NSAIDs in postoperative pain
-
Vesa Kontinen
The objectives of this presentation are to give an update on clinical pharmacology of non-steroidal anti-inflammatory analgesics (NSAIDs) in management of postoperative pain and discuss use of these drugs in specific patient groups.
Prostaglandins play important roles in many cellular responses and pathophysiologic processes including modulation of the inflammatory reaction, turnover of cartilage and bone, gastrointestinal cytoprotection, angiogenesis and cancer, hemostasis and thrombosis, and renal hemodynamics. The major target for NSAIDs is the cyclo-oxygenase pathway in the peripheral tissues. NSAIDs have also central actions in the spinal cord and brain. The relative contribution of peripheral and central sites of action is variable in different pain states is not complitely understood. It has been suggested that pharmacokinetic factors, such as the relative distribution to effect sites and sites where COX-inhibition is harmful (eg kidney), might partly explain differences in the efficacy and safety between various NSAIDs.
NSAIDs are effective analgesics in acute postoperative pain, especially when there is an inflammatory component. In severe postoperative pain it is not possible to study the effect of NSAIDs alone, but most commonly the opioid-sparing effect is studied, despite the shortfalls of the method. NSAIDs have been shown to relatively consistently reduce postoperative opioid consumption in average by 30–50%, and to reduce opioid-induced adverse effects, such as nausea & vomiting and sedation.
NSAIDs and coxibs have deleterious effect on renal function that can lead to both acute and chronic renal failure. The risk of acute renal failure associated to NSAID is increased in patients with hypertension, diabetes, and pre-existing renal diseases, including previous episodes of acute renal failure, exposure to other nephrotoxic drugs and contrast media, and the length of use. In patients with previously normal renal function and no perioperative problems with homeostasis, of NSAIDs for postoperative pain can be relatively safe to kidneys.
COX-1 has a key role in production of gastroprotective prostaglandins, and NSAIDs produce dyspepsia and peptic ulcer disease in chronic use. Coxibs are not completely devoid of adverse gastrointestinal effects, but the risk is significantly lower. In acute postoperative pain NSAIDs are usually used for a short period, and the risk of gastrointestinal problems is lower than in chronic use.
NSAIDs can lead to the development of congestive heart failure in susceptible individuals, but there are only few epidemiological investigations on this “forgotten” adverse effect. Since 2004 a lot has been written on thrombotic cardiovascular events associated to coxibs. In postoperative pain, NSAIDs or coxibs are in most cases used for a relatively short time, and therefore the cardiovascular risk profile is different from that in chronic use. Other risk factors for cardiovascular disease are importan for risk assessment for postoperative analgesia. NSAIDs (except ASA) reversibly inhibit COX-1 in platelets, and the effect on platelet aggregation and risk of bleeding is dependent on the half-life of the compound.
Prostaglandins are important in the regulation of osteoblast and osteoclast functions, and inhibition of prostaglandin production affect bone formation. COX-2 controls osteoclastogenesis, mechanotransduction, bone formation and fracture repair constitutively in the skeleton. Reports of impaired bone healing associated with NSAID treatment have therefore raised a concern, but here are no good clinical studies on this matter. Based on the importance of inflammation of the tissue healing in general, concern on the effect of NSAIDs on healing of surgical injury in other tissues, such as intestinal anastomoses, has also been raised. However, there is very little clinical evidence on this.
When considering the use of NSAIDs in postoperative pain, the analgesic good efficacy must be balanced against the known and assumed adverse effects. The assessment must be based on the individual characteristics of each patient, and compared to the risk profile of alternative methods of pain management.
© 2012 Scandinavian Association for the Study of Pain
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