A comprehensive analysis of intraoperative cytokine adsorption systems on early clinical outcomes after coronary artery bypass grafting

A comprehensive analysis of intraoperative cytokine adsorption systems on early clinical outcomes after coronary artery bypass grafting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A comprehensive analysis of intraoperative cytokine adsorption systems on early clinical outcomes after coronary artery bypass grafting SEVDA KURTULMUŞ, SİNAN ARSAN, ERTUĞRUL KILIÇ, FATİH ÖZTÜRK, ANIL GÜZEL, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8584906/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Cardiopulmonary bypass (CPB) induces a systemic inflammatory response mediated by cytokine release, which may contribute to postoperative cardiovascular and systemic organ dysfunction following coronary artery bypass grafting (CABG). Cytokine adsorption filters have been developed to attenuate this response; however, their clinical efficacy in CABG remains controversial and a matter of debate among physicians and healthcare systems. Methods This observational study compared early postoperative outcomes in 17 patients undergoing CABG with intraoperative cytokine adsorption using two different filter systems and 28 control patients undergoing CABG without cytokine filtration. Baseline demographic and operative characteristics were recorded. Clinical outcomes and inflammatory and biochemical markers, including C-reactive protein (CRP), procalcitonin, ferritin, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were measured at predefined perioperative time points. Results Baseline characteristics were comparable between groups, and no significant differences were observed between the two filter systems. Exploratory subgroup analyses stratified by hypertension and diabetes mellitus did not demonstrate a differential effect of cytokine filtration on the assessed outcomes. Compared with the Control group, the Filter group demonstrated a significantly shorter duration of mechanical ventilation (median 4 vs. 13 hours; p = 0.041) and a substantially lower requirement for inotropic support (5.8% vs. 60.7%; p < 0.001). Intra-aortic balloon pump use and re-exploration rates were significantly lower in the Filter group. Lactate levels following CPB and during the early postoperative period were significantly lower in the Filter group. Among inflammatory markers, only IL-8 levels at 24 hours postoperatively were significantly reduced, while IL-6, IL-10, TNF-α, and CRP showed no significant intergroup differences. Conclusions Intraoperative cytokine adsorption during CABG was associated with improved early postoperative clinical outcomes despite limited effects on most circulating inflammatory markers. These findings are hypothesis-generating and warrant confirmation in adequately powered randomized controlled trials to inform clinicians’ decision-making regarding their use in patients. Cardiopulmonary bypass Cytokine adsorption Coronary artery bypass grafting Inflammation Postoperative outcomes Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Cardiopulmonary bypass (CPB) enables cardiac surgery by providing temporary extracorporeal circulation to maintain systemic perfusion and oxygenation during operative arrest of the heart [ 1 – 4 ]. Despite its indispensable role, CPB triggers a systemic inflammatory response due to blood exposure to artificial surfaces, ischemia-reperfusion injury, and surgical trauma [ 5 – 7 ]. This inflammatory cascade activates leukocytes and complement pathways, leading to the release of pro-inflammatory cytokines, which may contribute to postoperative complications such as acute kidney injury, acute respiratory distress syndrome, prolonged intensive care unit (ICU) stay, and multiorgan dysfunction. Cytokine adsorption therapies have recently been introduced as an adjunctive strategy during CPB to attenuate this inflammatory response [ 8 , 9 ]. These hemoadsorption devices are designed to remove circulating cytokines, including interleukins and tumor necrosis factor-α, with the aim of reducing organ injury and improving postoperative recovery [ 10 ]. Although reductions in circulating inflammatory biomarkers have been reported, evidence linking these biochemical effects to clinically meaningful postoperative outcomes remain limited, particularly in patients undergoing isolated coronary artery bypass grafting (CABG). Most previous studies have focused on biochemical endpoints in contexts such as septic shock, orthotopic heart transplantation, valve surgery, infective endocarditis, elective cardiac surgery using CPB, and type A aortic dissection [ 11 – 18 ]. In contrast, data directly linking cytokine adsorption to early postoperative outcomes, such as duration of mechanical ventilation, hemodynamic support requirements, and ICU stay are scarce. Addressing this gap is essential to clarify the clinical relevance of cytokine filtration beyond laboratory findings and to guide its potential use in CABG patients. Cardiac surgery induces a systemic inflammatory response characterized by cytokines such as IL-6, IL-8, and TNF-α, which typically peak after CPB and normalize within 24 hours [ 19 , 20 ]. This response has been associated with multiorgan dysfunction, myocardial ischemia, low cardiac output, and increased infection risk [ 21 – 23 ]. While intraoperative adsorption and filtration devices are considered safe, consistent evidence demonstrating clinical benefit is limited [ 24 , 25 ]. Although cytokine adsorption has been increasingly adopted in selected clinical settings, its widespread use is limited by additional costs and resource utilization. Given the lack of robust data demonstrating clear clinical benefit in low-risk or elective procedures such as isolated CABG, the cost-effectiveness of routine intraoperative cytokine filtration remains uncertain. In this context, the present study aimed to investigate the association between intraoperative cytokine filter use during cardiopulmonary bypass and early postoperative outcomes in patients undergoing elective isolated CABG. The primary focus was to evaluate postoperative inflammatory and biochemical parameters, as well as clinically relevant endpoints, including duration of mechanical ventilation, need for vasoactive support, length of stay in intensive care unit, and total hospital stay. By integrating laboratory and clinical outcomes, this study aimed to determine whether modulating the CPB-related inflammatory response through cytokine adsorption is associated with measurable improvements in early postoperative recovery. We hypothesized that intraoperative cytokine filtration would be associated with more favorable early postoperative clinical outcomes beyond changes in circulating cytokine levels. While the use of filters is a matter of debate among physicians in terms of cardiopulmonary bypass, clarifying this issue also provides information in discussions about whether filter use constitutes an additional burden on the healthcare system. METHODS Study Design and Population This study included 45 adult patients (aged 44–80 years) who underwent elective isolated coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) between January 1, 2023, and December 31, 2023, at Marmara University Pendik Training and Research Hospital. The study was approved by the Marmara University Faculty of Medicine Ethics Committee (Approval No: 09.2023.374; Date: 03.01.2024). Patients were allocated into two groups. The Filter Group (n = 17) included patients who received intraoperative cytokine adsorption during CPB using either the Jafron HA330 device (Jafron, China; n = 8) or the CytoSorb® device (CytoSorbents Corporation, USA; n = 9). The Control Group (n = 28) consisted of patients who underwent CABG without cytokine filtration. Patients with chronic obstructive pulmonary disease were excluded to minimize confounding effects on postoperative respiratory outcomes, particularly duration of mechanical ventilation. Recorded comorbidities included hypertension, diabetes mellitus, chronic kidney disease, and the extent of coronary artery disease. Baseline demographic and clinical characteristics were comparable between the filtered and non-filtered groups, with no statistically significant differences observed (Table 1 ). Table 1 Patient Characteristics Variables All Population n = 45 Filter usage p No n = 28 Yes n = 17 Age, year 62.4 ± 8.57 63.4 ± 8.5 61 ± 8.8 0.342 Gender, n (%) Male 35 (77.7) 23 (82.1) 12 (70.5) 0.507 Female 10 (22.3) 5 (17.9) 5 (29.4) BMI, kg/m 2 28.5 ± 4.8 28.2 ± 5.12 29.1 ± 4.29 0.989 Smoker 36 (80.0) 22 (78.57) 14 (82.35) 0.765 Comorbidity, n (%) Diabetes mellitus 20 (44.4) 11 (39.3) 9 (52.9) 0.383 Hypertension 33 (73.3) 19 (67.8) 14 (82.3) 0.275 CKD 5 (11.1) 3 (10.7) 2 (11.76) 0.917 EuroSCORE II 0.9 (0.5–13.7) 1 (0.5–13.7) 0.8 (0.5–2.3) 0.337 Preoperative hospitalization time 7.2 (1–30) 8.07 (1–30) 5.76 (1–17) 0.195 Data are presented as mean ± standard deviation, median (interquartile range), or number (percentage). Categorical variables are presented as a number (%). EuroSCORE II values showed a right-skewed distribution. Baseline demographic characteristics, comorbidities, and operative variables were collected for both groups. The decision to apply cytokine adsorption was not based on predefined risk stratification criteria but on intraoperative clinical judgment and device availability. Importantly, patients were not selected for cytokine adsorption based on predefined high-risk criteria such as advanced age, elevated EuroSCORE II, prolonged cardiopulmonary bypass duration, or increased comorbidity burden. Cardiopulmonary Bypass and Cytokine Filter Application All procedures were performed using standard CPB techniques under moderate hypothermia (32–34°C). Cardiopulmonary bypass was established using a Stockert S5 heart-lung machine (LivaNova, Germany) with a Sorin Inspire™ membrane oxygenator. Two cytokine filter devices (Jafron HA330 and CytoSorb®), both based on similar hemoadsorption principles, were integrated into the cardiopulmonary bypass circuit using an identical parallel configuration with a standardized blood flow of 300 mL/min. Both hemoadsorption devices were applied using identical circuit configurations and standardized blood flow parameters and are designed to target middle-molecular-weight inflammatory mediators through non-selective adsorption mechanisms. Circuit pressures, pump flow parameters, and hematocrit levels were continuously monitored. Post-bypass lactate dehydrogenase (LDH) and plasma-free