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中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2024, Vol. 18 ›› Issue (04) : 222 -229. doi: 10.3877/cma.j.issn.1674-3903.2024.04.004

论 著

成人肝移植围手术期严重心血管事件危险因素分析及预测模型研究
王淑贤, 张良灏, 王利君, 张慧, 郭源, 许传屾, 李志强, 蔡金贞, 解曼, 饶伟†()   
  1. 266003 青岛大学附属医院器官移植中心
    266003 青岛大学附属医院器官移植中心消化内科
    266003 青岛大学附属医院器官移植中心肝病内科
  • 收稿日期:2023-10-10 出版日期:2024-08-08
  • 通信作者: 饶伟
  • 基金资助:
    山东省自然科学基金面上项目(ZR2023MH240)北京肝胆相照公益基金会“2023 年度人工肝专项基金”(iGandanF-1082023-RGG037)山东省人文社会科学项目(2021-SKZC-18)

The establishment of predictive model and influencing factors of major adverse cardiovascular events during perioperative period of adult liver transplantation

Shuxian Wang, Lianghao Zhang, Lijun Wang, Hui Zhang, Yuan Guo, Chuanshen Xu, Zhiqiang Li, Jinzhen Cai, Man Xie, We Rao†()   

  1. Organ Transplantation Center, Department of Hepatology, Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao 266003,China
  • Received:2023-10-10 Published:2024-08-08
  • Corresponding author: We Rao
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引用本文：

王淑贤, 张良灏, 王利君, 张慧, 郭源, 许传屾, 李志强, 蔡金贞, 解曼, 饶伟. 成人肝移植围手术期严重心血管事件危险因素分析及预测模型研究[J]. 中华移植杂志(电子版), 2024, 18(04): 222-229.

Shuxian Wang, Lianghao Zhang, Lijun Wang, Hui Zhang, Yuan Guo, Chuanshen Xu, Zhiqiang Li, Jinzhen Cai, Man Xie, We Rao. The establishment of predictive model and influencing factors of major adverse cardiovascular events during perioperative period of adult liver transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2024, 18(04): 222-229.

目的

探讨成人肝移植围手术期发生严重心血管事件(MACE)的影响因素,并创建列线图风险预测模型。

方法

回顾性分析2016 年1 月至2020 年12 月在青岛大学附属医院器官移植中心接受肝移植的545 例成人肝移植受者临床资料,根据围手术期是否发生MACE 分为MACE 组(57 例)和未发生MACE 组(488 例),比较两组受者围手术期相关资料。 采用Kaplan-Meier 法绘制生存曲线,应用log-rank 检验比较。 根据logistics 回归分析显示的独立危险因素,构建列线图,采用受试者工作特征(ROC)曲线判断列线图的预测价值。

结果

与未发生MACE 组受者相比,MACE 组受者年龄较大,术前终末期肝病模型(MELD)评分较高,既往有高血压、心脏病和肝性脑病史的受者比例更高,术中出血量及输注红细胞量更多,且术中无肝期时间、术后ICU 住院时间及机械通气时间更长,差异均有统计学意义(t=-2.544 和-2.924, χ2=9.815、6.506 和7.808,Z=-2.140,-2.464,-2.506,-4.847 和-4.243,P 均＜0.05)。 在门静脉和下腔静脉全部阻断后5 min 内、全部开放后5 min 内以及手术结束出手术室前,MACE 组受者乳酸水平均较未发生MACE 组升高,差异均有统计学意义(t=-2.291、-3.322 和-2.392,P 均＜0.05)。logistic 回归分析结果显示,年龄(OR=1.041,95%CI: 1.008～1.350,P＜0.05)、术前MELD 评分(OR=1.057,95%CI: 1.022～1.453,P＜0.05)和高血压病史(OR=2.149,95%CI: 1.061～4.804,P＜0.05)以及门静脉和下腔静脉全部开放后5 min 内乳酸水平(OR=1.334,95%CI 1.088 ～1.636,P＜0.05)是肝移植围手术期发生MACE 的独立危险因素。 根据多因素回归分析结果构建的列线图预测成人肝移植受者围手术期发生MACE 的ROC 曲线下面积为0.736,一致性指数为0.8,内部验证显示预测发生率与实际发生率拟合度较好。 MACE 组受者术后1 年总体生存率低于未发生MACE 组(84.2%和96.1%,P＜0.05)。

结论

年龄、术前MELD 评分、高血压病史、门静脉和下腔静脉全部开放后5 min 内乳酸水平是成人肝移植围手术期发生MACE 的独立危险因素,据此构建的列线图风险模型在预测成人肝移植围手术期MACE 发生方面具有较好的临床价值。

关键词: 肝移植, 心血管事件, 围手术期, 终末期肝病模型, 高乳酸血症, 列线图

Objective

To investigate the influencing factors and prognosis analysis of major adverse cardiovascular events (MACE) during perioperative period of adult liver transplantation, and to create a nomogram predict risk model.

