Original Article
Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital
Journal of Child Neurology 2015, Vol. 30(13) 1736-1742 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815579706 jcn.sagepub.com
Eman F. Halawa, MD1, Iman Draz, MD1, Dalia Ahmed, MD1, and Hala A. Shaheen, MD2
Abstract Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. Keywords convulsive status epilepticus, outcome, predictors Received July 21, 2014. Received revised February 16, 2015. Accepted for publication March 07, 2015.
Convulsive status epilepticus is the most common neurologic emergency in childhood.1 It is one of the most common lifethreatening medical emergencies in childhood. The annual incidence in developed countries ranges from 10 to 73 per 100 000. The highest reported incidence is in children below 2 years of age, with the greatest peak during the first year of life. This variability may be due to different socioeconomic and ethnic characteristics of the population or environmental factors as trauma and infections.2-4 Convulsive status epilepticus is associated with significant morbidity and mortality. The mortality rate ranges from 0% to 13%.2,5-7 Mortality is mostly due to the underlying cause as intracranial infections or severe neurologic disabilities. However, some children have convulsive status epilepticus regardless of the underlying etiology.8 Guidelines for management of status epilepticus are continuously evolving.9 The importance of rapidly terminating prolonged seizures has been emphasized among different treatment protocols. It is estimated that the disability and mortality associated with refractory convulsive status epilepticus is significantly higher than that for nonrefractory convulsive status epilepticus, with 42% disability and 39% mortality rates, especially after few weeks of follow-up.10 The longer a seizure lasts, the less likely it is to stop within the next few minutes.11
Determining the predicting factors of disability and mortality of convulsive status epilepticus is important to modulate the management guidelines and thus improving prognosis. Important factors that can adversely affect neurologic outcome of status epilepticus include etiology, duration of seizure, and patient’s age.2,12,13 This study was conducted out to determine etiology, demographic data, clinical profile, and the predictors of disability and mortality in children with convulsive status epilepticus in a tertiary hospital in Egypt.
Methods This cohort study was carried out at the Cairo University’s Specialized Pediatric Hospital which is a 520-bed, university-affiliated teaching hospital in Cairo, Egypt. It is a referral hospital that provides primary
1 2
Faculty of Medicine, Cairo University, Cairo, Egypt Fayoum University, Giza, Egypt
Corresponding Author: Eman F. Halawa, MD, Faculty of Medicine, Cairo University, 23 Dr Naguib Mahfouz Street, Abbass Akad Street, Nasr City, Cairo, 12334, Egypt. Email: [email protected]
Downloaded from jcn.sagepub.com at CMU Libraries - library.cmich.edu on October 19, 2015
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to tertiary care for children. It encompasses 2 pediatric emergency intensive care units with 16 and 14 beds, respectively. We included a convenient sample of all patients from 1 month to 12 years old with convulsive status epilepticus admitted to the pediatric emergency intensive care unit of Cairo University’s specialized pediatric hospital, from December 2011 to December 2012. Convulsive status epilepticus was strictly defined as continuous, generalized, convulsive seizure lasting more than 5 minutes or 2 or more seizures during which the patient does not return to baseline consciousness.14 Episodes of convulsive status epilepticus after the first episode were defined as recurrent when both events took place during hospitalization. Patients were categorized according to their time to achieve seizure control: less than 30 minutes, between 30 and 60 minutes, and more than 60 minutes. Refractory convulsive status epilepticus was defined as prolonged seizures that fail to terminate after administration of 2 antiepileptic drugs with different mechanisms of action or that require continuously administered medication to abort seizures, regardless of seizure duration.15 Outcome was measured by the condition on discharge using the Glasgow Outcome Score which ranges from 1 to 5, defined as follows: 1 ¼ death, 2 ¼ vegetative state, 3 ¼ severe disability, 4 ¼ moderate disability, and 5 ¼ good recovery.16 For the purpose of analysis, patients with score 5 were defined as having good outcome and patients with score 1 to 4 were defined as having bad outcome. A structured institutional treatment regimen of pediatric status epilepticus has been used since 2004 in the pediatric emergency intensive care units in Cairo University’s specialized pediatric Hospital. Step I: After securing airway, breathing, and circulation, and checking blood glucose, children who presented with prolonged seizure (>5 minutes) received an intravenous bolus dose of 0.1 mg/kg diazepam. If seizure control was not achieved within 5 minutes, the same dose of diazepam was repeated up to 2 times. Step II: If seizure control was not achieved within 15 minutes of step I, a loading dose of 20 mg/kg phenytoin (1 mg/kg/min) was given. In patients unresponsive to loading phenytoin, an additional 10 mg/kg phenytoin was loaded 10 minutes after the initial phenytoin loading. Step III: In patients unresponsive to step II, the loading of 20 mg/kg phenobarbital was given. If unresponsive, an additional 10 mg/kg phenobarbital was loaded and could be repeated