Intravenous versus Non-Intravenous Benzodiazepines for the Abortion of Seizures: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Background

The acquisition of intravenous access in the actively convulsing patient is difficult. This often delays the administration of the intravenous benzodiazepine necessary for seizure abortion. Delays in seizure abortion are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes and increased morbidity.

Objective

To assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non-IV benzodiazepine efficacy in the real world with regards to failure rates (primary outcome), interval to seizure control and observed complications (secondary outcomes).

Methods

A systematic review using Medline, Embase and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi-randomized controlled trials directly comparing an intra-venous to a non-intravenous (buccal, rectal, intranasal or intramuscular) benzodiazepine were included.

Results

Our search strategy retrieved 2604 citations for review. Total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non-IV BDZ was superior to IV BDZ (Odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56 to 0.92). However, no significant difference between the two treatments in pediatric subgroup (OR = 1.16; 95% CI = 0.74 to 1.81).

Non-IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69 to 5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52-0.95 minutes. Respiratory complications requiring intervention were similar between non-IV BDZ and IV BDZ, regardless of administration route (Risk Difference [RD] =0.00; 95% CI = -0.02 to 0.01).

Conclusions

Non-IV BDZ, compared to IV BDZ, abort seizures faster and have a superior efficacy and side effect profile. Higher quality studies and further evaluation in different age groups are warranted.

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