Intravenous Versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
The acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity.



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



A systematic review was performed 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 IV to non-IV (buccal, rectal, intranasal, or intramuscular) BDZ were included.



Our search strategy retrieved 2,604 citations for review. A 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] = 0.56-0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74-1.81). Non-IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69-5.13 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 = 0.00; 95% CI = -0.02 to 0.01).



Non-IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher-quality studies and further evaluation in different age groups are warranted.
Department of Emergency Medicine, King Saud Medical City, Riyadh, Saudi Arabia.
Abdussalam
A
Alshehri
Department of Neurology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Ahmad
A
Abulaban
Division of Neurosurgery, King Abdulaziz University, Jeddah, Saudi Arabia.
Rakan
R
Bokhari
Department of Neurology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.|King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Suleiman
S
Kojan
Department of Emergency Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.|College of Public Health and Health Informatics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Majid
M
Alsalamah
Department of Family Medicine and Primary Health Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia.|King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Mazen
M
Ferwana
Department of Internal Medicine, Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN.
Mohammad Hassan
MH
Murad
D061605:Administration, Intravenous; D001569:Benzodiazepines / Q000008:administration & dosage*; D002648:Child; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome
D001569:Benzodiazepines