局部枸橼酸抗凝在肝切除术后急性肾损伤连续性肾脏替代治疗中临床疗效评价

Safety and efficacy of regional citrate anticoagulation in continuous renal replacement therapy in the presence of acute kidney injury after hepatectomy

目的 评价局部枸橼酸抗凝（RCA）在肝切除术后急性肾损伤（AKI）连续性肾脏替代治疗（CRRT）中的临床效果及安全性.方法 回顾性分析2013年1月19日至2018年1月19日西安交通大学第一附属医院肝胆外科重症加强治疗病房（ICU）收治的肝切除术后发生AKI需进行床旁CRRT治疗患者的临床资料.根据不同抗凝方式将患者分为无抗凝组（NA组）、低分子肝素（LMHA）组和RCA组.观察患者围手术期一般资料,CRRT治疗前后肾功能、内环境、电解质及凝血功能等指标,CRRT治疗过程中滤器使用时间和数目以及不良事件（出血、频繁滤器凝血、代谢性碱中毒、代谢性酸中毒、低钙血症、枸橼酸蓄积等）发生情况;采用Kaplan-Meier生存曲线分析首套滤器使用寿命.结果 共纳入67例患者,其中NA组11例,LMHA组25例,RCA组31例.3组患者性别、年龄、基础疾病、病因（肿瘤）、术前肝功能Child-Pugh A或B级、CT血管成像（CTA）、血清肌酐（SCr）、血清胱抑素C（Cys C）、麻醉分级,手术方式,术中出血、输血、低血压及低血压持续时间,以及术后发生循环衰竭、肝功能不全和脓毒症等比较差异均无统计学意义,但RCA组ICU住院时间较LMHA组及NA组显著缩短（d：8.16±2.24比10.48±5.11、13.29±6.64,均P〈0.05）.与CRRT治疗前比较,RCA组及LMHA组CRRT治疗后能显著降低SCr、Cys C、乳酸（Lac）水平〔SCr（μmol/L）：89.02±21.90比248.30±55.32,105.10±49.00比270.10±156.00;Cys C（mg/L）：2.18±0.95比2.94±1.26,2.26±0.76比3.07±0.90;Lac（mmol/L）：2.21±1.46比3.62±1.73,2.37±1.24比4.03±1.69,均P〈0.05〕,而LMHA组及NA组CRRT治疗后可明显影响血红蛋白（Hb）、血小板计数（PLT）及活化部分凝血活酶时间（APTT）等指标〔Hb（g/L）：85.4±5.1比99.6±23.6,80.0±7.6比101.4±7.8;PLT（×109/L）：27.60±8.22比62.04±16.49,21.36±3.91比61.45±17.69;APTT（s）：63.07±10.25比41.52±3.65,49.56±5.77比41.09±3.45,均P〈0.05〕,同时NA组CRRT治疗后Cys C水平明显升高,凝血酶原时间（PT）明显延长〔Cys C（mg/L）：3.59±0.64比2.29±0.51,PT（s）：26.41±2.43比23.64±1.92,均P〈0.05〕.RCA组、LMHA组、NA组CRRT滤器使用时间及数目差异也有统计学意义（h：60.52±8.82、31.04±7.03、13.73±6.26,F=183.412,P〈0.001;个：2.03±0.60、3.12±0.73、4.64±1.29,F=45.933,P〈0.001）;同时RCA组出现的严重不良事件较LMHA组、NA组明显减少〔出血（例）：0比4、7,χ2=23.961,P〈0.001;频繁滤器凝血（例）：1比10、11,χ2=35.413,P〈0.001〕.Kaplan-Meier生存曲线分析显示,RCA组首套滤器使用寿命显著长于LMHA组及NA组（χ2=139.45,P〈0.05）.结论 RCA应用于肝切除术后并发AKI患者进行CRRT治疗安全有效,能够显著延长滤器寿命并减少出血风险.

