Pediatric Refractory Status Epilepticus Research Articles

A systematic review and meta-analysis of ketamine in pediatric status epilepticus.

Status epilepticus (SE) is a common neurological medical emergency in the pediatric population, with 10%-40% of cases progressing to refractory SE (RSE), requiring treatment with anesthetic infusions. We present a systematic review and meta-analysis of the use of ketamine for the treatment of pediatric SE and its potential advantages over other anesthetic infusions. This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic databases, including PubMed, Cochrane Library, Ovid, Embase, and Google Scholar, were searched with the keywords "pediatrics," "status epilepticus," and "ketamine treatment." Randomized trials, prospective and retrospective cohort studies, and case reports were considered for inclusion. Eighteen publications met the initial inclusion criteria. The 18 publications comprise 11 case reports, one nonconclusive clinical trial, two case series, and four retrospective cohorts. After excluding the case reports because of reporting bias, only the six case series and cohorts were included in the final analysis. There were 172 patients in the six included studies. The weighted age was 9.93 (SD = 10.29) years. The weighted maximum dose was 7.44 (SD = 9.39) mg/kg/h. SE cessation was attained in 51% (95% confidence interval = 43-59) of cases with the addition of ketamine. The heterogeneity was I2 = 0%, t2 = 0, χ2 (5) = 3.39 (p = .64). Pediatric RSE is difficult to treat, resulting in increased morbidity and mortality. Without strong recommendations and evidence regarding preferred agents, this review provides evidence that ketamine may be considered in managing SE in the pediatric population.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021. We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam. Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

ObjectiveThis study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non‐BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE).MethodsThis retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non‐BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non‐BZD ASM.ResultsWe included 293 patients with a median (interquartile range) age of 3.8 (1.3–9.3) years. Thirty‐six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997–.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out‐of‐hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73–3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40–6.03, p < .0001) compared to patients with in‐hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01–2.06, p = .04). Forty‐seven percent of patients (n = 94) with out‐of‐hospital onset did not receive treatment before hospital arrival. Among patients with out‐of‐hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival.SignificanceFailure to escalate from BZDs to non‐BZD ASMs occurs mainly in out‐of‐hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non‐BZD ASMs after two BZD doses during handoffs between prehospital and in‐hospital settings.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

ObjectiveThis study was undertaken to describe long‐term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE.MethodsWe performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients.ResultsFollow‐up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow‐up duration was 1.6 (.9–2.7) years. The in‐hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty‐six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1–134.5] h vs. 4 [1.6–16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008–1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale‐Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion.SignificanceAbout one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow‐up, with longer electroclinical RSE duration as a predictor.

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.

Reader Response: Association of Guideline Publication and Delays to Treatment in Pediatric Status Epilepticus.

Sánchez Fernández et al.1 reported that the publication of evidence on delays in treatment of pediatric refractory convulsive status epilepticus (rSE) was not associated with improvement in time to treatment of rSE (TTTSE). They propose interventions to reduce TTTSE. We would like to share a successful model that we implemented. In 2013, we identified delays in TTTSE in our institution.2 We saw no improvement in TTTSE after a dual intervention consisting of educational programs for healthcare professionals and the development of an electronic SE order set.3 This prompted us to develop an SE alert system that was modeled after our “code stroke” protocol.4 When an inpatient is suspected to have SE, the SE alert is activated by calling an operator who simultaneously pages the neurology and pharmacy house staff, the rapid response team, and the manager responsible for bed assignment. Use of this alert system led to considerable reduction in time to administration of second-line antiseizure medications (22.21 ± 3.44 minutes) compared with standard care (58.30 ± 6.72 minutes; p < 0.0001).4 Because many hospitals have alert protocols for management of acute stroke, SE alert systems could be replicated with local resources to facilitate timely management and coordinated care of SE in adults and children.

First-line medication dosing in pediatric refractory status epilepticus.

To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation. This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation. We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95). BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation. This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Tocilizumab in pediatric refractory status epilepticus and acute epilepsy: Experience in two patients

There is growing evidence for inflammation as a cause and/or consequence of seizures in epilepsy as certain inflammatory biomarkers are elevated. Interleukin (IL)-6, with pro-inflammatory and epileptogenic effects, can perpetuate seizures. Clinical and experimental data support its involvement in acute refractory situations, with some cases responding to treatment with tocilizumab, a humanized monoclonal antibody against the IL-6 receptor. We describe 2 pediatric cases of refractory epilepsy with an abrupt debut responding to tocilizumab. Advances in the knowledge of inflammatory biomarkers involved in epilepsy and the targeted treatment could have important benefits, especially in cases that are refractory to usual treatments.

