Background: The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.Methods: Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4 % albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.Results: Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median −68 μmol/L, interquartile range [IQR] −107.5 to −33.5,p = 0.001; SPAD: −59 μmol/L, −84.5 to +36.5,p = 0.001). However, bile acids (MARS: −39 μmol/L, −105.6 to −8.3,p < 0.001; SPAD: −9 μmol/L, −36.9 to +11.4,p = 0.131), creatinine (MARS: −24 μmol/L, −46.5 to −8.0,p < 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L,p = 0.314) and urea (MARS: −0.9 mmol/L, −1.93 to −0.10,p = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68,p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10 %, −0.8 to +20.9 %,p < 0.001; SPAD: +7 %, −7.5 to +15.5 %,p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.Conclusions: Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.Trial registration: German Clinical Trials Register (www.drks.de)DRKS00000371. Registered 8 April 2010.

Background: Our aim is to report the results of the ‘liver indication’ subset of patients in the CytoSorb International Registry. Methods: Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians. Results: Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24–72 h) in total. Serum bilirubin levels reduced significantly to −4.6 (95% CI: −6.329 to −2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event. Conclusions: We report the largest case series on hemoadsorption for ‘liver indication’ from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted.

Monitoring hepatic blood flow and function might be crucial in treating critically ill patients. Intra-abdominal hypertension is associated with decreased abdominal blood flow, organ dysfunction, and increased mortality. The plasma disappearance rate (PDR) of indocyanine green (ICG) is considered to be a compound marker for hepatosplanchnic perfusion and hepatocellular membrane transport and correlates well with survival in critically ill patients. However, correlation between PDRICG and intra-abdominal pressure (IAP) remains poorly understood. The aim of this retrospective study was to investigate the correlation between PDRICG and classic liver laboratory parameters, IAP and abdominal perfusion pressure (APP). The secondary goal was to evaluate IAP, APP, and PDRICG as prognostic factors for mortality. A total of 182 paired IAP and PDRICG measurements were performed in 40 critically ill patients. The mean values per patient were used for comparison. The IAP was measured using either a balloon-tipped stomach catheter connected to an IAP monitor (Spiegelberg, Hamburg, Germany, or CiMON, Pulsion Medical Systems, Munich, Germany) or a bladder FoleyManometer (Holtech Medical, Charlottenlund, Denmark). PDRICG was measured at the bedside using the LiMON device (Pulsion Medical Systems, Munich, Germany). Primary endpoint was hospital mortality. There was no significant correlation between PDRICG and classic liver laboratory parameters, but PDRICG did correlate significantly with APP (R = 0.62) and was inversely correlated with IAP (R = -0.52). Changes in PDRICG were associated with significant concomitant changes in APP (R = 0.73) and opposite changes in IAP (R = 0.61). The IAP was significantly higher (14.6 ± 4.6 vs. 11.1 ± 5.3 mmHg, p = 0.03), and PDRICG (10 ± 8.3 vs. 15.9 ± 5.2%, p = 0.02) and APP (43.6 ± 9 vs. 57.9 ± 12.2 mmHg, p < 0.0001) were significantly lower in non-survivors. PDRICG is positively correlated to APP and inversely correlated to IAP. Changes in APP are associated with significant concomitant changes in PDRICG, while changes in IAP are associated with opposite changes in PDRICG, suggesting that an increase in IAP may compromise hepatosplanchnic perfusion. Both PDRICG and IAP are correlated with outcome. Measurement of PDRICG may be a useful additional clinical tool to assess the negative effects of increased IAP on liver perfusion and function.

The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10− 5 from the GWAS. We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Introduction: Hepatobiliary elimination of endo- and xenobiotics is affected by different variables including hepatic perfusion, hepatocellular energy state and functional integrity of transporter proteins, all of which are altered during sepsis. A particular impairment of hepatocellular transport at the canalicular pole resulting in an accumulation of potentially hepatotoxic compounds would have major implications for critical care pharmacology and diagnostics. Methods: Hepatic transcellular transport, that is, uptake and hepatobiliary excretion, was studied in a rodent model of severe polymicrobial sepsis by two different biophotonic techniques to obtain insights into the handling of potentially toxic endo- and xenobiotics in sepsis. Direct and indirect in vivo imaging of the liver was performed by intravital multifluorescence microscopy and non-invasive whole-body near-infrared (NIRF) imaging after administration of two different, primarily hepatobiliary excreted xenobiotics, the organic anionic dyes indocyanine green (ICG) and DY635. Subsequent quantitative data analysis enabled assessment of hepatic uptake and fate of these model substrates under conditions of sepsis. Results: Fifteen hours after sepsis induction, animals displayed clinical and laboratory signs of multiple organ dysfunction, including moderate liver injury, cholestasis and an impairment of sinusoidal perfusion. With respect to hepatocellular transport of both dyes, excretion into bile was significantly delayed for both dyes and resulted in net accumulation of potentially cytotoxic xenobiotics in the liver parenchyma (for example, specific dye fluorescence in liver at 30 minutes in sham versus sepsis: ICG: 75% versus 89%; DY635 20% versus 40% of maximum fluorescence; P < 0.05). Transcutaneous assessment of ICG fluorescence by whole body NIRF imaging revealed a significant increase of ICG fluorescence from the 30th minute on in the bowel region of the abdomen in sham but not in septic animals, confirming a sepsis-associated failure of canalicular excretion. Conclusions: Hepatocytes accumulate organic anions under conditions of sepsis-associated organ dysfunction. These results have potential implications for monitoring liver function, critical care pharmacology and the understanding of drug-induced liver injury in the critically ill.