Different aprotinin applications influencing hemostatic changes in orthotopic liver transplantation.

The effect of different aprotinin applications on hemostatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective, open, and randomized study. From November 1989 to June 1990, 13 patients received aprotinin as a bolus of 0.5 Mill. Kallikrein inactivator units (KIU) on three occasions in the course of an OLT, whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by thrombelastography, were significantly lower in the infusion group. Tissue-type plasminogen activator (t-PA) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group. Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so. However, the use of packed red blood cells was significantly lower in the postoperative period, whereas there was no significant difference in fresh frozen plasma requirements between the two groups. All 23 patients have survived, and only one woman of each group required retransplantation due to severe host-versus-graft reactions. Furthermore, we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group. Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT.

Mediators of leukocyte activation play a role in disseminated intravascular coagulation during orthotopic liver transplantation.

Leukocytes play an important role in the development of disseminated intravascular coagulation (DIC). In the reperfusion phase of OLT a DIC-like situation has been described and has been held responsible for the high blood loss during this phase. We investigated the role of leukocytes in the pathogenesis of DIC in OLT by measuring the leukocytic mediators released upon activation (cathepsin B, elastase, TNF, neopterin) and the levels of thrombin-antithrombin III (TAT) complexes, seen as markers of prothrombin activation. Arterial blood samples were taken at 10 different time points during and after OLT. Samples were also taken of the perfusate released from the liver graft vein during the flushing procedure before the reperfusion phase. Aprotinin was given as a continuous infusion (0.2-0.4 Mill. KIU/hr) and its plasma levels were determined. Significantly elevated levels of neopterin (15-fold; P < 0.01), cathepsin B (440-fold; P < 0.01) in the perfusate, as compared with the systemic circulation, as well as their significant increases in the early reperfusion phase suggested that they were released by the graft liver. This was paralleled by elevated levels of elastase (1.3-fold, P < 0.05), TNF (1.5-fold, P = NS), and TAT complexes (1.4-fold; P < 0.1) in the perfusate. Significant correlations could be identified between the parameters of leukocyte activation and TAT complexes, whereas no correlation was observed between any of the parameters investigated and the aprotinin levels. Our results strongly indicate a release of leukocytic mediators from the graft liver during its reperfusion which seems to be related to the parallely increased prothrombin activation. No correlation could be seen between levels of aprotinin and levels of leukocytic mediators.

Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody.

Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past. The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation. In two groups of 33 patients each, postoperative survival, graft biopsies, liver function enzymes, and the clinical courses after OLT were evaluated. Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT. Furthermore, our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody. This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation.

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

Community views about the role of general practitioners in disease prevention.

The role of preventive medicine in reducing mortality and morbidity is now widely recognized. Although general practitioners appear to be in an excellent position to offer preventive care, there is evidence that they currently do not detect or intervene for common risk behaviours. One reason for this may be the general practitioner's perception that patients do not expect such preventive activities to be a part of the doctor's role. A postal survey of 309 people randomly selected from the community was undertaken to examine perceptions about the general practitioner's role in detection and intervention for smoking, alcohol abuse, emotional problems and hypertension. Responses to the survey from 264 usable questionnaires indicated that people in the community accepted the general practitioner's role in preventive care, with most respondents indicating that they would appreciate being asked about the risks examined, would like the offer of intervention and would try treatments in these areas offered by the doctor. Few respondents indicated that they would change doctors as a result of preventive activity.

Retrospective statistical analysis of coagulation parameters after 250 liver transplantations.

Extensive transfusion of blood components as a typical feature of OLT has been described by many authors. The perioperative requirement for transfusion, however, follows a downward trend, although the indications for OLT have been extended. Functional disturbances such as hyperfibrinolysis or platelet dysfunction, demonstrated by laboratory tests, such as platelet counts, PT, aPTT, TT, fibrinogen, and ATIII are often used to direct the transfusion of blood components, although preoperative data give insight only into the insufficient function of the old liver, which will be explanted and replaced by the donor graft. We have described a retrospective statistical analysis of laboratory data, clinical data, and perioperative blood requirements from 250 liver transplantations performed in our hospital from 1988 to 1992. The OLT was performed according to the usual surgical methods using a venovenous bypass system. Intraoperatively, volume was restored with packed RBC and FFP according to hemodynamic data, hemoglobin, and diuresis; clotting data were not used as indications for blood replacement. This analysis demonstrated that neither preoperative nor intraoperative clotting parameters were able to allow a prediction of the intraoperative requirement for transfusion of blood components; these findings parallel those of previous reports. With respect to other studies showing that perioperative transfusion rates correlated with postoperative infections and mortality, we strongly suggest that perioperative clotting measures as indicators for transfusion requirement should be analyzed with caution. Whether other diagnostic methods such as TEG are useful alternatives has to be determined.