A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain.

BACKGROUND: Although opioids are the mainstay of inpatient postoperative pain management, they do not block inflammation. The NSAID ibuprofen has antiinflammatory and analgesic properties, and a multimodal approach may reduce opioid requirements.

OBJECTIVE: This study was conducted to assess the effects of intravenously administered ibuprofen 400 and 800 mg q6h in postoperative pain management.

METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was conducted in 406 patients scheduled to undergo elective, single-site orthopedic or abdominal surgery. All patients received morphine administered by patient-controlled analgesia pump, or by hospital staff at the request of the patient, after surgery and were randomly assigned in a 1:1:1 ratio to receive ibuprofen 400 mg IV, ibuprofen 800 mg IV, or inactive vehicle (placebo). The first dose of study drug was administered intraoperatively at the initiation of wound closure, then every 6 hours for a total of 8 doses over the first 48 hours of the study. After the initial 8 doses, the protocol allowed for continued administration of IV ibuprofen or placebo every 6 hours, at the discretion of the investigator, for control of postoperative pain for a total of up to 120 hours (5 days). The ibuprofen and placebo were administered while patients had access to morphine throughout the duration of the study. The primary outcome measure was morphine use in the first 24 hours after surgery. Secondary measures were patient self-reports of pain scores at rest and with movement. Pain intensity was measured before (baseline) and at 1, 2, 3, 6, 9, 12, 15, 18, 24, 27, 30, 33, 36, 39, 42, 45, and 48 hours after the first administration of study medication, and then once daily through day 5 if the patient continued to receive study medication. Patients were assessed by study personnel for treatment-emergent adverse events (AEs).

RESULTS: A total of 406 patients were enrolled (319 women, 87 men; mean [SD] age, 45 [12] years; weight, 83.8 [19.1] kg; ibuprofen 400 mg IV, 134 patients; ibuprofen 800 mg IV, 138; and placebo, 134). In the intent-to-treat population, median morphine use was significantly reduced during the first 24 hours after administration of the study drug in patients who received ibuprofen 800 mg IV q6h (by 22% vs placebo; P = 0.030). The use of ibuprofen 800 mg IV q6h was associated with significant reductions in pain at rest and with movement across 3 time periods (1-24, 6-24, 12- 24 hours) compared with placebo. Ibuprofen 400 mg IV q6h was associated with significant reductions in pain at rest and with movement during the 6- to 24-hour and 12- to 24-hour time periods compared with placebo. The prevalences of AEs and abnormalities in laboratory measurements were not significantly different between patients who received IV ibuprofen and those who received placebo. Treatment-emergent AEs were reported in 368 of 406 patients (91%). With respect to the number of patients who experienced serious AEs, the differences in the 400-mg IV ibuprofen group (118/134 [88%]) and the 800-mg IV ibuprofen group (124/138 [90%]) compared with the placebo group (126/134 [94%]) were not statistically significant. There were significant reductions in the proportions of patients who experienced gastrointestinal disorders in the 400- and 800-mg IV ibuprofen groups compared with the placebo group (99/134 [74%] and 98/138 [71%], respectively, vs 113/134 [84%]; P = 0.05 and P = 0.009). There were significant reductions in the numbers of patients experiencing pyrexia in the 400- and 800-mg IV ibuprofen groups compared with the placebo group (9/134 [7%] and 10/138 [7%] vs 23/134 [17%]; P = 0.013 and P = 0.015). Dizziness occurred in a significantly greater proportion of patients in the ibuprofen 800-mg q6h group compared with the placebo group (P = 0.011).

CONCLUSIONS: In these patients undergoing postoperative pain management, ibuprofen 800 mg IV q6h was associated with significant reductions in morphine use and pain at rest and with movement compared with placebo. Ibuprofen IV was not associated with significant increases in AEs compared with placebo, with the exception of dizziness with the 800-mg dose. These findings suggest that ibuprofen 800 mg IV q6h was effective for postoperative pain management and was generally well tolerated. ClinicalTrials.gov identifier: NCT00225732.