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First-Line Anti-Epileptic Medication for Management of Acute Convulsive Seizures, When Intravenous Access Is Available [2015]

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First-Line Anti-Epileptic Medication for Management of Acute Convulsive Seizures, When Intravenous Access Is Available [2015] [2015] EPI 2: First-line anti-epileptic medication for management of acute convulsive seizures, when intravenous access is available [2015] SCOPING QUESTION: In adults with acute convulsive seizures, where intravenous access is available, which first-line anti- epileptic medication should be used to abort seizures when compared to comparator? Back to Table of Contents BACKGROUND Acute convulsive seizures are a medical emergency in adults that commonly present in emergency rooms and require prompt recognition and management. Although most seizures self-terminate within 5 minutes, seizures that last longer than 5–10 minutes are at high risk of continuing for at least 30 minutes. Once a seizure lasts for >5-10 minutes, it is unlikely to stop spontaneously within the next few minutes and so intervention is indicated (Shinnar et al., 2001). The current operational definition of status epilepticus (SE) is ≥5 minutes of continuous seizures or ≥2 discrete seizures without complete recovery of consciousness in between (Lowenstein et al., 2001). The use of this operational definition allows for starting treatment early (within 5-10 minutes). It is also recognized that for a majority of seizures occurring in the out-of-hospital settings it is virtually impossible to ascertain the onset, which makes it very difficult to determine even the approximate duration of the seizure. Therefore, the definition of SE has been expanded to include any patient who is brought convulsing to the emergency room (Lowenstein et al, 2001; Aldredge et al., 2001). Immediate treatment of acute convulsive seizures or SE is crucial to prevent adverse neurologic and systemic consequences. Multiple protocols for management of acute convulsive seizures and SE are available (Mazurkiewicz-Bełdzińska et al., 2014; Hirsch et al., 2013; Claassen et al., 2012; Minicucci et al., 2006). It has been shown that the use of any protocol for SE management leads to a better outcome, as compared to when a protocol is not used (Tirupathi et al., 2009). When selecting the most appropriate antiepileptic medications for seizure control, the pharmacokinetics of the intervention must also be considered. This includes, for example, the duration of action and the mode of administration. Diazepam has traditionally been the medication of choice for intravenous (IV) preparations of benzodiazepines. Recently, lorazepam is suggested as a preferred option in view of perceived better efficacy, reduced risk of respiratory depression and long duration of action (Appleton et al., 2008; Aneja, 2012). However, lorazepam needs refrigeration when stored, which may limit its use in low- and middle-income countries (LAMICs) in field settings (Anejja, 2012; Gottwald et al., 1999). [2015] This scoping question aims incorporate new evidence on these interventions published since 2009 and to identify and recommend the best first-line treatment option in adults with acute convulsive seizures, where IV access is available in LAMICs. PART 1: EVIDENCE REVIEW Population/ Intervention / Comparison / Outcome (PICO) Population: Adults presenting with SE or acute convulsive seizures where IV access is available Interventions: IV diazepam, IV lorazepam, IV midazolam, IV phenobarbital, IV phenytoin Comparison: One intervention vs. another intervention Outcomes: o Critical – Non-cessation of seizures, death, requirement for ventilator support Search strategy To identify relevant systematic reviews, the following databases were searched: Medline, Embase, The Cochrane Library, BMJ Clinical Evidence and PsychINFO up to July 2014. The search strategy developed by McMaster University was adapted and applied as follows: (meta analysis [Publication Type] OR meta analysis [Title/Abstract] OR meta analysis [MeSH Terms] OR review[Publication Type] OR search*[Title/Abstract]). The following additional terms were used: (status epilepticus OR acute seizures) AND (midazolam OR diazepam OR lorazepam OR phenobarbital OR phenytoin). In order to identify additional primary studies, the search strategy used in the Prasad et al.. (2005) Cochrane Review was replicated and applied as follows: (1) Cochrane Central Database of Controlled Trials (CENTRAL); (2) MEDLINE; (3) EMBASE. The search terms used included the following text words: (status epilepticus), (anti-epileptic therapy) and names of the medication (midazolam OR diazepam OR lorazepam OR phenobarbital OR phenytoin) in combination with any of the above words. This search was supplemented by the following search strategy