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Status Epilepticus is a time-sensitive emergency since untreated seizures lead to more seizures and delayed treatment contributes to morbidity and mortality. Providing sufficient evidence-based treatment early is essential to improve patient outcomes.

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Antiepileptic Drug Therapy for Status Epilepticus

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Kim D, Kim JM, Cho YW, Yang KI, Kim DW, Lee ST, et al

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE.

Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial

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Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, et al.

Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.

Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children with convulsive status epilepticus: the EcLiPSE RCT

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Appleton RE, Rainford NE, Gamble C, Messahel S, Humphreys A, Hickey H, et al.

To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management.

Levetiracetam versus Fosphenytoin in Pediatric Convulsive Status Epilepticus: A Randomized Controlled Trial

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Handral A, Veerappa BG, Gowda VK, Shivappa SK, Benakappa N, Benakappa A.

The aim of this study was to compare the efficacy and safety of intravenous levetiracetam and fosphenytoin in the management of pediatric status epilepticus.

Evaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study

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Vespa PM, Olson DM, John S, Hobbs KS, Gururangan K, Nie K, et al.

To measure the diagnostic accuracy, timeliness, and ease of use of Ceribell rapid response electroencephalography. We assessed physicians' diagnostic assessments and treatment plans before and after rapid response electroencephalography assessment. Primary outcomes were changes in physicians' diagnostic and therapeutic decision making and their confidence in these decisions based on the use of the rapid response electroencephalography system. Secondary outcomes were time to electroencephalography, setup time, ease of use, and quality of electroencephalography data.

Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus

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Guterman EL, Sanford JK, Betjemann JP, Zhang L, Burke JF, Lowenstein DH, et al.

To examine the use of benzodiazepines and the association between low benzodiazepine dose, breakthrough seizures, and respiratory support in patients with status epilepticus.

Multicenter Evaluation of Prehospital Seizure Management in Children

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Shah MI, Ostermayer DG, Browne LR, Studnek JR, Carey JM, Stanford C, et al.

We compared management of pediatric prehospital seizures across several EMS systems after protocol revision consistent with an evidence-based guideline.

First-line medication dosing in pediatric refractory status epilepticus

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Vasquez A, Ganza-Lein M, Abend NS, Amengual-Gual M, Anderson A, Arya R, et al.

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.

Diagnosis and Treatment of Status Epilepticus

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Lee SK.

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.

A Theoretical Paradigm for Evaluating Risk-Benefit of Status Epilepticus Treatment

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Amorim E, McGraw CM, Westover MB.

Aggressive treatment of status epilepticus with anesthetic drugs can provide rapid seizure control, but it might lead to serious medical complications and worse outcomes. Using a decision analysis approach, this concise review provides a framework for individualized decision making about aggressive and nonaggressive treatment in status epilepticus. The authors propose and review the most relevant parameters guiding the risk-benefit analysis of treatment aggressiveness in status epilepticus and present real-world-based case examples to illustrate how these tools could be used at the bedside and serve to guide future research in refractory status epilepticus treatment.

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

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Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, et al.

The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

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Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al.

Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.

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

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Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al.

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.

Rapid Response Electroencephalography for Urgent Evaluation of Patients in Community Hospital Intensive Care Practice

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Yazbeck M, Sra P, Parvizi J.

Limited access to specialized technicians and trained neurologists results in delayed access to electroencephalography (EEG) and an accurate diagnosis of patients with critical neurological problems. This study evaluated the performance of Ceribell Rapid Response EEG System (RR-EEG), which promises fast EEG acquisition and interpretation without traditional technicians or EEG-trained specialists.

Paramedic-Identified Enablers of and Barriers to Pediatric Seizure Management: A Multicenter, Qualitative Study

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Carey JM, Studnek JR, Browne LR, Ostermayer DG, Grawey T, Schroter S, et al.

The purpose of this study was to identify paramedic attitudes and beliefs regarding pediatric seizure management and regarding potential barriers to and enablers of adherence to evidence-based pediatric seizure protocols in multiple EMS systems.

Improving Prehospital Protocol Adherence Using Bundled Educational Interventions

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Marino MC, Ostermayer DG, Mondragon JA, Camp EA, Keating EM, Fornage LB, et a;.

To improve the quality of care for children with seizures and anaphylaxis in the prehospital setting using a bundled, multifaceted educational intervention.

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus

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Ganza-Lein M, Snchez Fernndez I, Jackson M, Abend NS, Arya R, Brenton JN, et...

To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes.

