ACM Advances in Clinical Medicine 2161-8712 Scientific Research Publishing 10.12677/ACM.2022.121069 ACM-48311 ACM20220100000_93273564.pdf 医药卫生 不同麻醉镇痛方式对胃癌患者术后胰岛素抵抗的影响 Effects of Different Anesthesia and Analgesia Methods on Insulin Resistance in Patients with Gastric Cancer after Operation 王 玉娟 2 1 张 子英 3 1 张 发展 3 1 于 洋 4 1 韩 永彬 3 1 李 瑜 5 1 青岛大学附属医院麻醉科，山东 青岛 日照市人民医院麻醉科，山东 日照 青岛大学附属医院麻醉科，山东 青岛；日照市人民医院麻醉科，山东 日照 日照市人民医院普外科，山东 日照 null 05 01 2022 12 01 470 476 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

目的：评价不同麻醉镇痛方式对胃癌患者术后恢复的影响，并探讨对术后胰岛素抵抗的影响及其作用机制。方法：60例胃癌患者随机分为两组，每组30例。一组为常规全麻组，术后采用静脉自控镇痛(PCIA)；另一组为全身麻醉复合硬膜外麻醉组，术后应用硬膜外自控镇痛(PCEA)。分别比较两组患者的麻醉术后首次排气时间、术后首次下地活动时间、住院天数、疼痛评分(VAS)、胰岛素抵抗指数(IRI)和急性反应蛋白(CRP)。结果：1) 两组患者一般资料比较，差异无统计学意义(P > 0.05)；2) PCEA组患者术后VAS明显低于PICA组，差异有统计学意义(P < 0.05)；3) PCEA组患者术后IRI明显低于PCIA组，差异有统计学意义(P < 0.05)，PCEA组患者术后CRP计数低于PCIA组，差异有统计学意义(P < 0.05)；4) PCEA组患者术后首次排气时间、术后首次下地活动时间及住院天数显著短于PCIA组，差异有统计学意义(P < 0.05)，术后并发症两组比较差异无统计学意义(P > 0.05)。结论：全身麻醉复合硬膜外麻醉应用硬膜外镇痛泵的方式能明显减轻胃癌患者术后疼痛感，有效减轻全身炎症反应，降低术后胰岛素抵抗，缩短住院时间，有利于患者术后康复。 Objective: To evaluate the effects of different anesthesia and analgesia methods on postoperative recovery of patients with gastric cancer, and to explore the effects on insulin resistance and its mechanism. Methods: Sixty patients with gastric cancer were randomly divided into two groups, thirty patients in each group. The first group was treated with general anesthesia, patients adopted patient-controlled intravenous analgesia (PCIA) after surgery; the other group was general anesthesia combined with epidural anesthesia, postoperative patients received continuous patient-controlled epidural analgesia (PCEA). Compare the first postoperative exhaust time and off-bed ambulation time, pain score (VAS), insulin resistance index (IRI) and acute reactive protein (CRP) in 2 groups after anesthesia, and record the hospital stay, postoperative complications and other conditions. Results: 1) There was no statistical significance in general data between the 2 groups (P > 0.05). 2) The postoperative VAS in PCEA group was significantly lower than that in PCIA group, with statistical significances (P < 0.05). 3) The postoperative IRI and CRP in the PCEA group were significantly lower than those in PCIA, all with statistical significances (P < 0.05). 4) The length of first postoperative exhaust time and off-bed ambulation time and hospital stay in PCEA group were significantly lower than those in PCIA group, all with statistical significances (P < 0.05), while there was no significant difference in postoperative complications among the two groups (P > 0.05). Conclusion: General anesthesia combined with epidural anesthesia and analgesia can shorten the first postoperative exhaust time and off-bed ambulation time obviously, reduce systemic inflammatory reaction and insulin resistance effectively, shorten the length of hospital stay and reduce hospitalization costs, and help to accelerate recovery of postoperative patients with gastric cancer.

