Blood transfusion in orthotopic liver transplantation: six-year experience

Patients undergoing orthotopic liver transplantation (OLT) are susceptible to massive blood loss and require transfusion. Possible reasons for increased transfusion demands include platelet abnormalities, thrombocytopenia secondary to hypersplenism, clotting factor deficiencies, fibrinolysis, increased surgical blood loss associated with portal hypertension and previous surgical procedures, and hypothermia. The purpose of this study was to review trends in blood product usage during our first 6 years of experience performing OLT.     

减少肝移植围手术期输血相关策略的研究进展

肝移植手术一直存在大量失血和输血的问题。在过去的二十年中,随着肝移植技术的不断成熟,围手术期输血量急剧减少,无输血肝移植成为现实。由于出血和输血都与肝移植的不良预后相关,减少出血和不必要的输血成为了肝移植围手术期的关键目标。本文总结了肝移植围手术期异体输血的不良影响、终末期肝病患者的凝血功能监测、肝移植受者的输血管理以及减少肝移植围手术期输血的策略,旨在为减少肝移植围手术期的输血需求提供参考。     

Minimizing blood loss in liver transplantation: progress through research and evolution of techniques

Blood loss during liver transplantation has long been recognized as an important cause of morbidity and, especially in the early days, also mortality. It is well known that blood transfusions are associated with an increased risk of postoperative complications, such as infections, pulmonary complications, protracted recovery, and a higher rate of reoperations. Many studies have been performed during the past decades to elucidate the mechanisms of increased blood loss in liver transplantation. In the late 1980s, primary hyperfibrinolysis was identified as an important mechanism of bleeding during liver transplantation. This has provided the scientific basis for the use of antifibrinolytic drugs in liver transplant recipients. Several randomized, controlled studies have shown the efficacy of these compounds in reducing blood loss and transfusion requirements during liver transplantation. In addition, increasing experience and improvements in surgical technique, anesthesiological care and better graft preservation methods have contributed to a steady decrease in blood transfusion requirements in most liver transplant programs. Several centers are now reporting liver transplantation without any need for blood transfusion in up to 30% of their patients. Despite these improvements, most patients undergoing liver transplantation still require blood transfusions that have a negative impact on outcome, emphasizing the need for further attempts to control blood loss by surgeons and anesthesiologists. This paper provides an overview of the clinical and research developments, which have contributed to a reduction in blood loss and transfusion requirements, resulting in an important reduction in morbidity and mortality after liver transplantation during the last two decades.     

Predictors of blood product use in orthotopic liver transplantation using the piggyback hepatectomy technique

Orthotopic liver transplantation (OLT) has historically been associated with massive blood loss and hemodynamic instability related to the coexistence of varices, coagulopathy, thrombocytopenia, and portal hypertension. Piggyback hepatectomy (PGB) is a technique increasingly utilized in OLT to avoid veno-venous bypass and vena cava clamping. This study evaluated the factors associated with blood loss and blood product requirement in PGB. METHODS: This study is a retrospective review of the anesthesia preoperative and operative notes and computerized lab values for all adult cadaveric liver transplants over a 42-month period. These data were combined with the liver transplant database for analysis. Approximately 98% of the transplants were performed using a standard piggyback approach with no use of veno-venous bypass. RESULTS: Data were included for all 526 transplants performed during this time period. Estimated blood loss (EBL) was 1000 cc. Median transfusion requirement was 3 units packed red blood cells, 7 units fresh frozen plasma, and 6 units platelets. Multivariate linear regression demonstrated that predictors of EBL were age, MELD score, preoperative hemoglobin, initial fibrinogen, initial central venous pressure, and total anesthesia time. Predictors of PRBC useage were age, MELD score, preoperative hemoglobin, initial fibrinogen, and anesthesia time. Postoperatively increased transfusion requirement was associated with increased length of hospital stay and lower 90-day and 1-year graft and patient survivals. CONCLUSION: These results demonstrate that PGB can be safely accomplished in nearly all liver transplant patients without venovenous bypass or vena cava clamping and with less warm ischemia, which may ultimately be associated with less perioperative morbidity and improved outcomes.     

