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Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial

BMJ 2006; 333 doi: https://doi.org/10.1136/bmj.38925.471146.4F (Published 07 September 2006) Cite this as: BMJ 2006;333:519

Re: Bleeding and NSAIDs

I would like to thank Dr Dawson for his comments and consideration of
the possible implications of our study findings. It is agreed that only a
small but significantly increased risk of major bleeding complications
among patients allocated to ibuprofen was demonstrated while no
significant differences were detected in use of red cell transfusions,
mean suction drainage volumes or mean post-operative haemoglobin. However
the finding that 5% of patients in the ibuprofen group experienced at
least one major bleeding event is almost identical to that demonstrated in
a recent survey of similar patients during the hospital admission period
conducted in the UK. As regards the episodes of melaena, haemorrhage (of
the surgical wound), haematuria and bleeding haemorrhoids, all were also
further formally reported as ‘serious adverse events’ most being either
considered life threatening or resulting in prolonged hospitalisation. We
did not collect data on warfarin use or prosthetic valves. It is usual
practice for patients to cease warfarin prior to admission for total hip
replacement surgery. If a patient was to remain on warfarin, it would be
considered they had a ‘bleeding disorder’ and therefore ineligible for
study participation.

It is probable that the number of serious bleeding events was
relatively small as patients with any history of a serious adverse
reaction to an NSAID, major gastrointestinal bleeds or known bleeding
disorders were ineligible for participation. However, even in this low
risk sample, the absolute difference in the percentage of patients with a
major bleeding event was 3%, equating to an additional bleeding event per
34 patients given this prophylactic treatment. Given the large numbers of
people undergoing total hip replacement surgery, this finding is not
inconsequential.

Acute pain during the hospital admission period was not monitored as
the aim of this study was to assess the effect of a routine prophylactic
strategy on long term ectopic bone related pain and disability. However,
prescribed narcotic analgesia during the admission period was recorded by
the collaborating research nurses. While there was no difference in the
number of patients receiving IV narcotics (85%), the mean dose received
per patient did appear to be slightly lower among patients allocated to
ibuprofen compared to patients allocated to placebo. Likewise, the number
of patients receiving intra-muscular or oral narcotics was slightly lower
among patients allocated to ibuprofen compared to placebo. It is planned
to analyse these important data further and report our findings. However,
again the risk of the adverse events associated with NSAIDs use in this
post operative period among patients undergoing total hip replacement
surgery would need to be weighed up against any advantages gained by a
possibly reduced short term requirement for narcotic analgesia.

The main aim of the HIPAID study was to assess the magnitude of risk
and long term benefit of introducing routine post operative NSAIDs based
prophylaxis for ectopic bone formation among all patients undergoing total
hip replacement surgery to allow more informed decision making. The main
finding of this study was that while the incidence of ectopic bone
formation was indeed reduced, there was no evidence of an overall
reduction in long term pain and disability. In addition, due to the large
number of participants randomised in this study, we were able to
demonstrate that even with a moderate dose of ibuprofen (1200mg daily)
there are real concerns regarding increased risk of major bleeding events.
However, it was not intended that the findings from this study would be
extrapolated to patients undergoing other forms of orthopaedic surgery.

1. Sharma S. Upper gastrointestinal bleeding after hip and knee
arthroplasty. Orthopedics. 2006;29:255-257.

Competing interests:
None declared

Competing interests: No competing interests

15 September 2006
Marlene Fransen
Senior Research Fellow
The George Institute