Interest of BIS monitoring to guide propofol infusion during the anhepatic phase of orthotopic liver transplantation

Objective

The anhepatic phase of orthotopic liver transplantation (OLT) is associated with significant changes in pharmacokinetics. The aim of this study was to compare the influence of this phase on propofol target concentrations during BIS guided target controlled infusion (TCI).

Study design

Prospective study.

Patients and methods

Eight patients aged 25 to 65 years, Child-Pugh status A-B scheduled for OLT were prospectively included. Anesthesia was performed using TCI of propofol (Diprifusor^®, Marsh pharmacokinetic model), sufentanil and cisatracurium. Propofol target concentration was adjusted to maintain BIS values between 40 and 50.

Results

To maintain stable BIS values, propofol target concentrations should be decreased during the anhepatic phase versus the dissection one (2.0 μg/ml ± 0.8 versus 3.0 μg/ml ± 0.9, p < 0.0001).

Conclusion

BIS could be useful to titrate propofol infusion during the anhepatic phase of OLT.     

肝性脊髓病肝脏移植术后的疗效观察

目的 为进一步探讨肝脏移植术对肝性脊髓病疗效观察。方法 对我院2例肝性脊髓病病人行原位肝移植术后进行临床资料回顾分析，随访时间最长2年5个月。结果 肝移植术后病人的临床症状、体征及生活质量均获得明显改善，四肢肌力得到有效恢复。结论 肝脏移植对肝性脊髓病是一种新的、从病因上治疗的有效方法。     

同种异体原位肝移植的肝动脉重建

目的 总结同种异体原位肝移植术中肝动脉吻合的经验。方法 回顾悸分析20例原位肝移植术中影响肝动脉吻合的因素和处理技巧。结果 16例行供、受者肝固有动脉端端吻合，3例供者肝总动脉与受者肝固有动脉吻合，1例供者肝总动脉与受者脾动脉吻合；术后彩色多普勒超声监测显示肝动脉血流通畅，均未发现有血栓形成或肝动脉狭窄，全部病例未发生胆道并发症，现存活15例。结论 合理选择吻合用血管是避免术后发生血栓形成和动脉狭窄的关键。     

静脉输注中等剂量氨甲环酸和乌司他丁对原位肝移植术患者纤溶功能的影响

目的 评价静脉输注中等剂量氨甲环酸和乌司他丁对原位肝移植术患者纤溶功能的影响.方法 拟行原位肝移植术患者30例,性别不限,年龄34 ～ 63岁,体重指数17 ～ 37 kg/m2,终末期肝病模型评分6～34分,ASA分级Ⅲ或Ⅳ级.采用随机数字表法,将患者随机分为3组(n=10):对照组(C组)、氨甲环酸组(T组)和乌司他丁组(U组).U组和C组气管插管后分别静脉输注乌司他丁100 000 U/h或生理盐水10 ml/h直至新肝期120 min;T组气管插管后静脉注射氨甲环酸负荷量1 g,随后以10 mg·kg-1 ·h-1速率静脉输注至新肝期120 min.分别于麻醉诱导前(T0)、无肝前期120 min(T1)、无肝期30 min(T2)、新肝期30 min(T3)、新肝期120 min(T4)和术毕(T5)时采集静脉血样,测定凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、国际标准化比值(INR)、纤维蛋白原(Fg)、D-二聚体(D-D)和纤维蛋白降解产物(FDP)的水平.记录术中出血量及输血情况.记录术后14 d内T组和U组肝动脉或门静脉血栓形成情况.结果 3组间血浆PT、APTT、Fg、INR、出血量和输血量差异无统计学意义(P＞0.05).与C组比较,T组T3-5时血浆D-D浓度降低,T4.5时血浆FDP＞ 20 μg/ml比率降低(P＜ 0.05或0.01),U组血浆D-D浓度和血浆FDP＞ 20μg/ml比率差异无统计学意义(P＞0.05).T组和U组未见肝动脉或门静脉血栓形成.结论 术中静脉输注中等剂量氨甲环酸可抑制原位肝移植术患者纤溶功能,但不足以减少出血量;术中静脉输注乌司他丁100 000 U/h对原位肝移植术患者纤溶功能无影响.     

