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一项比较初次全膝关节置换术中局部浸润镇痛和股神经阻滞术后罗哌卡因血浆浓度的随机研究。

A randomized study comparing plasma concentration of ropivacaine after local infiltration analgesia and femoral block in primary total knee arthroplasty.

作者信息

Affas Fatin, Stiller Carl-Olav, Nygårds Eva-Britt, Stephanson Niclas, Wretenberg Per, Olofsson Christina

机构信息

Department of Anaesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.

Department of Medicine, Clinical Pharmacology Unit, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.

出版信息

Scand J Pain. 2012 Jan 1;3(1):46-51. doi: 10.1016/j.sjpain.2011.09.001.

Abstract

Pain after total knee arthroplasty (TKA) is difficult to control. A recently developed and increasingly popular method for postoperative analgesia following knee and hip arthroplasty is Local Infiltration Analgesia (LIA) with ropivacaine, ketorolac and epinephrine. This method is considered to have certain advantages, which include administration at the site of traumatized tissue, minimal systemic side effects, faster postoperative mobilization, earlier postoperative discharge from hospital and less opioid consumption. One limitation, which may prevent the widespread use of LIA is the lack of information regarding plasma concentrations of ropivacaine and ketorolac. The aim of this academically initiated study was to detect any toxic or near-toxic plasma concentrations of ropivacaine and ketorolac following LIA after TKA. Methods Forty patients scheduled for primary total knee arthroplasty under spinal anaesthesia, were randomized to receive either local infiltration analgesia with a mixture of ropivacaine 300 mg, ketorolac 30mg and epinephrine or repeated femoral nerve block with ropivacaine in combination with three doses of 10mg intravenous ketorolac according to clinical routine. Plasma concentration of ropivacaine and ketorolac were quantified by liquid chromatography-mass spectrometry (LC-MS). Results The maximal detected ropivacaine plasma level in the LIA group was not statistically higher than in the femoral block group using the Mann-Whitney U-test (p = 0.08). However, the median concentration in the LIA group was significantly higher than in the femoral block group (p < 0.0001; Mann-Whitney U-test). The maximal plasma concentrations of ketorolac following administration of 30mg according to the LIA protocol were detected 1 h or 2 h after release of the tourniquet in the LIA group: 152-958 ng/ml (95% CI: 303-512 ng/ml; n = 20). The range of the plasma concentration of ketorolac 2-3 h after injection of a single dose of 10mg was 57-1216 ng/ml (95% CI: 162-420 ng/ml; n = 20). Conclusion During the first 24 h plasma concentration of ropivacaine seems to be lower after repeated femoral block than after LIA. Since the maximal ropivacaine level following LIA is detected around 4-6 h after release of the tourniquet, cardiac monitoring should cover this interval. Regarding ketorolac, our preliminary data indicate that the risk for concentration dependent side effects may be highest during the first hours after release of the tourniquet. Implication Femoral block may be the preferred method for postoperative analgesia in patients with increased risk for cardiac side effects from ropivacaine. Administration of a booster dose of ketorolac shortly after termination of the surgical procedure if LIA was used may result in an increased risk for toxicity.

摘要

全膝关节置换术(TKA)后的疼痛难以控制。一种最近开发且越来越受欢迎的用于膝关节和髋关节置换术后镇痛的方法是用罗哌卡因、酮咯酸和肾上腺素进行局部浸润镇痛(LIA)。该方法被认为具有某些优点,包括在创伤组织部位给药、全身副作用最小、术后活动更快、术后更早出院以及阿片类药物消耗更少。一个可能会阻碍LIA广泛应用的限制因素是缺乏关于罗哌卡因和酮咯酸血浆浓度的信息。这项学术发起的研究的目的是检测TKA后LIA后罗哌卡因和酮咯酸的任何有毒或接近有毒的血浆浓度。方法 40例计划在脊髓麻醉下进行初次全膝关节置换术的患者,被随机分为两组,一组接受含有300mg罗哌卡因、30mg酮咯酸和肾上腺素的混合液进行局部浸润镇痛,另一组按照临床常规接受罗哌卡因联合三次10mg静脉注射酮咯酸的重复股神经阻滞。通过液相色谱 - 质谱联用(LC - MS)对罗哌卡因和酮咯酸的血浆浓度进行定量。结果 使用曼 - 惠特尼U检验,LIA组中检测到的罗哌卡因血浆最大水平在统计学上并不高于股神经阻滞组(p = 0.08)。然而,LIA组的中位数浓度显著高于股神经阻滞组(p < 0.0001;曼 - 惠特尼U检验)。按照LIA方案给予30mg酮咯酸后,LIA组在松开止血带后1小时或2小时检测到酮咯酸的最大血浆浓度为152 - 958 ng/ml(95%CI:303 - 512 ng/ml;n = 20)。单次注射10mg后2 - 3小时酮咯酸的血浆浓度范围为57 - 1216 ng/ml(95%CI:162 - 420 ng/ml;n = 20)。结论 在最初24小时内,重复股神经阻滞术后罗哌卡因的血浆浓度似乎低于LIA后。由于LIA后罗哌卡因的最大水平在松开止血带后约4 - 6小时检测到,心脏监测应覆盖该时间段。关于酮咯酸,我们的初步数据表明,在松开止血带后的最初几个小时内,浓度依赖性副作用的风险可能最高。启示 对于因罗哌卡因导致心脏副作用风险增加的患者,股神经阻滞可能是术后镇痛的首选方法。如果使用LIA,在手术结束后不久给予一剂酮咯酸追加剂量可能会增加毒性风险。

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