates and very young infants (< 3 mo) with fever
(> 38.5°C): Cefotaxime 150 mg/kg/d IV/IM divided
8 hourly along with amikacin 15 mg/kg/d IV/IM OD for
7–10 d
4. Dysentry (bloody stools) and diarrhea during outbreak
of shigellosis: Ceftriaxone IV/IM 50–100 mg/kg/d for
7 d or Ciprofloxacin orally 20–30 mg/kg/d divided
12 hourly for 7–10 d.
5. Suspected Cholera (‘Rice water stools’ with high
purge rate i.e., > 10 large volume stools/d): Doxy-
cycline 300 mg OD for 3 d or Azithromycin 20 mg/
kg single dose. Treatment of cholera decreases du-
ration of disease and mortality, and controls the
transmission.

Table 10 Antibiotics used in acute diarrhea as per causative agent[2–4, 7, 9, 10]

Organism Drug of choice Doses

Shigella (severe dysentery Ciprofloxacin, ampicillin, ceftriaxone, or Ceftriaxone IV IM 50–100

and EIEC dysentery) trimethoprim-sulfamethoxazole (TMP-SMX). mg/kg/d qd, bid × 7 d
Most strains are resistant to many antimicrobials Ciprofloxacin PO 20–30 mg/kg/d bid × 7–10 d
10 mg/kg/d of TMP and 50 mg/kg/d of SMX bid × 5 d
V. cholera Doxycycline, azithromycin Doxycycline 300 mg OD for 3 d
or ciprofloxacin Azithromycin 20 mg/kg single dose
Ciprofloxacin PO 20–30 mg/kg/d qid for 5–10 d
EPEC, ETEC, EIEC TMP-SMX or ciprofloxacin 10 mg/kg/d of TMP and 50 mg/kg/d of SMX bid × 5 d
Ciprofloxacin PO 20–30 mg/kg/d qid for 5–10 d
Salmonella No antimicrobials for uncomplicated See treatment of Shigella
gastroenteritis in normal hosts caused
by non-typhoidal species.
Treatment is indicated in infants <3 mo,
patients <1 y with toxic look, severe colitis,
immuno-incompetent state (malignancy,
chronic GI disease, hemoglobinopathies, or HIV infection)
Clostridium difficile Discontinue offending antibiotic
Metronidazole (first line) PO 30 mg/kg/d divided tid × 5 d
Vancomycin (2nd line) PO 40 mg/kg/d qid × 7 d
Entamoeba histolytica Metronidazole PO 30–40 mg/kg/d tid × 7–10 d
Giardia lamblia Furazolidone or metronidazole or albendazole Furazolidone PO 25 mg/kg/d qid for 5–7 d
or quinacrine Metronidazole PO 30–40 mg/kg/d tid × 7 d
Albendazole PO 200 mg bid × 10 d
Campylobacter jejuni Erythromycin or azithromycin Erythromycin 50 mg/kg q8h, 5 d
Azithromycin 5–10 mg/kg qid, 5 d
Indian J Pediatr (March 2013) 80(3):235–246 243

8–24 h (depending upon Sr. Na+ values)a

6. Suspected amebiasis, or giardiasis (colitic stools,
anorexia and weight loss, persistent diarrhea, failure
to thrive): Metroinidazole oral 30–40 mg/kg/d divid-
ed 8 hourly for 7–10 d, and cryptosporidium
(nitazoxamide).

Increased (>145 mEq/L)

Hypertonic dehydration
7. Diarrhea in an immunocompromized child (HIV infec-
tion, lymphoreticular malignancy, receiving chemother-

1/3 normal saline

apy, underwent organ transplantation)

30–40 mEq/L
<10 mEq/L

24–36 h a
12–15 %
> 15 %
Antimicrobials to be given in acute diarrhea when the

10 %
pathogen is known are given in detail in Table 10.

The maximum accepted change in serum osmolality is 1–1.5 mOsmol/L per hour, thus it restricts change of serum Na+ to 0.5 –1 mEq/L per hour
Other Ways of Management

Maintenance fluids (Holiday Segar formula) + Deficit volume

Normal (135–145 meq/L)
Significant abnormalities in serum sodium concentration
can to occur in acute diarrhea. In patients receiving intrave-

Isotonic dehydration
nous rehydration further management of fluid and electro-

½ normal saline

50–80 mEq/L
lyte therapy with respect to serum sodium concentration is

Decreased
given in Table 11.

Variable

<5%

6–8 h
10 %
15 %

15 h
Enteral Feeding and Diet Selection [2]

Weight in kg × volume deficit

Give an age- appropriate diet-regardless of the fluid used
for ORT/maintenance. Infants require more frequent
Decreased (<135 mEq/L)
Hypotonic dehydration
breastfeedings. Older children need appropriately more
Table 11 Classification of dehydration depending upon sodium concentration and its management [4]

fluids and energy and micronutrient – rich foods (Energy

density 1 kcal/g). Give appropriate food (grains, dals,

80–100 mEq/L
Isotonic saline

bananas and vegetables) as frequent, small meals

<10 mEq/L

10–20 h
throughout the day (six meals/day); avoid high fibre,
<5%

4–6 h
bulky diet. Gradually increase energy intake as tolerated to 10 %
5%

reach an energy intake of 100 kcal/kg/d and protein intake

2–3 g/kg/d.
A lactose free diet is often recommended, but is needed

Other ½ of total volume replacement

in malnourished patients or after severe enteritis. ½ of total volume replacement

Zinc Therapy (Zinc supplementation) [2, 4, 10]

Zinc deficiency is widespread among children in devel-

oping countries. Supplementation treatment with zinc
(20 mg per day until diarrhea ceases) reduces the dura-
tion and severity of diarrheal episode in children in
Moderate

developing countries. Zinc supplements are given for

Severe
Mild

10–14 d during and after diarrhea in the doses of

Na+ concentration of repair solution

10 mg/kg for infants < 6 mo of age and 20 mg/d for

the children >6 mo of age. In addition to improving
Serum Sodium concentration

diarrhea, administration of zinc in community settings

Physiological derangement

Total volume requirement

leads to increased use of ORS and reduction in the use

Level of dehydration

of antimicrobials.
Rate of replacement
Deficit estimation
Total body water

Urine sodium

Probiotics [11, 12]

Treatment

Used alongside rehydration therapy, probiotics appear to be

safe and have clinically beneficial effects in shortening the
a
244
duration and reducing stool frequency in acute infectious
diarrhea [11, 12]. There are varieties of microorganisms
(Lactobacillus, Bifidobacterium) that have good safety re-
cord; therapy has not been standardized and most effective
and safe organisms and regimens for specific groups have
not been identified. The authors give their patients probi-
otics for 5 d.
Antimotility Agents [2, 4, 10]
Gut stasis following use of antimotility agents may lead to
invasion of the bowel wall by infecting organisms leading to
worsening of the condition. These agents are contra-indicated
in children with dysentery and probably should not be given to
infants and young children.
Fig. 2 Algorithm for
management of a patient
with diarrhea
Indian J Pediatr (March 2013) 80(3):235–246
Antiemetic Agents [2, 4, 10]
Phenothiazines are of little value and are associated
with potentially serious side effects. Ondensetron is an
effective and less toxic antiemetic agent (Dose: 2 mg in
children 8–15 kg, 4 mg in children >15–30 kg, 8 mg in
children >30 kg). A comprehensive approach to man-
agement of acute diarrhea is shown in Fig. 2.
Specific Aspects of Management of Acute Diarrhea
in Children with Severe Malnutrition
Diarrhea is a serious and often fatal event in children
with severe malnutrition [13, 14]. Management of acute
diarrhea in these children presents unique challenges as
Indian J Pediatr (March 2013) 80(3):235–246
malnutrition predisposes to severe and prolonged diar-
rhea due to underlying micronutrient deficiency (partic-
ularly zinc) that causes suppressed immune function.
Care of these children, in addition to correction of dehydra-
tion, must focus on management of malnutrition, con-
tinuation of feeding which lessens weight loss and early
detection and treatment of underlying infections and probable
sepsis [14].
Assessment of Dehydration
As mentioned earlier, typical signs of dehydration such
as skin turgor, sunken eyes, mental status and peripheral
temperature are unreliable for assessment of hydration
status in a malnourished child. In such children thirst,
dry tongue and inner side of cheek, and signs of hemo-
dynamic compromise (fast weak or absent pulses,
delayed capillary refill time and orthostatic changes in
BP, and hypotension) and reduced or absent urine flow
indicates severe dehydration [4].
Principles of Treatment
Malnourished children in shock should be treated as per
details given in the section earlier.
Children with signs of sepsis or in a state of severe
malnutrition should receive systemic broad spectrum anti-
biotics. General principles of dehydration correction re-
main same as that for any child with diarrhea with
following exceptions:
i. Reduced Osmolarity ORS [RO-ORS] with potassium
supplements should be preferred for rehydration and
maintenance.
ii. Dehydration should be corrected slowly over 12 h.
iii. ORT should be given at 10 ml/kg/h for first two hours
followed by at 5–10 ml/kg every hour for next 4–10 h (by
oral/nasogastric tube), adjusting it based on the capability
of child to drink, volume of fluid loss in stools and
vomiting.
iv. Careful frequent reassessment is needed for signs of
rehydration and overhydration.
v. Overhydration in a malnourished child is dangerous
and can precipitate heart failure because of poor
cardiac reserve and pumping capability contributed
by underlying nutritional cardiomyopathy, anemia
with volume overloaded state and acute illness re-
lated decompensation. An increase in pulse rate with
improved pulse volume, increase in respiratory rate, crepi-
tation over basal lung regions, appearance or increase in
245
edema and appearance of periorbital puffiness indicates
overhydration.
Prevention [2, 3, 7, 8]
Use this opportunity to educate parents about following
measures to prevent further episodes of diarrhea: Safe water
and sanitation, hand hygiene, exclusive breast feeding for
initial 6 mo, appropriate and safe weaning, safe food han-
dling habits, Vitamin A supplementation and vaccination-
against Rotavirus, Typhoid fever, and Measles.
Conflict of Interest None.
Role of Funding Source None.
References
1. WHO/UNICEF. Joint statement on clinical management of
acute diarrhea. New York: UNICEF; 2004. [cited on 25-09-
2011]. Available at: http://www.unicef.org/publications/index_
21433.html.
2. Department of Maternal, Child and Adolescent Health, World
Health Organization. ‘Diarrhea treatment guidelines including
new recommendations for the use of ORS and zinc supplemen-
tation for clinic-based healthcare Workers’. Arlington: USAID;
2005. [cited on 25-09-2011]. Available at: http://www.who.int/
maternal_child_adolescent/documents/a85500/en/index.html.
3. Bhutta ZA. Acute gastroenteritis in children. In: Kliegman S, St.
Geme Schor B, eds. Nelson textbook of pediatrics. 19th ed.
Philadelphia: Elsevier Saunders; 2011. pp. 1323–38.
4. Singhi S. Acute diarrhea. In: Singhi S, Surpure JS, eds. Synopsis of
Pediatric Emergency Care. 2nd ed. Delhi: PEEPEE; 2010. pp. 341–7.
5. Haque R, Mondal D, Duggal P, et al. Entamoeba histolytica infec-
tion in children and protection from subsequent amebiasis. Infect
Immun. 2006;74:904–9.
6. Ajjampur SS, Sankaran P, Kannan A, et al. Giardia duodenalis
assemblages associated with diarrhea in children in South India
identified by PCR-RFLP. Am J Trop Med Hyg. 2009;80:16–9.
7. Khan WA, Rogers KA, Karim MM, et al. Cryptosporidiosis among
Bangladeshi children with diarrhea: a prospective matched case–
control study of clinical features, epidemiology and systemic anti-
body responses. Am J Trop Med Hyg. 2004;71:412–9.
8. CDC Disasters. Guidelines for the management of acute diarrhea
after a disaster. Atlanta: Centers for Disease Control and Prevention;
2008. [cited on 25-09-2011]. Available at: http://emergency.cdc.gov/
disasters/disease/diarrheaguidelines.asp.
9. World Gastroenterology Organization (WGO). WGO practice
guideline: Acute diarrhea. Munich: World Gastroenterology
Organization (WGO); 2008. p. 28. [cited on 25-09-2011].
Available at: http://www.dphhs.mt.gov/publichealth/cdepi/documents/
WorldGastroenterologyOrganizationPracticeGuideline.pdf.
10. Bhatnagar S, Lodha R, Choudhury P, et al. IAP Guidelines 2006
on management of acute diarrhea. Indian Pediatr. 2007;44:380–9.
246
11. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics
for treating acute infectious diarrhoea. Cochrane Database
Syst Rev. 2010;11:CD003048. doi:10.1002/14651858.
CD003048.pub3.
12. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and
prevention of acute infectious diarrhea in infants and chil-
dren: a systematic review of published randomized, double-
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blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr.
2001;33:S17–25.
13. Sachdev HP, Kumar S, Singh KK, Satyanarayana L, Puri RK. Risk
factors for fatal diarrhea in hospitalized children in India. J Pediatr
Gastroenterol Nutr. 1991;12:76–81.
14. Uysal G, Sökmen A, Vidinlisan S. Clinical risk factors for fatal
diarrhea in hospitalized children. Indian J Pediatr. 2000;67:329–33.
Indian J Pediatr (April 2013) 80(4):326–333
DOI 10.1007/s12098-013-0987-x
'
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN GASTROINTESTINAL EMERGENCIES
Approach to a Child with Upper Gastrointestinal Bleeding
Sunit Singhi & Puneet Jain & M. Jayashree & Sadhna Lal
Received: 12 August 2012 / Accepted: 4 February 2013 / Published online: 17 March 2013
# Dr. K C Chaudhuri Foundation 2013
Abstract Upper gastrointestinal bleeding (UGIB) is a poten-
tially life threatening medical emergency requiring an appro-
priate diagnostic and therapeutic approach. Therefore, the
primary focus in a child with UGIB is resuscitation and
stabilization followed by a diagnostic evaluation. The differ-
ential diagnosis of UGIB in children is determined by age and
severity of bleed. In infants and toddlers mucosal bleed (gas-
tritis and stress ulcers) is a common cause. In children above
2 y variceal bleeding due to Extra-Hepatic Portal Venous
Obstruction (EHPVO) is the commonest cause of significant
UGIB in developing countries as against peptic ulcer in the
developed countries. Upper gastrointestinal endoscopy is the
most accurate and useful diagnostic tool to evaluate UGIB in
children. Parenteral vitamin K (infants, 1–2 mg/dose; chil-
dren, 5–10 mg) and parenteral Proton Pump Inhibitors
(PPI’s), should be administered empirically in case of a
major UGIB. Octreotide infusion is useful in control of
significant UGIB due to variceal hemorrhage. A tempo-
rarily placed, Sengstaken-Blakemore tube can be life
saving if pharmacologic/ endoscopic methods fail to
control variceal bleeding. Therapy in patients having
mucosal bleed is directed at neutralization and/or pre-
vention of gastric acid release; High dose Proton Pump
Inhibitors (PPIs, Pantoprazole) are more efficacious than
H2 receptor antagonists for this purpose.
Keywords Upper gastrointestinal bleeding . Endoscopy .
Variceal bleed . Octreotide
S. Singhi (*) : P. Jain : M. Jayashree
Department of Pediatrics Advanced Pediatrics Centre,
Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
S. Lal
Department of Gastroenterology,
Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India
Introduction
Upper gastrointestinal bleeding is usually defined as bleeding
from a site proximal to the ligament of Treitz at the level of
duodeno-jejunal flexure. Hematemesis is the cardinal sign
(vomiting of blood or coffee ground-like material) though
some children may present with malena (black, tarry stools).
Hematochezia (passage of bright red blood in stools) is usu-
ally a feature of lower gastrointestinal bleeding (GIB), but
some infants with UGIB can sometimes present with passage
of bright red blood from the rectum because of rapid gastro-
intestinal transit in a briskly bleeding child.
Etiology
The etiology of UGIB varies with age but considerable over-
lap exists between the different age groups [1]. Rate and extent
of bleeding is chiefly governed by the etiology of UGIB. In
India portal hypertension has been reported to be the com-
monest cause (95 %) in contrast to the developed countries
where non-variceal causes like peptic ulcer, esophagitis bleed-
ing are common (66 %). Extra-hepatic portal vein obstruction
(EHPVO) was the most common cause of variceal bleed in
Indian children [2, 3] (Table 1). While evaluating a child with
upper GI bleed it is important to keep the specific etiologies at
different ages in mind (Table 2).
Neonates
UGIB is rare in the first mo of life, but if seen must be
distinguished from swallowed maternal blood. Hemorrhagic
disease of the newborn due to vitamin K deficiency should be
considered in neonates not given vitamin K prophylaxis at
birth. Maternal idiopathic thrombocytopenia and maternal
NSAID use can also cause bleeding in the newborn. Other
causes include stress gastritis or ulcers, vascular anomalies,
coagulopathy caused by infection, liver failure, or a congenital
coagulation factor deficiency.
Indian J Pediatr (April 2013) 80(4):326–333 327

