Consensus statement for cancer patients requiring intensive care support.

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.

[Hemorrhagic shock : General principles]. / Hämorrhagischer Schock : Allgemeine Therapieprinzipien.

Bleeding associated with hemorrhagic shock is often seen in emergency medical services or in the intensive care unit. Identifying the origin of the bleeding and additional disorders helps to determine the degree of the hemorrhagic shock. In order to be effective, the initial therapy until blood products are available needs to be differentiated to be effective in terms of hemodynamic stabilization and coagulation. Crystalloidal and colloidal solutions should be used carefully since those solutions bear a risk within themselves. Treatment of acidosis and hypothermia can further reduce bleeding complications. Early and repeated monitoring of clotting should be performed simultaneously to shock therapy to permit specific treatment and substitution of coagulation factors if needed. Hemorrhagic shock therapy should be continued until bleeding is stopped.

Kidney biopsy in patients with diabetes mellitus.

BACKGROUND: The clinical consequences of the results obtained by kidney biopsy in patients with diabetes mellitus Type 1 or Type 2 have been controversial. Our study was conducted to assess clinical symptoms and histological diagnoses in patients with diabetes mellitus Type 1 and Type 2 undergoing kidney biopsy. DESIGN, SETTING AND PATIENTS: Observational study. The study included data from 567 consecutive renal biopsies of patients with diabetes mellitus Type 1 or 2 and chronic kidney disease (CKD) examined by standard histopathological procedures. The main outcome measures were incidence of diabetic nephropathy (DN) and glomerulonephritis (GN), predictors for the presence of both DN or GN. RESULTS: Approximately 70% of patients with diabetes mellitus Type 1 or 2 and evidence for CKD had DN. Glomerular diseases present in approximately 30% of patients with diabetes were predominantly immune complex GN and secondary focal glomerulosclerosis, followed by IgA-GN, which was associated with microhematuria (p = 0.01) and hypertension (p = 0.04). Only a minority had membranous GN, which was associated with nephrotic syndrome (p = 0.004). Progressive CKD predicted the presence of GN in diabetes mellitus Type 2 (r = -0.98; p = 0.02). CONCLUSION: GN is not uncommon in patients with diabetes and evidence for CKD. Kidney biopsy should therefore be considered in patients with diabetes and progressive CKD.

[Core curriculum Medical intensive care medicine of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN)]. / Curriculum Internistische Intensivmedizin.

Medical intensive care medicine treats patients with severe, potentially life-threatening diseases covering the complete spectrum of internal medicine. The qualification in medical intensive care medicine requires a broad spectrum of knowledge and skills in medical intensive care medicine, but also in the general field of internal medicine. Both sides of the coin must be taken into account, the treatment with life-sustaining strategies of the acute illness of the patient and also the treatment of patient's underlying chronic diseases. The indispensable foundation of medical intensive care medicine as described in this curriculum includes basic knowledge and skills (level of competence I-III) as well as of behavior and attitudes. This curriculum is primarily dedicated to the internist in advanced training in medical intensive care medicine. However, this curriculum also intends to reach trainers in intensive care medicine and also the German physician chambers with their examiners, showing them which knowledge, skills as well as behavior and attitudes should be taught to trainees according to the education criteria of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN).

[Hepatopulmonary interactions]. / Interaktionen von Leber und Lunge.

Liver-lung interactions are common in daily clinical practice. However, frequently they are not the focus of clinical attention. For example, 10% of patients with acute-on-chronic liver failure and more than 30% of patients with advanced stages of acute-on-chronic liver failure suffer from respiratory failure. Conversely, up to 20% of critically ill patients develop secondary liver failure as a consequence of cardiopulmonary diseases or sepsis during their stay in the intensive care unit. This article provides an overview of clinically relevant liver-lung interactions, consecutively acquired pulmonary and hepatic diseases and the therapeutic implications.

[Acute-on-chronic liver failure: a diagnostic and therapeutic challenge for intensive care]. / Das akut-auf-chronische Leberversagen als diagnostische und therapeutische Herausforderung der Intensivmedizin.