原位肝移植术中肝动脉变异及术后肝动脉血栓形成的处理

目的探讨肝移植术中肝动脉变异及术后肝动脉血栓形成的处理。方法统计2000年8月至2002年12月期间进行肝移植术的67例次供、受者肝动脉的变异情况；分析肝动脉的重建方式，探讨肝动脉变异与手术后肝动脉血栓形成的关系、肝动脉血栓形成的危险因素及肝动脉血栓形成后的处理。结果67例次供者肝脏和65例受者肝脏共出现肝动脉变异12例次，发生频率最高的为右肝动脉起源于肠系膜上动脉(5例)及左肝动脉起源于胃左动脉(3例)。肝动脉的重建方式如下：供者及受者肝总动脉与胃十二指肠动脉分叉处成型后吻合58例；腹主动脉与肝动脉搭桥2例；利用变异的肝动脉分支吻合7例。手术后发生肝动脉血栓形成3例，均经腹股沟处股动脉插管行肝动脉溶栓治疗，此3例患者中死亡1例。结论避免变异的肝动脉损伤、选择适当的肝动脉吻合方式可以保证移植肝脏的动脉血供。肝动脉血栓形成与肝动脉变异无关。作为肝动脉血栓形成后的保守治疗方法，肝动脉内溶栓治疗有可能避免2次移植。     

原位肝移植术后发生脑病的相关因素分析

目的分析同种原位肝移植术后发生脑病的相关因素。方法回顾性分析128例次肝移植受者的临床资料,肝功能采用Child-Pugh分级,病情评估采用UNOS分级。对肝移植术后发生脑病的相关因素采用χ2检验、方差分析或t检验进行单因素分析,将有意义的因素纳入多因素模型Logistic回归进行分析。结果128例次肝移植术后共发生脑病21例(16.41%),其中Child-PughC级患者19例,B级2例;UNOS1级16例,2级以上5例;脑病大多发生于术后1周内,慢性重型肝炎及二次肝移植受者发生率较高(P<0.05)。Child-PughC级患者中未发生脑病44例(对照组),发生脑病19例(脑病组),两组在术前总胆红素、感染、肝移植手术方式、术后血清肌酐水平、感染以及肾功能衰竭的发生率等方面比较,差异有统计学意义(P<0.05);上述临床因素经多因素模型进行两分类反应变量的Logistic回归(前进法)分析后显示,术后肾功能衰竭和手术方式两项与发生脑病有显著关系(P<0.01)。结论肝移植术后脑病的发生是综合因素的结果,术前肝功能情况较差(Child-PughC级)以及病情危重(UNOS1级)的患者,术后脑病的发生率较高。术后急性肾功能衰竭与脑病的发生密切相关。     

Mortality after orthotopic liver transplantation

An analysis was made of the causes of death in 22 of 50 patients receiving consecutive orthotopic liver transplants. A close look at the fatal course of these patients revealed three major patterns: surgical complications (27%), pathology of the hepatic artery anastomosis (23%), and cholestasis (32%). Technical factors were the major reasons for excessive peroperative blood loss, and not the coagulopathy accompanying the liver disease. The etiology of hepatic artery thrombosis is not known. It leads to irreversible damage of the graft, causing death due to acute hepatic failure or to cholangitis and sepsis. The only way to treat patients with this complication is retransplantation. Several factors can induce cholestasis. Retrospectively, it appears that this was mostly due to inappropriate immunosuppression, often a result of the difficult differential diagnosis between rejection and viral infection. Recognition of these three basic patterns should enable us to anticipate their subsequent complications. This may lead to a reduction in morbidity and mortality after liver transplantation.     

