Effects of dexamethasone in preventing postoperative emetic symptoms after total knee replacement surgery: a prospective, randomized, double-blind, vehicle-controlled trial in adult Japanese patients.

BACKGROUND: Postoperative emetic symptoms (nausea, retching, and vomiting) are common following total joint replacement, with an incidence as high as 83% when no prophylactic antiemetic is provided. However, most antiemetics currently used in Japan, such as antihistamines (eg, hydroxyzine), butyrophenones (eg, droperidol), and dopamine receptor antagonists (eg, metoclopramide), have been associated with adverse effects (AEs), such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal symptoms.
OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of 3 doses of intravenous dexamethasone monotherapy versus vehicle in preventing emetic symptoms after total knee replacement performed under combined general and epidural anesthesia.
METHODS: This prospective, randomized, double-blind, vehicle-controlled trial was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Adult Japanese patients scheduled to undergo total knee replacement were eligible. Patients were randomly assigned to 1 of 4 treatment groups: dexamethasone 4, 8, or 16 mg, or vehicle (control). Patients received combination anesthesia with sevoflurane and nitrous oxide in pure oxygen (general) and lidocaine (epidural). Study drugs were administered intravenously after the completion of surgery. An investigator blinded to treatment assignment monitored patients for emetic symptoms for 24 hours after the patient awoke. Patients rated their satisfaction with the study drug using a linear, 11-point scale (0 = complete satisfaction to 10 = complete dissatisfaction). Tolerability was assessed by the study investigator using spontaneous reporting and patient interview.
RESULTS: A total of 80 patients were enrolled (58 women, 22 men; mean [SD] age, 59 [10] years; mean [SD] height, 154 [7] cm; mean [SD] body weight, 55 [7] kg; 20 patients per treatment group). The demographic, clinical, and surgical data were comparable between the 4 treatment groups. The rates of emesis-free patients were 35% (7 patients), 70% (14), and 75% (15) with dexamethasone 4, 8, and 16 mg, respectively, compared with 30% (6) with vehicle (P = NS, 0.013, and 0.005, respectively). Median (range) patient satisfaction scores were significantly higher in the groups receiving dexamethasone 8 and 16 mg (both, 0.0 [0-9]) compared with controls (6.0 [0-10]) (P = 0.013 and 0.008, respectively). This effect was not found with the 4-mg dose. No clinically serious AEs attributed to the study drug were observed in any of the 4 treatment groups.
CONCLUSIONS: In this study of a small, select group of adult Japanese patients undergoing total knee replacement, the rates of emesis-free patients were higher with dexamethasone 8 and 16 mg compared with vehicle 24 hours after anesthesia induction. This effect was not found with the 4-mg dose. All treatments were well tolerated.

RCT Entities:   Population Interventions Outcomes