Intravenous Ibuprofen for Treatment of Post-Operative Pain: A Multicenter, Double Blind, Placebo-Controlled, Randomized Clinical Trial

Abstract

Background: Non-steroidal anti-inflammatory drugs are often used as components of multimodal therapy for postoperative pain management, but their use is currently limited by its side effects. The specific objective of this study was to evaluate the efficacy and safety of a new formulation of intravenous (IV) ibuprofen for the management of postoperative pain in a European population.

Methods and findings: A total of 206 patients from both abdominal and orthopedic surgery, were randomly assigned in 1:1 ratio to receive 800 mg IV-ibuprofen or placebo every 6 hours; all patients had morphine access through a patient controlled analgesia pump. The primary outcome measure was median morphine consumption within the first 24 hours following surgery. The mean±SEM of morphine requirements was reduced from 29,8±5,25 mg to 14,22±3,23 mg (p = 0,015) and resulted in a decrease in pain at rest (p = 0,02) measured by Visual Analog Scale (VAS) from mean±SEM 3.34±0,35 to 0.86±0.24, and also in pain during movement (p = 0,02) from 4.32±0,36 to 1.90±0,30 in the ibuprofen treatment arm; while in the placebo group VAS score at rest ranged from 4.68±0,40 to 2.12±0,42 and during movement from 5.66±0,42 to 3.38±0,44. Similar treatment-emergent adverse events occurred across both study groups and there was no difference in the overall incidence of these events.

Conclusions: Perioperative administration of IV-Ibuprofen 800 mg every 6 hours in abdominal surgery patient's decreases morphine requirements and pain score. Furthermore IV-Ibuprofen was safe and well tolerate. Consequently we consider appropriate that protocols for management of postoperative pain include IV-Ibuprofen 800 mg every 6 hours as an option to offer patients an analgesic benefit while reducing the potentially risks associated with morphine consumption.

Trial registration: EU Clinical Trials Register 2011-005007-33.

Fig 1. Distribution of patients randomized to receive IV-Ibuprofen or placebo for the management of postoperative pain.

ICF: Informed Consent Form. ^a Safety: all patients who received at least one dose of IV-Ibuprofen or placebo (patients from both type of surgery abdominal and orthopedic) ^b Efficacy: all patients from abdominal surgery who received at least 4 doses of IV ibuprofen or placebo within 30 minutes of the scheduled administration time. Reasons for exclusion from the efficacy population included adverse events, noncompliance, and lack of efficacy, among others that resulted in the failure to complete the study protocol. Excluded from Efficacy analysis all patients from Orthopaedic surgery (because of the low rate of enrolment of patients due to the type of anaesthetic technique used mostly regional type): Ibuprofen arm: ITT n = 15; PP n = 14. Placebo group: ITT n = 16; PP n = 14. ^c ITT = Intention to Treat: population consisted of all patients who were both randomized and treated. ^d PP = Per Protocol: population consisted of all patients from the ITT population who had received the study treatment for at least 24 hours.

Fig 2. Study Timeline.

^a Site closure. ^b IV-Ibuprofen 800 mg or saline placebo, up to 24 hours for abdominal surgery and up to 72 hours for orthopedic surgery. ^c Counted since the last dose administered.

Fig 3. Evolution of postoperative pain at rest.

Patients self-reported pain scores during the immediate 24 hours after surgery were plotted for the IV-ibuprofen and placebo treatment groups. Values are mean±SEM. *Treatment doses: First intra-operative administration (T = 0), followed by doses 2, 3, 4 and 5 administered at hours 6, 12, 18 and 24 after surgery.

Fig 4. Evolution of postoperative pain during movement.

Patients self-reported pain scores during the immediate 24 hours after surgery were plotted for the IV-ibuprofen and placebo treatment groups. Values are mean±SEM. *Treatment doses: First intra-operative administration (T = 0), followed by doses 2, 3, 4 and 5 administered at hours 6, 12, 18 and 24 after surgery.