ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation.

Enhanced recovery of patients after surgery ("ERAS") has become an important focus of perioperative management. From a metabolic and nutritional point of view, the key aspects of perioperative care include: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and if necessary tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in surgical patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1980. The guideline was discussed and accepted in a consensus conference. EN is indicated even in patients without obvious undernutrition, if it is anticipated that the patient will be unable to eat for more than 7 days perioperatively. It is also indicated in patients who cannot maintain oral intake above 60% of recommended intake for more than 10 days. In these situations nutritional support should be initiated without delay. Delay of surgery for preoperative EN is recommended for patients at severe nutritional risk, defined by the presence of at least one of the following criteria: weight loss >10-15% within 6 months, BMI<18.5 kg/m(2), Subjective Global Assessment Grade C, serum albumin <30 g/l (with no evidence of hepatic or renal dysfunction). Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

Recurrent cardiocirculatory arrest after kidney transplantation related to intravenous methylprednisolone bolus therapy.

BACKGROUND: Intravenous bolus therapy with steroids is often used in standard immunosuppression initially after organ transplantation and to treat acute graft rejection. Although this regimen in generally is safe, severe adverse effects can occur. METHODS: This letter gives a picture of the eventful clinical course of a patient with preexisting heard problems after renal transplantation. RESULTS: This case report proves lethal cardiopulmonary complications closely related to the recurrent intravenous administration of methylprednisolone in a risk patient. CONCLUSIONS: Severe side effects after the application of high-dose steroids are possible. If risk patients are identified, steroid bolus therapy should be avoided or, if not possible, should only be done under close monitoring.

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.

Allogeneic liver transplantation for hepatic veno-occlusive disease after bone marrow transplantation--clinical and immunological considerations.

Veno-occlusive disease (VOD) is a frequent complication early after bone marrow transplantation. In cases of severe liver failure treatment by allogeneic liver transplantation is possible. We report the clinical and immunological course of a patient after bone marrow transplantation for AML and subsequent allogeneic liver transplantation for severe hepatic VOD. After liver transplantation the patient recovered well clinically. Early after liver transplantation he had large numbers of liver donor T and NK lymphocytes in his circulation. He had no liver graft rejection, but he developed mild acute GVHD which was caused by liver graft-derived T lymphocytes. Two years after transplantation he had persistent microchimerism with donor liver cells detectable in his bone marrow. Now 36 months after transplantation, the patient has no evidence of recurrent leukemia, stable liver function, and no signs of graft-versus-host disease or bone marrow dysfunction.

Management of severe hepatic trauma by two-stage total hepatectomy and subsequent liver transplantation.

Even today major hepatic trauma remains a formidable surgical challenge with considerable deaths from exsanguination. Apart from conservative operative techniques that allow successful management in most cases, liver transplantation may be indicated in a more severe injury. This is a report on a patient with massive, unsalvageable liver trauma on whom the first two-staged procedure was successfully performed. After total hepatectomy as the first step and a prolonged anhepatic period of more than 14 hours, liver replacement by an allograft was carried out in a second operation. The patient recovered completely from the potentially lethal hepatic trauma and is alive more than 17 months later.

GM-CSF increases in vitro the respiratory burst of human neutrophils after liver transplantation.

OBJECTIVE: Superoxide production by polymorphonuclear neutrophils (PMNs) under cyclosporin A (CsA) therapy following kidney transplantation is impaired. We investigated if the respiratory burst of PMNs is similarly depressed in patients undergoing CsA treatment following orthotopic liver transplantation (OLTx). Additionally, the in vitro influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the superoxide anion production was examined during the respiratory burst. PATIENTS: 10 patients after OLTx and 10 healthy blood donors (control group). MEASUREMENTS AND RESULTS: PMNs were stimulated with bacteria (Escherichia coli) or a combination of tumour necrosis factor alpha (TNFalpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The respiratory burst was measured by oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by means of flow cytometry. No differences in respiratory bursts from OLTx patients compared to those from healthy blood donors could be seen. Under TNFalpha/FMLP stimulation, the respiratory burst was significantly increased after in vitro incubation with GM-CSF (500 U ml(-1)) in patients following OLTx (from 58.2 to 74.5 %) as well as in the control group (from 47.4 to 61.9%). CONCLUSIONS: Our results demonstrate that superoxide production is not impaired under CsA treatment following OLTx. The respiratory burst of these patients' PMNs can even be augmented by GM-CSF in vitro.

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

OBJECTIVE: 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: 1,800-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 +/- 3.71; 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.

Fat emulsions in parenteral nutrition after liver transplantation: The recovery of the allografts RES function and histological observations.