hemoglobin levels were assessed as surrogate markers of hemolysis. Given the limited number of patients in each subgroup, analyses comparing different hemoadsorption devices were considered exploratory and not powered to support definitive conclusions. Although two different hemoadsorption devices were used, both are based on similar adsorption principles targeting middle-molecular-weight inflammatory mediators; therefore, the results were analyzed primarily according to the presence or absence of cytokine filtration. Blood Sampling and Biomarker Analysis Blood samples were collected at predefined time points: preoperatively (baseline), 30 minutes after initiation of CPB, 30 minutes after termination of CPB, and postoperatively at 0, 6, and 24 hours. Plasma for cytokine analysis was separated by centrifugation at 3000 × g for 10 minutes at 4°C within 30 minutes of collection, aliquoted into Eppendorf tubes, and stored at -86°C in a Nuve DF 490 (461 L) deep freezer. A maximum of one freeze- thaw cycle was permitted prior to analysis. Cytokine levels, including IL-6, IL-8, IL-10, and TNF-α, were measured in batches at an external certified laboratory using the IMMULITE 2000 system (Siemens Healthineers). Routine biochemical parameters, including CRP, AST, ALT, serum creatinine, and total bilirubin, were analyzed in the hospital’s central laboratory using the Roche Cobas c702 analyzer (Roche, Hitachi). Complete blood count parameters were measured using the Sysmex XN-1000 analyzer (serial number 16490), and the international normalized ratio (INR) was determined with the Stago STA-R Max system. Blood lactate levels were assessed using the ABL800 FLEX blood gas analyzer. Cardiac and inflammatory biomarkers, including troponin, ferritin, N-terminal pro–B-type natriuretic peptide (Pro-BNP), and procalcitonin, were measured using the Roche Cobas e602 analyzer. Inter-assay coefficients of variation were maintained below 10%. Clinical Data Collection and Outcomes Electronic medical records were retrospectively reviewed to collect demographic characteristics (age, sex, body mass index, smoking status), operative variables (CPB duration, aortic cross-clamp time, number of grafts), perioperative transfusion requirements, and postoperative outcomes. Postoperative outcomes included duration of mechanical ventilation, requirement for vasopressor or inotropic support, intra-aortic balloon pump (IABP) use, arrhythmias, infection or sepsis, acute kidney injury (AKI), in-hospital mortality, and lengths of intensive care unit (ICU) and hospital stay. AKI was defined according to the kidney disease: Improving Global Outcomes (KDIGO) 2012 criteria. Sepsis was defined using the Sepsis-3 consensus definition (2016). Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin criteria (2012). New-onset postoperative atrial fibrillation was defined as atrial fibrillation requiring medical treatment. The primary outcome of this study was the duration of postoperative mechanical ventilation. Secondary outcomes included the requirement for inotropic or vasopressor support, intra-aortic balloon pump (IABP) use, postoperative lactate levels, length of intensive care unit (ICU) stay, total hospital length of stay, and changes in inflammatory and biochemical markers. Safety outcomes included postoperative arrhythmias, acute kidney injury, neurological complications, re-exploration, and in-hospital mortality. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables were assessed for normality and are presented as mean ± standard deviation or median (interquartile range), as appropriate. Between-group comparisons of normally distributed variables were conducted using the Student’s t-test. Repeated-measures analysis of variance (ANOVA) was used to evaluate changes in biochemical parameters over time between groups. Assumptions for repeated-measures analysis were assessed prior to model application. p-value < 0.05 was considered statistically significant, and F values were also presented for the relevant repeated measurements. RESULTS Patient Characteristics A total of 45 patients undergoing elective isolated coronary artery bypass grafting were included in the analysis. 17 patients comprised the Filter Group, while 28 patients served as the Control Group. Baseline demographic characteristics and preoperative clinical variables were comparable between the two groups. The mean age was similar between patients receiving cytokine filtration and those in the Control Group, with no statistically significant difference observed. The distribution of sex, body mass index, and smoking status did not differ significantly between groups. Common comorbid conditions, including hypertension, diabetes mellitus, and chronic kidney disease, were evenly distributed, and the extent of coronary artery disease was comparable (Table 1 ). No significant differences were identified in preoperative characteristics between groups. Operative characteristics, including the type and amount of cardioplegia used (Fig. 1 A), preoperative length of stay (Fig. 1 B), number of bypass grafts (Fig. 1 C), cardiopulmonary bypass time (Fig. 1 D), cross-clamp time (Fig. 1 E), and intraoperative urine output (Fig. 1 F), were analyzed and compared between groups. No statistically significant differences were observed between the groups with respect to baseline demographic, clinical, or operative characteristics, indicating comparable preoperative risk profiles. Effect of Intraoperative Cytokine Filtration on Postoperative Outcomes Cytokine filters were used in 17 patients (Jafron HA330 (n = 8) and CytoSorb® (n = 9)). There was no significant difference in the number of bypassed vessels between the Filter and Control Groups (mean 3.41 ± 0.79, p > 0.05) (Fig. 1 C). Likewise, the mean number of bypassed vessels did not differ significantly among patients receiving no filter, Type 1 (Jafron HA330), or Type 2 (CytoSorb®) cytokine adsorption devices. In this study, two different hemoadsorption devices (Jafron HA330 and CytoSorb®) were used. Exploratory device-specific subgroup analyses did not reveal statistically significant differences in any of the analyzed clinical or biochemical outcomes; however, these analyses were exploratory and not powered for definitive comparisons. We have summarized our postoperative clinical outcomes in Fig. 2 . The median duration of mechanical ventilation was significantly shorter in the Filter Group compared with the Control Group (4 vs. 13 hours, p = 0.041 ) (Fig. 2 A). The median length of intensive care unit (ICU) stay (Fig. 2 B) was also shorter in the Filter Group (2 vs. 4 days) (Fig. 2 B); however, this difference did not reach statistical significance (p = 0.335). Inotropic support was required in 5.8% of patients in the Filter Group compared with 60.7% in the Control Group, which was statistically significant ( p < 0.001 ) (Fig. 2 C). Postoperative re-exploration rates were significantly lower in the Filter Group than in the Control Group ( p = 0.043 ) (Fig. 2 D). Intra-aortic balloon pump (IABP) use was observed in 0% of patients in the Filter Group versus 25% in the Control Group ( p = 0.006 ) (Fig. 2 E). No statistically significant differences were observed between the groups with respect to postoperative atrial fibrillation (p = 0.575) (Fig. 2 F), ventricular arrhythmias (p = 0.270) (Fig. 2 G), postoperative neurological deficits (p = 0.210) (Fig. 2 H), requirement for extracorporeal membrane oxygenation (ECMO) (p = 0.442) (Fig. 2 I), total length of hospital stay (p = 0.079) (Fig. 2 J), or in-hospital mortality (p = 0.591) (Fig. 2 K). Although the rate of reintubation was lower in the Filter Group, this difference did not reach statistical significance (p = 0.083) (Fig. 2 L). Effect of Filters on Serum Cytokine Levels Serum cytokine and inflammatory marker levels were compared between the Filter and Control Groups at predefined perioperative time points (Fig. 3 ). At postoperative 24 hours, serum interleukin-8 (IL-8) levels were significantly lower in the Filter Group compared with the Control Group ( p = 0.033 ) (Fig. 3 A). No statistically significant differences were observed between the groups in serum interleukin-6 (IL-6) (p = 0.342) (Fig. 3 B), interleukin-10 (IL-10) (p = 0.345) (Fig. 3 C), tumor necrosis factor-alpha (TNF-α) (p = 0.330) (Fig. 3 D). Effect of Filters on Serum Biochemical Parameters Postoperative biochemical parameters were compared between the Filter Group and the Control Group at predefined time points (Fig. 4 ). No statistically significant differences were observed between the groups in C-reactive protein (CRP) (p = 0.594) (Fig. 4 A). Postoperative 24-hour procalcitonin levels tended to be lower in the Filter Group, although this difference did not reach statistical significance (p = 0.088) (Fig. 4 B). In contrast, serum lactate levels differed significantly between groups at multiple perioperative time points. Lactate levels measured 30 minutes after termination of cardiopulmonary bypass were significantly lower in the Filter Group compared with the Control Group ( p = 0.027 ). This difference persisted in the early postoperative period, with significantly lower lactate levels observed at postoperative 0 hour ( p = 0.036 ) and at postoperative 24 hours ( p = 0.048 ) (Fig. 4 C). There were no statistically significant differences between the groups in hemoglobin (p = 0.255) (Fig. 4 D), hematocrit (p = 0.211) (Fig. 4 E), ferritin (p = 0.223) (Fig. 4 F), creatinine (p = 0.520) (Fig. 4 G), aspartate aminotransferase (AST) (p = 0.188) (Fig. 4 H), alanine aminotransferase (ALT) (p = 0.217) (Fig. 4 I), or white blood cell count (WBC) (p = 0.351) (Fig. 4 J) or troponin (p = 0.783) (Fig. 4 K). Subgroup Analyses Exploratory subgroup analyses were performed to assess whether common comorbidities, including diabetes mellitus and hypertension, modified the association between intraoperative cytokine filtration and early postoperative outcomes. In the Control group, 11 patients had diabetes mellitus, and 19 had hypertension, whereas in the Filter group, 9 patients had diabetes mellitus and 14 had hypertension. Across all evaluated parameters, including duration of mechanical ventilation, requirement for inotropic support, intensive care unit length of stay, and major postoperative complications, subgroup analyses according to diabetes mellitus or hypertension did not reveal statistically significant differences between the Filter and Control groups (all p > 0.05). No significant interaction between cytokine filter use and these comorbidities was observed. Given