Background The efficacy of intravenous acetaminophen compared to its oral formulation for postoperative analgesia is unknown. We hypothesized that the addition of acetaminophen to a multimodal analgesia regimen would provide improved pain management in patients following total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based upon route of delivery. Methods The study was a single center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of intravenous versus oral acetaminophen in patients undergoing unilateral TKA. One hundred and seventy-four subjects were randomized to one of three groups: intravenous acetaminophen group (IV Group, n=57) received 1-gram intravenous acetaminophen and oral placebo prior to post-anesthesia care unit (PACU) admission; oral acetaminophen group (PO Group, n=58) received 1-gram oral acetaminophen and volume-matched intravenous normal saline; placebo group (Placebo Group, n=59) received oral placebo and volume-matched intravenous normal saline. Pain scores were obtained every 15 minutes during PACU stay. Average pain scores, maximum pain score, and pain scores before physical therapy were compared among the three groups. Secondary outcomes included total opiate consumption, time to PACU discharge, time to rescue analgesia, and time to breakthrough pain. Results The average PACU pain score was similar in the IV Group (0.56 ±0.99 [mean ±SD]) compared to the PO Group (0.67 ±1.20) (P=0.84) and Placebo Group (0.58 ±0.99) (P=0.71). Total opiate consumption at 6 hours (0.47mg hydromorphone equivalents ±0.56 vs 0.54 ±0.53 vs 0.54 ±0.61; P=0.69) and 24 hours (1.25 ±1.30 vs 1.49 ±1.34 vs 1.36 ±1.31; P=0.46) were also similar between the IV, PO, and Placebo Groups. No significant differences were found between all groups for any other outcome. Conclusion Neither intravenous nor oral acetaminophen provides additional analgesia in the immediate postoperative period when administered as an adjunct to multimodal analgesia in patients undergoing TKA in the setting of a spinal anesthetic.

Chronic postsurgical pain (CPSP) is a possible complication of various surgical procedures, which can impair patients' quality of life while also contributing to chronic opioid use. Multiple biopsychosocial factors put patients at risk for CPSP. Multimodal analgesia with the use of various pharmacologic and regional anesthetic techniques can help reduce the incidence and severity of CPSP. However, the relationship between various perioperative analgesic strategies and the development of CPSP is not fully understood. Although the use of multimodal analgesia will not automatically prevent CPSP and/or prolonged opioid consumption, there is potential to do so, especially by means of regional techniques.