Glasgow Meeting - May 2003

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both of the cyclooxygenase (COX-1 and COX-2) enzymes to varying degrees; consequently, they impair prostaglandin production in all tissues, causing adverse effects, especially in the gastrointestinal tract, respiratory system (aspirin- induced asthma), kidney and haematological system. Unfortunately, side-effects are common when these nonselective NSAIDs are given and many patients have contraindications to their use. The antiinflammatory actions of the NSAIDs are mediated by COX-2 inhibition, while the adverse effects may be considered to be predominantly caused by COX-1 inhibition. Therefore, the selective inhibition of COX-2 inhibitors offers real hope for safer NSAIDs; specific agents have now been developed to do this. COX-2 inhibitors are effective anti-inflammatory agents, and evidence of their analgesic efficacy after surgery is increasing. While they may have significantly less gastrointestinal and antiplatelet effects, the acute renal and pulmonary effects of selective COX-2 inhibitors have not been fully clarified.

Conventional NSAID are known to be effective for the treatment of moderate to severe postoperative pain ( 1998). Indeed, consideration of the evidence of the efficacy of NSAID has indicated that they should be employed as a fundamental component of analgesia together with paracetamol, and with the additional use of opioids if required (McQuay HJ 2000). Unfortunately, the adverse effects of NSAID and their consequent contraindications render them unsuitable for a considerable proportion of surgical patients(Cousins and Power 1999). The hope is that COX-2 inhibitors will have similar efficacy to conventional NSAIDs, fewer contraindications, and that they can be given to a higher proportion of surgical patients. In this respect, the current evidence for the efficacy of COX-2 inhibitors is encouraging: the Oxford Acute Pain League Table of Analgesics shows that COX-2 inhibitors have similar NNTs (number needed to treat) to established well proven NSAIDs (www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.html).

The recognised adverse effects of NSAIDs include peptic ulceration, bleeding, and renal impairment. Of these, bleeding is not a consideration with COX-2 inhibitors as they do not affect platelet cyclo-oxygenase. Interestingly, the debate over the question of whether COX-2 inhibitors may predispose to vascular events by impairing endothelial prostacyclin production whilst sparing platelet function is ongoing. COX-2 inhibitors seem to be associated with less peptic ulceration, although they are not entirely devoid of this problem. The situation is less clear with COX-2 inhibitors and the problems of aspirin induced asthma and renal impairment. Aspirin induced asthma is considered to be a contraindication to the use of NSAIDs (Power 1993), and research into the safety or otherwise of COX-2 inhibitors is required before these agents can be considered for use in such individuals. The problem of peri-operative renal impairment associated with NSAID use is recognised as a serious, multifactorial, issue (Jaquenod, Ronnedh et al. 1998), which restricts NSAID use in surgical patients. Unfortunately, COX-2 inhibitors are not devoid of renal effects, and more research is required to clarify their effects on peri-operative renal function.

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2. Jaquenod, M., Ronnedh, C., Cousins, M.J., Eckstein, R.P., Jordan, V., Mather, L.E., and Power, I., Factors influencing ketorolac-associated perioperative renal dysfunction., Anesthesia Analgesia, 86 (1998) 1090-1097.

3. McQuay, H. and Moore, A., An evidence-based resource for pain relief, Oxford University Press, Oxford, 1998.

4. McQuay HJ, Acute Pain. In: Tramer MJ (Ed.), Evidence based resource in anaesthesia and analgesia. BMJ Books, London, 2000, pp. 87-103.

5. Power, I., Aspirin-induced asthma [editorial], British Journal of Anaesthesia, 71 (1993) 619-621.