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张裕霞  张秀生  杜洪印  王亮  翁亦齐  李津源

作者单位：300192 天津市第一中心医院麻醉科

Changes of coagulation function in patients undergoing orthotopic liver transplantation

[abstract] objective To investigate Changes of coagulation status in one hundred patients undergoing orthotopic liver transplantation(OLT). Methods one hundred ASA III-IV patients, both males and females, affected by terminal hepatic cirrhosis submitted to OLT were enrolled in the study. Blood samples were collected immediately before operation, at 60 min after skin incision during the pre-anhepatic phase of OLT,  15 min and 30 min after clamping of portal vein, 15min and 60 min after reperfusion, 24h,48h and 72h after operation. Laboratory tests were performed for the determination of prothrombin time(PT), international normalized ratio(INR), activated partial thromboplastic time(APTT), thrombin time(TT), fibrinogen(Fg), d-dimer(DD), hemoglobin(HB), platelet and the concentration of serum calcium. Sonoclot analysis was measured before operation, at 60 min after skin incision during the pre-anhepatic stage,  30 min after clamping of portal vein, 15min and 60 min after reperfusion. Results TT and DD were prolonged during the anhepatic stage(p<0.05 or 0.01), and the values peaked after portal vein unclamping(P<0.01). The value of APTT significantly increased during the pre-anhepatic stage(P<0.01). the values of  PT and INR reached a peak at 60 min after reperfusion. The platelet count was reduced during the neohepatic phase (p<0.01). The value of HB decreased  during the whole operation(p<0.01). Levels of serum calcium and Fg significantly decreased during the anhepatic and neohepatic stages(p<0.05 or 0.01). Compared with the values before operation, except for the values of TT and HB, all the other values were recovered at 72h after operation. Conclusion Great changes of coagulation status take place during liver transplantation, and Severe coagulopathies can occur during the anhepatic and neohepatic stages.

[Key words] Orthotopic liver transplantation； coagulation function 

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肝移植术是治疗终末期肝病最有效的措施，如何纠正肝移植术病人的凝血功能是肝移植围术期最棘手的问题之一，调整凝血功能是提高肝移植术成功率的重要保证^[1,2]。本研究拟观察100例肝移植术病人围术期凝血功能的变化，从中探寻其变化规律。

资料与方法

病例选择  拟行肝移植术的终末期肝硬化病人100例，男92例，女8例，年龄25～67岁，体重45～<?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" />58 kg。其中肝炎后肝硬化91例，慢性重症肝炎9例。经典原位肝移植术15例，经典非转流原位肝移植术65例，背驮式原位肝移植术20例。

麻醉方法 所有病人麻醉前30min肌肉注射东莨宕碱0.3mg。入室后开放外周静脉，同时经桡动脉穿刺置管。采用气管内插管静吸复合麻醉。静脉注射咪唑安定0.1mg•kg-1、芬太尼2～5ug•kg-1、异丙酚1～2mg•kg-1及维库溴铵0.1mg•kg-1行麻醉诱导。麻醉维持：静脉持续泵入异丙酚2～4mg•kg-1•h-1，间断吸入1.0％～2.0％异氟醚。经右侧颈内静脉穿刺放置Swan-Ganz导管（公司，Baxter公司，美国）和三腔中心静脉导管。术中监测心电图、有创血压、肺动脉压、中心静脉压、脉搏血氧饱和度、心输出量、呼气末CO2分压、尿量、鼻温及血温。分别于术前（基础值）、无肝期前60min、无肝期15、30min、新肝期15、60min、术后24、48、72h从桡动脉采血，测定血小板计数、DIC凝血四项、D-二聚体和血清钙离子浓度（法国Stago公司STA-Compact全自动血凝仪），并于术前、无肝前期、无肝期30min、新肝期15、60min应用Sonoclot凝血与DP-2951型血小板功能分析仪（美国GNS公司）对凝血及血小板功能进行定性分析。

术中特殊用药：抑肽酶：手术开始先给首剂100～150万U，以后50万U•h-1持续静脉滴注直至无肝期结束；6-氨基乙酸：术前存在纤溶亢进时缓慢静脉注射2～6g；鱼精蛋白：进入新肝期，根据Sonoclot监测结果，慢静脉注射35～50mg。

统计学处理  应用SPSS11.0统计软件进行统计分析，计量资料以均数±标准差（±s）表示，组内比较采用单因素方差分析,P<0.05为差异有统计学意义。

结  果

手术时间（8.1±1.5）h，无肝期（55±14）min，术中出血量（3 246±643）ml。输注新鲜冰冻血浆（1 328±282）ml、浓缩红细胞（876±198）ml、全血（342±92）ml、纤维蛋白原（3.4±1.7）g、凝血酶原复合物（405±87）U、血小板（4.0±0.6）U，6-氨基乙酸用量为（1.3±0.5）g，抑肽酶用量为（462±38）万U、鱼精蛋白用量为（45±5）mg。

与基础值比较，TT在无肝期30min～术后72h升高，PT在新肝期15min～术后24h升高，APTT在无肝前期～术后72h升高，INR在新肝期15min～60 min升高，DD在无肝期15min～术后24h升高，Fg在无肝期15min～术后48h降低，血清钙离子在无肝期15min～新肝期60min降低，体温（T）随手术进行逐渐下降，进入无肝期后明显，新肝期后逐渐回升，见表1。从Sonoclot曲线变化趋势来看，凝血及血小板功能无肝前期和无肝期逐渐下降，刚进入新肝期最严重，Sonoclot曲线几乎呈-水平线，而后逐渐抬高，见图1。