Abstract
BackgroundCardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality. Hemoadsorption (HA) of cytokines may suppress inflammatory responses and improve outcomes. We tested a new sorbent used for HA (CytoSorb™; CytoSorbents Europe GmbH, Berlin, Germany) installed in the CPB circuit on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients’ perioperative course.MethodsIn this first pilot trial, 37 blinded patients were undergoing elective CPB surgery at the Medical University of Vienna and were randomly assigned to HA (n = 19) or control group (n = 18). The primary outcome was differences of cytokine levels (IL-1β, IL-6, IL-18, TNF-α, and IL-10) within the first five postoperative days. We also analyzed whether we can observe any differences in ex vivo lipopolysaccharide (LPS)-induced TNF-α production, a reduction of high-mobility box group 1 (HMGB1), or other inflammatory markers. Additionally, measurements for fluid components, blood products, catecholamine treatment, bioelectrical impedance analysis (BIA), and 30-day mortality were analyzed.ResultsWe did not find differences in our primary outcome immediately following the HA treatment, although we observed differences for IL-10 24 hours after CPB (HA: median 0.3, interquartile range (IQR) 0–4.5; control: not traceable, P = 0.0347) and 48 hours after CPB (median 0, IQR 0–1.2 versus not traceable, P = 0.0185). We did not find any differences for IL-6 between both groups, and other cytokines were rarely expressed. We found differences in pretreatment levels of HMGB1 (HA: median 0, IQR 0–28.1; control: median 48.6, IQR 12.7–597.3, P = 0.02083) but no significant changes to post-treatment levels. No differences in inflammatory markers, fluid administration, blood substitution, catecholamines, BIA, or 30-day mortality were found.ConclusionsWe did not find any reduction of the pro-inflammatory response in our patients and therefore no changes in their perioperative course. However, IL-10 showed a longer-lasting anti-inflammatory effect. The clinical impact of prolonged IL-10 needs further evaluation. We also observed strong inter-individual differences in cytokine levels; therefore, patients with an exaggerated inflammatory response to CPB need to be identified. The implementation of HA during CPB was feasible.Trial registrationClinicalTrials.gov: NCT01879176, registration date: June 7, 2013.
Highlights
Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality
One patient (HA) evolved a hemodynamical instability after skin incision leading to cardiopulmonary resuscitation and an acute onset of the CPB, so no adsorber could be installed, and in two patients (1 HA and 1 control) we lost the follow-up of our main outcome measurements, so we excluded them too
For the analysis of our primary outcome, we excluded the patients with unexpected post-treatment Extracorporeal membrane oxygenation (ECMO) therapy (n = 2) because of differences in cytokine exaggeration (Fig. 1)
Summary
Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality. We tested a new sorbent used for HA (CytoSorbTM; CytoSorbents Europe GmbH, Berlin, Germany) installed in the CPB circuit on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients’ perioperative course. Once activated by the extracorporeal circuit, they might lead to a dysregulation of inflammatory homeostasis and increased levels of both, pro- and anti-inflammatory plasma mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, and IL-18 [4, 6,7,8,9] This strong inflammatory response induces post-surgical monocyte immunosuppression which is indicated by an impaired production of ex vivo lipopolysaccharide (LPS)induced TNF-α exaggeration [10]. Hemoadsorption (HA) using the CytoSorbTM adsorber (CytoSorbents Europe GmbH, Berlin, Germany) is a recent technology that has shown rapid elimination of many key cytokines that cannot be filtered by using current blood purification techniques [12]
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