Sepsis Risk after On-pump vs Off-pump Coronary Artery Bypass Surgery: A MIMIC-IV Database Analysis

Sepsis Risk after On-pump vs Off-pump Coronary Artery Bypass Surgery: A MIMIC-IV Database Analysis | 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 Sepsis Risk after On-pump vs Off-pump Coronary Artery Bypass Surgery: A MIMIC-IV Database Analysis Xiaojie Yu, Yang Cao, Qingchun Liang, Lin Wang, Bing Liang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8416630/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Objective This study aims to compare the differences in postoperative sepsis between patients treated with coronary artery bypass grafting (CABG) with and without cardiopulmonary bypass (CPB), and investigate the related risk factors. Methods 6509 patients treated with CABG from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were categorized into on-pump and off-pump groups according to whether CPB was used. Binary logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select factors associated with sepsis occurrence in all patients and in on-pump group. Multivariate Cox proportional hazards analysis was used to assess the association between selected variables and postoperative sepsis. Results In the Baseline Characteristics, the prevalence of sepsis was significantly higher in the on-pump group than in the off-pump group. Multivariate logistic regression analysis indicates CPB is a risk factor for sepsis (OR = 6.822, 95% CI 5.883–7.922, P < 0.001). In on-pump group, three variables were selected using the Lasso method: comorbid pneumonia, serum lactate level in 24 hours after ICU admission, and length of ICU stays. Multivariate Cox regression analysis suggested that serum lactate levels (HR = 1.096, 95% CI 1.038–1.157, p < 0.001) and comorbid pneumonia (HR = 1.221, 95% CI 1.091–1.367, p < 0.001) are independent risk factors for postoperative sepsis, apart from CPB. Conclusion CPB, high serum lactate levels and comorbid pneumonia are independent risk factors for postoperative sepsis in patients receiving CABG surgery. Figures Figure 1 Figure 2 Figure 3 Introduction Coronary artery bypass grafting (CABG) is the most effective treatment for coronary heart disease and the most commonly performed cardiac surgery worldwide( 1 , 2 ). Patients treated with CABG showed a significant lower long-term mortality rate compared to those receiving drug therapy or percutaneous coronary intervention (PCI), especially for high-risk patients with coronary heart disease (CAD)( 1 , 3 ). There are two types of CABG surgery: using cardiopulmonary bypass (CPB) and without cardiopulmonary bypass (on-pump CABG and off-pump CABG). The debate over the advantages and disadvantages of the two procedures has been going on for over 30 years( 4 ). Although on-pump CABG offers a stable surgical field and consistent vascular patency, it is associated with potential adverse effects of extracorporeal circulation, including hemodilution, microembolic phenomena, and activation of systemic inflammation( 5 , 6 ). Conversely, off-pump CABG is thought to reduce postoperative complications such as bleeding, renal dysfunction, and sepsis( 7 , 8 ). Despite extensive comparisons between on-pump and off-pump CABG, important knowledge gaps remain regarding infection-related outcomes in the ICU. Large randomized trials such as CORONARY and GOPCABE primarily focused on major cardiovascular events and mortality( 9 , 10 ), yet excluded sepsis. Actually, sepsis is a severe and relatively common complication of postoperative cardiac surgery( 11 ). Previous studies on postoperative sepsis following cardiac surgery have often been limited by small sample sizes and inconsistent definitions of sepsis. Furthermore, clinically predictive indicators for early sepsis detection in high-risk subgroups— on-pump CABG patients—remain inadequately established. With the emergence of large-scale critical care databases, researchers can now explore clinical issues with greater statistical power and external validity. The Medical Information Mart for Intensive Care IV (MIMIC-IV) database, developed by the Massachusetts Institute of Technology and the Beth Israel Deaconess Medical Center, provides comprehensive ICU data from more than 70,000 admissions between 2008 and 2019( 12 ). This publicly available database includes detailed information on patient demographics, comorbidities, laboratory findings, vital signs, and clinical outcomes, enabling robust retrospective analyses. This study based on the MIMIC-IV database and aimed to investigate whether CPB is an independent risk factor for postoperative sepsis and to identify early warning indicators for sepsis in on-pump CABG patients. The findings are expected to contribute to the selection of CABG procedures and postoperative management, thereby advancing individualized perioperative risk assessment and precision treatment. Methods and materials Data source This retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 3.1) database, a large, freely accessible critical care database jointly developed by the Massachusetts Institute of Technology and the Beth Israel Deaconess Medical Center. It contains detailed clinical data for over 50,000 ICU admissions, including demographic information, vital signs, laboratory results, medication use, diagnoses, and procedural data. Data use was authorized after completion of the required training. All patient data are de-identified for privacy protection and the study proceeded in accordance with the Declaration of Helsinki. Study population Patients included in the study were required to have undergone coronary artery bypass grafting (CABG). Those patients