Outcome Predictors of Non Traumatic Coma with Infective Etiology in Children

Transcription

1 Available online at Original research article JPBMS ISSN NO CODEN JPBSCT JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES Outcome Predictors of Non Traumatic Coma with Infective Etiology in Children *Buch Pankaj M 1, Parmar Parin 2, Doshi Smita K 3, Chudasama Rajesh K 4 1M.D. (Pediatrics),Professor, Department of Pediatrics, M P Shah Medical College, Jamnagar, Gujarat, India, 2M.D. (Pediatrics), Assistant Professor, Department of Pediatrics, P D U Medical College, Rajkot, Gujarat, India. 3M.D. (Pediatrics), Professor & Head Department of Pediatrics, P D U Medical College, Rajkot, Gujarat, India. 4M.D. (Community Medicine), Associate Professor, Department of Community Medicine, M P Shah Medical College, Jamnagar, Gujarat, India. Abstract: Objective: To evaluate possible predictors of immediate outcome in non-traumatic coma in children with infective etiology. Method: An observational prospective study was conducted over a period of 15 months from 1 st June 2009 to 31 st August 2010 at Department of Pediatrics, Government Medical College, Rajkot, Gujarat, India. Children aged 6 months to 12 years presenting with non-traumatic coma with history, clinical features and laboratory studies suggestive of infective etiology were followed upto immediate outcome. A complete history, general and systemic examination at presentation was recorded. Relevant laboratory and radiological investigations were performed and GCS was recorded every 6 hourly until the immediate outcome. The etiology of coma was determined on the basis of history, clinical examination and investigations. Results: CNS infections (n=34), Respiratory tract infections (n=26) and sepsis (n=34) were most common etiology of non traumatic coma. Severe malnutrition and Anemia were comman associated conditions. Thirty Eight (40.4%) survived and Fifty six patients (59.6%) died. survival was better with Meningitis compared to sepsis (p=0.007). GCS <5 on admission, Shock on presentation, Hypothermia, associated severe Malnutrition and significant anemia, Severe dehydration,, abnormal breathing Pattern, Nonreactive Pupils and jaundice correlated significantly with mortality. On logistic regression poor pulse volume, GCS at 24 hrs <5, CNS infection, Jaundice; severe dehydration and significant Anemia were independent significant predictors of death. Conclusion: CNS infections, Respiratory infections and sepsis were most comman cause of non traumatic coma. Shock and Severe Malnutrition contributes to adverse outcome. Simple clinical signs and GCS were good predictors of outcome. Keywords: Non-traumatic coma in children, infective etiology, Predictors of mortality. Introduction: Non-traumatic coma (NTC) in childhood is an important pediatric emergency and accounts for high morbidity and mortality in pediatric age group. It can result from wide range of primary etiologies. Etiology of coma and clinical status at the time of admission are likely outcome predictors. Infection is the commonest etiology for coma in all age groups. [1-3] Coma in children is recognized to be a non-specific sign with a wide potential differential diagnosis. Among various etiological factors identified for non-traumatic coma, considerable regional diversity exists in them with infectious problems suggested to be more common in developing countries. There has been few case series in developing countries with specific reference to infective etiology and there are also differences in infective agents between developing and developed countries. Similarly prediction of outcome of coma is difficult early in the course of the illness, especially in children. There have been many studies suggesting prognostic parameters of coma in adults, but limited reviews are available for children. [2] Due to regional variations in etiology, study of common etiologies of non-traumatic coma due to infective causes in different regions is required. Also a comprehensive study of history, clinical features and laboratory parameters that may predict poor outcome in infective non-traumatic coma is desired. The current study was undertaken in an attempt to fulfill this requirement in the Referral and Pediatric Intensive care Unit by identifying common etiologies of infective NTC and also by identifying possible clinical and laboratory parameters as predictors