Intravenous acetaminophen is not an effective option for reducing opioid consumption after surgical intervention, compared with other analgesic agents, according to study results published in Pain Medicine.

Intravenous acetaminophen is approved for the management of moderate to severe pain with adjunctive opioid analgesics, but limited data are available on the opioid-sparing effect of intravenous acetaminophen after various surgical interventions. The objective of the current systematic review was to determine the opioid-sparing effect of intravenous acetaminophen following various types of surgical intervention.

MEDLINE, PubMed, EMBASE, and the Cochrane Library databases were searched to identify prospective, randomized, double-blind trials of intravenous acetaminophen compared with placebo or active-treatment group in adults undergoing surgery.

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Of 512 records identified, 179 full-text articles were assessed for eligibility; after exclusion of studies that failed to meet inclusion criteria, the systematic review included 37 studies with a total of 44 treatment cohorts.

In 14 of 44 (32%) treatment comparisons, acetaminophen produced a statistically significant opioid-sparing effect compared with active- or placebo-control treatments.

A significant reduction in opioid use with intravenous acetaminophen was more common in studies that compared intravenous acetaminophen with placebo (13 of 28 placebo cohorts showed a significant opioid-sparing effect) than in studies that included an active-treatment group (1 of 16 active-control cohorts). The active-control treatments included nonsteroidal anti-inflammatory drugs, metamizole, oral acetaminophen, tramadol, ketamine, or morphine infusion.

Intravenous acetaminophen was associated with reduced opioid consumption in 8 of 16 active-control cohorts and with increased opioid consumption in 7 of 16 cohorts.

The opioid-sparing effect of acetaminophen was more common in single-dose cohorts (8 of 18 cohorts, 44%) than in multidose cohorts (6 of 26 cohorts, 23%).

As for pain reduction with intravenous acetaminophen, in 13 of 28 (46%) placebo-controlled trials and in 2 of 16 active-control cohorts, intravenous acetaminophen was associated with a significant pain reduction. However, in 9 active-control cohorts, intravenous acetaminophen was associated with greater pain, and increased opioid consumption was documented in 6 of these cohorts.

The study had several limitations: Among them are the inclusion of studies with limited power to determine the opioid-sparing effect of intravenous acetaminophen, a lack of data on the clinical importance of the statistical differences in opioid consumption in some studies, and inherent heterogeneity in patient populations and surgical techniques.

“The results of this systematic analysis demonstrate that IV [intravenous] acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option,” concluded the researchers.


Hilleman DE, Malesker MA, Aurit SJ, Morrow L. Evidence for the efficacy of an opioid-sparing effect of intravenous acetaminophen in the surgery patient: a systematic review. Published online August 31, 2020. Pain Med. doi: 10.1093/pm/pnaa256