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

• Published in: Clinical therapeutics 2009-09, Vol.31 (9), p.1922-1935
• Main Authors: Southworth, Stephen, MD, Peters, Jeannine, PharmD, Rock, Amy, PhD, Pavliv, Leo, RPh, MBA
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Analgesia, Patient-Controlled - methods; analgesic; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - therapeutic use; anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; clinical trial; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; ibuprofen; Ibuprofen - administration & dosage; Ibuprofen - adverse effects; Ibuprofen - therapeutic use; Internal Medicine; intravenous; Male; Medical Education; Medical sciences; Middle Aged; Morphine - administration & dosage; Morphine - therapeutic use; NSAID; opioid; pain; Pain Measurement; Pain, Postoperative - drug therapy; Pharmacology. Drug treatments; Time Factors; Treatment Outcome; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2009.08.026

Abstract 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, doubleblind, 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