Updates in Refractory Status Epilepticus

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Marawar R, Basha M, Mahulikar A, Desai A, Suchdev K, Shah A.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Pediatric Prehospital Medication Dosing Errors: A National Survey of Paramedics

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Hoyle JD Jr, Crowe RP, Bentley MA, Beltran G, Fales W.

To describe paramedic training and practice regarding pediatric drug administration, exposure to pediatric drug dose errors and safety culture among paramedics and EMS agencies in a national sample.

Prehospital Glucose Testing for Children with Seizures: A Proposed Change in Management

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Remick K, Redgate C, Ostermayer D, Kaji AH, Gausche-Hill M.

Many Emergency Medicine Services (EMS) protocols require point-of-care blood glucose testing (BGT) for any pediatric patient who presents with seizure or altered level of conscious. Few data describe the diagnostic yield of BGT when performed on all pediatric seizures regardless of presenting mental status. We analyzed a large single center dataset of pediatric patients presenting with prehospital seizures to determine the prevalence of hypoglycemic seizures and the utility of repeat BGT in the emergency department (ED).

Pediatric status epilepticus: improved management with new drug therapies?

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Verrotti A, Ambrosi M, Pavone P, Striano P.

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated.

A Comparison of Intravenous Levetiracetam and Valproate for the Treatment of Refractory Status Epilepticus in Children

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gder R, Gzel O, Ceylan G, Ylmaz , An H.

Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer.

Impact of High-Fidelity Pediatric Simulation on Paramedic Seizure Management

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Shah MI, Carey JM, Rapp SE, Masciale M, Alcanter WB, Mondragon JA, et al.

The primary objective was to determine if PediSTEPPs enhances seizure protocol adherence in blood glucose measurement and midazolam administration for seizing children. The secondary objective was to describe management of seizing patients by EMS and Emergency Departments (EDs).

Management of Status Epilepticus in Children

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Claassen J, Goldstein JN.

Patients with prolonged or rapidly recurring convulsions lasting more than 5 min should be considered to be in status epilepticus (SE) and receive immediate resuscitation. Although there are few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason this was chosen as an Emergency Neurological Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first line therapy, as well as accelerated second line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurological critical care and electroencephalography monitoring. This protocol will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized.

Key Study: Utility of initial EEG in first complex febrile seizure

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Harini C, Nagarajan E, Kimia AA, de Carvalho RM, An S, Bergin AM, Takeoka M, ...

This retrospective study examined the utility of detected epileptiform abnormalities on the initial EEG following a first complex febrile seizure in predicting subsequent epilepsy.

Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children

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Momen AA, Azizi Malamiri R, Nikkhah A, Jafari M, Fayezi A, et al.

The aim of this study was to evaluate the efficacy and safety of intramuscular midazolam in controlling convulsive status epilepticus in children, by comparing it with rectal diazepam.

Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam--Pilot study

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Mundlamuri RC, Sinha S, Subbakrishna DK, Prathyusha PV, Nagappa M, Bindu PS, ...

This study was conducted to compare the efficacy of phenytoin, valproate and levetiracetam in patients with GCSE.

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population

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Welch RD, Nicholas K, Durkalski-Mauldin VL, Lowenstein DH, Conwit R, Mahajan ...

To examine the effectiveness of intramuscular (IM) midazolam versus intravenous (IV) lorazepam for the treatment of pediatric patients with status epilepticus (SE) in the prehospital care setting.

Factors related to delays in pre-hospital management of status epilepticus

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Kmppi L, Mustonen H, Soinila S.

This study was designed to identify factors related to delays in pre-hospital management of status epilepticus (SE).

Intravenous levetiracetam in Thai children and adolescents with status epilepticus and acute repetitive seizures

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Khongkhatithum C, Thampratankul L, Wiwattanadittakul N, Visudtibhan A.

This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents.

Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

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Alford EL, Wheless JW, Phelps SJ.

Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients.

Key Study: Emergency Management of febrile status epilepticus: results of the FEBSTAT study

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Seinfeld S, Shinnar S, Sun S, Hesdorffer DC, Deng X, Shinnar RC, O'Hara K, No...

The FEBSTAT study is a prospective study of the consequences of febrile status epilepticus. Acute management, and the relationship between treatment delay, total seizure duration and associated morbidity are analyzed.

Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial

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Chamberlain JM, Okada P, Holsti M, Mahajan P, Brown KM, Vance C, et al.

To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus

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Kim JS, Lee JH, Ryu HW, Lim BC, Hwang H, Chae JH, et al.

