Pediatric Convulsive Status Epilepticus Research Articles

Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT))

BackgroundPaediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment.MethodsA double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as ‘carbogen’.Due to the urgent need to treat the seizure, deferred consent is used.The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality.DiscussionIf safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff.Trial registrationEudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

Management of Pediatric Convulsive Status Epilepticus From the Perspective of Emergency Nurses: A Cross-sectional, Multicenter Study

IntroductionPediatric convulsive status epilepticus is one of the most common neurologic emergencies and should be managed by health care professionals as soon as possible based on current guidelines. This study aimed to determine the nursing approaches and management of pediatric convulsive status epilepticus from the perspective of emergency nurses in Turkey. MethodsA cross-sectional, multicenter study was conducted with 162 emergency nurses working in emergency departments in 35 different provinces in Turkey. The data were collected via an online form. Descriptive statistical methods were used in data analysis. ResultsMost emergency nurses (72.2%) attempted an intravenous access immediately to administer antiseizure medications during the stabilization phase. Approximately half the emergency nurses stated that rectal diazePAM was frequently administered in the initial therapy phase and intravenous diazePAM was administered in the second therapy phase. The emergency nurses had most difficulties attempting intravenous access, determining status epilepticus types, and calming the parents. DiscussionAs health care professionals and important members of the health team, emergency nurses have the responsibility to manage pediatric convulsive status epilepticus in the fastest and the most appropriate way based on current practice guidelines in emergency departments. When intravenous access is not available, nonintravenous benzodiazepines should be considered in the first-line treatment of pediatric convulsive status epilepticus, followed by immediate intravenous access.

Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.

This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE. The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated. The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety. The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.

Efficacy of intravenous clonazepam for paediatric convulsive status epilepticus.

To compare the efficacy of intravenous clonazepam (CLZ) for the initial management of convulsive status epilepticus (CSE) in children as a function of the first-line in-hospital dose used. This monocentric retrospective study included children who received a first dose of CLZ for CSE at Montpellier University Hospital, France, between January 2016 and June 2019. Data from medical records (clinical, treatment, course) were collected and compared as a function of the first CLZ dose used. Among the 310 children treated for CSE, 105 received at least one CLZ dose (median age 3 years; quartile 1-quartile 3 [Q1-Q3] = 1 years 2 months-6 years 6 months). Among these 105 patients, 24 (22%) received a dose less than 0.03 mg/kg (low dose) and 69 (65%) received a dose of at least 0.03 mg/kg (high dose). Seizure cessation rate was not different between the low- and high-dose groups (62.5% vs 76%; odds ratio 0.53, 95% confidence interval [CI] 0.19-1.44, p = 0.29). The administration of a second dose of CLZ was more frequent in the low- than the high-dose group (37.5% vs 16%; odds ratio 3.2, 95% CI 1.1-9.1, p = 0.04). Our study did not find any difference in seizure termination rate as a function of CLZ dose in children with CSE. However, a second CLZ dose was more frequently needed in the group receiving low (less than 0.03 mg/kg) CLZ.

Reducing Time to Electroencephalography in Pediatric Convulsive Status Epilepticus: A Quality Improvement Initiative

BackgroundPediatric convulsive status epilepticus (CSE) is a neurological emergency utilizing electroencephalography (EEG) to guide therapeutic interventions. Guidelines recommend EEG initiation within one hour of seizure onset, but logistic and structural barriers often lead to significant delays. We aimed to reduce the time to EEG in pediatric CSE. MethodsFrom 2017 to 2022, we implemented process improvements, including EEG order sets with priority-based timing guidance, technologist workflow changes, a satisfaction survey, and feedback from key stakeholder groups, over five plan-do-study-act (PDSA) cycles. Seizure start time, time of EEG order, and time to EEG initiation were extracted. Time to interpretable EEG was determined from manual review of the EEG tracing. ResultsTime from EEG order to interpretable EEG decreased by nearly 50%, from a median of 90 minutes to 48 minutes. There were clinically and statistically significant improvements in time from EEG order to EEG initiation, time from EEG order to interpretable EEG, and EEG start to interpretable EEG. Ongoing provider education and guidance enabled improvements, whereas a new electronic health care record negatively impacted electronic ordering. EEG technologists reported that they understood the importance of emergent EEG for clinical care and did not find that the new workflow caused excessive disruption. ConclusionsTimely access to EEG for pediatric patients with CSE can be improved through clinical processes that use existing devices and that maintain the benefits of full-montage EEG recordings. Similar process improvement efforts may be generalizable to other institutions to increase adherence to guidelines and provide improved care.

