Can the cytokine adsorber CytoSorb® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis

Abstract

Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.

Does adjunctive hemoadsorption with CytoSorb affect survival of COVID-19 patients on ECMO? Authors' response

“…It is also true that IL-6 may not be the optimal parameter for assessing the effectiveness of therapy with CytoSorb, as previously discussed [ 7 ]. This consideration is consistent with observations from another retrospective analysis [ 8 ]. However, this cannot explain the association of cytokine adsorption with mortality in the CYCOV trial.…”

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

“…In vitro studies have demonstrated the optimal capacity for removing broad-spectrum cytokines with removal rates of >90% at 120 min [125]. However, there have been reports that IL-6 did not decrease in clinical cases [127], and the evidence supporting its favorable outcomes on hemodynamic parameters and blood lactate levels has been limited to a case series [128]. Despite such promising experimental results, only a randomized controlled trial has evaluated the efficacy of CytoSorb ® in critically ill patients with sepsis.…”

Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb®—Basics, Indications and Perspectives—A Scoping Review

“…Procalcitonin is equally adsorbed, which must be taken into account in the interpretation of lab test results [ 30 , 32 ]. However, the IL6 concentration, which is frequently used to indicate start and efficacy of hemoadsorption therapy and for the assessment of the effect of hemoadsorption, has recently been questioned for its usefulness since the levels are balanced by the endogenous turn-over and the extracorporeal elimination [ 72 , 73 , 74 ]. CytoSorb ® therapy could be useful in septic shock [ 75 , 76 ], but indication, indication thresholds and duration of therapy are controversially discussed.…”

“…More retrospective studies demonstrated a mortality benefit for hemoadsorption [ 81 ], especially if CytoSorb ® therapy was started early (within 12 h) [ 82 ]. On the other hand, several recently published studies have failed to demonstrate any effect of hemoadsorption on mortality [ 74 , 83 ].…”