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE.

Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus

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Silbergleit R, Lowenstein D, Durkalski V, Conwit R

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). In children and adults with >5 min of convulsions and who are still seizing at paramedic arrival, midazolam administered by IM autoinjector was noninferior to IV lorazepam on the primary efficacy outcome with comparable safety. Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.

A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures

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Thakker A, Shanbag P.

The objective of this study is to compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of acute childhood seizures.

Key Study: Acute EEG findings in children with febrile status epilepticus: results of the FEBSTAT study

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Nordli DR Jr, Mosh SL, Shinnar S, Hesdorffer DC, Sogawa Y, Pellock JM, Lewis ...

Objective: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study prospectively addresses the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus.

Intramuscular versus intravenous therapy for prehospital status epilepticus

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Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Ba...

Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.

Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study

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Misra UK, Kalita J, Maurya PK.

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial

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Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi MR.

Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures.

Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial

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Javadzadeh M, Sheibani K, Hashemieh M, Saneifard H.

Acute seizure attack is a stressful experience both for health care personnel and parents. These attacks might cause morbidity and mortality among patients, so reliable methods to control the seizure preferably at home should be developed. This study was performed to measure the time needed to control seizure attacks using intranasal midazolam compared to the common treatment (intravenous diazepam) and to evaluate its probable side effects.

Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: experience from a children's hospital

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McTague A, Kneen R, Kumar R, Spinty S, Appleton R.

To report the effectiveness and safety of intravenous levetiracetam in the treatment of children with acute repeated seizures, and status epilepticus in a children's hospital.

Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study

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Arya R, Gulati S, Kabra M, Sahu JK, Kalra V.

Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures.

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics

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Silbergleit R, Lowenstein D, Durkalski V, Conwit R.

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting has been shown to be associated with improved outcomes. However, an increasing number of Emergency Medical System (EMS) protocols use an intramuscular (IM) route because it is faster and consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) is a double-blind randomized clinical trial to determine if the efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). Children and adults with >5 min of convulsions who are still seizing after paramedic arrival are administered study medication by IM autoinjector or IV infusion. The primary efficacy outcome is absence of seizures at emergency department (ED) arrival, without EMS rescue therapy. Safety outcomes include acute endotracheal intubation and recurrent seizures. Secondary outcomes include timing of treatment and initial seizure cessation. At the time of writing this communication, enrollment of all subjects is near completion and the study data will soon be analyzed.

Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols

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Shearer P, Riviello J.

Generalized convulsive status epilepticus (GCSE) has a high morbidity and mortality, such that the rapid delivery of anticonvulsant therapy should be initiated within minutes of seizure onset to prevent permanent neuronal damage. GCSE is not a specific disease but is a manifestation of either a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. It is mandatory to look for an underlying cause. First-line therapies for seizures and status epilepticus include the use of a benzodiazepine, followed by an infusion of a phenytoin with a possible role for intravenous valproate or phenobarbital. If these first-line medications fail to terminate the GCSE, treatment includes the continuous infusion of midazolam, pentobarbital, or propofol.

Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: a randomized controlled trial

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Sreenath TG, Gupta P, Sharma KK, Krishnamurthy S.

To determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children.

Emergency management of pediatric convulsive status epilepticus: a multicenter study of 542 patients

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Lewena S, Pennington V, Acworth J, Thornton S, Ngo P, McIntyre S, et al.

To perform a multicenter study examining the presentations and emergency management of children with convulsive status epilepticus (CSE) to sites within the Paediatric Research in Emergency Departments International Collaborative.

Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial

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Mpimbaza A, Ndeezi G, Staedke S, Rosenthal PJ, Byarugaba J.

Our goal was to compare the efficacy and safety of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children.

Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study

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Chin RF, Neville BG, Peckham C, Wade A, Bedford H, Scott RC.

Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE.

Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: a randomized controlled trial

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Mehta V, Singhi P, Singhi S.

An open-label, randomized controlled study was conducted at a tertiary care teaching hospital to compare efficacy and safety of intravenous sodium valproate versus diazepam infusion for control of refractory status epilepticus. Forty children with refractory status epilepticus were randomized to receive either intravenous sodium valproate or diazepam infusion. Refractory status epilepticus was controlled in 80% of the valproate and 85% of the diazepam patients. The median time to control refractory status epilepticus was less in the valproate group (5 minutes) than the diazepam group (17 minutes; P < .001). None of the patients in the valproate group required ventilation or developed hypotension, whereas in the diazepam group 60% required ventilation and 50% developed hypotension after starting diazepam infusion. No adverse effects on liver functions were seen with valproate. It is concluded that intravenous sodium valproate is an effective alternative to diazepam infusion in controlling refractory status epilepticus in children and is free of respiratory depression and hypotension.