the limited sample size, these findings should be interpreted as exploratory and hypothesis-generating. DISCUSSION The present proof-of-concept study demonstrates that intraoperative cytokine filtration during elective isolated coronary artery bypass grafting is associated with improvements in selected early postoperative clinical outcomes. Patients receiving cytokine adsorption exhibited significantly shorter durations of mechanical ventilation, a markedly reduced requirement for inotropic support, and lower postoperative lactate levels compared with those undergoing conventional cardiopulmonary bypass. These findings suggest a potential clinical benefit of cytokine filtration that extends beyond biochemical modulation alone. Although the reduction in mechanical ventilation duration reached statistical significance, the effect size was modest but clinically meaningful and supported by consistent improvements in hemodynamic and metabolic parameters, including reduced inotropic support requirements and lower postoperative lactate levels. The decision to apply intraoperative cytokine adsorption was not guided by predefined risk stratification criteria but was based on intraoperative clinical judgment and device availability. Importantly, patients were not selected based on markers of increased perioperative risk, such as advanced age, higher EuroSCORE II, prolonged cardiopulmonary bypass duration, or greater comorbidity burden. Consistent with this, baseline demographic characteristics, operative variables, and risk profiles, including EuroSCORE II, were well balanced between the Filter and Control groups. This reduces, although does not eliminate, the likelihood that the observed associations were driven by baseline differences rather than the intervention itself. Although two different hemoadsorption devices were used in this study, both systems are based on similar non-selective adsorption principles targeting middle-molecular-weight inflammatory mediators. Importantly, standardized circuit configuration and blood flow parameters were applied for both devices, and no device-specific differences were observed across the analyzed outcomes. Nevertheless, given the limited sample size, device-specific effects cannot be definitively excluded and should be addressed in future studies specifically designed to compare different hemoadsorption systems. Cardiopulmonary bypass is a well-recognized trigger of a complex systemic inflammatory response mediated by leukocyte activation, complement cascade stimulation, endothelial dysfunction, and the release of pro- and anti-inflammatory cytokines. Excessive inflammation has been implicated in postoperative hemodynamic instability, impaired microcirculatory perfusion, and organ dysfunction following cardiac surgery. Accordingly, strategies aimed at attenuating this inflammatory response, such as leukocyte depletion and cytokine adsorption, have attracted increasing attention [ 4 , 6 , 26 – 31 ]. In the present study, intraoperative cytokine filtration was associated with a substantial reduction in postoperative inotropic support requirements and intra-aortic balloon pump utilization, suggesting improved early hemodynamic stability. The significantly lower rates of intra-aortic balloon pump use and postoperative re-exploration observed in the Filter group are clinically relevant. Although direct evidence linking cytokine adsorption to these outcomes in isolated CABG is limited, they may reflect improved early postoperative hemodynamic stability and tissue perfusion through attenuation of CPB-related inflammatory responses. This interpretation is further supported by the concurrent reduction in postoperative lactate levels, suggesting improved tissue perfusion and metabolic recovery in the early postoperative period. Given the observational design of the study, these findings should be interpreted as associative rather than causal and warrant confirmation in prospective studies. Despite these favorable clinical outcomes, attenuation of systemic inflammatory biomarkers was selective rather than uniform. The absence of uniform reductions in circulating cytokine levels may reflect rapid cytokine kinetics, continuous intraoperative production, and the timing of predefined sampling intervals, particularly for cytokines such as IL-6 with pronounced perioperative peaks. Among the measured cytokines, only interleukin-8 (IL-8) levels at postoperative 24 hours were significantly lower in patients receiving cytokine filtration, while no significant differences were observed for IL-6, IL-10, TNF-α, or CRP. This finding highlights an important aspect of cytokine adsorption therapy: clinical benefits may not necessarily correlate with global reductions in circulating cytokine concentrations. IL-8, a potent neutrophil chemoattractant, plays a central role in leukocyte activation, endothelial injury, and microvascular dysfunction. Selective modulation of IL-8 may therefore exert disproportionate effects on microcirculatory flow and organ function, potentially explaining the observed clinical improvements despite limited changes in other inflammatory mediators. An important finding of the present study is that improvements in early clinical outcomes were observed despite the absence of consistent and marked reductions in circulating cytokine levels. This apparent dissociation between biochemical markers and clinical outcomes has been previously reported in hemoadsorption studies and suggests that the clinical effects of cytokine filtration may not be fully captured by static plasma cytokine measurements. Hemoadsorption may primarily modulate cytokine kinetics, attenuate peak inflammatory exposure, and reduce the duration of tissue-level inflammatory signaling rather than induce large absolute decreases in circulating concentrations measured at discrete time points. The absence of a significant reduction in IL-6 levels warrants further consideration. IL-6 exhibits rapid and pronounced perioperative release in response to surgical trauma and ischemia–reperfusion injury, often peaking during or immediately after cardiopulmonary bypass [ 32 , 33 ]. Its dynamic kinetic profile, coupled with continuous production from activated immune cells and ischemic tissues, may exceed the adsorption capacity of hemoadsorption devices and limit the detectability of sustained reductions at predefined sampling time points. Additionally, the relatively small sample size may have reduced the statistical power to detect modest differences in IL-6 concentrations. These observations suggest that the clinical effects of cytokine filtration observed in this study may not be solely dependent on IL-6 suppression, but rather on selective modulation of downstream inflammatory pathways. Therefore, the absence of a significant reduction in IL-6 levels should not be interpreted as a lack of biological effect of cytokine adsorption, but rather as a reflection of cytokine kinetics, continuous perioperative production, and the timing of predefined sampling intervals. Moreover, cytokine adsorption may exert beneficial effects through mechanisms not fully captured by circulating cytokine measurements. These may include modulation of endothelial activation, reduction of locally active inflammatory mediators, stabilization of the endothelial glycocalyx, and attenuation of microvascular permeability. Borin et al. demonstrated that cytokine filtration directly clears proinflammatory mediators, thereby reducing endothelial dysfunction, capillary leak, and tissue injury [ 34 ]. Additionally, hemoadsorption may influence other unmeasured inflammatory or vasoactive substances, such as damage-associated molecular patterns or complement fragments, which could further contribute to improved hemodynamic stability and metabolic recovery [ 34 – 36 ]. Our results are consistent with a growing body of literature supporting the use of cytokine filtration in cardiac surgery. Träger et al. reported significant reductions in IL-6 and TNF-α levels accompanied by improved hemodynamic stability (14), while Garau et al. demonstrated reduced systemic inflammation and shorter ICU stays with intraoperative cytokine adsorption [ 16 ]. He et al. and Wang et al. reported similar benefits, particularly in patients undergoing complex or prolonged CPB procedures [ 18 , 37 ]. These findings suggest that the clinical impact of cytokine filtration may be more pronounced in patients at higher inflammatory risk, a hypothesis supported by the observed reductions in inotropic support in the present study. Although ICU length of stay was numerically shorter in the Filter Group, this difference did not reach statistical significance, possibly due to limited sample size. However, conflicting results exist in the literature. Naruka et al. conducted a systematic review and meta-analysis that revealed only modest reductions in inflammatory markers with cytokine filtration, with limited evidence supporting improvements in clinical outcomes [ 10 ]. Similarly, Bernardi et al. found no significant differences in IL-6 or CRP levels between patients receiving cytokine adsorption and those who did not [ 24 ]. However, given the retrospective observational design of the present study, the findings should be interpreted as associations rather than causal effects and are intended to be hypothesis-generating. Although baseline demographic and operative characteristics were comparable between the Filter and Control groups, residual confounding cannot be completely excluded due to the observational nature of the study. Taken together, these findings suggest that intraoperative cytokine filtration may preferentially improve early hemodynamic and metabolic recovery rather than uniformly suppress systemic inflammatory markers. Despite these encouraging findings, the broader clinical implementation of intraoperative cytokine filtration warrants careful consideration, as hemoadsorption devices introduce additional costs and procedural complexity, and their routine use in elective isolated CABG remains controversial in the absence of consistent improvements in hard clinical endpoints [ 10 , 24 ]. Limitations Although the number of patients was sufficient to provide an initial assessment of the potential role of intraoperative cytokine adsorption in this patient population, a larger sample size would improve the robustness and generalizability of the findings. The relatively small sample size, particularly within the filter subgroups, may have limited the statistical power to detect modest differences in biochemical and clinical endpoints. Therefore, subgroup and device-specific comparisons should be interpreted as exploratory rather than confirmatory. In addition, the lack of long-term follow-up restricts the ability to assess the sustained clinical impact of cytokine adsorption beyond the early postoperative period. CONCLUSIONS In conclusion, intraoperative cytokine filtration during CABG was associated with favorable trends in early postoperative clinical parameters, including shorter mechanical ventilation duration, reduced inotropic support requirements, and improved metabolic markers. Although the biochemical effects were selective, the observed clinical associations suggest that cytokine adsorption may favorably influence postoperative recovery through mechanisms beyond measurable cytokine clearance. Given the retrospective observational design, these findings should be interpreted as hypothesis-generating rather than definitive evidence of efficacy, and confirmation in adequately powered prospective randomized trials is warranted. Until such evidence is available, the routine use of intraoperative cytokine filtration in elective isolated CABG should be approached cautiously, with careful consideration of patient selection and overall clinical context. Abbreviations AKI: acute kidney injury; CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass; ICU: intensive care unit; IL: interleukin; TNF-α: tumor necrosis factor-alpha. Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Marmara University Faculty of Medicine Clinical Research Ethics Committee (Protocol Code: 09.2023.374, Approval Date: 03 January 2024). Due to the retrospective nature of the study and the use of anonymized patient data, the requirement for informed consent to participate was waived by the Ethics Committee. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no specific funding for this work. Authors’ contributions SK designed the study, collected the data, performed the analysis, and drafted the manuscript. SA contributed to the study design. EK performed the primary statistical analyses and contributed to the writing of the manuscript. FÖ, AG, and AS collected the data, and contributed to the writing of the manuscript. All authors read and approved the final manuscript. Acknowledgements The authors acknowledge the use of artificial intelligence–assisted tools solely for language editing and grammar refinement. The authors take full responsibility for the content of the manuscript. References Leivaditis V, Maniatopoulos AA, Mulita F, Baikoussis NG, Mitsos S, Liolis E, et al. Between air and artery: a history of cardiopulmonary bypass and the rise of modern cardiac surgery. Heart Surg Forum. 2025;28(1):E1–E10. Matte GS, Kwon M, Mayer JE Jr. Fundamentals of cardiopulmonary bypass for congenital heart surgery. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 08 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviews received at journal 23 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 14 Jan, 2026 Editor assigned by journal 14 Jan, 2026 Editor invited by journal 14 Jan, 2026 Submission checks completed at journal 13 Jan, 2026 First submitted to journal 13 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8584906","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":575815156,"identity":"b5068364-4145-4153-ae2c-02e179f5d4ed","order_by":0,"name":"SEVDA 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1","display":"","copyAsset":false,"role":"figure","size":92441,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOperative characteristics of patients\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8584906/v1/1941b2e49b0929bd7123b429.png"},{"id":100663585,"identity":"2701d57b-8537-46ac-8f91-b405019226a2","added_by":"auto","created_at":"2026-01-20 09:08:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":125158,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative clinical outcomes according to cytokine filtration use\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8584906/v1/b26e7269860dd02a94195b5b.png"},{"id":100663179,"identity":"a7f8e5a3-cbfe-4133-93bd-a4934dd20c1c","added_by":"auto","created_at":"2026-01-20 09:05:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":136997,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in cytokine levels\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8584906/v1/ddaa3751e99a4800d7536d86.png"},{"id":100663434,"identity":"01a87b84-bdfa-4deb-b3f4-802616bbab7f","added_by":"auto","created_at":"2026-01-20 09:06:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":165171,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative Serum Biochemical Parameters in the Filter and Control Groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8584906/v1/cf0bd3522b83a5b051d5eaaf.png"},{"id":100667494,"identity":"8ae1872d-7944-4fc7-82e3-552729a966e5","added_by":"auto","created_at":"2026-01-20 09:47:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1268574,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8584906/v1/4da54347-4bf0-4e77-b4f2-c4cd15cef0dc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A comprehensive analysis of intraoperative cytokine adsorption systems on early clinical outcomes after coronary artery bypass grafting","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCardiopulmonary bypass (CPB) enables cardiac surgery by providing temporary extracorporeal circulation to maintain systemic perfusion and oxygenation during operative arrest of the heart [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Despite its indispensable role, CPB triggers a systemic inflammatory response due to blood exposure to artificial surfaces, ischemia-reperfusion injury, and surgical trauma [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This inflammatory cascade activates leukocytes and complement pathways, leading to the release of pro-inflammatory cytokines, which may contribute to postoperative complications such as acute kidney injury, acute respiratory distress syndrome, prolonged intensive care unit (ICU) stay, and multiorgan dysfunction.\u003c/p\u003e \u003cp\u003eCytokine adsorption therapies have recently been introduced as an adjunctive strategy during CPB to attenuate this inflammatory response [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These hemoadsorption devices are designed to remove circulating cytokines, including interleukins and tumor necrosis factor-α, with the aim of reducing organ injury and improving postoperative recovery [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although reductions in circulating inflammatory biomarkers have been reported, evidence linking these biochemical effects to clinically meaningful postoperative outcomes remain limited, particularly in patients undergoing isolated coronary artery bypass grafting (CABG). Most previous studies have focused on biochemical endpoints in contexts such as septic shock, orthotopic heart transplantation, valve surgery, infective endocarditis, elective cardiac surgery using CPB, and type A aortic dissection [\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In contrast, data directly linking cytokine adsorption to early postoperative outcomes, such as duration of mechanical ventilation, hemodynamic support requirements, and ICU stay are scarce. Addressing this gap is essential to clarify the clinical relevance of cytokine filtration beyond laboratory findings and to guide its potential use in CABG patients.\u003c/p\u003e \u003cp\u003eCardiac surgery induces a systemic inflammatory response characterized by cytokines such as IL-6, IL-8, and TNF-α, which typically peak after CPB and normalize within 24 hours [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This response has been associated with multiorgan dysfunction, myocardial ischemia, low cardiac output, and increased infection risk [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. While intraoperative adsorption and filtration devices are considered safe, consistent evidence demonstrating clinical benefit is limited [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Although cytokine adsorption has been increasingly adopted in selected clinical settings, its widespread use is limited by additional costs and resource utilization. Given the lack of robust data demonstrating clear clinical benefit in low-risk or elective procedures such as isolated CABG, the cost-effectiveness of routine intraoperative cytokine filtration remains uncertain.\u003c/p\u003e \u003cp\u003eIn this context, the present study aimed to investigate the association between intraoperative cytokine filter use during cardiopulmonary bypass and early postoperative outcomes in patients undergoing elective isolated CABG. The primary focus was to evaluate postoperative inflammatory and biochemical parameters, as well as clinically relevant endpoints, including duration of mechanical ventilation, need for vasoactive support, length of stay in intensive care unit, and total hospital stay. By integrating laboratory and clinical outcomes, this study aimed to determine whether modulating the CPB-related inflammatory response through cytokine adsorption is associated with measurable improvements in early postoperative recovery. We hypothesized that intraoperative cytokine filtration would be associated with more favorable early postoperative clinical outcomes beyond changes in circulating cytokine levels. While the use of filters is a matter of debate among physicians in terms of cardiopulmonary bypass, clarifying this issue also provides information in discussions about whether filter use constitutes an additional burden on the healthcare system.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Population\u003c/h2\u003e \u003cp\u003eThis study included 45 adult patients (aged 44\u0026ndash;80 years) who underwent elective isolated coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) between January 1, 2023, and December 31, 2023, at Marmara University Pendik Training and Research Hospital. The study was approved by the Marmara University Faculty of Medicine Ethics Committee (Approval No: 09.2023.374; Date: 03.01.2024).\u003c/p\u003e \u003cp\u003ePatients were allocated into two groups. The \u003cb\u003eFilter Group\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;17) included patients who received intraoperative cytokine adsorption during CPB using either the Jafron HA330 device (Jafron, China; n\u0026thinsp;=\u0026thinsp;8) or the CytoSorb\u0026reg; device (CytoSorbents Corporation, USA; n\u0026thinsp;=\u0026thinsp;9). The \u003cb\u003eControl Group\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;28) consisted of patients who underwent CABG without cytokine filtration.