非静脉转流原位肝移植围术期肾功能变化

目的 探讨非静脉转流原位肝移植围术期肾功能变化.方法 根据无肝期是否使用体外静脉-静脉转流（venovenous bypass,VVB）,分为非转流组（n=26）和转流组（n=29）.测定围术期血清肌酐（serum creatinine,Cr）和血清尿素氮（blood urea nitrogen,BUN）.又根据术后有无肾功能不全将病人分为有肾功能损害组（A组）和无肾功能损害组（B组）.结果 非转流组与转流组术后血清Cr和BUN均明显高于术前（P〈0.05）;两组之间无明显差异（P〉0.05）.有肾功能损害组术前血清BUN、血清总胆红素、术前肝功能Child C级人数、术前血清血Cr或血BUN增高人数明显高于无肾功能损害组（P〈0.05）,术中出血及输血量明显高于无肾功能损害组（P〈0.05）.结论 非静脉转流原位肝移植与VVB原位肝移植,术后均易出现肾功能损害.术前肝功能严重障碍、肾功能不全及术中大量出血是造成术后急性肾功衰的主要原因.     

Population pharmacokinetics of remifentanil in patients undergoing orthotopic liver transplantation

Backgroud Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation （OLT） and the influence of relevant factors.
Methods Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 IJg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 （baseline）, 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry （HPLC/MS/MS）. Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling （NONMEM）.
Results The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment （V1） and the volume of distribution in the peripheral compartment （V2） were influenced by body weight.
Conclusions The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V1 and V2.     

犬同种异体肝原位移植术中血流动力学变化

10例犬进行异体肝原位移植，观察阻断肝循环后及行体外静脉－静脉转流15min、40min时和新肝植入复流15min、40min时血流动力学变化。结果：在阻断血管和新肝植入复流时心率、动脉压及中心静脉压均呈急剧下降趋势，分别较基础值下降60％～30％。体外静脉－静脉转流可减轻阻断血管后的血流动力学变化。提示：在行犬异体肝原位移植时应行体外静脉－静脉转流，在阻断血管前和新肝植入复流前均应超量输血、输液。     

前列地尔对原位肝移植患者血流动力学的影响研究

目的 观察原位肝移植手术新肝期静脉泵注前列地尔(PGE1)对血流动力学的影响,为临床合理用药提供参考.方法 选取2011～2015年在该院移植中心接受原位肝移植的患者30例,采用计算机随机数字表法将其分为对照组、E1组和E2组,各10例;在原位肝移植手术新肝期,E1组与E2组患者分别以5、10 ng/(kg·min)静脉泵注PGE1,对照组泵注等量生理盐水,其余处理相同;在新肝期30 min分别纪录心率(HR)、平均动脉压(MAP)、肺动脉压(PAP)、心排血量(CO)、外周血管阻力(SVR).结果 3组患者年龄、体质量、手术时间、无肝期时间、失血量及输注量比较,差异均无统计学意义(P＞0.05).在门静脉、肝上下腔静脉开放后30 min,与对照组比较,E1组及E2组HR、CO均增加,MAP下降,但差异均无统计学意义(P＞0.05);E1组及E2组SVR和PAP均下降,且随PGE1使用剂量增加而下降,E1组及E2组患者PAP与对照组比较,差异均有统计学意义(P＜o.05),仅E2组SVR与对照组比较,差异有统计学意义(P＜0.05).结论 在处理肝移植新肝期PAP增高和CO降低时,静脉泵注PGE1可作为有效的处理办法.     

猪原位肝移植围术期血流动力学及生化代谢变化的研究

目的：在体外静脉－静脉转流下行原位猪肝移植术，观察围术期血流动力学及生化代谢和小剂量多巴胺、硝普钠对肾功能的保护作用。方法：随机选择健康杂种猪１６头，静脉复合麻醉下，经右颈外静脉插入Ｓｗａｎ－Ｇａｎｚ导管监测血流动力学，自右颈内动脉和颈外静脉采血监测血气和血生化。无肝期采用门静脉和股静脉Ｙ型连接后，再与左颈外静脉连接，进行体外静脉－静脉转流。无肝前期小剂量多巴胺、硝普钠静脉联合用药并观察尿量。结果：无肝期和新肝期血流动力学变化剧烈并伴有代谢性酸中毒；血清Ｋ＾＋在新肝期有一过性升高；未出现少尿或无尿。结论：原位肝移植术中即使应用体外静脉－静脉转流术仍有血流动力学、酸碱及电解质的显著变化，小剂量多巴胺与硝普钠联合应用有助于肾功能维护。     