Table 1 Causes of UGIB among Indian children presenting to a the setting of trauma, liver biopsy, and acute/chronic pancrea-
hospital (adapted from reference 2 & 3)
titis. Henoch-Schönlein purpura and vasculitis such as poly-
Cause Yachha et al. 1996 Mittal et al. 1994 arteritis nodosa are rarer causes of UGIB in this age group.

Varices 95 % 39.4 %
Esophagitis - 23.7 % Key Issues
Gastritis 1.3 % 7.2 %
Gastric ulcer - 1.2 % Initial Assessment and Stabilization
Duodenal ulcer - 0.42 %
Esophageal ulcer - 0.42 % As for any other emergency the first priority should be to
Henoch Schönlein purpura 1.3 % - assess the airway, breathing and circulation of a patient
ITP 1.3 % - presenting with UGIB. The most important aspect of the
Gastroduodenal artery 1.3 % - evaluation is to determine the degree and rapidity of blood
aneurysm loss. Orthostatic changes in blood pressure (more than
Unknown - 27.5 %
10 mm of Hg) suggest a moderate bleed (15–20 % of blood
loss) and warrant a more aggressive approach to manage-
Infants and Toddlers ment. Presence of signs of shock (tachycardia, prolonged
capillary refill time, cold-clammy skin, supine hypotension)
Stress ulcers and gastritis in a sick infant or toddler, peptic ulcers, indicates severe bleed of more than 25–30 % of blood loss
variceal bleeding in children with portal hypertension and vas- and a need for immediate volume expansion and stabiliza-
cular malformations can cause major bleeds in this age group. tion before proceeding to a diagnostic algorithm (Fig. 1).
Reflux esophagitis, esophageal or gastrointestinal foreign body, Once the patient is stable the following issues should be
communicating duplication cysts, NSAIDS and corrosive injury addressed before more elaborate diagnostic workup:
can cause non life threatening bleeds. History of a choking
episode, even if it was transient or occurred days or even weeks 1. Whether actual blood or ingested substances
before the bleeding episode, is an important clue for a foreign The first consideration in evaluating children who have
body. new-onset “bleeding” is to determine whether the material
passed is actual blood. A number of substances may
Older Children and Adolescents simulate bright red blood (food coloring, colored gelatin
or children’s drinks, red candy, beets, tomato skins, rifam-
Causes of UGIB in older children and adolescents are similar pin, phenytoin, antibiotic syrups) or malena (bismuth or
to those seen in adults. Varices, peptic ulcers, Dieulafoy’s iron preparations, charcoal, spinach, blueberries, grapes,
lesions and vascular malformations can cause major bleeds. licorice). For detecting blood in vomitus or nasogastric
Reflux esophagitis, Drug induced gastritis, Mallory Weiss aspirate, the Gastroccult® test is more accurate [4]. The
tears, communicating duplication cysts, stromal tumors, lym- test uses Gastroccult slides, sealed in special wrapper, and
phomas (rarely), Crohn’s disease and portal hypertensive gas- stored at room temperature (15–30 °C). One drop of
tropathy can cause minor bleeds. Haemobilia or bleeding from gastric sample is placed to the occult blood test area of
the pancreas (splenic artery aneurysm) should be considered in the slide and two drops of Gastroccult Developer is applied

Table 2 Age wise distribution

of etiology of UGIB in children
(Adapted from reference 1)
Age group Well appearing Ill appearing
Neonates Swallowed maternal blood Hemorrhagic gastritis
Hemorrhagic disease of newborn Necrotizing enterocolitis
Drugs- heparin, indomethacin Gastric stress ulcers
Thrombocytopenia, platelet dusfunction Disseminated intravascular coagulation
Infants Reflux esophagitis Hemorrhagic gastritis
Reactive gastritis Gastric stress ulcers
Arteriovenous malformation
Children Mallory-Weiss tear Esophageal varices ( liver disease)
Reflux esophagitis Hemorrhagic gastritis
Reactive gastritis Stress ulcers
328 Indian J Pediatr (April 2013) 80(4):326–333

Assess airway , breathing and circulation :

If signs of shock, orthostatic changes in
blood pressure, impaired responsiveness

Maintain airway, start oxygen, support breathing and circulation

Insert 2 large bore I.V. cannula
Blood for group and cross match, Hematocrit/coagulogram
Monitoring of vitals, oximetry
Volume replacement by crystalloids, start blood as soon as possible
Correct coagulopathy-vitamin K, + fresh frozen plasma/platelets
Nasogastric tube placement – for lavage and monitoring of ongoing bleed
Acid suppression therapy

Suspect Variceal Bleed Suspect Mucosal Bleed/Ulcer

Features suggestive of portal (History of drug intake,
hypertension, chronic liver disease abdominal pain, dysphagia, etc)
(splenomegaly, hepatomegaly)

Acid suppression therapy- High dose PPIs

Start Octreotide infusion,
Pediatric Gastroenterology consult
Controlled Not controlled
Controlled Not controlled
- Elective Endoscopy Endoscopy
- Continue PPIs
Emergency Endoscopic - Test and treat Ulcer found
sclerotherapy(EST) H. pylori

Endoscopic Management
Endoscopic
Not controlled Injection therapy
sclerotherapy (EST) or
(adrenaline+saline)/
variceal ligation (EVL)
Mechanical hemostasis-
Endoclip/Themocoagulation
Balloon tamponade
Continue PPIs- Test and treat
H. pylori

Planned Controlled Not controlled

Not controlled No Ulcer/Lesion
EST/EVL

TIPSS (Cirrhotics) or
Devascularisation / Shunt Surgical/ Intervention
Surgery Radiologist consult

Fig. 1 Algorithmic approach to management of a patient with significant acute upper GI bleed

