Period Of Orthotopic Liver Transplantation Research Articles

Thromboelastometry analysis of the heparin-like effect in the intra-operative period of orthotopic liver transplantation: An observational clinical trial

Introduction: Orthotopic liver transplant (OLT) can be followed by significant coagulopathy and the heparin-like effect (HLE). However, as the HLE may lead to important changes in blood coagulation, the objective of this study was to assess the prevalence of HLE in a cohort of patients undergoing liver transplantation. Materials and methods: This was a observational study including 50 patients ≥ 18 years of age who were submitted to OLT and monitored using ROTEM® delta, including 36 patients with altered INTEM coagulation time (CT) and 14 patients with normal INTEM CT. Samples were collected during the procedure to analyse the HLE. Results: Mild to moderate HLE was observed in 34% (17/50) of patients during surgery. Severe HLE was observed 10% (5/50) during surgery. Total 1-year survival was 80% (40/50) and mortality, 20% (10/50) (4% (2/5) with severe HLE in at NP; 5.9% (1/17) with mild/ moderate HLE in OS and in at NP, respectively, and in 11.8% (2/17) at AP, died 1-month postoperative). The transfusion of patients with severe HLE was (median [IQR]: red blood cells 3 [0.5-9.2] units), and those with mild/moderate HLE was (median [IQR]: red blood cells 1 [0.0 -2.0] and cryoprecipitate 10 [9.0-15.0] units). In the INTEM CT analysis, the average neohepatic phase (327.9 ± 161.1 s) was significantly prolonged when compared to OS (266.5 ± 134.4 s) and AP (253.02 ± 75.4 s); P = 0.013, respectively. Conclusion: The prevalence of HLE was considerable in neohepatic phase. In severe HLE, a high risk of mortality was identified in the neohepatic phase and a higher frequency of transfusion of red blood cells regardless of the surgical phase.

Evaluation of the perioperative period of orthotopic liver transplantation with veno-venous bypass and without it

Orthotopic liver transplantation (OLT) is the only treatment for many patients with end-stage chronic liver diseases. In patients with complete vena cava inferior (VCI) cross-clamping veno-venous bypass (VVB) is either used or not depending on the indications. The case management of the patient with complete VCI cross-clamping depends on the initial state of the recipient and the transplant team’s opinion.Aim. To compare the perioperative period of OLT depending on the method to conduct the main stage of the surgery: with the use of veno-venous bypass and without it with complete VCI cross-clamping.Materials and methods. In Group 1 (n = 20), OLT was performed without VVB with complete VCI cross-clamping; in Group 2 (n = 26), the surgery was conducted with veno-venous bypass. Patients in both groups were similar in age (46.15 ± 10.22 and 47.3 ± 9.29, respectively), in severity of the disease: Child-Pugh (10.15 ± 1.42 and 10.19 ± 2.45), MELD 16.47 ± 4.41 and 15.8 ± 4.95).Results. We determined and evaluated hemodynamic parameters, oxygen transport, the quantitative and qualitative infusion composition, urine output, characteristics of the postoperative period.Conclusion. Our data show that changes in hemodynamic and oxygen transport are associated with reperfusion syndrome and do not depend on the method of transplantation. At the same time, it reduces the blood loss, time of surgery, and the duration of postoperative mechanical ventilation and stay in the ICU after liver transplantation in patients without veno-venous bypass.

Dependence of platelet function on underlying liver disease in orthotopic liver transplantation

