A randomised controlled trial of placebo, droperidol or ondansetron to prevent nausea and vomiting after tonsillectomy in children receiving dexamethasone

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

Some recent articles have discussed biased methods for estimating risk ratios from adjusted odds ratios when the outcome is common, and the problem of setting confidence limits for risk ratios. These articles have overlooked the extensive literature on valid estimation of risks, risk ratios, and risk differences from logistic and other models, including methods that remain valid when the outcome is common, and methods for risk and rate estimation from case-control studies. The present article describes how most of these methods can be subsumed under a general formulation that also encompasses traditional standardization methods and methods for projecting the impact of partially successful interventions. Approximate variance formulas for the resulting estimates allow interval estimation; these intervals can be closely approximated by rapid simulation procedures that require only standard software functions.

Previous studies on dexamethasone's antiemetic and analgesic potential in children undergoing tonsillectomy have produced conflicting results. The aim of this study was to evaluate the effects of a single dose of dexamethasone on the incidence and severity of postoperative vomiting and pain in children undergoing electrocautery tonsillectomy under standardized general anesthesia. In a double-blinded study, 120 patients were randomly allocated to receive either dexamethasone 0.5 mg.kg(-1) (maximum dose 8 mg) iv or an equivalent volume of saline preoperatively. The incidence of early and late vomiting, need for rescue antiemetics, time to first oral intake, time to first demand of analgesia and analgesic consumption were compared in both groups. Pain scores used included Children's Hospital Eastern Ontario Pain Scale, "faces", and a 0-10 visual analogue pain scale. Compared with placebo, dexamethasone significantly decreased the incidence of early and late vomiting (P < 0.05, P < 0.001 respectively). Fewer patients in the dexamethasone group needed antiemetic rescue (P < 0.01). The time to first oral intake was shorter, and the time to first dose of analgesic was longer in the dexamethasone group (P < 0.01). Pain scores 30 min after extubation were lower (P < 0.05) in the dexamethasone group. At 12 and 24 hr postoperative swallowing was still significantly less painful in the dexamethasone group than in the control group (P < 0.01). Preoperative dexamethasone 0.5 mg.kg(-1) iv reduced both postoperative vomiting and pain in children after electrocautery tonsillectomy.