The James A. Rand Young Investigator's Award: What Is the Safest and Most Effective Dose of Intravenous Dexamethasone in Total Knee Arthroplasty? A Multicenter Randomized Controlled Trial

Background: The purpose of this multicenter, double-blinded, prospective, randomized controlled trial was to determine the safest and most effective dose of intravenous (IV) dexamethasone administered during primary total knee arthroplasty (TKA). Methods: There were 404 patients undergoing inpatient primary TKA randomized across 11 centers to receive four (n = 138), eight (n = 137), or 16 mg (n = 129) of IV dexamethasone intraoperatively. All sites utilized the same perioperative multimodal protocol. Opioid consumption measured in morphine milligram equivalents (MME), pain scores, nausea scores, vomiting episodes, and sleep duration was collected for 7 days postoperatively. Glucose levels were measured on postoperative day 1 (POD1). The mean age was 68 years, the mean body mass index was 33, and 62% were women. Independent sample t-tests were used for continuous data, and Chi-square and Fisher's exact tests were used for discrete data. Demographic characteristics were comparable between groups, suggesting successful randomization. Results: Patients who received 16 mg IV dexamethasone consumed less MME on POD1 (38 versus 37 versus 27 MME; P = 0.047) and had fewer vomiting episodes (P = 0.02). Patients who received 16 mg also had lower pain scores at rest at 24 hours, 48 hours, and one week. There were no differences in cumulative opioid consumption within the first 48 hours (P = 0.24), one week (P = 0.43), or pain with activity at any time point. The POD1 glucose was highest in patients who received 16 mg (P < 0.001). There were no differences in length of stay, hours slept, or 90-day complication rates between groups. Conclusions: High-dose (16 mg) IV dexamethasone in TKA reduces opioid consumption, pain, and vomiting on the first day after surgery. Outcomes, including opioid consumption, sleep, and nausea, are comparable beyond 24 hours for all doses. Level of Evidence: I. Prospective randomized controlled trial.