\u003c/p\u003e \u003cp\u003ePatients with chronic obstructive pulmonary disease were excluded to minimize confounding effects on postoperative respiratory outcomes, particularly duration of mechanical ventilation. Recorded comorbidities included hypertension, diabetes mellitus, chronic kidney disease, and the extent of coronary artery disease. Baseline demographic and clinical characteristics were comparable between the filtered and non-filtered groups, with no statistically significant differences observed (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003ePopulation\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;45\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eFilter usage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;28\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (77.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (70.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.507\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (29.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (78.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (82.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (39.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.383\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (67.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (82.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (11.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuroSCORE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 (0.5\u0026ndash;13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.5\u0026ndash;13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8 (0.5\u0026ndash;2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative hospitalization time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.2 (1\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.07 (1\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.76 (1\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (interquartile range), or number (percentage). Categorical variables are presented as a number (%). EuroSCORE II values showed a right-skewed distribution.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBaseline demographic characteristics, comorbidities, and operative variables were collected for both groups. The decision to apply cytokine adsorption was not based on predefined risk stratification criteria but on intraoperative clinical judgment and device availability. Importantly, patients were not selected for cytokine adsorption based on predefined high-risk criteria such as advanced age, elevated EuroSCORE II, prolonged cardiopulmonary bypass duration, or increased comorbidity burden.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCardiopulmonary Bypass and Cytokine Filter Application\u003c/h3\u003e\n\u003cp\u003eAll procedures were performed using standard CPB techniques under moderate hypothermia (32\u0026ndash;34\u0026deg;C). Cardiopulmonary bypass was established using a Stockert S5 heart-lung machine (LivaNova, Germany) with a Sorin Inspire\u0026trade; membrane oxygenator. Two cytokine filter devices (Jafron HA330 and CytoSorb\u0026reg;), both based on similar hemoadsorption principles, were integrated into the cardiopulmonary bypass circuit using an identical parallel configuration with a standardized blood flow of 300 mL/min. Both hemoadsorption devices were applied using identical circuit configurations and standardized blood flow parameters and are designed to target middle-molecular-weight inflammatory mediators through non-selective adsorption mechanisms. Circuit pressures, pump flow parameters, and hematocrit levels were continuously monitored. Post-bypass lactate dehydrogenase (LDH) and plasma-free hemoglobin levels were assessed as surrogate markers of hemolysis. Given the limited number of patients in each subgroup, analyses comparing different hemoadsorption devices were considered exploratory and not powered to support definitive conclusions. Although two different hemoadsorption devices were used, both are based on similar adsorption principles targeting middle-molecular-weight inflammatory mediators; therefore, the results were analyzed primarily according to the presence or absence of cytokine filtration.\u003c/p\u003e\n\u003ch3\u003eBlood Sampling and Biomarker Analysis\u003c/h3\u003e\n\u003cp\u003eBlood samples were collected at predefined time points: preoperatively (baseline), 30 minutes after initiation of CPB, 30 minutes after termination of CPB, and postoperatively at 0, 6, and 24 hours. Plasma for cytokine analysis was separated by centrifugation at 3000 \u0026times; g for 10 minutes at 4\u0026deg;C within 30 minutes of collection, aliquoted into Eppendorf tubes, and stored at -86\u0026deg;C in a Nuve DF 490 (461 L) deep freezer. A maximum of one freeze- thaw cycle was permitted prior to analysis. Cytokine levels, including IL-6, IL-8, IL-10, and TNF-α, were measured in batches at an external certified laboratory using the IMMULITE 2000 system (Siemens Healthineers).\u003c/p\u003e \u003cp\u003eRoutine biochemical parameters, including CRP, AST, ALT, serum creatinine, and total bilirubin, were analyzed in the hospital\u0026rsquo;s central laboratory using the Roche Cobas c702 analyzer (Roche, Hitachi). Complete blood count parameters were measured using the Sysmex XN-1000 analyzer (serial number 16490), and the international normalized ratio (INR) was determined with the Stago STA-R Max system. Blood lactate levels were assessed using the ABL800 FLEX blood gas analyzer. Cardiac and inflammatory biomarkers, including troponin, ferritin, N-terminal pro\u0026ndash;B-type natriuretic peptide (Pro-BNP), and procalcitonin, were measured using the Roche Cobas e602 analyzer. Inter-assay coefficients of variation were maintained below 10%.\u003c/p\u003e\n\u003ch3\u003eClinical Data Collection and Outcomes\u003c/h3\u003e\n\u003cp\u003eElectronic medical records were retrospectively reviewed to collect demographic characteristics (age, sex, body mass index, smoking status), operative variables (CPB duration, aortic cross-clamp time, number of grafts), perioperative transfusion requirements, and postoperative outcomes. Postoperative outcomes included duration of mechanical ventilation, requirement for vasopressor or inotropic support, intra-aortic balloon pump (IABP) use, arrhythmias, infection or sepsis, acute kidney injury (AKI), in-hospital mortality, and lengths of intensive care unit (ICU) and hospital stay. AKI was defined according to the kidney disease: Improving Global Outcomes (KDIGO) 2012 criteria. Sepsis was defined using the Sepsis-3 consensus definition (2016). Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin criteria (2012). New-onset postoperative atrial fibrillation was defined as atrial fibrillation requiring medical treatment. The primary outcome of this study was the duration of postoperative mechanical ventilation. Secondary outcomes included the requirement for inotropic or vasopressor support, intra-aortic balloon pump (IABP) use, postoperative lactate levels, length of intensive care unit (ICU) stay, total hospital length of stay, and changes in inflammatory and biochemical markers. Safety outcomes included postoperative arrhythmias, acute kidney injury, neurological complications, re-exploration, and in-hospital mortality.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables were assessed for normality and are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range), as appropriate. Between-group comparisons of normally distributed variables were conducted using the Student\u0026rsquo;s t-test. Repeated-measures analysis of variance (ANOVA) was used to evaluate changes in biochemical parameters over time between groups. Assumptions for repeated-measures analysis were assessed prior to model application. p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant, and F values were also presented for the relevant repeated measurements.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eA total of 45 patients undergoing elective isolated coronary artery bypass grafting were included in the analysis. 17 patients comprised the Filter Group, while 28 patients served as the Control Group. Baseline demographic characteristics and preoperative clinical variables were comparable between the two groups. The mean age was similar between patients receiving cytokine filtration and those in the Control Group, with no statistically significant difference observed. The distribution of sex, body mass index, and smoking status did not differ significantly between groups. Common comorbid conditions, including hypertension, diabetes mellitus, and chronic kidney disease, were evenly distributed, and the extent of coronary artery disease was comparable (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No significant differences were identified in preoperative characteristics between groups.\u003c/p\u003e \u003cp\u003eOperative characteristics, including the type and amount of cardioplegia used (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), preoperative length of stay (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), number of bypass grafts (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), cardiopulmonary bypass time (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eD), cross-clamp time (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eE), and intraoperative urine output (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eF), were analyzed and compared between groups. No statistically significant differences were observed between the groups with respect to baseline demographic, clinical, or operative characteristics, indicating comparable preoperative risk profiles.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEffect of Intraoperative Cytokine Filtration on Postoperative Outcomes\u003c/h3\u003e\n\u003cp\u003eCytokine filters were used in 17 patients (Jafron HA330 (n\u0026thinsp;=\u0026thinsp;8) and CytoSorb\u0026reg; (n\u0026thinsp;=\u0026thinsp;9)). There was no significant difference in the number of bypassed vessels between the Filter and Control Groups (mean 3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Likewise, the mean number of bypassed vessels did not differ significantly among patients receiving no filter, Type 1 (Jafron HA330), or Type 2 (CytoSorb\u0026reg;) cytokine adsorption devices. In this study, two different hemoadsorption devices (Jafron HA330 and CytoSorb\u0026reg;) were used. Exploratory device-specific subgroup analyses did not reveal statistically significant differences in any of the analyzed clinical or biochemical outcomes; however, these analyses were exploratory and not powered for definitive comparisons.