The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Dirk Schädler, Christine Pausch, Daniel Heise, Andreas Meier-Hellmann, Jörg Brederlau, Norbert Weiler, Gernot Marx, Christian Putensen, Claudia Spies, Achim Jörres, Michael Quintel, Christoph Engel, John A Kellum, Martin K Kuhlmann, Dirk Schädler, Christine Pausch, Daniel Heise, Andreas Meier-Hellmann, Jörg Brederlau, Norbert Weiler, Gernot Marx, Christian Putensen, Claudia Spies, Achim Jörres, Michael Quintel, Christoph Engel, John A Kellum, Martin K Kuhlmann

Abstract

Objective: We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure.

Methods: This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7.

Results: 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19).

Conclusions: In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Conflict of interest statement

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MKK received a research grant for study administration and coordination by Cytosorbents. GM has received honorary from Cytosorbents. DS and MKK received refunds of travelling expenses by Cytosorbents. The remaining authors have declared that no competing interests exist. The study was supported by Cytosorbents Corporation, New Jersey, United States and investigated a product marketed by Cytosorbents. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Cytosorbents does not employ and does not pay consultancies to any of the authors.

Figures

Fig 2. Interleukin-6 elimination (calculated as difference… — Fig 2. Interleukin-6 elimination (calculated as difference of arterial and venous Interleukin 6 values) in the treatment group studied during a specific kinetic day where Interleukin-6 measurements were performed before the start of the study intervention (T0), 15 minutes (T15), 60 minutes (T60), 180 minutes (T180) and 360 minutes (T360) after the start of the hemoperfusion.

Fig 3. Median and interquartile range for… — **Fig 3. Median and interquartile range for Interleukin-6 (IL-6) plasma levels in the treatment and in the control group (n = 75).**

Fig 4. Time course for log-transformed oxygenation… — Fig 4. Time course for log-transformed oxygenation index (Panel A), the ratio of arterial partial pressure of oxygen and inspired fraction of oxygen (P/F ratio) (Panel B) and multiple organ dysfunction score (MODS) (Panel C) in the control group (grey boxes) and in the treatment group (white boxes).
The number of patients available are displayed in the header of each panel.

Fig 5. CD4-cell-activation for control (grey boxes)… — **Fig 5. CD4-cell-activation for control (grey boxes) and treatment group (white boxes) on different study days.**
Values > 1000 are evaluated as 1000, values

**Fig 6. Median and interquartile ranges of…**

**Fig 6. Median and interquartile ranges of platelets (Panel A), white blood cells (WBC) (Panel…**

Fig 6. Median and interquartile ranges of platelets (Panel A), white blood cells (WBC) (Panel B), albumin (Panel C), total protein (Panel D) and body temperature (Panel E) of treatment and control group for study day 1 to 7 before and after the treatment if applicable.

See this image and copyright information in PMC

Fig 6. Median and interquartile ranges of… — Fig 6. Median and interquartile ranges of platelets (Panel A), white blood cells (WBC) (Panel B), albumin (Panel C), total protein (Panel D) and body temperature (Panel E) of treatment and control group for study day 1 to 7 before and after the treatment if applicable.

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Source: PubMed

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Abstract

Conflict of interest statement

Figures

References

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