Ernst R. Kuse

Total hepatectomy and liver transplantation as two-stage procedure.

ObjectiveThis article describes the experience with a bridging procedure for a prolonged anhepatic period during clinical liver transplantation in case of special emergency situations. Summary Background DataHepatic necrosis due to fulminant hepatitis or acute graft failure, as well as severe liver trauma are well-known and accepted indications for urgent liver transplantation. Prerequisite is the allocation of a suitable donor organ. If no allograft is available in time, patients with “toxic liver syndrome.” or exsanguinating hemorrhage have been shown to benefit from advanced total hepatectomy. MethodsAs a modification of the standard one-stage procedure, recipient hepatectomy and subsequent liver transplantation are performed in two separate operations. To bridge the prolonged anhepatic period and to allow decompression and return of venous blood, an end-to-side portocaval shunt is constructed temporarily. ResultsThirteen of thirty-two patients underwent hepatectomy but not transplantation subsequently, and died within 34 hours after progressive deterioration. In 19 of 32 patients, transplantation was realized 6–41 hours after hepatectomy; 9 of 19 patients died, mostly from sepsis. Ten of nineteen liver recipients survived the procedure including three unrelated late deaths; presently, seven patients are alive with a follow-up of 3 to 46 months. ConclusionsTwo-stage total hepatectomy with temporary portocaval shunt, and subsequent liver transplantation can be a life-saving approach in patients most likely to die of the sequelae of advanced liver or graft necrosis or exsanguination that cannot be controlled by conventional treatment or immediate liver transplantation.

Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients

AbstractObjective: Capillary leakage syndrome (CLS) is a frequent complication in sepsis, characterized by loss of intravasal fluids leading to generalized edema and hemodynamic instability despite massive fluid therapy. In spite of its importance no standardized diagnostic criteria are available for CLS. Design: Prospective clinical study. Setting: 1800-bed university hospital Patients: Six septic shock patients with CLS were compared to six control patients. Measurements and results: CLS was clinically determined by generalized edema, positive fluid balance, and weight gain. Plasma volume was measured by indocyanine green, red blood cell volume by chromium-51 labeled erythrocytes, and colloid osmotic pressure before and 90 min after the administration of 300 ml 20% albumin. Extracellular water (ECW) was measured using the inulin distribution volume and bioelectrical impedance analysis. Red blood cells averaged 20.2±1.0 ml/kg body weight in CLS patients and 23.3±4.1 in controls. ECW was higher in CLS patients than in controls (40.0±6.9 vs. 21.7±3.7 l; p<0.05). ECW of inulin was correlated with that measured by bioelectrical impedance analysis (r=0.74, p<0.01). The increase in colloid osmotic pressure over the 90 min was less in CLS patients than in controls (1.1±0.3 vs. 2.8±1.3 mmHg; p<0.05). Conclusion: These results suggest that measurements of an increased ECW using bioelectrical impedance analysis combined with a different response of colloid osmotic pressure to administration of albumin can discriminate noninvasively between patients with and those without CLS.

Reduction of catheter-related infections in neutropenic patients: a prospective controlled randomized trial using a chlorhexidine and silver sulfadiazine-impregnated central venous catheter

Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection. The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters (CVCs) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia. Proven CVC-related bloodstream infection (BSI) was defined as the isolation of the same species from peripheral blood culture and CVC tip (Maki technique). This randomized, prospective clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC (n=51) to a control arm using a standard uncoated triple-lumen CVC (n=55). Patients were treated for acute leukemia (n=89), non-Hodgkin’s lymphoma (n=10), and multiple myeloma (n=7). Study groups were balanced regarding to age, sex, underlying diseases, insertion site, and duration of neutropenia. The CVCs were in situ a mean of 14.3±8.2 days (mean±SD) in the study group versus 16.6±9.7 days in the control arm. Catheter-related colonization was observed less frequently in the study group (five vs nine patients; p=0.035). CVC-related BSI were significantly less frequent in the study group (one vs eight patients; p=0.02). In summary, in patients with severe neutropenia, CH-SS-impregnated CVCs yield a significant antibacterial effect resulting in a significantly lower rate of catheter-related colonization as well as CVC-related BSI.

Immunoprophylaxis with a monoclonal anti-IL-2 receptor antibody in liver transplant patients.

