Neurologic outcomes of pediatric epileptic patients with pentobarbital coma

doi:10.1016/S0887-8994(01)00311-3

Pediatric Neurology

Volume 25, Issue 3, September 2001, Pages 217-220

https://doi.org/10.1016/S0887-8994(01)00311-3 Get rights and content

Abstract

Status epilepticus is a life-threatening condition requiring emergent medical attention. Although initial therapies with antiepileptic drugs generally terminate seizures within 30 to 60 minutes, patients with refractory status epilepticus require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of refractory status epilepticus in children. The objective of this research was to evaluate the association between the response of pentobarbital coma and neurologic outcomes in refractory status epilepticus. Twenty-three subjects were treated with pentobarbital coma for at least 48 hours. Medical records were reviewed to collect patient demographic information, responses to treatment, and neurologic outcomes. Among the 23 patients reviewed, 12 patients were controlled with pentobarbital (responders), six were unresponsive to pentobarbital (nonresponders), and five patients relapsed after discontinuation or during tapering of pentobarbital (relapser). The mortality rate among the relapser and nonresponder groups combined was 90.9%, but no deaths occurred among the responder group (P < 0.001). The survival rate was greater among toddlers compared with neonates or older children. Failure of seizure control after pentobarbital coma was associated with a poor prognosis. The potential for serious complications of pentobarbital therapy among neonates highlights the need for careful dosing in this age group.

Introduction

Status epilepticus is usually controlled by using conventional antiepileptic drugs, such as phenytoin, benzodiazepines, and phenobarbital, in approximately 30 minutes. Persistent seizures lasting 60 minutes even after proper antiepileptic drug usage are defined as refractory status epilepticus [1], [2]. Currently, pentobarbital coma, midazolam, and propofol are being used in treatment of refractory status epilepticus. Among the methods of treatment, pentobarbital coma is the most universally accepted, but the duration of treatment or drug dosage is uncertain. Pentobarbital coma has been implemented in adults [3], [4], [5], [6], but only limited data are available among pediatric patients [7]. This study investigated the relationship between the clinical response to pentobarbital coma and neurologic outcomes among pediatric patients with refractory status epilepticus.

Section snippets

Patients and methods

Between May 1995 and May 1999, the Department of Pediatrics at Chonbuk National University Hospital treated 90 patients with pediatric status epileptic patients. All subjects had received conventional IV benzodiazepines (e.g., diazepam, lorazepam, midazolam), phenytoin sodium, and phenobarbital as needed. Repeat of loading dose could be used if seizure was persistent [8]. The study population consisted of 23 children (26.9%) with seizures refractory to conventional antiepileptics. All patients

Results

In this case series, 12 patients (52%) were controlled (responder group) with pentobarbital, whereas six patients (26%) were unresponsive (nonresponder group) to pentobarbital. A total of five patients (22%) relapsed after pentobarbital was discontinued or during tapering. Among 13 patients who survived refractory status epilepticus after therapy, eight (61.5%) developed permanent neurologic sequelae. The proportion of patients who died among patients who relapsed after therapy was

Discussion

This result demonstrated that pentobarbital coma was a uniformly effective treatment for patients of different ages and ethnic backgrounds and with different seizure types. The mortality rate in our study was 43.5%, and the handicapped rate of survived patients was 61.5%. If the pentobarbital therapy was not effective for refractory status epilepticus patients, other treatment modalities, such as a high dose of midazolam, anesthesia with propofol, IV valproic acids, and epileptic surgery, were

