AUTHOR=Prin Meghan, Pattee Jack, Douin David J., Scott Benjamin K., Ginde Adit A., Eckle Tobias
TITLE=Time-of-day dependent effects of midazolam administration on myocardial injury in non-cardiac surgery
JOURNAL=Frontiers in Cardiovascular Medicine
VOLUME=9
YEAR=2022
URL=https://www.frontiersin.org/articles/10.3389/fcvm.2022.982209
DOI=10.3389/fcvm.2022.982209
ISSN=2297-055X
ABSTRACT=BackgroundAnimal studies have shown that midazolam can increase vulnerability to cardiac ischemia, potentially via circadian-mediated mechanisms. We hypothesized that perioperative midazolam administration is associated with an increased incidence of myocardial injury in patients undergoing non-cardiac surgery (MINS) and that circadian biology may underlie this relationship.MethodsWe analyzed intraoperative data from the Multicenter Perioperative Outcomes Group for the occurrence of MINS across 50 institutions from 2014 to 2019. The primary outcome was the occurrence of MINS. MINS was defined as having at least one troponin-I lab value ≥0.03 ng/ml from anesthesia start to 72 h after anesthesia end. To account for bias, propensity scores and inverse probability of treatment weighting were applied.ResultsA total of 1,773,118 cases were available for analysis. Of these subjects, 951,345 (53.7%) received midazolam perioperatively, and 16,404 (0.93%) met criteria for perioperative MINS. There was no association between perioperative midazolam administration and risk of MINS in the study population as a whole (odds ratio (OR) 0.98, confidence interval (CI) [0.94, 1.01]). However, we found a strong association between midazolam administration and risk of MINS when surgery occurred overnight (OR 3.52, CI [3.10, 4.00]) or when surgery occurred in ASA 1 or 2 patients (OR 1.25, CI [1.13, 1.39]).ConclusionPerioperative midazolam administration may not pose a significant risk for MINS occurrence. However, midazolam administration at night and in healthier patients could increase MINS, which warrants further clinical investigation with an emphasis on circadian biology.