Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Early therapeutic intervention is of central prognostic importance in patients with HH to improve the hemodynamic impairment as early as possible, to reduce hyperammonemia and hepatic encephalopathy, to avoid progression of organ failure and to improve outcome. Studies reported that Molecular Adsorbent Recirculating System (MARS®) therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. The study hypothesis is that MARS® therapy in critically ill patients with severe HH improves hepatic hemodynamics and function and consecutively the course of the disease. 40 patients with suffering of severe HH with aminotransferase levels \> 40 times the upper limit of normal of more than 12 hours will be randomized 1:1 to MARS® therapy (n=20) or conventional therapy (n=20). 4 MARS®-sessions will be performed on three consecutive days, each for at least 12 hours. Treatment will be continued under special circumstances. The maximum duration of the treatment phase is 7 days. The primary endpoint is the difference of the indocyanine plasma disappearance rate at day 7. The expected duration of the study is 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Molecular adsorbent recirculating system (MARS®) can be used in patients with acute liver failure for bridging to liver transplantation. Studies reported that MARS® therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. Several groups observed an increase in arterial pressure, systemic vascular resistance index, a decrease in portal pressure and improvement of renal blood flow. Furthermore, studies demonstrated that MARS therapy reduces ammonia levels and improves hepatic encephalopathy.
Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology
Vienna, Vienna, Austria
RECRUITINGUniversity Medical Center Hamburg-Eppendorf
Hamburg, Hamburg, Germany
RECRUITINGdifference of the indocyanine plasma disappearance rate (ICG-PDR)
The primary endpoint will be the difference of the indocyanine plasma disappearance rate (ICG-PDR) at day 7. Only in case of major differences in baseline values of ICG-PDR we will use the change from baseline to day 7 of ICG-PDR (delta ICG-PDR) as outcome. Assuming normal distribution of ICG-PDR, we will formally test the null-hypothesis of no difference between intervention group and control using an independent sample t-test. The assumption of a normal distribution will be founded on visually inspecting a histogram and using the Shapiro Wilks test for normal distribution. If the assumption of normality does not hold data will be compared using the Mann-Whitney U-test. A p-level of \< 0.05 will be considered statistically significant. Furthermore a linear random coefficient model will be used to incorporate daily measurements of ICG-PDR during the course of the study in terms of a repeated measures design.
Time frame: Days 1-7
duration of vasopressor support
Time frame: 1-28
ICU - length of stay
Time frame: 1-28
hospital - length of stay
Time frame: 1-90
7-day mortality
Time frame: 7 days
28 day mortality
Time frame: 28 days
number of organ failure on day 7
Time frame: 7 days
number of organ failure on day 28
Time frame: 28 days
markers of liver function
especially occurrence of jaundice (defined as total bilirubin levels \> 3 mg/dL) will be documented
Time frame: 1-28
number of vasopressor free days
Time frame: 28 days
systemic hemodynamics
systemic blood pressure, heart rate, cardiac index, central venous oxygen saturation, systemic vascular resistance index, global enddiastolic volume index, stroke volume variation, extravascular lung water index, pulse pressure variation, intrathoracic blood volume index, cardiac function index, central venous pressure
Time frame: 7 days
number of complications of HH
following complications will be encountered: cholestasis, secondary sclerosing cholangitis, hepatic encephalopathy grade 3 \& 4, hypoglycemia, intraabdominal hypertension, new onset of infections, renal failure, hepatopulmonary syndrome
Time frame: 1-28
biomarkers
blood samples will be collected the assess markers of inflammation, markers of endothelial function, markers of cardiac function, markers of cholestasis, markers of liver cell necrosis etc
Time frame: 0-28
duration of mechanical ventilation
Time frame: 1-28
necessity of renal replacement therapy
Time frame: 1-28
duration of renal replacement therapy
Time frame: 1-28
90 days mortality
Time frame: 90 days
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