肝衰竭患者人工肝支持治疗应用局部枸橼酸抗凝的有效性和安全性Meta分析

许彪; 黄惠斌; 吉程程; 牟劲松; 王永刚; 李雷; 周越塑

doi:10.3969/j.issn.2095-5227.2022.02.010

肝衰竭患者人工肝支持治疗应用局部枸橼酸抗凝的有效性和安全性Meta分析

Efficacy and safety of regional citrate anticoagulation for artificial liver support in patients with liver failure: A meta-analysis

摘要

摘要:
背景肝衰竭患者进行人工肝支持治疗时应用局部枸橼酸抗凝方案至今仍存在争议。
目的系统评价肝功能衰竭患者人工肝支持治疗时应用局部枸橼酸抗凝的有效性和安全性。
方法计算机检索PubMed、Embase、Cochrane Library、万方数据库、中国知网、中国生物医学文献数据库自建库至2020年2月发表的有关肝衰竭患者应用局部枸橼酸抗凝的临床研究，由2名研究者按照纳入与排除标准独立筛选文献、提取资料并评价质量后，应用Medcalc15.6.1对单组率数据和治疗前后连续变量数据进行Meta分析，应用Stata/SE 15.1对单组连续变量进行Meta分析。
结果共8篇文献满足纳入标准，其中2篇中文文献，6篇英文文献。研究质量评估，高质量研究7项，中等质量研究1项。共211例患者，659例次人工肝支持治疗纳入分析。有效性方面，局部枸橼酸抗凝的人工肝治疗完成率为94.2%(95% CI：90.7% ~ 96.9%，I²=50.2%)，因滤器或管路血栓栓塞中断人工肝治疗的发生率为4.7%(95% CI：2.7% ~ 7.2%，I²=25.7%)，人工肝治疗前后总胆红素下降率为41.2%(95% CI：31.9% ~ 50.5%，I²=97.8%)。安全性方面，应用局部枸橼酸抗凝的人工肝治疗出血发生率为1.25%(95% CI：0.47% ~ 2.66%，I²=23.57%)，枸橼酸蓄积的发生率为25.7%(95% CI：7.5% ~ 50.0%，I²=94.5%)，人工肝治疗结束后Ca_ion较治疗前下降，治疗后2 h即恢复到治疗前水平。人工肝治疗前后pH无明显变化。肝衰竭患者经过局部枸橼酸抗凝的人工肝治疗，病情恢复或进行肝移植最终存活率为51.3%(95% CI：41.7% ～ 60.8%，I²=0)。
结论肝功能衰竭患者应用人工肝支持治疗时采用局部枸橼酸抗凝，对循环管路和滤器安全有效，但仍存在枸橼酸蓄积的风险。

Abstract:
Background The application of regional citrate anticoagulation in artificial liver support therapy for patients with liver failure is still controversial.
Objective To systematically evaluate the efficacy and safety of regional citrate anticoagulation (RCA) for artificial liver support in patients with liver failure.
Methods Studies about RCA for artificial liver support in patients with liver failure were retrieved in PubMed, Embase, the Cochrane Library, CNKI, Wanfang data and SinoMed from their foundation to February 2020. The literature screening and data extraction were performed by two researchers independently. Meta-analysis was performed by Medcalc15.6.1 for non-comparative binary data and continuous variable data before and after treatment, and by Stata/SE 15.1 for a single set of continuous variables.
Results A total of 8 articles that met the inclusion criteria were included, including 2 in Chinese and 6 in English. Research quality assessment showed that there were 7 high quality studies and 1 moderate quality study. Six hundred and fifty-nine artificial liver support sessions performed in 211 patients were enrolled in analysis. In terms of efficacy, the completion rate of artificial liver treatment with RCA was 94.2% (95% CI: 90.7% - 96.9%, I² = 50.2%), the incidence of interruption of artificial liver support due to occlusive clotting of the extracorporeal circuit was 4.7% (95% CI: 2.7% - 7.2%, I² = 25.7%), the decrease rate of serum total bilirubin before and after artificial liver treatment was 41.2% (95% CI: 31.9% - 50.5%, I² = 97.8%). In terms of safety, the incidence of hemorrhage during the artificial liver support with RCA was 1.25% (95% CI: 0.47% - 2.66%, I² = 23.57%), and the incidence of citrate accumulation was 25.7% (95% CI: 7.5% - 50.0%, I² = 94.5%). After the end of artificial liver support, systemic ionized calcium concentrations decreased compared with that before treatment, and returned to the pre-treatment level in 2 hours. There was no significant change in pH before and after artificial liver support. The liver failure patients who underwent artificial liver therapy with RCA obtained a survival rate of 51.3% (95% CI: 41.7% - 60.8%, I² = 0).
Conclusion It is safe and effective of RCA for artificial liver support in the patients with liver failure, but there is still a risk of citrate accumulation that require more attention by the clinicians.

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