肝移植术后肝动脉狭窄的防治策略

目的 探讨肝移植术后不同肝动脉狭窄类型治疗时机的选择和疗效.方法 2003年10月至2007年5月,本院共有21例肝移植病人术后发生肝动脉狭窄,其中19例接受肝动脉支架放置术,2例定期随访观察;同时监测介入治疗前后肝功能、肝动脉通畅程度变化及病人临床转归等情况.结果 肝移植术后肝动脉狭窄发生率为3.43%(21/613),诊断中位时间146 d.6例早期肝动脉狭窄病人均接受介入治疗,其中病死2例,存活4例病人中有2例再移植.15例晚期肝动脉狭窄病人中,13例接受介入治疗,其中病死4例,再移植2例,7例存活但肝功能反复出现异常.另外2例在肝门及肝内分支形成良好的侧支循环,肝功能维持稳定.结论 移植术后应根据肝动脉狭窄类型、胆道缺血损伤程度以及有无良好侧支循环代偿等综合因素采取个体化治疗策略.     

肝动脉重建的小鼠原位肝移植模型建立

目的 建立稳定的肝动脉重建的小鼠原位肝移植模型.方法 以"双袖套法"小鼠肝移植为基础,将带腹主动脉的供肝肝动脉与受体腹主动脉行端侧吻合.共完成小鼠原位肝移植70例,并观察术后24 h、1周、1个月受体存活率,术后1个月肝功能及肝组织病理变化.同时设立假手术组对照.结果 受体术后24 h、1周、1个月存活率分别为94.3%、91.4%、85.7%.术后1个月肝功能ALT:(39.20±2.09)U/L AST:(75.60±3.24)U/L.与对照组比较,差异无统计学意义(P>0.05).病理显示肝组织结构良好.结论 该方法可稳定地建立肝动脉重建的小鼠原位肝移植模型.     

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目的探讨肝移植术后肝动脉并发症的危险因素以及肝动脉并发症的预防和治疗手段：方法回顾性分析2004年中山大学附属第一医院实施的181例同种原位肝移植病人的临床资料。结果181例肝移植病人中与动脉相关的并发症共12例，发生率为6．6％（12／181）;术后近期发生的7例动脉相关并发症中，5例为动脉血栓形成，2例为误伤右副肝动脉而继发的大面积肝坏死；术后远期发生的5例动脉相关并发症中，动脉血栓形成2例和动脉广泛狭窄3例。所有12例与动脉相关的并发症中，接受再次肝脏移植者7例，3例行急诊肝动脉取栓术并重建肝动脉血流；2例进行溶栓治疗。因肝动脉并发症导致死亡6例，占该组肝移植病人死亡的28、6％（6／21）。结论显微外科技术在肝动脉吻合中的应用以及预防或及时纠正血液高凝状态，可以降低动脉并发症的发生率。肝动脉相关并发症的处理应采用个体化治疗方案，再血管化手术或再次肝移植是治疗肝动脉并发症的最常用方案。对已估计到即使行再动脉化术后肝功能也不能逆转的病人，应积极准备再次肝移植，且应在移植肝功能衰竭和严重感染出现之前进行.     

呋塞米与多巴胺联合应用对肝移植术无肝期肾功能及尿量的影响

目的比较背驮式原位肝移植术中持续输注小剂量多巴胺或呋塞米和多巴胺联合应用对无肝期肾功能和尿量的影响。方法背驮式原位肝移植术患者42例,ASAⅢ~Ⅳ级,随机分为多巴胺组(D组)和呋塞米-多巴胺组(F组),每组21例。两组均于麻醉诱导后静脉泵注多巴胺(2~5μg.kg-1.min-1)至术毕,F组则在无肝期开始时静注呋塞米0.1mg/kg。观察无肝期输液量、血液动力学和尿量,检测血清肌酐(Cr)和肌酐清除率(CCr)。结果与D组比较,F组无肝期尿量明显增多(P<0.05);两组无肝期时间、输液量和心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)、每搏量(SV)、心输出量(CO)、全身血管阻力(TSVR)、Cr、CCr差异无显著意义。结论肝移植术中持续泵注多巴胺和呋塞米联合应用可明显增加无肝期尿量。     