of mortality in these patients. Material and Method: Coma was defined as unintentional failure of the patients to open their eye spontaneously or in response to noise, inability to obey commands or localize painful stimulus with or without the ability to express comprehensible words or age appropriate language responses. [1, 4] This prospective study was conducted in Pediatric Intensive Care Unit (PICU) in the department of pediatrics, over a period of 15 months, from 1 st June 2009 to 31 st August All patients aged 6 months to 12 years presenting to emergency department with coma with less than 7 days history, without a preceding history of trauma and in whom infective etiology was suspected by history, physical examination and laboratory study. Clinical 1 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 12, Issue 12

2 suspicion of Infective etiology was later on confirmed by appropriate laboratory and other tests. The study was conducted after approval from institutional ethical committee of the medical college. Among total of 111 patients of Non traumatic coma, who were brought to Pediatric department, infective etiology was suspected in 94 of the patients and they were enrolled in the present study. Patients were followed up to immediate outcome, i.e., intact survival and discharge or expiry. After getting informed consent from the parents, they were interviewed for clinical history of the patients. A complete clinical examination of the patients at the time of admission, including vitals, general examination, and anthropometry with Indian Academy of Pediatrics (IAP) classification for malnutrition and systemic examination with particular emphasis on central nervous system were conducted. Modified Glasgow Coma Scale (GCS) was recorded on admission and then every 6 hourly till the immediate outcome. Bacterial meningitis, sepsis and Cerebral Malaria were defined as per standard guidelines. [5-6] Diagnosis of Tuberculus meningitis was based on criteria by Ahuja et al. [7] Encephalitis was defined as acute febrile encephalopathy with CSF pleocytosis with lymphocytic predominance (>5 cells/cu mm) and absence of any other alternative diagnosis. Coma following hypoxic cerebral injury such as after cardio respiratory compromise was considered to be hypoxic-ischemic. Relevant laboratory investigations and imaging studies were performed. Complete blood counts with peripheral smear for malaria parasite and Blood sugar were done in all patients. Electrolytes, Blood culture, Serum. C - reactive protein (S.CRP), chest X ray, Mantoux test, urine and stool examination, liver and renal function test were done as relevant as the department is catering poor patients with limited resources. Patients in whom CNS infection was suspected, cerebro-spinal fluid (CSF) microscopy and bacterial culture was performed. Brain imaging studies were done as necessary and possible. In cases when available investigations did not gave a clear diagnosis, clinical diagnosis was made with help of history, physical examination and demography. Outcomes were classified as survived or expired. Definition of study variables were as follows, Buch Pankaj M et al. / JPBMS, 2011, 12 (12) Table 1 : Etiology of coma and comparison with outcome in study population Diagnosis/Associated Condition Comparison with Outcome Total n=94 (1) Bradycardia: heart rate less than 90/min for an infant and less than 60 /min for older children, (2) Hypotension: blood pressure below 5 th centile for age and sex. (3) Shock: cold hands with rapid weak pulse and capillary filling time more than 3 seconds. [8] (4) Hyperthermia: Axillary temperature more than 37.5 o C. [9] (5) Hypothermia: Axillary temperature less than 36 o C. (6) Severity of coma: as per score obtained on modified Glasgow coma scale. (7) Anaemia and its grade were defined as per standard guidelines. [10] Data was entered and analyzed with help of Epi Info version The study variables were analyzed for their association with immediate outcome by applying chi square test and Fisher s exact test as applicable. All P values were two tailed and P<0.05 was considered statistically significant. Variables that were found statistically significant on chi-square test were further analyzed using logistic regression analysis for their independent association with mortality. Results: A total of 94 comatose children (44 boys, 50 girls) were included in the study. Mean age of our Patients was 35.6 months. 