ABSTRACT.
Nontraumatic coma (NTC) is a considerable cause of morbidity and mortality in children. This prospective observational study aimed to determine the clinico-etiological profile of NTC in children and delineate clinical signs predicting mortality in Upper Egypt from June 2019 to May 2020. All children from 1 month of age to 16 years who were admitted with NTC were included in the study. All patients received full histories and physical examinations, including Glasgow Coma Scale (GCS). Routine laboratory investigations including complete blood count, electrolytes, blood sugar, serum creatinine, and liver function tests were performed for all patients. Specific investigations such as metabolic studies, lumbar punctures, brain computed tomography scans, and magnetic resonance imaging were done when indicated. The precise etiology was determined and clinical presentations for survivors and nonsurvivors were compared. Among the 137 cases of NTC identified, central nervous system (CNS) infections were the most common cause leading to 38 cases, followed by toxic causes in 37 cases, status epilepticus in 22 cases, and metabolic causes in 21 cases. Hypothermia, hypotension, abnormal respiratory patterns, muscle hypotonia, absent corneal reflex, presence of shock, and need for mechanical ventilation were significantly correlating with mortality. The estimated mortality rate was 18.2% and all cases with GCS < 5 died. Toxic causes were the most commonly identified etiology in patients who died. In conclusion, the authors identified several etiologies for NTC in Upper Egypt and their corresponding clinical signs at presentation. This information can be used to improve the clinical care provided to children with NTC.
INTRODUCTION
Coma is a state of unarousable unresponsiveness in which the patient lies with closed eyes and without awareness of self and surroundings. 1 Impaired consciousness and coma are signals for widespread dysfunction of the central nervous system (CNS). It could point to damage involving the cerebral cortex, diencephalon, or the brainstem with considerable risk of morbidity and mortality. 2 Nontraumatic coma (NTC) is caused by a wide variety of conditions, some of which are more common than the others. It constitutes an important pediatric emergency and clinical evaluation can be vital for diagnosis in some cases. Intracranial hemorrhage (ICH) and CNS infection are common causes of structural coma, whereas nonstructural etiologies may result from poisoning, epilepsy, metabolic derangement, hepatic encephalopathy, and uremic encephalopathy. 3 It is difficult to predict the outcome of coma early in the course of illness, especially in children. There have been many studies suggesting useful prognostic parameters for coma in adults, but limited research has been published about the prognosis of NTC in children. 4 Depending on the underlying etiology of NTC, some children experience a full neurological recovery, whereas other children suffer considerable morbidity and mortality. 5, 6 Coma because of an underlying metabolic, endocrine, or toxic etiology is often reversible with rapid and appropriate treatment. As the etiology of NTC greatly impacts the management approach, it is useful to categorize patients based on the presence of focal or lateralizing signs, versus those without focal or lateralizing signs and those with versus without signs of meningeal irritation. Focal or lateralizing signs point to cerebrovascular events, whereas signs of meningeal irritation points to meningoencephalitis. Lack of focal findings on examination suggests metabolic, infectious, or toxic causes of NTC. 7, 8 As there are scarce details about NTC in our country, this study was designed to identify common etiologies and delineate possible clinical parameters predicting mortality in these patients. In southern Egypt and nearby Iran, the geographical regions and hot climate conditions have resulted in increased incidence of scorpion stings, which could also be an etiology of NTC. 9, 10 A better understanding of the causes and outcome of NTC in Upper Egypt is essential to improve how we approach and manage NTC.
MATERIALS AND METHODS
Subjects.
This prospective observational study was conducted in the pediatric emergency and intensive care units (ICUs) of South Valley University Hospital, Qena Governorate, in the southern region of Egypt from June 2019 to May 2020. All children from 1 month to 16 years of age who were admitted with NTC were included in the study. Coma was estimated by nonintentional failure of spontaneous eye opening or in response to noise, inability to obey commands, or localize painful stimulus with or without the ability to express words or age-appropriate language responses. 11 Children with neurological developmental delay or preexisting neurological illness such as cerebral palsy were excluded from the study.
