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Bleeding and NSAIDs
- James S Dawson (10 September 2006)
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Optimal management requires correct dose by the correct route and at the correct time
- Hamzeh Hussein, Dr. Andrew Toner- SHO Anaesthetic (14 September 2006)
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Re: Bleeding and NSAIDs
- Marlene Fransen (15 September 2006)
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Re: Optimal management requires correct dose by the correct route and at the correct time
- Marlene Fransen (15 September 2006)
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NSAIDs are very useful after hip replacement surgery
- David J Wilkinson, Oliver Seyfried (20 September 2006)
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James S Dawson, SHO Anaesthesia Birmingham
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The paper by Fransen and colleagues is interesting. I note in the results that the authors identify that there was 'a significantly increased risk of major bleeding complications among those in the ibuprofen group' during the admission period, though there was no difference in use of blood products (autologous or non-autologous), or in suction drain volumes or haemoglobin between the groups. This surely waters down their argument of ibuprofen precipitating 'major bleeding'. There was no difference in the rates of bleeding between the two groups at the surgical site. It would be interesting to know more about the episodes of melaena, 'haemorrhage' (of undisclosed nature) and of the extent of haematuria and bleeding haemorrhoids. It would also be interesting to know the numbers of patients taking warfarin or with prosthetic valves in the two groups. The numbers of bleeding events are small, and by ignoring just one bleeding event in the ibuprofen group, statistical significance of 'major bleeding’ is abolished to a P value of 0.1 (using a Chi Sqaure). Ibuprofen is a very useful agent as an adjunct in pain management in many groups of patients, especially in the perioperative, as are other NSAIDs. Interestingly the authors make no mention of acute pain scores in the perioperative period, or of use of opiates between groups, or of the incidence of constipation or nausea and vomiting between groups. I would sorry to see NSAIDs banned from the orthopaedic wards based on this study, as I observe on a daily basis that they have clear benefits, in the short term at least. 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): randomised controlled trial. BMJ 2006; 333: 519-21. Competing interests: None declared |
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Hamzeh Hussein, Senoir House Officer- Anaesthetics Anaesthetic and Critical Care Department, Dr. Andrew Toner- SHO Anaesthetic
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We read with great interest the article by Fransen and colleagues (1). There are few points we would like to highlight: Firstly, the efficacy dose-response curve for NSAIDs is flat compared with the dose-response for adverse effects such as gastrointestinal symptoms, dizziness, and drowsiness (3). Increasing the dose to improve analgesia is therefore more likely to increase adverse effects than to improve analgesia. Optimal management requires that the correct drugs are available, and that they are given in the correct dose by the correct route and at the correct time. British National Formulary (BNF) recommends: initially 1.2-1.8g daily in 3-4 divided doses; increased if necessary to max. 2.4g daily;maintenance dose 0.6-1.2 g daily may be adequate. It is still controversial whether the increased harm caused by COX-2 selective NSAIDs a dose-related phenomenon or not? Secondly, non steroidal anti-inflammatory drugs (NSAIDs) are known to reversibly affect platelet function (2). The safety of regional anaesthesia in these group of patients remains a crucial issue amongst anaesthetists (62%, 8% had spinal and epidural respectively). Thirdly, we think that the availability of ibuprofen preparation to the public, duration of stay, number of outpatient appointments and post- operative physiotherapy sessions; all might be very important variables. 1. Fransen M et al. 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: 519. 2. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clin Pharmacol Ther 2006; 80 (3):264-274. 3. Eisenberg E et al. Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. J Clin Oncol 1994; 12 , 2756-2765. Dr. Hamzeh Hussein-SHO Anaesthetics Dr. Andrew Toner- SHO Anaesthetics Anaesthetic and Critical Care Department Royal Surrey county Hospital Egerton Road Guildford, GU2 7XX Competing interests: None declared |
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Marlene Fransen, Senior Research Fellow The George Institute
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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 |
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Marlene Fransen, Senior Research Fellow The George Institute
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The comments made by Dr Hussein and Dr Toner-Sho regarding the dose- response relationship for adverse events associated with NSAIDs use are well-supported by the literature. As regards the comments concerning the safety of participants who received regional anaesthesia is our study, this issue was discussed by the members of the HIPAID Management Committee at the time of developing the study design. Spinal or epidural anaesthesia is traditionally considered contra- indicated in patients with significant disorders of blood coagulation, due to an increased risk of the rare event of spinal haematoma causing neural damage. However, there is no agreement about its risk among patients whose coagulation may be mildly altered by low to moderate doses of NSAIDs.1 It was decided, however, that patients receiving regional anaesthesia would be ineligible for study participation unless any spinal catheter had been removed at least 2 hours prior to randomisation.2 It was also concluded that any variations in the use of NSAIDs or number of outpatient appointments and physiotherapy visits between patients during the follow-up period would be balanced by the randomisation procedure in this large study. 1. Royal College of Anaesthetists. Guidelines for the use of non- steroidal anti-inflammatory drugs in the perioperative period. 1998. 2. Horlocker TT, et al. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management. Anesthesia Analgesia. 1997;85:874-885. Competing interests: None declared |
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David J Wilkinson, Consultant anaesthetist Homerton hospital, London E9 6SR., Oliver Seyfried
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EDITOR - Fransen et al conclude that ibuprofen should not be used as routine prophylaxis for preventing ectopic bone formation in patients undergoing total hip replacement and stress the failure to decrease chronic pain and discomfort following the use of this drug. [1] While we understand the recommendation not to give non-steroidal anti- inflammatory drugs (NSAIDs) routinely (drugs with such a well known list of adverse effects should always be prescribed on a patient by patient basis) we are concerned that misinterpretation of this study may predispose some clinicians to withhold these drugs early on in the peri- operative phase. NSAIDs are recognised to be useful adjuncts in those who have undergone recent surgery.[2.3.] Not only do they provide profound analgesia but they also decrease opiate usage in those without continuous intrathecal or epidural analgesia and with appropriate patient choice and prescription they have an acceptable side effect profile. Regular opiate prescription in the post-operative period may lead to respiratory depression can have other serious consequences, especially for the elderly such as constipation. The final paragraph of Drs Birrell and Lohmander’s excellent Editorial stating that “on balance, this study shows that NSAIDs should not be given routinely after hip replacement surgery” [4] may be taken out of context. This conclusion could result in many elderly patients experiencing either unnecessary post operative pain or unfortunate side effects of opioid analgesia. Oliver Seyfried SHO Anaesthesia David Wilkinson, Consultant Anaesthetist Homerton University Foundation NHS Trust, Homerton Row, London E9 6SR davidwilkinson1@compuserve.com Competing interests: None declared References: 1. Fransen M., Anderson C., Douglas J., Macmahon S., Neal B., Norton R., Woodward M., Cameron ID., Crawford R., Lo SK., Tregonning G., Windolf M. Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial. British Medical Journal 2006; 333: 519-521. 2. Cashman JN., Dolin SJ. Respiratory and haemodynamic effects of acute postoperative pain management: evidence from published data. British Journal of Anaesthesia 2004; 93: 212-223. 3. Burns JW, Aitken HA, Bullingham RE, et al. Double-blind comparison of the morphine sparing effect of continuous and intermittent im administration of ketorolac. British Journal of Anaesthesia 1991;67:235- 238. 4. Birell F, Lohmander S. Non-steroidal anti-inflammatory drugs after hip replacement. British Medical Journal 2006; 333: 507-508. Competing interests: None declared |
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