Article Text

other Versions

Download PDFPDF
Association of perioperative midazolam use and complications: a population-based analysis


Introduction The benzodiazepine midazolam is the main sedative used in the perioperative setting, resulting in anxiolysis and a reduction in anesthetic dose requirements. However, benzodiazepine use is also associated with potentially serious side effects including respiratory complications, and postoperative delirium (POD). A paucity of population level data exists on current perioperative midazolam use in adult orthopedic surgery and its effects on complications. Using a large national dataset, we aimed to determine perioperative midazolam utilization patterns and to analyze its effect on postoperative outcomes.

Methods Patients who underwent total knee and hip arthroplasty (TKA/THA) were identified from Premier database (2006–2019). Primary exposure of interest was midazolam use on the day of surgery. Multivariable logistic regression models were run to determine if midazolam was associated with postoperative cardiac and pulmonary complications, delirium, and in-hospital falls.

Results Among 2,848,897 patients, more than 75% received midazolam perioperatively. This was associated with increased adjusted odds for in-hospital falls in TKA/THA (OR 1.1, 95% CI 1.07 to 1.14)/(OR 1.1, 95% CI 1.06 to 1.16), while a decrease in the adjusted odds for cardiac complications in TKA/THA (OR 0.94, 95% CI 0.91 to 0.97)/(OR 0.93, 95% CI 0.89 to 0.97), and pulmonary complications (OR 0.92, 95% CI 0.87 to 0.96) (all p<0.001) was seen. Most notably, the concurrent use of midazolam and gabapentinoids significantly increased the adjusted odds for postoperative complications, including pulmonary complications (OR 1.22, 95% CI 1.18 to 1.27)/(OR 1.29, 95% CI 1.22 to 1.37), naloxone utilization (OR 1.56, 95% CI 1.51 to 1.60)/(OR 1.49, 95% CI 1.42 to 1.56), and POD (OR 1.45, 95% CI 1.38 to 1.52)/(OR 1.32, 95% CI 1.23 to 1.34) in THA/TKA.

Conclusion Perioperative midazolam use was associated with an increase in postoperative patient falls, and a decrease in cardiac complications. Notably, the combined use of midazolam and gabapentinoids was associated with a substantial increase in the odds for respiratory failure and delirium. Given the high prevalence of benzodiazepines perioperatively, the risk benefit profile should be more clearly established to inform perioperative decision making.

  • anesthesia
  • conduction
  • analgesia
  • epidemiology

Data availability statement

Data may be obtained from a third party and are not publicly available. Data obtained from a third party, Premier (Premier Healthcare Solutions, Charlotte, North Carolina, USA), and are not publicly available.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.