Measurements.
All patients were evaluated at the time of admission with complete history and physical examinations, including complete neurological exams. Comas were identified in patients with a Glasgow Coma Scale (GCS) ≤ 8 12 and GCS of less than 6 was reported to have poor outcomes. 13 For children less than 5 years old, the James’ adapted GCS (JGCS) with a score of ≤ 8 was used to identify patients with comas. 14 Both the GCS and JGCS are assessment tools with a 15-point scale measuring patients verbal, motor, and eye responses. As young children may not use words in a manner that fits the standard GCS, the JGCS developed a verbal score for children less than 5 years old, describing age-appropriate measure of verbal responsiveness that corresponds with the standard GCS verbal score. Rather than assessing the verbal responses as in the GCS (none, incomprehensible sounds, inappropriate words, confused, and oriented verbal responses scored 1–5, respectively), the JGCS uses assigns a score of 1–5 based on if a patient has no verbal response, moans in response to pain, cries in response to pain, irritable/crying, or coos and babbles. Van de Voorde et al. 15 reported that JGCS had the same predictive ability for disability and mortality as the standard GCS in children (0–18 years).
Routine laboratory investigations including complete blood count, electrolytes, blood sugar, serum creatinine, and liver function tests were performed for all patients. Specific investigations such as blood and cerebral spinal fluid (CSF) cultures, metabolic studies, lumbar punctures, brain computed tomography (CT) scans, and magnetic resonance imaging (MRI) were done when indicated. Lumbar puncture was delayed or not performed if a contraindication existed, including signs of elevated intracranial pressure, focal neurological signs, local infection in the area of puncture, signs of bleeding disorders, or cardiorespiratory compromise. Direct gram stains were done on CSF as well as inoculation onto chocolate agar and blood agar. Blood cultures were considered negative if no growth was seen after 7 days of incubation. Samples from positive blood cultures were evaluated by gram stains to determine subsequent choice of enriched and/or selective media for subculture. Polymerase chain reaction (PCR) was performed to detect viral pathogens in suspected encephalitis.
Protocol for assessing cases.
We worked to appropriately diagnose all children with NTC. Encephalitis, bacterial meningitis, status epilepticus, diabetic ketoacidosis, hypoglycemia, and inborn errors of metabolism (IEM) were diagnosed as delineated here. Diagnostic criteria for viral encephalitis included an altered mental status or impaired consciousness that persist more than 24 hours along with two or more of the following: fever, seizure activity, focal neurological deficit, leucocytic count in CSF > 5 cells/mm3 with a lymphocyte predominance, abnormal brain imaging (CT or MRI) or electroencephalogram (EEG), and no other specific diagnosis. 16 Bacterial meningitis was diagnosed using the World Health Organization criteria for meningitis. These criteria include clinical symptoms of meningitis (i.e., fever, headache, neck stiffness, bulging fontanel, or altered mental status) and CSF with elevated protein (> 100 mg/dL), decreased glucose (< 40 mg/dL), and leukocytosis (> 100 cells/mm3) with at least 80% neutrophils. 17 The diagnosis of status epilepticus was given when patients had > 30 minutes of continuous seizure activity or two or more sequential seizures without fully regaining consciousness in between over a time period of > 30 minutes. 18 Status epilepticus can stem from prolonged febrile convulsion, epilepsy, CNS infections, metabolic derangements, and poisonings. In our study, we listed the diagnosis of status epilepticus for children with epilepsy separately from status epilepticus from other causes. Diabetic ketoacidosis, hypoglycemia, and IEM were all qualified together as “metabolic” etiologies. Cases of NTC that had unexplained or intractable seizures, persistent metabolic acidosis, persistent vomiting, a positive family history, and/or familial consanguinity were screened for IEM. Blood sample collection was done via a heel prick. The first drop of blood was discarded, then the next blood drops applied to the center of the circles of filter paper, making sure that each drop would permeate through the back of the filter paper. All the rings were filled, then the filter papers shipped to referral laboratory for performing Tandem mass spectrometry (MS/MS) to diagnose IEM. Congenital malformations, obstruction of cerebrospinal fluid flow including complications from attempted surgical correction, and shunt dysfunction were all classified as CNS anomalies.
