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

Feng Yin, Wei Ma, Qiao Liu, Liu-Lin Xiong, Ting-Hua Wang, Qian Li, Fei Liu, Feng Yin, Wei Ma, Qiao Liu, Liu-Lin Xiong, Ting-Hua Wang, Qian Li, Fei Liu

Abstract

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].

Keywords: intravenous acetaminophen; morphine consumption; multimodal analgesia; opioid-sparing; orthopedic surgery.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Yin, Ma, Liu, Xiong, Wang, Li and Liu.

Figures

FIGURE 1
FIGURE 1
Flow CONSORT diagram of study recruitment. mITT, modified intention-to-treat.
FIGURE 2
FIGURE 2
Intensity of pain at rest (A) and during movement (B) during the first 24 h after surgery. There is no significant difference between the acetaminophen group and placebo group (p > 0.05). NRS, numerical rating scale.
FIGURE 3
FIGURE 3
Area under the curve (AUC) of pain intensity-time at rest (A) or during movement (B). The two groups did not differ significantly for any AUC (p > 0.05).

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