Severe rhabdomyolysis frequently results in acute kidney injury (AKI) due to myoglobin accumulation with the need of kidney replacement therapy (KRT). The present study investigated whether the application of Cytosorb® (CS) led to an increased rate of kidney recovery in patients with KRT due to severe rhabdomyolysis. Adult patients with a myoglobin-concentration >10,000 ng/ml and KRT were included from 2014 to 2021. Exclusion criteria were chronic kidney disease and CS-treatment before study inclusion. Groups 1 and 2 were defined as KRT with and without CS, respectively. The primary outcome parameter was independence from KRT after 30 days. Propensity score (PS) matching was performed (predictors: myoglobin, SAPS-II, and age), and the chi²-test was used. 35 pairings could be matched (mean age: 57 vs. 56 years; mean myoglobin: 27,218 vs. 26,872 ng/ml; mean SAPS-II: 77 vs. 76). The probability of kidney recovery was significantly (p = .04) higher in group 1 (31.4 vs. 11.4%, mean difference: 20.0%, odds ratio (OR): 3.6). Considering patients who survived 30 days, kidney recovery was also significantly (p = .03) higher in patients treated with CS (61.1 vs. 23.5%, mean difference: 37.6%, OR: 5.1). In conclusion, the use of CS might positively affect renal recovery in patients with severe rhabdomyolysis. A prospective randomized controlled trial is needed to confirm this hypothesis.

Introduction: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients’ outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb® (CS) reduces mortality in patients with hyperbilirubinemia. Methods: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. Results: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. Conclusion: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.

Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients’ blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration > 10 mg/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12 h). Relative reduction (RR) was calculated using the formula $$\:\:{\boldsymbol{RR}}\:{\boldsymbol{\left(\%\right)}}=\frac{{\boldsymbol{concentration\left(pre-post\right)}}}{{\boldsymbol{concentration\left(pre\right)}}}*{\boldsymbol{100}}$$ . A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (r_start=0.64, p = 0.008; r_6h = 0.85, p < 0.001, r_12h = 0.72, p = 0.002) was observed. In the first six hours of CS-application, a significant elimination of TBA (median TBA: 30.8→20.1µmol/l, p < 0.001) and bilirubin (median bilirubin: 17.1→11.9 mg/dl, p < 0.001) was observed. The median RR after 6 h was 26.1% and 39.8% for bilirubin and TBA, respectively. No further reduction was observed after 12 h (RR_bilirubin: – 0.6%, RR_TBA: 1.8%). There was an at least moderate correlation between bilirubin and TBA in patients with cholestatic liver dysfunction. Therefore, bilirubin seems to be a suitable surrogate parameter for TBA elimination during CytoSorb application.

Background: The treatment of critically ill patients in intensive care units is becoming increasingly complex. For example, organ transplants are regularly carried out, the recipients are seriously ill, and the postoperative course can be complicated. This is why organ replacement and hemadsorption procedures are becoming increasingly important. Adsorption processes are used for specific indications, such as hyperinflammation, hepatic dysfunction, or rhabdomyolysis, in critically ill patients. Nevertheless, there is still a knowledge gap in terms of safety, interactions, and application. This case report provides an example of the thought process that went into deciding whether to apply an adsorption process, as well as other necessary treatment modifications resulting from the application. Case presentation: We present the case of a 26-year-old Italian man with a complicated postoperative period after lung transplant with the need of organ support systems and hemadsorption therapy. Besides operative difficulties of the transplant and massive bleeding, the patient developed a severe liver failure of unknown origin with highly elevated bile acids, which indicated the use of the CytoSorb^® cytokine adsorber. Since there are indications that undesired drug elimination may occur and that saturation kinetics have not yet been comprehensively investigated, there were a number of aspects to consider during application. For example, the patient received additional vancomycin dosing and vancomycin blood levels were monitored. Further, to avoid premature saturation of the adsorber, the cartridge was changed every 8 hours. These adjustments resulted in a continuous reduction in bile acids while maintaining stable vancomycin blood levels, which is critical in immunosuppressed patients. Conclusion: The report focuses on two main aspects regarding a safe and sufficient usage of CytoSorb^® in the intensive care medicine. First, shortened changing periods increase the elimination rate of the adsorber, which is quickly saturated by bigger molecules, for example, bile acids. Second, additional vancomycin dosing during CytoSorb^® application avoids under dosing since CytoSorb^® eliminates vancomycin.

Introduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear which covariates influence Ang-II concentration in the early phase of sepsis, especially if extracorporeal therapies also do. Methods: Ang-II concentrations were measured in 171 patients with sepsis after the first day of antibiotic treatment between 03/2013 and 01/2015. Ang-II was correlated with potential influencing factors (Spearman correlation). A multivariate model was established including the significant correlating parameters. The Mann–Whitney U test and the Kruskal–Wallis test were used to detect significant differences in Ang-II concentration. Results: The median Ang-II concentration was 8015 pg/mL (interquartile range (IQR): 5024–14,185). A total of forty patients were treated with kidney replacement therapy (KRT) and 20 were supported by venovenous extracorporeal membrane oxygenation (vv-ECMO). Sequential organ failure assessment (SOFA) score (r = 0.541), creatinine clearance (r = −0.467), urinary output (r = −0.289), interleukin (IL)-6 (r = 0.529), C-reactive protein (CRP) (r = 0.241), platelet count (r = −0.419), bilirubin (r = 0.565), lactate (r = 0.322), KRT (r = 0.451), and fluid balance (r = 0.373) significantly correlated with Ang-II concentration and were included in the multivariate model. There, creatinine clearance (p < 0.01, b = −26.3, 95% confidence interval (CI) −41.8–−10.8), fluid balance (p = 0.002, b = 0.92, 95% CI 0.33–1.51), and CRP (p = 0.004, b = 127.6, 95% CI 41.6–213.7) were associated with Ang-II concentration. Furthermore, patients with KRT (median: 15,219 pg/mL, IQR: 10,548–20,270) had significantly (p < 0.01) higher Ang-II concentrations than those with vv-ECMO support (median: 6412 pg/mL, IQR: 5246–10,257) or those without extracorporeal therapy (median: 7156 pg/mL, IQR: 4409–12,741). Conclusion: Increased CRP, positive fluid balance, and impaired kidney function were associated with higher Ang-II concentrations in critically ill patients in the early stage of sepsis in this post hoc analysis. In particular, patients with KRT had very high Ang-II concentrations, whereas the use of vv-ECMO was not related to higher Ang-II concentrations. The significance for clinical practice should be clarified by a prospective study with standardized measurements.

Background/Objectives: Patients with shock suffer from hyperlactatemia, which can lead to endothelial dysfunction. The use of the adsorber Cytosorb^® (CS) is recommended in these patients as it may contribute to higher lactate clearance and hemodynamic stabilization. However, it is unclear whether CS can directly adsorb lactate and can therefore increase lactate clearance. Methods: The Cyto-SOLVE trial included patients undergoing continuous kidney replacement therapy combined with CS application. Patients with a lactate concentration > 2 mmol/L and measurements of lactate pre- and post-adsorber, as well as measurements in the blood 10 min and 1, 3, 6, and 12 h after initiation were selected. Lactate clearance was calculated using the following formula: bloodflow_(mL/min) × concentration_pre−post/concentration_pre. A t-test was used with the collected samples. Changes in the lactate concentration and vasopressor requirement were recorded before initiation and at the end of therapy. Results: Sixty-five lactate concentrations were measured pre- and post-CS application, as well as in patients’ blood, in a total of 14 patients (median age of 52 years, 10 males, median SAPS-II 67). There was no significant change in the lactate concentration pre- and post-CS application (mean pre-CS: 6.7 mmol/L, mean post-CS: 6.9 mmol/L, RR: −0.2, 95% confidence interval (CI): −0.4–0.1, p = 0.13, Cohen’s d: 0.90). The mean lactate clearance was −6 mL/min (standard deviation (SD): 21 mL/min), with no correlation with the initial lactate concentration or blood flow. In contrast, the mean lactate clearance measured using the dialyzer was 39 mL/min (SD: 28 mL/min). When comparing values before and after treatment, no significant change was observed in the lactate blood concentrations (mean of 9.0 vs. 8.5 mmol/L), nor in the requirement for vasopressin (median of 1.9 vs. 1.8 IE/h) or norepinephrine (mean of 2.7 vs. 2.6 mg/h). Conclusions: The adsorber CS cannot directly adsorb lactate, unlike kidney replacement therapy. Therefore, it is not suitable for achieving faster extracorporeal lactate elimination. Understanding the adsorption spectrum is of great relevance and should be considered when using CS in clinical practice.