Methods

The clinical data of 545 adult recipients who underwent liver transplantation in the Affiliated Hospital of Qingdao University from January 2016 to December 2020 were retrospectively analyzed. According to the occurrence of MACE during the perioperative period, the patients were divided into MACE group (57 cases) and non-MACE group(488 cases). The perioperative data of the two groups were compared. Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. According to the independent risk factors shown by logistics regression analysis, nomograms were constructed, and receiver operating characteristic (ROC) curves were used to determine the predictive value of nomograms.

Results

Compared with the non-MACE group, recipients in MACE group were older, had higher preoperative model for end-stage liver disease (MELD) scores, had a higher proportion of recipients with previous history of hypertension, heart disease and hepatic encephalopathy, more intraoperative blood loss and red blood cell transfusion, and had longer intraoperative anhepatic phase time, postoperative ICU length of stay and mechanical ventilation time, and the differences were statistically significant (t= -2. 544 and-2.924, χ2 = 9. 815, 6. 506 and 7. 808, Z=-2. 140,-2. 464,-2. 506,-4. 847 and -4. 243,P＜0.05). Within 5 min after total occlusion of the portal vein and inferior vena cava, within 5 min after total opening, and before exit from the operating room at the end of surgery, lactate levels of the MACE group were increased compared with the non-MACE group, and the differences were statistically significant (t=-2.291, -3.322 and -2.392, all P＜0.05). Logistic regression analysis showed that age (OR=1.041, 95%CI 1.008-1.350, P＜0.05), preoperative MELD score (OR=1.057, 95%CI 1.022-1.453, P＜0.05) and history of hypertension (OR=2.149, 95%CI 1.061-4.804, P＜0.05)as well as lactate level within 5 min after total opening of the portal vein and inferior vena cava (OR=1.334, 95%CI 1.088-1.636, P＜0.05) were independent risk factors for MACE during perioperative period of adult liver transplantation. The nomogram constructed according to the results of multivariate regression analysis predicted the perioperative occurrence of MACE in adult liver transplant recipients with an area under curve of 0.736 and a concordance index of 0.8, and internal validation showed a good fit between the predicted incidence and the actual incidence. The overall survival rate at 1 year after surgery was lower in the MACE group than in the non-MACE group (84.2% and 96.1%, P＜0.05).

Conclusions

Age, preoperative MELD score, history of hypertension and lactate level within 5 min after total opening of the portal vein and inferior vena cava were independent risk factors for perioperative MACE in adult liver transplantation. The risk prediction model has a good clinical value in predicting the occurrence of perioperative MACE in adult liver transplantation.