Acute-on-chronic liver failure (ACLF) is an emerging clinical syndrome in patients with underlying liver disease that is usually triggered by one or multiple insults and characterized by progressive hepatic and nonhepatic organ failure, a significant risk of infections, and high short-term mortality rates. Despite our incomplete understanding of the underlying pathophysiology, ACLF requires timely diagnostic and therapeutic measures aiming at the identification and elimination of causative factors as well as the prevention of complications to improve the prognosis of affected patients.

[Acute liver failure]. / Akutes Leberversagen.

Acute liver failure (ALF) is a rare condition with fatal outcome. Characteristic is rapid onset of liver damage without preexisting liver diseases, including hepatic encephalopathy and coagulopathy. Early and correct diagnosis is essential for further management of patients, since diagnosis impacts therapy choice. Survival of patients with ALF has improved dramatically due to advances in critical care medicine and the use of liver transplantation.

Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe complication of liver cirrhosis associated with excess short-term mortality rates. Orthotopic liver transplantation (OLT) is a potentially life-saving therapeutic modality for acute-on-chronic liver failure patients, but selection of transplant candidates with an acceptable post-transplant outcome is difficult. AIM: To assess the risk of liver transplantation in patients with ACLF, and to determine parameters that predict post-transplant survival in this patient cohort. METHODS: We retrospectively analysed all 250 patients with cirrhosis who underwent their first liver transplantation between 2009 and 2014 at our institution, and assessed post-transplant outcomes. RESULTS: Of 250 cirrhotic liver transplant recipients, 98 patients fulfilled the diagnostic criteria for acute-on-chronic liver failure in the 3-month pre-transplant period. Compared to non-ACLF patients, ACLF was associated with significantly higher short-term morbidity and mortality after liver transplantation (90-day patient survival 96.1% non-ACLF vs 72.4% ACLF patients, P < 0.0001). Clinical improvement in the pre-transplant period, as defined by recovery of at least one previously failed organ system, was observed in 37 of 98 acute-on-chronic liver failure patients, mostly within several days after diagnosis. Most notably, clinical improvement prior to liver transplantation was associated with excellent post-transplant survival rates that approximated non-ACLF transplant recipients. Following the 90-day post-transplant period, patient survival and long-term graft functions were comparable between ACLF and non-ACLF liver transplant recipients for up to 5 years. CONCLUSIONS: Acute-on-chronic liver failure predicts adverse outcome after orthotopic liver transplantation. Given the dismal prognosis without transplantation, however, our results indicate that ACLF patients can be transplanted with comparably good outcomes, in particular patients who improve under conservative therapeutic measures.

Outcome and natural course of renal dysfunction in liver transplant recipients with severely impaired kidney function prior to transplantation.

BACKGROUND: Since introduction of the MELD score in the liver allograft allocation system, renal insufficiency has emerged as an increasing problem. Here we evaluated the course of kidney function in patients with advanced renal insufficiency prior to liver transplantation (LT). METHODS: A total of 254 patients undergoing LT at the University Medical Centre Hamburg-Eppendorf (2011-2015) were screened for renal impairment (GFR < 30 ml/min) prior to LT in this observational study. RESULTS: Eighty (32%) patients (median 60 years; M/F: 48/32) had significant renal impairment prior to LT. Median follow-up post-LT was 619 days. Patient survival at 90 days, one year and two years was 76%, 66% and 64%, respectively. Need for dialysis postoperatively but not preoperatively was associated with increased mortality (p < 0.05). Renal function improved in 75% of survivors, but 78% of patients had chronic kidney disease ≥ stage 3 at end of follow-up. Of eight (16%) survivors remaining on long-term dialysis, so far only four patients have received a kidney transplant. CONCLUSION: Postoperative dialysis affected long-term mortality. In 75% of survivors renal function improved, but still the majority of patients had an impaired renal function (CKD stage 3-5) at end of follow-up. Future studies should elucidate the impact of kidney dysfunction and dialysis on recipients' long-term survival.

Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?

INTRODUCTION: Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.

[Extracorporeal therapies in hepatic diseases]. / Extrakorporale Therapien bei Lebererkrankungen.

Acute and acute-on-chronic liver failure have different underlying causes and are associated with hepatic or extrahepatic organ failure. Depending on etiology, up to 20% of critically ill patients suffer from hepatic dysfunction, which contributes to increased morbidity and mortality. A variety of extracorporeal procedures including renal replacement therapies, artificial and bioartificial liver support, and plasma exchange are used in the management of patients with liver diseases. Several randomized controlled studies of artificial liver support and plasma exchange proved the safety of these procedures and demonstrated improvement of hepatic encephalopathy and hemodynamics. A survival benefit could be observed in some of the randomized, controlled trials. In contrast, renal replacement therapy in critically ill patients with liver diseases has been assessed in retrospective case series and was associated with high mortality rates in liver cirrhosis. In summary, extracorporeal therapies are a cornerstone of therapeutic options in critically ill patients with hepatic failure. In addition to the comparison of different procedures, future studies should assess the timing of initiation as well as duration, and identify criteria of therapeutic futility of extracorporeal therapies in this population.

[Hepatocardiac disorders : Interactions between two organ systems]. / Hepatokardiale Wechselwirkungen : Interaktionen zweier Organsysteme.

Interactions between the hepatic portal and cardiovascular systems are frequently found in patients with liver disease. Cirrhotic cardiomyopathy (CCMP) is defined as reduced cardiac function in patients with liver cirrhosis in the absence of other known causes of cardiac disease. The typical hyperdynamic circulatory state by means of increased cardiac output and reduced systemic vascular resistance may mask left ventricular failure. Portopulmonary hypertension (POPH) is defined as increased pulmonary arterial pressure and the presence of portal hypertension, and is associated with increased mortality. Targeted medical therapies include vasodilators such as prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Hypoxic or ischaemic hepatitis (HH) is defined by a sharp increase of serum aminotransferase levels due to liver cell necrosis as result of cardiac, circulatory or respiratory failure. An overview of these diseases is provided in this article.

Fibroblast growth factor receptor 4 (FGFR4) is expressed in adult rat and human retinal photoreceptors and neurons.

The fibroblast growth factor (FGF) family, with its prototype members acidic FGF (FGF-1) and basic FGF (FGF-2), binds to four related receptor tyrosine kinases, termed FGFR1, R2, R3, and R4, expressed on most types of cells in tissue culture. In many respects, the FGFR appear similar to other growth factor receptors; thus, dimerization of receptor monomers on ligand binding is likely to be a requisite for activation of the kinase domains, leading to receptor trans-phosphorylation. Within the central nervous system (CNS), including retina, FGFR1 and R2 have been widely described as the predominant forms. FGFR4 is reported to be strongly expressed only during early stages of development, and apart from one small region (the lateral habenular nucleus) is not detectable in adult CNS. Screening of different neural and nonneural tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that whereas FGFR1 and R2 were strongly expressed in adult cortex, cerebellum, retina, and kidney, robust FGFR4 expression was only seen in retina and kidney. FGFR4 mRNA was present within fractions of the outer and inner nuclear layers isolated from adult rat retinas, and could also be detected in pure photoreceptor cultures prepared from young rat retinas. On the contrary, FGFR4 mRNA could not be detected in primary cultures of retinal Müller glia or pigment epithelium, indicating specific enrichment in retinal neurons. In situ hybridization studies of adult rat retina showed FGFR4 expression in all retinal cellular layers, especially prominent in the outer nuclear layer. FGFR4 protein was detected by immunoblotting of homogenates of rat retina, with specific antibody binding to bands at 115, 47, and 30 kDa. FGFR4 mRNA and protein were also reliably detected in postmortem adult human retina. The potential roles of these signal transduction molecules in FGF-induced biological responses in the retina are discussed.

[Shock liver and cholestatic liver in critically ill patients]. / Schockleber und Cholestase beim kritisch Kranken.

