Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

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 = 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 anti-emetic 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).

The antiemetic efficacy of droperidol added to morphine patient-controlled analgesia: a randomized, controlled, multicenter dose-finding study.

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.