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

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.

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.

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.

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