directly over the sample. The test is read within 60 s.
The development of any trace of blue color in the occult
blood test area is regarded as a positive for occult blood.
Simultaneously, functionality of test should be tested. For
this, one drop of Gastroccult Developer is added between
the positive and negative Performance Monitor areas and
results interpreted within 10 s. If the slide and developer are
functional, blue color will appear in the positive area, and
the negative area will remain colorless.
2. In a neonate- whether it is patient’s own blood or
swallowed blood
This is often applicable for neonates. The Apt-
Downey Test is used to differentiate between swallowed
maternal blood and patient’s blood.
Indian J Pediatr (April 2013) 80(4):326–333
3. Is there a pulmonary, oral or ENT source of bleed?
Bleeding from these sources may mimic GI bleed
especially when the blood is swallowed. It may be seen
in conjunction with epistaxis, sore throat or may follow
dental procedures or tonsillectomy. Hence these areas
must be explored to rule out in cases of doubt.
4. Level of bleeding
Vomiting of bright red or coffee ground vomitus is
the classic presentation of upper GI bleeding. Bloody
diarrhea and bright red blood mixed or coating normal
stool are the classic presentations of lower GI bleeding.
However, hematochezia, malena, or occult GI blood
loss could represent upper or lower GI bleeding. In case
of acute-onset hematochezia or malena, the level of
bleeding can be confirmed by passage of a nasogastric
tube. Presence of blood in the stomach and clearing of
nasogastric aspirate with lavage are diagnostic of UGIB.
Diagnostic Evaluation
Focused History
History is directed at finding the likely source and cause of
bleed. It should include the following:
& Recent or recurrent epistaxis: it raises the possibility of a
nasopharyngeal source of bleeding.
& Recent onset of jaundice and/or change in stool color:
may suggest underlying liver disease.
& History of easy bruising or bleeding: may suggests
a disorder of coagulation, platelet dysfunction, or
thrombocytopenia.
& History of any co-morbid illnesses: Personal or family
history of liver, kidney or heart disease, or coagulation
disorders.
& Epigastric pain, food pain relationship, may be an indi-
cator of gastritis, esophagitis or ulcer disease.
& Details of recent medications ingested as well as an
‘over the counter’ or ‘alternative’ drug history is impor-
tant to assess potential contributions from medications
that may induce ulceration (such as NSAIDs and corti-
costeroids). Even short-term use of ibuprofen can cause
gastric ulcers and hematemesis.
& History of previous bleeding episodes can point to
EHPVO, vascular malformations and duplication cysts.
Physical Examination
Focused physical examination, besides assessing the sever-
ity of bleed, should include a good inspection of skin (for
petechiae and echymoses, and vascular malformations) and
mucous membranes of the nose and throat (for bleeding),
329
and palpation of abdomen for localized tenderness and
organomegaly.
& The presence of hepatosplenomegaly and prominent
abdominal vessels and a protruding abdomen may indi-
cate portal hypertension and bleeding from esophageal
varices,
& Epigastric tenderness might suggest acute gastritis or
peptic ulcer disease.
& Vascular malformations like hemangiomas and telangi-
ectases should also be noted.
& Clinical evidences of bleeding diathesis like petechiae,
echymoses, purpura etc. should also be noted.
& Stigmata of chronic liver disease
Investigations
In an emergency setting only a few laboratory tests are
essential in the beginning to evaluate UGIB. These include
complete blood count, prothrombin time (PT) and partial
thromboplastin time (PTT), liver function tests and blood
grouping and cross matching if there is significant bleed.
Testing for H. pylori (urea breath test, stool antigen and
serological tests) is indicated in a patient with a probability
of peptic ulcer. Additional laboratory evaluation depends on
the result of the initial evaluation, the patient’s response to
treatment, and clinical suspicion of a particular diagnosis.
Radiographic Studies
Abdominal ultrasound is useful in patients where extra
hepatic portal hypertension, portal hypertension due to liver
disease, hemobilia, splenic artery aneurysm or large vascu-
lar anomalies are suspected. Doppler blood flow can identi-
fy evidence of cirrhosis and portal blood flow dynamics.
Endoscopy
Upper gastrointestinal endoscopy is the gold standard for
diagnosis and treatment of UGIB. It is the procedure of
choice for all patients with UGIB. In the hands of skilled
endoscopist, this procedure now can diagnose the etiology
in 85– 90 % of cases. It is indicated to identify the site of the
bleeding, to diagnose the specific cause of the bleeding, and
to initiate therapeutic interventions when indicated. In case
the endoscopic appearance suggests esophagitis, gastritis or
duodenitis a biopsy should be obtained; in suspected peptic
ulcer disease antral biopsies for H. pylori work up (histo-
logical examination, rapid urease test, and culture) should be
taken. Though there is no definite time frame given, in all
cases of major upper GI bleed, an early endoscopy (within
first 24 h) is recommended by most of the reviews [5].
Endoscopy is contraindicated in hemodynamically unstable
330
patients; it should be considered only after stabilization
because early endoscopy (<6 h after presentation) in such
patients has not improved outcomes.
CT Angiography
CT angiography may help to delineate vascular malforma-
tions beyond the duodenum, in areas not accessed by routine
upper GI endoscope.
Nuclear Scintigraphy
In patients with persistent bleeding in whom endoscopy fails
to identify a bleeding site, radioisotope-tagged red blood
cell scans using technetium 99 m-sulfur colloid may be
capable of detecting the site of bleeding. This modality is
useful only if the rate of bleeding exceeds 0.1 ml/min.
However, this modality has significant false localization
and false-negative rates [1].
Angiography
Celiac/ Superior mesenteric artery angiography is used se-
lectively in children with non variceal massive bleeding,
e.g., from a peptic ulcer, that obscures endoscopic evalua-
tion and therapy. It is also very useful in Hemobilia, splenic
artery aneurysms and some types of vascular malformations.
Bleeding must be more than 0.5 ml/min to be detected by
angiography [6]. Angiography is not only helpful in making
the diagnosis but also facilitates embolic coil/fibric/glue
occlusion of the arterial branches supplying the lesion in
case of vascular malformation.
Some newer investigations are available in a few centres for
the evaluation of upper GI bleed from obscure areas beyond the
duodenum (Capsule Endoscopy/ Double Balloon Enteroscopy)
and in the liver or pancreas (Endosonography) in older children.
Management
The initial steps in management of severe acute GI Bleed
include assessment, resuscitation, re-evaluation, identifica-
tion of the cause and source of bleeding, and commencing
appropriate treatment (Fig. 1). This requires a multidisci-
plinary approach. Early consultation from pediatric gastro-
enterologist is recommended for patients who have active
ongoing bleed. The Interventional Radiologist and the Pe-
diatric Surgeon must be kept in the picture in case of the
failure/non-feasibility of endoscopic therapy, massive bleed-
ing, recurrent bleeding, bleeding associated with significant
abdominal pain. Care in the Pediatric Intensive Care setting
can be life saving in the early part of the management before
specific therapy can be instituted.
Indian J Pediatr (April 2013) 80(4):326–333
Resuscitation and Stabilization
Children presenting with symptoms and signs of upper GI
bleeding require prompt recognition during triage so that
timely resuscitation can be initiated and hemodynamic sta-
bility restored.
Airway Treatment should begin with airway protection. In-
tubation is indicated in obtunded patients or in those with
uncontrolled massive hemetemesis to prevent aspiration and
to facilitate upper endoscopy if it is necessary for bleeding
control.
Breathing Supplemental oxygen should be provided to all
patients. The adequacy of the breathing efforts must be
assessed and supported if needed.
Circulation Patients are assessed for hypovolemia and
shock to determine requirements for fluid infusion and
transfusion of packed erythrocytes. Large bore venous ac-
cess should be obtained to restore blood volume. Preferably
2 cannulae should be in place: one for fluid/blood resusci-
tation and the second for sampling and drugs. Peripheral
venous access may be difficult in a child with hypovolemic
shock due to peripheral vasoconstriction, therefore intraos-
seus access should be considered for large volume resusci-
tation. Subsequently central venous access may be
required. Fluid resuscitation should begin with crystalloids
(20 ml/ kg) while the blood is being arranged. The rate of
blood transfusion is determined by the severity of the
hypovolemia, continuing active bleeding, and presence of
co-morbidities. Blood transfusion is not needed in a
hemodynamically stable patient that has a hematocrit
above 24 % at presentation. Over transfusion (volume
overexpansion) should be avoided especially in variceal
bleed. Hematocrit should not exceed 30 %. This can
increase the portal venous pressure and aggravate the
UGIB.
Reassessment and Monitoring Vitals should be monitored
every 10 min –15 min till the child is stabilized and then
hourly for 24 h after stoppage of bleeding or stabilization.
Nasogastric Aspiration
Nasogastric aspiration and saline lavage are indicated in all
patients with UGIB to confirm the presence of intragastric
blood; to determine the rate of gross bleeding; to check for
ongoing or recurrent bleeding; to clear gastric field for endo-
scopic visualization; to prevent aspiration of gastric contents;
to prevent hepatic encephalopathy in patients of cirrhosis.
Lavage with iced or cooled solutions has not shown any
recognized advantage over room temperature solutions.
Indian J Pediatr (April 2013) 80(4):326–333
Some observers believe that solutions at 32 °C may interfere
with local coagulation mechanisms [7].
Correction of Coagulopathies
Parenteral vitamin K should be administered empirically
even when results of coagulogram are pending (infants,
1–2 mg/dose; children, 5–10 mg/ dose). Coagulopathy
with an international normalized ratio (INR) higher than
1.5 or abnormal partial thromboplastin time (PTT) should
be corrected with fresh frozen plasma (10 ml/kg initially);
cryoprecipitates may be tried in the face of severe coa-
gulopathy especially if volume of fluid has to be restrict-
ed; Factor VIIa has little additional advantage, even in
chronic liver disease, and is not routinely recommended;
Platelets transfusion is also not recommended unless there
is active bleeding with low platelet counts. All these
products should be included in the calculated resuscitation
fluids.
Pharmacotherapy
Variceal Bleed
Pharmacological therapy has the advantages of being gen-
erally applicable and capable of being initiated as soon as a
diagnosis of variceal hemorrhage is suspected. A meta-
analysis comparing emergency sclerotherapy and pharma-
cological treatment shows a similar efficacy with fewer side
effects with the latter thereby suggesting that pharmacolog-
ical therapy should be considered first-line treatment of
variceal bleeding [8].
Octreotide is a somatostatin analog that decreases splanch-
nic blood flow and has fewer hemodynamic adverse effects
than vasopressin. Pediatric studies have shown that it controls
UBIG in up to 70 % of children [9]. It is the drug of choice for
variceal bleeds and initiated as a bolus injection of 1 mcg/kg
(up to a maximum of 50 mcg) followed by continuous infu-
sion of 1 mcg/kg per h, which may be increased hourly by
1 mcg/kg per h up to 4 mcg/ kg per h [1]. Infusion should be
continued for at least 24–48 h after the bleeding has stopped to
prevent recurrence. The major adverse effect of octreotide is
hyperglycemia.
Vasopressin and Terlipressin Vasopressin use has largely
been replaced by octreotide and now by Terlipressin. The
usual dose is 0.002 to 0.005 units/kg per min for 12 h, and
then tapered over 24 to 48 h (maximum, 0.2 units/min) [1].
Its use is limited by the side effects of vasoconstriction.
Nitroglycerin has also been used to decrease portal pressure
and, when used in conjunction with vasopressin, may ame-
liorate some of its untoward effects. Vasopressin has been
replaced by its longer acting and safer analogue Terlipressin
331
which has been found to be as effective as Octreotide in
adults. Experience with Terlipressin in children is limited
though it is expected to be equally effective. An advantage
is intermittent 4–6 hourly dosing.
Somatostatin is also used for control of active bleed, in a
dose of 250 mcg/kg IV bolus followed by 250 mcg/kg/h
continuous infusion. In case of response, the infusion can be
maintained for 2 to 5 d, while frequently monitoring for
hyperglycemia [1]. Side effects include abdominal discom-
fort, flushing, nausea, bradycardia, steatorrhoea and
dyspepsia.
Prokinetic Agents Erythromycin has been used as a prokinetic
agent to clear the stomach of blood prior to emergent endos-
copy. Metoclopramide has also been used to act as a prokinetic
for similar reasons besides acting as a ‘pharmacologic tampo-
nade’ – it increases the lower esophageal sphincter tone.
Mucosal Bleeds
Mucosal bleeding is most common type of upper GI bleed in
critically ill children. Therapy in these groups of patients is
directed at neutralizing and/or preventing the release of acid.
The various agents used include:
Proton Pump Inhibitors (PPIs) are more efficacious
than H2 receptor antagonists. Pantoprazole is used for
control of active bleed. Dosage in children are: for body
weight <40 kg: 0.5 to 1 mg/kg per day IV once daily;
>40 kg: 20 to 40 mg once daily (maximum,
40 mg/d). These can be started empirically as it is
important to raise the gastroduodenal pH to maintain
clot stability. High dose PPI infusion has been found
to decrease the need for endoscopic therapy.
H2 Receptor Antagonists are used for control of active
bleed and prevention of rebleeds. E.g. Ranitidine can be
used as either continuous or bolus infusion; in the
former 1 mg/kg is given initially followed by infusion
of 2 to 4 mg/kg per day while in the latter 3 to 5 mg/kg
per day is divided into every 8 hourly infusions.
Treatment for H. pylori infection with a H2 blockers or
PPIs plus any two antibiotics (mainly nitromidazoles-
metronidazole/tinidazole, macrolides- clarithromycin,
amoxicillin and beta-lactames) for 10–14 d is recom-
mended in patients with peptic ulcer disease positive for
H. pylori or with no identifiable cause. American Col-
lege of Gastroenterology recommends four specific
drug regimens that use above referred combination of
three medications [10] or Bismuth- containing quadru-
ple therapy Bismuth subsalicylate, metronidazole, tet-
racycline all in 4 daily doses, and ranitidine or PPI
332
twice a day for 10–14 d. These combinations are
expected to cure 70 % to 85 % of infections [10].
Endoscopic Techniques
Variceal Bleed
Upper gastrointestinal endoscopy should be performed as
soon as possible after initial stabilization. Endoscopic ther-
apy should be done if variceal source of hemorrhage is
confirmed. A meta-analysis has shown that endoscopic var-
iceal ligation (EVL) is superior to sclerotherapy in the initial
control of bleeding. However EVL cannot be performed in
infants and toddlers due to the large size of available devi-
ces; EST is the mainstay of therapy in this group. Combi-
nation of pharmacological and endoscopic therapy is the
most rational approach in the treatment of acute variceal
hemorrhage [11]. Endoscopic injection of ‘tissue glue’ is
effective for controlling bleeding gastric varices. Argon
Plasma Coagulation can be used for bleeding portal hyper-
tensive gastropathy lesions, e.g., GAVE- Gastric Antral
Vascular Ectasias.
Non Variceal Ulcer Bleeds
In case of peptic ulcers with stigmata indicating high risk
of rebleed (spurting or oozing vessel in ulcer base/
adherent clot), any of the following endoscopic therapy
may be given: Injection therapy with adrenaline and
saline, mechanical hemostasis (Endoclip Devices) with
or without adrenaline, or thermocoagulation with or with-
out adrenaline.
Balloon Tamponade
In patients with variceal bleed who continue to bleed despite
pharmacologic and endoscopic methods, a Sengstaken-
Blakemore tube can be placed to stop hemorrhage by me-
chanically compressing esophageal and gastric varices.
However, its use is associated with potentially lethal com-
plications such as aspiration, migration, and necrosis/perfo-
ration of the esophagus with mortality rates as high as 20 %
[12]. The tube should never be kept inflated for durations
exceeding 12 h in children.
Surgical Treatment
Consultation with a pediatric surgeon and interventional
radiologist is necessary for children with massive bleed-
ing, ongoing significant blood loss, and failed endoscopic
procedure. Approaches to manage refractory variceal
hemorrhage include insertion of transjugular intrahepatic
porto-systemic shunt stents (in sinusoidal and post
Indian J Pediatr (April 2013) 80(4):326–333
sinusoidal portal hypertension), selective or non-selective
surgically created portosystemic shunts, and nonshunt
procedures aimed at interrupting and ligating varices
directly (devascularization) [13]. Non variceal bleed can
be tackled by transcatheter embolization by an interven-
tion radiologist. If this is not technically feasible or
expertise is unavailable, surgical ligation / resection can
be resorted to.
Key Points
& Upper GI bleeding is often a medical emergency.
& Specific etiologies at different ages should be kept in
mind while assessing pediatric patients.
& Variceal bleed is the most common cause of significant
upper GI bleeding in children.
& Immediate stabilization should be given priority before
proceeding to diagnostic algorithm.
& Upper GI endoscopy is the gold standard for diagnosis
and treatment of UGIB.
& Therapy in patients with mucosal bleeds is directed at
neutralization and/or prevention of the gastric acid re-
lease. Proton Pump Inhibitors (PPIs) are more effica-
cious than H2 receptor antagonists.
& Octreotide and terlipressin are useful in control of sig-
nificant UGIB especially due to variceal hemorrhage.
& Refractory variceal hemorrhage or non-variceal hemor-
rhage requires multidisciplinary approach.
Conflict of Interest None.
Role of Funding Source None.
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1994;61:651–4.
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and children. J Pediatr Gastroenterol Nutr. 1986;5:173–86.
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7. Ponsky JL, Hoftman M, Swayngim OS. Saline irrigation in gastric
hemorrhage: The effect of temperature. J Surg Res. 1980;28:204–5.
8. D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclero-
therapy versus vasoactive drugs for variceal bleeding in cirrhosis: A
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troenterology guideline on the management of Helicobacter pylori
infection. Am J Gastroenterol. 2007;102:1808–25.
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atology. 2007;46:922–38.
12. Avgerinos A, Armonis A. Balloon tamponade technique and effi-
cacy in variceal haemorrhage. Scand J Gastroenterol Suppl.
1994;207:11–6.
13. Superina RA, Alonso EM. Medical and surgical management of
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Indian J Pediatr (March 2013) 80(3):219–225
DOI 10.1007/s12098-012-0955-x
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN GASTROINTESTINAL EMERGENCIES
Emergency Management of Lower Gastrointestinal Bleed
in Children
Binesh Balachandran & Sunit Singhi
Received: 2 July 2012 / Accepted: 21 December 2012 / Published online: 25 January 2013
# Dr. K C Chaudhuri Foundation 2013
Abstract Lower gastro intestinal bleed (LGIB) is de-
fined as any bleeding that occurs distal to the ligament
of Treitz (situated at the duodeno jejunal junction). It
constitutes the chief complaint of about 0.3 % of chil-
dren presenting to the pediatric emergency department
(ED). Among Indian children the most common causes
are colitis and polyps. In most of the cases of LGIB
the bleeding is small and self limiting, but conditions
like Meckel’s diverticulum often presents with life
threatening bleeds. The approach in ED should include
in order of priority—assessment and maintenance of
hemodynamic stability, confirmation of LGIB and then
to attempt for specific diagnoses and their management.
This is achieved with help of rapid cardiopulmonary
assessment, focused history and examination. The man-
agement of all serious hemodynamically significant
bleeds includes, rapid IV access, volume replacement
with normal saline 20 ml/kg, blood sampling (for cross
matching, hematocrit, platelet, coagulogram and liver
function tests), Inj. Vit K 5–10 mg IV, acid suppression
with H2 antagonists/PPI and nasogastric lavage to rule
out upper gastrointestinal bleed. Continuous ongoing
monitoring of vital signs is important after stabilization.
In ill looking infant, infectious colitis, Necrotizing
enterocolitis (NEC), Hirschsprung enterocolitis and vol-
vulus and in older infants and children, intussuscep-
tions, typhoid fever, volvulus should be looked for.
B. Balachandran : S. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre,
Post Graduate Institute of Medical Education and Research
(PGIMER), Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Proctosigmoidoscopy remains the first investigation to
be done and reveals majority of etiology. Multidetector
CT scan, Tc 99 m RBC scan, angiography and Push
enteroscopy are the further investigation choices accord-
ing to the clinical condition of the child. Intra operative
enteroscopy is reserved for refractory cases with an ob-
scure etiology.
Keywords Children . Lower gastrointestinal bleed .
Proctosigmoidoscopy . Infectious colitis
Introduction
Lower gastro intestinal bleed in children is a common clin-
ical problem, but most of the cases are benign and self
limiting. It constitutes the chief complaint of about 0.3 %
of children presenting to the pediatric emergency depart-
ment [1]. The sight of blood in a child’s stool is always
anxiety provoking and mandates an aggressive attempt at
determining a diagnosis.
Definitions
Any bleeding that occurs distal to the ligament of Treitz
(situated at the duodeno jejunal junction) is classified as
lower gastrointestinal bleed (LGIB). Hematochezia
refers to the passage of bright red blood per rectum. It
usually suggests LGIB (typically from colon), but rarely
can occur in massive upper gastrointestinal bleeds
(UGIB). Melena refers to the passage of black, sticky
(tarry) stools and is generally a symptom of UGIB, and
usually indicates a blood loss of at least 2 % of blood
volume.
220 Indian J Pediatr (March 2013) 80(3):219–225