\u003c/p\u003e \u003cp\u003eWe have summarized our postoperative clinical outcomes in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median duration of mechanical ventilation was significantly shorter in the Filter Group compared with the Control Group (4 vs. 13 hours, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.041\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The median length of intensive care unit (ICU) stay (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) was also shorter in the Filter Group (2 vs. 4 days) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eB); however, this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.335).\u003c/p\u003e \u003cp\u003eInotropic support was required in 5.8% of patients in the Filter Group compared with 60.7% in the Control Group, which was statistically significant (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Postoperative re-exploration rates were significantly lower in the Filter Group than in the Control Group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.043\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Intra-aortic balloon pump (IABP) use was observed in 0% of patients in the Filter Group versus 25% in the Control Group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.006\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eE).\u003c/p\u003e \u003cp\u003eNo statistically significant differences were observed between the groups with respect to postoperative atrial fibrillation (p\u0026thinsp;=\u0026thinsp;0.575) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eF), ventricular arrhythmias (p\u0026thinsp;=\u0026thinsp;0.270) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eG), postoperative neurological deficits (p\u0026thinsp;=\u0026thinsp;0.210) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eH), requirement for extracorporeal membrane oxygenation (ECMO) (p\u0026thinsp;=\u0026thinsp;0.442) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eI), total length of hospital stay (p\u0026thinsp;=\u0026thinsp;0.079) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ), or in-hospital mortality (p\u0026thinsp;=\u0026thinsp;0.591) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eK).\u003c/p\u003e \u003cp\u003eAlthough the rate of reintubation was lower in the Filter Group, this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.083) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eL).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Filters on Serum Cytokine Levels\u003c/h2\u003e \u003cp\u003eSerum cytokine and inflammatory marker levels were compared between the Filter and Control Groups at predefined perioperative time points (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003e). At postoperative 24 hours, serum interleukin-8 (IL-8) levels were significantly lower in the Filter Group compared with the Control Group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.033\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003eNo statistically significant differences were observed between the groups in serum interleukin-6 (IL-6) (p\u0026thinsp;=\u0026thinsp;0.342) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), interleukin-10 (IL-10) (p\u0026thinsp;=\u0026thinsp;0.345) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eC), tumor necrosis factor-alpha (TNF-α) (p\u0026thinsp;=\u0026thinsp;0.330) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Filters on Serum Biochemical Parameters\u003c/h2\u003e \u003cp\u003ePostoperative biochemical parameters were compared between the Filter Group and the Control Group at predefined time points (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e). No statistically significant differences were observed between the groups in C-reactive protein (CRP) (p\u0026thinsp;=\u0026thinsp;0.594) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Postoperative 24-hour procalcitonin levels tended to be lower in the Filter Group, although this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.088) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eIn contrast, serum lactate levels differed significantly between groups at multiple perioperative time points. Lactate levels measured 30 minutes after termination of cardiopulmonary bypass were significantly lower in the Filter Group compared with the Control Group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.027\u003c/em\u003e). This difference persisted in the early postoperative period, with significantly lower lactate levels observed at postoperative 0 hour (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.036\u003c/em\u003e) and at postoperative 24 hours (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.048\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eThere were no statistically significant differences between the groups in hemoglobin (p\u0026thinsp;=\u0026thinsp;0.255) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eD), hematocrit (p\u0026thinsp;=\u0026thinsp;0.211) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eE), ferritin (p\u0026thinsp;=\u0026thinsp;0.223) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eF), creatinine (p\u0026thinsp;=\u0026thinsp;0.520) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eG), aspartate aminotransferase (AST) (p\u0026thinsp;=\u0026thinsp;0.188) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eH), alanine aminotransferase (ALT) (p\u0026thinsp;=\u0026thinsp;0.217) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eI), or white blood cell count (WBC) (p\u0026thinsp;=\u0026thinsp;0.351) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eJ) or troponin (p\u0026thinsp;=\u0026thinsp;0.783) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eK).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Analyses\u003c/h2\u003e \u003cp\u003eExploratory subgroup analyses were performed to assess whether common comorbidities, including diabetes mellitus and hypertension, modified the association between intraoperative cytokine filtration and early postoperative outcomes. In the Control group, 11 patients had diabetes mellitus, and 19 had hypertension, whereas in the Filter group, 9 patients had diabetes mellitus and 14 had hypertension.\u003c/p\u003e \u003cp\u003eAcross all evaluated parameters, including duration of mechanical ventilation, requirement for inotropic support, intensive care unit length of stay, and major postoperative complications, subgroup analyses according to diabetes mellitus or hypertension did not reveal statistically significant differences between the Filter and Control groups (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No significant interaction between cytokine filter use and these comorbidities was observed. Given the limited sample size, these findings should be interpreted as exploratory and hypothesis-generating.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe present proof-of-concept study demonstrates that intraoperative cytokine filtration during elective isolated coronary artery bypass grafting is associated with improvements in selected early postoperative clinical outcomes. Patients receiving cytokine adsorption exhibited significantly shorter durations of mechanical ventilation, a markedly reduced requirement for inotropic support, and lower postoperative lactate levels compared with those undergoing conventional cardiopulmonary bypass. These findings suggest a potential clinical benefit of cytokine filtration that extends beyond biochemical modulation alone. Although the reduction in mechanical ventilation duration reached statistical significance, the effect size was modest but clinically meaningful and supported by consistent improvements in hemodynamic and metabolic parameters, including reduced inotropic support requirements and lower postoperative lactate levels.\u003c/p\u003e \u003cp\u003eThe decision to apply intraoperative cytokine adsorption was not guided by predefined risk stratification criteria but was based on intraoperative clinical judgment and device availability. Importantly, patients were not selected based on markers of increased perioperative risk, such as advanced age, higher EuroSCORE II, prolonged cardiopulmonary bypass duration, or greater comorbidity burden. Consistent with this, baseline demographic characteristics, operative variables, and risk profiles, including EuroSCORE II, were well balanced between the Filter and Control groups. This reduces, although does not eliminate, the likelihood that the observed associations were driven by baseline differences rather than the intervention itself.\u003c/p\u003e \u003cp\u003eAlthough two different hemoadsorption devices were used in this study, both systems are based on similar non-selective adsorption principles targeting middle-molecular-weight inflammatory mediators. Importantly, standardized circuit configuration and blood flow parameters were applied for both devices, and no device-specific differences were observed across the analyzed outcomes. Nevertheless, given the limited sample size, device-specific effects cannot be definitively excluded and should be addressed in future studies specifically designed to compare different hemoadsorption systems.\u003c/p\u003e \u003cp\u003eCardiopulmonary bypass is a well-recognized trigger of a complex systemic inflammatory response mediated by leukocyte activation, complement cascade stimulation, endothelial dysfunction, and the release of pro- and anti-inflammatory cytokines. Excessive inflammation has been implicated in postoperative hemodynamic instability, impaired microcirculatory perfusion, and organ dysfunction following cardiac surgery. Accordingly, strategies aimed at attenuating this inflammatory response, such as leukocyte depletion and cytokine adsorption, have attracted increasing attention [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28 CR29 CR30\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present study, intraoperative cytokine filtration was associated with a substantial reduction in postoperative inotropic support requirements and intra-aortic balloon pump utilization, suggesting improved early hemodynamic stability. The significantly lower rates of intra-aortic balloon pump use and postoperative re-exploration observed in the Filter group are clinically relevant. Although direct evidence linking cytokine adsorption to these outcomes in isolated CABG is limited, they may reflect improved early postoperative hemodynamic stability and tissue perfusion through attenuation of CPB-related inflammatory responses.