原位肝移植的常用手术方式及应用体会

目的探讨经典原位肝移植术、改良背驮式肝移植术、原位肝移植腔静脉成形术在临床应用中的利弊。方法对2001年10月至2004年5月实施的155例病人的159次肝移植术式进行回顾性分析，其中经典原位肝移植术94例，改良背驮式肝移植术48例（包括改良背驮＋术中门一腔静脉端侧吻合转流8例），原位肝移植腔静脉成形术17例；术中行血管架桥5例，其中因门静脉闭锁及栓塞行供肝门静脉与受体肠系膜上静脉间架桥2例，因动脉变异分支细小不能利用行供肝腹腔干与受体腹主动脉间架桥3例。159例次肝移植手术均未应用体外静脉转流技术。结果原位肝移植腔静脉成形术的手术时间、无肝期最短，术中失血输血量最少，其术中对循环和肾功能的影响与经典术式相仿。经典原位肝移植术与背驮式肝移植术相比流出道不畅发生率较低，总手术时间较短（平均少30min），但无肝期较长（平均长8min），术中及术后肾上腺出血发生率较高，对肾功能影响较大，三组术后ICU留置天数差异亦无显著性意义（P=0．542）。结论不同的肝脏移植术式各有其优缺点，术者的经验以及对术式的熟悉程度会影响手术方式的选择，从原则上讲，手术方式的选择应根据具体病情及术中情况而决定。     

肝移植手术出血特点及其对术后呼吸功能恢复的影响

目的研究肝移植手术中出血特点以及失血/输血量对术后呼吸功能恢复的影响。方法回顾性分析我科于2001年月2～2006年月948例几种不同病因肝移植患者手术过程出血特点以及失血、输血量对呼吸功能恢复的影响。结果病肝切除阶段是主要的出血时间段,广泛渗血为主要特点;不同疾病病因手术出血量明显不同。出血量最多为肝癌合并肝硬化、其它依次为肝硬化、急性重症肝炎、无肝硬化肝癌(P<0.05)。术中出血量大于5000ml明显影响患者术后呼吸功能的恢复,并且造成较高的围手术期并发症及死亡率(P<0.05)。结论肝移植术中大出血与术后呼吸功能恢复和术后并发症关系密切,是影响肝移植成败的重发因素之一。因此,尽量减少手术中出血是非常重要的。     

91例肝移植手术方式分析

目的:探讨经典原位肝移植术、改良背驮式肝移植术和原位肝移植腔静脉成形术在临床应用中的利弊。方法:对2001年10月至2003年8月实施的91例肝移植术式进行总结,其中经典原位肝移植术24例(A组),改良背驮式肝移植术43例和改良背驮加术中门鄄腔静脉端侧吻合转流8例(B组),原位肝移植腔静脉成形术16例(C组);91例肝移植手术均未应用体外静脉转流技术。结果:原位肝移植腔静脉成形术的手术时间、无肝期最短(P<0.05),且术中输血量较改良背驮式肝移植术和经典原位肝移植术少(P<0.05)。3组术后ICU留置天数无显著差异(P=0.542)。结论:经典原位肝移植术、改良背驮式肝移植术和原位肝移植腔静脉成形术是肝移植的基本术式;从趋势上看,改良背驮式肝移植术将成为主流术式;对某一个具体病例选择何种术式需根据病情及术中情况决定。     

Transfusion free surgery: single institution experience of 27 consecutive liver transplants in Jehovah's Witnesses

BACKGROUND: Despite the risks associated with transfusion, the medical community continues to view blood as a safe and abundant product. In this article, we provide an effective strategy to accomplish orthotopic liver transplantation without transfusion. STUDY DESIGN: From June 1999 through July 2004, 27 liver transplantations were performed in Jehovah's Witness patients at the USC-University Hospital (24 adults, 3 children). Nineteen of these were living donor (LD) and eight were deceased donor (DD) liver transplants. Preoperative blood augmentation with erythropoietin and iron was achieved. At induction, all LD and six of eight DD recipients underwent acute normovolemic hemodilution (ANH), and the operation was conducted under conditions of moderate anemia. Cell scavenging techniques were used. Acute normovolemic hemodilution and salvaged blood were returned as needed during bleeding or on completion of transplantation. RESULTS: The preoperative liver disease severity score was higher in the deceased donor group. We had 100% graft and patient survivals in the LD group, and 75% in the DD recipients. Two DD recipients died. The remaining are all alive and well, with a mean followup of 965 days (range 266 to 1,979 days) in the LD group and 624 days (range 119 to 1,132 days) in the DD group. CONCLUSIONS: Preoperative blood augmentation and acute normovolemic hemodilution provide a safe cushion against operative blood loss. Elective living donor liver transplantation allows full implementation of a transfusion-free strategy in the setting of early hepatic failure, portal hypertension, and anemia. This feat is an important step toward global standardization of transfusion-free surgical practice and an important response to widespread blood shortages and transfusion risks.     

