Aprepitant for antiemesis after laparoscopic gynaecological surgery : A randomised controlled trial

Abstract

BACKGROUND: Ondansetron, a 5-HT3 receptor antagonist, and aprepitant, a neurokinin-1 receptor antagonist, block the emetic effect of serotonin and neurokinin, respectively. Aprepitant combined with ondansetron can be more effective for preventing emesis in patients at high risk of postoperative nausea and vomiting (PONV). OBJECTIVE: To investigate the prophylactic effect of combining aprepitant with ondansetron compared with ondansetron alone on PONV in patients with fentanyl-based patient-controlled analgesia (PCA) after laparoscopic gynaecological surgery. DESIGN: Single-centre, double-blinded randomised controlled trial. SETTING: A major university hospital in Seoul, Korea, between July 2012 and April 2013. PATIENTS: One hundred and twenty-five female patients (American Society of Anesthesiologists' physical status 1 or 2) with fentanyl-based intravenous PCA after gynaecological laparoscopy were recruited to the study, and 110 completed the protocol. INTERVENTIONS: Oral aprepitant 80 mg or placebo was given 1 h before anaesthesia. In all patients, ondansetron 4 mg was administered intravenously at the end of surgery and 12 mg was added to the PCA solution. MAIN OUTCOME MEASURES: The primary outcome measure was complete response (no PONV and no rescue antiemetics) up to 48 h postoperatively. RESULTS: There was no difference in the proportion of complete responses to 48 h between the groups (P = 0.05), but in the post-anaesthesia care unit and up to 24 h postoperatively, the proportion was significantly higher in the aprepitant and ondansetron group than in the ondansetron only group (76 vs. 50%, P = 0.004 and 38 vs. 16%, P = 0.011, respectively). In the aprepitant and ondansetron group, the time to first PONV was delayed (P = 0.014) and the incidence of nausea up to 24 h postoperatively was lower (P = 0.014). However, there were no differences in the incidences of retching or vomiting, the severity of nausea, use of rescue antiemetics or the incidence of side-effects. CONCLUSION: Aprepitant 80 mg orally with ondansetron is effective in suppressing early PONV up to 24 h postoperatively and delays the time to first PONV in patients with fentanyl-based intravenous PCA after gynaecological laparoscopy. However, the combination prophylaxis with aprepitant and ondansetron failed to reach the predefined primary study outcome when compared with ondansetron alone. TRIAL REGISTRATION: Clinicaltrial.gov identifier: NCT01897337.