Theo H.N. Groenland

Auxiliary Partial Liver Transplantation for End-Stage Chronic Liver Disease

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipients liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.

Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP®)

After the introduction of solvent/detergent-treated plasma (ESDEP®) in our hospital, an increased incidence of hyperfibrinolysis was observed (75% vs 29%;P = 0.005) compared with the use of fresh frozen plasma for liver transplantation. To clarify this increased incidence, intraoperative plasma samples of patients treated with fresh frozen plasma or ESDEP were analyzed in a retrospective observational study. During the anhepatic phase, plasma levels of d-dimer (6.58 vs 1.53 &mgr;g/mL;P = 0.02) and fibrinogen degradation products (60 vs 23 mg/L;P = 0.018) were significantly higher in patients treated with ESDEP. After reperfusion, differences increased to 23.5 vs 4.7 &mgr;g/mL (d-dimer, P = 0.002) and 161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of plasma received per packed red blood cell concentrate, clotting tests, and levels of individual clotting factors did not show significant differences between the groups. &agr;2-Antiplasmin levels, however, were significantly lower in patients receiving ESDEP during the anhepatic phase (0.37 vs 0.65 IU/mL;P < 0.001) and after reperfusion (0.27 vs 0.58 IU/mL;P = 0.001). Analysis of &agr;2-antiplasmin levels in ESDEP alone showed a reduction to 0.28 IU/mL (normal >0.95 IU/mL) because of the solvent/detergent process. Therapeutic consequences for the use of ESDEP in orthotopic liver transplantation are discussed in view of an increased incidence of hyperfibrinolysis caused by reduced levels of &agr;2-antiplasmin in the solvent/detergent-treated plasma.

The appearance of donor heparin in the recipient after reperfusion of a liver graft

The release of heparin has been mentioned as one of the causes of hypocoagulability after reperfusion of the liver graft. It has been ascribed to endogenous heparin released from the donor liver or to exogenous heparin in the preservation fluid that is released into the recipient after sequestration into the graft during preservation. The aim of this study was to investigate whether systemic administration of heparin to the donor before the hepatectomy contributes to the appearance of heparin in the recipient after reperfusion. We studied 20 patients undergoing an auxiliary heterotopic liver transplantation; 15 donors had received heparin immediately before circulation arrest (median 300 IU/kg body weight), but 5 had not. The thrombin time (TT),* activated partial thromboplastin time (aPTT), and heparin neutralization test were determined at several intervals during the transplantation.

Monitoring heparin and haemostasis during reconstruction of the abdominal aorta

In spite of its unpredictable kinetics, heparin is still not generally monitored during peripheral vascular surgery. To evaluate heparin levels and neutralisation, plasma heparin concentrations were measured using a chromogenic substate method during 20 consecutive operations on the Abdominal Aorta. This was combined with measuring activated partial thromboplastin time (APTT), thrombin time (ThT), prothrombin time (PT), antithrombin-III (AT-III) and fibrinogen concentration. Heparin concentration 5 min after administration and the elimination rate showed a wide variation. Using a standard dosage for all patients resulted in plasma heparin levels that are potentially too low in some patients. The APTT and ThT were found to be unsuitable for an exact calculation of heparin levels. Protamine administration based on the surgeons judgement of haemostasis was inadequate. Furthermore an intraoperative decrease of AT-III and fibrinogen was seen in eight patients. It is advisable and possible to have direct monitoring of heparin concentration during peripheral vascular surgery.