Etiology Initial examination should be concentrated on the assess-

Western literature states allergic colitis and anorectal
fissures as the most common causes in infancy, while
infectious enteritis and anorectal fissures constituted
the most common causes in older children [1]. The
causes of LGIB in children from developing countries
[2–4] are given in Table 1. Among Indian children
infectious colitis and polyps are the most common
causes [2, 3].
Many clinical conditions can be mistaken for lower
GI bleed. For example, menstrual blood, commercial
dyes, ampicillin and hematuria could mimic hematoche-
zia. While substances like iron, lead, licorice, blueber-
ries, spinach, bismuth, charcoal and beets may be
mistaken for melena.
Most of the causes result in mild blood loss, but
substantial bleeding can occur with Meckel diverticu-
lum, inflammatory bowel disease, Henoch-Schönlein
purpura, intussusception, vascular anomalies, infectious
colitis and intestinal duplications. Differential diagnoses
of child with LGIB according to clinical presentation
[5] are given in Table 2, and those according to age [5,
6] are given in Table 3
Clinical Evaluation
The objectives of the evaluation in the emergency room are
1. To assess hemodynamic stability
2. To ascertain if this is blood
3. To differentiate between upper and lower GI bleed
4. To determine specific diagnosis and site of bleed.
ment of airway, breathing and circulation. Any abnormali-
ties in these should be tackled then and there.
Initial Assessment and Stabilization
Assess for signs of intravascular volume depletion.
These may be the only reliable signs of severity of
bleed. Color of stool may not help. A large amount of
bleed may occur in the bowel lumen and remain
hidden from the direct observation; it may result in
underestimation of severity of bleeding. The presence
of signs of volume depletion in form of tachycardia
(indicates >15 % of blood loss), delayed capillary
refill time, and or hypotension (indicates >30 % of
blood loss) call for immediate expansion of intravas-
cular space, irrespective of the amount of apparent
bleed.
Presence of pallor, sweating, restlessness, lethargy and
unexplained tachycardia may be the other clues to severe
underlying bleed requiring urgent attention.
In an older child orthostatic changes in heart rate
by 20 beats/min and systolic blood pressure by
10 mmHg (i.e., on moving the child from supine to
sitting position) is a good indicator of severe blood
loss.
Focused History and Examination
A focused history and examination not only clinches the
diagnosis, but also gives an idea about the severity of the
bleed. The following information should be sought in the
history:

Table 1 Causes of LGIB among

children from developing Cause Yachha et al. Khurana et al. Mandan et al.
countries 1996 [3] (%) 1998 [4] (%) 2004 [5] (%)

Colitis 42 23.5 18
Polyps 41 54.1 75
Solitary rectal ulcer syndrome 4.5 4.7 3.5
Typhoid fever with complication 4.5
Portal colopathy 3 1.2
Henoch schonlein Purpura 2.4
Lympho nodular hyperplasia 3
A-V malformation 1.5
Hemorrhoids 1.5
Pseudo membranous colitis 1.2
Foreign body 0.5
Idiopathic 1.5 12.9
Indian J Pediatr (March 2013) 80(3):219–225 221

Table 2 Differential diagnosis of LGIB depending on the clinical 6. A history of abnormal bleeding from other sites (bleed-
presentation
ing and clotting disorders)
Hematochezia, Melena 7. Past episodes of gastrointestinal hemorrhage
• Intestinal ischemia 8. Recent use of nonsteroidal anti-inflammatory agents
○ Complicating intussusception, mid-gut volvulus, incarcerated or any other medications (intestinal ulcers)
hernia, or mesenteric thrombosis
Insertion of a naso gastric tube and aspiration is an easy
• Meckel diverticulum
and a rapid way of excluding upper gastro intestinal bleed as
• Upper GI source of bleeding
a cause of melena/hematochezia.
• Bleeding and clotting disorders
Look for the signs suggestive of specific etiologies, such as:
• Typhoid fever with complication
• Vasculitis & Oro buccal pigmentation suggestive of Peutz-Jegher’s
○ Henoch-Schonlein purpura syndrome
• Sloughed polyp & Sausage shaped mass in abdomen in case - intussusceptions
• Intestinal or colonic ulcer & Cutaneous bruising -abnormal hemostasis, jaundice -
○ NSAID gastropathy, Crohn disease liver failure
• Ulcerative colitis & Eczema -milk allergy
• Vascular malformations (including angiodysplasia) & Clubbing- Cirrhosis, inflammatory bowel disease and
Rectal Bleeding with Signs of Colitis (Bloody Diarrhea, Abdominal cystic fibrosis
Cramps, Tenesmus, Nighttime Stooling) & Cutaneous hemangiomas may indicate vascular abnor-
• Infectious colitis malities in intestine
○ Salmonella, Shigella, Campylobacter jejuni, Escherichia coli & Fissures and anal tags in perianal area may indicate an
O157:H7, Clostridium difficile, Entamoeba histolytica, Trichuris underlying Inflammatory Bowel Disease
trichiura etc. & On per rectal examination look for stool impaction and
• Hemolytic-uremic syndrome rectal polyps
• Necrotizing enterocolitis
• Eosinophilic proctocolitis The common causes and the respective signs and symp-
• Inflammatory bowel disease toms [5, 6] are summarized in the Table 4
○ Ulcerative colitis, Crohn disease
Rectal Bleeding with Normal Stool Pattern
• Juvenile polyp Investigations
• Nodular lymphoid hyperplasia
• Eosinophilic colitis & Hemogram (Hemoglobin, hematocrit, total and differen-
• Inflammatory bowel disease tial leukocyte counts) should be obtained in all patients
• Vascular malformation with significant or ongoing bleeds/hemodynamical in-
Bright Red Blood Coating Normal or Hard Stool stability. A platelet count and a coagulogram should be
• Anal fissure done to rule out bleeding and clotting disorders in all
• Rectal prolapse such cases.
• Solitary rectal ulcer & Stool examination is indicated in all children with colitis
• Internal hemorrhoids symptoms and those presenting with blood mixed stools.
• Beta-hemolytic streptococcal cryptitis One should look for the presence of pus cells, ova cysts
• Ulcerative proctitis and parasites. A stool culture is indicated when pus cells
and/or colitis symptoms are present.
& Plain X ray abdomen (erect and cross table prone lateral)
have limited role in emergency evaluation of LGIB. It is
1. Duration and amount of bleeding indicated if there is associated abdominal distension and/
2. Color of the blood or clinical suspicion of necrotizing enterocolitis, and
3. Consistency of accompanying stool obstruction.
4. Is the blood mixed in the stool or coating the outside? & USG abdomen is diagnostic in intussusceptions and is
Does blood drip in the toilet after bowel movement indicated in all suspected cases and also in cases with
(anorectal bleed)? necrotizing enterocolitis, and obstruction.
5. Associated symptoms (such as abdominal pain, fever, & Proctosigmoidoscopy is diagnostic as well as therapeu-
diarrhea, weight loss and fatigue) tic if the bleed is rectosigmoidal in origin. It can detect
222 Indian J Pediatr (March 2013) 80(3):219–225