Randomized study of intravenous valproate and phenytoin in status epilepticus

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Agarwal P, Kumar N, Chandra R, Gupta G, Antony AR, Garg N.

The evidence based data to guide management in patients of benzodiazepine refractory status epilepticus (SE) is still lacking. We conducted a randomized study to evaluate the comparative effect of intravenous (IV) phenytoin and intravenous valproate (IV VA) in patients of benzodiazepine refractory SE.

Key Study: Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children

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Teng D, Dayan P, Tyler S, Hauser WA, Chan S, Leary L, Hesdorffer D

Objective: To determine the likelihood of intracranial pathologic conditions requiring emergency neurosurgical or medical intervention among children without meningitis who presented to the pediatric emergency department after a first complex febrile seizure.

Sodium valproate vs phenytoin in status epilepticus: a pilot study

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Misra UK, Kalita J, Patel R.

Sixty-eight patients with convulsive status epilepticus (SE) were randomly assigned to two groups to study the efficacy of sodium valproate (VPA) and phenytoin (PHT). Seizures were aborted in 66% in the VPA group and 42% in the PHT group. As a second choice in refractory patients, VPA was effective in 79% and PHT was effective in 25%. The side effects in the two groups did not differ. Sodium valproate may be preferred in convulsive SE because of its higher efficacy.

Nonconvulsive status epilepticus in children: clinical and EEG characteristics

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Tay SK, Hirsch LJ, Leary L, Jette N, Wittman J, Akman CI.

To analyze the epidemiological, clinical, and electroencephalograpic features in pediatric patients with NCSE.

Key Study: Meningitis is a common cause of convulsive status epilepticus with fever

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Chin RF, Neville BG, Scott RC

Objective: In children with convulsive status epilepticus with fever, to determine the likelihood of acute bacterial meningitis, the proportion that are treated with antibiotics, and the proportion that have diagnostic CSF sampling.

Intramuscular midazolam vs intravenous diazepam for acute seizures

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Shah I, Deshmukh CT.

To determine effectiveness of intramuscular midazolam to control acute seizures in children as compared to intravenous diazepam.

Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial

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McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al.

Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs.

Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children

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Mahmoudian T, Zadeh MM.

Midazolam, a water-soluble benzodiazepine, is usually given intravenously in status epilepticus. The aim of this study was to determine whether intranasal midazolam is as safe and effective as intravenous diazepam in the treatment of acute childhood seizures. Seventy children aged 2 months to 15 years with acute seizures (febrile or afebrile) admitted to the pediatric emergency department of a general hospital during a 14-month period were eligible for inclusion. Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.2 mg/kg were administered after intravenous lines were established. Intranasal midazolam and intravenous diazepam were equally effective. The mean time to control of seizures was 3.58 (SD 1.68) minutes in the midazolam group and 2.94 (SD 2.62) in the diazepam group, not counting the time required to insert the intravenous line. No significant side effects were observed in either group. Although intranasal midazolam was as safe and effective as diazepam, seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Intranasal midazolam can possibly be used not only in medical centers, but also in general practice and at home after appropriate instructions are given to families of children with recurrent seizures.

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

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Yu KT, Mills S, Thompson N, Cunanan C.

To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures.

Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study

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Figin T, Gurer Y, Tezi T, Senbil N, Zorlu P, Okuyaz C, et al.

In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol.

Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

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Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M.

To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures.

Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial

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Scott RC, Besag FM, Neville BG.

Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures.

A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group

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Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al.

Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram).

A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children

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Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y.

To compare treatment of ongoing seizures using intramuscular (IM) midazolam versus intravenous (IV) diazepam.

Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus.

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Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E.

Lorazepam was compared with diazepam for the treatment of acute convulsions and status epilepticus in 102 children in a prospective, open, 'odd and even dates' trial. Convulsions were controlled in 76 per cent of patients treated with a single dose of lorazepam and 51 per cent of patients treated with a single dose of diazepam. Significantly fewer patients treated with lorazepam required additional anticonvulsants to terminate the seizure. Respiratory depression occurred in 3 per cent of lorazepam-treated patients and 15 per cent of diazepam-treated patients. No patient who received lorazepam required admission to the intensive care unit for either respiratory depression or persisting status epilepticus. Rectally administered lorazepam appeared to be particularly valuable (100 per cent efficacy) when venous access was not possible.

