Thromboelastography-Guided Transfusion Decreases Intraoperative Blood Transfusion During Orthotopic Liver Transplantation: Randomized Clinical Trial

Objective

To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery.

Material and Methods

Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group.

Results

In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival.

Conclusion

Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.     

Validation of McCluskey Index for Massive Blood Transfusion Prediction in Liver Transplantation

BackgroundThe McCluskey index has been used as a tool to predict massive bleeding (>6 red blood cells units) during orthotropic liver transplantation. The objective of this study is to verify its efficacy at our institution.Materials and MethodsBetween May 1998 and December 2017, we performed 1216 orthotropic liver transplantations, of which 1016 had sufficient data registered with respect to hemoderivative transfusion. We divided these patients into groups based on the original study of McCluskey. This study was approved by the ethical committee of our Institution and was performed in accordance with the Declaration of Helsinki.ResultsThe mean Model for End-Stage Liver Disease score in the 4 groups was 7.5 (range, 7-8) for low risk; 13 (range, 3-32) for medium risk, 17 (range, 8-41) for high risk, and 25 (range, 11-36) for very high risk (P < .001). No significant differences were observed regarding body mass index or hospital stay. No differences have been found in the number of suboptimal donors among the groups. With respect to hemoderivative transfusions, we observed the following for red blood cells: 7 (range, 6-8) units for low risk; 5.5 (range, 0-74) for medium risk; 7 (range, 0-73) for high risk, and 12 (range, 5-30) for very high risk (P < .001) and transfusion of plasma: 12 (range, 10-15) units for low risk; 11 (range, 0-89) for medium risk; 14 (range, 0-76) for high risk, and 13 (range, 3-30) for very high risk (P = .001).ConclusionsThe McCluskey index is a good indicator of the risk of hemorrhage and hence the necessity of transfusion.     

原位肝移植患者术时止凝血变化的初步临床研究

研究原位肝移植术中的出血与全身止血凝血改变的关系。方法:本文对一例肝豆状核变性患者原位肝移植手术中凝血、抗凝及纤溶系统的功能进行了系统的观察。结果:发现在移植术中凝血抗凝系统的功能逐渐降低,在无肝期及重新灌注早期达最低点,随后逐渐恢复,而纤溶系统的功能随手术的进行而逐步增强,在无肝期及重新灌注期达最高峰。结论:原位肝移植术中的出血是综合因素引起的,手术各阶段的出凝血变化有其本身的特点。     

Predictive Variables Affecting Transfusion Requirements in Orthotopic Liver Transplantation

Introduction and Aims

Adult orthotopic liver transplantation (OLT) is associated with considerable blood product requirements. The aim of this study was to assess the ability of preoperative information to predict intraoperative red blood cell (RBC) transfusion requirements among adult liver recipients.

Methods

Preoperative variables with previously demonstrated relationships to intraoperative RBC transfusion were identified from the literature: sex, age, pathology, prothrombin time (PT), factor V, hemoglobin (Hb), and platelet count (plt). These variables were then retrospectively collected from 758 consecutive adult patients undergoing OLT from 1997 to 2007. Relationships between these variables and intraoperative blood transfusion requirements were examined by both univariate analysis and multiple linear regression analysis.

Results

Univariate analysis confirmed significant associations between RBC transfusion and PT, factor V, Hb, Plt, pathology, and age (P values all < .001). However, stepwise backward multivariate analysis excluded variables Plt and factor V from the multiple regression linear model. The variables included in the final predictive model were PT, Hb, age, and pathology. Patients suffering from liver carcinoma required more blood products than those suffering from other pathologies. Yet, the overall predictive power of the final model was limited (R² = .308; adjusted R² = .30).

Conclusion

Preoperative variables have limited predictive power for intraoperative RBC transfusion requirements even when significant statistical associations exist, identifying only a small portion of the observed total transfusion variability. Preoperative PT, Hb, age, and liver pathology seem to be the most significant predictive factors but other factors like severity of liver disease, surgical technique, medical experience in liver transplantation, and other noncontrollable human variables may play important roles to determine the final transfusion requirements.     