Table 3 Causes of LGIB with

respect to patient’s age, Ill-appearing Well-appearing
appearance and rate
of bleeding High rate of bleeding Low rate of bleeding

Infant Infectious colitis Meckle’s diverticulum Swallowed maternal blood

Necrotizing enterocolitis
(NEC)
Hirschsprung enterocolitis
Volvulus
2 to 5 y Intussusception
Typhoid fever
Volvulus
Henoch-Schönlein purpura
Hemolytic-uremic syndrome
Older child Infectious colitis
Rare causes of bleeding:
vascular malformation, Typhoid fever
hemobilia, intestinal duplication,
submucosal mass, neutropenic Ulcerative colitis
colitis (typhlitis) Henoch-Schonlein purpura
Bleeding and clotting disorders Intestinal ischemia
can present in any age group
Anal fissure
Milk protein intolerance
Eosinophilic proctocolitis
Infectious colitis
Nodular lymphoid hyperplasia
Meckel’s diverticulum Infectious colitis
Sloughed juvenile polyp Juvenile polyp
Ulcerative colitis Anal fissure
Nodular lymphoid hyperplasia
Ulcerative colitis/Crohn
disease
Perianal streptococcal cellulitis
Rectal prolapse/rectal ulcer
Ulcerative colitis Infectious colitis
Meckel’s diverticulum Ulcerative colitis/Crohn
disease
Juvenile polyp
Hemorrhoids
Rectal trauma/Sexual abuse

evidence of colitis, rectal varices, polyps and hemor-
rhoids [2]. Colonoscopy after bowel preparation (with
poly ethylene glycol) is the investigation of choice in
proximal colonic bleeds. It also allows examination of
the terminal ileum and is therapeutic in many cases.
& Nuclear scans: The nuclear scan can be done using
either technetium sulphur colloid or [99Tcm]
pertechnetate-labeled red blood cells. Tc 99 m pertech-
nate scan is commonly employed . It is particularly
useful in cases of bleeding Meckel’s diverticulum. Tc
99 RBC scan detects ongoing bleeds if it is at least
0.1 ml/min [7] and so is more sensitive than angiogra-
phy but less specific than endoscopic or angiographic
study [8]. The reported sensitivity and specificity of
RBC scans range from 78.6–97 % and 70.4–100 %
respectively [9]. Many clinicians prefer to do it
before the conventional angiography, as it is non
invasive and helps in selecting the artery (e.g.,

Table 4 Common causes of LGIB in children and their clinical presentation

Condition Clinical feature

Infectious colitis Abdominal cramps, stool mixed with blood and mucus, fever
Necrotizing enterocolitis Preterm infant with abdominal distension, feed intolerance
Hirschsprung enterocolitis Delayed passage of meconium, chronic constipation, abdominal distension
Intussusception Episodic pain, vomiting. Red currant jelly stool
Henoch schonlein purpura Purpura, joint pain, abdominal pain
Inflammatory bowel disease Most commonly among 5–16 y-old. Occult bleed or bloody diarrhea; also have
aphthous ulcers, joint pain, anorexia, fever, growth failure and skin lesions
Allergic colitis Well appearing, normal weight top fed infant with loose stool mixed with blood
and anemia onset after introduction of milk.
Anal fissure Most commonly among 6–24 mo. History of constipation with painful passage
of large hard stools streaked with bright red blood
Meckel’s diverticulum, vascular anomalies Painless massive bleeding in a previously well child usually < 5 y
Polyps Most commonly in 2–8 y-olds. Painless passage of small amount of bright red blood
on the surface of stool
Indian J Pediatr (March 2013) 80(3):219–225 223

Fig. 1 Management algorithm

Assessment of Airway, Breathing, Circulation
for lower gastrointestinal bleed
in pediatric emergency

Ongoing severe bleed

Hemodynamic instability

Insert 2 large bore IV cannula/ central line

Small amount of
bleed Volume replacement with N. Saline 20ml/kg

Stable/ well Blood for cross matching, hematocrit, platelet, coagulogram and
looking child liver function tests

Vit K 5-10 mg IV stat

Acid suppression (H2 antagonist/PPI)-Pantaprazole 2mg/kg

bolus, then 0.2 mg/kg/h infusion.

NG lavage to rule out UGIB

FF Plasma/Blood transfusion-if indicated

Ongoing monitoring of vital signs

Plan investigations according to the

clinical presentation e.g.,
ProctoSigmoidoscopy
No cause/site of bleeding
1. Signs of colitis – stool microscopy
Cause found found
and culture
2. Suspicion of NEC, obstruction or Cause found
intussusception – Multidetector CT
radiograph and ultrasound scan
Treat accordingly
examination of abdomen Tc 99m RBC scan
(Table 5)
3. Recurrent/ persistent bleed –
Angiography
consider Sigmoidoscopy/
colonoscopy Push enteroscopy

Cause not found

11
Intra operative enteroscopy

superior mesenteric artery, celiac trunk etc.) for con-
ventional angiography. The sulphur colloid scan has
a relatively higher sensitivity but due to its shorter
half life, intermittent bleeds are more often missed
[10]. Radionuclide scan is usually well tolerated by
the patient but the accuracy rating for localizing
bleeding is highly variable (24–91 %) [11]
& Selective mesenteric angiography(superior and inferior
mesenteric artery) requires an ongoing bleed of at least
0.5 ml/mt. It is very helpful in diagnosis of vascular
causes of LGIB and allows therapeutic interventions,
e.g., Sclerosant injection or embolisation of the vessel
in such cases. Angiography requires no special bowel
preparation and it may be the first investigation i.e.,
before colonoscopy in a hemodynamically unstable pa-
tient with massive bleed, where endoscopy can be
difficult to perform. Angiography has a specificity of
100 % but a sensitivity of only 30–47 % [11, 12].
Digital subtraction angiography (DSA) has been
reported to be more sensitive than conventional
screen-film angiography [13]
& Contrast enema and barium studies do not have much
role in LGIB. These are indicated only if there is a
clinical suspicion of Hirschsprung disease.
& Multidetector computed tomography (MDCT) is an
emerging modality for the diagnosis of LGIB. It can
detect bleeding as low as 0.3 ml/mt. The sensitivity of
CT in localizing the LGIB is more in patients with active
bleed (91–92 %) than in patients with obscure hemor-
rhage (45–47 %) [14, 15]. In pediatric patients, the
reported sensitivity, specificity and diagnosis accuracy
of MDCT in LGIB are 82 %, 50 %, and 74 % respec-
tively [16]. It is a time efficient investigation and needs
no bowel preparation and is noninvasive. The additional
anatomic information provided by CT is helpful for
further therapeutic angiographic procedures. However
this may miss an intermittent bleeding and causes sig-
nificant radiation exposure.
224 Indian J Pediatr (March 2013) 80(3):219–225

Table 5 Specific treatment

of common conditions Condition Treatment
causing LGIB
Infectious colitis
• Campylobactor and Yersinia Erythromycin, azithromycin
• E. coli Antibiotic treatment of enterohemorrhagic E.coli infection—
no benefit
• Salmonella Ampicillin, septran, cefotaxime, ceftriaxone
• Shigella Ampicillin, Ceftriaxone
• Clostridium difficile Metronidazole, oral vancomycin
• Giardia lamblia Metronidazole
• Amebic dysentery Metronidazole
Necrotizing enterocolitis Antibiotics, surgery if needed
Anal fissure Dietary modification, stool softeners,
good toilet training, local anesthetic gels
Hemorrhoids Banding, sclerosant injection, surgery
Polyps Polypectomy
Meckel’s diverticulum Surgical excision
Intussusception Radiological reduction or surgery
Cow’s milk allergy Withdrawal of milk and milk products, substitute
with casein hydrolysate formula
Hirschsprung’s disease with enterocolitis Antibiotics and surgery
Henoch Schönlein purpura Supportive therapy, steroids
Inflammatory bowel disease Steroids and other immunosuppressants
Nodular lymphoid hyperplasia Supportive treatment
Arterio venous malformations Endoscopic/angiographic treatment, surgery

& Other investigations: Capsule endoscopy does not have
much role in acute management of LGIB. It is more useful
in diagnosis of obscure bleeds. Explorative Laparotomy is
reserved as a last step of investigation and maybe needed
if the bleeding is torrential and an exact localization is not
possible even after other investigative modalities.
Treatment
the ongoing loss of coagulation factors. Platelet transfusion is
indicated if the platelet count is <50,000.
An algorithm for evaluation and treatment [18–20] of
LGIB is given in Fig. 1. The sequence of investigations like
colonoscopy, angiography, and nuclear scans depends large-
ly on the facilities available and the expertise of available
gastroenterologist. No pediatric studies evaluating such
treatment protocols are currently available. Specific man-
agement of selected conditions are given in Table 5.

