Intravenous vs Oral Acetaminophen as an Adjunct to Multimodal Analgesia After Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Clinical Trial.

Background: The efficacy of intravenous (IV) acetaminophen compared with 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 after total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based on the route of delivery.

Methods: The study was a single-center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of IV vs oral acetaminophen in patients undergoing unilateral TKA. One hundred seventy-four subjects were randomized to one of the 3 groups: IV acetaminophen group (IV group, n = 57) received 1 g IV acetaminophen and oral placebo before postanesthesia care unit (PACU) admission; oral acetaminophen group (PO group, n = 58) received 1 g oral acetaminophen and volume-matched IV normal saline; placebo group (Placebo group, n = 59) received oral placebo and volume-matched IV 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 3 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 ± standard deviation]) compared with the PO group (0.67 ± 1.20; P = .84) and Placebo group (0.58 ± 0.99; P = .71). Total opiate consumption at 6 hours (0.47 mg hydromorphone equivalents ± 0.56 vs 0.54 ± 0.53 vs 0.54 ± 0.61; P = .69) and at 24 hours (1.25 ± 1.30 vs 1.49 ± 1.34 vs 1.36 ± 1.31; P = .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 IV 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.