Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia

Abstract

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.

A Contemporary Review of the Use of Extracorporeal CytoSorb® Hemoadsorption Therapy in Patients with Infective Endocarditis

“…Currently, CytoSorb ® (CytoSorbents Europe GmbH, Berlin, Germany), HA 330 (Jafron Biomedical Co., Ltd., Zhuhai, China), and Toraymyxin™ (Toray Medical Co., Ltd., Tokyo, Japan) are three mainstream hemoadsorbers that are widely used in critical care settings [27]. Among them, CytoSorb ® , a CE-approved hemoadsorber, can significantly remove cytokines, bilirubin, toxic bile acids, and myoglobin in the circulating blood [28][29][30][31]. Equipped with highly porous, biocompatible sorbent polystyrene divinylbenzene beads, CytoSorb ® cartridges have a total surface area of >45,000 m 2 and are capable of adsorbing various hydrophobic cytokine molecules with a molecular weight ranging from 5 to 55 kDa [22].…”

Clarification on the Efficacy of Extracorporeal Purification Techniques in Critically Ill Patients with Liver Dysfunction

“…We have carefully reviewed the recent study by Gräfe et al [1], titled "Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb ® and Mortality in Critically Ill Patients with Hyperbilirubinemia," published in Blood Purification on October 11, 2023. We would like to express some concerns and seek clarification on certain aspects of the study.…”

“…This finding contradicts previous studies, which [6] reported significant bilirubin, AST and vasopressor reduction by hemadsorption. As Gräfe et al [1] did not quantify bilirubin removal by hemadsorption, it becomes challenging to assess the effectiveness of this particular blood purification technique in the described scenario. Moreover, the quantitative impact of all the extracorporeal therapies, including CytoSorb, on bilirubin levels may not be assessed by means of systemic measurements alone.…”

A Contemporary Review of the Use of Extracorporeal CytoSorb® Hemoadsorption Therapy in Patients with Infective Endocarditis

“…Currently, CytoSorb® (CytoSorbents Europe GmbH, Berlin, Germany), HA 330 (Jafron Biomedical Co., Ltd, Zhuhai, China) and Toraymyxin™ (Toray Medical Co., Ltd, Tokyo, Japan) are three mainstream hemoadsorbers that are widely used in critical care settings [27]. Among them, CytoSorb®, a CE-approved hemoadsorber, can significantly remove cytokines, bilirubin, toxic bile acids, and myoglobin in the circulating blood [28][29][30][31]. Equipped with highly porous, biocompatible sorbent polystyrene divinylbenzene beads, CytoSorb® cartridges have a total surface area of > 45,000 m 2 and are capable of adsorbing various hydrophobic cytokine molecules within the 5-55 kDa molecular weight range [22].…”