421例同种原位肝移植肝动脉重建体会

目的探讨肝移植手术过程中肝动脉重建的技术要点,分析肝移植术后肝动脉合并症发生的原因。方法回顾性总结2000年5月至2006年5月,6年间我院连续实施的同种原位肝移植421例患者的临床资料,分析肝移植手术过程中可能影响肝动脉重建的因素,以及术后肝动脉合并症发生的可能原因,总结术中肝动脉重建的技术要点。结果421例肝移植患者中共发生肝动脉相关合并症者14例,发生率为3.3%,肝移植术后血管合并症主要是动脉血栓形成及肝动脉狭窄。14例合并症患者中死亡9例,死亡率为64.3%。按合并症出现时间分类,早期动脉合并症8例,死亡6例,晚期动脉合并症6例,死亡3例。结论供肝动脉的完整性、供受体动脉的重建方法以及显微外科技术的应用是影响肝动脉重建结果的重要因素。     

Successful orthotopic liver transplantation for treatment of a hepatic yolk sac tumor

Yolk sac tumors (YSTs) represent 3% of malignancies in childhood and most commonly arise in the gonads. Hepatic YSTs are rare and previous reported cases were treated with resection and/or chemotherapy with mixed results. We present the first case of an unresectable hepatic YST in a 2-year-old boy treated successfully with liver transplantation.     

原位肝移植肝动脉并发症的防治

目的 探讨原位肝移植肝动脉并发症的预防及治疗。方法 回顾性分析1999年2月至2001年2月完成的22例原位肝移植，其中4例行体外静脉转流下的原位肝移植术，17例行背驮式原位肝移植，1例为活体供肝部分肝移植。11例供肝的肝固有动脉与受者的肝固有动脉吻合，4例供者脾动脉与受者肝总动脉吻合，3例供者腹腔动脉与受者肝总动脉吻合，2例应用供者髂动脉在供者肝固有动脉与受者腹主动脉间架桥吻合，1例供者肝右动脉与受者肝固有动脉吻合，1例供者肝固有动脉与受者异位肝右动脉吻合。术后以多普勒超声扫描监测肝动脉血流。结果 1例术后5d时发生肝动脉血栓形成，以尿酶介入溶栓后出现吻合口出血，再次手术行肝动脉吻合。21例无肝动脉并发症发生。15例随访1－20个月，多普勒超声扫描提示肝动脉血流、形态正常，胆道造影未见肝外胆管狭窄，血清学检查提示肝功能状态良好。结论 原位肝移植预防肝动脉并发症的关键在于血管吻合时操作精细，实现血管内膜对内膜的无张力吻合。     

Incidence and outcome of arterial complications after orthotopic liver transplantation

Abstract  Arterial complications can be a major factor in morbidity and mortality after orthotopic liver transplantation (OLT), as they may cause graft failure, sepsis and complications of the biliary tract. From September 1988 to December 1994, 571 OLT were performed in 529 patients. The follow-up period ranged from 8 to 83 months. Actuarial 1–, 3– and 5-year survival figures were 91 %, 87 % and 85 %, respectively. In 12 cases (2.1 %) complications of the arterial anastomoses were observed. Early arterial complications occurred in eight cases from various causes, while late arterial complications were exclusively Thromboses and developed in four patients 8, 12, 26 and 37 months after surgery, respectively. The main clinical course in patients with arterial thromboses was septic cholan-gitis with destruction of the biliary tree. Although 70% of the grafts with arterial thrombosis were lost, 30 % could, at least temporarily, be salvaged by other treatment options. Provided adequate treatment is carried out, arterial complications do not affect overall patient survival.     

肝、胰Ⅰ期联合移植治疗合并糖尿病的良性终末期肝病一例

目的 对1例原位肝、异位胰腺I期联合移植进行总结.方法 对1例终末期肝病合并2型糖尿病的患者施行肝、胰I期联合移植,肝脏为原位移植,胰腺异位移植于右侧髂窝,胰液空肠引流.术后采用他克莫司、霉酚酸酯及糖皮质激素预防排斥反应,并辅以两剂达利珠单抗.结果 术后移植胰腺功能良好,第2天即停用胰岛素.术后14 d,移植肝出现轻度急性排斥反应,调整他克莫司的用量后逆转.受者已存活15个月,移植肝脏及胰腺功能均正常.结论 肝、胰联合移植是治疗终末期肝病合并糖尿病的有效方法.     