Re-evaluating Blood Markers as Predictors of Outcome in Multivisceral and Intestinal Transplantation

BackgroundMultivisceral transplant (MVTx) and isolated intestinal transplant (ITx) are complex surgical procedures. The subsequent proinflammatory state in the immediate postoperative period makes interpretation of blood markers difficult.MethodWe aimed to establish the course of various blood markers after MVTx/ITx, and to evaluate their use as diagnostic markers of complications. This was a single center prospective cohort. We analyzed blood markers collected preoperatively, on alternate days for the first postoperative week, and then weekly for 4 weeks. This study was in compliance with The Declaration of Helsinki.ResultsOver a 16-month period (July 2017-October 2018), 20 subjects aged 2 to 67 years with a median age of 24.5 years received MVTx/ITx. Twelve recipients (60%) had an infection. Neutrophil lymphocyte count ratio (NLCR) was higher than established upper limits of normal, regardless of infection status. NLCR and white blood cell count were useful to identify infected MVTx/ITx recipients, with P values <.05 for 2 and 1 of 7 time points post transplant, respectively. Higher preoperative eosinophil% predicted future acute cellular rejection (P value .023).ConclusionsThis is the first study to extensively track the course of blood markers post MVTx/ITx and identified NLCR and white blood cell count as potential diagnostic blood markers of infection.     

Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation

Background: Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.

Methods: Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.

Results: Patients receiving transexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving transexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving transexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.     

Predicting Fluid Responsiveness in Patients Undergoing Orthotopic Liver Transplantation: Effects on Intraoperative Blood Transfusion and Postoperative Complications

ObjectiveTo test the hypothesis that the restrictive volume therapy decreases blood transfusion requirement during liver orthotopic transplantation (OLT) without increasing acute renal complications and hospital length stay.Material and MethodsWe conducted a retrospective cohort study (n = 89), randomized into 2 groups: A (liberal fluid strategy) and B (restrictive therapy). We analyzed packed red blood cells (PRBCs) units, transfused units of fresh frozen plasma (FFP), colloids, crystalloids, perioperative renal function, and hospital length stay. For comparison of proportions, we used the χ² test and Student t test to compare means (parametric). A logistic regression model was constructed to evaluate the association of all these variables with probability of PRBCs transfusion.ResultsIn group A, 88.4% of patients required intraoperative transfusion of PRBCs, with a mean of 8.5 ± 7.02 IU, compared with 82.2% in group B with a mean of 5.02 ± 4.5 IU (P < .001). We also found differences in the following variables: FFP transfusion rate was 95.3% (mean, 15.02 ± 8.2 IU) in group A and 75.6% (mean, 8.7 ± 6.04 IU) in B (P < .001). The amount of colloid was 50% (mean, 692.8 ± 409.6 mL) in group A and 28.9% (mean, 607.6 ± 316.7 mL) in B (P = .032). Platelet concentrates transfusion was 79.1% (mean, 2.05 ± 1.1 IU) in group A and 51.1% (mean, 2.0 ± 1.08 IU) in B (P = .014). As an important effect of restrictive fluid therapy, renal function was assessed; no differences in mean creatinine or acute renal failure in the immediate postoperative period were observed. There was no difference in hospital length stay. Logistic regression modelling identified 3 variables as significant predictors of transfusion: Fluid administration policy, preoperative hemoglobin and FFP units transfused. Furthermore, an increase of preoperative hemoglobin is associated with a lesser probability of transfusion.ConclusionsThese results show that fluid restriction management for OLT decreased blood products requirements, especially FFP. This could suggest that liberal fluid management may aggravate, rather than prevent, bleeding in these patients. We did observed any no difference in failure of renal function.     