The immunosuppressive effect of a monoclonal antibody (moAb), BT563, directed to the alpha-chain of the IL-2R (CD25), was analyzed in a prospective nonrandomized trial and a prospective randomized trial. Primary objectives were evaluation of the incidence of acute rejections and infections; secondary objectives were safety and tolerability of the moAb. A total of 28 patients were enrolled (phase II) to receive 10 mg/day of BT563 (12 days) as immunoprophylaxis in combination with cyclosporine, azathioprine, and low-dose steroids. Subsequently 32 patients were randomly assigned (phase III) to receive BT563 (10 mg/day) for 12 days or ATG (5 mg/kg/day) for 7 days in addition to cyclosporine and low-dose steroids. No side effects of the BT563 treatment were noted. The actuarial survival was 82% at 12 months in the phase II trial and 92% at 12 months in both arms of the phase III trial. There was one acute rejection in the phase II trial. No acute rejections were noted in the BT arm of the phase III trial and 5 acute rejections were treated in the ATG arm. In the phase II trial 7 infectious episodes were observed, while one infection was seen in the BT arm and 7 in the ATG arm of the triple immunosuppression phase III trial. In all patients circulation of coated CD25+ lymphocytes was observed during BT563 treatment; there was no evidence of depletion or modulation of CD25+ cells. Mean serum levels of BT563 ranged from 1.6 to 7.6 microgram/ml throughout the therapy. An antimurine response was seen in 82% (phase II) and 100% (phase III) of the patients. Antirabbit antibodies were found in 56% of the patients treated with ATG. Analysis of the antimurine response specificity revealed in 56% blocking anti-isotypic antibodies and only in 3% of the patients an anti-idiotypic response. The data of the study presented suggest that therapy with an anti IL-2R moAb is at least equal to ATG application according to the incidence of acute rejections and infections.

Long-term safety, tolerability and efficacy of daclizumab (Zenapax) in a two-dose regimen in liver transplant recipients.

A major thrust of transplantation research is to find more effective and less broadly toxic immunosuppressive agents. One potential way is the use of monoclonal antibodies directed to IL‐2Rα.

Perioperative parenteral and enteral nutrition for patients undergoing orthotopic liver transplantation. Results of a questionnaire from 16 European transplant units

Abstract The present clinical experience in perioperative nutrition for patients undergoing orthotopic liver transplantation was evaluated by a questionnaire, answered by 16/21 European transplant units (76.1%). There is agreement, that malnutrition reflects per se the severity of chronic liver disease and should be not considered, in general, to exclude patients from the transplant waiting list. Most centers administer postoperative nutrition without difference to other patients after gastrointestinal major surgery. A combination of parenteral and enteral nutrition is preferred. Experience with preoperative nutritional support and use of new immunomodulating substances is rather limited.

Urodilatin: a new approach for the treatment of therapy‐resistant acute renal failure after liver transplantation

Abstract A pilot study was performed in patients after liver transplantation (Ltx) to examine the effect of continuous intravenous urodilatin (URO, CDD/ANP‐95–126)‐infusion as an alternative therapy of acute renal failure (ARF) resistant to conventional therapy. Eight patients who developed ARF after liver transplantation and fulfilled requirements for haemo‐dialysis/haemofiltration were treated. After URO infusion was started, renal function improved and all patients developed a strong diuresis and natriuresis within 2–4h. The extracellular expansion due to sodium and water retention in anuric/oliguric ARF lead to an increased central venous pressure (CVP) and elevated blood pressure. During the URO infusion CVP declined and systolic, as well as diastolic, blood pressure were stable. In six patients where haemodialysis/haemofiltration could be avoided, serum creatinine (SC) and blood urea nitrogen (BUN) declined during URO treatment and creatinine clearance (CC) also improved significantly. Fluid and electrolyte disturbances changed promptly and normalized. This was in concordance with renal excretion of electrolytes. Two patients still required haemodialysis/haemofiltration. The six patients who did not require haemodialysis/haemofiltration after URO treatment normalized concerning their renal function and did well in a control period of 12 weeks. The study shows that continuous low dose URO infusion may present a new concept for treatment of postoperative acute renal failure resistant to conventional therapy.

