Mather L E
Department of Anaesthesia and Pain Management, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Drugs. 1992;44 Suppl 5:1-12; discussion 13. doi: 10.2165/00003495-199200445-00003.
Until recently, nonsteroidal anti-inflammatory drugs (NSAIDs) were regarded as weak analgesic agents with a potent antiplatelet effect that severely limited their perioperative usefulness. However, the recent development of injectable NSAIDs has stimulated a re-evaluation of the potential role of this class of drugs in postoperative pain management. In general surgery, NSAIDs have been shown to be effective analgesics when administered after surgery, as judged by either a reduction in pain scores and/or by an opioid sparing effect. Parenteral NSAIDs alone, notably ketorolac and diclofenac, may be adequate or even preferred analgesic agents after minor surgery. In dental surgery, NSAIDs produce greater initial analgesia than steroids, although the latter produce greater suppression of swelling and less functional loss. NSAID pretreatment results in only modest suppression of swelling compared with placebo. These data suggest that the acute analgesic effects of NSAIDs in oral surgery and probably other models result from suppression of a nociceptive process, rather than a generalised anti-inflammatory effect. This view challenges the traditional association between inhibition of prostaglandin synthesis and the therapeutic effects of these drugs. The variety of NSAIDs leads to a range in half-lives from short, e.g. diclofenac (1 h), intermediate, e.g. ketorolac (5h), to long, e.g. tenoxicam (60h), which has implications for both convenience of the dosage regimen and drug accumulation. For some racemic NSAIDs (e.g. ibuprofen), metabolic 'activation' of the inactive R-enantiomer to the active S-enantiomer occurs. Renal dysfunction may increase both the plasma concentration and body residence time of NSAIDs, thereby increasing the risk of adverse effects. The concomitant effects of anaesthesia have not yet been studied. The principal concern regarding the use of perioperative NSAIDs is the risk of decreased haemostasis and wound healing. Although it has been found that NSAIDs prolong bleeding times in patients, values generally remain below the upper limits of those in generally healthy patients. Healing of gastrointestinal anastomoses may be compromised by NSAID administration but corneal healing and bone remodelling are not. There is a need for further research into the potential for renal side effects with NSAIDs in the perioperative setting, where the effects of anaesthesia and surgery may increase the risk of side effects, particularly in elderly patients. The main benefits of NSAIDs derive from opioid sparing (e.g. reduction in perioperative nausea and vomiting and improvement in ventilation), although some studies allude to an enhanced quality of analgesia from the combination compared with either NSAID or opioid alone. The question of pre- vs postinjury treatment with NSAIDs remains unresolved.
直到最近，非甾体抗炎药（NSAIDs）还被视为弱镇痛药，其强大的抗血小板作用严重限制了它们在围手术期的应用。然而，注射用NSAIDs的最新进展促使人们重新评估这类药物在术后疼痛管理中的潜在作用。在普通外科手术中，术后使用NSAIDs已被证明是有效的镇痛药，这可通过疼痛评分降低和/或阿片类药物节省效应来判断。单独使用胃肠外NSAIDs，尤其是酮咯酸和双氯芬酸，在小手术后可能是足够的甚至是首选的镇痛药。在牙科手术中，NSAIDs产生的初始镇痛效果比类固醇更强，尽管后者对肿胀的抑制作用更强且功能丧失更少。与安慰剂相比，NSAIDs预处理对肿胀的抑制作用仅为中等程度。这些数据表明，NSAIDs在口腔手术以及可能在其他模型中的急性镇痛作用是由于抑制了伤害感受过程，而不是普遍的抗炎作用。这一观点挑战了前列腺素合成抑制与这些药物治疗效果之间的传统关联。NSAIDs种类繁多，半衰期从短的（如双氯芬酸，1小时）、中等的（如酮咯酸，5小时）到长的（如替诺昔康，60小时）不等，这对给药方案的便利性和药物蓄积都有影响。对于一些消旋NSAIDs（如布洛芬），无活性的R-对映体可代谢“活化”为活性S-对映体。肾功能不全可能会增加NSAIDs的血浆浓度和体内停留时间，从而增加不良反应的风险。麻醉的伴随作用尚未得到研究。围手术期使用NSAIDs的主要担忧是止血和伤口愈合受影响的风险。尽管已发现NSAIDs会延长患者的出血时间，但数值通常仍低于一般健康患者的上限。NSAIDs给药可能会影响胃肠吻合口的愈合，但不会影响角膜愈合和骨重塑。有必要进一步研究围手术期使用NSAIDs时肾副作用的可能性，因为麻醉和手术的影响可能会增加副作用的风险，尤其是在老年患者中。NSAIDs的主要益处源于阿片类药物节省（如减少围手术期恶心和呕吐以及改善通气），尽管一些研究暗示与单独使用NSAIDs或阿片类药物相比，联合使用可提高镇痛质量。NSAIDs在损伤前还是损伤后治疗的问题仍未解决。