Regarding imaging, conventional EEGs were obtained with eight channels and scalp electrodes placed using the international 10–20 system with bipolar and referential montages using Nihon Kohden equipment and interpreted by one of our pediatric neurologists. Brain CT scans were obtained on GE Lightspeed Ultra 8 Slice scanner with a slice thickness 5–8 mm (Radimage Technologies Private Limited, Haryana, India). Brain MRI was performed with Siemens Sempra 1.5 T superconducting MRI scanner, with an eight-channel neurovascular coil (Siemens Medical Solutions USA, Inc.). CT and MRI reports were interpreted by two qualified radiologists in our hospital.
The protocol for managing NTC started by focusing on maintenance of airway and systemic circulation followed by correcting significant metabolic derangements. Shock and hypoglycemia were rapidly treated and adequate nutrition was maintained. Clinical seizures were treated immediately and a standard protocol for the management of status epilepticus was followed. In ICUs, the status epilepticus protocol consisted of intravenous (IV) diazepam (0.15–0.2 mg/kg/dose; repeated once if needed). If seizures continued, IV phenytoin was given 15–18 mg/kg at a rate of 50 mg/minute. If seizures were still not controlled, general anesthesia was initiated and IV phenobarbital was used with a bolus of 10–15 mg/kg followed by a maintenance rate of 0.5–1 mg/kg/hour.
For proven meningitis and viral encephalitis, a third-generation cephalosporin or acyclovir were given, respectively. Diabetic ketoacidosis was treated in the ICU with IV fluids and electrolyte replacement in addition to insulin therapy. The treatment of organophosphorus poisoning included decontamination and atropine. Pralidoxime was added in the presence of nicotinic manifestations. Antivenom was the main treatment of envenomation. For all envenomations, supportive measures were implemented and a ventilator was readied in case mechanical ventilation became indicated.
All patients were followed until hospital discharge or time of death, if this occurred in the hospital. Mortality rate was calculated based on whether the patient died in the hospital or survived until discharge. This study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000 and approved by ethical committee of our university (SVU/MED/PED502/4-2019). Consent was taken from parents for participation in the study.
STATISTICAL ANALYSES
Statistical analyses of data collected from children admitted with NTC were compared using SPSS version 20 for Windows (Chicago, IL). Continuous variables were expressed as mean ± SD, and categorical variables were expressed as frequency. The study variables were analyzed for their association with immediate outcomes by applying χ2 test and Fisher’s exact test as applicable. Fisher’s exact test was used mainly when the sample size was small. Statistically significant variables found on χ2 and Fischer’s exact tests were further analyzed using logistic regression analysis for their independent association with mortality. A P value of < 0.05 was considered statistically significant.
RESULTS
During the 1-year study, a total of 137 cases of NTC were identified and enrolled in the study. Of these 137, 61 (44.5%) cases were < 5 years, 29 (21.2%) were between 5 and 10 years of age, and 47 (34.3%) were > 10 years old. Table 1 shows causes of NTC by age. Central nervous system infections were the most common cause in 38 (27.7%) cases, followed by toxic causes in 37 (27%) and status epilepticus in 22 (16%) cases. Viral encephalitis was the most common CNS infection followed by bacterial meningitis and brain abscesses. Contiguous infections (otitis media and mastoiditis) caused two of the brain abscesses, whereas remote infections (one in the course of severe pneumonia and two in the course of septicemia) led to three additional brain abscesses. Scorpion envenomation was the most common toxic cause of NTC followed by organophosphates poisoning. Scorpion envenomation was more frequent in children 5–10 years of age and those > 10 years than those younger than 5 years. On the other hand, organophosphates poisoning was more frequent in those younger than 5 years and > 10 years than children 5–10 years of age. Diabetic ketoacidosis was the most common metabolic cause being more frequent in children < 5 years and > 10 years old. Inborn errors of metabolism were detected in two cases. One patient had glutaric acidemia and another patient had propionic academia. Glutaric and proprionic acidemia are specific inherited disorders of metabolism that have marked diagnostic difficulty in low- and middle-income countries where access to advanced diagnostic approaches is limited because of resource constraints.