Hepatic reticuloendothelial function during parenteral nutrition including an MCT/LCT or LCT emulsion after liver transplantation – a double‐blind study

Abstract.It has been demonstrated that total parenteral nutrition (TPN) modulates the function of the hepatic reticuloendothelial system (RES). The objective of this study was to evaluate the impact of two different TPN lipid emulsions on the recovery of allograft RES function after orthotopic liver transplantation (OLTx). In a prospective, double-blind study, OLTx patients were randomly assigned to two treatment groups. Group I (n=13) received a TPN regimen that included long-chain triglycerides (LCT). Group II (n=9) received a TPN regimen that included a fat emulsion consisting of both medium-chain triglycerides (MCT) and LCT. At baseline, i.e., on days 2 or 3 after OLTx (t1), before lipids for TPN were started, hepatic RES function was determined using the human serum albumin millimicrosphere technique (K-value, 1/min). A second measurement (t2) was obtained after 7 days of TPN, including one of the studys two fat emulsions. The mean (± SD) K-value (1/min) was 0.48±0.16 in the LCT group and 0.55±0.28 in the MCT/LCT group at t1, and it improved to 0.62±0.21 in the LCT group and to 0.86±0.32 in the MCT/LCT group at t2. RES function recovery was significantly better in the MCT/LCT group (P≤0.05). MCT/LCT emulsion appears to be the TPN fat emulsion of choice after OLTx as it seems to have less impact on hepatic RES recovery.

Management of herpes simplex virus type 1 pneumonia following liver transplantation

SummaryInterstitial pneumonia caused by Herpes simplex virus type 1 (HSV-1) is a severe complication of orthotopic liver transplantation (LTX). The records of patients were reviewed who had an LTX at the age of 16 years or older between 1991 and 1994 with a mean follow-up of 21 months (range, 10 to 44 months). Six patients were included who had fever of >38°C, deterioration of arterial blood gases, radiological evidence of interstitial pneumonia and proof of HSV-1 in bronchoalveolar lavage fluid. All patients were anti-HSV-IgG positive before LTX. All patients were successfully treated with intravenous acyclovir, mechanical ventilation and reduced immunosuppression. Three patients who received cyclosporin A had a rejection which was successfully treated by switching to FK 506. Four patients were discharged in good health. One patient died 36 months after LTX of an unrelated cause. One patient died of urosepsis on postoperative day 139. Acyclovir together with mechanical ventilation and reduced immunosuppression proved to be an effective treatment for HSV-1 pneumonia following LTX.ZusammenfassungDie von Herpes Simplex Virus Typ 1 (HSV-1) verursachte interstitielle Pneumonie ist eine schwere Komplikation der orthotopen Lebertransplantation (LTX). Wir werteten die Akten von allen Patienten über 16 Jahre aus, die 1991–1994 eine LTX erhielten mit einer mittleren Verlaufsbeobachtung von 21 Monaten (10–44 Monate). Sechs Patienten erfüllten die diagnostischen Kriterien für eine HSV-Pneumonie mit Fieber >38°C, verschlechterter arterieller Blutgasanalyse, radiologischen Zeichen einer interstitiellen Infiltration und Nachweis von HSV-1 in der bronchoalveolären Lavageflüssigkeit. Vor der Transplantation waren alle Patienten anti-HSV-IgG positiv. Alle Patienten wurden erfolgreich behandelt mit Acyclovir, Beatmung und reduzierter Immunsuppression. Drei Patienten unter Cyclosporin A hatten eine Abstoßung, die durch Umstellung auf FK 506 erfolgreich behandelt wurde. Vier Patienten wurden in gutem Zustand entlassen. Ein Patient starb 36 Monate nach LTX an einer anderen Erkrankung. Ein Patient verstarb an Urosepsis am postoperativen Tag 139. Gabe von Acyclovir, reduzierte Immunsuppression und Beatmung ist eine effektive Behandlung der HSV-1 Pneumonie nach Lebertransplantation.

Procalcitonin – a new diagnostic tool in complications following liver transplantation

ObjectiveDoes procalcitonin (PCT) allow differentiation between infection and rejection following liver transplantation in the case of fever of unknown origin (FUO)?DesignOpen prospective trial.Settingtransplant intensive care unit at a university hospital.PatientsForty patients after liver transplantation.InterventionsLiver biopsy for diagnosis of rejection, transcutaneous aspiration cytology for monitoring of lymphocyte activation.MeasurementsProcalcitonin from EDTA plasma, APACHE II, Sepsis, score (Elbute and Stoner).ResultsEleven patients suffered an infectious complication resulting in an increase in PCT levels (2.2–41.7 ng/ml). Eleven patients developed a rejection episode; none of these patients showed a rise in PCT levels. The statistical difference between PCT levels in rejection and infection was significant (p<0.05) on the day of diagnosis.ConclusionPCT allows differentiation between rejection and infection in the case of FUO. Elevation of PCT plasma levels develops early postoperatively due to operation trauma, and, in the case of FUO with no rise in PCT, a rejection may be suspected.