 胰岛素抵抗，麻醉方式，硬膜外麻醉，镇痛，胃癌, Insulin Resistance Anesthesia Method Epidural Anesthesia Analgesia Gastric Cancer 摘要

目的：评价不同麻醉镇痛方式对胃癌患者术后恢复的影响，并探讨对术后胰岛素抵抗的影响及其作用机制。方法：60例胃癌患者随机分为两组，每组30例。一组为常规全麻组，术后采用静脉自控镇痛(PCIA)；另一组为全身麻醉复合硬膜外麻醉组，术后应用硬膜外自控镇痛(PCEA)。分别比较两组患者的麻醉术后首次排气时间、术后首次下地活动时间、住院天数、疼痛评分(VAS)、胰岛素抵抗指数(IRI)和急性反应蛋白(CRP)。结果：1) 两组患者一般资料比较，差异无统计学意义(P > 0.05)；2) PCEA组患者术后VAS明显低于PICA组，差异有统计学意义(P < 0.05)；3) PCEA组患者术后IRI明显低于PCIA组，差异有统计学意义(P < 0.05)，PCEA组患者术后CRP计数低于PCIA组，差异有统计学意义(P < 0.05)；4) PCEA组患者术后首次排气时间、术后首次下地活动时间及住院天数显著短于PCIA组，差异有统计学意义(P < 0.05)，术后并发症两组比较差异无统计学意义(P > 0.05)。结论：全身麻醉复合硬膜外麻醉应用硬膜外镇痛泵的方式能明显减轻胃癌患者术后疼痛感，有效减轻全身炎症反应，降低术后胰岛素抵抗，缩短住院时间，有利于患者术后康复。

 关键词

胰岛素抵抗，麻醉方式，硬膜外麻醉，镇痛，胃癌

 Effects of Different Anesthesia and Analgesia Methods on Insulin Resistance in Patients with Gastric Cancer after Operation<sup> </sup>

Yujuan Wang1,2, Ziying Zhang2, Fazhan Zhang2, Yang Yu3, Yongbin Han2, Yu Li1*

1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao Shandong

2Department of Anesthesiology, People’s Hospital of Rizhao, Rizhao Shandong

3Department of General Surgery, People’s Hospital of Rizhao, Rizhao Shandong

Received: Dec. 24th, 2021; accepted: Jan. 14th, 2022; published: Jan. 26th, 2022

 ABSTRACT

Objective: To evaluate the effects of different anesthesia and analgesia methods on postoperative recovery of patients with gastric cancer, and to explore the effects on insulin resistance and its mechanism. Methods: Sixty patients with gastric cancer were randomly divided into two groups, thirty patients in each group. The first group was treated with general anesthesia, patients adopted patient-controlled intravenous analgesia (PCIA) after surgery; the other group was general anesthesia combined with epidural anesthesia, postoperative patients received continuous patient-controlled epidural analgesia (PCEA). Compare the first postoperative exhaust time and off-bed ambulation time, pain score (VAS), insulin resistance index (IRI) and acute reactive protein (CRP) in 2 groups after anesthesia, and record the hospital stay, postoperative complications and other conditions. Results: 1) There was no statistical significance in general data between the 2 groups (P > 0.05). 2) The postoperative VAS in PCEA group was significantly lower than that in PCIA group, with statistical significances (P < 0.05). 3) The postoperative IRI and CRP in the PCEA group were significantly lower than those in PCIA, all with statistical significances (P < 0.05). 4) The length of first postoperative exhaust time and off-bed ambulation time and hospital stay in PCEA group were significantly lower than those in PCIA group, all with statistical significances (P < 0.05), while there was no significant difference in postoperative complications among the two groups (P > 0.05). Conclusion: General anesthesia combined with epidural anesthesia and analgesia can shorten the first postoperative exhaust time and off-bed ambulation time obviously, reduce systemic inflammatory reaction and insulin resistance effectively, shorten the length of hospital stay and reduce hospitalization costs, and help to accelerate recovery of postoperative patients with gastric cancer.