Table 1.
Causes of NTC by age
| Cause of NTC (total number = 137) | < 5 years, N (%), Total = 61 | 5–10 years, N (%) Total = 29 | > 10 years, N (%), Total = 47 | |
|---|---|---|---|---|
| Infections (38) | Acute bacterial meningitis (6) | 4 (6.6) | 2 (6.9) | 0 (0) |
| Viral encephalitis (27) | 11 (18) | 9 (31) | 7 (14.9) | |
| Brain abscess (5) | 3 (4.9) | 1 (3.4) | 1 (2.1) | |
| Toxic (37) | Scorpion envenomation (21) | 6 (9.8) | 6 (20.7) | 9 (19.1) |
| Organophosphates poisoning (15) | 7 (11.5) | 1 (3.4) | 7 (14.9) | |
| Snake envenomation (1) | 0 (0) | 0 (0) | 1 (2.1) | |
| Status epilepticus (children with epilepsy) (22) | 4 (6.6) | 8 (27.5) | 10 (21.2) | |
| Metabolic (21) | Diabetic ketoacidosis (16) | 7 (11.5) | 3 (10.3) | 6 (12.8) |
| Hypoglycemia (3) | 2 (3.3) | 1 (3.4) | 0 (0) | |
| Inborn errors of metabolism (2) | 2 (3.3) | 0 (0) | 0 (0) | |
| CNS anomalies (9) | 7 (11.5) | 2 (6.9) | 0 (0) | |
| ICH (6) | 4 (6.6) | 2 (6.9) | 0 (0) | |
| Drowning (2) | 0 (0) | 2 (6.9) | 0 (0) | |
| Unknown (2) | 2 (3.3) | 0 (0) | 0 (0) | |
CNS = central nervous system; ICH = intracranial hemorrhage; N (%) = number (percentage); NTC = nontraumatic coma.
Table 2 shows frequency of clinical findings according to etiology of NTC. Hypotension, abnormal respiratory patterns, absent corneal reflex, papilledema, muscle hypotonia, cranial nerve palsy, and GCS < 6 were significantly more common in NTC cases because of toxic and IC hemorrhage causes. Complications such as shock, pneumonia, pulmonary edema, and arrhythmia more commonly occurred with toxic etiologies. Need for mechanical ventilation and inotropes were more common with toxic and IC hemorrhage causes. Table 3 shows mortality associated with NTC by etiology. The mortality rate was higher for patients with toxic induced comas (38.2%) than from CNS infections (20.6%) and status-epileptics (11.8%). Table 4 shows the clinical features of patients at admission in relation to outcome. Mortality was higher in children older than 10 years and younger than 5 years and males had higher mortality than females. Some clinical features were associated with significantly higher mortality if present at admission, including hypothermia, hypotension, abnormal respiratory patterns, absent corneal reflex, papilledema, cranial nerve palsy, and lower GCS. Complications, mechanical ventilation, and inotropes were significantly associated with higher mortality. Significant variables were considered for multivariate analyses (Table 5). The independent factors predicting poor outcome were toxic causes, IC hemorrhage, presence of hypothermia, hypotension, abnormal respiratory pattern, hypotonia, absent corneal reflex, GCS < 6, presence of shock, and need for mechanical ventilation.
Table 2.