 Objective To evaluate the clinical effect and safety of regional citrate anticoagulation （RCA） in continuous renal replacement therapy （CRRT） for acute kidney injury （AKI） after hepatectomy.Methods A retrospective analysis of the clinical data of all patients with AKI after hepatectomy for CRRT admitted to surgical intensive care unit （ICU） of the First Affiliated Hospital of Xi＇an Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed. According to the different anticoagulants, the patients were divided into no anticoagulant group （NA group）, low molecular heparin anticoagulation （LMHA） group and RCA group. The general data of patients during the perioperative period; renal function, the internal environment, electrolyte and blood coagulation function before and after CRRT; the filter time, the number of filters and adverse events （bleeding, frequent filter blood coagulation, metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation, etc.） during CRRT were collected. Kaplan-Meier survival curve was used to analyze the life span of the first filter during different anticoagulation. Results A total of 67 cases were included in this study, including 11 in the NA group, 25 in the LMHA group and 31 in the RCA group. There was no significant difference in gender, age, underlying disease, etiology （tumor）, Child-Pugh stage （A or B）, CT angiography （CTA）, basic renal function [serum creatinine （SCr）, cystatin C （Cys C）], the American Society of Anesthesiologists （ASA） stage; surgical approach; intraoperative bleeding volume, blood transfusion, blood pressure, time of duration of low blood pressure; and postoperative circulatory failure, hepatic insufficiency and sepsis among three groups. However, the length of ICU stay in RCA group was significantly less than the LMHA group and NA group （days： 8.16±2.24 vs. 10.48±5.11, 13.29±6.64, bothP〈 0.05）. Compared with before CRRT, the levels of SCr, Cys C and Lac were significantly decreased in RCA group and LMHA group after CRRT [SCr （μmol/L）： 89.02±21.90 vs. 248.30±55.32, 105.10±49.00 vs. 270.10±156.00; Cys C （mg/L）： 2.18±0.95 vs. 2.94±1.26, 2.26±0.76 vs. 3.07± 0.90; Lac （mmol/L）： 2.21±1.46 vs. 3.62±1.73, 2.37±1.24 vs. 4.03±1.69, allP 〈 0.05]; in addition, LMHA group and NA group had significant effects on hemoglobin （Hb）, platelet count （PLT） and activated partial thromboplastin time （APTT） after CRRT [Hb （g/L）： 85.4±5.1 vs. 99.6±23.6, 80.0±7.6 vs. 101.4±7.8; PLT （×109/L）： 27.60±8.22 vs. 62.04±16.49, 21.36±3.91 vs. 61.45±17.69; APTT （s）： 63.07±10.25 vs. 41.52±3.65, 49.56±5.77 vs. 41.09± 3.45, allP 〈 0.05]; at the same time, Cys C level and prothrombin time （PT） in the NA group after CRRT treatment were significantly increased compared with the others [Cys C （mg/L）： 3.59±0.64 vs. 2.29±0.51, PT （s）： 26.41±2.43 vs. 23.64±1.92 , bothP 〈 0.05]. Finally, the time of filters （hours： 60.52±8.82, 31.04±7.03, 13.73±6.26,F = 183.412, P 〈 0.001） and the number of filter during treatment （number： 2.03±0.60, 3.12±0.73, 4.64±1.29,F = 45.933,P 〈0.001） in the RCA group, LMHA group and NA group had statistically significant difference. Meanwhile, the incidence of adverse events such as bleeding （0 vs. 4, 7,χ2 = 23.961,P 〈 0.001） and frequent filter coagulation （1 vs. 10, 11,χ2 =35.413,P 〈 0.001） in RCA group was significantly lower than that in LMHA group and NA group. Kaplan-Meier survival analysis showed that the life time of the first filter in RCA group was significantly longer than that in LMHA group and NA group （χ2 = 139.45,P 〈 0.05）.Conclusion The application of RCA in patients with AKI after hepatectomy during CRRT is safe and effective, which can significantly prolong the life of the filter and reduce the risk of bleeding.