Keywords:Insulin Resistance, Anesthesia Method, Epidural Anesthesia, Analgesia, Gastric Cancer

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 1. 引言

1997年丹麦Kehlet教授提出多学科策略，其主要目的在于减少手术给病人带来的创伤，改善临床结局、降低病人的医疗费用 [ 1 ]，并由此衍生出加速康复外科(enhanced recovery after surgery, ERAS)这一概念。近年来随着该理念的发展，已从最早的结直肠肿瘤手术 [ 2 ] 推广到胃、食管、十二指肠等上消化道 [ 3 ] 手术领域，但该方案的实施离不开麻醉医学理论支持 [ 4 ]。现代麻醉学管理的目标已经由传统的为外科提供优越的手术条件，保证患者手术时安全，进一步发展为合理调控围术期应激反应，采用一系列有效措施优化围术期患者管理，控制手术创伤性刺激反应，维持重要器官功能，减少不良反应，提高患者康复质量，合理的麻醉管理是加速康复外科的重要组成部分 [ 5 ]。

胃癌手术是一种创伤应激较大的手术，手术后随着大量应激激素释放和组织对胰岛素敏感性降低，机体产生高代谢和一系列碳水化合物代谢改变，引起外科胰岛素抵抗(IR)即“应激性糖尿病”，其主要表现为高血糖、高胰岛素和高乳酸血症，IR在一定程度上是机体对抗外界不良刺激的一种适应性反应，但是当IR严重时，会引起全身集体代谢紊乱，引起负氮平衡，使机体抗感染、抗休克能力显著降低，最终可引起酮症酸中毒等多种并发症。术后的胰岛素抵抗是影响患者预后的一个重要因素 [ 6 ]。

本研究通过观察不同麻醉镇痛方式对胃癌患者术后恢复的影响，为ERAS理念下选择合理的麻醉方式提供临床理论依据，并从麻醉角度探讨术后胰岛素抵抗的影响及其作用机制，为临床诊治创伤后胰岛素抵抗提供理论依据。

 2. 资料与方法 2.1. 一般资料

随机选取我院普外科自2018年1月至2020年9月期间，行腹腔镜胃癌根治术患者60例，术前均经胃镜病理证实为胃癌，其中男性34例，女性26例，年龄32.0~72.0岁，体质指数(BMI) 19.3~30.2 kg/m2。入组前病人均取得医院伦理委员会及患者或家属的知情同意。

 2.2. 研究方法 2.2.1. 入组标准

1) 胃镜病理证实为胃癌，影像学检查无远处转移，所有病人均行腹腔镜下胃癌根治术；2) 围手术期未行放化疗，未服用影响机体代谢的药物；3) 手术前凝血系列及血糖正常；4) 白细胞计数大于4.0 × 109/L，血小板计数大于100.0 × 109/L，血红蛋白大于120 g/L；5) 伦理委员会讨论通过并进行临床试验注册。

 2.2.2. 排除标准

1) 糖耐量异常、糖尿病、凝血异常，出血倾向、口服抗凝药物或止血等药物；2) 体重指数大于30.0或体重指数小于15.0；3) 内分泌代谢性疾病；4) 术前合并脑、心、肺、肝、肾等疾病；5) 已发生远处转移，多源发性肿瘤或合并其他部位的肿瘤；6) 术前2周内接受输血、营养支持等治疗。

