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Background Delirium is an important postoperative complication. Recent research suggested that 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonists may have clinical effect in the treatment and prevention of delirium. We investigated the association between 5-HT 3  receptor antagonists and the occurrence of postoperative delirium (POD). Methods Retrospectively, the electronic medical records were reviewed in patients aged ≥ 65 years who underwent orthopedic lower limb surgery under regional anesthesia (spinal or combined spinal-epidural anesthesia) and administered intravenous 0.075 mg palonosetron or 0.3 mg ramosetron prior to the end of surgery between July 2012 and September 2015. POD incidence and anesthesia-, surgery-, and patient-related factors were evaluated. To investigate the association between 5-HT 3  receptor antagonists and the occurrence of POD, multivariable logistic regression analysis was performed. Results Of the 855 patients included, 710 (83%) were administered 5-HT 3  receptor antagonists. POD was confirmed in 46 (5.4%) patients. 5-HT 3  receptor antagonists reduced the POD incidence by 63% (odds ratio [OR] 0.37; 95% confidence interval [CI], 0.15–0.94;  P  = 0.04). Moreover, the POD incidence decreased by 72% (OR 0.28, 95% CI 0.10–0.77,  P  = 0.01) when palonosetron was administered. Other identified risk factors for POD were emergency surgery, older age, hip surgery, lower body mass index, and intraoperative propofol sedation. Conclusion 5-HT 3  receptor antagonists may be related with a significantly reduced risk for POD in older patients undergoing orthopedic lower limb surgery. Notably, palonosetron was more effective for POD prevention.

5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older patients undergoing orthopedic lower limb surgery