Coagulation and fibrinolysis in the first human auxiliary partial liver transplantation in rotterdam

Abstract Coagulation and fibrinolysis parameters were extensively monitored during and after a case of auxiliary partial liver transplantation (APLT). Preoperative coagulation tests demonstrated a severe liver dysfunction. Routine coagulation tests were prolonged and low levels of fibrinogen, antithrombin III (AT-III), and ( α 2 -antiplasmin ( α 2 -AP) were measured. Pro-urokinase (pro-UK), total Uk-antigen and plasminogen activator inhibitor (PAI) activity were increased (6.2; 5.4 ng/ml and 12.5 IU/ml, respectively). During transplantation no major changes in haemostasis were detected by either standard coagulation tests or thrombelastography and only a minimal increase of fibrinogen degradation products (0.6–1.0 μg/ml) was seen just before graft recirculation up till the end of the operation. PAI levels remained high during the operation and neither tissue-type plasminogen activator (t-PA) nor active urokinase (u-PA) were detectable. After APLT, graft function was reflected by normalisation of coagulation parameters and increase of AT-III and α 2 -AP to normal levels. Pro-Uk and PAI activity levels decreased after transplantation to normal values; a transient increase of t-PA activity (max. 1360 mIU/ml) was seen from the tenth to nineteenth day. It was demonstrated that a heterotopically placed partial liver allograft can provide synthesis of haemostasis factors and inhibitors and restore clearance which is adequate to reverse coagulopathy.

Antifibrinolytics in liver transplantation

Since Starzl performed the first human liver transplantation in 1963, many orthotopic liver transplantations (OLT) have been carried out worldwide. In the first 3 decades, liver transplantation was an operation with a high risk for significant blood loss. During the last decade, however, blood loss diminished gradually in most centers brought on by an improvements in anesthesiology care and surgical techniques, and better graft preservation. Still, excessive bleeding can be a major problem during liver transplantation. Mor et al and Ramos et al, among others, described a significant negative correlation between intraoperative blood transfusion requirements and hospital stay and survival. Despite better care for the liver transplant patient, important independent risk factors such as preoperative medical condition (Child-Pugh classification, United Network of Organ Sharing classification), kidney function, cold ischemia time of the donor liver, and operation time play a role in the ultimate blood loss and blood transfusion requirements during liver transplantation. Most of these factors cannot be influenced by the anesthesiologist. The seriousness of the pre-existing coagulation disorders is expressed, for example, by the Child-Pugh classification. Specific intraoperative disturbances in the hemostatic system, especially hyperfibrinolysis, also determine blood loss and transfusion requirements during liver transplantation. Knowledge of the underlying mechanism and treatment options is mandatory for anesthesiologists involved in liver transplantation. Hemostatic function is maintained by a sensitive balance between 2 proteolytic cascades: the coagulation system and the fibrinolytic system. Production and regulation of proteins involved in coagulation and fibrinolysis are controlled primarily by the liver. Yet the balance between the 2 systems can be disturbed seriously. Also, the balance between activators and inhibitors in the fibrinolytic system can be disturbed. Especially during the anhepatic and postreperfusion stages, abnormal

Heterotopic vs. orthotopic liver transplantation for chronic liver disease: A case-control comparison of short-term and long-term outcomes

Between 1986 and 1990 we performed heterotopic liver transplantation (HLT) in 17 patients with chronic liver disease. In spite of theoretical advantages and favorable short‐term results, we abandoned HLT because of doubts about the long‐term outcome and the improved results of standard orthotopic liver transplantation (OLT). There are, however, no studies comparing the long‐term survival after HLT and OLT for chronic liver disease. We performed a case‐control study of HLT vs. OLT, with long‐term patient and graft survival as the main outcome measures. Known confounders and differences in baseline characteristics between HLT and OLT patients were corrected for. At 1 year, 5 of the 17 HLT patients had died, compared with 9 of the 34 OLT patients (relative risk [RR], 1.15; 95% confidence interval [CI], 0.33–4.02; P = 0.83). After correction for confounders, the long‐term risk of graft failure (RR, 18.0; 95% CI, 1.5–223.5; P = 0.02) and of death (RR, 5.2; 95% CI, 0.8–34.8; P = 0.09) was higher after HLT than after OLT. The main causes of graft loss and death at more than 1 year after HLT were de novo malignancies and a variety of biliary complications. In conclusion, our data, from 1 of the largest single‐center series of HLTs available, showed no significant difference between HLT and OLT in 1‐year survival. However, the long‐term outcome of HLT was inferior. HLT cannot be recommended as an alternative to OLT for any of the indications we studied, even though only 1 of the late deaths was definitely related to the heterotopic technique. (Liver Transpl 2005;11:396–401.)