Treatment of pediatric convulsive status epilepticus.

Status epilepticus is one of the most common life-threatening neurological emergencies in childhood with the highest incidence in the first 5 years of life and high mortality and morbidity rates. Although it is known that a delayed treatment and a prolonged seizure can cause permanent brain damage, there is evidence that current treatments may be delayed and the medication doses administered are insufficient. Here, we summarize current knowledge on treatment of convulsive status epilepticus in childhood and propose a treatment algorithm. We performed a structured literature search via PubMed and ClinicalTrails.org and identified 35 prospective and retrospective studies on children <18 years comparing two and more treatment options for status epilepticus. The studies were divided into the commonly used treatment phases. As a first-line treatment, benzodiazepines buccal/rectal/intramuscular/intravenous are recommended. For status epilepticus treated with benzodiazepine refractory, no superiority of fosphenytoin, levetirazetam, or phenobarbital was identified. There is limited data on third-line treatments for refractory status epilepticus lasting >30 min. Our proposed treatment algorithm, especially for children with SE, is for in and out-of-hospital onset aids to promote the establishment and distribution of guidelines to address the treatment delay aggressively and to reduce putative permanent neuronal damage. Further studies are needed to evaluate if these algorithms decrease long-term damage and how to treat refractory status epilepticus lasting >30 min.

Pediatric Status Epilepticus: Treat Early and Avoid Delays.

Pediatric convulsive status epilepticus (cSE) is a neurologic emergency with potential for morbidity and mortality. Rapid treatment and escalation of therapies to achieve early seizure control is paramount in preventing complications and providing the best patient outcomes. Although guidelines recommend early treatment, cessation of out-of-hospital SE is undermined by treatment delay and inadequate dosing. Logistical challenges include prompt seizure recognition, first-line benzodiazepine (BZD) availability, comfort and expertise in administration of BZD, and timely arrival of emergency personnel. In-hospital, SE onset is additionally impacted by delays to first- and second-line treatment and availability of resources. This review presents an evidence-based, clinically oriented review of pediatric cSE, including its definitions and treatments. It provides evidence and rationale for timely treatment of first-line BZD treatment followed by prompt escalation to second-line antiseizure medication therapies for established SE. Treatment delays and barriers to care are discussed, with practical considerations for opportunities for areas of improvement in the initial treatment of cSE.

Creation of a Novel Child Simulator and Curriculum to Optimize Administration of Seizure Rescue Medication

Although most cases of pediatric convulsive status epilepticus start in the prehospital setting, many patients do not receive treatment. The use of prehospital seizure rescue medications by caregivers is crucial, but studies suggest a lack of proper training on medication use. We created a novel proof of principle mannequin and simulation for training proper administration of rectal diazepam, with a scoring paradigm to standardize and assess the educational process. Twenty-three health care providers (nurses and nurse practitioners, residents/fellows, and attending physicians) and 5 patient guardians/parents were included in the study. The rectal diazepam simulator displayed a high degree of physical and emotional realism (mean ≥ 4/5 on Likert scale survey) that effectively decreased time to treatment (-12.3 seconds; SD, 16.3) and improved the accuracy of medication delivery in a simulation setting (-4.2 points; SD, 3.1). The scoring technique had appropriate interrater reliability (≥86% on all but 2 prompts) and was a feasible instrument to assess the effectiveness of the educational intervention. A unique procedure-focused child simulator and rescue medication score offer an innovative and effective means to train caregivers on the use of lifesaving seizure rescue medications.