大鼠原位肝移植动物模型制作要点

目的建立稳定的大鼠原位肝移植模型。方法参照Kamada等法建立大鼠原位肝移植模型，经门静脉灌注肝脏，改进肝上下腔静脉吻合法为单线连续缝合法。结果210只大鼠原位肝移植24h存活率为91．0％(191／210)，平均无肝期17min，1周生存率为85．2％(179／210)。结论改进大鼠原位肝移植肝上下腔静脉吻合法，可缩短受体无肝期，减少手术并发症发生率，并能提高原位肝移植大鼠的生存率。     

Correlation Between Blood Transfusion and Blood Glucose Levels in Adult Living Donor Liver Transplantation

Background

To evaluate the effect of dextrose contained in banked blood products on the changes of blood glucose levels in adult living donor liver transplantation patients retrospectively.

原位肝移植手术的麻醉管理

肝移植术是治疗晚期肝病最有效的措施。同种异体原位肝移植术可分为无肝前期（从切皮开始至阻断门静脉、下腔静脉为止）,无肝期（从门静脉、下腔静脉阻断开始至开放门静脉或下腔静脉为止）,及新肝期（即开放门静脉或下腔静脉,使供肝得到血液灌注）。不同时期的血流动力学及内环境变化部各有特点。根据本院多年的实践,我们对此类手术的麻醉管理宗旨是：提前干预、良性循环、目标管理,维持内稳态及重要器官功能稳定。     

External Biliary Fistula in Orthotopic Liver Transplantation

During orthotopic liver transplantation (OLT), various situations may occur in which biliary reconstruction is neither technically feasible nor recommended. One bridge to a delayed anastomosis can be an external biliary fistula (EBF). This procedure allows the surgeon to execute hemostatic maneuvers, such as abdominal packing; therefore, biliary reconstruction can be subsequently performed in a bloodless operative field without edematous tissues. EBF can be made by placing in the donor biliary tract a cannula that is fixed to the bile duct using 2-0 silk ties and secured outside the abdominal wall. The biliary anastomosis will be performed within 2 days after the OLT. The aim of this study was to examine the safety of EBF in terms of the incidence of biliary complications compared with a direct anastomosis. Among 1634 adult OLTs performed in 17 years in our center, 1322 were carried out with termino-terminal hepaticocholedochostomy (HC-TT); two with side-to-side hepaticocholedochostomy; 208 with hepaticojejunostomy (HJ); 31 with EBF and delayed HC-TT, and 71 with EBF and delayed HJ. Biliary complication rates in the EBF group were 24.5%, including 23.9% in the delayed HJ and 25.8% in the delayed HC-TT. Biliary complication incidence among all OLTs was 24.6% (P = NS). No complications related to the procedure were observed. Therefore, EBF is a safe technique without a higher biliary complication rate. It may be useful when a direct biliary anastomosis is dangerous.     

Metabolic Alkalosis After Orthotopic Liver Transplantation

To ascertain the etiology of metabolic alkalosis (MA) following orthotopic liver transplantation (OLT) the records of patients with 123 consecutive OLTs from 1995 to 2000 were reviewed. Metabolic alkalosis occurred in 51.2% of patients. Patients with MA had a larger fluid deficit (-3991 +/- 4324 vs. -1018 +/- 4863, p < 0.05), cumulative furosemide dose (406 +/- 356 vs. 243 +/- 189, p < 0.02), and citrate load from blood transfusions (9164 +/- 4870 vs. 7809 +/- 3967, p < 0.05). There was no difference in serum lactate concentration (3.15 +/- 1.63 vs. 3.11 +/- 1.91) in patients with and without MA. The duration of ICU stay was longer in patients with MA (14.9 +/- 15.3 vs. 5.3 +/- 3.9 days, p < 0.004). Treatment of severe MA in 19 (15.4%) patients consisted of 0.1 N hydrochloric acid and/or acetazolamide. Hypokalemia and hypomagnesemia occurred in 37.4% and 59.3% of patients, respectively. In conclusion, MA is a common post-OLT complication that is associated with a longer ICU stay. Diuretic-induced volume depletion, the citrate load from blood transfusions, hypokalemia, and hypomagnesemia contribute to the pathogenesis of MA in OLT.     

Renal Dysfunction After Orthotopic Liver Transplantation

Background

Identification of risk factors of acute renal failure (ARF) after orthotopic liver transplantation (OLT) may avoid the development and attenuate the impact on patient outcome. Therefore, the incidence and risk factors of ARF after OLT at Siriraj Hospital were analyzed.

