Impact of benzodiazepines on time to awakening in post cardiac arrest patients.

Aim: Although guidelines recommend use of short acting sedation after cardiac arrest, there is significant practice variation. We examined whether benzodiazepine use is associated with delayed awakening in this population.

Methods: We performed a retrospective single center study including comatose patients treated after in- or out-of-hospital cardiac arrest from January 2010 to September 2019. We excluded patients who awakened within 6 h of arrest, those who arrested due to trauma or neurological event, those with nonsurvivable primary brain injury and those with refractory shock. Our primary exposure of interest was high-dose benzodiazepine (>10 mg of midazolam equivalents per day) administration in the first 72-h post arrest. Our primary outcome was time to awakening. We used Cox regression to test for an independent association between exposure and outcome after controlling for biologically plausible covariates.

Results: Overall, 2778 patients presented during the study period, 621 met inclusion criteria and 209 (34%) awakened after a median of 4 [IQR 3-7] days. Patients who received high-dose benzodiazepines awakened later than those who did not (5 [IQR 3-11] vs. 3 [IQR 3-6] days, P = 0.004). In adjusted regression, high-dose benzodiazepine exposure was independently associated with delayed awakening (adjusted hazard ratio 0.63 (95% CI 0.43-0.92)). Length of stay, awakening to discharge, and duration of mechanical ventilation were similar across groups.

Conclusion: High-dose benzodiazepine exposure is independently associated with delayed awakening in comatose survivors of cardiac arrest.