 2.2.3. 麻醉和手术方法

60例患者入院后明确术前诊断，详细记录60例病人一般情况，术前夜晚22:00开始禁饮食，术前抽取空腹血测定血糖、胰岛素、超敏反应蛋白，术前置鼻胃管。60位患者随机分为两组，全麻诱导前PCEA组患者在T8-9间隙行硬膜外穿刺置管，明确硬膜外导管位置正确后，给予罗哌卡因3 ml，硬膜外腔注射，5 min后测试麻醉平面，再开始进行麻醉常规诱导。两组患者的静脉麻醉诱导用药是丙泊酚，把控浓度为2.0~3.0 mg/L，舒芬太尼用量约0.3~0.5 ug/kg，顺式阿曲库胺0.2 mg/kg；麻醉维持用药是七氟烷，维持最低肺泡有效浓度；通过调整麻醉用药浓度，维持麻醉深度指数在D2-E1级，术后PCEA组接硬膜外镇痛泵，PCIA组接静脉镇痛泵。所有手术均行腹腔镜下胃癌根治术，术中均未输入血制品，术中补液均用林格氏液和万汶，不含葡萄糖及胰岛素制品，记录手术时间、术中补液量、出血量及并发症。

 2.2.4. 术后镇痛方法

PCIA组静脉自控镇痛泵配方：舒芬太尼100 ug加生理盐水共100 ml；负荷剂量为5 ml，患者自控为2 ml/次，正常工作时为2 ml/h；PCEA组硬膜外自控镇痛泵配方：罗哌卡因75 mg加NS 100 ml，负荷剂量为5 ml，患者自控为2 ml/次，正常工作时为2 ml/h。

 2.3. 观察指标及检测方法

1) 所有患者分别于术后1、6、12、24、48 h应用VAS评分评价两组患者镇痛效果：无痛为0分，轻度疼痛1~3分，中度疼痛4~6分，重度疼痛7~9分，剧烈疼痛10分；2) 所有入组患者分别于术前4小时和术后12、24、48 h空腹抽取外周静脉血约5 ml，其中2 ml用全自动化分析仪测定血浆葡萄糖浓度及超敏C反应蛋白(CRP)；另外3 ml使用全自动化学发光免疫分析仪测定血清胰岛素浓度；3) 对于胰岛素敏感性的测定目前公认的是DeFronzo等建立和发展的葡萄糖–高胰岛素钳夹技术，被认为是测定胰岛素抵抗指数的金标准，但这种方法操作复杂，价格昂贵，120分钟内需频繁抽血24次，临床实行难度大，基于以上缺点最近美国国家卫生院的研究表明由Matthews等设计的稳态模式评估法(homeostasis model assessment, HOMA)计算胰岛素抵抗指数(HOMA-IR)反应胰岛素敏感程度，该法使用简单，方便可重复性高，其公示为：HOMA-IR = FPG (mmol/L) × FINS (mU/L)/22.5。HOMA-IR作为简易胰岛素敏感性指数，HOMA-IR值越高，表明机体胰岛素敏感性越低，IR越严重。由于HOMA-IR值为非正态分布，美国国立卫生研究院(NIH)的研究显示：在与血糖钳夹试验比较后，对数化的HOMA-IR [ln (HOMA-IR)]与其显著相关，多元回归分析显示ln (HOMA-IR)是所有与胰岛素抵抗相关的临床指标中最强的相关指数，故本研究将胰岛素敏感性指标取HOMA-IR自然对数ln (HOMA-IR)用于分析；4) 记录病人术后首次排气时间、首次下地活动时间、住院天数及并发症。

 2.4. 统计学方法

采用SPSS22.0统计学软件进行统计学分析，计量资料以均数 ± 标准差( x ¯ ± s )表示，采用t检验，计数资料采用χ2检验。P < 0.05表示差异有统计学意义。

