Is intravenous lorazepam really more effective and safe than intravenous diazepam as first-line treatment for convulsive status epilepticus? A systematic review with meta-analysis of randomized controlled trials

Abstract

Some guidelines or expert consensus indicate that intravenous (IV) lorazepam (LZP) is preferable to IV diazepam (DZP) for initial treatment of convulsive status epilepticus (SE). We aimed to critically assess all the available data on efficacy and tolerability of IV LZP compared with IV DZP as first-line treatment of convulsive SE. Systematic search of the literature (MEDLINE, CENTRAL, EMBASE, ClinicalTrials.gov) to identify randomized controlled trials (RCTs) comparing IV LZP versus IV DZP used as first-line treatment for convulsive SE (generalized or focal). Inverse variance, Mantel-Haenszel meta-analysis to obtain risk ratio (RR) with 95% confidence intervals (CI) of following outcomes: seizure cessation after drug administration; continuation of SE requiring a different drug; seizure cessation after a single dose of medication; need for ventilator support; clinically relevant hypotension. Five RCTs were included, with a total of 656 patients, 320 randomly allocated to IV LZP and 336 to IV DZP. No statistically significant differences were found between IV LZP and IV DZP for clinical seizure cessation (RR 1.09; 95% CI 1.00 to 1.20), continuation of SE requiring a different drug (RR 0.76; 95% CI 0.57 to 1.02), seizure cessation after a single dose of medication (RR 0.96; 95% CI 0.85 to 1.08), need for ventilator support RR 0.93; 95% CI 0.61 to 1.43, and clinically relevant hypotension. Despite its favorable pharmacokinetic profile, a systematic appraisal of the literature does not provide evidence to strongly support the preferential use of IV LZP as first-line treatment of convulsive SE over IV DZP.