Liver dysfunction is frequently observed in critically ill patients. Its occurrence is associated with high morbidity and mortality. The most frequent entities of hepatic dysfunction in the intensive care unit are shock liver and cholestatic liver dysfunction with incidence rates up to 10 and 30 %, respectively.Both conditions are frequently triggered by hypoxic and/or ischemic events, most commonly cardiogenic shock and sepsis/septic shock. However, several other potential contributors have been identified especially for cholestatic liver dysfunction. Apart from chronic liver diseases and malignancies, iatrogenic factors such as total parenteral nutrition, high pressure ventilation, surgical procedures, drugs and blood transfusions promote its occurrence.In shock liver and in cholestatic liver disease, early detection and therapy of the underlying disease is the only established treatment.

[Extracorporeal therapy of patients with liver disease in the intensive care unit]. / Extrakorporale Therapien bei Patienten mit Lebererkrankungen auf der Intensivstation.

Acute and acute-on-chronic liver failure are often associated with development of organ failure. Its occurrence is associated with high morbidity and mortality. Extracorporeal replacement therapies are frequently necessary in these patient populations. Replacement therapies can be divided into renal replacement therapies and liver support therapies. These therapies consist of artificial liver support systems (i.e., MARS(®) system, Prometheus(®)), which are able to remove water-soluble and albumin-bound toxins, and of bioartifical liver support systems. This manuscript provides a review of current practice in the extracorporeal support of patients with liver diseases in the intensive care unit.

[Pulmonary complications in liver diseases]. / Pulmonale Komplikationen bei Lebererkrankungen.

Pulmonary-hepatic vascular disorders are frequent complications in patients with portal hypertension and cirrhosis. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax are relevant disease entities in these patients. HPS occurs in up to 30 % of patients with cirrhosis and is associated with a more than 2-fold increased mortality. The diagnosis of HPS should be established early by arterial blood gas analysis and contrast-enhanced echocardiography, whereas POPH is diagnosed by the presence of pulmonary arterial hypertension evaluated via right heart catheterization and the presence of portal hypertension. Therapeutic options include initiation of long-term oxygen therapy and liver transplantation in patients with severe HPS. Patients with POPH should receive targeted medical therapies with endothelin receptor antagonists, phosphodiesterase-5 inhibitors and/or prostanoids. In contrast, ß-blockers should be avoided. This review summarizes current knowledge regarding pulmonary-hepatic vascular disorders, with a focus on HPS.

Gender-specific differences in energy metabolism during the initial phase of critical illness.

BACKGROUND/OBJECTIVES: Women and men differ in substrate and energy metabolism. Such differences may affect energy requirements during the acute phase of critical illness. SUBJECTS/METHODS: Data of 155 critically ill medical patients were reviewed for this study. Indirect calorimetry in each patient was performed within the first 72 h following admission to the medical intensive care unit after an overnight fast. RESULTS: In overweight (body mass index (BMI) ≥25 kg/m(2)) but not in normal-weight patients, resting energy expenditure (REE) adjusted for body weight (REEaBW) differed significantly between women and men (17.2 (interquartile range (IQR) 15.2-20.7) vs 20.9 (IQR 17.9-23.4) kcal/kg/day, P<0.01). Similarly, REE adjusted for ideal body weight (REEaIBW) was significantly lower in women compared with men (25.5 (IQR 22.6-28.1) vs 28.0 (IQR 25.2-30.0) kcal/kg/day, P<0.05). In overweight patients, gender was identified as an independent predictor of REEaBW in the multivariate regression model (r=-2.57 (95% CI -4.57 to -0.57); P<0.05), even after adjustment for age, simplified acute physiology score (SAPS II), body temperature, body weight and height. CONCLUSIONS: REEaBW decreases with increasing body mass in both sexes. This relationship differs between women and men. Overweight critically ill women show significantly lower REEaBW and REEaIBW, respectively, compared with men. These findings could affect the current practice of nutritional support during the early phase of critical illness.