 3. 结果 3.1. 两组患者一般资料比较

两组患者性别、BMI、年龄、麻醉学ASA分级、手术时间、失血量比较，差异均无统计学意义(P值均>0.05)。见表1。

Comparison of general information among two groups (n = 30, x ¯ ± s
组别 性别(例) 年龄(岁) BMI (kg/m2) ASA分级(例) 手术时间(h) 术中失血量(ml)
男 女 I级 II级 III级
PCIA组 18 12 57.23 ± 2.43 23.10 ± 2.40 5 23 2 4.89 ± 0.43 23.1 ± 64.5
PCEA组 16 14 56.12 ± 2.71 22.90 ± 3.10 6 23 1 5.01 ± 0.47 479.7 ± 50.1
统计量 χ2= 0.27 t = 1.67 t = 0.28 χ2= 0.43 t = 1.03 t = 0.516
P值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05

表1. 两组患者一般资料比较(n = 30, x ¯ ± s )

 3.2. 两组患者手术前后胰岛素抵抗指数比较

两组患者比较，术前4 h胰岛素抵抗指数差异无统计学意义(P值 > 0.05)，术后12、24、48 h胰岛素抵抗指数差异均有统计学意义(P值均<0.05)。见表2。

 3.3. 两组患者手术前后急性反应蛋白含量比较

两组患者比较，术前4 h急性反应蛋白含量差异无统计学意义(P值 > 0.05)，术后12、24、48 h急性反应蛋白含量差异均有统计学意义(P值均<0.05)。见表3。

Comparison of insulin resistance index before and after surgery among two groups (n = 30, x ¯ ± s
组别 术前4 h 术后12 h 术后24 h 术后48 h
PCIA组 2.76 ± 0.45 10.21 ± 0.71 23.23 ± 1.53 37.32 ± 2.13
PCEA组 2.65 ± 0.43 6.67 ± 0.43 11.11 ± 1.43 19.32 ± 2.39
t值 1.01 23.36 31.70 30.80
P值 >0.05 <0.05 <0.05 <0.05

表2. 两组患者手术前后胰岛素抵抗指数比较(n = 30, x ¯ ± s )

Comparison of acute reactive protein content before and after surgery among two groups (n = 30, x ¯ ± s , mg/L
组别 术前4 h 术后12 h 术后24 h 术后48 h
PCIA组 4.01 ± 2.42 64.50 ± 4.10 81.43 ± 5.89 101.26 ± 6.82
PCEA组 4.23 ± 2.17 49.20 ± 3.36 57.21 ± 5.26 69.52 ± 5.35
t值 0.37 15.81 16.80 20.06
P值 >0.05 <0.05 <0.05 <0.05

表3. 两组患者手术前后急性反应蛋白含量比较(n = 30, x ¯ ± s , mg/L)

 3.4. 两组患者术后疼痛评分、早期恢复指标及住院天数比较

两组患者比较，术后1 h疼痛评分差异无统计学意义(P值 > 0.05)，术后6、12、24、48 h疼痛评分差异均有统计学意义(P值均<0.05)；术后早期恢复指标(首次排气时间、首次下床活动时间)及住院天数差异均有统计学意义(P值均<0.05)。见表4、表5。

Comparison of pain score after surgery among two groups (n = 30, x ¯ ± s
组别 术后1 h 术后6 h 术后12 h 术后24 h 术后48 h
PCIA组 1.92 ± 0.31 4.65 ± 0.51 4.92 ± 0.29 4.98 ± 0.41 4.12 ± 0.41
PCEA组 1.79 ± 0.32 1.82 ± 0.33 1.92 ± 0.37 2.54 ± 0.61 1.97 ± 0.36
t值 1.60 10.55 34.95 18.18 21.58
P值 >0.05 <0.05 <0.05 <0.05 <0.05

表4. 两组患者术后疼痛评分比较(n = 30, x ¯ ± s )

Comparison of early recovery indicator after surgery and length of hospital stay among two groups (n = 30, x ¯ ± s
组别 首次排气时间 首次下床活动时间 住院天数
PCIA组 3.31 ± 0.55 2.45 ± 0.73 11.19 ± 0.78
PCEA组 1.56 ± 0.43 1.34 ± 0.41 8.15 ± 0.71
t值 13.73 7.26 15.79
P值 <0.05 <0.05 <0.05