Key words: Liver transplantation, Cardiovascular events, Perioperative period, Model for end-stage liver disease, Hyperlactic acidemia, Nomogram
图1 成人肝移植受者入选标准流程图 注: MACE.严重心血管事件
表1 肝移植围手术期未发生MACE 组和MACE 组受者基线资料比较
组别 例数 性别(例,男/女) 年龄(岁,x¯±s) 术前BMI(kg/m2,x¯±s) 术前MELD评分(分,x¯±s) 术前Child Pugh评分[分,M(P25,P75)] 术前左心室射血分数(%,x¯±s) 术前白蛋白[g/L,M(P25,P75)] 术前凝血酶原时间(s,x¯±s)
未发生MACE组 488 408/80 52±9 24.2±3.6 11.4±8.3 12(9,13) 63.7±2.9 33.0(29.0,33.0) 16.2±7.0
MACE组 57 44/13 55±10 24.0±3.8 15.3±9.6 8(6,10) 63.2±2.1 32.0(28.5,37.9) 17.2±5.9
t/χ2/Z值 - 1.483 -2.544 0.471 -2.924 -3.771 1.494 -0.788 1.096
P值 - ＞0.05 ＜0.05 ＞0.05 ＜0.05 ＞0.05 ＞0.05 ＞0.05 ＞0.05
组别 例数 既往史(例,有/无) 供肝重量(g,x¯±s) 手术时间(min,x¯±s) 无肝期时间[min,M(P25,P75)] 供肝冷缺血时间[min,M(P25,P75)]
高血压 糖尿病 心脏病 肝性脑病 上消化道出血
未发生MACE组 488 46/442 65/423 4/484 56/432 133/355 1 379±300 505±114 55(47,64) 319(270,391)
MACE组 57 13/44 7/50 3/54 14/43 14/43 1 442±367 506±108 61(50,72) 346(280,460)
t/χ2/Z值 - 9.815 0.048 6.506 7.808 0.188 -1.246 -0.033 -2.140 -2.048
P值 - ＜0.05 ＞0.05 ＜0.05 ＜0.05 ＞0.05 ＞0.05 ＞0.05 ＜0.05 ＞0.05
组别 例数 术中相关指标[M(P25,P75)] 术后ICU住院时间[h,M(P25,P75)] 术后机械通气时间[h,M(P25,P75)]
输注红细胞(U) 液体总入量(mL) 出血量(mL) 尿量(mL)
未发生MACE组 488 8.0(4.0,12.0) 6 172(5 307,7 492) 1 000(600,2 000) 2 190(1 532,3 008) 91(69,119) 19(15,41)
MACE组 57 10.0(6.0,14.5) 6 285(5 155,7 796) 1 500(800,2 000) 2 000(1 692,3 000) 141(87,190) 39(18,107)
t/χ2/Z值 - -2.464 -0.405 -2.506 -0.083 -4.847 -4.243
P值 - ＜0.05 ＞0.05 ＜0.05 ＞0.05 ＜0.05 ＜0.05
表2 肝移植围手术期未发生MACE 组和MACE 组受者术中不同阶段血气分析结果(±s)
组别 例数 入手术室后动脉穿刺成功后即刻
pH值 钠离子浓度(mmol/L) 钾离子浓度(mmol/L) 乳酸(mmol/L)
未发生MACE组 488 7.43±0.05 140.8±4.8 3.56±0.41 1.50±1.18
MACE组 57 7.42±0.05 140.1±5.6 3.54±0.49 1.68±1.14
t值 - 0.526 0.968 0.31 -1.065
P值 - ＞0.05 ＞0.05 ＞0.05 ＞0.05
组别 例数 门静脉和下腔静脉全部阻断后5min内
pH值 钠离子浓度(mmol/L) 钾离子浓度(mmol/L) 乳酸(mmol/L)
未发生MACE组 488 7.39±0.05 145.5±5.3 3.98±0.43 2.97±1.74
MACE组 57 7.39±0.05 143.1±4.5 4.13±0.49 3.53±2.00
t值 - 0.949 1.438 -2.464 -2.291
P值 - ＞0.05 ＞0.05 ＜0.05 ＜0.05
组别 例数 门静脉和下腔静脉全部开放后5min内
pH值 钠离子浓度(mmol/L) 钾离子浓度(mmol/L) 乳酸(mmol/L)
未发生MACE组 488 7.35±0.06 145.5±4.9 3.85±0.81 4.92±2.18
MACE组 57 7.34±0.09 145.8±5.5 3.83±0.91 6.60±3.74
t值 - 0.634 -0.462 0.141 -3.322
P值 - ＞0.05 ＞0.05 ＞0.05 ＜0.05
组别 例数 出手术室前
pH值 钠离子浓度(mmol/L) 钾离子浓度(mmol/L) 乳酸(mmol/L)
未发生MACE组 488 7.39±0.06 146.0±4.6 3.71±0.40 4.57±2.82
MACE组 57 7.38±0.06 146.6±6.0 3.77±0.48 6.00±4.40
t值 - 0.753 -0.732 -1.047 -2.392
P值 - ＞0.05 ＞0.05 ＞0.05 ＜0.05
表3 成人肝移植受者围手术期发生MACE 影响因素的logistic 回归分析
参数 β值 标准误 Waldχ2值 P值 OR值 95%CI
年龄(岁) 0.042 0.016 6.649 ＜0.05 1.041 1.008～1.350
术前MELD评分(分) 0.049 0.016 9.621 ＜0.05 1.057 1.022～1.453
高血压病史 1.039 0.386 7.249 ＜0.05 2.149 1.061～4.804
门静脉和下腔静脉全部开放后5min内乳酸水平(mmol/L) 0.212 0.051 17.082 ＜0.05 1.334 1.088～1.636
图2 成人肝移植受者围手术期发生MACE 的列线图风险预测模型 注: MACE. 严重心血管事件; MELD. 终末期肝病模型
图3 成人肝移植围手术期发生MACE 列线图风险预测模型的受试者工作特征曲线 注: MACE. 严重心血管事件; AUC.曲线下面积
发生风险的内部验证
图5 肝移植围手术期未发生MACE 组和MACE 组受者术后1 年生存曲线 注: MACE. 严重心血管事件
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