Iran J Pediatr

Original Article Dec 2009; Vol 19 (No 4), Pp:393-398

Etiology and Outcome of Non­traumatic Coma in Children

Admitted to Pediatric Intensive Care Unit

Fariba Khodapanahandeh*, MD; Najmeh Ghasemi Najarkalayee, MD

Department of Pediatric, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran

Received: Nov 10, 2008; Final Revision: Mar 06, 2009; Accepted: Jun 05, 2009

Abstract
Objective: Non‐traumatic coma is a relatively common condition in children that may cause
considerable mortality and morbidity. The purpose of this study was to determine clinical
presentation, etiology and outcome of non‐traumatic coma in children.
Methods: In a retrospective cross sectional study over a period of 5 years, files of 150 children
aged between 1 month and 14 years admitted with non‐traumatic coma to pediatric intensive
care unit of Rasool Akram hospital were reviewed. Historical, presenting symptoms, clinical
and laboratory data were collected. Etiology of coma was determined on the basis of clinical
history and relevant investigations. The outcome was recorded as died or neurological
condition at discharge as normal, mild or sever disability. Chi‐square test was used to test the
differences in categorical variables.
Findings: There were 63 (42%) boys and 87 (58%) girls. The mean±SD age of patients was
2.7±2.35 years. Systemic presentations including nausea, vomiting, fever, lethargy and poor
feeding were more prominent in children under 2 years. Etiology of coma in 49 patients
(32.7%) was infectious (meningitis, encephalitis, respiratory and systemic). Other causes were
status epilepticus 44 (29.4%), metabolic (diabetic ketoacidosis, inborn errors of metabolism)
11 (7.3%), intoxications 10 (6.7%), accidental (drowning, electrical shock, suffocation) 9 (6%),
shunt dysfunction (secondary to congenital brain malformations) 7 (4.6%), others (acute
disseminated encephalomyelitis, vasculitis, hypertensive encephalopathy) 11 (7.3%), unknown
9 (6%). Infection occurred significantly (P=0.002) in children under 2 years of age, whereas
accidents and intoxications were more prominent (P=0.004) in those between 2 and 6 years.
Overall 25 children (16.6%) died. Of those survived 16 became severely disabled. Accidents and
infections had higher mortality compared to other groups (P<0.001 and P=0.02 respectively).
Conclusion: Our results showed that infection was the most common cause of non‐traumatic
coma in childhood. Accidents and infection had higher mortality than other causes.

Iranian Journal of Pediatrics, Volume 19 (Number 4), December 2009, Pages: 393­398