Fluids administration and coagulation characteristics in patients with different model for end-stage liver disease scores undergoing orthotopic liver transplantation

Background There have been many studies investigating the impact of the model for end-stage liver disease (MELD) score on predicting post-transplant outcome. But it is unclear whether MELD is correlated to intraoperative fluid therapy and coagulation status. We investigated the relationship between the severity of liver diseases as measured by MELD score and intraoperative fluid requirements and the changes of coagulation characteristics.Methods Ninety patients were included in this retrospective study. The patients were stratified into three groups according to the MELD scores: <15 (low), 15–25 (medium) and >25 (high). Intraoperatively, volume was restored with allogeneic and/or salvaged red blood cells (RBC), fresh-frozen plasma (FFP), platelet and other types of fluids according to hemodynamic data, hematocrit, and clotting data. Intraoperative coagulation data, blood requirements and other fluids administered were compared among the 3 groups. Results Before surgery, in addition to the three variables used to calculate MELD scores in other baseline laboratory values, including ratio of activated partial thromboplastin time (R-APTT), D-Dimer, hematocrit, platelet and blood urea nitrogen (BUN) were significantly different among the 3 groups. The blood loss increased with increasing MELD. The volume of RBC (allogeneinc, salvaged and total), FFP, platelet and the total volume of transfusion were also significantly different among the three groups (P<0.01). The requirements for prothrombin complex and fibrinogen showed a similar pattern. During operation, the changing trends of each coagulation variable were different. Compared with baseline, during each intraoperative stage, INR and R-APPT increased in the low MELD group. While in the medium MELD and high MELD groups, INR did not changed significantly during the operation, and R-APPT significantly increased only after reperfusion. Conclusions This study provided some useful information for perioperative management of patients undergoing liver transplantation. Careful preoperative planning and resource preparation are crucial for patients with high MELD scores. Close communication between surgeon, anesthesiologist and the transfusion staff of blood bank before and during surgery should be stressed.     

不同体积大鼠原位肝移植的试验研究

目的探讨三种不同体积(100%、50%和30%)大鼠原位肝移植术后生存时间,肝功能变化等情况。评估移植物体积对于大鼠原位肝移植的影响。方法建立100%、50%和30%体积的大鼠原位肝移植模型,观察术后生存时间,术后肝功能改变及肝脏组织病理改变。结果术后14d生存率分别为:85%、70%和10%。术后肝功能变化表明30%肝移植组术后损伤较重。病理显示50%及30%肝移植组术后肝脏损害严重,30%组尤为明显。结论移植物的体积对于术后存活率具有明显影响,但外科技术的改进可能提高小移植物受体的术后存活率。     

原位肝移植术中血流动力学、内稳态变化及麻醉处理

目的: 探讨原位肝移植(orthotopic liver transplan tation,OLT)围手术期的血流动力学、内稳态变化和麻醉处理。方法: 终末期肝病患者14例,采用气管内静吸复合全麻。右心置入Swan-Ganz导管监测不同时期血流动力学变化,同时监测内环境各项指标的变化。结果: 血流动力学变化显示,在无肝期肺小动脉楔压(pulmonary arterial wedge pressure,PAWP)、平均动脉压(MAP)、中心静脉压(central venous pressure,CVP)较术前明显下降(P<0.01);在腔静脉开放时CVP较术前明显升高(P<0.01)、PAWP升高(P<0.05)、MAP下降(P<0.01);术毕继续维持较高水平平均肺动脉压(MPAP)(P<0.01);心输出量在腔静脉阻断及开放时较术前降低(P<0.05)。结论: 血流动力学主要发生于无肝期和新肝早期,此期间加强监测、及时处理,可得到基本纠正。     

Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats

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重型肝炎和肝癌肝移植的麻醉管理

目的 对重型肝炎和肝癌患者肝移植围术期的麻醉管理进行总结,为临床处理提供借鉴.方法 回顾43例静吸复合全麻下因重型肝炎（A组）或肝癌（B组）施行改良背驮式肝移植术的麻醉管理,统计围术期血流动力学、出入量、酸碱电解质变化、凝血功能、凝血-抗纤溶药物及血管活性药物用量.结果 两组病人血流动力学变化趋势一致,无肝期10min,新肝期10min血管活性药物用量两组差异无显著性（P＞0.05）;晶体液、白蛋白输入量B组多于A组,血小板输入量A组多于B组（P＜0.05）;红细胞输入量A组虽多于B组,但统计学上差异无显著性（P＞0.05）;术中各期经相应治疗,两组酸碱电解质的变化趋势相同;围术期clot rate、血小板计数、纤维蛋白原水平A组均低于B组（P＜0.05）,凝血酶原复合物和纤维蛋白用量A组大于B组,但统计学上差异无显著性（P＞0.05）;两组患者围术期凝血-纤溶系统功能的变化趋势大致相同.结论 重型肝炎围术期凝血功能较肝癌患者差,术中需输注血小板量较多;围术期经过积极监测和及时处理,两组血流动力学、凝血-纤溶系统功能、酸碱电解质变化趋势基本相同.     

原位肝移植术Narcotrend指数变化与早期肝功能恢复的关系

目的研究心脏死亡器官捐献(DCD)供体原位肝移植术中Narcotrend麻醉深度监测指数变化与早期肝功能恢复的关系。方法选择DCD供体原位肝移植术患者40例,在Narcotrend监测下实时调整异丙酚-瑞芬太尼靶控输注(TCI)参数,维持深度在D2~E1阶段。门静脉开放后,维持靶控参数不变,观察Narcotrend指数(NI)变化,当NI值比基础值升高超过20时,加深麻醉并记录所需时间(S)。分别于术前(T1),手术开始后1 h(T2),门静脉开放后2 h(T3)、24 h(T4)、48 h(T5)、72 h(T6)抽取静脉血检测天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血清总胆红素(TBIL)、直接胆红素(DBIL)。S值取其中位数,将高于和低于这个中位数的病例分为H、L两组进行比较。结果手术后24 h两组AST、DBIL比较差异有统计学意义(P0.05)。手术后48 h两组ALT、AST和TBIL比较差异有统计学意义(P0.05)。手术后72 h大部分指标均有所回落,H组和L组比较只有TBIL差异有统计学意义(P0.05)。结论 NI值变化趋势监测可以指导麻醉深度的调控,还能帮助我们从侧面了解DCD供肝早期恢复状况。     

Reduced-size orthotopic liver transplantation with different grade steatotic grafts in rats

Objective To explore the survival time, pathological change and liver regeneration in different kinds of reduced-size liver transplantation in rats using steatotic grafts. Methods Macrovesicular and microvesicular steatotic rat liver models were established by feeding rats with a diet consisting of 79% standard chow, 20% lard and 1% cholesterol for different time periods. With modified two cuff vascular anastomoses and end-to-end sutures on the bile duct, reduced-size orthotopic rat liver transplantations were performed in an attempt to explore the ratio of graft weight to recipient body weight, recipient original liver weight and histological and electron-microscopic findings in comparison with whole rat liver transplantations. Results A one-week survival rates for the rats undergoing whole liver transplantation, and those in the 70% reduced-size orthotopic liver transplantation (ROLT) group, the 60%ROLT group and the 50%ROLT group (grade Ⅰ macrosteatotic grafts) were 91.67%, 75%, 75% and 25%. A 2-week survival rate was 83.33%, 75%, 58.33% and 0 respectively. And their graft recipient body weight (GRBW) values SD were 3.56%±0.36%, 2.53%±0.15%, 2.28%±0.12% and 1.83%±0.16%, respectively. In grade Ⅱ macrosteatotic grafts, the one-week survival rate for those undergoiong whole liver transplantation and those in the 70% ROLT group was 83.33% and 25%. In the microsteatosis grafts for whole liver transplantation, 70% ROLT, 60% ROLT and 50% ROLT, the one-week survival rate was 83.33%, 75%, 75% and 33.33%; and the 2-week survival rate was 75%, 66.67%, 66.67% and 0, respectively. The survival rate of the 50% ROLT group using grade Ⅰ macrosteatotic grafts or grafts mainly with microsteatosis was significantly different from that of other groups. While using macrosteatotic grafts in grade Ⅱ, the 1-week survival rate of the 70% ROLT group was very poor. Pathological findings after operation included liver regeneration and portal space with mild lymphocyte infiltration. Improvement in steatosis and dilation of the central vein and sinusoids was observed in some rats.Conclusions In the successful and long-term survival of rat reduced-size liver transplantation using grade Ⅰmacrosteatotic grafts or grafts with microsteatosis, the GRBW values should be over 2.28%±0.12%, and the value of graft-recipient liver weight should be over 60%. Steatotic livers in grade Ⅱ should not be used as grafts in ROLT. Steatosis was improved and even totally cured in some long-term survival rats.     