All children with ongoing/significant bleed and those with
hemodynamic instability should be admitted in the hospital.
Those children with colitis symptoms, with stool for pus cell
positive can be treated on OPD basis provided they have no
signs of dehydration and the oral intake is good.
The most important step in managing a child with LGIB is
the continuous monitoring of vital signs and arrangement with
blood bank for likely need for blood. In majority of the cases
(up to 80 %) the bleeding responds to supportive management
alone, but episodes of rebleeding can occur [17].
If clinical deterioration occurs without obvious blood loss,
this should be considered as hidden bleed in the bowel lumen.
Blood transfusion is required in cases with hemodynamic
instability. Transfusion of fresh frozen plasma is required once
every 2–3 units of packed red blood cells (PRBC), to correct
Conflict of Interest None.
Role of Funding Source Used available resources of department of
pediatrics.
References
1. Teach SJ, Fleisher GR. Rectal bleeding in the pediatric emergency
department. Ann Emerg Med. 1994;23:1252–8.
2. Ya c h h a S K , K h a n d u r i A , S h a r m a B C , K u m a r M .
Gastrointestinal bleeding in children. J Gastroenterol Hepatol.
1996;11:903–7.
3. Khurana AK, Saraya A, Jain N, Chandra M, Kulshreshta R. Profile
of lower gastrointestinal bleeding in children from a tropical coun-
try. Trop Gastroenterol. 1998;19:70–1.
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4. Mandhan P. Sigmoidoscopy in children with chronic lower gastro-
intestinal bleeding. J Pediatr Child Health. 2004;40:365–8.
5. Boyle JT. Gastrointestinal bleeding in infants and children. Pediatr
Rev. 2008;29:39–52.
6. Silber G. Lower gastrointestinal bleeding. Pediatr Rev.
1990;12:85–93.
7. Squires Jr RH. Gastrointestinal bleeding. Pediatr Rev. 1999;20:95–101.
8. Dusold R, Burke K, Carpentier W, Dyck WP. The accuracy of
technetium-99 m-labeled red cell scintigraphy in localizing gastro-
intestinal bleeding. Am J Gastroenterol. 1994;89:345–8.
9. Currie GM, Kiat H, Wheat JM. Scintigraphic evaluation of acute
lower gastrointestinal hemorrhage: current status and future direc-
tions. J Clin Gastroenterol. 2010;45:92–9.
10. Voeller GR, Bunch G, Britt LG. Use of technetium-labeled red
blood cell scintigraphy in the detection and management of gas-
trointestinal hemorrhage. Surgery. 1991;110:799–804.
11. Farrell JJ, Friedman LS. Review article: the management of lower
gastrointestinal bleeding. Aliment Pharmacol Ther. 2005;21:1281–98.
12. Fiorito JJ, Brandt LJ, Kozicky O, Grosman IM, Sprayragen S. The
diagnostic yield of superior mesenteric angiography: correlation
with the pattern of gastrointestinal bleeding. Am J Gastroenterol.
1989;84:878–81.
13. Kruger K, Heindel W, Dolken W, Landwehr P, Lackner K.
Angiographic detection of gastrointestinal bleeding. An
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14. Geffroy Y, Rodallec MH, Boulay-Coletta I, Julles MC, Ridereau-
Zins C, Zins M. Multidetector CT angiography in acute gastroin-
testinal bleeding: why, when, and how. Radiographics. 2011;31:
E35–46.
15. Laing CJ, Tobias T, Rosenblum DI, Banker WL, Tseng L,
Tamarkin SW. Acute gastrointestinal bleeding: emerging role of
multidetector CT angiography and review of current imaging
techniques. Radiographics. 2007;2:1055–70.
16. Shih SL, Liu YP, Tsai YS, Yang FS, Lee HC, Chen YF. Evaluation
of arterial phase MDCT for the characterization of lower gastroin-
testinal bleeding in infants and children: preliminary results. AJR
Am J Roentgenol. 2010;194(2):496–9.
17. Longstreth GF. Epidemiology and outcome of patients hospitalized
with acute lower gastrointestinal hemorrhage: a population-based
study. Am J Gastroenterol. 1997;92:419–24.
18. Al Qahtani AR, Satin R, Stern J, Gordon PH. Investigative mo-
dalities for massive lower gastrointestinal bleeding. World J Surg.
2002;26:620–5.
19. Leung AK, Wong AL. Lower gastrointestinal bleeding in children.
Pediatr Emerg Care. 2002;18:319–23.
20. Singhi S, Surpure JS. Synopsis of pediatric emergency care. 2nd
ed. Delhi: Peepee; 2010.
Indian J Pediatr (May 2013) 80(5):411–420
DOI 10.1007/s12098-012-0918-2
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN EMERGENCY MEDICINE
Approach to a Child with Bleeding in the Emergency Room
Deepak Bansal & Sapna Oberoi & R. K. Marwaha &
Sunit C. Singhi
Received: 1 June 2012 / Accepted: 26 October 2012 / Published online: 27 December 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract A bleeding child is a cause of great concern
and often, panic, for parents and pediatricians alike.
Causes of bleeding could be trivial or secondary to an
underlying bleeding disorder or a potentially serious
systemic illness. Based on etiology, they can be catego-
rized into disorders affecting platelets or the coagulation
cascade and can be inherited or acquired. A systematic
approach with relevant clinical history and examination
along with appropriate laboratory investigations aid in
reaching the diagnosis promptly. Indication and admin-
istration of blood products including fresh frozen plas-
ma, cryoprecipitate, random donor and single donor
apheresis platelets is elaborated. Management of hemo-
philia, Von Willebrand disease, disseminated intravascu-
lar coagulation and bleeding in cyanotic congenital heart
disease, among other causes is outlined. Role of antifi-
brinolytic therapy, desmopressin and recombinant factor
VIIa is briefly described. The review outlines the ap-
proach to a bleeding child in the emergency room.
Practical points in history, examination, investigations
and management are discussed. Management in resource
constraint setting of developing countries is addressed.
Keywords DIC . FFP . ITP . RICE . Tranexamic acid . VWD
D. Bansal : S. Oberoi : R. K. Marwaha
Hematology -Oncology Unit, Department of Pediatrics,
Advanced Pediatric Centre,
Post Graduate Institute of Medical Education and Research,
Chandigarh, India
S. C. Singhi (*)
Department of Pediatrics and Pediatric Emergency and Intensive
Care, Advanced Pediatrics Centre, Post Graduate Institute of
Medical Education and Research,
Chandigarh 160012, India
e-mail: sunit.singhi@gmail.com
Introduction
A child with bleeding is a relatively common hemato-
logical emergency encountered by pediatricians in every
day practice. Common causes include disorders affect-
ing coagulation or platelets; they could be inherited or
acquired. The initial approach, differential diagnosis,
investigations and management of children with bleed-
ing are outlined in this review. Bleeding in a neonate
and the local causes of bleeding, e.g., trauma, varices,
etc. are not dealt here.
Common Causes of Bleeding
Broadly, bleeding disorders can be inherited or ac-
quired. Inherited disorders typically present in infancy
or early childhood, however, can manifest later in adult
life. A contributory family history can often be eli-
cited; pedigree charts with at least three generations
should be explored. Common inherited disorders in-
clude hemophilia A/B, von Willebrand disease (VWD)
and platelet function defects [1]. At presentation, be-
sides bleeding, the children typically appear well. The
rare exception is a child with hemodynamic instability
resulting from a massive bleed. Common acquired
causes of bleeding include immune thrombocytopenic
purpura (ITP), liver disease, vitamin K deficiency, dis-
seminated intravascular coagulation (DIC), sepsis,
aplastic anemia and leukemia. These children typically
present with a relatively short history of bleeding and
are comparatively ‘unwell’, except in ITP. A family
history of bleeding is lacking. Pallor, lymphadenopa-
thy, organomegaly or other findings of the underlying
disease may be evident [1, 2].
412 Indian J Pediatr (May 2013) 80(5):411–420

Systemic Bleeding Disorder vs. Local Etiology
At the outset, it should be identified whether bleeding is due
to a local cause or result of a systemic bleeding disorder.
Typically, recurrent bleeding from a single site is likely to
have a local etiology (e.g., trauma, tumor, surgery) and
concurrent bleeding from multiple sites is usually due to a
systemic bleeding disorder. Self-limiting isolated recurrent
epistaxis, particularly in young boys is often due to frequent
nose picking and detailed investigations are unwarranted.
Similarly, it is uncommon for a bleeding disorder to present
as recurrent isolated hematuria. Frequent bruises limited to
the shin are often physiological, due to susceptibility of the
vessels in the region devoid of subcutaneous fat.
in infancy. It is commonly observed in infants who have
not received vitamin K prophylaxis at birth, typically in
the setting of a home delivery. In older children, it may
occur due to underlying liver disease, malabsorption or
chronic diarrhea.
& Acute ITP typically occurs in children 2–6 y of age.
Acute onset, widespread mucocutaneous bleeds (pete-
chiae, purpura or epistaxis) in an otherwise well-child,
following a viral infection is the typical presentation.
& Children with severe VWD or platelet function defect
usually present with mucocutaneous bleeding in early
childhood. Less severe disease may manifest in adoles-
cence with recurrent epistaxis or menorrhagia.

Type of Bleeding
The step following the clinical suspicion of a bleeding disorder
is to identify whether the bleeding is due to a primary hemostatic
defect or a clotting factor deficiency (Table 1) [1, 3]. Bleeding
from umbilical stump is typical of factor XIII deficiency, but
may occur in deficiencies of fibrinogen or factor X, as well. The
common disorders of bleeding are listed in Table 2 [2].
Age and Gender
These provide valuable clues towards the diagnosis.
& Inherited coagulation disorders typically manifest when
a child begins to bear weight in infancy.
& Infants with Wiskott-Aldrich syndrome, an X-linked
recessive immunodeficiency disorder, may present with
thrombocytopenic purpura and/or eczema beginning in
early infancy.
& Clinical presentation of Vitamin K deficiency bleeding
(VKDB), earlier known as hemorrhagic disease of new-
born may range from ecchymosis to an intracranial bleed
Family History
X-linked recessive inheritance is observed in factor VIII and
IX deficiency. All other coagulation factor deficiencies, e.g.,
factor V, VII, X, XI or XIII have autosomal recessive inheri-
tance. VWD has an autosomal inheritance. It is classified into
three types: Type 1, 2 and 3. Type 1, 2A, 2B and 2 M have
autosomal dominant pattern of inheritance, while type 2 N and
3 are inherited recessively. It is important to remember that a
negative family history does not rule out the possibility of an
inherited disorder. Spontaneous mutation has been observed
in up to one third of patients with hemophilia [1].
Medical History
A past history of prolonged or difficult to control bleeding
during common surgical procedures, viz., dental extraction,
circumcision, appendectomy, tonsillectomy or following vac-
cination should be elicited. A major inherited bleeding disor-
der is unlikely if patient has had an uneventful surgery in the
past. Recent ingestion of drugs that effect platelet function/

Table 1 Clinical manifestations of primary hemostatic defect vs. clotting factor deficiency

Clinical characteristic Primary hemostatic defect Clotting factor deficiency

(e.g., Quantitative and qualitative (e.g., Hemophilia and
platelet defects, VWD or vessel wall defects) coagulation disorders)

Site of bleeding Skin, mucous membrane Soft tissues, muscles, joints

Bleeding following minor cuts Yesa Not usualb
Petechiae Present Absent
Ecchymosis Small, superficial Large, deeper, palpable
Hemarthrosis Rare Common
Soft tissue hematomas Rare Characteristic
Bleeding following trauma, surgery Immediatea Delayedc
a
Defect in primary phase of hemostasis leads to impaired production of the platelet plug
b
Primary phase of hemostasis is intact
c
Defect in secondary phase of hemostasis leads to impaired production of fibrin clot
Indian J Pediatr (May 2013) 80(5):411–420 413

Table 2 Common platelet and coagulation disorders causing bleeding count is normal. Purpura localized to palms and soles may
in children
indicate rickettsial infection. Purpuric or ecchymotic lesions
Platelet disorders that are at unusual site or of unusual shape, particularly in a
Thrombocytopenia female child should arouse a suspicion of child abuse.
Decreased platelet survival Children with purpura fulminans (thrombotic DIC) may
● Immune mediated have well-demarcated purple papules with erythematous
○ Immune thrombocytopenia borders, along with petechiae and ecchymosis. Pallor, jaun-
○ Collagen vascular diseases dice, lymphadenopathy, hepatomegaly or splenomegaly
○ Drug induced point towards an underlying systemic disorder, including
● Disseminated intravascular coagulation infections, leukemia, infiltrative disorders or liver disease.
● Hemolytic uremic syndrome Presence of splenomegaly typically goes against the diag-
● Thrombotic thrombocytopenic purpura nosis of ITP or aplastic anemia.
● Wiskott-Aldrich syndrome
Decreased platelet production
● Malignancies (leukemia, neuroblastoma)
Investigations
● Sepsis: viral and bacterial
● Aplastic anemia
The initial laboratory evaluation for bleeding disorder
includes a complete blood count with review of the periph-
Platelet sequestration
eral smear, prothrombin time (PT) and activated partial
● Congestive splenomegaly
thromboplastin time (aPTT).
● Large hemangiomas (Kasabach-Merritt syndrome)
Disorders of platelet function
Complete Blood Count
Congenital
● Glanzmann’s thrombasthenia
A complete blood count obtained from a well calibrated
● Bernard-Soulier syndrome
electronic coulter will promptly identify or refute thrombocy-
Acquired
topenia as the cause of bleeding. Uncommonly, spurious
● Drug induced: aspirin
thrombocytopenia may result from EDTA induced clumping
Coagulation disorders
of platelets; examination of peripheral smear will confirm the
presence of platelet clumps. A low hemoglobin may be sec-
Congenital
ondary to the underlying bleed. However, anemia dispropor-
● Hemophilia A (Factor VIII), Hemophilia B
(Factor IX) and other factor deficiencies tionate to bleeding is ominous and may suggest underlying red
● Von Willebrand disease cell destruction, bone marrow failure or leukemia. WBC count
Acquired provides information suggestive of sepsis or leukemia.
● Disseminated intravascular coagulation
● Vitamin K deficiency Peripheral Blood Smear
● Liver disease
● Warfarin therapy
Commonly overlooked, a smear provides valuable informa-
● Renal disease
tion about platelet size, morphology and presence of clump-
● Cyanotic congenital heart disease
ing. Giant sized platelets are commonly observed in ITP or
inherited disorders including Bernard-Soulier syndrome.
Wiskott-Aldrich syndrome is characterized by micro-
number, including aspirin, valproate, chloramphenicol, or thrombocytopenia. Schistocytes may suggest microangio-
non-steroidal anti-inflammatory drugs, should be explored. pathic hemolytic anemia, observed in hemolytic uremic
syndrome, thrombotic thrombocytopenic purpura or sepsis.

