Perioperative Use of NSAIDs and Coxibs Stephan A. Schug, MD(Cgn), FANZCA, FFPMANZCA Professor of Anaesthesiology, Pharmacology an Anaesthesiology !

nit, !ni"ersity of #estern Australia $ Director of Pain Me icine, %oyal Perth &ospital Nociception and pain perception can be inhibited or blocked at a number of levels along the nociceptive pathway by different mechanisms of action of various medications. Multimodal analgesia for postoperative pain relief is defined as the achievement of improved pain relief through the synergistic or at least additive effects of different agents (with different mechanisms of action or with different sites of action). This should then lead to improved analgesia, lowered doses of analgesics needed, reduced side effects and thereby earlier mobilisation and recovery. Data from a number of studies demonstrate the value of using conventional non steroidal anti inflammatory drugs (N!"#Ds) in improving $uality of analgesia and reducing overall opioid consumption, thereby diminishing the incidence of opioid related adverse events. %owever, despite the efficacy of N!"#Ds in the perioperative setting, they have associated risks that can limit their use in clinical practice. #n &''&, the discovery of the two isoen(ymes of cyclo o)ygenase, *+, & and *+, -, opened the opportunity for the development of new anti inflammatories, the co)ibs. .ntil then the anti inflammatory, analgesic and anti pyretic properties of the N!"#Ds were intrinsically linked to a wide range of potentially fatal adverse effects. The hypothesis underlying the co)ibs was the intention to separate inhibition of the /good0 *+, & (constitutive, protective for stomach and kidney, enabling platelet aggregation) from the inhibition of the /bad0 *+, - (inducible in inflammation, pain and fever). #n an ama(ingly short time the structural analysis of the isoen(ymes enabled the pharmaceutical industry to tailor make inhibitors selective for the one isoen(yme *+, -. *eleco)ib is now widely used for treatment of pain of arthritic origin, while specific co)ibs for treatment of acute pain are only now becoming available. 1areco)ib is the first parenterally available co)ib for #M and #2 use and opens new options for postoperative pain management. The effectiveness of these agents has been well demonstrated and is comparable to that of classical N!"#Ds. The opioids sparing effects and the improvement of analgesia of their use in multimodal analgesia offer further benefits. 3ith regard to side effects, co)ibs are superior to classical N!"#Ds. The selectivity of co)ibs for *+, - is obvious in a complete lack of effect on platelet aggregation, as platelets only contain *+, &. This is a ma4or advantage of these drugs in perioperative use. 5urthermore, with short term use, there is without doubt a significantly reduced gastrointestinal to)icity with ulcer rates similar to placebo. #n addition, co)ibs do not induce bronchospasm in aspirin sensitive asthmatics. These properties and possibly less inhibition of bone healing have made co)ibs and in particular pareco)ib the increasingly preferred agents for use in the perioperative period and in acute pain situations. %owever, the /good guy, bad guy0 hypothesis did not work out completely, as it became obvious, that *+, - is a constitutive en(yme in kidney, brain, ovary and uterus. #n particular the e)pression of the *+, - in the kidney (in the renal corte) (macula densa) and medullary interstitium) e)plains that the renal and cardiovascular side effect profile of the co)ibs is not different from that of classical N!"#Ds. #n the perioperative period, these risks need to be considered, in particular in patients with hypovolaemia and hypotension. #n conclusion, co)ibs are an important improvement over classical N!"#Ds, but regrettably not the harmless panacea of nonopioid analgesia. %owever, pareco)ib and celeco)ib will make perioperative analgesia more safe.

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References: !chug !". The role of *+, - inhibitors in the treatment of postoperative pain. 6ournal of *ardiovascular 1harmacology -7789 :;(!uppl. &)< !=- =8. Tan T>, !chug !". !afety aspects of postoperative pain management. ?eviews in "nalgesia -778, '(&)< :@ @A. !chug !", Manopas ". .pdate on the role of non opioids for postoperative pain treatment. Best 1ractice C ?esearch *linical "naesthesiology -77;9 -&(&)< &@ A7