Survey About Second-Line Agents for Pediatric Convulsive Status Epilepticus.

Convulsive status epilepticus (CSE) is the most common neurological emergency in children. It is a frequent cause of admission to pediatric intensive care units and is associated with significant short- and long-term morbidity. Management of CSE is a step-wise approach: first-line antiseizure agents (typically benzodiazepines) followed by a second-line agent before deeper anesthesia usually accompanied by intubation and ventilation. Current guidelines in the United Kingdom specify phenytoin as the second-line agent of choice for CSE. Two recent large international randomized controlled trials compared the efficacy of phenytoin with that of another second-line agent levetiracetam. Both studies found levetiracetam to be noninferior to phenytoin. We conducted an online survey of clinicians across 67 emergency departments that treat children and 29 pediatric intensive care units in the United Kingdom and Ireland to assess their current and preferred second-line agents for treating pediatric CSE in light of recently published evidence. The survey was distributed via the Pediatric Emergency Research in United Kingdom and Ireland network and the Pediatric Critical Care Society. We found that although most clinicians use phenytoin, as per current guidelines, they seek greater flexibility in choice of second-line agent, with levetiracetam being the preferred alternative to phenytoin. To facilitate use of levetiracetam for treatment of CSE in pediatrics, it should be included as a second-line agent in addition to phenytoin in the next update of the National Institute for Health and Care Excellence and other United Kingdom clinical guidelines.

Transcranial photobiomodulation (808nm) attenuates pentylenetetrazole-induced seizures by suppressing hippocampal neuroinflammation, astrogliosis, and microgliosis in peripubertal rats.

.Significance: Transcranial photobiomodulation (tPBM) at 808 nm attenuates pentylenetetrazole (PTZ)-induced seizures and convulsive status epilepticus (CSE) in peripubertal rats by protecting neurons from injury and parvalbumin-positive interneurons from apoptosis, and preserving the integrity of perisomatic inhibitory networks. However, the effects of tPBM on neuroinflammation, astrogliosis, and microgliosis in epileptic rat brains are unknown. Thus, further study to unveil these aspects is needed for understanding the phenomena of tPBM on pediatric CSE prevention.Aim: To evaluate the effects of tPBM on neuroinflammation, astrogliosis, and microgliosis in peripubertal rat hippocampus with PTZ-induced seizures and SE.Approach: An 808-nm diode laser was applied transcranially to peripubertal rats prior to PTZ injection. Immunofluorescence staining of neuron-specific enolase (NSE) was used as a marker of neuroinflammation, glial fibrillary acid protein (GFAP) for astrogliosis, ionized calcium-binding adapter molecule 1 (Iba-1) for microgliosis, and mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) for confirming the involvement of cytochrome c oxidase (CCO).Results: tPBM significantly reduced NSE immunoreactivity in CA3 in PTZ-treated rats, GFAP immunoreactivity in CA1, and Iba-1 immunoreactivity in CA3. Enhancement of hippocampal MT-CO1 reflected that tPBM acted in CCO-dependent manner.Conclusions: tPBM (808) attenuated PTZ-induced seizures and SE by suppressing neuroinflammation, astrogliosis, and microgliosis in peripubertal rats.

Disability and Mortality in Convulsive Status Epilepticus in Children at 3 Months' Follow-Up: A Prospective Study from India.