who were aged less than 18 years and whose ICU admission duration was less than 24 hours were excluded. For patients with multiple admissions, only the first ICU admission was extracted. Based on whether cardiopulmonary bypass (CPB) was used during surgery, these patients were then categorized into an on-pump group and an off-pump group. The procedure for selecting patients enrolled in the study is illustrated in Fig. 1 . Data extraction Clinical variables were extracted from the MIMIC-IV (version 3.1) database using Structured Query Language (SQL). Demographic characteristics were collected along with vital signs and laboratory tests within 24 hours of ICU admission including: age, gender, heart rate, mean arterial pressure (MAP), oxygen saturation (SpO2), white blood cell count (WBC), hemoglobin, hematocrit, platelet, glucose, anion gap, lactate, prothrombin time (PT) and partial thromboplastin time (PTT). To assess illness severity, Sequential Organ Failure Assessment (SOFA) score, Simplified Acute Physiology Score (SAPS) II and Oxford Acute Severity of illness Score (OASIS) at admission were also collected. Comorbidities including sepsis, acute kidney injury, Hypertension, type 2 diabetes, heart failure, myocardial infarction, acute renal failure, pneumonia, stroke, hyperlipidemia and chronic obstructive pulmonary disease (COPD). The Medications used including dobutamine, dopamine, epinephrine, norepinephrine, phenylephrine, milrinone, vasopressin. Length of hospital stays, length of ICU stays, Hospital mortality, ICU mortality, 28-day mortality and ventilation hours are also collected. Statistical Analysis A normality check on the continuous variables showed that all continuous variables in this study showed non-normal distribution. Therefore, these non-normally distributed variables were reported as median interquartile ranges (IQRs) and compared using the Mann-Whitney U test. Categorical variables are presented as numbers and proportions and were compared using the Pearson chi-square or Fisher exact test. Variables with missing rates greater than 5% were excluded. Of the remaining variables, continuous and categorical variables were interpolated using means and modes, respectively. Kaplan-Meier curves for the sepsis incidence within 15 days of ICU admission in on-pump and off-pump groups was constructed and compared by log-rank test. Risk factors for sepsis following coronary artery bypass grafting were identified using multivariate logistic regression analysis with odds ratios (ORs) and 95% confidence interval (CI). On-pump group patients were categorized into sepsis and non-sepsis cohorts to detect variables showing significant inter-cohort differences by Mann-Whitney U test and Pearson chi-square test. Then the Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to screen risk factors among these variables. Multivariate Cox proportional hazards analysis which incorporated the selected variables from the Lasso regression was used to calculate the hazard ratios (HRs) and 95% CI of these remaining risk factors. All statistical analyses were performed using R studio (version R4.4.3). A two-sided P value < 0.05 was regarded as statistically significant. The diagnosis of sepsis is based on The Third International Consensus Definitions for Sepsis and Septic Shock (sepsis-3)( 13 ), which identified by suspected or documented infection together with an acute increase in the SOFA score of ≥ 2 points from baseline. Results Patient Characteristics Overall, 6,509 patients in the ICU were included in the study, comprising 2,889 in on-pump group (44.4%) and 3,620 in off-pump group (55.6%). The median age of the study population was 69 years, and off-pump group had a higher proportion of males (79.6% versus 75.6%). On-pump group patients had generally higher SAPS II and OASIS scores than off-pump group patients and longer ventilation durations. There were no statistically significant differences between the two groups in Length of ICU stays or in-hospital mortality. However, compared to on-pump group patients, off-pump group patients were admitted with a higher prevalence of comorbidities such as type 2 diabetes and myocardial infarction. The baseline characteristics of these two groups are shown in Table 1. Of the 6509 patients, 772 had sepsis diagnoses documented in their medical records somewhat earlier than the ICU admission time while other data were not missing. These cases were included in the baseline profiles and multivariate binary logistic regression analysis but excluded from the Multivariate Cox proportional hazard analysis. Association between CPB and postoperative sepsis incidence A total of 3,152 patients (48.4%) developed sepsis after admission to ICU following CABG, with on-pump group patients showing a significantly higher sepsis incidence than off-pump group patients (74.1% vs. 27.9%, P<0.001). The Kaplan-Meier curves depicted in Figure 2 illustrate the distribution of postoperative sepsis within 15 days of ICU admission for patients in on-pump group and off-pump group. The cumulative incidence curve for on-pump group consistently remained below that of off-pump group (log-rank test, p<0.05), indicating that patients undergoing CABG with cardiopulmonary bypass experienced a significantly poorer sepsis-free probability within 15 days postoperatively. We employed logistic regression to assess the impact of each variable on sepsis in all patients. CPB demonstrated a significant positive effect on sepsis prevalence (OR = 6.822, 95% CI 5.883-7.922, P<0.001) (Table 2). Feature selection in on-pump group We screened for variables other than CPB that could lead to postoperative sepsis in on-pump