Frequency of clinical findings according to etiology of NTC
| Clinical features of NTC | Infections (38), N (%) | Toxic (37), N (%) | Status (22), N (%) | Metabolic (21), N (%) | CNS anomalies (9), N (%) | ICH (6), N (%) |
|---|---|---|---|---|---|---|
| Hypothermia (23) | 4 (10.5) | 10 (27) | 2 (9) | 3 (14.3) | 3 (33.3) | 1 (16.6) |
| Hypotension (33) | 6 (15.9) | 13 (35.1) | 5 (22.7) | 5 (23.8) | 2 (22.2) | 2 (33.2) |
| Abnormal respiratory pattern (6) | 1 (2.6) | 3 (8.1) | 0 | 0 | 0 | 2 (33.3) |
| Absent corneal reflex (11) | 2 (5.3) | 6 (16.2) | 0 | 1 (4.7) | 1 (11.1) | 1 (16.6) |
| Papilledema (25) | 8 (21.2) | 1 (29.7) | 1 (4.5) | 1 (4.7) | 1 (11.1) | 3 (50) |
| Cranial nerve palsy (22) | 6 (15.9) | 10 (27) | 1 (4.5) | 0 | 3 (33.3) | 2 (33.3) |
| Hypotonia (39) | 13 (34.2) | 21 (56.7) | 0 | 0 | 2 (22.2) | 3 (50) |
| GCS < 6 (34) | 13 (34.2) | 17 (45.9) | 0 | 0 | 1 | 3 (50) |
| Shock (21) | 4 (10.6) | 15 (40.5) | 1 (4.5) | 0 | 0 | 1 (16.6) |
| Pneumonia (23) | 7 (18.4) | 12 (32.4) | 1 (4.5) | 1 (4.7) | 2 (22.2) | 0 |
| Pulmonary edema (10) | 2 (5.3) | 8 (21.6) | 0 | 0 | 0 | 0 |
| Arrhythmia (9) | 3 (7.9) | 4 (10.8) | 0 | 0 | 1 (11.1) | 1 (16.6) |
| Need for MV (19) | 5 (13.1) | 10 (27) | 3 (16.5) | 0 | 0 | 1 (16.6) |
| Need for inotropes (15) | 3 (7.9) | 8 (21.6) | 3 (16.5) | 0 | 0 | 1 (16.6) |
CNS = central nervous system; GCS = Glasgow coma scale; ICH = intracranial hemorrhage; MV = mechanical ventilation; NS = nonsignificant; significant P value < 0.05; N (%) = number (percentage); NTC = nontraumatic coma.
Table 3.
Mortality associated with NTC by etiology
| Variable (total number = 137) | Survivors, N (%), Total = 103 | Nonsurvivors, N (%), Total = 34 | P value | |
|---|---|---|---|---|
| Cause | Infections (38) | 31 (30) | 7 (20.6) | 0.043 |
| Toxic (37) | 24 (23.3) | 13 (38.2) | 0.041 | |
| Status (22) | 18 (17.5) | 4 (11.8) | 0.42 | |
| Metabolic (21) | 19 (18.4) | 2 (5.9) | 0.018 | |
| CNS anomalies (9) | 6 (5.8) | 3 (8.8) | 0.67 | |
| ICH (6) | 3 (2.9) | 3 (8.8) | 0.037 | |
| Drowning (2) | 2 (1.9) | 0 (0) | 0.23 | |
| Unknown (2) | 1 (0.95) | 1 (2.9) | 0.78 | |
CNS = central nervous system; ICH = intracranial hemorrhage; NS = nonsignificant; significant P value < 0.05; N (%) = number (percentage); NTC = nontraumatic coma.
Table 4.
