远隔缺血预处理联合控制性低中心静脉压在肝切除术中的应用

高苑淞; 杨柳; 吴悠; 张娜; 田春

doi:10.3969/j.issn.1001-5256.2023.04.017

远隔缺血预处理联合控制性低中心静脉压在肝切除术中的应用

DOI: 10.3969/j.issn.1001-5256.2023.04.017

重庆医科大学附属永川医院麻醉科，重庆 402160

基金项目:

重庆市科卫联合医学科研项目 (2020FYYX033);

重庆市永川区自然科学基金 (Ycstc);

重庆市永川区自然科学基金 (2020nb0229)

伦理学声明：本研究方案于2020年7月6日经由重庆医科大学附属永川医院伦理委员会审批，批号：2020.89。患者及其家属均知情同意并签字。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：高苑淞负责收集数据，资料分析，撰写论文；吴悠参与收集数据；杨柳、张娜负责数据统计和资料分析；田春负责课题设计，拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
田春，Tianchun314@163.com (ORCID：0000-0001-9107-167X)

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出版历程
- 收稿日期: 2022-08-26
- 录用日期: 2022-09-26
- 出版日期: 2023-04-20

Application of remote ischemic preconditioning combined with controlled low central venous pressure in hepatectomy

Department of Anesthesiology, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing 402160, China

Research funding:

Chongqing Municipal Science and Health Joint Medical Research Project of China (2020FYYX033);

The Science Foundation of Yongchuan, Chongqing (Ycstc);

The Science Foundation of Yongchuan, Chongqing (2020nb0229)

More Information

Corresponding author: TIAN Chun, Tianchun314@163.com (ORCID: 0000-0001-9107-167X)

摘要

摘要: 目的评价远隔缺血预处理(RIPC) 联合控制性低中心静脉压(CLCVP)在肝切除术中的应用效果。方法选取2021年5月—2022年4月择期在重庆医科大学附属永川医院行部分肝切除术患者80例，采用随机数表法分成对照组(C组)、CLCVP组(L组)、RIPC组(R组)、RIPC联合CLCVP组(RL组)，每组20例。L组接受CLCVP干预，R组接受RIPC干预，RL组同时接受CLCVP和RIPC干预。比较患者术前第1天(D0)、术后第1天(D1)、术后第3天(D3)、术后第5天(D5)、术后第7天(D7) TNFα、ALT、AST、TBil和患者围术期一般情况。正态分布的计量资料组间比较采用单因素方差分析或重复测量方差分析，偏态分布的计量资料组间比较采用Kruskal-Wallis H检验；计数资料组间比较采用χ²检验。结果 RL组患者手术持续时间(H=14.278, P=0.015)、总输液量(H=24.175, P=0.001)、出血估计量(H=45.625, P＜0.001)均低于R组。分组和时间因素对四组患者TNFα、ALT、AST均具有显著交互作用(P值分别为＜0.001、0.010、0.012)。RL组患者D1的TNFα均低于L组(P值均＜0.001)。RL组患者D1(P=0.008)、D7(P＜0.001)ALT水平均低于L组。结论 RIPC联合CLCVP技术能够有效减少肝切除术患者术中出血量，提供清晰手术视野和缩短手术时间；同时还能通过降低患者TNFα，抑制机体炎症反应，但不能有效减轻CLCVP技术下肝切除术后的肝缺血-再灌注损伤。
- 缺血预处理 /
- 中心静脉压 /
- 再灌注损伤 /
- 肝切除术
Abstract: Objective To investigate the application effect of remote ischemic preconditioning (RIPC) combined with controlled low central venous pressure (CLCVP) in hepatectomy. Methods A total of 80 patients who underwent elective partial hepatectomy in Yougchuan Hospital Affiliated to Chongqing Medical University from May 2021 to April 2022 were enrolled and divided into control group (group C), CLCVP group (group L), RIPC group (group R), and RIPC+CLCVP group (group RL) using a random number table, with 20 patients in each group. The patients in group L received CLCVP, those in group R received RIPC, and those in group RL received both CLCVP and RIPC. The patients were compared in terms of perioperative general status and the levels of tumor necrosis factor-α (TNFα), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin on preoperative day 1(D0), postoperative day 1(D1), postoperative day 3(D3), postoperative day 5(D5), and postoperative day 7(D7). A one-way analysis of variance or a repeated measures analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups; the chi-square test was used for comparison of categorical data. Results Compared with group R, group RL had a significantly shorter time of operation (H=14.278, P=0.015), a significantly lower total infusion volume (H=24.175, P=0.001), and a significantly lower estimated blood loss (H=45.625, P < 0.001). Group and time factors had significant interaction effects on TNFα, ALT, and AST in the four groups (P < 0.001; P=0.010; P=0.012). Group RL had a significantly lower level of TNFα than group L on D1(P < 0.001) and D3(P < 0.001). Group RL had a significantly lower level of ALT than group L on D1(P=0.008) and D7(P < 0.001). Conclusion For patients undergoing hepatectomy, RIPC combined with CLCVP can effectively reduce intraoperative blood loss, provide a clear surgical field, and shorten the time of operation; meanwhile, it can also inhibit inflammatory response by reducing TNFα, but it cannot effectively alleviate hepatic ischemia-reperfusion injury after hepatectomy under the context of CLCVP.
- Ischemic Preconditioning /
- Central Venous Pressure /
- Reperfusion Injury /
- Hepatectomy

