Treatment Of 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.

Enteral Ketamine for Status Epilepticus in Children with Epilepsy

BackgroundApproximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy. MethodsPatient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed. ResultsNine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations. ConclusionsEnteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time.

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.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial

BackgroundGeneralised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.MethodsThis was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.ResultsA total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes.ConclusionsVPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Optimal Management of Status Epilepticus in Children in the Emergency Setting: A Review of Recent Advances.

Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.

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.

Efficacy of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children.

Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS). In this study, 185 patients diagnosed with CSE or ARS and aged between 1month and 18years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated. A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36months were significantly related to seizure recurrence (p < 0.01). Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. This study is registered as PROSPERO CRD42020201953. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Parenteral Long-Acting Antiseizure Medications Are Used More Often to Treat Seizure Clusters Than Convulsive Status Epilepticus in the Pediatric Emergency Department.

Objective:Recent trials provide high-quality evidence for second-line treatment of convulsive status epilepticus (CSE) in children. However, the most effective medications for other seizure emergencies are poorly understood without established treatment algorithms. We investigated children presenting to the emergency department with repetitive or prolonged convulsions who required intravenous long-acting antiseizure medications, to determine the relative importance and treatment responsiveness of status epilepticus and seizure clusters. Methods: Retrospective observational study in the emergency department, Royal Children's Hospital, Melbourne, Australia (annual census 90 000) using hospital electronic medical records data of patients presenting with seizures in 2018. For patients receiving parenteral long-acting antiseizure medications, seizures were categorized as convulsive status epilepticus, nonconvulsive status epilepticus, and seizure clusters. Results: 1468 patients (2% of all visits) presented with seizures to the emergency department in 2018. Long-acting antiseizure medications were administered to 97 (7%) children for the emergency management of seizures. The majority presented with seizure clusters (n = 69; 71%). Only 11 (11%) were in convulsive status epilepticus and 17 (18%) in nonconvulsive status epilepticus. In convulsive status epilepticus, nonconvulsive status epilepticus, and seizure clusters, phenytoin was used in 27%, 53%, and 58% and levetiracetam in 73%, 47%, and 32%, respectively. Conclusions:Convulsive status epilepticus represents a small portion of patients requiring parenteral long-acting antiseizure medications. Seizure clusters accounted for >6 times the number of convulsive status epilepticus, yet evidence and treatment algorithms are lacking.

Valproic Acid as Adjuvant Treatment for Convulsive Status Epilepticus

Valproic Acid as Adjuvant Treatment for Convulsive Status Epilepticus

Efficacy and safety of levetiracetam versus phenytoin as second-line drugs for the treatment of children with convulsive status epilepticus: a Meta analysis

Objective To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children. Methods English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis. Results Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE (RR=1.12, 95%CI:1.00-1.24, P=0.05), but there was no significant difference between the two groups in the recurrence rate of epilepsy within 24 hours (RR=0.82, 95%CI:0.22-3.11, P=0.77) and the rate of further antiepileptic drug therapy (RR=0.97, 95%CI:0.64-1.45, P=0.87). There was no significant difference in the incidence rate of adverse events between the two groups (RR=0.77, 95%CI:0.55-1.09, P=0.15). Conclusions LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.

Different Attitudes in the Management of Different Types of Status Epilepticus

Purpose: The aim is to identify current diagnostic and therapeutic approach to different types of status epilepticus (SE) including convulsive SE (CSE), non-CSE (NCSE), and epilepsia partialis continua (EPC) to detect unmet needs and problems encountered during the management of these neurological emergencies in our country, Turkey. Methods: The specifically designed SE survey included 31 questions that were related to the incidence, the distribution of etiological causes, the diagnostic process, and the treatment approaches of the neurologists and individual electroencephalography (EEG) facilities of the institutions. Results: The total number of respondents was 152 with a median years of experience in professional practice of 10.8 years (1–39 years). The great majority of the neurologists preferred diazepam plus phenytoin as the first choice drug in the treatment of CSE. Of the respondents, only 55% accepted the SE as refractory after applying the second drug and they monitored these patients in the intensive care unit (ICU). Most of the participants (67.7%) did not provide any treatment except the standard medical approaches, while only 39 (30.7%) had used immunotherapy in the treatment of super-refractory SE. Forty-seven respondents (37%) indicated that they had difficulty identifying NCSE on EEG. While 37% of the participants treated EPC patients with preserved consciousness in ICU by general anesthesia, only 15% were previously applied immunotherapy. Strikingly, 41% of the participants stated that they did not feel themselves as sufficiently competent in terms of practical and theoretical knowledge about the management of SE. Conclusion: We demonstrated that there are no standardized attitudes for the management of different types of SE among neurologists. It is worth to emphasize that the neurologists did not feel themselves sufficiently competent in terms of practical and theoretical knowledge, especially with regard to the subtypes of SE.