Background Convulsive status epilepticus (CSE) is a common neurological emergency with high mortality, morbidity, and poor quality of life. There is a paucity of follow-up studies from developing nations in pediatric age group. Objectives This article looks for clinico-etiological profile of CSE and estimates the immediate and short-term mortality in children with CSE and its predictive factors. Methodology This prospective longitudinal study was done at a tertiary care institute of Northern India. The patients between the ages of 1 and 16 years with CSE were enrolled after informed consent, they were observed in the hospital, and survived patients were followed till 3 months after discharge. Results A total of 200 patients (58% males) were enrolled. Acute symptomatic (63.5%) was the most common etiology. Twenty-five (12.5%) patients died during hospital stay; at discharge, 160 (80%) had good recovery and rest had a varying range of disability. The predictive factors for poor outcome were female gender, duration of CSE > 1 hour at presentation, generalized seizures, Glasgow Coma Scale < 8 at presentation, refractory status epilepticus, need for critical care support, and acute symptomatic etiology. On follow-up, two patients died at 1-month and one at 3-month follow-up, the cause of death was probably seizures in two patients and feed aspiration in one patient. Seven patients deteriorated from good recovery scoring to moderate disability during the time interval between first and second follow-up, none of them reported apparent repeat seizures. Conclusion Pediatric CSE is associated with immediate poor outcome; risk of death and new disabilities persist after discharge thus proper follow-up is essential.

Time Elapsed from Onset of Pediatric Convulsive Status Epilepticus to Antiepileptic Administration-An Experience of Single Institute.

Data regarding time elapsed from the onset of pediatric convulsive status epilepticus (CSE) to antiepileptic (AED) administration remains scarce after the adoption of standard treatment-guidelines in Indian healthcare settings. A prospective observational analysis was performed on 52 children presenting to anurban, academic tertiary care teaching hospital diagnosed with CSE and evolving to refractory CSE (RCSE). Time frames of AED administration were compared to the adopted 'Status Epilepticus Management Protocol'. Fifty-two patients [36 (69.2%) male] were enrolled, with a median age of 4.1 y. After CSE onset, the median (p25-p75) time until the administration of the first-line, second-line, and third-line therapy phases of AED doses were 30 (25-37) min, 68 (48-79) min, and 105 (100-135) min, respectively. The second dose of non-BZD AED was administered at a median (p25-p75) of 90 (71-95) min. Twenty-six (50%) patients received at least one continuous infusion. The time elapsed from CSE onset to AED administration and escalation from one class to another was delayed.

Efficacy and Safety of Levetiracetam vs. Phenytoin as Second Line Antiseizure Medication for Pediatric Convulsive Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE). PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020. The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO. Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias. The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.

Time to Treatment in Pediatric Convulsive Refractory Status Epilepticus: The Weekend Effect

BackgroundTime to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency. MethodsWe performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus. ResultsWe included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01). ConclusionsThe time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.

Automated identification and quality measurement for pediatric convulsive status epilepticus.

Treatment delays for refractory convulsive status epilepticus (RCSE) are associated with worse outcomes. In the United States, treatment for pediatric RCSE is slower than guidelines recommend. To address this gap, the American Academy of Neurology and Child Neurology Society (AAN/CNS) developed a quality measure: the percentage of RCSE patients that receive third-line treatment within 60minutes. We aimed to develop computable phenotypes for convulsive status epilepticus (CSE) and RCSE to automate calculation of the quality measure. From an observational cohort of children presenting to the emergency department for seizures or epilepsy, we identified presentations of RCSE and its precursors: CSE and benzodiazepine-resistant status epilepticus (BRSE). These served as a gold standard for computable phenotype development. Using multivariate analyses, we constructed and evaluated statistical models for case identification. We then evaluated adherence to the AAN/CNS RCSE quality measure. From 664 charts, we identified 56 patients with CSE, 36 with BRSE, and 18 with RCSE. Four predictors were used: International Classification of Diseases (ICD) codes, and receiving first-, second-, or third-line agents shortly after presentation to the emergency department (ED). Combinations of these predictors identified CSE with 84% sensitivity and 81% positive predictive value (PPV), BRSE with 67% sensitivity and 89% PPV, and RCSE with 94% sensitivity and 85% PPV. Median (interquartile range [IQR]) time to treatment for first-line agent was 13 (5-27) minutes for CSE, second-line for BRSE was 24 (9.5-43.5) minutes, and third-line for RCSE was 52 (27-87) minutes. Sixty percent of RCSE patients received a third-line agent within 60minutes of ED arrival. RCSE and its precursors can be identified automatically with high fidelity allowing automated calculation of time to treatment and the RCSE quality measure. This has the potential to facilitate quality improvement work and improve care for RCSE.

