A Randomized Trial Comparing the Safety and Efficacy of Intravenous Ibuprofen versus Ibuprofen and Acetaminophen in Knee or Hip Arthroplasty

Background: All surgical procedures are associated with a degree of pain. The experience ofuncontrolled post-operative pain can have significant implications on health care costs. Recentstudies have demonstrated that intravenous (IV) ibuprofen is an effective, safe, well-toleratedanalgesic when administered for both abdominal hysterectomy and orthopedic surgery. The use ofibuprofen leads to a reduction in pain severity at rest and with movement and also decreases narcoticconsumption. IV acetaminophen has also been shown to be effective in alleviating pain for surgicalprocedures. Given the established safety and efficacy of IV ibuprofen and IV acetaminophen forperioperative pain, we were interested in determining if any potential synergies are afforded by thesimultaneous administration of both medications in orthopedic surgery patients.Objectives: Compare the safety and efficacy of the perioperative administration of IV ibuprofenalone and in combination with IV acetaminophen in total knee or hip arthroplasty.Study Design: Randomized, single center, trial.Setting: Tertiary care center in Philadelphia, Pennsylvania, United States.Methods: Seventy-eight patients undergoing elective knee or hip arthroplasty were randomizedinto 2 groups. Group 1 received 800 mg of IV ibuprofen at induction, and 800 mg of IV ibuprofenevery 6 hours until discharge or for up to 5 days. Group 2 received 800 mg IV ibuprofen at inductionand 1000 mg IV acetaminophen at closure, and 800 mg IV ibuprofen plus 1000 mg IV acetaminophenevery 6 hours until discharge for up to 5 days. The primary endpoint was demonstrated using thevisual analog scale (VAS) pain scores. Secondary endpoints included opioid requirements, qualityof recovery scale (QoR), length of post-anesthesia care unit (PACU) stay, antiemetic consumption,opioid consumption, and opioid related adverse events.Results: Patients in Group 2 had lower VAS scores (P < 0.002) by day 3 only. Opioid requirementsand adverse events were significantly less in Group 2 which was also statistically significant. Timeto discharge from the PACU for Group 1 on average was 55 minutes and 38 minutes for Group 2(P = 0.178) which was not statistically significant although may have clinical significance. Lengthof hospital stay was also evaluated; however, no statistical significance was noted between the 2groups (P = 0.138). There was no significant difference in QoR scores which were 177 (SD = 15.44)for Group 1 (n = 35) and 179.5 (SD = 16.30) for Group 2 (n = 39).Limitations: The study is a single center study with the attendant risk of convenience bias. The totalnumber of patients is also small and may call into question the reproducibility of the results. No costanalysis was undertaken as part of this study. Further research should aim at prospectively designedmulti-center double blinded randomized control trials with an analysis of the pharmacoeconomicsof the use of these agents.Conclusion: IV ibuprofen combined with IV acetaminophen demonstrated additional benefit interms of improved pain scores on post-operative day 3 only, fewer potential adverse events relatedto opioid use, and decreased use of opioids when compared to IV ibuprofen alone.Key Words: Acute pain, post-operative pain, randomized controlled trial, surgery, NSAID, analgesia,acetaminophen