表5. 两组患者术后早期恢复指标及住院天数比较(n = 30, x ¯ ± s )

 4. 讨论

加速康复外科(ERAS)在世界范围内得到了广泛推广并取得了良好效果，ERAS是一个多学科交叉概念，是一系列术前、术中、术后措施的综合应用，其中麻醉作为ERAS的重要组成部分，其减少手术创伤、降低围手术期并发症的发生率、促进病人康复发挥了重要作用 [ 7 ]，选择合理的麻醉及镇痛方式是改善围手术期结局与加速术后康复的先决条件 [ 8 ]，术前禁饮食还会增加患者的饥渴感、紧张感和不适感 [ 9 ]，机体处于饥饿状态本身就是一种应激 [ 10 ]，加上手术应激，从而容易导致术后发生胰岛素抵抗。

术后胰岛素抵抗是指肝脏、肾脏、骨骼肌等胰岛素靶器官对胰岛素的敏感性和反应性降低，当胰岛素抵抗严重时，会导致代谢功能紊乱引起高血糖，持续的高血糖使机体感染风险性增加，不利于手术伤口的愈合，对机体恢复产生不利影响。有研究显示，术后胰岛素抵抗的现象自麻醉开始时产生，至术后24 h内显著，较大的腹部手术胰岛素抵抗可持续2~3周 [ 11 ]，胃癌手术作为创伤应激程度较大的手术，胰岛素抵抗的发生率为49% [ 6 ]，因此减轻胃癌病人术后胰岛素抵抗有利于术后病人的恢复，改善临床结局。

通过本次研究，我们发现PCEA组患者术后胰岛素抵抗指数、超敏C反应蛋白明显低于PCIA组，其原因可能是硬膜外镇痛复合全身麻醉发挥了有效的神经阻滞作用 [ 12 ]，可减少手术引起的神经及内分泌代谢应激反应，减轻全身炎症反应，降低术后胰岛素抵抗 [ 13 ]，其主要机制在于 [ 14 ]：抑制体内TNF-α、MIF、MCP-1等炎症介质的生成，影响单核细胞核内炎症反应相关因子的表达等 [ 15 ]，减少了术后炎性反应，有利于机体的恢复 [ 16 ]。

此外本次研究结果还显示，PCEA组患者术后6、12、24、48 h的疼痛评分均显著低于PCIA组，PCEA组患者术后首次排气时间、首次下床活动时间及住院天数较PCIA组明显缩短，表明硬膜外复合全身麻醉应用硬膜外镇痛泵可减轻术后疼痛感，加速患者术后恢复，其主要机制可能是PCEA组可明显降低术后阿片类药物暴露量，降低术后肺部感染、肠梗阻、深静脉血栓等发生率 [ 17 ] [ 18 ]，缩短住院时间 [ 19 ] [ 20 ]，本研究中未出现硬膜外麻醉及镇痛失败的情况，表明PCEA麻醉方式在胃癌的麻醉应用是安全有效的。

 5. 总结

综上所述，硬膜外复合全身麻醉应用硬膜外镇痛泵临床效果显著，能够减轻术后胰岛素抵抗，缓解手术疼痛，减少术后并发症，缩短住院时间，节省医疗费用，促进患者早日康复。由于本研究为小样本的随机对照试验，尚需多中心、大样本的随机对照双盲试验对该结论加以进一步研究论证。

 基金项目

青岛市民生科技计划项目(编号：18-6-1-85-nsh)。

 文章引用

王玉娟,张子英,张发展,于 洋,韩永彬,李 瑜. 不同麻醉镇痛方式对胃癌患者术后胰岛素抵抗的影响Effects of Different Anesthesia and Analgesia Methods on Insulin Resistance in Patients with Gastric Cancer after Operation[J]. 临床医学进展, 2022, 12(01): 470-476. https://doi.org/10.12677/ACM.2022.121069

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