2g daily dose of IV acetaminophen reduces opioid use in post-orthopaedic surgery pain: Study

China: Administering 500 mg intravenous acetaminophen every 6 h post orthopedic surgery is associated with a statistically significant, but not clinically meaningful reduction of 24-h morphine consumption in adults, without significantly increasing the risk of postoperative adverse effects, states a phase3 trial data published in the Frontiers in Pharmacology.

Opioids are the fundamental treatments for postoperative pain, but they are associated with adverse effects such as nausea, vomiting, respiratory depression, and risk of addiction. Multimodal analgesia has emerged as an approach capable of alleviating postoperative pain, shortening hospitalization, enhancing recovery, and increasing the satisfaction extent of patients while reducing opioid use and therefore opioid-related adverse events. Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after 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.

Feng Yin, Sichuan University, China, and colleagues conducted a study 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.

The study model was a multicenter, randomized, double-blind, placebo-controlled phase III trial. Researchers enrolled 235 patients who underwent orthopedic surgery and randomly assigned them to receive intravenous acetaminophen 500 mg every 6 h or a placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analyzed.

Key findings of the study,

• The patients in the acetaminophen group consumed significantly less morphine than the placebo group [8.7 mg vs. 11.2 mg] during the first 24 h after surgery.

• In the modified intention-to-treat analysis, the mean amount of consumed morphine was 8.7 mg in the acetaminophen group compared to 11.2 mg in the placebo group. The difference in mean values was 2.5 mg.

• The per-protocol analysis demonstrated that the consumed morphine was 8.3 mg and 11.7 mg in the acetaminophen group and the placebo group, respectively. The difference in means: 3.4 mg.

• The two groups did not differ significantly in terms of pain intensity and adverse events.

The authors conclude that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant.

Reference:

Yin F, Ma W, Liu Q, Xiong LL, Wang TH, Li Q, Liu F. 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. Front Pharmacol. 2022 Jul 22;13:909572. doi: 10.3389/fphar.2022.909572