同种异体原位肝移植15例报告

目的 总结临床肝移植的经验。方法 对１０例晚期肝硬变、２例肝内胆管扩张症、１例肝内胆管结石、１例布－加氏综合征、１例胆管细胞癌患者施行了原位肝移植。结果 １５例患者术后移植肝活力恢复良好；死亡３例，１例死于肿瘤转移，２例死于感染，余１２例存活良好，已有３例存活超过１年。结论 完善的手术技术及正确的围手术期处理是肝移植成功的关键。     

ASA 评分在肝癌患者外科治疗风险评估中的作用

目的：探讨ASA评分对肝癌患者外科治疗风险评估的价值。 方法：回顾2006年1月—2010年12月419例原发性肝癌肝切除患者围手术期临床资料,分析患者ASA评分与临床因素的关系,并对可能的相关因素作单因素筛选后行多因素回归分析,分析肝癌术后并发症及术中输血有关的影响因素。 结果：统计分析显示,肝癌患者术前并发症及术前血红蛋白影响ASA评分;随着ASA评分上升,患者术中失血量、输血量、术后并发症及住院天数明显高增加（均P<0.05）。多因素回归分析结果显示,ASA评分、失血量、肝硬化、年龄、丙氨酸转氨酶（ALT）水平是术后并发症发生的独立影响因素（均P<0.05）;ASA评分、手术时间、肿瘤直径是术中输血的独立影响因素（均P<0.05）。 结论：ASA评分是肝癌患者围手术期风险较好的早期预测指标。     

肺移植围手术期大量输血的危险因素及其预后分析

目的  探讨肺移植围手术期大量输血的危险因素及其对预后的影响。方法  回顾性分析159例肺移植受者的临床资料。根据围手术期输血量将受者分为大量输血组（20例）和非大量输血组（139例）。比较两组受者的临床资料,分析肺移植围手术期大量输血的危险因素,总结两组受者的预后情况。结果  两组受者术前抗凝治疗、血红蛋白量、原发病为特发性肺纤维化或特发性肺动脉高压的例数,术中发现胸腔粘连例数、手术时间、各种成分输血量比较,差异均有统计学意义（均为P < 0.05）。术前抗凝治疗,术中发现胸腔粘连、使用体外膜肺氧合（ECMO）及手术时间长是肺移植围手术期大量输血的危险因素（均为P < 0.05）。大量输血组原发性移植物功能障碍（PGD）3级发生率和术后30 d内病死率均高于非大量输血组（均为P < 0.01）。体质量指数（BMI）低和大量输血是受者术后30 d内死亡的危险因素（P=0.048、P < 0.001）。大量输血组受者的1年生存率低于非大量输血组（P < 0.001）。结论  术前抗凝治疗及术中发现胸腔粘连、使用ECMO和手术时间长是肺移植围手术期大量输血的危险因素,大量输血对受者预后有不良影响。     

Liver transplantation in patients with portal vein thrombosis and central portacaval shunts.

The authors have analyzed the impact of pre-existing portal vein pathology on the outcome of orthotopic liver transplantation. The incidence was high in patients suffering from chronic active hepatitis, hypercoagulable states, trauma or previous dissection of the porta hepatis, and splenectomy. The existence of portal vein thrombosis (23 patients) or surgical central portosystemic shunt (10 patients) was documented by preoperative Doppler sonogram or angiography (26/33), or operative findings of occluded vein (7/33). Successful thrombectomy and dismantling of portacaval shunts were achieved in most cases (24/33). Only nine patients required the placement of an interposition vein graft to the superior mesenteric vein. The intraoperative course was characterized by increased blood loss and coagulopathy, significantly higher than in patients with a patent portal vein. When compared with all liver transplants, the immediate postoperative complication rate was higher for primary nonfunction (33% versus 8%), re-exploration for intraperitoneal bleeding and hematomas, and morbid infections. Rethrombosis rate of thrombectomized veins or vein graft was low (2/33). The mortality rate was 35% in the presence of portal vein thrombosis (PVT) and 30% for portacaval shuct (PCS), both significantly higher than the 12% for other orthotopic liver transplant (OLT) patients. These results are expected to improve with better patient selection, surgical experience, and anticipation of the complex postoperative course. The authors conclude that PVT or the presence of PCS are not contraindications to orthotopic liver transplantation.     

肝移植患者术前的凝血治疗

目的探讨肝移植患者术前凝血治疗的时机、目标和方法选择.方法回顾性分析我院2002-2004年实施肝移植手术的168例病例资料.统计患者术前凝血酶原时间（PT）、凝血酶原活动度（PTA）、国际标准化比率（INR）、纤维蛋白原（FIB）、活化的部分凝血酶原时间（APTT）、血小板计数（PLT）和相应的凝血治疗措施,术中出血量、各种血制品的用量.分析术前因素与术中出血的关系,PTA分级与术中出血量、术中各种血制品用量的关系,术前血浆置换对术中出血量和术中输血制品量的影响.结果术前PTA趋于正常,术中出血量则少,对于严重凝血障碍的患者,术前应调整PTA至30%以上;术前实施血浆置换可以显著减少重症肝炎患者的术中出血量和血制品用量.结论肝移植患者术前应根据具体情况选择合适的治疗方法,尽量改善患者的凝血状态,以减少术中出血和血制品用量.     