Objective The purpose of the present study was to explore the platelet function during the perioperative period of orthotopic liver transplantation (OLT) due to the underlying liver disease. Methods The blood coagulation parameters, platelet surface markers and the determination of platelet aggregation were analyzed in 34 patients who underwent OLT. Blood samples were drawn preoperatively, anhepatic, 10 min and 1 hour after reperfusion, 1 day, 3 and 7 days postoperatively. Conventional coagulation screens, thrombopoietin (TPO) serum levels, P-selectin, GPIIb/IIIa and GPIb binding sites on the surface of platelets as evaluated by flow cytometry and platelet aggregation response were measured. Results Coagulation factors, maximum aggregation and rate of aggregation were significantly different before transplantation due to the underlying liver disease. Further we found a markedly depressed GPIIb/IIIa and P-selectin expression and a reduced rate of aggregation in all patients throughout the study. In contrast maximum aggregation of platelets was restored on the third day after reperfusion without intergroup differences and almost comparable to healthy controls. An inverse correlation was found between peripheral platelet count pre-transplantation and peak TPO concentrations one weak post-transplantation. Conclusions In the entire process of OLT, coagulation factors, maximum aggregation and rate of platelet aggregation depend on the surgical phases during transplantation and on the underlying liver disease. The data obtained in this study might contribute to a better understanding of the pathophysiology and assessment of bleeding risk in OLT.

Changes in plasma S-100 beta and neuron-specific enolase in peri-operative period of orthotopic liver transplantation and its relationship with encephalopathy after operation

To observe the changes in plasma S-100 beta and neuron-specific enolase (NSE) and to study their relationship with encephalopathy after orthotopic liver transplantation (OLT). Thirty patients without neurological disease undergoing OLT were studied. Plasma S-100 beta and NSE were examined at three time points: after induction of anesthesia (T1), at the end of operation (T2) and 24 hours after reperfusion of the transplant (T3). The difference of plasma S-100 beta and NSE between encephalopathy group and non-encephalopathy group was analyzed. Eleven patients were complicated with encephalopathy after OLT. In 30 patients, S-100 beta at T2 [(3.715+/-1.523) microg/L] was higher than that at T1 [(1.478+/-0.809) microg/L, P<0.01]; S-100 beta at T3 [(1.765+/-0.894) microg/L] decreased to normal level (T1). NSE at T2 [(26.684+/-7.973) microg/L] was higher than that at T1 [(14.012+/-4.612) microg/L, P<0.01]. At T3, the level of plasma NSE [(18.105+/-7.345) microg/L] was decreased, but higher than that at T1. Plasma S-100 beta and NSE in encephalopathy group (11 cases) and non-encephalopathy group (19 cases) showed the same tendency of change as all of the patients. Plasma S-100 beta at T3 in encephalopathy group [(2.007+/-0.854)microg/L] was higher than that in non-encephalopathy group [(1.468+/-0.903) microg/L, P<0.05], and it was correlated with the presence of encephalopathy (r=0.385, P=0.039), but not at T1 and T2. Plasma NSE at three time points showed no relationship to the presence of encephalopathy. The increase in plasma S-100 beta and NSE during OLT indicates the occurrence of damage to the brain. But plasma S-100 beta and NSE cannot predict encephalopathy after OLT.

Hemostatic variation during perioperative period of orthotopic liver transplantation without venovenous bypass

ObjectivesTo measure the variations of different parameters in the hemostatic system and to analyze their roles in the development of hemostatic disorder in patients with orthotopic liver transplantation (OLT) procedures routinely performed without venovenous bypass. MethodsThe blood coagulation and fibrinolysis parameters were analyzed in 20 patients who underwent liver transplantation. Blood samples were drawn from the radial artery at serial time points during perioperative period. Prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, vWF, antithrombin III (AT-III), protein C (PC), tissue factor pathway inhibitor (TFPI), plasminogen (PLG), α2-antiplasmin (α2-AP), and D-dimer were analyzed. ResultsHemoglobin, platelet count, and fibrinogen were significantly decreased during anhepatic and reperfusion phases compared with preoperative values (P<0.01). VWF activity only showed significant increase during the reperfusion 60 min compared with preoperative value (P<0.05). PT, INR, aPTT, and TT were prolonged progressively, and they reached the maximum values at the beginning reperfusion 15 min compared with preoperative values (P<0.01). The AT-III, PC, TFPI, PLG, and α2-AP levels were decreased significantly and D-dimer level was elevated significantly throughout the intraoperative period. In the postoperative period, these parameters progressively returned to preoperative levels. ConclusionsIn the entire process of OLT operation, coagulation defects, hyperfibrinolysis and platelet numbers decrease could develop hemostatic disorder. The data obtained in this study might contribute to a better understanding of the pathophysiology and assessment of bleeding risk in the OLT.

