Hemoadsorption with CytoSorb®

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.

Background Septic shock, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a highly lethal condition that causes substantial morbidity and mortality among critically ill patients. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators causing refractory hypotension, tissue damage, metabolic acidosis and ultimately multiple organ failure. In this context, cytokine reduction by hemoadsorption represents a new concept for blood purification, developed to attenuate the overwhelming systemic levels of pro-inflammatory and anti-inflammatory mediators released in the early phase of sepsis. Methods In the present case series, we evaluated the impact of a new hemoadsorption device (CytoSorb) used as adjunctive therapy, on hemodynamics and clinically relevant outcome parameters in 26 critically ill patients with septic shock and in need of renal replacement therapy. Results We found that treatment of these patients with septic shock was associated with hemodynamic stabilization and a reduction in blood lactate levels. Actual mortality in the overall patient population was lower than mortality predicted by acute physiology and chronic health evaluation II (APACHE II). These effects seem to be more pronounced in patients in whom therapy started within 24 h of sepsis diagnosis, whereas a delay in the start of therapy was associated with a poor response to therapy in terms of reduction of catecholamine demand and survival. Moreover, from our patient population, medical patients seemed to benefit more than post-surgical patients in terms of survival. Treatment using the CytoSorb device was safe and well-tolerated with no device-related adverse events during or after the treatment sessions. Conclusion Hemoadsorption using CytoSorb resulted in rapid hemodynamic stabilization and increased survival, particularly in patients in whom therapy was started early. Given the positive clinical experience of this case series, randomized controlled trials are urgently needed to define the potential benefits of this new treatment option.

Background Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use blood purification devices in terms of removing sepsis-associated mediators and endotoxins. Methods In vitro hemoperfusion was performed using oXiris®, CytoSorb®, and Toraymyxin®. Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h. For each device, the removal of 27 inflammatory mediators was measured over time. Endotoxin removal mediated by oXiris and Toraymyxin was assessed using hemoperfusion over 6 h. Results Endotoxin (lipopolysaccharide) removal was most rapid with Toraymyxin; mean adsorptive clearance over the first 30 min was ~ 20 ml/min vs ~ 8 ml/min with oXiris (p < 0.05). There was minimal endotoxin removal with CytoSorb (1 ml/min). At 120 min, there was no significant difference between the endotoxin removal rates using oXiris (mean ± standard deviation, 68.0 ± 4.4%) and Toraymyxin (83.4 ± 3.8%); both were significantly higher vs CytoSorb (− 6.3 ± 4.9%; p < 0.05). Total removal with oXiris was 6.9 μg vs 9.7 μg for Toraymyxin, where the total lipopolysaccharide quantity introduced was approximately 15.8 μg. Removal rates of pro-/anti-inflammatory cytokines and other inflammatory mediators were similar between oXiris and CytoSorb and were higher with CytoSorb and oXiris vs Toraymyxin. Granulocyte colony-stimulating factor was only effectively adsorbed by CytoSorb (99.4%). Differences were detected between the adsorption mechanism of the devices; binding to oXiris was mainly ionic, while CytoSorb was hydrophobic. No specific protein adsorption was found qualitatively with Toraymyxin. Conclusions Adsorption rate kinetics varied for individual inflammatory mediators using the three blood purification devices. Mechanisms of adsorption differed between the devices. oXiris was the only device tested that showed both endotoxin and cytokine removal. oXiris showed similar endotoxin adsorption to Toraymyxin and similar adsorption to CytoSorb for the removal of other inflammatory mediators. Differences in device removal capacities could enable treatment to be more tailored to patients. Electronic supplementary material The online version of this article (10.1186/s40635-018-0177-2) contains supplementary material, which is available to authorized users.