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图 1 患者肝功能指标

注：与C组比较，*P＜0.01；与R组比较，#P＜0.01；与L组比较，∧P＜0.01；与RL组比较，+P＜0.01。

Figure 1. Liver function variables of patients

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表 1 患者基线资料

Table 1. Baseline characteristics of patients

项目	C组(n=20)	L组(n=20)	R组(n=20)	RL组(n=20)	统计值	P值
男/女(例)	12/8	15/5	11/9	13/7	χ²=1.893	0.595
年龄(岁)	61.0(52.0~61.0)	53.5(48.0~62.0)	55.0(53.0~58.8)	55.5(52.0~58.0)	H=1.324	0.732
BMI(kg/m²)	23.1±2.1	23.6±2.5	23.7±3.2	23.9±3.7	F=0.284	0.837
ASA分级(Ⅰ/Ⅱ，例)	4/16	6/14	4/16	5/15	χ²=0.829	0.938
既往合并症[例(%)]
高血压	7(35.0)	4(20.0)	6(30.0)	6(30.0)	χ²=1.159	0.763
糖尿病	2(10.0)	4(20.0)	3(15.0)	2(10.0)	χ²=1.205	0.893
COPD	1(5.0)	0	2(10.0)	1(5.0)	χ²=2.097	0.899
肝硬化	14(70.0)	15(75.0)	17(85.0)	13(65.0)	χ²=2.260	0.520
D0生化检查
红细胞(×10¹²/L)	4.4±0.6	4.2±0.3	4.3±0.5	4.4±0.5	F=0.356	0.785
白细胞(×10⁹/L)	6.8±2.5	6.7±2.4	6.4±2.3	6.0±1.4	F=0.617	0.606
中心粒细胞百分比(%)	65.7±10.2	68.4±10.4	66.8±11.6	65.7±10.8	F=0.272	0.845
TNFα(pg/mL)	85.2±10.7	81.2±10.3	80.0±10.9	83.7±11.1	F=0.970	0.412
ALT(U/L)	27.0(18.0~47.0)	29.0(15.3~40.0)	29.0(13.0~39.0)	28.0(13.0~37.5)	H=1.407	0.704
AST(U/L)	27.0(19.0~31.0)	34.0(20.8~58.8)	27.0(17.5~34.0)	33.5(20.0~41.0)	H=3.227	0.358
TBil(μmol/L)	8.7(5.1~11.5)	11.5(6.9~13.0)	9.3(5.8~10.5)	8.7(6.2~17.7)	H=4.264	0.234
白蛋白(g/L)	37.5±5.5	38.6±5.6	40.3±4.1	40.1±3.8	F=1.528	0.214
PT(s)	11.8±1.8	12.3±1.9	11.5±1.1	11.9±1.8	F=0.693	0.559
Cr(μmol/L)	56.0(54.0~63.5)	66.5(45.0~71.0)	65.0(49.0~69.0)	60.0(51.0~63.0)	H=2.274	0.436
BUN(mmol/L)	5.1±1.8	5.3±1.6	5.5±1.0	5.1±2.0	F=0.390	0.761