Development of a novel outcome prediction score (PEDSS) for pediatric convulsive status epilepticus: A longitudinal observational study.

The objectives of this study were to evaluate ENDIT score and develop a novel outcome prediction score for outcome of pediatric convulsive status epilepticus (CSE) at the hospital and 3months postdischarge. Children and adolescents aged 1month to 14years, presenting with CSE to a tertiary care teaching center in North India from January 2017 to March 2019, were screened for enrollment. In-hospital and 3-month postdischarge outcome were defined as poor if Pediatric Cerebral Performance Category Scale (PCPCS) score dropped by ≥2 levels. Overall, 61 patients were enrolled for final analysis after applying exclusion and inclusion criteria. The area under the receiver operating characteristic (ROC) curve for ENDIT score in predicting mortality and differentiating good from poor outcome at the hospital and at 3months postdischarge was 0.74 (95% confidence interval [CI] = 0.58-0.89), 0.7 (95% CI = 0.57-0.83), and 0.72 (95% CI = 0.6-0.82), respectively. Based on predictors in the present cohort that were significantly different between good and poor outcome cases at the hospital and 3months postdischarge, a new six-point score named PEDSS (pre-status epilepticus PCPCS, background electroencephalographic abnormalities, drug refractoriness, semiology, and critical sickness) was developed. The area under ROC curves for PEDSS score in predicting mortality and differentiating good from poor outcome at the hospital and at 3months postdischarge were 0.93 (95% CI = 0.87-0.99), 0.8 (95% CI = 0.7-0.9), and 0.89 (95% CI = 0.8-0.96), respectively. The best cutoff PEDSS scores for predicting mortality and poor outcome at the hospital and at 3months postdischarge were ≥4, ≥3, and ≥3, respectively. The PEDSS score has high predictive accuracy for mortality and differentiating good from poor outcome at the hospital and 3months postdischarge in pediatric CSE. Future studies should be planned to validate it in various geographical and health care settings and in adults.

Levetiracetam for convulsive status epilepticus in childhood: systematic review and meta-analysis

ImportanceProlonged seizures are life-threatening emergencies associated with significant morbidity.ObjectiveTo determine the efficacy and safety of levetiracetam in treating convulsive status epilepticus (CSE) in childhood.Data sources and study selectionsPubMed, Embase, the...

Institutional Pediatric Convulsive Status Epilepticus Protocol Decreases Time to First and Second Line Anti-Seizure Medication Administration

PurposeConvulsive status epilepticus (CSE) is a medical emergency associated with high rates of morbidity and mortality. Although guidelines for CSE management recommend rapid treatment of seizures, prior studies show that compliance with these guidelines is low. In this study, we assessed if implementation of a paper-based clinical pathway for the treatment of CSE improves the timeliness and appropriate dosing of first and second line anti-seizure medications (ASM). MethodsA non-digital CSE treatment protocol was implemented as part of a quality improvement initiative in 2016. A retrospective analysis was subsequently conducted on cases of CSE originating in the pediatric emergency department (ED) from 2012-2019. Standard descriptive statistics were used to assess patient demographics as well as the timing and dosing of the first and second line ASMs used in our protocol (lorazepam [LZP] and fosphenytoin [FOS]). Statistical process control charts (XmR charts) were used to assess the variation in time to drug administration before and after implementation of the protocol. Results153 cases of CSE were identified (72 prior to and 81 after protocol implementation). Among patients who were actively having seizures on arrival to the ED (n = 44), the median time from arrival to ASM administration decreased from 15 to 11 minutes for the first LZP dose (p = 0.23), 23 to 10 minutes for the second LZP dose (p = 0.06), and 40 to 25 minutes for the PHE dose (p = 0.04). There was no improvement in time to LZP administration after seizure onset among those with seizure onset after hospital arrival (5 minutes before/after implementation for the first LZP dose and 15 to 14 minutes for second LZP dose); however, the time to FOS decreased from 42 to 22 minutes (p = 0.86). Statistical process control charts showed a universal decrease in variation for time to each drug administration after protocol implementation. Whereas FOS dosing was largely appropriate before and after protocol implementation, appropriate dosing of LZP did not improve, with only about half of patients receiving the recommended dose. ConclusionThe implementation of a paper-based treatment protocol for CSE was associated with a decreased time to ASM administration among patients who arrived to the ED, particularly for the second-line ASM. Approaches for improving appropriate benzodiazepine dosing are needed.