Antiepileptic Drug Therapy for Status Epilepticus

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Kim D, Kim JM, Cho YW, Yang KI, Kim DW, Lee ST, et al

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE.

Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial

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Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, et al.

Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.

Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children with convulsive status epilepticus: the EcLiPSE RCT

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Appleton RE, Rainford NE, Gamble C, Messahel S, Humphreys A, Hickey H, et al.

To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management.

Levetiracetam versus Fosphenytoin in Pediatric Convulsive Status Epilepticus: A Randomized Controlled Trial

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Handral A, Veerappa BG, Gowda VK, Shivappa SK, Benakappa N, Benakappa A.

The aim of this study was to compare the efficacy and safety of intravenous levetiracetam and fosphenytoin in the management of pediatric status epilepticus.

Evaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study

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Vespa PM, Olson DM, John S, Hobbs KS, Gururangan K, Nie K, et al.

To measure the diagnostic accuracy, timeliness, and ease of use of Ceribell rapid response electroencephalography. We assessed physicians' diagnostic assessments and treatment plans before and after rapid response electroencephalography assessment. Primary outcomes were changes in physicians' diagnostic and therapeutic decision making and their confidence in these decisions based on the use of the rapid response electroencephalography system. Secondary outcomes were time to electroencephalography, setup time, ease of use, and quality of electroencephalography data.

Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus

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Guterman EL, Sanford JK, Betjemann JP, Zhang L, Burke JF, Lowenstein DH, et al.

To examine the use of benzodiazepines and the association between low benzodiazepine dose, breakthrough seizures, and respiratory support in patients with status epilepticus.

Multicenter Evaluation of Prehospital Seizure Management in Children

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Shah MI, Ostermayer DG, Browne LR, Studnek JR, Carey JM, Stanford C, et al.

We compared management of pediatric prehospital seizures across several EMS systems after protocol revision consistent with an evidence-based guideline.

First-line medication dosing in pediatric refractory status epilepticus

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Vasquez A, Ganza-Lein M, Abend NS, Amengual-Gual M, Anderson A, Arya R, et al.

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.

Diagnosis and Treatment of Status Epilepticus

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Lee SK.

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.

A Theoretical Paradigm for Evaluating Risk-Benefit of Status Epilepticus Treatment

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Amorim E, McGraw CM, Westover MB.

Aggressive treatment of status epilepticus with anesthetic drugs can provide rapid seizure control, but it might lead to serious medical complications and worse outcomes. Using a decision analysis approach, this concise review provides a framework for individualized decision making about aggressive and nonaggressive treatment in status epilepticus. The authors propose and review the most relevant parameters guiding the risk-benefit analysis of treatment aggressiveness in status epilepticus and present real-world-based case examples to illustrate how these tools could be used at the bedside and serve to guide future research in refractory status epilepticus treatment.

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

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Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, et al.

The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

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Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al.

Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.

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

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Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al.

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.

Rapid Response Electroencephalography for Urgent Evaluation of Patients in Community Hospital Intensive Care Practice

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Yazbeck M, Sra P, Parvizi J.

Limited access to specialized technicians and trained neurologists results in delayed access to electroencephalography (EEG) and an accurate diagnosis of patients with critical neurological problems. This study evaluated the performance of Ceribell Rapid Response EEG System (RR-EEG), which promises fast EEG acquisition and interpretation without traditional technicians or EEG-trained specialists.

Paramedic-Identified Enablers of and Barriers to Pediatric Seizure Management: A Multicenter, Qualitative Study

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Carey JM, Studnek JR, Browne LR, Ostermayer DG, Grawey T, Schroter S, et al.

The purpose of this study was to identify paramedic attitudes and beliefs regarding pediatric seizure management and regarding potential barriers to and enablers of adherence to evidence-based pediatric seizure protocols in multiple EMS systems.

Improving Prehospital Protocol Adherence Using Bundled Educational Interventions

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Marino MC, Ostermayer DG, Mondragon JA, Camp EA, Keating EM, Fornage LB, et a;.

To improve the quality of care for children with seizures and anaphylaxis in the prehospital setting using a bundled, multifaceted educational intervention.

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus

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Ganza-Lein M, Snchez Fernndez I, Jackson M, Abend NS, Arya R, Brenton JN, et...

To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes.

