A prospective, randomized, double-blind, placebo-controlled study to assess the antiemetic effects of midazolam on postoperative nausea and vomiting in women undergoing laparoscopic gynecologic surgery

Abstract

Background: Postoperative nausea and vomiting (PONV) are distressing and frequent adverse effects (AEs) in women undergoing laparoscopic gynecologic surgery. Midazolam has been reported to be effective for preventing PONV in adults undergoing middle ear surgery and children undergoing strabismus surgery or tonsillectomy.

Objective: The aim of this study was to assess the antiemetic effects of midazolam on PONV in women undergoing laparoscopic gynecologic surgery.

Methods: This prospective, randomized, double-blind, placebo-controlled study was conducted (January-December 2009) at the Department of Anesthesiology, Ushiku Aiwa General Hospital (Ibaraki, Japan). Nonpregnant Japanese women (aged 22-54 years) undergoing myomectomy, hysterectomy, salpingo-oophorectomy, or oophorectomy were randomized to receive 1 of 2 different midazolam doses (50 or 75 μg/kg IV) or placebo immediately after induction of anesthesia. Anesthesia was induced with propofol 2 mg/kg IV, and vecuronium 0.1 mg/kg IV was used to facilitate tracheal intubation. After tracheal intubation, anesthesia was maintained with sevoflurane 1.0% to 3.0% (inspired concentration) and air in oxygen. All episodes of PONV during the first 24 hours after anesthesia were assessed by an investigator 24 hours postoperatively; the investigator was blinded as to which treatment each patient had received. The patients were asked if nausea, vomiting, or retching had occurred. Details were recorded of any other AEs, as well as any spontaneous complaints.

Results: A total of 90 nonpregnant Japanese women were enrolled (mean [SD] age, 35 [6] years; mean height, 159 [6] cm; mean weight, 53 [8] kg). Each study group comprised 30 patients and was comparable with regard to patient demographic characteristics and types of surgery. The rate of patients experiencing PONV during the first 24 hours after anesthesia with midazolam 50 μg/kg was 30% (P = 0.004 vs placebo) compared with 27% with midazolam 75 μg/kg (P = 0.002 vs placebo) and 67% with placebo. The difference in the incidence of PONV between patients receiving midazolam 75 μg/kg and those receiving midazolam 50 μg/kg was not statistically significant. No clinically important AEs due to the study drug were observed in any of the groups.

Conclusion: Midazolam 50 μg/kg was not significantly different from midazolam 75 μg/kg in the incidence of PONV, and both doses were associated with significantly less PONV compared with placebo during the first 24 hours after anesthesia in these Japanese women undergoing laparoscopic gynecologic surgery.