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

Abstract

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.

Evolution of an Opioid Sparse Pain Management Program for Total Knee Arthroplasty With the Addition of Intravenous Acetaminophen

“…However, 2 recent meta-analyses have shown mixed results, citing limited quality evidence supporting the use of IV acetaminophen and the need for future randomized controlled trials [13,14]. In contrast, 2 recent prospective trials found modest improvements in pain and opioid consumption [18,20]. Patients receiving IV acetaminophen in our study reported lower pain scores and less narcotic use, specifically for the first 24 hours postoperatively, compared to patients receiving oral acetaminophen.…”

“…However, other studies have not clearly demonstrated a change in pain in the recovery room with either oral or IV acetaminophen following TKA [20]. A recent, prospective, randomized, double-blind clinical trial examining the administration of IV vs oral acetaminophen administered in the operating room did not find a decrease in pain in patients who received IV acetaminophen intraoperatively [20]. An explanation offered by the authors is that average pain scores were less than 1 with the authors' multimodal pain management regimen across all groups, as well as an overlap effect from spinal analgesia, on average 3.5 hours, potentially decreasing the ability to identify a difference between the 2 modalities.…”

“…In particular, administering IV acetaminophen intraoperatively may reduce pain in the immediate postoperative period [22]. However, other studies have not clearly demonstrated a change in pain in the recovery room with either oral or IV acetaminophen following TKA [20]. A recent, prospective, randomized, double-blind clinical trial examining the administration of IV vs oral acetaminophen administered in the operating room did not find a decrease in pain in patients who received IV acetaminophen intraoperatively [20].…”

Effectiveness of intravenous acetaminophen for postoperative pain management in hip and knee arthroplasties: a population-based study

“…Multiple smaller studies demonstrate beneficial effects of intravenous APAP as such a solution, including lower pain scores,30 31 shorter hospital length of stay,32 and better patient comfort. On the other hand, O’Neal et al 33 found no additional analgesic or opioid-sparing effects of oral or intravenous APAP when administered to patients immediately after TJA in 174 patients. Meta-analyses and larger population-based studies yield similarly equivocal results.…”

Contemporary Perioperative Analgesia in Total Knee Arthroplasty: Multimodal Protocols, Regional Anesthesia, and Peripheral Nerve Blockade

“…35 However, in a double-blind randomized controlled trial of 176 TKA patients, pain relief and opioid consumption was equivalent among IV acetaminophen, oral acetaminophen, and placebo groups. 36 Given the questionable efficacy of acetaminophen, concerns for potential hepatotoxicity are best handled via avoidance in patients with known liver disease. 37 Nonsteroidal anti-inflammatory drugs (NSAIDs) often play an important role in multimodal analgesia.…”