86% patients were below 6 years of age and 14% patients were above 6 years with Male to Female ratio of 0.88:1.0. Etiological profile has been summarized in table 1. CNS infection accounting for coma was observed in 36.1% of Patients, where as severe respiratory infection as a major etiological factor presenting with coma due to cardio respiratory compromise was observed alone or in combination in 29.7% of patients. Similarly sepsis was observed in36.1% Patients. Immediate Outcome: Thirty Eight patients survived and Fifty six patients died. Mortality in present study was 56.4% for infants, 59.5% for age group of 1-3 years, 45.5% between age of 4-5 years and 45.8% above 6 years of age. Mortality was significantly higher with Sepsis (P<0.001) and viral Encephalitis (P>0.05) compared to bacterial meningitis and Cerebral Malaria presenting with coma. As a group CNS infection has significant better survival compared to Sepsis and severe respiratory infection. (P value <0.001) Survived n=38 Expired n=56 P-Value Acute bacterial Meningitis 9 6(66.6%) 3(33.4%) 0.34 Tuberculus meningitis 8 5(62.5%) 3(37.5%) 0.35 Viral Encephalitis 9 1(11.1%) 8(88.9%) 0.12 Cerebral Malaria 8 6(75%) 2(25%) 0.08 Resp.tract Infection* 26 14(53.8%) 12(46.2%) 0.10 Sepsis 34 6(17.6%) 28(82.4%) Resp.tract infection*=respiratory tract infection Predictors of Immediate Outcome on Admission: As summarized in table 2 predictors of immediate outcome were GCS <5 on admission and during subsequent examination at 24 hours, Shock on presentation, hypothermia, associated severe malnutrition, severe dehydration, abnormal breathing pattern, nonreactive pupils, associated anemia, and jaundice correlated significantly with mortality. They were further analyzed by logistic regression for their independent association with outcome. Age less than 6 years (odds ratio 1.63; 95%CI ), poor pulse volume 2 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 12, Issue 12

3 ( odds ratio 1.53 ; 95%CI ), GCS at 24 hrs <5 (odds ratio 2.43; 95%CI ), CNS infection (odds ratio 2.73; 95%CI ) jaundice (odds ratio 4.09; 95%CI ), severe dehydration (odds ratio5.48; 95%CI ) and associated anemia (odds ratio 3.89; 95%CI ) were significant independent predictors of death. (Table 3) Table 2: clinical parameters significantly associated with immediate adverse outcome Parameter/Variable comparison with outcome N Survived Expired P value Shock Severe Malnutrition Hypothermia <0.001 Severe dehydration * Jaundice * Abnormal Breathing * Non reactive pupils <0.001 Mod.to sev. Anemia GCS<5 on admission GCS<5 at 6 hrs <0.001 GCS<5 at 12 hrs <0.001 GCS<5 at 24 hrs *=Fisher s Exact test, Mod. to sev. Anaemia=Moderate to severe Anaemia, GCS=modified Glasgow coma scale Table 3: independent Predictors of immediate mortality in non traumatic coma with infective etiology Variable Comparison with immediate outcome of coma Total Survived Died Odd s ratio (95% CI) Age < 6years ( ) > 6year Poor Pulse volume ( ) GCS at 24 hrs < ( ) CNS infection ( ) Jaundice ( ) Severe Dehydration ( ) Moderate to severe Anaemia ( ) Discussion Pediatric coma has been a non specific sign of many systemic illnesses. NTC is a common presentation in pediatric patients accounting for an estimated 10-15% of all hospital admissions but with few studies on infective etiology. [1-4,12,14] Present study aimed at infective etiology among non traumatic coma as etiological profile is different in developing and developed countries. Despite its prevalence, associated morbidity and mortality, studies from developing countries are limited. In current study, associated severe malnutrition as well as anemia was observed in significant proportion of patients which was indirectly contributing to infant and childhood Mortality. In comatose patients poor score of modified Glasgow coma scale denotes wide spread damage to brain stem structures and/or cerebral hemispheres and may predict adverse outcome. GCS reflects integrity of cerebral hemispheres. Low score of GCS at time of admission is associated with higher mortality. (P <0.001 in present study) This finding was also observed in other studies as well published from same region. [1-2] at the same time No improvement of GCS over 24 hours of hospital stay was also associated with significant mortality, this is especially important for developing countries with resource limited