Key Words: Non‐traumatic coma; Morbidity; Epilepsy; Meningitis

* Corresponding Author;
Address: Pediatric Ward, Rasool Akram Hospital, Sattar Khan Ave, Niyaesh St, Tehran, IR Iran
E-mail: fariba.khodapanahandeh@gmail.com
© 2009 by Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, All rights reserved.
394 Non-traumatic coma in children; F Khodapanahandeh, NGh Najarkalayee
Introduction
Non‐traumatic coma (NTC) is a common cause of
morbidity and mortality in children. Episodes
were defined on the basis of a Glasgow Coma
Score (GCS) of less than 12 for more than six
hours[1,2]. Many acutely ill children are not fully
conscious because pathologic processes may
affect the parts of the central nervous system
that mediate consciousness; alteration in the
state of consciousness is a common feature of
many different conditions.
Many of these children make a full
neurological recovery. However, depending on
the underlying etiology non‐traumatic coma may
cause considerable mortality and morbidity in
pediatric age group[2,3,4]
Considering the fact that acute non‐traumatic
coma is a common problem in pediatric practice
accounting for 10‐15% of all hospital
admissions, it makes a heavy demand on
intensive care units[5]. Etiology of coma and
clinical status at the time of presentation are
likely predictors of outcome[2,6,7]. Outcome of
non‐traumatic coma was classified based on
several prospective population based
studies [2,3,7] .
A better understanding of causes and outcome
is essential to help to improve the approach and
to plan rational management of non‐traumatic
coma. In a retrospective cross sectional study we
reviewed the etiology, clinical signs and outcome
of non‐traumatic coma in a pediatric intensive
care unit.
Subjects and Methods
In a cross sectional retrospective study files of
150 children aged between 1 month and 14
years admitted with non‐traumatic coma to the
pediatric intensive care unit of Rasool Akram
Hospital over a period of 5 years (2002‐2007)
were reviewed. Coma was defined as significant
depression of consciousness level as a GCS of
less than 12 for more than 6 hours. In those less
than 5 years of age modified GCS was used. GCS
is checked routinely by our physicians and
nursing staff in every child with altered level of
consciousness.
Children who presented with coma as a final
stage of malignant diseases and those due to
head trauma were excluded from the study.
Presenting symptoms, historical, clinical and
laboratory data were collected. The etiology of
coma was determined on the basis of history,
clinical signs, physical examination and relevant
laboratory investigations (lumbar puncture,
neuroimag‐ing, metabolic work‐up).
Presenting manifestations were classified as CNS
related, non CNS and organ specific.
Etiology was classified into infectious,
epilepsy, metabolic, intoxication, accidents,
shunt dysfunction (secondary to congenital
brain malformation), others (acute disseminated
encephalomyelitis, vasculitis, hypertensive
encephalopathy).
Outcome was determined by patients' death
or neurological condition at the time of
discharge. Assessment of clinical neurological
status included cranial and peripheral motor and
sensory neurological examination, including
cerebellar function performed for all children.
Neurological outcome was divided into four
groups:
• Normal: normal or no change from
premorbid neurological examination.
• Mild disability: mild (grade 4) weakness or
ataxia, isolated cranial nerve palsy, mild
alteration of tone, power or deep tendon
reflexes.
• Moderate disability: moderate weakness
(grade 3) or ataxia, multiple cranial nerve
involvement.
• Sever disability: sever weakness (<grade 3)
or ataxia, tetraplegia, vegetative state.
In assessing the effect of age on etiology and
mortality, children were divided into three age
groups: less than 2 years; 2‐6 years; and 6.1‐14
years of age.
Statistical analysis was conducted using
Statistical Package for Social Sciences (SPSS).
Descriptive statistics expressed as mean and
standard deviation. Chi‐Square analysis was
performed to test for differences in proportions
of categorical variables between two or more
groups. The level of P<0.05 was considered as
being significant.
 Iran J Pediatr; Vol 19 (No 4); Dec 2009 395