the McMaster University search strategy as follows: [2015] (randomized controlled trial [Publication Type] OR randomized[Title/Abstract] OR placebo[Title/Abstract]). The following additional terms were used: (status epilepticus OR acute seizures) AND (midazolam OR diazepam OR lorazepam OR phenobarbital OR phenytoin). Inclusion and exclusion criteria for this review Type of studies Randomized controlled trials (RCTs) Types of participants Adults ( > 18 years of age) presenting with an acute seizure (either hospital or community setting) and who received treatment with an IV anti-epileptic medication, irrespective of the duration of the presenting convulsion. These included those presenting de novo with a first convulsion and those with an established diagnosis of epilepsy. Any and all causes of the convulsion (including convulsive status epilepticus) were included in the review. In scenarios where studies on adults were not available, studies on children or studies with both adults and children enrolled were included. Types of interventions In adults presenting with an acute seizure including status epilepticus, we included trials if they compared one treatment with another. Specific medication included intravenous benzodiazepines (diazepam, lorazepam and midazolam), intravenous phenytoin and phenobarbital. Combination therapies (e.g. diazepam plus phenytoin) were excluded. Types of outcome measures i. Non-cessation of seizures: The term ‘non-cessation of seizures’ was used rather than ‘cessation of seizures’ (which is used in the various studies) to be in consistent with Prasad et al.’s (2014) Cochrane Review on which the evidence profile is based. This outcome was used in the Cochrane Review to maintain uniformity with the other outcomes, which were unfavorable. The timeline for non-cessation of seizures have not been specified in the Cochrane Review and varies across studies. ii. Death iii. Requirement for ventilator support [2015] Data collection and analysis Two members of the research team independently assessed trials for inclusion. The methodological quality of each trial was assessed using the following criteria: Randomization method; Baseline comparability of the trial arms; Blinding; and Whether the published data permitted an intention-to-treat (ITT) analysis. Data were independently extracted by two review authors and cross-checked. Data on the number of participants sought for each outcome event by allocated treatment group in order to allow for an ITT analysis. Included in GRADE tables or footnotes Prasad M, Krishnan PR, Sequeira R, Al-Roomi K (2014). Anticonvulsant therapy for status epilepticus. Cochrane Database of Systematic Reviews.9:CD003723. doi:10.1002/14651858.CD003723.pub3 Chamberlain JM, Okada P, Holsti M, Mahajan P, Brown KM, Vance C et al. (2014). Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial. The Journal of the American Medical Association.311(16):1652-1660. doi:10.1001/jama.2014.2625. Gathwala G, Goel M, Singh J, Mittal K (2012). Intravenous diazepam, midazolam and lorazepam in acute seizure control. Indian Journal of Pediatrics. 79(3):327-332. doi:10.1007/s12098-011-0505-y. Excluded from GRADE tables and footnotes Appleton R, Macleod S, Martland T (2008). Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews.3:CD001905. REASON FOR EXCLUSION: Review is not focused on treatment in adults. [2015] Sreenath TG, Gupta P, Sharma KK, Krishnamurthy S (2010). Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: a randomized controlled trial. European Journal of Paediatric Neurology. 14(2):162-168. doi:10.1016/j.ejpn.2009.02.004. REASON FOR EXCLUSION: One of the interventions was a combination treatment, which was not the intervention of interest. PICO Table Population: Adults presenting with SE or acute convulsive seizures where IV access is available Relevant Intervention Comparison Outcome Systematic review/study selected and justification for use GRADE table IV lorazepam IV diazepam Non-cessation of Update of the Prasad et al. (2014) Cochrane Review meta-analysis, with Table 1 seizure inclusion of the following studies: Chamberlain et al. (2014) Gathwala et al. (2012) Death Update of the Prasad et al. 2014 Cochrane Review meta-analysis with inclusion of the following studies Chamberlain et al. 2014 Gathwala et al. 2012 Requirement for Update of the Prasad et al. (2014) Cochrane Review meta-analysis with ventilator support inclusion of the following studies Chamberlain et al. 2014 Gathwala et al. 2012 IV lorazepam IV phenytoin Non-cessation of Recent and relevant Prasad et al.’s (2014) Cochrane Review Table 2 seizures Death None Requirement for Recent and relevant Prasad et al.’s (2014) Cochrane Review ventilator support IV lorazepam IV phenobarbital Non-cessation of Recent and relevant Prasad et al.’s (2014) Cochrane Review Table
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