A Randomized Trial Comparing the Safety and
Efficacy of Intravenous Ibuprofen versus Ibuprofen
and Acetaminophen in Knee or Hip Arthroplasty
Authors: Gupta Anita 
Published: February 2021

Background: All surgical procedures are associated with a degree of pain. The experience of
uncontrolled post-operative pain can have significant implications on health care costs. Recent
studies have demonstrated that intravenous (IV) ibuprofen is an effective, safe, well-tolerated
analgesic when administered for both abdominal hysterectomy and orthopedic surgery. The use of
ibuprofen leads to a reduction in pain severity at rest and with movement and also decreases narcotic
consumption. IV acetaminophen has also been shown to be effective in alleviating pain for surgical
procedures. Given the established safety and efficacy of IV ibuprofen and IV acetaminophen for
perioperative pain, we were interested in determining if any potential synergies are afforded by the
simultaneous administration of both medications in orthopedic surgery patients.
Objectives: Compare the safety and efficacy of the perioperative administration of IV ibuprofen
alone 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 randomized
into 2 groups. Group 1 received 800 mg of IV ibuprofen at induction, and 800 mg of IV ibuprofen
every 6 hours until discharge or for up to 5 days. Group 2 received 800 mg IV ibuprofen at induction
and 1000 mg IV acetaminophen at closure, and 800 mg IV ibuprofen plus 1000 mg IV acetaminophen
every 6 hours until discharge for up to 5 days. The primary endpoint was demonstrated using the
visual analog scale (VAS) pain scores. Secondary endpoints included opioid requirements, quality
of 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 requirements
and adverse events were significantly less in Group 2 which was also statistically significant. Time
to 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. Length
of hospital stay was also evaluated; however, no statistical significance was noted between the 2
groups (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 total
number of patients is also small and may call into question the reproducibility of the results. No cost
analysis was undertaken as part of this study. Further research should aim at prospectively designed
multi-center double blinded randomized control trials with an analysis of the pharmacoeconomics
of the use of these agents.
Conclusion: IV ibuprofen combined with IV acetaminophen demonstrated additional benefit in
terms of improved pain scores on post-operative day 3 only, fewer potential adverse events related
to 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