经典原位肝移植术血流动力学变化的临床意义

目的 :回顾性探讨经典原位肝移植术中血流动力学变化及处理。方法 :经典原位肝移植病人100例 ,无肝期选用体外静脉 -静脉转流(VVB)50例 ,非转流(NON -VVB)50例。采用Swan -Ganz漂浮导管监测无肝前期、无肝期5min、15min新肝期5min、15min及术毕各时段血流动力学参数变化。结果 :①VVB组 ,转流初始5min及再灌注10min血流动力学变化明显 ,(P<0.05)。②NON -VVB组门静脉下腔静脉阻断和再灌注时血流动力学变化均明显 ,MAP下降30 %、PCWPMPAP下降20 %、CVP及CO下降40 %(P<0.05)。结论 :原位肝移植无肝期采用VVB有助于维持血流动力学平稳。NON -VVB原位肝移植无肝期 ,采取快速输血输液 ,适当调整血管活性药物应用 ,再灌注时提前纠正酸中毒 ,补充钙剂对抗高钾对心脏的抑制等措施 ,可明显缩短血流动力学不稳定时间     

不同肝功能分级患者非转流下原位肝移植术中血流动力学及氧代谢的变化

目的:研究不同肝功能分级患者在非转流原位肝移植手术(orthotopic liver transplantation ,OLT)过程中血流动力学及氧代谢参数的变化趋势.方法:40例肝病患者全麻下行OLT,常规麻醉诱导后放置Swan-Ganz导管监测平均肺动脉压(mean pulmonary artery pressure, mPAP)、中心静脉压(central venous pressure, CVP)、肺毛细血管楔压(pulmonary capillary wedge pressure, PCWP)和心排血量(cardiac output, CO).分别于诱导后30 min(T1)、门静脉阻断即刻(T2)、阻断30 min(T3)、开放10 min和60 min(T4、T5)及术毕(T6)监测血流动力学指标并记录心排血量指数(cardiac index, CI)、每搏指数(stroke volume index, SVI)、外周(system vascular resistance index, SVRI)和肺血管阻力指数(pulmonary vascular resistance index, PVRI);同时在以上各时点取桡动脉及肺动脉血行血气分析并计算氧供(oxygen delivery,DO2)和氧耗(oxygen consumption,VO2).结果:Child C级患者各时点mPAP及T1和T2时的CVP均高于Child A级和B级患者.所有患者门静脉开放后的PCWP均显著高于开放前,其中Child C级PCWP在T1,T2和术毕较Child A级和B级患者高.Child C级患者T1时SVRI和T3时PVRI显著低于Child A级患者.患者术中DO2均超过1 000 mL/min,VO2均低于正常值并于术毕恢复.结论:不同Child分级肝病患者,术中血流动力学呈高排低阻型,术中过高的PCWP和CVP与临床表现不一致.不同肝功能分级患者术中VO2低于正常值,并于术毕恢复正常.     

肾移植术后早期肝功能异常

目的　探讨肾移植术后 3个月内环孢菌素A(CsA)免疫抑制剂引起肝损害的治疗措施。方法　对19例肾移植术后出现肝功能异常的病例进行分析 ,测定肝功能异常时CsA谷值浓度 ;及时调整免疫抑制剂用量 ,配合保肝利胆治疗。结果　治疗 2～ 4周后 ,17例患者肝功能恢复正常 ;2例无效者 ,将CsA改为他克莫司 (FK5 0 6 )治疗 1个月后 ,肝功能指标逐渐恢复正常。结论　低剂量CsA、霉酚酸酯 (MMF)、泼尼松 (Pred)三联是目前较为理想的免疫抑制剂治疗方案 ,结合保肝利胆治疗 ,对减少术后早期CsA肝毒性的发生有一定疗效。     

大鼠原位肝移植模型的手术操作技巧探讨

目的:探讨建立稳定大鼠原位肝移植模型的手术操作技巧。方法:采用二袖套法行大鼠原位肝移植,供体经腹主动脉进行肝脏冷灌注,肝上下腔静脉采用手缝合法进行吻合;门静脉和肝下下腔静脉用袖套法吻合;胆总管采用单管内支架胆管端端吻合。结果:大鼠原位肝移植52例,手术成功45例(86.5%),1周内存活43例(82.7%),1个月内存活36例(69.2%),供体手术时间(30.6±4.0)min,受体手术时间(46.0±5.5)min,无肝期为(20.0±2.5)min。结论:大鼠原位肝移植模型稳定可靠,可为肝移植提供理想的研究手段;良好的肝脏灌注,改进的肝上下腔静脉吻合法可以缩短无肝期,提高大鼠肝移植的生存率。     

