Acetaminophen and Postoperative Pain and/or Opiod Use

We reviewed seventeen randomized clinical trials that represented the best available evidence including fifteen high quality and two moderate quality studies to assess the ability of IV or oral acetaminophen to reduce pain and/or opioid consumption during the perioperative period following TJA. ADDIN EN.CITE.DATA [2-18] Among the included studies, eleven studies investigated IV acetaminophen compared to placebo, five studies investigated IV acetaminophen compared to oral acetaminophen, and three studies compared oral acetaminophen to placebo. ADDIN EN.CITE.DATA [2-18] Despite the numerous high and moderate quality randomized clinical trials, only a limited amount of meta-analyses were able to be performed due to inconsistency in the reporting of outcomes and timepoints for reporting the outcomes.

            Intravenous acetaminophen has been shown with limited heterogeneity in direct meta-analyses to demonstrate favorable reductions in postoperative pain and opioid consumption compared to placebo. Among the studies reporting on postoperative pain, direct meta-analysis of IV acetaminophen demonstrated lower 6-hour sum of pain intensity differences (outcome is a four-point scale that summarizes the treatment benefit over a specific time period) and postoperative pain scores (i.e. visual analogue scale and numeric pain rating scale) between 24- and 48-hours compared to placebo following surgery. Additionally, direct meta-analysis of opioid consumption measured 24-hours following TJA had improved outcomes for IV acetaminophen compared to placebo.

            Due to the lack of consistent outcomes, no meta-analysis could be performed comparing IV and oral acetaminophen. However, among the five high quality randomized clinical trials investigating the comparison of IV and oral acetaminophen, no difference was observed between the routes of administration to reduce postoperative pain and/or opioid consumption.[4, 9, 10, 14, 17] Similarly, no meta-analysis could be performed comparing oral acetaminophen and placebo. Only three high quality randomized studies were available to assess the ability of oral acetaminophen to reduce postoperative pain and/or opioid consumption compared to placebo.[6, 9, 16] Qualitative review of the available literature would suggest oral acetaminophen reduces postoperative pain and opioid consumption, but the results do not consistently favor oral acetaminophen over placebo at statistically significant levels.

            Although IV acetaminophen has been shown to be superior to placebo and equivalent to oral acetaminophen with regards to reduction in postoperative pain and/or opioid consumption, the lack of overwhelming evidence supporting the superiority of oral acetaminophen compared to placebo has resulted in a downgrade of the recommendation from strong to moderate for oral acetaminophen. Furthermore, the strength of the recommendation for IV acetaminophen was downgraded from strong to moderate due to concerns regarding the significantly higher cost of IV acetaminophen compared to oral acetaminophen. However, the US Food and Drug Administration has granted approval for marketing of a generic IV acetaminophen starting in December 2020, which is has the potential to dramatically reduce the cost and change the downgrade of the recommendation of IV acetaminophen.