Updates in Refractory Status Epilepticus

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Marawar R, Basha M, Mahulikar A, Desai A, Suchdev K, Shah A.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Pediatric Prehospital Medication Dosing Errors: A National Survey of Paramedics

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Hoyle JD Jr, Crowe RP, Bentley MA, Beltran G, Fales W.

To describe paramedic training and practice regarding pediatric drug administration, exposure to pediatric drug dose errors and safety culture among paramedics and EMS agencies in a national sample.

Prehospital Glucose Testing for Children with Seizures: A Proposed Change in Management

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Remick K, Redgate C, Ostermayer D, Kaji AH, Gausche-Hill M.

Many Emergency Medicine Services (EMS) protocols require point-of-care blood glucose testing (BGT) for any pediatric patient who presents with seizure or altered level of conscious. Few data describe the diagnostic yield of BGT when performed on all pediatric seizures regardless of presenting mental status. We analyzed a large single center dataset of pediatric patients presenting with prehospital seizures to determine the prevalence of hypoglycemic seizures and the utility of repeat BGT in the emergency department (ED).

Pediatric status epilepticus: improved management with new drug therapies?

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Verrotti A, Ambrosi M, Pavone P, Striano P.

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated.

A Comparison of Intravenous Levetiracetam and Valproate for the Treatment of Refractory Status Epilepticus in Children

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gder R, Gzel O, Ceylan G, Ylmaz , An H.

Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer.

Impact of High-Fidelity Pediatric Simulation on Paramedic Seizure Management

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Shah MI, Carey JM, Rapp SE, Masciale M, Alcanter WB, Mondragon JA, et al.

The primary objective was to determine if PediSTEPPs enhances seizure protocol adherence in blood glucose measurement and midazolam administration for seizing children. The secondary objective was to describe management of seizing patients by EMS and Emergency Departments (EDs).

Management of Status Epilepticus in Children

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Claassen J, Goldstein JN.

Patients with prolonged or rapidly recurring convulsions lasting more than 5 min should be considered to be in status epilepticus (SE) and receive immediate resuscitation. Although there are few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason this was chosen as an Emergency Neurological Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first line therapy, as well as accelerated second line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurological critical care and electroencephalography monitoring. This protocol will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized.

Key Study: Utility of initial EEG in first complex febrile seizure

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Harini C, Nagarajan E, Kimia AA, de Carvalho RM, An S, Bergin AM, Takeoka M, ...

This retrospective study examined the utility of detected epileptiform abnormalities on the initial EEG following a first complex febrile seizure in predicting subsequent epilepsy.

Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children

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Momen AA, Azizi Malamiri R, Nikkhah A, Jafari M, Fayezi A, et al.

The aim of this study was to evaluate the efficacy and safety of intramuscular midazolam in controlling convulsive status epilepticus in children, by comparing it with rectal diazepam.

Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam--Pilot study

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Mundlamuri RC, Sinha S, Subbakrishna DK, Prathyusha PV, Nagappa M, Bindu PS, ...

This study was conducted to compare the efficacy of phenytoin, valproate and levetiracetam in patients with GCSE.

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population

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Welch RD, Nicholas K, Durkalski-Mauldin VL, Lowenstein DH, Conwit R, Mahajan ...

To examine the effectiveness of intramuscular (IM) midazolam versus intravenous (IV) lorazepam for the treatment of pediatric patients with status epilepticus (SE) in the prehospital care setting.

Factors related to delays in pre-hospital management of status epilepticus

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Kmppi L, Mustonen H, Soinila S.

This study was designed to identify factors related to delays in pre-hospital management of status epilepticus (SE).

Intravenous levetiracetam in Thai children and adolescents with status epilepticus and acute repetitive seizures

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Khongkhatithum C, Thampratankul L, Wiwattanadittakul N, Visudtibhan A.

This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents.

Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

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Alford EL, Wheless JW, Phelps SJ.

Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients.

Key Study: Emergency Management of febrile status epilepticus: results of the FEBSTAT study

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Seinfeld S, Shinnar S, Sun S, Hesdorffer DC, Deng X, Shinnar RC, O'Hara K, No...

The FEBSTAT study is a prospective study of the consequences of febrile status epilepticus. Acute management, and the relationship between treatment delay, total seizure duration and associated morbidity are analyzed.

Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial

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Chamberlain JM, Okada P, Holsti M, Mahajan P, Brown KM, Vance C, et al.

To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus

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Kim JS, Lee JH, Ryu HW, Lim BC, Hwang H, Chae JH, et al.

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE.

Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus

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Silbergleit R, Lowenstein D, Durkalski V, Conwit R

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). In children and adults with >5 min of convulsions and who are still seizing at paramedic arrival, midazolam administered by IM autoinjector was noninferior to IV lorazepam on the primary efficacy outcome with comparable safety. Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.

A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures

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Thakker A, Shanbag P.

The objective of this study is to compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of acute childhood seizures.

Key Study: Acute EEG findings in children with febrile status epilepticus: results of the FEBSTAT study

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Nordli DR Jr, Mosh SL, Shinnar S, Hesdorffer DC, Sogawa Y, Pellock JM, Lewis ...

Objective: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study prospectively addresses the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus.

Intramuscular versus intravenous therapy for prehospital status epilepticus

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Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Ba...

Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.

Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study

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Misra UK, Kalita J, Maurya PK.

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial

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Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi MR.

Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures.

Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial

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Javadzadeh M, Sheibani K, Hashemieh M, Saneifard H.

Acute seizure attack is a stressful experience both for health care personnel and parents. These attacks might cause morbidity and mortality among patients, so reliable methods to control the seizure preferably at home should be developed. This study was performed to measure the time needed to control seizure attacks using intranasal midazolam compared to the common treatment (intravenous diazepam) and to evaluate its probable side effects.

Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: experience from a children's hospital

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McTague A, Kneen R, Kumar R, Spinty S, Appleton R.

To report the effectiveness and safety of intravenous levetiracetam in the treatment of children with acute repeated seizures, and status epilepticus in a children's hospital.

Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study

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Arya R, Gulati S, Kabra M, Sahu JK, Kalra V.

Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures.

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics

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Silbergleit R, Lowenstein D, Durkalski V, Conwit R.

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting has been shown to be associated with improved outcomes. However, an increasing number of Emergency Medical System (EMS) protocols use an intramuscular (IM) route because it is faster and consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) is a double-blind randomized clinical trial to determine if the efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). Children and adults with >5 min of convulsions who are still seizing after paramedic arrival are administered study medication by IM autoinjector or IV infusion. The primary efficacy outcome is absence of seizures at emergency department (ED) arrival, without EMS rescue therapy. Safety outcomes include acute endotracheal intubation and recurrent seizures. Secondary outcomes include timing of treatment and initial seizure cessation. At the time of writing this communication, enrollment of all subjects is near completion and the study data will soon be analyzed.

Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols

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Shearer P, Riviello J.

Generalized convulsive status epilepticus (GCSE) has a high morbidity and mortality, such that the rapid delivery of anticonvulsant therapy should be initiated within minutes of seizure onset to prevent permanent neuronal damage. GCSE is not a specific disease but is a manifestation of either a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. It is mandatory to look for an underlying cause. First-line therapies for seizures and status epilepticus include the use of a benzodiazepine, followed by an infusion of a phenytoin with a possible role for intravenous valproate or phenobarbital. If these first-line medications fail to terminate the GCSE, treatment includes the continuous infusion of midazolam, pentobarbital, or propofol.

Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: a randomized controlled trial

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Sreenath TG, Gupta P, Sharma KK, Krishnamurthy S.

To determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children.

Emergency management of pediatric convulsive status epilepticus: a multicenter study of 542 patients

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Lewena S, Pennington V, Acworth J, Thornton S, Ngo P, McIntyre S, et al.

To perform a multicenter study examining the presentations and emergency management of children with convulsive status epilepticus (CSE) to sites within the Paediatric Research in Emergency Departments International Collaborative.

Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial

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Mpimbaza A, Ndeezi G, Staedke S, Rosenthal PJ, Byarugaba J.

Our goal was to compare the efficacy and safety of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children.

Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study

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Chin RF, Neville BG, Peckham C, Wade A, Bedford H, Scott RC.

Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE.

Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: a randomized controlled trial

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Mehta V, Singhi P, Singhi S.

An open-label, randomized controlled study was conducted at a tertiary care teaching hospital to compare efficacy and safety of intravenous sodium valproate versus diazepam infusion for control of refractory status epilepticus. Forty children with refractory status epilepticus were randomized to receive either intravenous sodium valproate or diazepam infusion. Refractory status epilepticus was controlled in 80% of the valproate and 85% of the diazepam patients. The median time to control refractory status epilepticus was less in the valproate group (5 minutes) than the diazepam group (17 minutes; P < .001). None of the patients in the valproate group required ventilation or developed hypotension, whereas in the diazepam group 60% required ventilation and 50% developed hypotension after starting diazepam infusion. No adverse effects on liver functions were seen with valproate. It is concluded that intravenous sodium valproate is an effective alternative to diazepam infusion in controlling refractory status epilepticus in children and is free of respiratory depression and hypotension.

