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.
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.
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VA and CC are joint first authors.
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Contributors VA: this author helped in study design/planning, interpretation of results, manuscript draft, and review. CC: this author helped in study design/planning, interpretation of results, manuscript preparation, and review. HZ: this author helped in study design/planning, data analysis, interpretation of results, manuscript preparation, and review. JP: this author helped in study design/planning, interpretation of results, and manuscript review. JB: this author helped in study design/planning, interpretation of results, and manuscript review. AI: this author helped in study design/planning, interpretation of results, and manuscript review. LP: this author helped in study design/planning, interpretation of results, and manuscript review. SGM: this author helped in study design/planning, interpretation of results, manuscript preparation, and review. SGM is the guarantor of the study and affirms that the manuscript is an honest, accurate and transparent account of the current data analysis; that no important aspects of the study have been omitted, and that any discrepancies from the study as originally planned have been explained.
Funding This work was supported by the Research and Education Fund, Department of Anesthesiology, Critical Care & Pain, Hospital for Special Surgery.
Competing interests SGM is a one-time consultant for Sandoz Inc and Teikoku. He is the owner of a US Patent for a Multicatheter Infusion System. US-2017-0361063. He is the owner of SGM Consulting, LLC and co-owner of FC Monmouth, LLC. None of the above relations influenced the conduct of the present study. All other authors declare no competing interest.
Provenance and peer review Not commissioned; externally peer reviewed.