Findings traumatic coma accounting for 49 (32.7%) cases

followed by epilepsy (causing prolonged seizure
A total of 150 patients were included in the activity leading to status epilepticus) as the
study. There were 63 (42%) boys and 87 (58%) second common etiology with 44 (29.4%) cases.
girls. The mean age of patients was 2.47 years Other etiologies were metabolic (diabetic
(range 1 month ‐ 14 years ±2.35). ketoacidosis, inborn errors of metabolism) 11
There were 62 (41.3%) patients under the age (7.3%), intoxication (opiate, narcotics) 10
of 2 years, 61 (40.6%) between 2 and 6 years (6.7%), accidents (drowning, electrical shock,
and 27 (18%) between 6 and 14 years. Clinical suffocation, etc) 9 (6%), shunt dysfunction
manifestations at admission to PICU were secondary to congenital brain malformation 7
divided into three groups: CNS specific, systemic (4.6%), others (ADEM, vasculaitis, hypertensive
and other organ related symptoms (Table 1). encephalopathy) 11 (7.3%) and unknown causes
9 (6%).
Infection and congenital etiology were
Table 1: Presenting manifestations at admission significantly more common in children younger
in children with non‐traumatic coma than 2 years of age (P=0.002 and P=0.009
Manifestation No (%) respectively), whereas accidents and
intoxications occurred more prominently in
CNS related
52 (34.8) those between 2 and 6 years of age (P=0.004).
Seizure
Headache 6 (4) Epilepsy causing prolonged seizure and altered
Irritability 7 (4.6) level of consciousness was more common in
Behavioral change 3 (2) children older than 6 years (P=0.008). Table 2
Systemic shows a summery of age distribution and
Nausea and vomiting 25 (16.4) etiology of non‐traumatic coma.
Fever 21 (14.2) Outcome: 25 (16.6%) patients died and 125
Lethargy 10 (6.6) survived. Of the 125 survivors 82 were
Poor feeding 4 (2.6) discharged with normal neurological
Poor weight gain 3 (2) examination, 9 had mild disability, 18 were
Organ specific moderately disabled and 16 were severely
Respiratory tract Infection 9 (6) disabled. There was a significant association
Gastrointestinal Infection 6 (4) between etiology and mortality. Accidents and
Rash 4 (2.6) infectious etiology had higher mortality
Total 150 (100) compared with other groups (P<0.001 and
P=0.02 respectively).
Mortality was 25% (14 of 26) among those
Systemic presentations were particularly less than 2 years, 11.4% (7 of 61) among 2‐6
evident in children less than 2 years of age years and 14.8% (4 of 27) among 6.1‐14 years.
(P=0.009) compared to other age groups. Table 3 shows neurological outcome by etiology
Infection (meningitis, encephalitis, respiratory for all children.
and systemic) was the commonest cause of non‐

Table2: A summary of age distribution and etiology of non‐traumatic coma in children

Age
Infection Epilepsy Metabolic Intoxication Accidents Congenital Others Unknown Total
(yrs)
<2 51.3% 7.7% 6.6% 6.3% 1.1% 10.8% 14.2% 12% 100%
2­6 31.4% 18.3% 4.2% 12.1% 13.5% 6.2% 3.1% 11.2% 100%
6.1­14 22.6% 27.3% 6.1% 5.4% 5.8% 5.3% 14.3% 13.2% 100%
Total 32.7% 29.4% 7.3% 6.7% 6% 4.6% 7.3% 6% 100%
396 Non-traumatic coma in children; F Khodapanahandeh, NGh Najarkalayee

Table 3: Etiology of non‐traumatic coma and age in children

Etiology No Normal Mild Moderate Sever Dead Total
Infection 49 33.6% 12.1% 11.8% 12.5% 30% 100%
Epilepsy 44 74.2% 9.3% 9.5% 5.4% 2.6% 100%
Metabolic 11 39.4% 12.6% 19.7% 15.5% 12.8% 100%
Intoxication 10 80.8% 19.2% 0% 0% 0% 100%
Accidents 9 9% 0% 9.2% 37.8% 44% 100%
Congenital 7 54.7% 15.3% 15.8% 0% 14.2% 100%
Others 11 36.3% 11.2% 17.1% 17.8% 17.6% 100%
Unknown 9 54.6% 0% 22.9% 11.3% 11.2% 100%