Is “Intra–operating Room” Thromboelastometry Useful in Liver Transplantation? A Case-Control Study in 303 Patients

Coagulation monitoring during liver transplantation (LT) is, even today, fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a proven technique for controlling the various parameters that influence coagulation. However, there are no studies linking “intra–operating room” TEM (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft recipients analyzing variables associated with operative complications and long-term LT outcomes. The results showed that orTEM reduced the use of blood products in patients with Model for End-Stage Liver Disease scores of ≥21, retransplantation, and high surgical difficulty and important intraoperative bleeding. In addition, results in survival and postoperative complications were better when orTEM was used. In conclusion, we confirm that use of orTEM is associated with less use of blood products and a lower rate of complications after LT.     

Intraoperative cell salvage with autologous transfusion in liver transplantation

Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.     

难治性复发肝肿瘤的肝移植

目的探讨难治性复发肝肿瘤行肝移植的难点及围手术期处理注意事项。方法总结2003年9月至2004年9月我科施行的14例肝移植，其中难治性复发肝肿瘤9例（A组），其余5例术前未接受任何有创治疗（B组），分析两组术前治疗情况、术中探查情况、病肝游离时间、无肝期时间、术中出血、输血及止血药物使用情况、手术死亡率、术后肾上腺糖皮质激素的减撤及化疗等情况。结果A组术中病肝游离时间、无肝期时间明显较B组长，出血、输血量及止血药物的用量均明显大于B组，手术死亡2例均为A组病例。术后存活的肝癌病例均行全身化疗，肾上腺糖皮质激素于3个月内停药，至今均无瘤生存。结论难治性复发肝肿瘤的肝移植较一般肝移植手术难度大，对术者要求更高，术中监护和补充凝血因子极为重要。围手术期抗肿瘤治疗、术后尽早减撤肾上腺糖皮质激素对术后无瘤生存有积极意义。     

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.     

Successful Living Donor Liver Transplantation in Portomesenteric Thrombosis

Chronic portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to the risks involved and higher morbidity. In this report, we describe a surgical strategy for living donor liver transplant in patient with complete PVT using venovenous bypass from the inferior mesenteric vein (IMV) and then using a jump graft from the IMV for portal inflow into the graft. IMV is a potential source for portal inflow in orthotopic liver transplant.     

A review of aprotinin in orthotopic liver transplantation: can its harmful effects offset its beneficial effects?

Blood transfusion can adversely affect patient outcome and graft survival in orthotopic liver transplantation (OLT). With this respect, prophylactic aprotinin administration decreases blood loss, transfusion requirements, and the hemodynamic changes associated with graft reperfusion in patients undergoing OLT. However, data indicate limiting the use of aprotinin in OLT: (a) clinical, biological, echocardiographic, and postmortem findings recorded in patients with chronic liver disease or undergoing OLT suggest that a continuous prothrombotic state exists in these patients. Whether the inhibition of fibrinolysis associated with aprotinin therapy will expose some patients to untoward thrombosis is questionable; (b) aprotinin does not appear to alter postoperative outcome in patients undergoing OLT; (c) aprotinin decreases blood transfusion requirements only when surgery is associated with significant blood loss. However, at the present time, median transfusion requirements of 2 to 5 red blood cell units are required in OLT.     

同种异体肝脏移植手术后早期胸腹腔出血的处理

目的：总结同种异体肝脏移植手术后早期胸腹腔出血的病因、临床表现及处理对策。方法：对2000年8月－2002年1月12例同种异体肝脏移植手术后早期发生胸腹腔出血病人的资料，分析出血原因、早期临床表现、处理方法、病人的转归，探讨对此类病人的治疗对策。结果：12例中最常见的出血原因是早期腹腔手术创面的渗血，其次为肝动脉溶栓后引起的腹腔出血，出血量均较大。12例病人中6例接受了二次开腹止血手术，5例发生急性肾功能衰竭。12例病人中4例死亡，其中3例死亡原因与肾功能衰竭直接有关。结论：原位肝移植手术后早期胸腹腔出血的发生率较高，二次开腹止血要果断、准确、积极，输血和使用止、凝血药物时，应注意肾脏功能的保护。