twice so that the total loading dose would be 40 mg/kg. Step IV: If the child continued to exhibit convulsions, a bolus of midazolam intravenously (0.15 mg/kg/dose) was given, and then the dose is increased every 5 minutes up to 0.6 mg/kg/min. After achieving seizure control, the infusion was continued for at least 24 hours. Subsequently, midazolam infusion was gradually decreased by 0.05 mg/kg/min every 6 hours until tapering was completed. If a seizure continued for 60 minutes after the infusion (0.6 mg/kg/min), the amount of midazolam in the maintenance infusion was increased up to 1.2 mg/kg/min. Step V: Unresponsive patients were intubated and an initial loading dose of 10 mg/kg intravenous thiopental was given followed by a continuous intravenous maintenance infusion of 3 to 5 mg/kg/h. After stabilization, the following data were recorded: demographic details, developmental history, history of coexisting medical diseases, history of epilepsy, antiepileptic drug use, and seizure type. Also, general examination, neurologic examination, and funduscopy were performed. Investigations including full blood count, blood sugar, serum calcium, serum electrolytes, blood urea, serum
creatinine, lumbar puncture, electroencephalography (EEG), computed tomographic (CT) scan, magnetic resonance imaging (MRI) of the skull, and metabolic screening were performed. Continuous EEG monitoring was performed during step IV/V of management protocol to adjust dose according to burst suppression pattern. Further, during the hospital stay, the outcome, subsequent need for intubation, and days spent in pediatric emergency intensive care unit were also noted. The etiology types were classified as follows: 1.
2.
3.
4.
5.
6.
Prolonged febrile seizures in a previously neurologically healthy child aged between 6 months and 5 years during a febrile (temperature >38 C) illness and in the absence of definite intracranial infection. Acute symptomatic convulsive status epilepticus in a previously neurologically normal child, within a week of an identified acute neurologic insult, including bacterial meningitis, viral intracranial infection, metabolic derangements, drug-related effects, head injury, hypoxia or anoxia, or cerebrovascular disease. Remote symptomatic convulsive status epilepticus in the absence of an identified acute insult but with a history of a preexisting central neurologic abnormality more than 1 week before an attack of convulsive status epilepticus. Acute on remote symptomatic convulsive status epilepticus: Convulsive status epilepticus that occurred within a week of an acute neurologic insult or febrile illness and occurred in a child with a history of previous neurologic abnormality, including epilepsy. This category included children with cerebral palsy with a febrile illness not of central nervous system origin, and children with obstructed ventriculoperitoneal shunts for hydrocephalus. Idiopathic/cryptogenic epilepsy-related convulsive status epilepticus that is not symptomatic and occurred in children with a previous diagnosis of idiopathic/cryptogenic epilepsy or when the episode of convulsive status epilepticus is the second unprovoked seizure that has led to a diagnosis of idiopathic epilepsy. Unclassified convulsive status epilepticus that cannot be classified into any other group.
This classification scheme was synthesized from those described in several previous reports.2,17,18 The research was approved by the local institutional review board of Cairo University’s Specialized Pediatric Hospital. Informed consent was obtained after proper orientation of caregivers of included patients about the objectives of the study and the procedures done. The data were coded and entered using the statistical package SPSS, version 15. The data were summarized using descriptive statistics: mean, standard deviation, median, and interquartile range values for quantitative variables and number and percentage for qualitative values. The normal distribution of the variables was tested by one sample Kolmogorov-Smirnov test by SPSS. Statistical differences between groups were tested using chi-square test for qualitative variables, and independent sample t test for quantitative normally distributed variables, whereas a nonparametric Mann-Whitney test was used for quantitative variables that are not normally distributed. Logistic regression analysis was done to test for significant predictors of poor outcome. P value less than or equal to .05 was considered statistically significant.
Results During the study period, 294 patients with new-onset seizures were identified; 70 (23.8%) presented in convulsive status epilepticus. They constituted 11.3% of total ICU admission during
Downloaded from jcn.sagepub.com at CMU Libraries - library.cmich.edu on October 19, 2015
1738
Journal of Child Neurology 30(13)
Table 1. The Etiology of Status Epilepticus in Different Age-Groups.a Etiology Prolonged febrile seizures Acute symptomatic CNS infection, n Metabolic derangement, n Hemorrhagic stroke, n Neoplastic, n Remote symptomatic Acute on top of remote symptomatic Idiopathic/cryptogenic Unclassified Total
Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital
Journal of Child Neurology 2015, Vol. 30(13) 1736-1742 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815579706 jcn.sagepub.com
Eman F. Halawa, MD1, Iman Draz, MD1, Dalia Ahmed, MD1, and Hala A. Shaheen, MD2
Abstract Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. Keywords convulsive status epilepticus, outcome, predictors Received July 21, 2014. Received revised February 16, 2015. Accepted for publication March 07, 2015.
