Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function.

BACKGROUND: Extracorporeal circulation during major cardiac surgery triggers a systemic inflammatory response affecting the clinical course and outcome. Recently, extracellular vesicle (EV) research has shed light onto a novel cellular communication network during inflammation. Hemoadsorption (HA) systems have shown divergent results in modulating the systemic inflammatory response during cardiopulmonary bypass (CPB) surgery. To date, the effect of HA on circulating microvesicles (MVs) in patients undergoing CPB surgery is unknown. METHODS: Count and function of MVs, as part of the extracellular vesicle fraction, were assessed in a subcohort of a single-center, blinded, controlled study investigating the effect of the CytoSorb device during CPB. A total of 18 patients undergoing elective CPB surgery with (n = 9) and without (n = 9) HA device were included in the study. MV phenotyping and counting was conducted via flow cytometry and procoagulatory potential was measured by tissue factor-dependent MV assays. RESULTS: Both study groups exhibited comparable counts and post-operative kinetics in MV subsets. Tissue factor-dependent procoagulatory potential was not detectable in plasma at any timepoint. Post-operative course and laboratory parameters showed no correlation with MV counts in patients undergoing CPB surgery. CONCLUSION: Additional artificial surfaces to the CPB-circuit introduced by the use of the HA device showed no effect on circulating MV count and function in these patients. Larger studies are needed to assess and clarify the effect of HA on circulating vesicle counts and function. Trial registration ClinicalTrials.Gov Identifier: NCT01879176; registration date: June 17, 2013; https://clinicaltrials.gov/ct2/show/NCT01879176.

Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent.

BACKGROUND: Cardiopulmonary 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. METHODS: In 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-1ß, 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. RESULTS: We 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. CONCLUSIONS: We 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 REGISTRATION: ClinicalTrials.gov: NCT01879176, registration date: June 7, 2013.

A randomised trial of oral versus intravenous opioids for treatment of pain after cardiac surgery.

BACKGROUND: Cardiac surgery and sternotomy are procedures accompanied by substantial postoperative pain which is challenging to treat. In general, intravenous (IV) opioids are used in the immediate postoperative phase, followed by oral opioids. Oral opioids are easier to use and generally less expensive. Our goal was thus to determine whether a new opioid preparation provides adequate analgesia after sternotomy. In particular, we tested the primary hypothesis that total opioid use (in morphine equivalents) is not greater with oral opioid compared with patient-controlled IV morphine. Our secondary hypothesis was that analgesic efficacy is similar with oral and IV opioids. METHODS: A total of 51 patients having elective cardiac surgery were enrolled in this study. After rapid postoperative respiratory weaning, the patients were randomised into one of two groups receiving different types of analgesia: oral Targin (a combination of oxycodone-hydrochloride and the opioid antagonist naloxone hydrochloride-dihydrate) or patient-controlled IV morphine. Pain score (visual analogue scale), sedation (Ramsey score), respiratory rate and side effects were assessed at 3, 5, 7, 9 and 11 h after surgery, and every 6 h throughout the third postoperative evening. RESULTS: The total opioid dose in morphine equivalent doses was significantly lower with oral opioid than with IV morphine (adjusted geometric means [95 % confidence interval]: 34 [29; 38] vs. 69 [61; 78] mg, respectively). Pain scores were similar in each group. CONCLUSIONS: Analgesic quality was comparable with oral and IV opioids, suggesting that postoperative pain even after very painful procedures can be sufficiently managed with oral opioids.

Hemoadsorption does not Have Influence on Hemolysis During Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) induces hemolysis, which manifests as plasma free hemoglobin. We investigated in a post hoc analysis of a single-center, blinded, controlled study whether the use of a novel hemoadsorption device (CytoSorb, CytoSorbents Europe GmbH, Berlin, Germany) affects hemolysis during CPB. A total of 35 patients undergoing elective CPB surgery with an expected CPB duration of more than 120 min were included in the analysis. The hemoadsorption device was used in 17 patients (intervention group) and not used in 18 patients (control group). The primary outcome was differences of postoperative free hemoglobin and haptoglobin levels. As secondary outcomes, we investigated differences in postoperative lactate dehydrogenase and bilirubin levels. Postoperative free hemoglobin levels were not significantly different between the groups. However, there were statistically significant differences between the treatment and control groups in the median levels of haptoglobin (58.4 vs. 17.9 mg/dL, respectively; P < 0.01) and lactate dehydrogenase (353.0 vs. 432.0 U/L, respectively; P < 0.05) on postoperative day 1. Thus, in this study, we did not find an effect on hemolysis in patients treated with hemoadsorption, though lower haptoglobin level and higher secondary hemolysis markers on postoperative day 1 in patients not treated with the hemoadsorber may be an indication of some moderate effect of the device. Studies with larger samples are needed to clarify the significance of the small differences detected in this study.