Examination Bleeding and Clotting Time

A search for bleeds from head to toe should be performed to
look for petechiae, purpura, gingival bleeding, ecchymosis,
hematomas, and hemarthrosis. Purpura localized to the low-
er body (buttocks, legs, ankles), with or without joint swell-
ing suggests a possibility of Henoch-Schönlein purpura
(HSP). The rash in HSP results from vasculitis; platelet
Bleeding time is measure of interaction of platelets with the
blood vessel wall (primary hemostatic pathway). Clotting
time gives a rough estimate of the integrity of intrinsic
clotting pathway. Sensitivity and specificity of both is not
acceptable, particularly in children. These tests are largely
obsolete except in rare situations.
414
PT (Prothrombin time) and aPTT (Activated Partial
Thromboplastin Time)
The sample for coagulation assay must be obtained prior to
the administration of a plasma product or any coagulation
factor. If a product has been administered in emergency, the
lag period required for investigative work-up is dependent
on the half-life of the factor under consideration. e.g., for
suspected hemophilia A/B, it is reasonable to sample after
10 d. A sample drawn from a clean venepuncture site,
without air bubbles or tissue fluid contamination, along with
the correct blood to anticoagulant ratio (9:1), is crucial for
an accurate result. An incorrectly and hastily collected sam-
ple is a common cause for falsely elevated result in the
emergency room [4]. The approximate normal values for
children are: PT: 10–11 s and aPTT: 26–35 s [1]. Prothrom-
bin time is prolonged due to deficiency of extrinsic pathway
(tissue factor, factor VII) or common pathway factors (II, V,
X, and fibrinogen). aPTT is prolonged due to deficiency of
intrinsic pathway (VIII, IX, XI, or XII), common pathway
factors, or in the presence of inhibitors (e.g., lupus antico-
agulant and heparin). An approach to a child with bleeding
is graphically illustrated in Fig. 1.
Mixing Studies
In a child with suspected coagulation disorder, result of
an abnormal PT or aPTT should be followed by a
mixing study. This aids in differentiating between a
clotting factor deficiency and presence of an inhibitor
(e.g., lupus anticoagulant or antibodies to factor).
Patient's plasma is mixed in a 1:1 ratio with normal
pooled plasma, and the abnormal test is repeated. Nor-
malization of clotting test (PT or aPTT) following a 1:1
dilution with normal pooled plasma indicates deficiency
of a factor. Majority of inhibitors will not be effectively
diluted following the addition of normal pooled plasma.
Thus, an abnormal test following dilution indicates the
presence of an inhibitor [4, 5].
Coagulation-Factor Assay
When a factor deficiency is suggested by clinical histo-
ry or a mixing study, specific coagulation-factor assay is
performed to confirm the diagnosis and assess the se-
verity of deficiency.
Fibrinogen, Fibrin Degradation Products and D-dimer
Normal plasma fibrinogen level is 200–400 g/L. Fibrinogen
is decreased in congenital afibrinogenemia, hypfibrinogene-
mia and in consumption states, e.g., DIC. Fibrin degradation
products and D-dimer are indicators of a fibrinolytic state.
Indian J Pediatr (May 2013) 80(5):411–420
Elevated levels are observed in DIC, recent trauma or sur-
gery and venous thromboembolism [4, 6].
Bleeding Child with Normal First Line Investigations
In a bleeding child with normal platelet count and PT/aPTT,
possible diagnosis include VWD, factor XIII deficiency, plate-
let function disorder and vascular abnormality. Services of a
hematologist may be obtained at this juncture who may order
specific tests, including platelet aggregation studies.
Management
Initial Stabilization
Vitals should be recorded in a bleeding child as the bleeds
may be substantial and life threatening. Stabilization of
airway, breathing and circulation is the priority in any child
in a decompensated state. The severity of bleeds governs the
speed/extent of investigations versus administration of treat-
ment. e.g., a coagulation disorder with intracranial bleed
will require urgent action vs. a patient with hemarthrosis.
Specific Management
This is directed towards the underlying etiology.
Undiagnosed Coagulation Disorder
In the setting of severe hemorrhage occurring in an undiag-
nosed coagulation disorder, fresh frozen plasma (FFP) should
be administered, as it contains all the clotting factors. The
average concentration of factor in FFP is 1 unit/ml; the typical
dose is 15 ml/kg.
Hemophilia
Acute Hemarthrosis
In a child presenting with acute hemarthrosis, initial replace-
ment with factor (factor VIII in hemophilia A and factor IX
in hemophilia B) should be given to raise the factor level to
40-60 %. A lower goal of 10-20 % may be acceptable if
there is resource constraint [7, 8]. If symptoms do not abate,
or if the hemarthrosis is severe, a second dose should be
given 12–24 h later. Factors are often not an option to a large
majority of patients in India due to cost constraints (1 vial of
250 units of factor VIII: ~Rs 2800; 1 vial of 600 units of
factor IX: ~Rs 11,000). Thus, FFP or cryoprecipitate are
Indian J Pediatr (May 2013) 80(5):411–420 415

Petechiae/Purpura/Abnormal bleeding

History and examination to differentiate

between primary hemostatic and
coagulation disorder (Table 1)

Screening tests
• Complete blood count
• Peripheral smear: Platelet size/morphology
• PT and aPTT

Thrombocytopenia?

Yes No

Prolonged PT and aPTT? PT and aPTT

Abnormal Normal
Yes No

• DIC • ITP
• Sepsis • HUS • Child abuse
• TTP • HSP
• Acute leukemia • Factor XIII deficiency
• Aplastic anemia • Von Willebrand disease#
• Platelet function disorder*
• Vascular disorders e.g., Hereditary
hemorrhagic telengiectasia,
Ehler- Danlos syndrome

Abnormal PT and normal aPTT Normal PT and abnormal aPTT Abnormal PT and aPTT

• Early liver disease • Factor VIII, IX, XI deficiency • Liver disease

• Factor VII deficiency • Moderate to severe VWD • Vitamin K deficiency
• Warfarin • DIC
• Deficiency of fact or II, X or V
• Massive transfusion
• Excessive heparin

Fig. 1 Step wise approach to a child with bleeding. CBC Complete thrombocytopenic purpura; HSP Henoch-Schönlein purpura. #Thrombo-
blood count; PT: Prothrombin time; aPTT Activated partial thrombo- cytopenia is observed in type 2B VWD. *Mild thrombocytopenia can be
plastin time; DIC Disseminated intravascular coagulation; ITP Immune present in Bernard-Soulier syndrome
thrombocytopenia; HUS Hemolytic uremic syndrome; TTP Thrombotic

often administered as the only feasible, though, inferior Composition, dose and indications of FFP and cryoprecipi-
alternative. FFP can be administered to patients with hemo- tate are illustrated in Table 3. The formula for calculating the
philia A as well as B, whereas cryoprecipitate can only be replacement dose of factor VIII and IX in patients with
used in hemophilia A, as it does not contain factor IX. haemophilia is outlined below.
416 Indian J Pediatr (May 2013) 80(5):411–420

Table 3 Composition,
dose and indications of Component Contents Indications and Dose
plasma derived products
in a bleeding child Fresh frozen plasma All coagulation factors: ● Correction of bleeding due to excess warfarin,
[9–11] (1 unit: 150–300 ml) 1 unit of factor/ml of vitamin K deficiency, or deficiency of multiple
FFP & plasma proteins coagulation factors (e.g., DIC, liver disease,
massive blood transfusion with coagulopathy)
● For infusion or plasma exchange in TTP-HUS
● Congenital or acquired coagulation factor
deficiency; only when virus-inactivated
concentrates are unavailable
● Dose: 10–15 ml/kg

Cryoprecipitate 1 unit contains: vWF ● Factor XIII deficiency

(1 unit: 10–20 ml)
(80 U), factor VIII ● Congenital or acquired deficiency of fibrinogen
(80–110 U), factor XIII
● Hemophilia A and VWD; only when virus-
(40–60 U), fibrinogen
inactivated concentrates are unavailable
(150–250 mg), fibronectin
(30–60 mg) ● Dose: 1–1.5 units/10 kg

Factor VIII
One unit of recombinant or plasma derived factor VIII raises
the measured factor level by 2 %.
Dose of factor VIII ðunitsÞ ¼ Desired rise ðU=dlÞð%Þ
 weight of the patient ðkgÞ
 0:5
Half-life: 10–12 h, Technique: slow IV push at a rate not to
exceed 100 units/min Frequency: q 12 hourly, factor is
stable at room temperature for 12 h
Factor IX
One unit of plasma derived factor IX raises the measured
factor level by 1 %.
Dose of factor IX ðunitsÞ ¼ Desired rise ðU=dlÞð%Þ
 weight of the patient ðkgÞ
(*If recombinant factor IX is used, the dose is increased by
1.2-1.5 units, because of the poor recovery of factor IX in
some patients)
Half-life: 18–24 h. Technique: slow IV push at a rate not to
exceed 100 units/min. Frequency: q 24 hourly, factor is
stable at room temperature for 12 h
Example A 10 kg child with hemophilia A presents with
acute hemarthrosis of right knee to the emergency room.
What is the dose of Factor VIII or FFP or cryoprecipitate
that should be administered?
Answer The choice of product is determined by finances and
availability. To achieve a factor level of 40 U/dl on day 1, the
required dose of recombinant VIII is 200 units (40 units/dL X
10 kg X 0.5). If cost is a limitation, the dose of factor can be
reduced to half. One ml of FFP will provide 0.8-1 unit, and 1
unit of cryoprecipitate contains 80–110 units of factor VIII. To
raise the factor level by 20 %, the dose of FFP and cryopreci-
pitate will therefore be 200 ml and 2 units (40 ml), respectively.
Cryoprecipitate is preferred over FFP due to lower chances of
volume overload. The corresponding dose of recombinant fac-
tor IX in a child with hemophilia B, who presents with similar
scenario will be 480 units (40 X 10 X 1.2), to raise the factor IX
level by 40 U/dl. It is a common practice to round the dose to
the nearest vial size, to prevent wastage of the expensive
factors.
RICE Therapy
Along with the factor replacement, analgesics, Rest, Immobi-
lization, Cold compression and Elevation (RICE) should be
advised as well. Rest is done in the position of function (a sling
for an upper limb bleed and bed rest or splint for lower limb
bleed) for one day, followed by avoidance of weight bearing for
next 3–4 d. Application of ice aids by decreasing pain and
swelling. It can be performed with crushed ice cubes wrapped
in a wet towel or with cold packs, intermittently for a period of
5–15 min over 24–48 h. Ice should not be applied directly to the
skin, as prolonged application can lead to skin damage. It is not
useful, if applied beyond 48 h [8]. Wrapping the joint gently
with bandage or elastic stocking may help in limiting the
bleeding and supporting the joint. The application of these
adjunctive interventions is not evidence based; however, they
are commonly recommended, as they help in reducing pain,
swelling and promoting early mobilization [7, 12–14].
In a landmark order, in 2007, the Delhi High Court had
directed the Delhi state Government to make factors available
to patients with hemophilia [15]. Under the scheme, below-
Indian J Pediatr (May 2013) 80(5):411–420
poverty-line families are to be supplied factors free of cost. This
was followed by a similar ruling in Lucknow, Uttar Pradesh, in
response to a public interest litigation [15]. Based on these
developments, hospital authorities should be convinced to make
factors available in the hospital at least for emergency use.
Intracranial Bleed and Other Hemorrhages
In patients with head trauma, a quick neurological examina-
tion, followed by CT head should be performed. Factor re-
placement should not be delayed pending the imaging. Raised
intracranial pressure, if any, should be managed with medical
measures. Level of the appropriate factor should be immedi-
ately raised to 100 % and a level of 50-60 % should ideally be
maintained for at least 2 wk. If resources are limited, a dose of
30–50 U/kg of factor VIII or 60–100 U/kg of factor IX may be
used for 3–5 d, followed by maintenance with lower doses,
depending on the response [7, 14]. In children with known
inhibitors to factor VIII or IX, administration of activated
prothrombin complex (FEIBA, 1 vial of 500 units costs~Rs
25,000) or activated factor VIIa may be considered, in con-
sultation with a hematologist [1]. Treatment of commonly
observed hemorrhages in hemophilia is outlined in Table 4.
Bleeding in Platelet Disorders
Platelets are transfused to control bleeding in quantitative or
qualitative platelet disorders. Platelets are available as random
donor platelets (RDP) or as single donor apheresis platelets
(SDAP). The differences are outlined in Table 5. Although both
are effective, SDAP is better than RDP in ease of leucoreduc-
tion, decreasing risk of septic platelet transfusion reactions,
reducing exposures to multiple donors and transfusion frequen-
cy, and in treating alloimmunization [17–19]. Indication and
dose of platelets is often a dilemma. It is important to remember
that transfusion trigger in a thrombocytopenic patient depends
not only on the platelet count, but also on its etiology and the
clinical condition of the patient. Platelet transfusion is futile and
not indicated in majority of patients with ITP as the transfused
platelets are quickly destroyed due to circulating antibodies. In
stable children with non-immune thrombocytopenia, a transfu-
sion trigger of 10×106/μL is now widely accepted. A few
studies have even recommended a lower threshold of 5×106/
μL [20–22]. The common indications for platelet transfusions
are listed in Table 6.
Bleeding in Von Willebrand Disease
Desmopressin is helpful in controlling mild bleeding in
patients with type 1 and 2A VWD, but not in type 2B and
417
3. It is recommended that every patient with VWD should
have therapeutic trial of desmopressin to assess the
response at diagnosis or when the patient is not bleeding.
In responsive patients, 0.3 μg/kg (maximum 20 μg) of
desmopressin diluted in 50 mL saline is administered i.v
over 20–30 min. Although i.v route is the most effective,
subcutaneous injection or nasal spray (150 μg/puff) can
be used as well [23, 24]. The desired concentration of
the drug as a nasal spray is not available in India. The
commercially available nasal spray (Minirin: 10 μg/puff),
indicated for nocturnal enuresis and diabetes insipidus, is
too dilute to be used for VWD. Facial flushing, headache,
hyponatremia, hypo/hypertension and tachyphylaxis are com-
mon adverse effects. VWF concentrate is preferred for major
bleeds. High purity VWF concentrate is not available in the
market. Hence, intermediate purity factor VIII concentrates
containing VWF are used (Immunate: 1 vial0500 units of
factor VIII and 290 units of VWF; cost~Rs 3400). Initial dose
of 40–60 units/kg followed by 20–40 units/kg q 12–24 h is
recommended. Antifibrinolytic agents should be used con-
comitantly in patients with mucosal bleeds [23, 24].
Disseminated Intravascular Coagulation
The cornerstone of treatment of DIC is the aggressive
management of the underlying etiology. In some children,
this may resolve the DIC, however, in some it may not.
Patients with persistent coagulation abnormalities are at
risk of hemorrhage or thrombosis and require supportive
care, including component replacement and/or anticoagu-
lation. Transfusion of platelets or FFP is not indicated to
correct the coagulation abnormalities in a child who is
asymptomatic or has minor bleeds (e.g., skin petechiae).
It should be reserved for children with active bleeding or prior
to invasive procedures, with an aim of maintaining the platelet
count above 50×106/μL and fibrinogen concentration above
1 g/L. Clotting factors are replaced by FFP or by cryoprecipi-
tate. The latter is particularly indicated for hypofibrinogene-
mia (fibrinogen <1 g/L).
The benefit of routine anticoagulation has not been prov-
en by randomized controlled trials [25, 26]. However, recent
guidelines do recommend prophylactic doses of heparin or
low molecular weight heparin in non-bleeding critically ill
patients with DIC due to increased risk of thromboembolism
[26–28]. Therapeutic use of heparin is generally limited to
the situations where thrombosis predominates, such as arte-
rial or venous thromboembolism, severe purpura fulminans
associated with acral ischemia or vascular skin infarction
without evidence of clinical bleeding. Continuous infusion
of unfractionated heparin is probably the best choice given
the risk of bleeding in these children [26]. The monitoring of
aPTT may be intricate because of already prolonged aPTT
418 Indian J Pediatr (May 2013) 80(5):411–420

