Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany.
Eur J Pain. 2012 Jul;16(6):838-48. doi: 10.1002/j.1532-2149.2011.00062.x. Epub 2011 Dec 19.
Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin production in wound fluid, but the onset of action is variable due to delayed post-operative absorption.
In this study, we investigated the preoperative administration of etoricoxib in patients undergoing hip replacement. They received 120 mg etoricoxib or placebo 2 h before surgery and 1 day after in a double-blinded, randomized, parallel group design.
A total of 11 patients were randomized (placebo n = 5; verum n = 6). We found high and constant levels of the drug in blood, central nervous system and wound fluid already at the end of surgery (t(max) < 2 h). This was accompanied by inhibition of prostaglandin production in the wound tissue (treatment p < 0.05), suppression of interleukin 6 increase in plasma (treatment p < 0.01), and - despite existing standard pain relief procedures - higher satisfaction with analgesics (time vs. treatment p < 0.05) and less demand for opioids (treatment p < 0.01) and intrathecal bupivacaine (treatment p = 0.05) administration.
Administration of etoricoxib 2 h before surgery allows for an effective drug concentration in critical tissues, a reduction of the production of pro-inflammatory mediators and for better pain relief.
术前给予环氧化酶-2 抑制剂似乎很有吸引力,因为这些药物可以减轻术后疼痛,而且不会增加术后出血、哮喘发作和应激性胃肠道溃疡的风险。在之前的一项研究中,我们已经证实,术后给予依托考昔可减少伤口液中的前列腺素生成,但由于术后吸收延迟,其作用起效时间会有所不同。
在这项研究中,我们调查了髋关节置换术患者术前给予依托考昔的情况。他们以双盲、随机、平行组设计接受术前 2 小时给予 120mg 依托考昔或安慰剂,术后 1 天再给予相同药物。
共有 11 名患者被随机分配(安慰剂组 n=5;依托考昔组 n=6)。我们发现,在手术结束时(t(max)<2 小时),药物在血液、中枢神经系统和伤口液中已经达到高且稳定的水平。这伴随着伤口组织中前列腺素生成的抑制(治疗 p<0.05)、血浆中白细胞介素 6 增加的抑制(治疗 p<0.01),以及尽管存在标准的止痛程序,患者对镇痛药的满意度更高(时间 vs. 治疗 p<0.05),对阿片类药物(治疗 p<0.01)和鞘内布比卡因(治疗 p=0.05)的需求更少。
术前 2 小时给予依托考昔可使关键组织中的药物浓度达到有效水平,减少促炎介质的产生,并提供更好的止痛效果。