Clinical features of studied patients at admission in relation to outcome
| Clinical features of NTC (total number = 137) | Survivors, N (%), Total = 103 | Nonsurvivors, N (%), Total = 34 | P value | |
|---|---|---|---|---|
| Age | < 5 years (61) | 41 (39.8) | 20 (58.8) | 0.038 |
| 5–10 years (29) | 27 (79.4) | 2 (5.9) | < 0.001 | |
| > 10 years (47) | 35 (33.9) | 12 (35.2) | 0.178 | |
| Sex | Males (61) | 42 (40.8) | 19 (55.9) | 0.025 |
| Females (76) | 61 (59.2) | 15 (44.1) | 0.029 | |
| Hypothermia at admission (23) | 5 (4.9) | 18 (52.9) | < 0.001 | |
| Hypotension at admission (33) | 10 (9.7) | 23 (67.6) | < 0.001 | |
| Abnormal respiratory pattern (6) | 1 (0.97) | 5 (14.7) | 0.006 | |
| Absent corneal reflex (11) | 4 (3.9) | 7 (20.6) | 0.009 | |
| Papilledema (25) | 7 (6.8) | 18 (52.9) | < 0.001 | |
| Cranial nerve palsy (22) | 7 (6.8) | 15 (44.1) | < 0.001 | |
| Hypotonia (39) | 16 (15.5) | 23 (67.6) | < 0.001 | |
| GCS | Score 8 (27) | 24 (23.3) | 3 (8.8) | 0.006 |
| Score 7 (37) | 29 (28.2) | 8 (23.4) | 0.96 | |
| Score 6 (38) | 32 (31.1) | 6 (17.6) | 0.008 | |
| Score 5 (27) | 18 (17.5) | 9 (26.5) | 0.047 | |
| Score 4 (4) | 0 (0) | 4 (11.7) | 0.024 | |
| Score 3 (4) | 0 (0) | 4 (11.7) | 0.024 | |
| Complications | Shock (21) | 8 (7.8) | 13 (38.2) | 0.009 |
| Pneumonia (23) | 7 (6.7) | 16 (47) | 0.006 | |
| Pulmonary edema (10) | 5 (4.9) | 5 (14.7) | 0.039 | |
| Arrhythmia (9) | 3 (2.9) | 6 (17.6) | 0.047 | |
| Need for mechanical ventilation (19) | 5 (4.9) | 14 (41.1) | 0.008 | |
| Need for inotropes (15) | 5 (4.9) | 10 (29) | 0.031 | |
GCS = Glasgow coma scale; NS = non-significant; significant P value < 0.05; N (%) = number (percentage); NTC = nontraumatic coma.
Table 5.
Multivariate regression analysis to determine independent risk factors of mortality
| Variable | Confidence | ||||
|---|---|---|---|---|---|
| Odd ratio | Interval (95%) | P value | |||
| Lower | Upper | ||||
| Etiology of NTC | CNS infections | 1.81 | 0.79 | 4.18 | 0.64 |
| Toxic causes | 4.03 | 1.52 | 10.68 | 0.014 | |
| Metabolic causes | 1.21 | 0.67 | 2.19 | NS | |
| ICH | 2.73 | 1.03 | 7.25 | 0.019 | |
| Clinical features of NTC | Hypothermia | 5.58 | 1.76 | 17.92 | 0.009 |
| Hypotension | 3.66 | 2.03 | 6.53 | 0.007 | |
| Abnormal respiration | 1.97 | 1.02 | 3.74 | 0.032 | |
| GCS < 6 | 2.42 | 1.17 | 5.03 | 0.007 | |
| Hypotonia | 1.49 | 1.36 | 4.58 | 0.006 | |
| Absent corneal reflex | 2.96 | 1.32 | 6.63 | 0.006 | |
| Shock | 3.73 | 1.24 | 11.26 | 0.009 | |
| Need for MV | 3.89 | 1.9 | 7.8 | 0.008 | |
CNS = central nervous system; GCS = Glasgow coma scale; ICH = intracranial hemorrhage; MV = mechanical ventilation; NS = nonsignificant; significant P value < 0.05; NTC = nontraumatic coma.