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Lestaurtinib (CEP-701) reduces the duration of limbic status epilepticus in periadolescent rats
2023, Epilepsy Research
The timely abortion of status epilepticus (SE) is essential to avoid brain damage and long-term neurodevelopmental sequalae. However, available anti-seizure treatments fail to abort SE in 30% of children. Given the role of the tropomyosin-related kinase B (TrkB) receptor in hyperexcitability, we investigated if TrkB blockade with lestaurtinib (CEP-701) enhances the response of SE to a standard treatment protocol and reduces SE-related brain injury.
SE was induced with intra-amygdalar kainic acid in postnatal day 45 rats under continuous electroencephalogram (EEG). Fifteen min post-SE onset, rats received intraperitoneal (i.p.) CEP-701 (KCEP group) or its vehicle (KV group). Controls received CEP-701 or its vehicle following intra-amygdalar saline. All groups received two i.p. doses of diazepam, followed by i.p. levetiracetam at 15 min intervals post-SE onset. Hippocampal TrkB dimer to monomer ratios were assessed by immunoblot 24 hr post-SE, along with neuronal densities and glial fibrillary acid protein (GFAP) levels.
SE duration was 50% shorter in the KCEP group compared to KV (p < 0.05). Compared to controls, SE induced a 1.5-fold increase in TrkB dimerization in KV rats (p < 0.05), but not in KCEP rats which were comparable to controls (p > 0.05). The KCEP group had lower GFAP levels than KV (p < 0.05), and both were higher than controls (p < 0.05). KCEP and KV rats had comparable hippocampal neuronal densities (p > 0.05), and both were lower than controls (p < 0.05).
Given its established human safety, CEP-701 is a promising adjuvant drug for the timely abortion of SE and the attenuation of SE-related brain injury.
Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children
2020, Seizure
Citation Excerpt :
A vasopressor was also required in most cases in previous reports [12,14,16]. Pneumonia was observed in 11 cases as another complication, but it is also frequently seen during general anaesthetic therapy, and was not more frequent compared to the findings of previous reports [12–14,16]. Barbiturates often have a prolonged recovery period; actually, the median time to wake-up was 46 h in this study.
To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children.
This was a review of a prospectively-collected database between April 2012–March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications.
All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis.
We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.
Pediatric refractory and super-refractory status epilepticus
2019, Seizure
Citation Excerpt :
The nature of RSE/SRSE is highly heterogeneous and several factors may contribute to the patients’ prognosis. Mortality estimates in pediatric RSE are 13.7–43.5% [8–10,24], related to etiology, patients’ age (<3 years old), and initial EEG findings (i.e.multifocal or generalized abnormalities) [8]. The underlying etiology is usually recognized as a primary predictor of outcomes [6,7,24,145,146].
To summarize the available evidence related to pediatric refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE), with emphasis on epidemiology, etiologies, therapeutic approaches, and clinical outcomes.
Narrative review of the medical literature using MEDLINE database.
RSE is defined as status epilepticus (SE) that fails to respond to adequately used first- and second-line antiepileptic drugs. SRSE occurs when SE persist for 24 h or more after administration of anesthesia, or recurs after its withdrawal. RSE and SRSE represent complex neurological emergencies associated with long-term neurological dysfunction and high mortality. Challenges in management arise as the underlying etiology is not always promptly recognized and therapeutic options become limited with prolonged seizures. Treatment decisions mainly rely on case series or experts’ opinions. The comparative effectiveness of different treatment strategies has not been evaluated in large prospective series or randomized clinical trials. Continuous infusion of anesthetic agents is the most common treatment for RSE and SRSE, although many questions on optimal dosing and rate of administration remain unanswered. The use of non-pharmacological therapies is documented in case series or reports with low level of evidence. In addition to neurological complications resulting from prolonged seizures, children with RSE/SRSE often develop systemic complications associated with polypharmacy and prolonged hospital stay.
RSE and SRSE are neurological emergencies with limited therapeutic options. Multi-national collaborative efforts are desirable to evaluate the safety and efficacy of current RSE/SRSE therapies, and potentially impact patients’ outcomes.
Baseline and outcome assessment in pediatric status epilepticus
2019, Seizure
To summarize different aspects of short and long-term outcomes associated with SE, including mortality, recurrence, subsequent epilepsy, neurocognitive dysfunction, imaging abnormalities, and health-related quality of life.
We searched MEDLINE for studies that assessed the short-term and long-term outcome of status epilepticus in pediatric population, including mortality, recurrence of seizure and status epilepticus, neurological, cognitive, or behavioral impairment, and health-related quality of life. We excluded studies that exclusively assessed the adult population.