Methods

The study was retrospectively analyzed from the OLT patients at the Siriraj Hospital between January 2002 and December 2009. ARF was defined as an increased in serum creatinine level more than 1.5 times within the first week postoperation compared with the preoperative level.

Results

A total of 81 liver transplant patients were analyzed. The mean age was 52.45 years (range, 22 to 71) and there were 25 women (30.86%) and 56 men (69.14%). Indications for OLT were end-stage liver cirrhosis (n = 43, 53.09%), hepatocellular carcinoma (n = 36, 44.44%), and fulminant hepatic failure (n = 2, 2.47%). Fifty-eight patients (71.60%) developed ARF, and the perioperative mortality of these was 18.97%. The univariate analysis identified the presence of preoperative coagulopathy, prolonged intraoperative hypotension, more blood loss, and postoperative hypotension as the risk factors of ARF. By the multivariate analysis, prolonged intraoperative hypotension more than 30 minutes and presence of postoperative hypotension were the independent risk factors of ARF. During the intraoperative and postoperative periods, ARF group required more blood and blood components transfusion, longer intensive care unit stay, and higher in-hospital mortality. Seven patients (12.07%) in the ARF group required postoperative renal replacement therapy. Four patients (9.52%) developed chronic renal failure, and one of them required long-term hemodialysis.

Conclusions

ARF was a common complication after OLT, which caused increased morbidity and mortality. Although some patients required dialysis, most of them recovered normal renal function. Prolonged intraoperative hypotension and presence of postoperative hypotension were the independent risk factors of ARF after OLT.     

Outcomes of Orthotopic Liver Transplantation in Non-malignant End-stage Liver Diseases

Background

Orthotopic liver transplantation (OLT) is an effective treatment for patients who have end-stage liver disease. The aim of this study is to compare outcomes of OLT in fulminant hepatic failure (FHF) and non-fulminant hepatic failure (non-FHF) patients.

Methods

A retrospective review of adult patients who underwent OLT for non-malignant end-stage liver diseases between 2002 and 2011 at Siriraj Hospital was performed. All explanted liver histopathology results were reviewed. The clinical factors and overall results of OLT were analyzed.

Results

Of the 137 patients, 72 patients had non-malignant diagnoses. Eleven patients were diagnosed with FHF, whereas 61 patients were in the non-FHF group. The most common indication for liver transplantation was chronic viral hepatitis. One- and 5-year survival rates (95% confidence interval) in the FHF group were 91% (51%–99%) and 91% (51%–99%), respectively, whereas those in the non-FHF group were 74% (61%–83%) and 66% (52%–77%), respectively. Multivariate cox regression analysis revealed no statistically significant difference of survival between both groups (P = .34).

Conclusions

The post-OLT outcomes in non-malignant patients were comparable between FHF and non-FHF groups in terms of survival. OLT remains the only therapeutic option for the FHF patients.     

背驮式原位肝移植的手术配合

回顾1例乙型肝炎肝硬化病人(失代偿期)行背驮式原位肝脏移植的手术配合过程.提示术前做好病人心理护理、器械准备,熟悉手术步骤、确定最佳配合程序,量化分类管理器械物品等,是确保手术顺利进行的关键.     

治疗原发性肝癌行肝移植的相关问题

肝移植是20世纪60年代后期兴起的重大新技术，已成为终末期肝病最有效的临床治疗手段。国内自20世纪70年代后期开展此技术，因为各种原因至90年代后期方进入成熟阶段，迄今全国肝移植例数已逾4000例。原发性肝癌作为终末期肝病，一直是肝移植的重要适应证之一，但由于早年肝癌肝移植的结果并不理想，患者多在2年内肿瘤复发死亡，因而国外不少中心已经不把晚期肝癌作为手术适应证，而仅把小肝癌作为肝移植受者。国内在肝移植早期，多以晚期肝癌为主要指征，近年由于肝移植手术技术的成熟，亦逐渐趋于以小肝癌为主要指征。但由于我国肝癌每年有11万多人死于此病，占全世界肝癌死亡人数的53％，临床     

