Efficacy and safety of intravenous acetaminophen (2 g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial

Background: Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after an orthopedic surgery. The opioid-sparing efficacy of intravenous acetaminophen has been established at a daily dose of 4 g. However, it is still unclear for the daily dose of 2 g of acetaminophen, which is recommended by the China Food and Drug Administration Center for Drug Evaluation, in terms of its efficacy and safety. Objectives: This study aimed to evaluate the efficacy and safety of intravenous acetaminophen at a daily dose of 2 g for reducing opioid consumption and pain intensity after orthopedic surgery. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 235 patients who underwent orthopedic surgery were randomly assigned to receive intravenous acetaminophen 500 mg every 6 h or placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analysed. Results: For the mean (standard deviation) morphine consumption within 24 h after surgery, intravenous acetaminophen was superior to placebo both in the modified intention-to-treat analysis [8.7 (7.7) mg vs. 11.2 (9.2) mg] in the acetaminophen group and the placebo group, respectively. Difference in means: 2.5 mg; 95% confidence interval, 0.25 to 4.61; p = 0.030), and in the per-protocol analysis (8.3 (7.0) mg and 11.7 (9.9) mg in the acetaminophen group and the placebo group, respectively. Difference in means: 3.4 mg; 95% confidence interval: 1.05 to 5.77; p = 0.005). The two groups did not differ significantly in terms of pain intensity and adverse events. Conclusion: Our results suggest that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by Chinese adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02811991].