Following liver transplantation, the effect of post-operative parenteral nutrition with MCT LCT (Medium Chain Triglycerides/Long Chain Triglycerides) fat emulsions on the recovery of allografts RES function was investigated in a randomised prospective study of three groups of patients (group I, n = 14: 50g MCT LCT fats twice weekly, group II, n = 15: 0.7 g/kg body weight per day MCT LCT fats, group III, n = 17: 1.5 g/kg body weight per day MCT LCT fats). RES function was assessed using the (99m)Tc-HSA-MM-Clearance ((99m)Technitium-Human serum albumen-Millimicrosphere-Clearance). There were no statistically significant differences in the recovery of RES function between the groups. A negative effect on RES function as a result of the administration of MCT LCT fat emulsions up to 1.5 g/kg b.w. per day can therefore be excluded. The evaluation of liver biopsies before the administration of fats and at the end of TPN (Total Parenteral Nutrition) showed no evidence, in the 20 patients investigated, of any fatty changes in the liver caused by the infusion of fat.

Nutrition of liver transplant patients.

Good cooperation between the hepatologist, surgeon and anesthesiologist is required to determine the appropriate perioperative nutritional management for the liver transplant patient. For preoperative risk stratification, nutritional assessment according to resting energy expenditure by indirect calorimetry, and body cell mass by bioelectrical impedence analysis, may be superior to anthropometric parameters. When considering impaired glucose tolerance in the early postoperative period, requirements of energy intake and macronutrients are no different from those established in major abdominal surgery. Preference should be made to use the enteral route whenever possible. Fat emulsions containing medium- and long-chain triglycerides have neither a negative impact on reticulo-endothelial system recovery of the graft, nor any obvious metabolic advantages. There is no evidence for the routine use of branched-chain amino acids. Even in the case of good graft function, long term dietary evaluation and counselling may be useful. Impaired glucose tolerance, hyperlipidemia and hypercholesterolemia should be considered carefully. The role of preoperative nutritional therapy using oral supplements and the value of immune-enhancing substrates should be evaluated with special regard to a decrease in postoperative septic complications and for possible impact on immune tolerance after transplantation.

Surgery and transplantation - Guidelines on Parenteral Nutrition, Chapter 18.

In surgery, indications for artificial nutrition comprise prevention and treatment of catabolism and malnutrition. Thus in general, food intake should not be interrupted postoperatively and the re-establishing of oral (e.g. after anastomosis of the colon and rectum, kidney transplantation) or enteral food intake (e.g. after an anastomosis in the upper gastrointestinal tract, liver transplantation) is recommended within 24 h post surgery. To avoid increased mortality an indication for an immediate postoperatively artificial nutrition (enteral or parenteral nutrition (PN)) also exists in patients with no signs of malnutrition, but who will not receive oral food intake for more than 7 days perioperatively or whose oral food intake does not meet their needs (e.g. less than 60-80%) for more than 14 days. In cases of absolute contraindication for enteral nutrition, there is an indication for total PN (TPN) such as in chronic intestinal obstruction with a relevant passage obstruction e.g. a peritoneal carcinoma. If energy and nutrient requirements cannot be met by oral and enteral intake alone, a combination of enteral and parenteral nutrition is indicated. Delaying surgery for a systematic nutrition therapy (enteral and parenteral) is only indicated if severe malnutrition is present. Preoperative nutrition therapy should preferably be conducted prior to hospital admission to lower the risk of nosocomial infections. The recommendations of early postoperative re-establishing oral feeding, generally apply also to paediatric patients. Standardised operative procedures should be established in order to guarantee an effective nutrition therapy.

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.

Pharmacokinetics of cefotaxime in patients after liver transplantation.

The pharmacokinetics of cefotaxime including formation of its active metabolite desacetyl-cefotaxime were assessed after liver transplantation in three groups of patients (four patients per group): --during the postoperative recovery phase (group 1), --during an episode of allograft nonfunction (group 2), --during an episode of allograft rejection (group 3). All patients received a single dose of 1 g cefotaxime intravenously. Concentrations of cefotaxime and its metabolite were determined in plasma and urine until 6 to 72 h after medication. The terminal half-life of cefotaxime increased and total clearance decreased due to an impairment of drug metabolism, mainly in patients with a nonfunctioning allograft and during rejection. Thus, no desacetyl-cefotaxime was detectable in urine of any patient and none in plasma of 2/4 patients with a nonfunctioning allograft. In addition, a moderate impairment of renal function in several patients contributed to the delayed elimination of cefotaxime and its metabolite. It can be concluded that liver function after transplantation is correlated with the ability to eliminate cefotaxime. Therefore, administration of half the normal dose is recommended particularly in patients with a nonfunctioning allograft or during rejection.

Procalcitonin-a new diagnostic tool in complications following liver transplantation.

OBJECTIVE: Does procalcitonin (PCT) allow differentiation between infection and rejection following liver transplantation in the case of fever of unknown origin (FUO)? DESIGN: Open prospective trial. SETTING: transplant intensive care unit at a university hospital. PATIENTS: Forty patients after liver transplantation. INTERVENTIONS: Liver biopsy for diagnosis of rejection, transcutaneous aspiration cytology for monitoring of lymphocyte activation. MEASUREMENTS: Procalcitonin from EDTA plasma, APACHE II, Sepsis, score (Elbute and Stoner). RESULTS: Eleven 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. CONCLUSION: PCT 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.