set up for early identification of this important general danger sign as described in IMNCI [8-9] at grass route level so patients can be referred timely, with appropriate prereferral treatment for better survival. Infective pathologies remain the prime reason for comatose pediatric patients in developing countries and among infective etiology, CNS infections accounts for significant proportion. As reported by other studies. [1-2,12-13, 17-18] it was also observed that survival for CNS infection as one group is comparatively better than severe respiratory infection and sepsis which might be leading to cardio respiratory compromise with possible hypoxic ischemic damage to brain. Among infective causes of non traumatic coma Sepsis and respiratory tract infections were present in significant proportion in present study. C P Wong et. al. [12] also observed that systemic, Respiratory and CNS infections accounted for 90% of Infective etiology in their study. However in other studies sepsis was not a major cause leading to coma. [1,13,16-18] Such variation might be because of type of patients, time and problems while referral being catered by different hospitals vary significantly. At the same time malnutrition is also a significant problem in developing countries and it is commonly associated with severe infections including sepsis. The overall mortality in present study of 59.6% was higher than earlier study from India in which 26.7% mortality was observed in infective etiology but they have observed this mortality for only CNS infections. At the same time mortality rate was 72.3% below age of 6 years in same study. [2] Our study had 86% patients below six years of age so there is no much difference in mortality pattern. In a study from Pakistan, infections emerged as major cause of mortality (n=23/29, 79%) [1] So this affirms that still the infective etiology is a major cause presenting with non traumatic coma and high mortality in younger children. As already stated patients with severe malnutrition are at increased risk of developing sepsis and many of them also presented with severe dehydration (n=12) due to diarrhea with concomitant serious systemic infection. One of important finding in present study was 3 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 12, Issue 12

4 shock which was observed in 33 patients out of them 27 patients expired. Hypotension was also a poor prognostic sign in other studies. [2,13] This finding signifies the importance of immediate referral with pre-referral cardio respiratory stabilization and appropriate fluid resuscitation might improve outcome in pediatric coma with infective etiology in developing countries. Prognosis in coma also depends on its severity and one of important clinical tool for assessment is by modified GCS [15] in present study modified coma scale recorded at time of admission has significant association with outcome(p<0.001). Same has been observed by others. [2] Hypothermia was associated with poor prognosis in present study (P<0.001) and 30 out of 34 patients died. Same finding was observed by Johnston and Seshia in their study with 100% mortality among hypothermic children. [19] Different abnormal breathing pattern may be seen in coma depending on part of brain involved. abnormal breathing pattern including apneustic, ataxic, Chyene-Stokes respiration or neurological hyperventilation had significant association with poor outcome in present study. This further confirms observations of other studies. [2,19] Non reactive pupils at admission was strong predictor of mortality.(p<0.001)same has been consistently observed in other studies from developing as well as developed countries. [2,13,17] at the same time 1/3 rd of our patients with non reactive pupils on admission survived. In present study associated severe malnutrition, anemia, severe dehydration and jaundice correlated significantly with mortality. Severe Malnutrition did not showed significance as an independent predictor for mortality but it might be underlying factor contributing significantly to mortality. Number of patients presenting with jaundice as well as neck rigidity was very less to signify them as an independent variable that can affect mortality although found statistically significant. Associated Anemia was also significant for adverse immediate outcome but this finding to signify as independent predictor of mortality