Study on coagulation change by pretreatment during perianesthetic period of orthotopic liver transplantation

目的 探讨同种异体原位肝移植围麻醉期预处理对凝血功能的影响.方法 18例ASA Ⅲ-Ⅳ级因终末期肝病而行原位肝移植的患者,术前及麻醉诱导后进行预处理,并在不同时期采血检测凝血酶原时间(PT)、活化的部分凝血酶原时间(APTT)、纤维蛋白原(FIB)、D-二聚体(D-dimer)、血小板(PLT)及血清钙离子浓度并进行动态观察.同时应用SONOCLOT凝血及血小板功能分析仪对凝血与血小板功能进行定性分析,记录术中出血量及输血量.结果 术中PT、APTT逐渐延长,门脉开放初期达到高峰,新肝再灌注后PT、APTT又逐渐缩短;D-dimer总体上呈现逐渐增加的趋势,再灌注后逐渐下降,但始终高于术前水平.大多数病人全血凝固时间(ACT)在手术开始前即开始延长,新肝期最为突出,新肝后期逐渐缩短.凝结速率(CR)新肝期明显减慢,以后逐渐恢复.血小板功能(PF)在新肝初期最差,到术毕明显恢复.结论 肝移植术中的早期预处理,并适时个体化调整有利于改善凝血功能障碍,维持术中的相对稳定,减少术中术后出血和输血。

Renal Function in Patients with Orthotopic Liver Transplantation

Due to multiple reasons, acute renal failure (ARF) commonly develops in the early postoperative period of orthotopic liver transplantation (OLT) recipients. The records of OLT recipients between 1999 and 2004 were evaluated. Age, gender, primary disease, history of diabetes, immunosuppressive drugs, pre- and postoperative renal function tests, serum electrolytes, dialysis, liver functions tests, and renal function tests in follow-up period were noted. We followed 16 patients with OLT in our center. ARF developed in 8 patients. Dialysis was performed in only 2 patients, and other patients with ARF were managed with conservative measures. Hypertensive crisis and cerebrovascular stroke developed in 1 diabetic hypertensive patient.

Risk factors for postoperative acute renal failure at a new orthotopic liver transplantation program

ACUTE RENAL failure (ARF) is a frequently observed complication during the postoperative period of orthotopic liver transplantation (OLT) when the rate of reported renal failure varies according to the postoperative period and serum creatinine levels considered. Although some patients require dialysis, most recover normal renal function. ARF is one of the most frequent causes of morbidity and mortality after OLT, and Nuno et al indicate a 7.8 higher probability of mortality in patients who have undergone ARF, and 15 times higher than that for those patients who required dialysis. Various factors are outstanding in the preoperative and postoperative periods, as well as during surgery, which could explain the occurrence of ARF. Preoperative factors include: diabetes mellitus, a history of ascites and encephalopathy, and previous kidney lesion. Crawford et al described the occurrence of glomerular lesions as universal to all patients with end-stage liver disease. During surgery, hypovolemia, the number of packed red blood cell (PRBC) units required and the time of total ischemia are described as associated factors. Several series correlate the use of nephrotoxic drugs, such as cyclosporine A (CyA), as a factor which could contribute to renal lesions. However, this may also be the result of complications such as sepsis and multiorgan failure. The purpose of this study is to assess the factors associated with the development of renal failure during the immediate postoperative period of an initial OLT program.