DISCUSSION
Nontraumatic coma is one of the most important medical emergencies in pediatric intensive care. Nontraumatic coma requires rapid diagnosis and treatment. Knowledge of the most frequent etiologies of NTC, associated clinical signs, and predicted mortality might improve outcomes. This study attempts to identify the common etiological factors and clinical characteristics of NTD in Upper Egypt and elucidate predictors of mortality in these patients. Our study builds on several other studies showing CNS infections as most commonly causing NTCs, followed by toxic causes. These etiologies are slightly different than those found in Turkey where hypoxic ischemic encephalopathy was as common as CNS infections. 19 – 22 In accordance with Gwer et al., 23 our study showed that viral encephalitis was the most common CNS infection. This differs from other studies that revealed a higher frequency of acute bacterial meningitis. 24 Interestingly, in our study, toxic causes approximated the same frequency as CNS infections, especially scorpion envenomation and organophosphates poisoning. Additionally, we found toxic causes as the most common cause of death, which is different from other studies where CNS infections were documented as the most common cause of mortality. 24 – 26
It is possible that the increase in scorpion envenomation is because of our climate. The south of Egypt is the hottest area in Egypt, scorpions have a known thermophilic nature, 27 and scorpion envenomation is considered a major health problem facing our inhabitants. Organophosphate poisoning is also a well-known cause of harm in our area, whether unintentional or suicidal. Organophosphates are used excessively as insecticides and pesticides in our area. Our region is mainly dependent on agriculture with pesticides readily available, even in homes. Therefore, pesticides are easily accessible by children exposing them to unintentional poisonings. Older children usually work with their parents on the farms; therefore, they are more susceptible to skin contact and inhalation of organophosphates used for pest control. Additionally, in rural areas, there is wide use of remedies for scalp pediculosis that contain organophosphates. This adds to the danger of contact exposure and skin absorption. That we noticed the highest incidence of organophosphate poisoning in children more than 10 years old may be because of increased incidence of suicidal attempts in this age. The organophosphate poisoning in children less than 5 years is more likely explained by accidental ingestion. Overall mortality in our study was 18.2%, which is comparable to studies done by Forsberg et al., 6 Chelliah et al., 28 and Khodapanahandeh and Najarkalayee, 29 who reported 35%, 8.6%, and 16.6% mortality rates, respectively. We detected the highest mortality from NTCs to be in children below 5 years of age. This may be because of higher serum toxin levels in poisoned children in relation to their small body mass and excessive vulnerability of the heart and other organs to higher venom or toxin uptake in young children. 30 Furthermore, congenital CNS malformations increased risk of mortality in this age group. In agreement with the study of Ahmed et al., 24 hypothermia, hypotension, and abnormal respiratory pattern were found to be significantly associated with mortality. Owolabi et al. 31 reported abnormal breathing patterns as significantly associated with deaths because of NTC, but they also noticed significantly higher mortality in the presence of systemic hypertension, which we did not find. Our study was also consistent with their finding that lower GCS score was accompanied with poor prognosis and higher mortality rate. 6, 28 Furthermore, all of our patients who presented with a GCS less than 5 died. Owolabi et al. 31 reported that patients with 3–5 GCS scores had a greater possibility of death and prolongation of coma than those with scores of 6–8. Another important cause of mortality in our patients was shock. Shock occurred in 21 of our studied patients, and 13 of these patients died. This correlates with the study of Pankaj et al., 32 and signifies the importance of prompt recognition and treatment of shock, including immediate transfer of hypotensive children with NTC to sites where cardiorespiratory stabilization and appropriate fluid resuscitation can occur, or improving the ability for resuscitation to be initiated at all cites where children present.
The main strength of this study is its prospective design that avoids mistakes of retrospective studies implemented by absent or inaccurate records. However, this study has some limitations. First, it is a single-centered study that limits the generalizability of our findings. Another limitation is the small sample size of study. More studies on a larger scale and multiple centers are recommended, and are needed to further elucidate risk factors for NTC and better specify which factors predict and alter outcomes.
CONCLUSION
In our area of Upper Egypt, CNS infections are the most common cause of NTC in childhood, whereas exposures to toxins such as scorpion envenomation and organophosphate poisoning are the leading cause of death associated with NTCs.
Supplemental Material
ACKNOWLEDGMENTS
The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.
Note: Supplemental table appears at www.ajtmh.org.
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