Convulsive status epilepticus is the most common neurologic emergency in childhood.1 It is one of the most common lifethreatening medical emergencies in childhood. The annual incidence in developed countries ranges from 10 to 73 per 100 000. The highest reported incidence is in children below 2 years of age, with the greatest peak during the first year of life. This variability may be due to different socioeconomic and ethnic characteristics of the population or environmental factors as trauma and infections.2-4 Convulsive status epilepticus is associated with significant morbidity and mortality. The mortality rate ranges from 0% to 13%.2,5-7 Mortality is mostly due to the underlying cause as intracranial infections or severe neurologic disabilities. However, some children have convulsive status epilepticus regardless of the underlying etiology.8 Guidelines for management of status epilepticus are continuously evolving.9 The importance of rapidly terminating prolonged seizures has been emphasized among different treatment protocols. It is estimated that the disability and mortality associated with refractory convulsive status epilepticus is significantly higher than that for nonrefractory convulsive status epilepticus, with 42% disability and 39% mortality rates, especially after few weeks of follow-up.10 The longer a seizure lasts, the less likely it is to stop within the next few minutes.11
Determining the predicting factors of disability and mortality of convulsive status epilepticus is important to modulate the management guidelines and thus improving prognosis. Important factors that can adversely affect neurologic outcome of status epilepticus include etiology, duration of seizure, and patient’s age.2,12,13 This study was conducted out to determine etiology, demographic data, clinical profile, and the predictors of disability and mortality in children with convulsive status epilepticus in a tertiary hospital in Egypt.
Methods This cohort study was carried out at the Cairo University’s Specialized Pediatric Hospital which is a 520-bed, university-affiliated teaching hospital in Cairo, Egypt. It is a referral hospital that provides primary
1 2
Faculty of Medicine, Cairo University, Cairo, Egypt Fayoum University, Giza, Egypt
Corresponding Author: Eman F. Halawa, MD, Faculty of Medicine, Cairo University, 23 Dr Naguib Mahfouz Street, Abbass Akad Street, Nasr City, Cairo, 12334, Egypt. Email: [email protected]
Downloaded from jcn.sagepub.com at CMU Libraries - library.cmich.edu on October 19, 2015
Halawa et al
1737
to tertiary care for children. It encompasses 2 pediatric emergency intensive care units with 16 and 14 beds, respectively. We included a convenient sample of all patients from 1 month to 12 years old with convulsive status epilepticus admitted to the pediatric emergency intensive care unit of Cairo University’s specialized pediatric hospital, from December 2011 to December 2012. Convulsive status epilepticus was strictly defined as continuous, generalized, convulsive seizure lasting more than 5 minutes or 2 or more seizures during which the patient does not return to baseline consciousness.14 Episodes of convulsive status epilepticus after the first episode were defined as recurrent when both events took place during hospitalization. Patients were categorized according to their time to achieve seizure control: less than 30 minutes, between 30 and 60 minutes, and more than 60 minutes. Refractory convulsive status epilepticus was defined as prolonged seizures that fail to terminate after administration of 2 antiepileptic drugs with different mechanisms of action or that require continuously administered medication to abort seizures, regardless of seizure duration.15 Outcome was measured by the condition on discharge using the Glasgow Outcome Score which ranges from 1 to 5, defined as follows: 1 ¼ death, 2 ¼ vegetative state, 3 ¼ severe disability, 4 ¼ moderate disability, and 5 ¼ good recovery.16 For the purpose of analysis, patients with score 5 were defined as having good outcome and patients with score 1 to 4 were defined as having bad outcome. A structured institutional treatment regimen of pediatric status epilepticus has been used since 2004 in the pediatric emergency intensive care units in Cairo University’s specialized pediatric Hospital. Step I: After securing airway, breathing, and circulation, and checking blood glucose, children who presented with prolonged seizure (>5 minutes) received an intravenous bolus dose of 0.1 mg/kg diazepam. If seizure control was not achieved within 5 minutes, the same dose of diazepam was repeated up to 2 times. Step II: If seizure control was not achieved within 15 minutes of step I, a loading dose of 20 mg/kg phenytoin (1 mg/kg/min) was given. In patients unresponsive to loading phenytoin, an additional 10 mg/kg phenytoin was loaded 10 minutes after the initial phenytoin loading. Step III: In patients unresponsive to step II, the loading of 20 mg/kg phenobarbital was given. If unresponsive, an additional 10 mg/kg phenobarbital was loaded and could be repeated twice so that the total