\u003c/p\u003e \u003cp\u003eThis interpretation is further supported by the concurrent reduction in postoperative lactate levels, suggesting improved tissue perfusion and metabolic recovery in the early postoperative period. Given the observational design of the study, these findings should be interpreted as associative rather than causal and warrant confirmation in prospective studies.\u003c/p\u003e \u003cp\u003eDespite these favorable clinical outcomes, attenuation of systemic inflammatory biomarkers was selective rather than uniform. The absence of uniform reductions in circulating cytokine levels may reflect rapid cytokine kinetics, continuous intraoperative production, and the timing of predefined sampling intervals, particularly for cytokines such as IL-6 with pronounced perioperative peaks. Among the measured cytokines, only interleukin-8 (IL-8) levels at postoperative 24 hours were significantly lower in patients receiving cytokine filtration, while no significant differences were observed for IL-6, IL-10, TNF-α, or CRP. This finding highlights an important aspect of cytokine adsorption therapy: clinical benefits may not necessarily correlate with global reductions in circulating cytokine concentrations. IL-8, a potent neutrophil chemoattractant, plays a central role in leukocyte activation, endothelial injury, and microvascular dysfunction. Selective modulation of IL-8 may therefore exert disproportionate effects on microcirculatory flow and organ function, potentially explaining the observed clinical improvements despite limited changes in other inflammatory mediators.\u003c/p\u003e \u003cp\u003eAn important finding of the present study is that improvements in early clinical outcomes were observed despite the absence of consistent and marked reductions in circulating cytokine levels. This apparent dissociation between biochemical markers and clinical outcomes has been previously reported in hemoadsorption studies and suggests that the clinical effects of cytokine filtration may not be fully captured by static plasma cytokine measurements. Hemoadsorption may primarily modulate cytokine kinetics, attenuate peak inflammatory exposure, and reduce the duration of tissue-level inflammatory signaling rather than induce large absolute decreases in circulating concentrations measured at discrete time points.\u003c/p\u003e \u003cp\u003eThe absence of a significant reduction in IL-6 levels warrants further consideration. IL-6 exhibits rapid and pronounced perioperative release in response to surgical trauma and ischemia\u0026ndash;reperfusion injury, often peaking during or immediately after cardiopulmonary bypass [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Its dynamic kinetic profile, coupled with continuous production from activated immune cells and ischemic tissues, may exceed the adsorption capacity of hemoadsorption devices and limit the detectability of sustained reductions at predefined sampling time points. Additionally, the relatively small sample size may have reduced the statistical power to detect modest differences in IL-6 concentrations. These observations suggest that the clinical effects of cytokine filtration observed in this study may not be solely dependent on IL-6 suppression, but rather on selective modulation of downstream inflammatory pathways. Therefore, the absence of a significant reduction in IL-6 levels should not be interpreted as a lack of biological effect of cytokine adsorption, but rather as a reflection of cytokine kinetics, continuous perioperative production, and the timing of predefined sampling intervals.\u003c/p\u003e \u003cp\u003eMoreover, cytokine adsorption may exert beneficial effects through mechanisms not fully captured by circulating cytokine measurements. These may include modulation of endothelial activation, reduction of locally active inflammatory mediators, stabilization of the endothelial glycocalyx, and attenuation of microvascular permeability. Borin et al. demonstrated that cytokine filtration directly clears proinflammatory mediators, thereby reducing endothelial dysfunction, capillary leak, and tissue injury [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Additionally, hemoadsorption may influence other unmeasured inflammatory or vasoactive substances, such as damage-associated molecular patterns or complement fragments, which could further contribute to improved hemodynamic stability and metabolic recovery [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur results are consistent with a growing body of literature supporting the use of cytokine filtration in cardiac surgery. Tr\u0026auml;ger et al. reported significant reductions in IL-6 and TNF-α levels accompanied by improved hemodynamic stability (14), while Garau et al. demonstrated reduced systemic inflammation and shorter ICU stays with intraoperative cytokine adsorption [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. He et al. and Wang et al. reported similar benefits, particularly in patients undergoing complex or prolonged CPB procedures [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. These findings suggest that the clinical impact of cytokine filtration may be more pronounced in patients at higher inflammatory risk, a hypothesis supported by the observed reductions in inotropic support in the present study. Although ICU length of stay was numerically shorter in the Filter Group, this difference did not reach statistical significance, possibly due to limited sample size.\u003c/p\u003e \u003cp\u003eHowever, conflicting results exist in the literature. Naruka et al. conducted a systematic review and meta-analysis that revealed only modest reductions in inflammatory markers with cytokine filtration, with limited evidence supporting improvements in clinical outcomes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Similarly, Bernardi et al. found no significant differences in IL-6 or CRP levels between patients receiving cytokine adsorption and those who did not [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, given the retrospective observational design of the present study, the findings should be interpreted as associations rather than causal effects and are intended to be hypothesis-generating. Although baseline demographic and operative characteristics were comparable between the Filter and Control groups, residual confounding cannot be completely excluded due to the observational nature of the study.\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that intraoperative cytokine filtration may preferentially improve early hemodynamic and metabolic recovery rather than uniformly suppress systemic inflammatory markers. Despite these encouraging findings, the broader clinical implementation of intraoperative cytokine filtration warrants careful consideration, as hemoadsorption devices introduce additional costs and procedural complexity, and their routine use in elective isolated CABG remains controversial in the absence of consistent improvements in hard clinical endpoints [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eAlthough the number of patients was sufficient to provide an initial assessment of the potential role of intraoperative cytokine adsorption in this patient population, a larger sample size would improve the robustness and generalizability of the findings. The relatively small sample size, particularly within the filter subgroups, may have limited the statistical power to detect modest differences in biochemical and clinical endpoints. Therefore, subgroup and device-specific comparisons should be interpreted as exploratory rather than confirmatory. In addition, the lack of long-term follow-up restricts the ability to assess the sustained clinical impact of cytokine adsorption beyond the early postoperative period.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn conclusion, intraoperative cytokine filtration during CABG was associated with favorable trends in early postoperative clinical parameters, including shorter mechanical ventilation duration, reduced inotropic support requirements, and improved metabolic markers. Although the biochemical effects were selective, the observed clinical associations suggest that cytokine adsorption may favorably influence postoperative recovery through mechanisms beyond measurable cytokine clearance. Given the retrospective observational design, these findings should be interpreted as hypothesis-generating rather than definitive evidence of efficacy, and confirmation in adequately powered prospective randomized trials is warranted. Until such evidence is available, the routine use of intraoperative cytokine filtration in elective isolated CABG should be approached cautiously, with careful consideration of patient selection and overall clinical context.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAKI: acute kidney injury; CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass; ICU: intensive care unit; IL: interleukin; TNF-\u0026alpha;: tumor necrosis factor-alpha.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Marmara University Faculty of Medicine Clinical Research Ethics Committee (Protocol Code: 09.2023.374, Approval Date: 03 January 2024). Due to the retrospective nature of the study and the use of anonymized patient data, the requirement for informed consent to participate was waived by the Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSK designed the study, collected the data, performed the analysis, and drafted the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSA contributed to the study design.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEK performed the primary statistical analyses and contributed to the writing of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFÖ, AG, and AS collected the data, and contributed to the writing of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the use of artificial intelligence–assisted tools solely for language editing and grammar refinement. The authors take full responsibility for the content of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLeivaditis V, Maniatopoulos AA, Mulita F, Baikoussis NG, Mitsos S, Liolis E, et al. Between air and artery: a history of cardiopulmonary bypass and the rise of modern cardiac surgery. Heart Surg Forum. 2025;28(1):E1\u0026ndash;E10.