8/13/2019 Perioperative Use of NSAIDs and Coxibs

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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 thenociceptive pathway by different mechanisms of action of various medications. Multimodal analgesiafor postoperative pain relief is defined as the achievement of improved pain relief through thesynergistic or at least additive effects of different agents (with different mechanisms of action or withdifferent sites of action). This should then lead to improved analgesia, lowered doses of analgesicsneeded, reduced side effects and thereby earlier mobilisation and recovery.Data from a number of studies demonstrate the value of using conventional non steroidal antiinflammatory drugs (N!"#Ds) in improving $uality of analgesia and reducing overall opioidconsumption, thereby diminishing the incidence of opioid related adverse events.%owever, despite the efficacy of N!"#Ds in the perioperative setting, they have associated risks thatcan limit their use in clinical practice.

#n &''&, the discovery of the two isoen ymes of cyclo o ygenase, *+ & and *+ -, opened theopportunity for the development of new anti inflammatories, the co ibs. ntil then the antiinflammatory, analgesic and anti pyretic properties of the N!"#Ds were intrinsically linked to a widerange of potentially fatal adverse effects. The hypothesis underlying the co ibs was the intention toseparate inhibition of the /good0 *+ & (constitutive, protective for stomach and kidney, enablingplatelet 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 pharmaceuticalindustry 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 treatmentof acute pain are only now becoming available. 1areco ib is the first parenterally available co ib for #Mand #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 classicalN!"#Ds. The opioids sparing effects and the improvement of analgesia of their use in multimodalanalgesia 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 *+ &. Thisis a ma4or advantage of these drugs in perioperative use.5urthermore, with short term use, there is without doubt a significantly reduced gastrointestinal to icitywith ulcer rates similar to placebo. #n addition, co ibs do not induce bronchospasm in aspirin sensitiveasthmatics. These properties and possibly less inhibition of bone healing have made co ibs and inparticular pareco ib the increasingly preferred agents for use in the perioperative period and in acutepain 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 therenal 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 withhypovolaemia and hypotension.

#n conclusion, co ibs are an important improvement over classical N!"#Ds, but regrettably not theharmless panacea of nonopioid analgesia. %owever, pareco ib and celeco ib will make perioperativeanalgesia more safe.

Recommended Reading: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. Best1ractice C ?esearch *linical "naesthesiology -77;9 -&(&)< &@ A7