Liver transplantation and risk of bleeding

Purpose of reviewBlood loss in orthotopic liver transplantation has declined during the past decade. Recent papers addressed this issue and emphasized its importance, because there is a significant correlation between intraoperative blood transfusion requirements and postoperative morbidity. This review addresses changes in practice that might have led to reduced blood loss. Recent findingsMany preoperative variables that predict blood loss during orthotopic liver transplantation have been found. These vary between studies. Differences in perioperative blood loss, transfusion criteria and intraoperative management of coagulation may account for the interhospital variations in transfusion of red blood cells during orthotopic liver transplantation. Therefore, a risk index developed in one centre should not be applied without evaluation in other centres. Introduction of the piggyback technique and close monitoring of coagulation with thromboelastography have led to reduced blood transfusion requirements. Use of antifibrinolytics has shown to decrease blood loss. Recombinant factor VIIa is not indicated for treatment of coagulation abnormalities during orthotopic liver transplantation, and its use is justified only as rescue therapy. SummaryRecent changes in blood conservation practices in orthotopic liver transplantation are presented and discussed.

Double-blind placebo controlled study of the effects of etomidate-alfentanil anesthesia in electroconvulsive therapy.

The effect of etomidate and alfentanil on heart rate, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure was compared with etomidate and placebo during electroconvulsive therapy (ECT). We also studied the influence of alfentanil on seizure duration using both the cuff method and 2-lead electroencephalographs on the prevention of myoclonus induction by etomidate, on duration of apnea and on postictal agitation after ECT. We enrolled 21 consecutive patients in a prospective placebo-controlled, within patient blocked randomized study. Alfentanil significantly reduced heart rate, diastolic arterial pressure, and mean arterial pressure both before and after the stimulus. The increase in these variables during the convulsion was not affected, compared with placebo. Alfentanil had no effect on seizure duration. However, apnea duration was prolonged during the alfentanil sessions as compared with placebo (73 seconds). Alfentanil did not significantly reduce the occurrence of myoclonus after etomidate as compared with placebo, nor did postictal agitation after ECT appear more often with alfentanil. Alfentanil could be useful to reduce tachycardia and hypertension during ECT in high-risk patients without effects on seizure duration. Alfentanil itself has no proconvulsive effect in combination with etomidate.

A comparative study on changes in hemostasis in orthotopic and auxiliary liver transplantation in pigs

Abstract. We compared blood loss and hemostasis in pigs which had undergone either orthotopic liver transplantation (OLT) (group A, n= 12) or auxiliary heterotopic partial liver transplantation (APLT) (group B, n= 11). Blood samples were taken at regular intervals during and after the operations. In both groups, nine animals survived longer than 24 h and data from these animals were used for analysis. Median (range) intraoperative blood loss was 825 ml (250–1500 ml) in OLT and 425 ml (300–750) in APLT (P < 0.01). Routine clotting times, as the activated partial thromboplastin time, prothrombin time and thrombin time, snowed no major intraoperative changes in either group. Fibrinogen levels decreased in both groups, but no significant difference was found between the two groups. The only significant difference between group A and B was a more sustained increase in fibrinolytic activity after graft recirculation in group A. Postoperatively, restoration of fibrinogen, antithrombin‐III and α2‐antiplasmin levels was slightly faster in group B, resulting in significantly higher levels during the first day. We conclude that, in this animal model, APLT is associated with significantly lower blood loss and less severe fibrinolytic activity, than OLT. This difference might result from the lack of an anhepatic period and the reduced surgical trauma in auxiliary heterotopic liver transplantation.