needs further study. Bradycardia on admission was not significantly associated with mortality in present study. In study by Ahmed S et al. [1] similar finding was observed but in study by Bansal A et al. [2] significant association was observed with mortality and six of seven patients with Bradycardia on admission died. So this clinical finding might need further study. Conclusion: CNS infections, Respiratory infections and sepsis were most common cause of non traumatic coma in present study. Shock and Severe Malnutrition contributes significantly for adverse outcome. Simple clinical signs and GCS were good predictors of outcome which can be well utilized in developing countries in small hospitals and resource limited setup. Although appropriate statistical tests were applied to minimize error, this remains a observational prospective study with small sample size. The findings of this study cannot be generalized though they are in relevance with present scenario in resource poor set up and in developing countries where infective etiology predominates for non traumatic coma and severe Malnutrition and anemia also very common contributing factor to mortality. To validate such findings larger studies are needed but at the same time this study has reaffirmed the Importance of clinical variables and modified GCS score for predicting outcome in non traumatic coma and need for understanding importance of severe malnutrition and anemia for better survival and reduction of infant and childhood mortality even in non traumatic coma. References: 1.Saba A, Ejaz K, Muhammad S, Salim M, Khan M. Non traumatic coma in pediatric patients: etiology and predictors of outcome. J Pak Med Assoc 2011; 61: Bansal A, Singhi S, Singhi P, Khandelwal N and Ramesh S. Non Traumatic coma. Indian J Pediatr 2005; 72: Trubel HK, Nortony E, Lister G. Outcome of coma in children. Curr opinion Peditr.2007; 15: Awasthi S. Moin S, Iyer SM, Rehman H. Modified Glasgow coma scale to predict mortality in children with acute infections of central nervous system. Nat Med J Ind 1997;10: Kliegman R, Behrman R, Jenson H, Stanson B, editors. Nelson Textbook of Pediatrics,18th ed. Elsevier:2008; World Health organization. Management of Severe Malaria: A Practical Handbook 2nd ed. Geneva; Ahuja GK, Mohan KK, Prasad K, Behri M. Diagnostic criteria for tuberculous meningitis and their validation. Tuber Lung Dis 1994; 75: Ministry of Health & Family Welfare. Participant Manual of Facility Based IMNCI. New Delhi: Government of India Publication; Ministry of Health & Family Welfare. Participant Module no 5 of IMNCI. Assess and classify the sick child. New Delhi: Government of India; World health Organization. Iron deficiency Anaemia: assessment, prevention and control. A guide for program managers. Geneva, ; Tasker RC, Col GF.EM, Acute encephalopathy of childhood and intensive care. In; Bret, EM, Editor. Pediatric neurology, 3rd edn.edinburgh; Churchill Livingstone, 1996; pp C P Wong, R J Forsyth P Kelly JA Eyre. Incidence, etiology and outcome of non- traumatic coma: a population based study. Arch Dis Child 2001; 84: Seshia SS, Seshia MMK, Sachdeva RK. Coma in childhood. Dev Med Child Neurol 1977; 19: Abend NS, Lichet DJ. Predicting outcome in children with hypoxic ischemic encephalopathy. Pediatrr crit care Med 2008; 9: Nayana PrabhaPC, Nalini P, Serene VT. Role of Glasgow coma scale in pediatric nontraumatic coma. Indian pediatr 2003; 40: Sofiah A, Hussain HM. Childhood non traumatic coma in Kuala Lumpur, Malaysia. Ann Trop Pediatr 1997; 17: Ogunmekan AO. Non traumatic coma in childhood etiology, clinical findings, morbidity, prognosis and mortality. J Trop Pediatr 1983; 29: Vijaykumar K, Knight R, Prabhakar P, Murphy PJ, Sharpes PM.Neurological outcome in children with non traumatic coma admitted to a regional pediatric intensive care unit. Arch Dis Child 2003; 88: Johnston B, seshila SS. Prediction of outcome in nontraumatic coma in childhood. Acta neurol Scand 1984; 69: Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 12, Issue 12

5 Source of funding: - Nil Conflict of Interest: - Not declared *Corresponding Author:- Dr. Pankaj Buch., Professor, Department of Pediatrics, M P Shah Medical College, Jamnagar, Gujarat, India. Pin: Contact no.: Quick response code (QR-Code) for mobile user to Assess JPBMS website electronically 5 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 12, Issue 12