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表 2 患者麻醉手术一般情况

Table 2. Anesthesia and surgery data of patients

项目	C组(n=20)	L组(n=20)	R组(n=20)	RL组(n=20)	统计值	P值
手术持续时间(min)	260.0(210.0~415.0)	220.0(190.0~300.0)¹⁾²⁾	285.0(195.0~483.8)	200.0(135.0~295.0)¹⁾²⁾	H=9.053	0.029
肝脏血供阻断时间(min)	62.0(47.0~109.3)	72.0(63.0~97.0)	74.0(49.0~95.0)	67.0(46.8~96.0)	H=0.462	0.927
肝脏切除范围[例(%)]					χ²=3.211	0.810
肝叶切除	3(15.0)	4(20.0)	5(25.0)	2(10.0)
肝段切除	12(60.0)	14(70.0)	12(60.0)	14(70.0)
不规则肝切除	5(25.0)	2(10.0)	3(15.0)	4(20.0)
术后住院时间(d)	10.4±2.1	11.8±2.2	10.3±1.9	11.4±2.1	F=2.421	0.072
总输液量(L)^a	2.8(2.1~3.5)	2.3(2.0~2.5)¹⁾²⁾	3.0(2.5~3.4)	2.0(2.0~2.5)¹⁾²⁾	H=20.192	＜0.001
碳酸氢钠输入量(mL)^b	90.0(12.5~145.0)	100.0(90.0~195.0)²⁾	60.0(0~80.0)	90.0(0~100.0)	H=9.952	0.019
术中尿量(mL)	467.5±202.8	465.5±257.9	470.0±120.7	455.5±239.2	F=0.019	0.997
出血估计量(mL)	253.0±48.8	159.0±59.0¹⁾²⁾	285.5±37.5	138.5±31.5¹⁾²⁾	F=68.719	＜0.001
输血[例(%)]	3(15.0)	0	3(15.0)	1(5.0)	χ²=4.080	0.296
升压药[例(%)]^c	3(15.0)	6(30.0)	2(10.0)	4(20.0)	χ²=2.720	0.491
呋塞米[例(%)]	1(5.0)	5(25.0)	2(10.0)	4(20.0)	χ²=3.769	0.335
苏醒延迟[例(%)]^d	11(55.0)	9(45.0)	3(15.0) ¹⁾³⁾	5(25.0)	χ²=8.671	0.035
术后并发症情况[例(%)]	2(10.0)	5(25.0)	1(5.0)	3(15.0)	χ²=3.381	0.377
新发肺部感染	1(5.0)	2(10.0)	0	2(10.0)
术后切口愈合不良[例(%)]	0	1(5.0)	0	0
术后认知功能障碍	0	1(5.0)	0	0
胸腔积液	0	1(5.0)	1(5.0)	0
麻痹性肠梗阻	1(5.0)	0	0	1(5.0)
注：a, 输液策略为晶胶比1∶1；b, 术中应用5%碳酸氢钠严格控制代谢性酸中毒，使动脉血气分析碱剩余维持在-3~3 mmol/L；c, 术中需使用去甲肾上腺素、麻黄碱、多巴胺等药物维持血压；d, 苏醒延迟即从全身麻醉停药到可被唤醒睁眼或自主睁眼超过90 min。与C组比较，1)P＜0.05；与R组比较，2)P＜0.05；与L组比较，3)P＜0.05。

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