高危出血风险患者无抗凝连续性肾脏替代治疗中AN69 ST膜对滤器寿命影响的研究

The effect of AN69 ST membrane on filter lifetime in continuous renal replacement therapy without anticoagulation in patients with high risk of bleeding

目的：评估高危出血风险患者在无抗凝的连续性肾脏替代治疗（CRRT）中使用AN69 ST膜能否延长滤器寿命。方法采用单中心前瞻性双盲随机对照交叉研究，选择2013年3月1日至12月31日河北医科大学第四医院重症医学科收治的需行CRRT治疗，且因存在高危出血风险而不能应用抗凝的患者为研究对象。按随机数字表法分为Ⅰ组和Ⅱ组，所有患者均应用4个滤器治疗，即2个AN69 ST100膜滤器（A）和2个传统AN69 M100膜滤器（B），Ⅰ组按照A—B—A—B的顺序应用，Ⅱ组按照B—A—B—A的顺序应用。详细记录患者的临床资料，比较AN69 ST膜与传统AN69膜的滤器寿命、患者的凝血功能，以及出血并发症的发生情况。结果共入选17例存在高危出血风险需行无全身抗凝CRRT的患者，Ⅰ组10例，Ⅱ组7例。两组患者性别、年龄、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、序贯器官衰竭评分（SOFA）、急性肾损伤协作网（AKIN）分期、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、国际标准化比值（INR）、血小板计数（PLT）、使用机械通气比例差异无统计学意义，但Ⅱ组血管活性药物应用率显著高于Ⅰ组〔100.0%（7/7）比30.0%（3/10），χ^2＝8.330，P＝0.010〕。AN69 ST膜的滤器寿命为（15.92±2.10）h，传统AN69膜的滤器寿命为（16.12±1.38）h，二者比较差异无统计学意义（n＝34，t＝0.088，P＝0.942）。Kaplan-Meier生存曲线分析也未发现两种膜滤器寿命存在显著差异（χ^2＝1.589，P＝0.208）。应用logistic线性回归分析显示，基础凝血指标APTT、 PT、 INR、 PLT对第1个滤器寿命无影响〔APTT：优势比（OR）＝0.977，95%可信区间（95%CI）＝0.892～1.071，P＝0.623； PT：OR＝1.001，95%CI＝0.901～1.109，P＝0.988；INR：OR＝1.078，95%CI＝0.348～3.340，P＝0.896；PLT：OR＝0.996，95%CI＝0.974～1.019，P＝0.735〕。两组存在差异的指标血管活性药物应用率对滤器寿命亦无影响（OR＝2.541，95%CI＝0.239～26.955，P＝0.439）。进一步分析导致滤器寿命终止的主要原因为滤器凝血（占88.2%），其他原因包括导管相关性问题、患者死亡及非计划性转运。两组治疗后12 h凝血功能均无差异，且均未发生出血并发症。结论在高危出血风险患者的无抗凝CRRT中，与使用传统AN69膜比较，使用表面经聚乙烯亚胺处理过的AN69 ST膜并不能延长滤器寿命。

ObjectiveTo evaluate whether AN69 ST membrane would prolong filter lifetime in continuous renal replacement therapy （CRRT） without anticoagulation in patients with high risk of bleeding.Methods A single-center, prospective, randomized, double-blind control trial with crossover design was conducted. From March 1st to December 31st in 2013, patients who were admitted to Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University meeting CRRT treatment indications, but could not receive systemic anticoagulation because of high risk of bleeding were studied. The selected patients were randomly divided into two groups according to a random number table, and four filters consisting of two AN69 ST100 membrane filters （A） and two traditional AN69 M100 membrane filters （B） were used for them. GroupⅠ with the filter order of A-B-A-B, and groupⅡ with the order of B-A-B-A. The clinical data of patients was recorded in detail, and conventional AN69 ST and AN69 membrane filter lifetime, their influence on coagulability, and the incidence of bleeding complications were compared.Results Seventeen patients were enrolled, with 10 in groupⅠ, and 7 in groupⅡ. The basic medical characteristics including gender, age, acute physiology and chronic health evaluationⅡ （APAECHⅡ） score, sequential organ failure score （SOFA）, Acute Renal Injury Network （AKIN） stage, activated partial thromboplastin time （APTT）, prothrombin time （PT）, international normalized ratio （INR）, platelet count （PLT）, and use of mechanical ventilation were not significantly different between two groups. But the use of vasoactive drug was more frequent in groupⅡcompared with that of groupⅠ[100.0% （7/7） vs. 30.0% （3/10）,χ^2 = 8.330,P = 0.010]. AN69 ST filter lifetime （n =34） was （15.92±2.10） hours, there was no statistically significant difference compared with that of AN69 membrane （t = 0.088,P = 0.942）, filter lifetime of which （n = 34） was （16.12±1.38） hours. It was also found by Kaplan-Meier survival analysis that there was no significant difference between the two membrane filter lifetime （χ^2=1.589,P =0.208）. Logistic regression analysis showed that the life of the first filter was not correlated with coagulation indicators, including APTT, PT, INR, and PLT [APTT： odds ratio （OR） = 0.977, 95% confidence interval （95%CI） = 0.892-1.071, P = 0.623; PT：OR = 1.001, 95%CI = 0.901-1.109,P = 0.988; INR：OR = 1.078, 95%CI = 0.348-3.340,P = 0.896;PLT：OR = 0.996, 95%CI = 0.974-1.019,P = 0.735]. The application rate of vasoactive drugs, which was different between two groups for basic medical indications showed no effect on filter life time （OR = 2.541, 95%CI = 0.239-26.955,P = 0.439）. Reasons of clotting in filters were also analyzed, and it was found that blood coagulation in the filter ranked the top （88.2%）, and the other reasons were catheter-related problems, death, and unscheduled transport. No difference in blood coagulation function was found in both groups after treatment for 12 hours, and there was no bleeding complication.ConclusionDuring the CRRT without systemic anticoagulant, both surface-treatment with polyethyleneimine AN69 and AN69 ST membrane cannot prolong filter lifetime.