Mortality in pediatric SE is relatively low, while morbidity poses more challenges. The underlying cause of SE has been shown to be a major determinant in the outcome after SE. However, it is difficult to establish the net effect of SE on outcome due to the heterogeneity of the studies. Notably, this review highlights that health-related quality of life, an important aspect of long-term outcome in pediatric SE, is under-addressed and merits further investigation.
There is a need to acquire high-quality long-term data evaluating QoL, neuroimaging, use of continuous infusions, and cognitive and behavioral outcome of children who experience SE.
Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus
2019, Seizure
To summarize the evidence regarding dietary, immunological, surgical, and other emerging treatments for refractory status epilepticus (RSE)/super-RSE (SRSE).
Narrative literature review including relevant human studies.
Hypothermia and brenaxolone were tested in randomized controlled trials for RSE/SRSE management, while other interventions have only limited evidence for their efficacy and safety. Clinical trials including the HYBERNATUS study found the efficacy of therapeutic hypothermia to be no better than placebo for RSE/SRSE, and raised concerns about its safety. Ketogenic diet has shown possible efficacy in RSE/SRSE in several case series, with electrographic seizure resolution within 7 days in 20%–90% patients in larger (n = 8–17) reports. A review of 37 pediatric patients reported seizure control with immunotherapy in only 7 patients. A phase 3 double-blind trial showed that brexanolone was no better than placebo for successful wean of 3rd line anesthetic agent(s) and freedom from RSE for ≥24 hours. Epilepsy surgery has been reported to successfully control seizures in small series; however, pre-surgical evaluation is confounded by ongoing ictal activity and anesthetic infusions. Vagus nerve stimulation was reported to be associated with cessation of RSE/SRSE in 21/28 patients in a review of anecdotal reports. There is no evidence for use of pyridoxine and magnesium outside of specific indications.
There is only anecdotal evidence for dietary, immunological, surgical, and other treatments for RSE/SRSE, often confounded by multiple concurrent treatments, and heterogeneity in their use and assessment of outcomes. Clinical trials for therapeutic hypothermia and brexanolone have not shown a significant advantage over comparators.
High dose phenobarbitone coma in pediatric refractory status epilepticus; a retrospective case record analysis, a proposed protocol and review of literature
2018, Brain and Development
Citation Excerpt :
First, Crawford et al. [10], in their 1988 study administered HD-PHB by 2 protocols: continuous infusion in eight patients, and repeated boluses in 42 patients. In subsequent report by Kim et al. [11] in 2001, 26 children were administered pentobarbital with a loading dose of 5 mg/kg followed by continuous infusion at 1–3 mg/kg/hour. The ideologies of the two protocols were combined and an initial bolus of phenobarbitone followed by continuous infusion up to 3 mg/kg/hour was instituted.
Ongoing refractory status epilepticus is associated with significant morbidity and mortality. Therapeutic coma induction with midazolam, thiopentone, phenobarbitone or propofol is indicated when conventional antiepileptics fail to abort seizure. Of these, the most extensively studied is midazolam. Amongst the remaining three, phenobarbitone has the most favourable pharmacological profile, but has not been studied adequately, more so in the pediatric age group. The current retrospective case records analysis is an attempt to describe use of phenobarbitone coma in pediatric refractory status epilepticus.
Case records of patients, admitted with status epilepticus to the pediatric inpatient services of a tertiary care teaching hospital of North India between January 2014 and December 2016 were reviewed. Those with refractory status epilepticus who failed to respond to midaolam infusion and phenobarbitone coma was used were included for analysis.
Overall, 108 children presented in status, of which 34 developed refractory status epilepticus. Of these 34, 21 responded to midazolam infusion and in 13 high dose phenobarbitone coma following a standardised protocol was used. Amongst these 13 (8 males and 5 females, median age 6 years, IQR: 2.5–9.5), 12 responded and 1 succumbed. The median time to clinical seizure resolution and desired electroencephalographic changes post phenobarbitone initiation were 16 (IQR: 12–25) and 72 h (IQR: 48–120) respectively.
High dose phenobarbitone appears to be an effective therapeutic modality in pediatric refractory status epilepticus. The current study provides a protocol for its use which can be validated in future studies with larger sample size.

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Neurologic outcomes of pediatric epileptic patients with pentobarbital coma

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Pediatr Neurol

Pediatr Neurol

It’s time to revise the definition of status epilepticus

Epilepsia

Barbiturate anesthesia in the treatment of status epilepticusclinical experiences with 14 patients

Neurology

Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus

Epilepsia

Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus

Neurology