Infection and associated risk factors in the immediate postoperative period of pediatric liver transplantation: A study of 176 transplants

Objective. To describe the characteristics of infections occurring in the immediate postoperative period of orthotopic liver transplantation (OLT) in children in a pediatric intensive care unit (PICU) and the associated risk factors. Design. Retrospective cohort study.Setting. Multidisciplinary 16‐bed pediatric intensive care unit in a tertiary university hospital. Patients. One hundred and thirty‐three pediatric patients (range 6 M to 22 yr) who underwent 176 liver transplantations and were admitted to the pediatric intensive care unit for at least 48 h.Results. A total of 180 infectious episodes (IE) occurred in 78 (59%) patients who underwent 96 (54.5%) liver transplantations (1.35 IE/patient; 1.02 IE/transplantation). The mean stay was 15.4±1.1 d (mean ±SD) and 22 patients died in the pediatric intensive care unit. One hundred and thiryt‐one IE (72.8%) were bacterial, 31 (17.2%) fungal, and 14 (7.8%) mixed bacterial and fungal. 39% of the IE appeared in the first postoperative week and 27% in the second postoperative week. The most common sites of infection were abdomen (48.3%) and blood stream (26.1%). Bacteria, alone or with fungi, were present in 145 IE (1.1 IE/patient). Gram‐positive aerobic bacteria (63%) predominated over gram‐negative bacteria (54%) and fungi. Fungi were present in 45 IE; 53.4% of the infections occurred in lung (73% yeasts). The risk factors for infection that were identified were related with younger age, lower body weight, longer cold ischemia time, partial graft, and the volume of packed red blood cell transfusions. Infected patients had more postoperative complications and longer stay in the PICU (21±16 vs. 8±6 d), but no increase in mortality. The risk of infection increased 2.38 times with partial grafts and 1.1 times with each intraoperative transfusion of 20 ml/kg of packed red blood cells (RBC). Conclusions. Infection in the immediate postoperative period of pediatric OLT was related with a high morbidity but was not related significantly with increased mortality. The main risk factors for infection in the postoperative period of OLT were related essentially with small recipient size and the inherent complexity of the operation. Routine oropharyngeal decontamination is recommended, as well as early administration of oral nystatin in preoperative intestinal decontamination. The risk of infection increased 2.38 times with partial grafts and 1.1 times with the transfusion of every 20 ml of packed RBC.

Lactate blood levels in the perioperative period of orthotopic liver transplantation.

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P < or = 0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/l in 47 of 49 patients from group A, while they plateaued above 4 mmol/l in all patients from group B. Group A patients had lower alanine aminotransferase levels (P < or = 0.001), higher prothrombin activity, (P < or = 0.01), and greater bile flow (P < or = 0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant

To evaluate the effects of nicardipine on hepatic blood flow in patients with recent liver transplants. Secondly, to evaluate the liver extraction of nicardipine in order to determine the influence of liver transplantation on its disposition. Prospective self-controlled clinical study. University hospital intensive care unit. Eight patients in the early postoperative period of orthotopic liver transplantation. Patients were given 5 mg of i.v. nicardipine. Systemic and splanchnic haemodynamic and metabolic parameters were measured before nicardipine administration (T0) and at 5 min (T1), 30 min (T2), and 120 min (T3) after administration. A catheter was inserted into a hepatic vein to determine the total hepatic blood flow (HBF) and the hepatic extraction coefficient of nicardipine. Nicardipine caused no significant changes in HBF, oxygen delivery, oxygen uptake, hepatic venous oxygen saturation, or the hepatic venous partial pressure of oxygen. Likewise, neither blood lactate concentrations nor arterial and hepatic venous lactate-pyruvate ratios were modified by nicardipine. The hepatic extraction coefficient of nicardipine was approximately 0.70 in the first 3 min after complete infusion, then decreased and remained stable at approximately 0.50, showing a non-linear first-pass metabolism pattern. Nicardipine administration after liver transplantation appears to have no deleterious effects on HBF. Nicardipine can be classified as a drug of intermediate hepatic extraction coefficient, whose elimination partly depends on hepatic enzyme activity.

Effect of type of lipid on substrate oxidation rates in the postoperative period of orthotopic liver transplantation

Effect of type of lipid on substrate oxidation rates in the postoperative period of orthotopic liver transplantation

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.

Mechanisms of hypertension during and after orthotopic liver transplantation in children

The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.