Predictors of Systolic Heart Failure and Mortality Following Orthotopic Liver Transplantation: a Single-Center Cohort

ObjectivesThe purpose of this study was to identify risk factors that may predict heart failure with reduced ejection fraction (HFrEF) following orthotopic liver transplantation (OLT) and associated mortality.BackgroundHFrEF following OLT is a poorly understood phenomenon, reported in 3% to 7% of transplanted patients.MethodsThis is a retrospective analysis of 176 consecutive patients who underwent OLT from 2010 to 2017. Multivariate logistic regression was used to identify associations between cardiovascular risk factors and perioperative variables with post-OLT HFrEF, defined as reduction in left ventricular ejection fraction of at least 10% and left ventricular ejection fraction less than or equal to 40% with acute heart failure symptoms. Multivariate cox proportional hazards regression (with inverse probability weighting by propensity scores) was used to evaluate effects of HFrEF on 1-year mortality.ResultsOf the176 patients, 14% developed HFrEF with a median of 5 days. History of heart failure (OR 10.99, 2.15–56.09; P = .04) and intraoperative transfusion of greater than 11 units of packed red blood cells (OR 3.377, 1.025–11.13; P = .045) were associated with increased incidence of HFrEF. Pre-transplant hemoglobin greater than 8.5 g/dL (OR 0.252, CI 0.0954- 0.665; P = .05) was protective against HFrEF. Thirty-three percent of HFrEF group died within 1 year (HR 7.36, 2.57–21.12; P < .001).ConclusionsThe incidence of acute HFrEF post-OLT is 14% and is associated with a 7-fold increase in 1-year mortality. Cirrhotic cardiomyopathy and stress-induced cardiomyopathy maybe the underlying mechanisms. Our study identified risk factors associated with post-OLT HFrEF and should provide additional guidance for risk stratification of patients undergoing OLT.     

同种原位肝移植肝脉重建技巧

目的：探讨和总结同种原位肝移植术中肝动脉重建技术。方法：回顾性分析我院近一年来所施行18例原位肝移植术中肝动脉重建方式和技巧。结果15例行供受体肝固有动脉端端吻合,2例供体肝总动脉与受体肝固有动脉吻合,1例供体总动脉与受体脾动脉吻合。术后彩色色普勒超声监测显示肝动脉血流通畅,均未发现有血栓菜成或肝动脉狭窄,全部病例未发生胆道并发症。结论：成功的肝动脉重建技术防止肝移植术后肝动脉血栓形成或肝动脉狭窄的关键。     

Alcohol Abstinence and Orthotopic Liver Transplantation in Alcoholic Liver Cirrhosis

Patients diagnosed with acute alcoholic hepatitis (AAH) are routinely managed medically and not considered suitable for orthotopic liver transplantation (OLT). The eligibility for OLT in these patients has been questioned due to the social stigma associated with alcohol abuse, based on the fact that AAH is “self-induced” with an unacceptably high recidivism rate. Many centers in Europe and the United States require abstinence periods between 6 and 12 months before OLT listing. AAH outcomes in the literature are poor, in particular due to patient noncompliance during the immediate 3 months preceeding OLT. Between January 1997 and December 2007, 246 patients were evaluated in our center for alcoholic liver disease: 133 (54%) were listed for OLT (I-OLT), including 110 (83%) who underwent transplantation and 8 (6%) still listed as well as 15 (11%) removed from consideration. One hundred thirteen (46%) patients had no indication for OLT (NO I-OLT), including 18 (16%) who died, 81 (71%) still monitored, and 14 (12%) lost to follow-up. Patient survival rates post-OLT were 79%, 74%, 68%, and 64% at 1, 3, 5, and 10 years, respectively. Explant (native liver) pathologic examination revealed AAH in 8 (7.2%) patients who underwent OLT. In this group, patient survival and the post-OLT recidivism rate were statistically identical to the overall group of transplant recipients.