周丽丽,王贵龙,高鸿,刘艳秋,郭耀军
ZHOU Lili,WANG Guilong,GAO Hong,LIU Yanqiu,GUO Yaojun

• 1:东莞东华医院麻醉科
• 2:贵州医科大学麻醉学院
• 3:贵州医科大学附院麻醉科

摘要(Abstract)：

目的:观察不同血浆靶控浓度瑞芬太尼致痛觉过敏的发生情况及其对血清中强啡肽表达水平的影响。方法:择期行妇科腹腔镜手术的患者60例,随机均分为对照组(C组)术中间断追加芬太尼1μg/(kg·h)、小剂量瑞芬太尼组(S组,2μg/L)、中剂量瑞芬太尼组(M组,4μg/L)及大剂量瑞芬太尼组(L组,6μg/L);于诱导前,术后苏醒即刻、苏醒后15 min、30 min、1 h、2 h、6 h、24 h记录视觉模拟评分(VAS),记录各组患者痛觉过敏发生情况及术后哌替啶用量,用ELISA法检测诱导前、停药后7 min、苏醒后15 min、1 h测定血清强啡肽浓度。结果:M组、L组患者苏醒即刻、苏醒后15 min、30 min、1 h及2 h VAS评分明显高于C组、S组(P<0.05);与C组比较,S组、M组与L组痛觉过敏发生率均明显增高(P<0.05),哌替啶用量均明显增高(P<0.05);与诱导前比较,M组、L组停药后7 min、苏醒后15 min及1 h血清强啡肽水平明显增加(P<0.05)。结论:大、中剂量瑞芬太尼可增加患者术后痛觉过敏的发生风险,其机制可能与强啡肽的表达增加有关。
Objective: To observe the effects of different concentrations of remifentanil on hyperalgesia and serum dynorphin levels. Methods: Sixty female patients undergoing gynecologic laparoscopic surgery were randomly divided into four groups: control group(group C) with additional fentanyl 1 μg/(kg·h), low-dose remifentanil group(group S, 2 μg/L), medium dose remifentanil group(group M, 4 μg/L) and high dose remifentanil group(group L, 6 μg/L). VAS scores and hyperalgesia were recorded before induction, immediately after awakening, 15 min, 30 min, 1 h, 2 h, 6 h and 24 h after awakening. The dosages of pethidine were measured after the surgery. Serum dynorphin levels were assayed by ELISA at induction, at 7 min after drug withdrawal, and at 15 min and 1 h after awakening. Results: The VAS scores of patients were significantly higher in groups M and L than those in groups C and S at immediately after awaking, at 15 minutes, 30 minutes, 1 h and 2 h after awaking(P<0.05). The incidence rates of hyperalgesia and the dosages of meperidine in groups S, M and L were significantly increased(P<0.05, P<0.05) relative to group C, respectively. Compared with before induction, serum dynorphin levels were significantly increased at 7 min after drug withdrawal, 15 min and 1 h after awaking in groups M and L(P<0.05). Conclusion: The large and medium dosages of remifentanil may increase the incidence rates of postoperative hyperalgesia in patients, and the mechanism may be related to the increased expression of dynorphin.

关键词(KeyWords)： 痛觉过敏;强啡肽;瑞芬太尼;麻醉;视觉模拟评分;腹腔镜
hyperalgesia;dynorphin;remifentanil;anesthesia;visual analogue scale;laparoscopic operation

Abstract:

Keywords:

基金项目(Foundation): 贵州省卫生计生委科学技术基金(gzwjkj2016-1-007)

作者(Author): 周丽丽,王贵龙,高鸿,刘艳秋,郭耀军
ZHOU Lili,WANG Guilong,GAO Hong,LIU Yanqiu,GUO Yaojun

DOI: 10.19367/j.cnki.1000-2707.2019.09.022

参考文献(References)：

• [1] MARUTA T,KODAMA Y,TANAKA I,et al.Comparison of the effect of continuous intravenous infusion and two bolus injections of remifentanil on haemodynamic responses during anaesthesia induction:a prospetive randomised single-centre study[J].BMC Anesthesiol,2016,16(1):110-118.
• [2] CHOU Y W,TING C K,WANG H Y,et al.Enhanced recovery after surgery:prediction for early extubation in video-assisted thoracic surgeny using a response surface model in anesthesia[J].J Formos Med Assoc,2019,37(1):10-19.
• [3] SANTONOCITO C,NOTO A,CRIMI C,et al.Remifentanil-induced postoperative hyperalgesia:current perspectives on mechanisms and therapeutic strategies[J].Local Reg Anesth,2018,9(11):15-23.
• [4] SONG C,LIU P,ZHAO Q,et al.TRPV1 channel contributes to remifentanil-induced postoperative hyperalgesia via regulation of NMDA receptor trafficking in dorsal root ganglion[J].J Pain Res,2019,15(12):667-677.
• [5] YU E H,TRAN D H,LAM S W,et al.Remifentanil tolerance and hyperalgesia:short-term gain,long-term pain[J].Anaesthesia,2016,71(11):1347-1362.
• [6] NAVRATILOVA E,JI G,PHELPS C,et al.Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain[J].Pain,2019,160(4):824-832.
• [7] FERRE G,CIAPIICKI G,DEMANGE P,et al.Structure and dynamics of dynorphin peptide and its receptor[J].Vitam Florm,2019,111:17-47.
• [8] PODVIN S,YAKSH T,HOOK V.Emerging role of spinal dynorphin in chronic pain,a therapeutic perspective[J].Annual Review of Pharmacology and Toxicology,2016,56:511-533.
• [9] COMELON M,RAEDER J,STUBHAUG A,et al.Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia[J].British Journal of Anaesthesia,2016,116(4):524-530.
• [10]YI P,PRYZBYLKOWSKI P.Opioid induced hyperalgesia[J].Pain Medicine,2015,16(SUP 1):32-36.
• [11]EISENBERG E,SUZAN E,PUD D.Opioid-induced hyperalgesia (OIH):a real clinical problem or just an experimental phenomenon[J].Journal of Pain and Symptom Management,2015,49(3):632-636.
• [12]WEINBROUM A A.Postoperative hyperalgesia-A clinically applicable narrative review[J].Pharmacological Research,2017,120:188-205.
• [13]KIM S H,STOICEA N,SOGHOMONYAN S,et al.Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia:a systematic review[J].American Journal of Therapeutics,2015,22(3):62-74.
• [14]TANG R,EVANS H,CHAPUT A,et al.Multimodal analgesia for hip arthroplasty[J].Orthop Clin North Am,2009,40(3):377-387.
• [15]CAMPILLO A,GONZALEZ-CUELLO A,CABANERO D,et al.Increased spinal dynorphin levels and phospho-extracellular signal-regulated kinases 1 and 2 and c-Fos immunoreactivity after surgery under remifentanil anesthesia in mice[J].Mol Pharmacol,2010,77(2):185-194.

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