Efficacy and safety of anti-epileptic drugs in patients with active convulsive seizures when no IV access is available: Systematic review and meta-analysis

•Earliest termination of acute seizure is critical.•Numerous non-intravenous routes for benzodiazepines are available.•Available evidence has ‘very low’ to ‘moderate’ quality.•Preference may be guided by availability, expertise and social preference.

ObjectivesTo explore the existing evidence for anti-convulsant drugs and their routes of administration in treating acute seizures in children and adults when intravenous access is not available.MethodsAll major databases including Medline via Ovid, PubMed, Cochrane CENTRAL, Embase, and Google Scholar were searched till May 2015. Randomized and quasi-randomized controlled trials comparing two anti-convulsant drugs (at least one comparator being administered through non-intravenous route) for treatment of acute seizures were included.Outcome measuresPrimary outcome measure was proportion of children with clinical seizure cessation within 10 min of drug administration. Secondary outcome measures were time taken to clinical seizure cessation from the time of admission and from the time of drug administration, and incidence of significant adverse effects.ResultsOut of the 19,165 citations, 26 studies were finally included. Regarding the primary outcome measure, the quality of evidence was ‘moderate’ for following 3 comparisons: buccal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.06–1.24), intra-nasal lorazepam being same as intravenous lorazepam (RR 1.04; 95% CI, 0.89–1.22) and intramuscular paraldehyde (RR 1.22; 95% CI, 0.99–1.52). The quality of evidence was ‘very-low’ for 1 comparison: per-rectal lorazepam being superior to per-rectal diazepam (RR 3.17; 95% CI, 1.63–6.14). The quality of evidence was ‘low’ for following 2 comparisons: sub-lingual lorazepam being inferior to rectal diazepam (RR 0.71; 95% CI, 0.62–0.81), and intranasal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.05–1.25). The rest of the comparisons did not show any difference, but the quality of evidence was ‘low’ to ‘very low’. The time to seizure cessation after drug administration was lower in the intravenous group. However, time to seizure cessation after presentation (includes time for drug administration) was lower in the non-intravenous group. Significant adverse effects were infrequently reported and when present, were similar in both the groups.ConclusionsWhen intravenous access is not available, non-intravenous routes of administration of benzodiazepines should be considered for the control of acute seizures in children/adults. The preference may be guided by availability, expertise and social preference. [PROSPERO No: CRD42015019012].