Diagnosis and Treatment of Status Epilepticus.

The definition of status epilepticus (SE) was revised recently in accordance with the various evidences of neuronal injury and changes in clinical settings. Currently, the most acceptable duration of continuous seizure activity is 5 minutes. In 2015, the International League Against Epilepsy Task Force, which was convened to develop a definition and classification of SE, presented a new classification based on four axes: 1) semiology, 2) etiology, 3) electroencephalogram (EEG) correlates, and 4) age. The essential element of nonconvulsive SE (NCSE) is the presence of neurological abnormalities induced by a prolonged epileptic process. The definition of refractory SE involves either clinical or electrographic seizures that persist after adequate doses of an initial benzodiazepine and acceptable second-line antiseizure drugs. The use of EEG is critical in the diagnosis and treatment of NCSE. However, there are a wide range of EEG abnormalities in NCSE. Both the Neurocritical Care Society and the American Epilepsy Society have suggested a paradigm for treating convulsive SE (CSE). The first-line treatment of CSE with benzodiazepine is well-established. The second-line treatment comprises intravenous (IV) doses of fosphenytoin (phenytoin), valproate, phenobarbital, levetiracetam, or midazolam. Although fosphenytoin (phenytoin) and valproate are commonly used in NCSE, the effectiveness of antiepileptic drugs (AEDs) on NCSE has not been well studied. New AEDs such as IV levetiracetam and lacosamide can also be used to treat NCSE with fewer side effects and drug-drug interactions. For refractory SE, general anesthesia with IV midazolam, propofol, pentobarbital, or thiopental could be applied. Use of ketamine, megadose phenobarbital therapy, and multiple combinations of various AEDs including high doses of oral AEDs can also be considered. New-onset refractory status epilepticus (NORSE) and its subcategory, febrile infection-related epilepsy syndrome, involve autoimmune processes. AEDs alone are poorly effective in the treatment of SE in autoimmune encephalitis. Immunotherapy such as steroids, immunoglobulin, rituximab, or tocilizumab can be effective.

Electroencephalographic Seizures in Emergency Department Patients After Treatment for Convulsive Status Epilepticus.

It is unknown how often and how early EEG is obtained in patients presenting with status epilepticus. The Established Status Epilepticus Treatment Trial enrolled patients with benzodiazepine-refractory seizures and randomized participants to fosphenytoin, levetiracetam, or valproate. The use of early EEG, including frequency of electrographic seizures, was determined in Established Status Epilepticus Treatment Trial participants. Secondary analysis of 475 enrollments at 58 hospitals to determine the frequency of EEG performed within 24 hours of presentation. The EEG type, the prevalence of electrographic seizures, and characteristics associated with obtaining early EEG were recorded. Chi-square and Wilcoxon rank-sum tests were calculated as appropriate for univariate and bivariate comparisons. Odds ratios are reported with 95% confidence intervals. A total of 278 of 475 patients (58%) in the Established Status Epilepticus Treatment Trial cohort underwent EEG within 24 hours (median time to EEG: 5 hours [interquartile range: 3-10]). Electrographic seizure prevalence was 14% (95% confidence interval, 10%-19%; 39/278) in the entire cohort and 13% (95% confidence interval, 7%-21%) in the subgroup of patients meeting the primary outcome of the Established Status Epilepticus Treatment Trial (clinical treatment success within 60 minutes of randomization). Among subjects diagnosed with electrographic seizures (39), 15 (38%; 95% confidence interval, 25%-54%) had no clinical correlate on the video EEG recording. Electrographic seizures may occur in patients who stop seizing clinically after treatment of convulsive status epilepticus. Clinical correlates might not be present during electrographic seizures. These findings support early initiation of EEG recordings in patients suffering from convulsive status epilepticus, including those with clinical evidence of treatment success.

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...

Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children

PurposeAlthough phenytoin is one of the most commonly used antiepileptic drugs (AEDs), it has potential serious side effects and drug interactions. Levetiracetam is a relatively newer AED with favorable pharmacokinetics and could be an effective and safer option for the treatment of convulsive status epilepticus (CSE). We aimed to compare the efficacy and safety profile of intravenous levetiracetam and phenytoin as second-line treatment agents in children with CSE and acute repetitive seizures (ARS). MethodTwo hundred seventy-seven patients aged between 1 month and 18 years who received intravenous levetiracetam or phenytoin as a second-line AED with the diagnosis of CSE or ARS were retrospectively evaluated. Drug efficacy was defined as control of seizures without the need for any additional medication after completion of the infusion and no recurrence in the following 12 h. The primary outcome was drug efficacy. The secondary outcomes included application of an additional second-line AED, induction of anesthesia, and admission to the intensive care unit (ICU), and drug-related adverse reactions. ResultsNo differences were found between the two treatment groups with regard to patient characteristics and seizure type. The efficacy of levetiracetam was higher than that of phenytoin (77.6% vs 57.7%, P = 0.011) in children with CSE. There was no significant difference between the efficacy rates of levetiracetam and phenytoin for ARS (55.8% vs 58.8%, P = 0.791). Overall, drug efficacy was 70.9% for levetiracetam and 58.1% for phenytoin (P = 0.048). For CSE, the need for additional second-line treatment, anesthesia induction, and ICU admission was higher in the phenytoin group (P = 0.001, P = 0.038, P = 0.02, respectively). Drug-related adverse reactions were more frequent in the phenytoin group than the levetiracetam group (23.3% vs 1.4%; P < 0.001). The most common adverse reaction in the phenytoin group was hypotension. Phenytoin-related anaphylaxis was detected in one patient. No serious adverse effects related to levetiracetam were observed. ConclusionsIntravenous levetiracetam seems as effective as intravenous phenytoin in emergency treatment of children with ARS and more effective for CSE in stopping the seizure with less risk of recurrence. Levetiracetam has fewer cardiovascular side effects and has a safer profile than phenytoin. Intravenous levetiracetam is a favorable option as a first second-line AED for pediatric seizures.

Pharmacotherapy for Pediatric Convulsive Status Epilepticus.

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABAA receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-d-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

Is it a Tie at This Point in the Game? Efficacy of Levetiracetam and Phenytoin for the Second-Line Treatment of Convulsive Status Epilepticus.

[Box: see text].

Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial

Phenytoin is the current standard of care for second-line treatment of paediatric convulsive status epilepticus after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, can be given more quickly, is potentially more efficacious, and has a more tolerable adverse effect profile. We aimed to determine whether phenytoin or levetiracetam is the superior second-line treatment for paediatric convulsive status epilepticus. ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand. Children aged between 3 months and 16 years, with convulsive status epilepticus that failed first-line benzodiazepine treatment, were randomly assigned (1:1) using a computer-generated permuted block (block sizes 2 and 4) randomisation sequence, stratified by site and age (≤5 years, >5 years), to receive 20 mg/kg phenytoin (intravenous or intraosseous infusion over 20 min) or 40 mg/kg levetiracetam (intravenous or intraosseous infusion over 5 min). The primary outcome was clinical cessation of seizure activity 5 min after the completion of infusion of the study drug. Analysis was by intention to treat. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12615000129583. Between March 19, 2015, and Nov 29, 2017, 639 children presented to participating emergency departments with convulsive status epilepticus; 127 were missed, and 278 did not meet eligibility criteria. The parents of one child declined to give consent, leaving 233 children (114 assigned to phenytoin and 119 assigned to levetiracetam) in the intention-to-treat population. Clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). One participant in the phenytoin group died at 27 days because of haemorrhagic encephalitis; this death was not thought to be due to the study drug. There were no other serious adverse events. Levetiracetam is not superior to phenytoin for second-line management of paediatric convulsive status epilepticus. Health Research Council of New Zealand, A+ Trust, Emergency Medicine Foundation, Townsville Hospital Private Practice Fund, Eric Ormond Baker Charitable Fund, and Princess Margaret Hospital Foundation.

Levetiracetam versus phenytoin for treatment of convulsive status epilepticus in pediatric population: a randomized controlled trial

Background: Status epilepticus is a major medical and neurological emergency. Despite advances in treatment, it is still associated with significant morbidity and mortality. The objective of the study was to compare the efficacy of levetiracetam versus phenytoin in treatment of convulsive status epilepticus.Methods: A Randomized control trial, was conducted at tertiary care hospital, Udaipur, Rajasthan, over a period of March 2017 to September 2018. Total 250 patients (age group 6 months to 18 years) who were presented with status epilepticus in PICU, were enrolled. These patients were divided into two groups by simple randomization. Levetiracetam was given to one group, while phenytoin was given to another group. Efficacy was decided by cessation of clinical seizure activity within 30 minutes of starting of drug infusion and patient was observed for recurrence of seizure within 24 hours.Results: A total of 250 patients were enrolled in this study. Seizure terminated in 107 patients in phenytoin group (85.6%) and in 114 patients in levetiracetam group (91.2%). The difference was significant. Recurrence of seizure (with in 24 hour) was high in phenytoin group (14.4%) in comparison with levetiracetam group (8.8%). Most common adverse effect in both the groups on treatment was hypotension, though in phenytoin group it was significantly higher than patients on levetiracetam group (7.2% v/v 2.4%).Conclusions: Levetiracetam may be an effective alternative to phenytoin as a second line drug in the management of benzodiazepine resistant convulsive status epilepticus in children.