Kevin Roedl

Coagulation parameters and major bleeding in critically ill patients with cirrhosis

Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d‐dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d‐dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 109/L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One‐year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups). Conclusion: Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556‐568)

Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients

BACKGROUND & AIMS Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH. METHODS Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented. RESULTS Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p<0.05). Cardiogenic shock (p<0.001), septic shock (p<0.001) and active alcohol consumption (p<0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p<0.05), but did not affect 90-day- and 1-year-mortality, respectively. CONCLUSIONS Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND & AIMS Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis. METHODS 145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients. RESULTS vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%. CONCLUSIONS HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.

Renal replacement therapy in critically ill liver cirrhotic patients – Outcome and Clinical Implications

Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long‐term.

Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis.

Retention of bile acids (BAs) plays a central role in hepatic damage and disturbed BA signalling in liver disease. However, there is lack of data regarding the association of BAs with clinical complications, acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF). Thus, we aimed to evaluate the impact of circulating serum BAs for complications in patients with cirrhosis.

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.

Shock liver and cholestatic liver in critically ill patients

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.

Hepatocardiac disorders. Interactions between two organ systems

ZusammenfassungInteraktionen zwischen dem kardialen und hepatalen System sind häufige Komplikationen bei Patienten mit Lebererkrankungen. Eine reduzierte kardiale Funktion ohne zugrunde liegende kardiale Erkrankung bei Patienten mit Leberzirrhose wird als zirrhotische Kardiomyopathie (CCMP) bezeichnet. Die typische hyperdyname Kreislaufregulation äußerst sich durch ein gesteigertes Herzzeitvolumen sowie einen herabgesetzten systemischen Gefäßwiderstand und kann so eine manifeste Herzinsuffizienz maskieren. Die portopulmonale Hypertension (POPH), eine Form der pulmonalarteriellen Hypertonie in Zusammenhang mit portaler Hypertension, ist eine seltene, doch schwerwiegende Komplikation bei Patienten mit chronischer Lebererkrankung. Als medikamentöse Therapieoption stehen Vasodilatoren, wie Prostazykline, Endothelinrezeptorantagonisten und Phosphodiesterase-5-Hemmer, zur Verfügung. Die hypoxische Hepatitis (HH) oder auch Schockleber geht mit einem fulminanten Transaminasenanstieg bedingt durch Leberzellnekrose infolge von kardialem, zirkulatorischem oder respiratorischem Versagen einher. Im folgenden Beitrag wird eine Übersicht über die genannten Krankheitsbilder gegeben.AbstractInteractions 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.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.

Long-term neurological outcomes in patients aged over 90 years who are admitted to the intensive care unit following cardiac arrest

BACKGROUND The number of cardiac arrests (CA) in the group of very elderly patients (≥ 90 years) is expected to increase markedly due to the world`s rapidly ageing population. However, only little is known about long term outcome, CA- and intensive care unit (ICU) characteristics of patients ≥ 90 years (nonagenarians) suffering from CA. METHODS This single-center retrospective study included all adult patients ≥ 90 years after CA and return of spontaneous circulation (ROSC) which were treated at our ICU between January 1st 2008 and September 15th 2016. Patients were followed at least 1-Year after ICU discharge for assessment of survival and neurological outcome. Aim of the study was to evaluate CA- and patients characteristics, as well as ICU- and neurological outcome after CA in patients ≥ 90 years. RESULTS 657 patients ≥ 90 years were treated at our ICU during the study period, of these we could identify 48 patients with CA and successful resuscitation. 27 (56%) were female and the median age was 91.7 (90.7 - 92.6) years. 41 (85%) patient suffered from in-hospital CA. Cardiac events leading to CA were observed in 19 (40%) patients. Initial rhythm was shockable (VT/VF) in 12 (25%) patients and time to ROSC was median 4 (1.6 - 9.5) minutes. Patients after CA who survived the ICU stay had significantly lower SAPS II score (44 (36 - 55) vs. 58 (46.5 - 75.5), p < 0.05), lower maximum lactate (2.8 (1.9 - 4.3) mmol/l vs. 6.2 (4 - 9) mmol/l, p < 0.001) and higher pH (7.29 (7.26 - 7.38) vs. 7.23 (7.12 - 7.32), p < 0.05) on admission compared to patients with CA who did not survive the ICU stay. Overall, after CA, 39 (81%) patients needed mechanical ventilation, 44 (92%) received catecholamine support, 17 (35%) received red blood cell transfusion and 4 (8%) received renal replacement therapy. Mechanical ventilation and red blood cell transfusion was significantly more common in ICU non-survivors (both p < 0.05). 19 (46%) patients survived the ICU-stay, of these 86% had favourable neurological outcome (CPC I/II) at ICU discharge. One year survival rate was 23% (n = 11), of these 55% (n = 6) had favorable neurological outcome. CONCLUSIONS 46% of successfully resuscitated nonagenarians survived the ICU stay, the majority with favourable neurological outcome at ICU discharge. Resuscitation and post-CA care, in the highly selected group of very elderly patients (≥ 90 years), seems to be justified.

Acid–base status and its clinical implications in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease

BackgroundAcid–base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid–base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease.ResultsOne hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values < 7.1 showed a 100% mortality rate. Acidosis attributable to lactate and unmeasured anions was independently associated with mortality in liver cirrhosis.ConclusionsCirrhosis and especially ACLF are associated with metabolic acidosis and acidemia owing to lactate and unmeasured anions. Acidosis and acidemia, respectively, are associated with increased 28-day mortality in liver cirrhosis. Lactate and unmeasured anions are main contributors to metabolic imbalance in cirrhosis and ACLF.