Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Anesthesia/OR Economics
Introduction: Postoperative nausea and vomiting (PONV) remains one of the most common complication after gynecologic surgery. The availability of a highly effective prophylactic antiemetic which was devoid of side effects would be extremely useful. In a randomized, double-blind study design, a novel antiemetic with NK-1 receptor blocking activity (CP122,721) was compared to ondansetron when administered alone and in combination to women undergoing major gynecologic surgery.
Methods: 68 consenting women undergoing total abdominal hysterectomy procedures were randomly assigned to one of three prophylactic treatment groups according to an IRB approved protocol. Each group received the study drug (CP122,721) 200 mg or placebo orally (PO) 60-90 min prior to surgery, and ondansetron 4 mg IV or saline 2 ml prior to the end of the procedure: Group 1- placebo PO and ondansetron 4 mg IV; Group 2- CP122-721 200 mg PO and saline 2 ml IV; and Group 3- CP122-721 200 mg PO and ondansetron 4 mg IV. All patients received a standardized general anesthesia consisting of midazolam 2 mg IV, thiopental 4 mg/kg IV, sufentanil 0.5 [micro sign]g/kg (or fentanyl 5 [micro sign]g/kg) and rocuronium 0.6 mg/kg (or cisatracurium 0.2 mg/kg). Anesthesia was maintained with desflurane 3-6% and N2 O 50-70% in oxygen. Patients assessed their level of nausea and pain upon arrival in the PACU and 0.5, 1, 1.5 2, 4, 8, 12 hr postoperatively using 100 mm visual analog scales (VAS), with 0=none to 100=severe. Emetic episodes, rescue antiemetics and postoperative complications were also recorded. All patients utilized morphine PCA for postoperative pain control. Data were compared using ANOVA and Chi-square test, with p-values<0.05 considered statistically significant.
Results: Demographic characteristics, history of PONV and motion sickness, as well as baseline vital signs, and duration of anesthesia and surgery were similar for all three antiemetic treatment groups. Although there were no differences among the three groups with respect to nausea VAS scores, the incidence of the emetic episodes was significantly lower in Groups 2 and 3 compared to Group 1 (Figure 1). Survival analysis revealed that the time intervals for 75% of the patients to remain free from nausea and emesis were 96, 75, 298 min, respectively (Figure 2). There were no clinically-significant adverse events attributed to the study medication. (Table 1)
Conclusions: Prophylactic administration of oral CP122,721 demonstrated advantages over ondansetron in preventing emetic episodes during the first 36 hr after lower abdominal surgery. Furthermore, the combination of ondansetron and CP122,721 provided the longest interval "free" of any PONV symptoms.