The antiemetic dose response of droperidol when it is added to patient-controlled analgesia with morphine is not well known. We randomly allocated adults who received postoperative morphine patient-controlled analgesia (1-mg bolus, 5-min lockout) to one of four regimens: no droperidol (control) or 5, 15, or 50 micro g of droperidol per milligram of morphine. Efficacy and adverse effects were recorded during 24 h and were analyzed with number needed to treat (NNT) and number needed to harm with 95% confidence intervals. Data from 82 controls, 82 patients receiving droperidol 5 micro g, 82 receiving droperidol 15 micro g, and 83 receiving droperidol 50 micro g were analyzed. Average consumption of droperidol per 24 h was 0.2 mg with the 5- micro g regimen, 0.61 mg with the 15- micro g regimen, and 2.04 mg with the 50- micro g regimen. In controls, the incidence of nausea was 48.8%; with droperidol 5 micro g, it was 42.7% (NNT compared with control, 16 [95% confidence interval, 4.7 to -11]); with 15 micro g, it was 32.9% (NNT, 6.3 [3.3-100]); and with 50 micro g, it was 21.7% (NNT, 3.7 [2.4 to 7.6]). In controls, the incidence of vomiting was 24.4%; with droperidol 5 micro g, it was 23.2% (NNT compared with control, 82 [7 to -8.5]); with 15 micro g, it was 22.0% (NNT, 41 [6.5 to -9.6]); and with 50 micro g, it was 12% (NNT, 8.1 [4.2-142]). In controls, the incidence of pruritus was 12.2%; with droperidol 5 micro g, it was 6.1% (NNT compared with control, 16 [6.7 to -37]); and with 15 and 50 micro g, it was 2.4% (NNT, 10 [5.7-52]). In controls, the incidence of sedation was 2.4%; with droperidol 5 micro g, it was 8.5% (number needed to harm (NNH) compared with control, 16 [7.7 to -123]); with 15 micro g, it was 6.1% (NNH, 27 [10 to -40]); and with 50 micro g, it was 18.1% (NNH, 6.4 [4.1-15]). There were no extrapyramidal symptoms and no cardiac adverse events. There was no difference in patient satisfaction. The optimal antiemetic dose of droperidol is 15-50 micro g/mg of morphine. Larger doses may have more antivomiting efficacy but are likely to be unacceptably sedating.
BACKGROUND Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV.OBJECTIVE To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness.DESIGN The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING Four public hospitals in Switzerland.PATIENTS A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients.INTERVENTIONS Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo.MAIN OUTCOME MEASURES The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug.RESULTS Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P ¼ 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects.CONCLUSION This randomised trial failed to show antiemetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION clinicaltrials.gov (NCT01975727).
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