The Effect of CytoSorb on Inflammatory Markers in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Objectives: The effectiveness of CytoSorb at removing inflammatory mediators in critically ill patients is controversial.

Data sources: Electronic databases were searched from inception to May 2023.

Study selection: Randomized controlled trials reporting the effects of CytoSorb therapy on inflammatory parameters in critically ill patients with hyperinflammatory conditions were included.

Data extraction: Two authors screened articles for eligibility, extracted data, and assessed the risk of bias, conflicts of interest, and certainty of evidence (CoE). The primary outcome was interleukin (IL)-6 at 1 day after initiation of the therapy. Secondary outcomes included various inflammatory markers at 1, 2, 3, and 5 days and mortality. Data were pooled if at least three trials reported the outcome of interest. We conducted meta-analyses of the data using a random-effects model.

Data synthesis: Seventeen trials ( n = 855) were included. Fourteen trials were judged to have notable concern about conflicts of interest. Seven trials were performed in medical ICU patients with hyperinflammatory conditions and 10 in complex cardiovascular surgery under cardiopulmonary bypass. Hemoadsorption with CytoSorb was not associated with lower IL-6 at 1 day (mean difference -5.98 [95% CI, -30.44 to 18.48] pg/mL), 2 days, 3 days, or 5 days after initiation of the treatment, as well as the concentration of procalcitionin. The levels of C-reactive protein were not lower with CytoSorb at 1, 2, and 3 days. The use of CytoSorb was associated with higher mortality at latest follow-up (relative risk = 1.22 [95% CI, 1.02-1.45]) and at 30 days. CoE ranged from low to very low.

Conclusions: The use of CytoSorb hemoadsorption in a mixed population of critically ill patients with hyperinflammatory conditions does not exhibit a consistent decrease in IL-6 and other inflammatory parameters within the first 5 days of treatment. The significant uncertainty surrounding these findings highlights the need for further investigations.

Trial registration: ClinicalTrials.gov NCT02566525.

Figure 1.

Flow diagram for the selection of studies. CENTRAL = Cochrane Central Register of Controlled Trials.

Figure 2.

Interleukin-6 (IL-6). Forest plot of the mean difference in IL-6 levels at different time-points with CytoSorb hemoadsorption or conventional therapy.

Figure 3.

C-reactive protein (CRP) levels. Forest plot of the mean difference in CRP levels at different time-points with CytoSorb hemoadsorption or conventional therapy.

Figure 4.

Procalcitonin (PCT). Forest plot of the mean difference in PCT levels at different time-points with CytoSorb hemoadsorption or conventional therapy.

Figure 5.

Mortality. Forest plot of the relative risk of mortality at 30 days/in-hospital and at longest follow-up available with CytoSorb hemoadsorption and control therapy.