Antiemetic efficacy of a droperidol-morphine combination in patient-controlled analgesia. Randomized, double-blind trial of dolasetron versus droperidol for prophylaxis of postoperative nausea and vomiting in patients undergoing TRAM flap breast reconstruction surgery. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.
To evaluate the antiemetic effectiveness and side effects of adding low-dose droperidol to morphine delivered via a patient-controlled analgesia (PCA) device.
                Randomized, double-blind, clinical study.
                University-affiliated women's hospital.
                60 healthy women, 18 to 60 years of age, who underwent total abdominal hysterectomy with a standardized anesthetic regime.
                After surgery, the control group (n = 20) had access via PCA to two cartridges, each containing morphine 1 mg/ml and saline 1 ml. The two treated groups (n = 20 each) had access via PCA to either droperidol 0.5 mg or droperidol 1 mg added to two cartridges containing morphine 1 mg/ml.
                Preoperative data, including each patient's history of nausea and vomiting with and without previous anesthesia, motion sickness, smoking, and alcohol intake, and date of her last menstrual period, were obtained. All patients received a standardized anesthetic with droperidol 0.5 mg given at closure of the peritoneum. Among those patients who received droperidol added to morphine for their postoperative analgesic regimen, fewer required rescue antiemetic medication (p < 0.05, test of trend in proportions), and they had a lower incidence of vomiting (p < 0.05, test of trend in proportions), as well as a decrease in the number of times a rescue antiemetic was needed during the 24-hour postoperative period (linear trend, p = 0.013).
                An intermittent intake of low-dose droperidol with morphine given via a PCA delivery system in two treatment groups gave evidence for a dose-response relation between the amount of droperidol added and the proportion of patients needing a rescue antiemetic. The same result applied to the proportion of patients having an emetic episode and the number of times a rescue antiemetic had to be administered. There was no evidence that the low dose of droperidol added to morphine delivered via a PCA device increased unwanted side effects. Clinical observation indicates that patients undergoing transverse rectus abdominus musculocutaneous (TRAM) flap breast reconstruction surgery frequently experience postoperative nausea and/or vomiting (PONV). No controlled trials have evaluated the role of pharmacologic prophylaxis of PONV in this population. A prospective randomized, double-blinded, active-controlled trial comparing intraoperative intravenous droperidol 1 mg with dolasetron 50 mg was conducted. Seventy-one patients were included in the intention-to-treat analysis. The incidence of the primary end point of PONV within 24 hours after surgery was 81.8% versus 78.9% for droperidol and dolasetron, respectively (p = 0.8). No significant differences were detected in the time to onset of PONV, incidence of severe nausea or emesis, or incidence of emesis alone. Time to rescue antiemetic use was longer in the droperidol group (7.1 vs. 1.3 hours, p = 0.002). Adverse effects were similar between the two groups. No PONV-related complications occurred during the trial period. The incidence of PONV in TRAM flap breast reconstruction surgery patients remains high despite prophylactic intraoperative antiemetic administration. Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.
                We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly.
                Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk.
                Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
                Copyright 2004 Massachusetts Medical Society
This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.