Safety and Efficacy of Routine Postoperative Ibuprofen for Pain and Disability Related to Ectopic Bone Formation after Hip Replacement Surgery (HIPAID):  Randomized Controlled Trial 

Background:  In order to reduce the risk of ectopic bone formation, routine prophylaxis with a short course of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) has been advocated in all patients undergoing total hip arthroplasty.

 

Objective:  The purpose of this study was to determine the benefits and risks of an NSAID as prophylaxis for ectopic bone formation in patients undergoing total hip replacement or revision surgery.

 

Methods:  This was a double blind, randomized, parallel group, placebo-controlled trial.  It was conducted at 20 hospitals in Australia and New Zealand between February 2002 and May 2004.  Patients identified within 24 hours of completed total hip replacement surgery were eligible for inclusion, irrespective of age, reason for surgery, or procedure performed.  Patients were excluded from the study if there was a definite indication for treatment with an NSAID or a definite contraindication for treatment with an NSAID.  Patients were also excluded from the study if they had taken an NSAID other than low dose aspirin in the 48 hours prior to the operation or if they had a postoperative spinal catheter within two hours before randomization.  A total of 902 patients were enrolled into the study:  452 in the ibuprofen group and 450 in the placebo group.  Patients received either ibuprofen two 200 mg tablets by mouth three times daily or matching placebo tablets starting within 24 hours after surgery and continuing for 14 days.  The primary outcome measures were the changes from baseline to follow-up in self reported hip pain and physical function measured by the Western Ontario and McMaster Universities arthritis index (WOMAC) questionnaire.  The secondary outcome measures were general health status of the medical outcomes study short form 36; patients’ global assessment of effectiveness of treatment; frequency of use of analgesia for hip pain; ability to get “about the house” and ability to get “out of the house”; time spent participating in physical activity during the past week; objective measures of physical performance; radiographic evidence of ectopic bone formation according to Brooker classification; and major bleeding complications during hospital admission.  Red cell transfusions, suction drainage volumes, and postoperative hemoglobin concentrations were also recorded.  The power of the study was 87%.  All analyses were completed according to the principle of intention to treat.

 

Results:  In total, 875 patients started the randomized treatment, and 188 stopped prematurely:  106 (24%) in the ibuprofen group and 82 (19%) in the placebo group (p<0.06).  In addition, 27 patients in the ibuprofen group were lost to follow-up and 22 patients in the placebo group.  There were no differences between the groups for improvements in hip pain (mean difference – 0.1, 95% CI – 0.4 to 0.2, p=0.59) or physical function (- 0.1, CI – 0.4 to 0.2, p=0.48) within 6 to 12 months after surgery.  There were no significant differences between the groups on the secondary outcomes of general health status, global assessments of functioning, participation in physical activity, or objective measures of physical performance.  There was a highly significant decrease in the risk of developing ectopic bone of any grade and in the risk of developing severe ectopic bone among patients in the ibuprofen group.  The difference in the numbers of serious adverse events between the groups was not significant.  However, there was an increased risk of major bleeding complications among patients in the ibuprofen group (risk ratio 2.09, CI 1.00 to 4.39, p=0.046).  There were no differences between groups in the proportion of patients requiring red cell transfusion (p=0.35), suction drainage volumes (p=0.71), or postoperative hemoglobin concentrations (p=0.80).  The authors conclude that ibuprofen routinely administered after total hip replacement surgery does not result in better long-term clinical outcomes, despite significantly decreasing the risk of ectopic bone formation.  Postoperative ibuprofen also increases the risk of serious bleeding complications.

 

Strengths:  The design of the study was appropriate for the information requested; the study used a placebo-group and double blind approach.  The primary outcome measures were appropriate to evaluate hip pain and function.

 

Weaknesses:  The inclusion/exclusion criteria were not clearly specified in the study.  The data was handled on an intent-to-treat basis regardless of the large number of dropouts or patients lost to follow-up.  Subgroup analyses were not performed to test for group differences in factors, such as, age, Brooker scores, other medication use, etc.  The major bleeding complications in the ibuprofen group were not clearly defined.  In addition, other anticoagulants were not taken into consideration as possible reasons for the bleeding complications.  Six to 12 months may not have been an adequate length of time to assess a response in the patients in the ibuprofen group.

 

Conclusion:  Ibuprofen showed no benefit over placebo in postoperative pain and physical function after hip replacement surgery.  More studies that include subgroup analyses, lower dropout rates, and longer durations need to be conducted to determine the clinical usefulness of this treatment.  Until further studies are conducted, routine prophylaxis with a short course of postoperative NSAIDs should not be advocated for all patients undergoing total hip replacement or revision surgery.

 

Fransen M, Anderson C, Douglas J, MacMahon S, Neal B, Norton R, et al.  Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID):  randomized controlled trial.  BMJ 2006 Sep 9;333(7567):519.

 

Carrie M. Simpson, Pharm.D. Candidate