Preoperative Olanzapine and Quality of Recovery after Ambulatory Surgery: A Randomized Clinical Trial

Background: Postdischarge nausea and vomiting (PDNV) negatively impact recovery after surgery. Preoperative administration of olanzapine 10 mg decreases PDNV but increases sedation. No data are available on the impact of olanzapine on global quality of recovery. Methods: This was a single-center, randomized, double-blind, placebo-controlled trial in 18-50-year-old female patients undergoing ambulatory surgery under general anesthesia. Participants received oral olanzapine 5 mg or placebo in addition to antiemetic prophylaxis with dexamethasone and ondansetron. The primary outcome was Quality of Recovery-40 (QoR-40) on postoperative day (POD) 1. Secondary outcomes included QoR-40 on POD 2, postdischarge nausea (any and severe) through POD 2, and postanesthesia care unit (PACU) length of stay. QoR-40 analyses used mixed-effects models adjusted for baseline preoperative QoR-40 scores. The group differences and corresponding 95% confidence intervals (CI) were reported. Results: A total of 384 participants received olanzapine (n = 191) or placebo (n = 193). Compared with placebo, olanzapine was associated with higher QoR-40 scores on POD 1 (difference, 9.0 points [95% CI, 6.1 to 11.8]; p<0.001). The POD 2 difference was 4.8 points (95% CI, 2.0 to 7.6; nominal p=0.001), and this secondary outcome remained significant after false discovery rate correction. Olanzapine was associated with lower odds of any nausea (OR, 0.43; 95% CI, 0.28 to 0.66) and severe nausea (OR, 0.26; 95% CI, 0.14 to 0.48) on POD 1. On POD 2, olanzapine was associated with lower odds of any nausea (OR, 0.48; 95% CI, 0.30 to 0.76), but not severe nausea (OR, 0.65; 95% CI, 0.30 to 1.40). PACU length of stay did not differ between groups. The significance of these prespecified secondary outcomes was unchanged after false discovery rate correction. Conclusions: When combined with dexamethasone and ondansetron, a single preoperative dose of olanzapine 5 mg improved global quality of recovery after discharge from ambulatory surgery. Trial Registration: ClinicalTrials.gov NCT05676294.