Discussion the presentation of previously unrecognized

Consciousness requires normal functioning of
both hemispheres as well as the ascending
reticular activating system (ARAS). ARAS is a
somewhat diffuse and poorly circum‐scribed
group of neurons that lie in the reticular
formation of the brain which extends from the
lower medulla to the midbrain and
diencephalon.
Coma is produced by disease or conditions
that cause bilateral cerebral cortical dysfunction,
or both. Childhood coma is a non‐specific
consequence of a variety of serious pathologic
processes[8]. A practical classification for the
etiology of coma in children produces three
categories: infectious or inflammatory,
structural, metabolic or toxic[9].
Infection was the commonest cause of non‐
traumatic coma in our study. The importance of
infection as an etiology of non‐traumatic coma is
also supported by other studies[2,3,6,7]. The
importance of infective etiologies in children is
in sharp contrast to adult hospital based series
where degenerative and cerebrovascular
patholo‐gies predominate[10].
Epilepsy causing prolonged seizure activity
was the second commonest cause contributing
to almost one third of cases of non‐traumatic
coma in our study. The result is compatible with
the series from Britain and Nigeria[2,5]. In
contrast, it was seen in only 5‐10% of cases in
some other studies[3,7].
Clinicians managing children in non‐traumatic
coma are often concerned that the illness may be
inborn error of metabolism. In the present study
5 of 11 children in metabolic group had diabetic
ketoacidosis. Two children had been diagnosed
of metabolic disease prior to admission. In only
four children the inborn error of metabolism
was suspected as a result of the presenting
episode of coma. In addition, three patients in
unknown group had suspected metabolic causes
for coma.
Unfortunately, the exact type of inborn error
of metabolism was not clear in our patients.
The percentage of patients with metabolic
disease in present study was comparable to
other studies[2,7].
Systemic symptoms (nausea and vomiting,
fever, lethargy, poor feeding, poor weight gain)
occurred significantly in children less than 2
years old. This finding was compatible with
other studies[2,3,7].
The overall mortality of 16.6% in present
study was lower as compared to other pediatric
hospital based series, 26% from Nigeria[6] and
about 35% in India and Malaysia series[3,7]. Our
mortality rate was slightly higher than UK study
of 12%[2]. Although mortality following non‐
traumatic coma was high in these studies but it
is considerably lower than reported adult
hospital data where mortality rates of 60% and
neurologically intact survivor rates of 10% are
seen[10]
In the present study incidence and outcome of
coma was not associated with gender. Other
studies did not show any significant difference in
the incidence of coma between the two sexes
Iran J Pediatr; Vol 19 (No 4); Dec 2009
either[2,6,7]. However, earlier studies[11] had
shown a greater mortality in male (42%)
compared to female children (20%).
Mortality rate among children under 2 years
was significantly higher in our study.
Other studies also showed that mortality was
higher in younger children[2,3].
In our study accidents and infectious etiology
showed higher mortality rates compared to
other etiology groups. In the study by Arun
Bansal et al[3] infectious etiology resulted in
highest death rate followed by toxic metabolic
etiology. Study from Malaysia[7] also reported
highest death rate in infectious group.
Among survivors of infectious disease in our
study only one third had normal outcome and
the remainder left hospital with some degree of
disability. This is compatible with Wong, Bansal
and Sofiah studies[2,3,7]. In contrast, some earlier
studies revealed that 60% to 75% of the
infectious group had a good outcome compared
with 36% and 47% respectively in the metabolic
group[12‐14].
Non‐traumatic refractory increased
intracranial pressure is a leading cause of
morbidity and mortality in these children and
decompressive craniotomy with or without
opening the dura is an effective and lifesaving
technique that should be considered[15,16].
Because of the retrospective nature of our
study it was not possible to provide information
on cognitive and adaptive outcome among
survivors.
Forsyth et al[13] have highlighted significant
cognitive dysfunction following non‐traumatic
coma in childhood, and provided further support
for the hypothesis of increased vulnerability of
very young brains to cognitive malfunction
following brain injury.
Pediatric non‐traumatic coma is an important
health problem making significant demands of
intensive and high dependency care resources. It
can result from a wide variety of primary
etiologies, posing a diagnostic challenge on
medical staff. A better understanding of the
causes and outcome of this heterogeneous group
of children will aid a design of protocols for their
investigation and management.
397
Conclusion
The present study demonstrated that infection
was the commonest cause of non‐traumatic
coma. Accidents and infection etiology had
higher mortality compared to other groups.
Systemic presentations at admission were
particularly common in children under 2 years
of age.
Acknowledgment
The study was approved by the research
committee of Iran University of Medical Sciences.
We would like to thank nursing staff of the
pediatric intensive care unit of Rasool Akram
Hospital for their love and endless devotion to
critically sick children.
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