Randomized study of intravenous valproate and phenytoin in status epilepticus

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Agarwal P, Kumar N, Chandra R, Gupta G, Antony AR, Garg N.

The evidence based data to guide management in patients of benzodiazepine refractory status epilepticus (SE) is still lacking. We conducted a randomized study to evaluate the comparative effect of intravenous (IV) phenytoin and intravenous valproate (IV VA) in patients of benzodiazepine refractory SE.

Key Study: Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children

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Teng D, Dayan P, Tyler S, Hauser WA, Chan S, Leary L, Hesdorffer D

Objective: To determine the likelihood of intracranial pathologic conditions requiring emergency neurosurgical or medical intervention among children without meningitis who presented to the pediatric emergency department after a first complex febrile seizure.

Sodium valproate vs phenytoin in status epilepticus: a pilot study

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Misra UK, Kalita J, Patel R.

Sixty-eight patients with convulsive status epilepticus (SE) were randomly assigned to two groups to study the efficacy of sodium valproate (VPA) and phenytoin (PHT). Seizures were aborted in 66% in the VPA group and 42% in the PHT group. As a second choice in refractory patients, VPA was effective in 79% and PHT was effective in 25%. The side effects in the two groups did not differ. Sodium valproate may be preferred in convulsive SE because of its higher efficacy.

Nonconvulsive status epilepticus in children: clinical and EEG characteristics

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Tay SK, Hirsch LJ, Leary L, Jette N, Wittman J, Akman CI.

To analyze the epidemiological, clinical, and electroencephalograpic features in pediatric patients with NCSE.

Key Study: Meningitis is a common cause of convulsive status epilepticus with fever

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Chin RF, Neville BG, Scott RC

Objective: In children with convulsive status epilepticus with fever, to determine the likelihood of acute bacterial meningitis, the proportion that are treated with antibiotics, and the proportion that have diagnostic CSF sampling.

Intramuscular midazolam vs intravenous diazepam for acute seizures

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Shah I, Deshmukh CT.

To determine effectiveness of intramuscular midazolam to control acute seizures in children as compared to intravenous diazepam.

Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial

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McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al.

Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs.

Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children

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Mahmoudian T, Zadeh MM.

Midazolam, a water-soluble benzodiazepine, is usually given intravenously in status epilepticus. The aim of this study was to determine whether intranasal midazolam is as safe and effective as intravenous diazepam in the treatment of acute childhood seizures. Seventy children aged 2 months to 15 years with acute seizures (febrile or afebrile) admitted to the pediatric emergency department of a general hospital during a 14-month period were eligible for inclusion. Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.2 mg/kg were administered after intravenous lines were established. Intranasal midazolam and intravenous diazepam were equally effective. The mean time to control of seizures was 3.58 (SD 1.68) minutes in the midazolam group and 2.94 (SD 2.62) in the diazepam group, not counting the time required to insert the intravenous line. No significant side effects were observed in either group. Although intranasal midazolam was as safe and effective as diazepam, seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Intranasal midazolam can possibly be used not only in medical centers, but also in general practice and at home after appropriate instructions are given to families of children with recurrent seizures.

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

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Yu KT, Mills S, Thompson N, Cunanan C.

To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures.

Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study

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Figin T, Gurer Y, Tezi T, Senbil N, Zorlu P, Okuyaz C, et al.

In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol.

Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

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Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M.

To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures.

Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial

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Scott RC, Besag FM, Neville BG.

Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures.

A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group

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Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al.

Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram).

A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children

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Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y.

To compare treatment of ongoing seizures using intramuscular (IM) midazolam versus intravenous (IV) diazepam.

Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus.

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Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E.

Lorazepam was compared with diazepam for the treatment of acute convulsions and status epilepticus in 102 children in a prospective, open, 'odd and even dates' trial. Convulsions were controlled in 76 per cent of patients treated with a single dose of lorazepam and 51 per cent of patients treated with a single dose of diazepam. Significantly fewer patients treated with lorazepam required additional anticonvulsants to terminate the seizure. Respiratory depression occurred in 3 per cent of lorazepam-treated patients and 15 per cent of diazepam-treated patients. No patient who received lorazepam required admission to the intensive care unit for either respiratory depression or persisting status epilepticus. Rectally administered lorazepam appeared to be particularly valuable (100 per cent efficacy) when venous access was not possible.