B Vangerow

C1-Inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h-DAF transgenic porcine kidneys

Abstract: At present, the major barrier to successful discordant xenotransplantation of unmodified or complement regulator transgenic porcine xenografts is acute vascular xenograft rejection (AVR). AVR is associated with the intragraft deposition of induced recipient xenoreactive antibodies and subsequent complement activation. In a life‐supporting pig to primate kidney xenotransplantation setting using h‐DAF transgenic donor organs and postoperative immunosuppression, episodes of AVR were either treated with boluses of cyclophosphamide and steroids or with the same regimen supplemented by a three‐day course of C1‐Inhibitor, a multifunctional complement regulator. In 8 out of 10 animals stable initial graft function was achieved; in all animals one or more episodes of AVR were observed. When, in 4 animals, C1‐Inhibitor was added to the standard anti‐rejection treatment regimen, AVR was successfully reversed in 6 out of 7 episodes, while in another group of 4 animals receiving the standard anti‐rejection treatment 0 out of 4 episodes of AVR responded to treatment. Response to anti‐rejection treatment was associated with a significant increase in recipient survival time. We conclude that AVR of h‐DAF transgenic porcine kidneys can be successfully treated by additional short‐term fluid phase complement inhibition.

Predictors of respiratory function deterioration after transfer of critically ill patients

Objectives: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. Design: Prospective, clinical, observational study. Setting: 1800-bed university teaching hospital. Subjects: 98 mechanically ventilated patients were investigated during transfer. Measurement and main results: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxgen tension (PaO2), fractional inspired oxygen (FIO2), PaO2/FIO2 ratio, lowest PaO2/FIO2 ratio, minimal PaO2 and maximal FIO2, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55 %) there was a decrease in the PaO2/FIO2 ratio, and a decrease of more than 20 % from baseline was noted in 23 of the transferred patients (24 %). Age > 43 years and FIO2 > 0.5 were identified as predictors for respiratory deterioration. Conclusions: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91 %), combined with a false-positive rate in 17 of 49 (35 %).

Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor.

Abstract The extent of complement and contact activation is related to outcome in sepsis. A low functional index of their main blocker C1-esterase inhibitor (C1-INH) is considered as a relative deficiency of C1-INH and might contribute to the development of fatal complications in the intensive care unit. The first results of therapeutic intervention with C1-INH concentrate in septic shock are promising. We report on our experience of C1-INH concentrate administration in a young woman with Carolis disease as ultimate rescue therapy for septic shock with capillary leakage syndrome after combined liver and kidney transplantation. No focus of infection was detectable and thus surgical intervention was not indicated. Antibiotic therapy at that time included vancomycin, tobramycin, meropenem and fluconazol. Hemodynamic stabilization occurred within hours after administration of C1-INH concentrate. Simultaneously a reduction in vasopressor medication was possible and negative fluid balance was achieved.

Cardiac output measurement by arterial thermodilution in piglets.

M easuring cardiac output (CO) in critically ill infants is often helpful after major cardiac surgery because surgical outcome may be improved by maintaining adequate CO (1). The measurement of CO by using a pulmonary artery catheter (PAC) in small infants, especially in those of ,10 kg, is rarely used because of technical difficulties of placement, invasiveness, and potential complications. The recent development of a small arterial thermistortipped catheter may overcome some of the technical problems associated with central cannulation and catheterization of the pulmonary artery. Insertion of such a catheter can be performed into the femoral or axillary artery through a 22-gauge cannula (2).The aim of this investigation was to evaluate the accuracy of CO measurements in piglets of 10.2 6 1.1 kg obtained by arterial trans-cardiopulmonary thermodilution (ATD) by using an arterial thermistor-tipped catheter compared with conventional pulmonary arterial thermodilution (PATD) by using a PAC.

Low-dose dopexamine in patients undergoing hemihepatectomy: an evaluation of effects on reduction of hepatic dysfunction and ischaemic liver injury

Background: Hepatic dysfunction is a common problem in patients after hemihepatectomy. Treatment with low‐dose dopamine has been shown to be beneficial in hemihepatectomy patients. We hypothesized that dopexamine, a synthetic vasoactive catecholamine, due to its specific pharmocodynamic profile may be more effective in reducing hidden ischaemic episodes in the hepato‐splanchnic region during and after temporary total cross‐clamping of hepatic inflow in these patients.