loading dose would be 40 mg/kg. Step IV: If the child continued to exhibit convulsions, a bolus of midazolam intravenously (0.15 mg/kg/dose) was given, and then the dose is increased every 5 minutes up to 0.6 mg/kg/min. After achieving seizure control, the infusion was continued for at least 24 hours. Subsequently, midazolam infusion was gradually decreased by 0.05 mg/kg/min every 6 hours until tapering was completed. If a seizure continued for 60 minutes after the infusion (0.6 mg/kg/min), the amount of midazolam in the maintenance infusion was increased up to 1.2 mg/kg/min. Step V: Unresponsive patients were intubated and an initial loading dose of 10 mg/kg intravenous thiopental was given followed by a continuous intravenous maintenance infusion of 3 to 5 mg/kg/h. After stabilization, the following data were recorded: demographic details, developmental history, history of coexisting medical diseases, history of epilepsy, antiepileptic drug use, and seizure type. Also, general examination, neurologic examination, and funduscopy were performed. Investigations including full blood count, blood sugar, serum calcium, serum electrolytes, blood urea, serum
creatinine, lumbar puncture, electroencephalography (EEG), computed tomographic (CT) scan, magnetic resonance imaging (MRI) of the skull, and metabolic screening were performed. Continuous EEG monitoring was performed during step IV/V of management protocol to adjust dose according to burst suppression pattern. Further, during the hospital stay, the outcome, subsequent need for intubation, and days spent in pediatric emergency intensive care unit were also noted. The etiology types were classified as follows: 1.
2.
3.
4.
5.
6.
Prolonged febrile seizures in a previously neurologically healthy child aged between 6 months and 5 years during a febrile (temperature >38 C) illness and in the absence of definite intracranial infection. Acute symptomatic convulsive status epilepticus in a previously neurologically normal child, within a week of an identified acute neurologic insult, including bacterial meningitis, viral intracranial infection, metabolic derangements, drug-related effects, head injury, hypoxia or anoxia, or cerebrovascular disease. Remote symptomatic convulsive status epilepticus in the absence of an identified acute insult but with a history of a preexisting central neurologic abnormality more than 1 week before an attack of convulsive status epilepticus. Acute on remote symptomatic convulsive status epilepticus: Convulsive status epilepticus that occurred within a week of an acute neurologic insult or febrile illness and occurred in a child with a history of previous neurologic abnormality, including epilepsy. This category included children with cerebral palsy with a febrile illness not of central nervous system origin, and children with obstructed ventriculoperitoneal shunts for hydrocephalus. Idiopathic/cryptogenic epilepsy-related convulsive status epilepticus that is not symptomatic and occurred in children with a previous diagnosis of idiopathic/cryptogenic epilepsy or when the episode of convulsive status epilepticus is the second unprovoked seizure that has led to a diagnosis of idiopathic epilepsy. Unclassified convulsive status epilepticus that cannot be classified into any other group.
This classification scheme was synthesized from those described in several previous reports.2,17,18 The research was approved by the local institutional review board of Cairo University’s Specialized Pediatric Hospital. Informed consent was obtained after proper orientation of caregivers of included patients about the objectives of the study and the procedures done. The data were coded and entered using the statistical package SPSS, version 15. The data were summarized using descriptive statistics: mean, standard deviation, median, and interquartile range values for quantitative variables and number and percentage for qualitative values. The normal distribution of the variables was tested by one sample Kolmogorov-Smirnov test by SPSS. Statistical differences between groups were tested using chi-square test for qualitative variables, and independent sample t test for quantitative normally distributed variables, whereas a nonparametric Mann-Whitney test was used for quantitative variables that are not normally distributed. Logistic regression analysis was done to test for significant predictors of poor outcome. P value less than or equal to .05 was considered statistically significant.
Results During the study period, 294 patients with new-onset seizures were identified; 70 (23.8%) presented in convulsive status epilepticus. They constituted 11.3% of total ICU admission during
Downloaded from jcn.sagepub.com at CMU Libraries - library.cmich.edu on October 19, 2015
1738
Journal of Child Neurology 30(13)
Table 1. The Etiology of Status Epilepticus in Different Age-Groups.a Etiology Prolonged febrile seizures Acute symptomatic CNS infection, n Metabolic derangement, n Hemorrhagic stroke, n Neoplastic, n Remote symptomatic Acute on top of remote symptomatic Idiopathic/cryptogenic Unclassified Total