The onset of pediatric refractory status epilepticus is not distributed uniformly during the day

PurposeTo evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. MethodWe analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. ResultsWe analyzed 368 patients (58% males) with a median (p25 – p75) age of 4.2 (1.3–9.7) years. The MESOR was 15.3 (95% CI: 13.9–16.8) and the amplitude was 3.2 (95% CI: 1.1–5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am–12 pm) and trough at night (11 pm–12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am–3 am) with a minimum during the afternoon (2 pm–3 pm) (p = 0.0179). ConclusionsThe distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am–12 pm) and a trough at night (11 pm-12am).

Clinico-Etiological Profile of Pediatric Refractory Status Epilepticus at a Public Hospital in India.

Background and PurposeRefractory status epilepticus (RSE) has been infrequently studied in Indian children. This research was conducted to study the clinico-etiological profiles and short-term outcomes of children aged 1 month to 12 years with convulsive RSE, at a public hospital.MethodsThe study was conducted between 1st April 2016 and 28th February 2017 after receiving clearance from an Institutional Ethics Committee. All children (aged 1 month to 12 years) who presented to the pediatrics department of a tertiary-care public hospital with convulsive status epilepticus (SE), or who developed SE during their hospital stay, were enrolled. All patients were investigated and managed according to a standard protocol. Outcomes were assessed based on the Glasgow Outcome Scale. Details of children who progressed to RSE were compared to those without RSE.ResultsFifty children (28 males) with CSE were enrolled, of which 20 (40%) progressed to RSE. Central nervous system (CNS) infection was the most common etiology (53% in SE and 55% in RSE, p > 0.05). Non-compliance with anti-epileptic drugs was the second most common etiology. The overall mortality rate was 38%, and although the odds of death in RSE (50%) were higher than in SE (30%), this difference was not statistically significant (p = 0.15). The odds of having a poor outcome was six times higher in children with RSE as compared to those with SE (odds ratio, 6.0; 95% confidence interval, 1.6–22.3; p = 0.005).ConclusionsWhen managing CNS infections, pediatricians need to be aware of the high risk of developing RSE. In addition, the possibility of RSE should be considered and managed promptly in an intensive-care setting, to reduce the mortality and morbidity of this severe neurological condition.

Platform Session – Electroencephalography/Epilepsy: Clinical characteristics and outcomes of pediatric super refractory status epilepticus

Introduction There is limited literature on pediatric super refractory status epilepticus (SRSE). We aimed to identify clinical variables associated with the occurrence of SRSE and to describe variability in SRSE treatment in a cohort of children admitted to pediatric intensive care units (ICU) with refractory status epilepticus (RSE). Methods This prospective, observational study was performed at 14 US hospitals. Inclusion criteria: (1) hospital admission between June 2011 and September 2017, (2) convulsive RSE defined as focal or generalized convulsive seizures at onset that continued after administration of at least 2 anti-seizure drugs (ASDs), including one non-benzodiazepine ASD or use of continuous infusion (CI) and (3) age 1 month to 21 years. We divided the cohort into SRSE and non-SRSE groups. SRSE was defined as continuous or intermittent seizures lasting ⩾ 24 h following initiation of CI. We used Fisher’s exact test and Wilcoxon rank sum test in the univariate analysis. Results The initial cohort included 264 patients with a median (p25–p75) age of 4 (1.23–9.50) years. Thirty-five patients (19 males) were identified as SRSE cases, with a median age of 4.5 (1.91–8.45) years. Univariate analysis did not show significant differences between the groups for: sex, age, etiology, prior SE, diagnosis of epilepsy, in-hospital seizure onset, generalized tonic-clonic seizures or continuous SE. SRSE patients had delayed first line treatment initiation (71(15–135.5) vs. 16(5–40.5) min; p = 0.017), longer ICU stay (17(9–42) vs. 3(1.86–8.66) days; p Conclusion SRSE patients had delayed first-line treatment administration in comparison to non-SRSE patients. Once SRSE was established, children had significantly higher morbidity and mortality. Treatment approaches were heterogeneous, probably reflecting limited evidence to guide clinical decision-making in SRSE. (Funded by the Pediatric Epilepsy Research Foundation and Epilepsy Research Fund ).

Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus

PurposeTo describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). MethodsRSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded. ResultsFourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range [IQR] 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD.EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline. ConclusionsThis series suggests efficacy and safety of KD for treatment of pediatric RSE.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

High dose phenobarbitone coma in pediatric refractory status epilepticus; a retrospective case record analysis, a proposed protocol and review of literature

BackgroundOngoing 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. MethodsCase 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. ResultsOverall, 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. ConclusionHigh 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.

Intravenous Immunoglobulins for Refractory Status Epilepticus: A Scoping Systematic Review of the Pediatric Literature

AbstractOur goal was to perform a scoping systematic review of the literature on the use of intravenous immunoglobulins (IVIGs) for refractory status epilepticus (RSE) in pediatric patients. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, ClinicalTrials.gov (inception to June 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendation Assessment Development and Education (GRADE) methodology by two independent reviewers. We identified 21 original articles. Eighty-seven pediatric patients were described as having received IVIG therapy for RSE. The mean age was 7.8 years (range: 2–17.5 years). Seizure response occurred in 14 of the 87 patients (16.1%), with 3 (3.4%) and 11 (12.6%) displaying partial and complete responses, respectively. Seventy-three of the 87 patients (83.9%) failed to display any seizure response to IVIG therapy. No complications related to IVIG therapy were recorded. The majority of patients had moderate to severe neurological deficits upon follow-up. Oxford level 4, GRADE D evidence exists to suggest little to no impact on seizure control in pediatric autoimmune RSE. Routine use of IVIG for pediatric RSE cannot be recommended at this time and should be considered experimental.

Acute Resective Surgery for the Treatment of Refractory Status Epilepticus.

To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. Nine patients, aged 20-68years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Anesthetic considerations for pediatric electroconvulsive therapy.

Electroconvulsive therapy is being used more frequently in the treatment of many chronic and acute psychiatric illnesses in children. The most common psychiatric indications for pediatric electroconvulsive therapy are refractory depression, bipolar disorder, schizophrenia, catatonia, and autism. In addition, a relatively new indication is the treatment of pediatric refractory status epilepticus. The anesthesiologist may be called upon to assist in the care of this challenging and vulnerable patient population. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment. Dexmedetomidine is likely the most appropriate preoperative anxiolytic as oral benzodiazepines are relatively contraindicated. Methohexital, though becoming less available at many institutions, remains the gold standard for induction of anesthesia for pediatric electroconvulsive therapy though ketamine, propofol, and sevoflurane are becoming increasingly viable options. Proper planning and communication between the multidisciplinary teams involved in the care of children presenting for electroconvulsive therapy treatments is vital to mitigating risks and achieving the greatest therapeutic benefit.

Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related Epilepsy Syndrome: A Case Series.

Febrile illness-related epilepsy syndrome is a catastrophic epileptic encephalopathy that is highly refractory to most antiepileptic drugs leading to high morbidity and mortality. The authors report the use of a pediatric infusion protocol of continuous intravenous magnesium sulfate for the control of seizures in 2 children with febrile illness-related epilepsy syndrome refractory to multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary care children’s hospital. Both patients, 2 and 16 years of age, respectively, were treated with continuous magnesium sulfate infusion. Serum magnesium concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No significant adverse effects were observed. Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome.

Complications during the management of pediatric refractory status epilepticus with benzodiazepine and pentobarbital infusions.

Sir, Patten et al. in their interesting study compared complications in the management of refractory status epilepticus (RSE) treated with benzodiazepine and pentobarbital infusions. The authors addressed that children with RSE, who required pentobarbital therapy had a longer hospital stay and were more likely develop hypotension, require inotropic support, need intubation, mechanical ventilation, peripheral nutrition, and blood products. Furthermore, they were more likely to develop hypertension and movement disorder after or during weaning.[1] I presume that these results ought to be cautiously taken owing to the presence of the following three limitations. (1) The data were taken from a single center. (2) The study period was relatively short (3 years). (3) The size of the studied cohort was small (n = 28). Conducting a large scale multicenter study over an extended period could better evaluate that the issue. Despite the aforementioned three limitations, the observation in Patten et al's. study[1] on more complications associated with pentobarbital infusion compared to benzodiazepine infusion renders pentobarbital less recommended first-line in treating patients with RSE. This observation supports the recently published Indian consensus guidelines on the management of childhood convulsive status epilepticus[2] and recommendations of the Italian League Against Epilepsy,[3] which stress that the initial management of RSE should consist of a parenteral benzodiazepine (lorazepam, diazepam, or midazolam) by any route feasible and when first-line anti-epileptic drugs fail, sodium phenytoin, and phenobarbital should be used. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.