原位肝移植肝动脉并发症的预防和治疗

目的 总结分析原位肝移植肝动脉重建及其并发症的防治经验,提高肝移植疗效和受体存活率。方法 总结1995年5月至2005年4月实施的122例肝移植临床资料,肝动脉重建采用供者腹腔动脉干Carrell’s袖片或肝总动脉-脾动脉汇合部与受者肝左-右动脉汇合部袖片吻合21（16．76％）,与受者胃十二指肠-肝固有动脉汇合部吻合87例（71．76％）,采用髂动脉-腹主动脉搭桥14例（11．48％）。术后根据凝血酶原时间（PT）,应用普通肝素或低分子肝素预防性抗凝。术中、术后应用多普勒超声监测肝动脉血供。结果 术后肝动脉血栓形成（HAT）3例,肝动脉狭窄（HAS）2例。1例HAT于术后19d死于多器官功能衰竭,另4例通过放射介入治疗治愈。其余病例随访2～62个月,未见肝动脉血栓形成（HAT）和肝动脉狭窄（HAS）。本组肝动脉并发症发生率为4．10％。结论 正确地选择肝动脉重建吻合的部位和术后有效的抗凝治疗可减少HAT和HAS的发生,多普勒超声监测能早期发现HAT和HAS,挽救移植物,避免再移植。     

Increased apoptosis of hepatocytes in vascular occlusion after orthotopic liver transplantation

Early vascular occlusion is liable to cause graft failure, and differential diagnosis between this condition and primary nonfunction (PNF) caused by preservation injury may be difficult. Apoptosis has been detected in immunomediated cytotoxicity and is known to be triggered by mild ischemia. In a retrospective analysis we investigated the role of apoptosis in vascular occlusion, PNF, and acute allograft rejection to improve the differential diagnosis of early graft failure. The liver graft histology of 75 patients (46 male, 29 female) a median 47 (1–64) years of age was screened semiquantitatively for the rate of apoptosis on the hematoxylin-eosin stain (HE) and by the in situ end nick labeling technique (TUNEL). This cohort included all patients who developed PNF (n = 9) or vascular occlusion (n = 11) after orthotopic liver transplantation (OLT) in the years 1992 to 1996. Within this period of time we performed 205 OLTs on 189 patients. We further included 22 patients with early acute rejection and 11 controls. The highest rates of apoptotic hepatocytes were seen in vascular occlusion (P < 0.001). Grafts with PNF were explanted 1–3 days after OLT and showed hepatocytes that were 100 % necrotic. Cases of acute early rejection showed a significantly higher apoptotic cell count than did normal controls (P < 0.003), increasing in direct proportion to the severity of rejection. Screening biopsies for the rate of apoptosis can improve the efficacy and accuracy of differential diagnosis of early graft failure. Received: 27 January 1999/Revised: 7 September 1999/Accepted: 13 September 1999     

肝移植术后肝动脉并发症的再次肝移植治疗

目的 探讨再次肝移植治疗肝移植术后肝动脉并发症的可行性及手术时机.方法 回顾性分析2003年12月至2006年12月收治的13例肝动脉并发症患者再次肝移植的临床资料.结果 再次肝移植的无肝期、手术时间和首次移植比较差异无统计学意义(P=0.291,P=0.312),术中出血量、ICU停留时间和首次移植比较差异有统计学意义[(3.1±1.1)L比(1.5±0.9)L(P=0.005),(4.3±1.8)d比(3.2±2.5)d(P=0.015)].围手术期病死率为38.5%(5/13),其中移植间隔1个月内死亡1例(1/4),超过1个月死亡4例(4/9).死亡原因分别为急性肾功能衰竭2例、严重感染2例、心肌梗死1例.8例存活,随访6～51个月,中位生存时间22.5个月.结论 再次肝移植是治疗肝移植术后肝动脉并发症导致不可逆性肝功能损害时的惟一有效手段.选择适宜的手术时机和手术方式、调整免疫抑制方案、加强围手术期管理是提高再次肝移植疗效的关键.     

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation

Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62%), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n=12) and those without (n=22). The two groups were similar in age, sex, Child's stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421±335 vs 183±126; P<0.025), and this was even more evident when rejection occurred (626±375 vs 195±129; P<0.001). Furthermore, during an acute rejection reaction, three cases showed a true steal phenomenon through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.