同种异体原位肝脏移植13例次临床经验

目的 总结原位肝脏移植经验。方法 对12例患者实施13例次原位肝脏移植(包括1例再次肝移植),其中5例终末期肝硬化、4例原发性肝癌、1例肝癌术后肝功能衰竭、1例肝豆状核变性、1例慢性肾功能衰竭合并肝炎后肝硬化。手术方式:经典原位肝移植10例,改良背驮式肝移植2例,再次肝移植1例。结果 全组成功9例,最长存活超过2年;围手术期死亡4例,直接死亡原因脑出血1例、急性呼吸窘迫综合征1例、急性肾功能衰竭1例、肝动脉血栓1例。结论 肝脏移植是治疗各种终末期肝病的有效手段,但应严格掌握适应证,减少术后并发症的发生是提高肝移植成功率及长期存活率的关键。     

脾切除对肝移植患者的影响

目的探讨术前或术中脾切除对肝移植患者的影响.方法回顾浙江大学医学院附属第一医院1999年2月至2005年5月间收治的403例施行肝移植患者中有脾切除的29例患者的临床资料,将其分成术前脾切除组（23例）和术中脾切除组（6例）,分别与同期随机抽取的未合并有脾切的肝移植患者58例作对照,就其手术时间、出血、输血、感染、急性排斥、生存率及术后血小板恢复情况等方面进行对比分析.结果术前脾切组和术中脾切组分别与无脾切组相比手术耗时明显延长,术中、术后输血明显增加,细菌感染率也显著增高.脾切后急性排斥反应发生率未见显著降低.术中脾切组累积生存率明显低于无脾切组（P=0.0001）.术后第14天各组平均血小板水平恢复正常,但是术后第30天脾切组的平均血小板水平均高于正常.结论肝移植术前或术中脾切除,对肝移植患者均无益处,脾切除应严格掌握适应证.     

原位肝移植的术中输血

目的：总结原位肝移植术中输血的经验 。方法：分析28例原位肝移植的临床资料及输血情况。结果：28例肝移植受者术中输血总量平均为(9 517±7 680) ml，其中1例婴儿肝移植受者输血总量为920 ml，2例原位肝移植受者实施超大剂量输血，分别达28 740 ml，38 580 ml；术前贫血或/和血小板减少的肝移植受者术中输血并未增多。结论：肝移植术前备血总量可控制在5 000~10 000 ml，应有应对超大剂量输血的措施；血常规结果不能作为肝移植受者术前备血的依据。     

应用脂变供肝行减体肝移植的实验研究

目的　探讨大鼠脂变供肝用于减体肝移植的适宜植肝量及病理类型。方法　采用 70 %、60 %、5 0 %大鼠减体肝移植 (ROLT)模型 ,观察术后存活率、肝质量 /体质量、移植肝 /受体原肝及病理的改变。结果　大鼠Ⅰ级脂变的全肝移植和 70 %、60 %、5 0 %ROLT的 1周存活率分别为 91.67% ,75 % ,75 % ,2 5 % ;2周存活率分别为 83 .3 3 % ,75 % ,5 8.3 3 % ,0。Ⅱ级脂变的全肝及 70 %ROLT的 1周存活率为 83 .3 3 %和 2 5 %。小泡性脂变为主的供肝 ,其全肝及 70 %、60 %、5 0 %ROLT移植的 1周存活率分别为 83 .3 3 % ,75 % ,75 % ,3 3 .3 3 % ;2周存活率分别为 75 % ,66.67% ,66.67% ,0。Ⅰ级或以小泡性脂变为主的供肝 5 0 %ROLT的生存率与其它组相比均有显著性差异。术后病理可见肝再生及脂变减轻或消失 ,中央静脉及肝窦扩张。结论　要获得较高的术后存活率 ,大鼠Ⅰ级或以小泡性脂变为主的供肝行减体肝移植其移植肝 /受体体质量应大于 ( 2 .2 8± 0 .12 ) % (即移植肝 /受体原肝 >60 % ) ;而Ⅱ级脂变供肝不宜用于减体肝移植 ;术后脂变可减轻或逆转