Table 4 Outline of treatment of bleeds in hemophilia in the emergency room [1, 7, 14, 16]

Type of bleed No resource constraints Significant resource constraints

Desired plasma level Duration (d) Desired plasma level Duration (d)

Hemophilia Hemophilia Hemophilia Hemophilia

A B A B

Acute hemarthrosis 40-60 % 40-60 % 1-2, may be longer if 10-20 % 10-20 % 1–2, may be longer
or muscle hematomas response is inadequate if response is inadequate
(except iliopsoas)
Iliopsoas
• Initial 80-100 % 60-80 % 1-2 20-40 % 15-30 % 1-2
• Maintenance 30-60 % 30-60 % 3–5, sometimes longer 10-20 % 10-20 % 3–5, sometimes
as secondary prophylaxis longer as
during physiotherapy secondary prophylaxis
during physiotherapy
CNS
• Initial 80-100 %a 60-80 %b 1-7 50-80 % 50-80 % 1–3
• Maintenance 50 % 30 % 8-21 30-50 % 30-50 % 4–7
20-40 % 20-40 % 8–14 (up to 21)
Hematuriac 50 % 40 % 3-5 20-40 % 15-30 % 3-5
Gastrointestinal
• Initial 80-100 % 60-80 % 1-6 30-50 % 30-50 % 1–3
• Maintenance 50 % 30 % 7-14 10-20 % 10-20 % 4–7
Epistaxisd 20-30 % 20-30 % 1 d or longer 10-20 % 10-20 % 1 d or longer if
if response is inadequate response is inadequate
a
To achieve a plasma level of 100 %, administer 50–75 U/kg factor VIII concentrate as bolus, followed by a continuous infusion of 4–5 U/kg/h, to
maintain factor VIII >100 U/dL for 24 h. Subsequently administer 2-3/kg/h for 5–7 d to maintain factor level >50 U/dL.
b
To achieve a plasma level of 100 %, administer 80–100 U/kg factor IX concentrate at outset, followed by 20–40 U/kg q 12–24 h to maintain factor
IX >30 U/dL for 5–7 d
c
Treat painless hematuria with bed rest and vigorous hydration (3 L/m2 /d) for 48 h. Raise the patient’s factor level if there is pain or persistent gross
hematuria. Avoid antifibrinolytics. Rule out other causes if hematuria is persistent. Prednisone (1 mg/kg x 3–5 d) can be used, though the benefit is
unclear
d
If bleeding is not controlled by firmly pinching the nose for 15–20 min. and with antifibrinolytic agents

due to DIC. Thus, instead of conventional doses, weight may be administered without the intention of prolonging the
adjusted doses (e.g., 10 U/kg/h) of unfractionated heparin aPTT to 1.5-2.5 times the control.

Table 5 Random donor

vs. single donor aphere-
sis platelets [19]
Parameter Random donor platelets Single donor apheresis platelets
Method of collection Prepared from single whole blood Collected from a single donor
unit by plaletet rich plasma or by automated apheresis technique
buffy coat centrifugation technique using an apheresis kit
Volume of one unit 50-70 ml 200-300 ml
Platelet content per unit 5-7×1010/cumm 3-6×1012/cumm
(1 bag of SDAP06–8 bags of RDP)
Donor exposure More Less
Donor availability Easy Difficult
Leucoreduction Difficult Easy
Dose Weight <10 kg: 10-15 ml/kg Weight <30 kg: half unit
Weight >10 kg: 1 unit/10 kg Weight >30 kg: one unit
Cost (Rs) Less More
Indian J Pediatr (May 2013) 80(5):411–420
Table 6 Indications for platelet transfusion in children [17, 18, 21]
Indications of prophylactic platelet transfusions
■ Platelet count <10×106/μLa
■ Platelet count 20–40×109/μl and one or more of the following
● DIC in association with induction therapy for leukemia
e.g., acute promyelocytic leukemia
● Extreme hyperleukocytosis
● Prior to invasive procedures
Indications of therapeutic platelet transfusions
■ ITP with major and/or dangerous bleeding (e.g., severe
intestinal, intracranial or intraocular haemorrhage)
■ Acute disseminated intravascular coagulation with major
bleeding and platelet count <50×106/μL
■ Platelet function defects (congenital or acquired) with active
bleeding
■ Surgical patient with active bleeding and platelet count
<50-100×106/μL
■ During massive transfusions with platelet count <75×106/μL
a
In a stable patient threshold can be decreased to 5×106 /μL
Vitamin K Deficiency Bleeding
Infants with vitamin K deficiency bleeding should receive
250–300 μg/kg (maximum 10 mg) of i.v vitamin K without
any delay. As a rough guide, 1–2 mg of vitamin K is more
than sufficient to correct the deficiency in majority of infants
[29, 30]. It may be administered by subcutaneous route, but
not by intramuscular route, if venous access is difficult.
Correction of coagulation parameters within 2–6 h of ad-
ministration of vitamin K is diagnostic of VKDB. FFP (10–
15 ml/kg) is indicated if urgent control of bleeding is desired
in case of life threatening hemorrhage [1, 30].
Bleeding in Liver Disease
Treatment of bleeding in a child with hepatic failure is
arduous. Enhanced hemostasis following FFP or other plas-
ma products is usually transient. Recombinant Factor VIIa
rapidly normalises PT in these patients, however the effica-
cy in on-going bleeding is unclear [31]. Thus, it should be
reserved for rescue therapy in active hemorrhage.
Bleeding in Cyanotic Congenital Heart Disease
Children with cyanotic heart disease can present with
bruising or mucocutaneous bleeding due to hemostatic
abnormalities resulting from chronic hypoxic state. The
abnormalities include thrombocytopenia, abnormal
platelet function, reduced coagulation factors and
elevations of PT/aPTT. Phlebotomy performed for
419
symptomatic hyperviscosity helps to restore hemostasis as
well. However, in severe hemorrhage, FFP and platelet trans-
fusions should be given to control bleeding [32, 33].
Antifibrinolytic Therapy
Control of bleeding from mucosal surfaces, particularly
epistaxis, gum bleeding and menorrhagia in platelet or
coagulation disorders, can be aided with antifibrinolytic
agents. Two agents, aminocaproic (Hamostat; 1 vial of
5000 mg costs~Rs 75, one tablet of 500 mg costs~Rs 6)
and tranexamic acid (Trenaxa; 1 injection of 500 mg costs~
Rs 45, one tablet of 500 mg costs~Rs 13) are available.
Tranexamic acid is preferred due to its longer half-life,
higher potency and lower toxicity. Aminocaproic acid is
administered as a stat dose of 100–200 mg/kg (maximum:
10 g), followed by 50–100 mg/kg/dose q 6 hourly
(maximum dose: 5 g). The dose of tranexamic acid is
25–50 mg/kg q 6–8 h [1]. Tranexamic acid is absorbed from
the buccal mucosa and subsequently secreted in the saliva.
Hence, in oral bleeding, hemostasis is better achieved with a
mouth-wash rather than by swallowing. Patient should be
advised to crush the tablets in 10–15 ml of water and retain
the solution in the mouth for nearly 5 min before swallow-
ing (‘swish and swallow’). For younger children, tablets can
be crushed and made into paste with water; this can be
applied at the site of bleeding in the mouth. Antifibrinolytic
agents are contraindicated in hematuria; formation of clots
can result in colic and obstruction of outflow from the renal
pelvis [1, 14].
Recombinant Factor VIIa
Recombinant factor VIIa acts by producing a ‘thrombin burst’
on the surface of activated platelets. This results in activation
of platelets at the site of injury, increased platelet adhesion and
activation of factor XIII. It leads to the formation of a tight
fibrin hemostatic plug. It has the potential to enhance hemo-
stasis in patients with severe bleeding, even in the absence of
underlying coagulation defect. Hence, it is referred to as a
‘general hemostatic agent’ [34]. This has led to several off-
label uses of the drug. The FDA approved indications include
treatment of bleeding in children with hemophilia with inhib-
itors and congenital factor VII deficiency. In addition, Euro-
pean guidelines recommend its use for bleeding in platelet
function defects (e.g., Glanzmann's thrombasthenia), which
is not responsive to platelet concentrates. Off-label uses
include, ITP with severe haemorrhage not responding to
standard therapies, post-surgical/traumatic hemorrhage, in-
tracranial bleed and liver transplantation. The benefit is
unproven in these conditions, and hence may be used as
a ‘last resort’ [31, 35, 36]. Standard dose is 90–120 μg/kg
420
q 2–3 h, till the cessation of bleeding. The high cost
(Novo-seven: 1 vial01 mg, cost~Rs 42,000) precludes
administration in majority.
Conflict of Interest None.
Role of Funding Source None.
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PGIMER
Management Protocols in
Pediatric Emergency Medicine
Advanced Pediatrics Centre – Postgraduate Institute of Medical Education and Research

Published By
Indian Journal of Pediatrics, New Delhi, India
www.ijppediatricsindia.in
2015
CONTENTS
 Initial Assessment and Triage in ER
 Approach to a Child with Breathing Difficulty
 Acute Community Acquired Pneumonia in Emergency Room
 Acute Upper Airway Obstruction
 Acute Chest Pain
 Approach to a Child with Sore Throat
 Acute Bronchial Asthma
 Approach to a Child with Lower Airway Obstruction and Bronchiolitis
 Airway Foreign Body Aspiration
 Fainting Attacks in Children
 Non-Traumatic Coma and Altered Mental Status
 Approach to Headache in Emergency Department
 Management of Acute Seizure and Status Epilepticus in Pediatric Emergency
 Raised Intracranial Pressure (ICP): Management in Emergency Department
 Approach to a Child with Acute Flaccid Paralysis
 Tumor Lysis Syndrome
 Superior Mediastinal Syndrome: Emergency Management
 Febrile Neutropenia: Outline of Management
 Hyperleukocytosis: Emergency Management
 Management of a Child with Vomiting
 Management of Acute Diarrhea in Emergency Room
 Approach to a Child with Upper Gastrointestinal Bleeding
 Emergency Management of Lower Gastrointestinal Bleed in Children
 Approach to a Child with Bleeding in the Emergency Room