Dose-ranging effect of systemic diphenhydramine on postoperative quality of recovery after ambulatory laparoscopic surgery: A randomized, placebo-controlled, double-blinded, clinical trial

Study objective: Diphenhydramine is an antihistamine with previously demonstrated analgesic and antiemetic properties. However, it is unknown if the beneficial perioperative properties of diphenhydramine can translate to a better quality of postsurgical recovery. The main objective of the current investigation was to investigate dose-ranging effects of diphenhydramine on quality of recovery after surgery. Setting: Tertiary hospital in the United States. Design: A prospective, randomized, double-blind trial. Intervention: Saline, diphenhydramine 25 >mg, or diphenhydramine 50 mg given intravenously before induction. Measurements: The primary outcome was global Quality of Recovery-40 at 24 hours. Postoperative pain, nausea, opioid consumption, and discharge time were also evaluated. Main results: Ninety subjects were randomized, and 75 completed the study. The median (interquartile range) Quality of Recovery-40 scores were not different among study groups: 164 (151-189), 169 (159-181), and 172 (157-185) for the saline, 25-mg diphenhydramine, and 50-mg diphenhydramine groups, respectively (P =.74). Postoperative nausea was decreased in the 50-mg group, 3 of 24 (12.5%), compared with the saline group, 12 of 27 (44%), P =.01. There was an inverse linear association between postoperative opioid consumption and quality of recovery (R² = 0.37, P <.001). Conclusions: Diphenhydramine does not provide dose-ranging improvements on postoperative quality of recovery after ambulatory laparoscopic gynecologic surgery. Our results support a recent concept that not all postoperative nausea and vomiting symptoms are clinically important. Future studies evaluating postoperative nausea and vomiting should include patient-centered outcomes to validate the clinical importance of the examined interventions.