Convulsive status epilepticus in children recently diagnosed with epilepsy and long-term health-related quality of life

PurposeThe objective of this study was to delineate the long-term impact of pediatric convulsive status epilepticus (CSE) on health-related quality of life (HRQOL) in children recently diagnosed with epilepsy. MethodsChildren with newly-diagnosed epilepsy were recruited between 2004–2007 through a Canada-wide population-based study, the Health-Related Quality of Life Study in Children with Epilepsy Study (HERQULES). Eligible children were 4–12 years of age at epilepsy diagnosis; consequently, children with the more catastrophic syndromes and epileptic encephalopathies typically diagnosed at younger ages were ineligible. Participants were followed over 10 years, and neurologists identified those with CSE in the first two years after epilepsy diagnosis. HRQOL was self-reported by adolescents and young adults (AYAs) in the long-term, and reported by parents at multiple time points throughout the 10-year follow-up. ResultsA total of 204 AYAs were followed over the long-term, 12 of whom had a history of CSE. Parents of those with CSE reported poorer HRQOL in their children two years after the epilepsy diagnosis, (Cohen’s d = 0.58, p = .037), though not at the 10-year follow-up (d = 0.28, p = .19). Results from AYAs’ self-reports at the 10-year follow-up were similar, such that mean HRQOL scores were poorer for AYAs with CSE, though this difference was not significant (d = 0.39, p = .11). Results were similar when adjusting for HRQOL at the time of epilepsy diagnosis. ConclusionThese findings suggest that compromised HRQOL in the short-term after CSE may resolve over the long-term. It will be important for future studies to focus on patient-reported outcomes in reporting the long-term sequelae of CSE.

Comparison of Phenytoin, Valproate and Levetiracetam in Pediatric Convulsive Status Epilepticus: A Randomized Double-blind Controlled Clinical Trial

To compare the efficacy of phenytoin, valproate, and levetiracetam in the management of pediatric convulsive status epilepticus. Randomized double-blind controlled clinical trial. Pediatric critical care division in a tertiary care institute from June, 2016 to December, 2018. 110 children aged three month to 12 year with convulsive status epilepticus. Patients not responding to 0.1 mg/kg intravenous lorazepam were randomly assigned (1:1:1) to receive 20 mg/kg of phenytoin (n=35) or valproate (n=35) or levetiracetam (n=32) over 20 minutes. Patients with nonconvulsive status epilepticus, recent hemorrhage, platelet count less than 50,000 or International normalized ratio (INR) more than 2, head injury or neurosurgery in the past one-month, liver or kidney disease, suspected or known neurometabolic or mitochondrial disorders or structural malformations, and allergy to study drugs; and those who were already on any one of the study drugs for more than one month or had received one of the study drugs for current episode, were excluded. The primary outcome was the proportion of patients that achieved control of convulsive status epilepticus at the end of 15 minutes after completion of the study drug infusion. Secondary outcomes were time to control of seizure, rate of adverse events, and the requirement of additional drugs to control seizure, length of ventilation, hospital stay, and functional status after three months (Glasgow Outcome Scale). The study was stopped after the planned mid-interim analysis for futility. Intention to treat analysis was done. There was no difference in primary outcome in phenytoin (31/35, 89%), valproate (29/35, 83%), and levetiracetam (30/32, 94%) (P=0.38) groups. There were no differences between the groups for secondary outcomes. One patient in the phenytoin group had a fluid-responsive shock, and one patient in the valproate group died due to encephalopathy and refractory shock. Phenytoin, valproate, and levetiracetam were equally effective in controlling pediatric convulsive status epilepticus.