\u003c/li\u003e\n\u003cli\u003eMatte GS, Kwon M, Mayer JE Jr. Fundamentals of cardiopulmonary bypass for congenital heart surgery. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, editors. Nadas\u0026rsquo; Pediatric Cardiology. 3rd ed. Philadelphia: Elsevier; 2025. p. 719\u0026ndash;730.\u003c/li\u003e\n\u003cli\u003eIsmail A, Semien G, Sharma S, Collier SA, Miskolczi SY. Cardiopulmonary bypass. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.\u003c/li\u003e\n\u003cli\u003eDeisch P, Soukup SM, Adams P, Wild MC. 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Circulation. 2005;112(19):2912\u0026ndash;2920.\u003c/li\u003e\n\u003cli\u003eFranke A, Lante W, Fackeldey V, Becker HP, Thode C, Kuhlmann WD, Markewitz A. Proinflammatory and anti-inflammatory cytokines after cardiac operation: different cellular sources at different times. Ann Thorac Surg. 2002;74(2):363\u0026ndash;370.\u003c/li\u003e\n\u003cli\u003eNaruka V, Salmasi MY, Rad AA, Marczin N, Lazopoulos G, Moscarelli M, et al. Use of cytokine filters during cardiopulmonary bypass: a systematic review and meta-analysis. Heart Lung Circ. 2022;31(11):1493\u0026ndash;1503.\u003c/li\u003e\n\u003cli\u003eKogelmann K, Jarczak D, Scheller M, Dr\u0026uuml;ner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care. 2017;21:74.\u003c/li\u003e\n\u003cli\u003eHetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to \u0026beta;-hemolytic streptococcus-induced necrotizing fasciitis treated with cytokine adsorption therapy. Int J Artif Organs. 2014;37(6):422\u0026ndash;426.\u003c/li\u003e\n\u003cli\u003eNemeth E, Kovacs E, Racz K, Soltesz A, Szigeti S, Kiss N, et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation\u0026mdash;an observational study. Clin Transplant. 2018;32(4):e13211.\u003c/li\u003e\n\u003cli\u003eTr\u0026auml;ger K, Fritzler D, Fischer G, Schr\u0026ouml;der J, Skrabal C, Liebold A, Reinelt H. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series. Int J Artif Organs. 2016;39(3):141\u0026ndash;146.\u003c/li\u003e\n\u003cli\u003eTotsugawa T, Kuinose M, Yoshitaka H, Tsushima Y, Ishida A, Chikazawa G, et al. Intraoperative direct hemoperfusion with polymyxin-B immobilized fiber column for infective endocarditis. Gen Thorac Cardiovasc Surg. 2011;59:98\u0026ndash;104.\u003c/li\u003e\n\u003cli\u003eGarau I, M\u0026auml;rz A, Sehner S, Reuter DA, Reichenspurner H, Z\u0026ouml;llner C, Kubitz JC. Hemoadsorption during cardiopulmonary bypass reduces interleukin-8 and TNF-\u0026alpha; serum levels: a randomized controlled trial. Minerva Anestesiol. 2019;85(7):715\u0026ndash;723.\u003c/li\u003e\n\u003cli\u003eGorjipour F, Totonchi Z, Gholampour Dehaki M, Hosseini S, Tirgarfakheri K, Mehrabanian M, et al. Cytokines and outcomes in pediatric cardiopulmonary bypass surgery. Perfusion. 2019;34(8):651\u0026ndash;659.\u003c/li\u003e\n\u003cli\u003eWang J, Chen B, Xie J, Chen H, Li L, Zhang W, et al. Effect of blood hemoperfusion therapy in acute type A aortic dissection surgery. Blood Purif. 2022;51(4):321\u0026ndash;329.\u003c/li\u003e\n\u003cli\u003eHohn A, Malewicz-Oeck NM, Buchwald D, Annecke T, Zahn PK, Baumann A. Removal of cytokines during cardiac surgery (RECCAS): a randomized controlled trial. Crit Care. 2024;28(1):406.\u003c/li\u003e\n\u003cli\u003eMcGuinness J, Bouchier-Hayes D, Redmond J. Understanding the inflammatory response to cardiac surgery. 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Efficacy of CytoSorb\u0026reg;: a systematic review and meta-analysis. Crit Care. 2023;27(1):215.\u003c/li\u003e\n\u003cli\u003eB\u0026uuml;y\u0026uuml;kkol H. Kardiyopulmoner bypass\u0026rsquo;ta kullanılan d\u0026ouml;rt farklı membran oksijenat\u0026ouml;r\u0026uuml;n karşılaştırılması. PhD Thesis. İstanbul: İstanbul \u0026Uuml;niversitesi; 2020.\u003c/li\u003e\n\u003cli\u003ePaparella D, Yau TM, Young E. Cardiopulmonary bypass-induced inflammation: pathophysiology and treatment. Eur J Cardiothorac Surg. 2002;21(2):232\u0026ndash;244.\u003c/li\u003e\n\u003cli\u003evan Oeveren W, Kazatchkine MD, Descamps-Latscha B, Maillet F, Fischer E, Carpentier A, Wildevuur CR. Deleterious effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1985;89(6):888\u0026ndash;899.\u003c/li\u003e\n\u003cli\u003eLi Y, Lin H, Zhao Y, Li Z, Liu D, Wu X, et al. Del Nido cardioplegia in adult cardiac surgery: a meta-analysis. ASAIO J. 2018;64(3):360\u0026ndash;368.\u003c/li\u003e\n\u003cli\u003eHyde RA, Ishikawa MY, Jung EK, Langer R, Leuthardt EC, Myhrvold NP, et al. Device and method for reducing inflammatory mediators. US Patent US20120065432A1. 2012.\u003c/li\u003e\n\u003cli\u003eFujii Y. Novel leukocyte removal filter in cardiopulmonary bypass. Expert Rev Med Devices. 2016;13(1):5\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eYue Y, Wang C, Benedict C, Huang G, Truongcao M, Roy R, et al. IL-10 deficiency alters myocardial repair. Circ Res. 2020;126(3):315\u0026ndash;329.\u003c/li\u003e\n\u003cli\u003eSquiccimarro E, Stasi A, Lorusso R, Paparella D. Systemic inflammatory reaction to cardiac surgery. Artif Organs. 2022;46(4):568\u0026ndash;577.\u003c/li\u003e\n\u003cli\u003eBorin MC, Martins CR, dos Reis DP, Ribeiro GJC, Tupinambas JT, de Castro Zocrato K, et al. Cytokine filtration in cardiac surgery for endocarditis. Int J Technol Assess Health Care. 2024;40(S1):S140\u0026ndash;S141.\u003c/li\u003e\n\u003cli\u003eGovender K, Cabrales P. Extracorporeal circulation impairs microcirculation. J Appl Physiol. 2022;132(3):794\u0026ndash;810.\u003c/li\u003e\n\u003cli\u003eBanerjee D, Feng J, Sellke FW. Strategies to attenuate inflammatory response in CPB. Front Surg. 2024;11:1224068.\u003c/li\u003e\n\u003cli\u003eHe Z, Lu H, Jian X, Li G, Xiao D, Meng Q, et al. Resin hemoperfusion during adult CPB. Blood Purif. 2022;51(1):31\u0026ndash;37.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cardiopulmonary bypass, Cytokine adsorption, Coronary artery bypass grafting, Inflammation, Postoperative outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8584906/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8584906/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCardiopulmonary bypass (CPB) induces a systemic inflammatory response mediated by cytokine release, which may contribute to postoperative cardiovascular and systemic organ dysfunction following coronary artery bypass grafting (CABG). Cytokine adsorption filters have been developed to attenuate this response; however, their clinical efficacy in CABG remains controversial and a matter of debate among physicians and healthcare systems.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis observational study compared early postoperative outcomes in 17 patients undergoing CABG with intraoperative cytokine adsorption using two different filter systems and 28 control patients undergoing CABG without cytokine filtration. Baseline demographic and operative characteristics were recorded. Clinical outcomes and inflammatory and biochemical markers, including C-reactive protein (CRP), procalcitonin, ferritin, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were measured at predefined perioperative time points.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBaseline characteristics were comparable between groups, and no significant differences were observed between the two filter systems. Exploratory subgroup analyses stratified by hypertension and diabetes mellitus did not demonstrate a differential effect of cytokine filtration on the assessed outcomes. Compared with the Control group, the Filter group demonstrated a significantly shorter duration of mechanical ventilation (median 4 vs. 13 hours; p\u0026thinsp;=\u0026thinsp;0.041) and a substantially lower requirement for inotropic support (5.8% vs. 60.7%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Intra-aortic balloon pump use and re-exploration rates were significantly lower in the Filter group. Lactate levels following CPB and during the early postoperative period were significantly lower in the Filter group. Among inflammatory markers, only IL-8 levels at 24 hours postoperatively were significantly reduced, while IL-6, IL-10, TNF-α, and CRP showed no significant intergroup differences.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIntraoperative cytokine adsorption during CABG was associated with improved early postoperative clinical outcomes despite limited effects on most circulating inflammatory markers. These findings are hypothesis-generating and warrant confirmation in adequately powered randomized controlled trials to inform clinicians\u0026rsquo; decision-making regarding their use in patients.\u003c/p\u003e","manuscriptTitle":"A comprehensive analysis of intraoperative cytokine adsorption systems on early clinical outcomes after coronary artery bypass grafting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 08:20:21","doi":"10.21203/rs.3.rs-8584906/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-08T04:51:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T14:40:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290065752527604963827527569712045230766","date":"2026-05-04T12:44:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215891689852702155108305420640868095184","date":"2026-04-29T12:05:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T21:15:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134031705783985001733632368951741753294","date":"2026-04-23T00:59:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-14T17:36:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-14T16:17:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-14T05:53:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T19:23:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-01-13T19:17:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6b81dc6-7d50-4474-9a64-9b0b18ccc21c","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-08T04:51:57+00:00","index":76,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T14:40:31+00:00","index":75,"fulltext":""},{"type":"reviewerAgreed","content":"290065752527604963827527569712045230766","date":"2026-05-04T12:44:46+00:00","index":74,"fulltext":""},{"type":"reviewerAgreed","content":"215891689852702155108305420640868095184","date":"2026-04-29T12:05:04+00:00","index":69,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-20T08:20:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 08:20:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8584906","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8584906","identity":"rs-8584906","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}