group patients, who had a higher incidence of sepsis. On-pump group patients were divided into two subgroups based on occurrence of sepsis, and the characteristics of the two groups were compared. Continuous variables were analyzed using the Mann-Whitney U test, while categorical variables were compared using the chi-square test. Significant intergroup differences are shown in Table 3. After univariate analysis, variables with P<0.05 were retained for further Lasso-Cox regression analysis for feature selection. The Lasso regression model with 10-fold cross-validation was then applied to these candidate variables to select the most informative predictors. The optimal penalty parameter (λ) was determined using the one standard error rule (λ 1se ), at which the model demonstrated good balance between accuracy and simplicity. At λ 1se , three variables with non-zero coefficients were identified: comorbid pneumonia, serum lactate level in 24 hours after ICU admission, and length of ICU stays were associated with the occurrence of postoperative sepsis. The coefficient path plot shown in Figure 3a demonstrated gradual shrinkage of regression coefficients with increasing λ, and the cross-validation curve in Figure 3b indicated that the optimal λ was achieved at λ 1se =0.032. Multivariate Cox regression analysis revealed that after adjusting for the above three variables selected by Lasso method, high serum lactate levels and comorbid pneumonia were risk factors for developing sepsis within 15 days postoperatively, with hazard ratios (HR) of 1.096 (95% CI 1.038-1.157, p<0.001) and 1.221 (95% CI 1.091-1.367, p<0.001) respectively. However, the length of ICU stays had no significant association with sepsis (HR=1.002, 95% CI 0.989-1.014, p=0.812)[shown in Table 4]. Discussion In this large retrospective cohort study based on the MIMIC-IV database, we found that among patients admitted to the ICU after CABG, the rate of sepsis was significantly higher in on-pump group compared to off-pump group. Multivariate logistic regression analysis indicated that the use of CPB was an independent predictor of sepsis. Kaplan-Meier curves likewise demonstrated that during the high-risk window for surgery-related sepsis—specifically within 15 days postoperatively( 14 )—the incidence of sepsis was notably higher in the on-pump group than in the off-pump group. Then we attempted to identify other factors responsible for the dramatic sepsis prevalence in on-pump group. Using Lasso-Cox regression analysis, we found that comorbid pneumonia and serum lactate levels within 24 hours of ICU admission were significantly associated with the occurrence of sepsis. This study revealed that the different surgical procedures of CAGB impact patients' short-term prognosis. It is important to evaluate postoperative serum lactate levels and lung function to assess the risk of postoperative sepsis. Regarding the potential increased risk of sepsis associated with CPB, its mechanism may involve multiple complex inflammatory pathways. The blood contacting the artificial tubing during CPB which triggers complement activation, cytokine release, and leukocyte adhesion, leading to systemic inflammatory response and transient immunosuppression[14]. These immune disturbances may increase susceptibility to postoperative infection and sepsis. Previous studies have demonstrated that levels of interleukin-8, interleukin-6, and tumor necrosis factor receptors 1 and 2 released were higher in the off-pump group compared to the on-pump group[5]. The increase of these pro-enflammatory factors may be one of the causes for the postoperative complications in the on-pump group. As a severe inflammatory response affecting millions of patients worldwide, sepsis contributing to one-third to one-half of all hospital deaths, especially in intensive care units( 15 ). The sepsis-3 proposed in 2016 no longer relies on systemic inflammatory response syndrome (SIRS) as the diagnostic criterion. Instead, it is based on the Sequential Organ Failure Assessment (SOFA) score, emphasizing that organ failure is the central symptom of sepsis( 13 ). The new definition of sepsis is more suitable for clinical practice and promotes early recognition and intervention of sepsis. According to sepsis-3 guidelines, higher serum lactate levels usually indicate tissue hypoxia, suggesting potential organ dysfunction. The lung is also generally the first organ injured during sepsis( 16 ). A prospective study conducted in 40 intensive care units across 16 countries found that among patients with sepsis, the respiratory system usually reached highest SOFA scores in the shortest time during the progression of multiple organ failure( 17 ). Acute respiratory distress syndrome (ARDS) is the late stage of acute lung injury, and its symptoms of hypoxemia and respiratory distress are also typically the earliest clinical manifestations in patients with sepsis( 18 ). Therefore, early postoperative monitoring of pulmonary function could assist in promptly recognizing and intervening in sepsis. Despite the prevalence of postoperative inflammatory responses in the on-pump group, there was no significant mortality difference between the two groups during hospitalization in this study. And the main advantage of on-pump CABG is more complete revascularization. Robertson et al. found that the frequency of complete revascularization was significantly higher in the on-pump group than in the off-pump group( 19 ). Two famous large randomized controlled trials, ROOBY and CORONARY, also proved this point( 20 , 21 ). In terms of five-year mortality, the on-pump group also had a significant benefit in survival rates (15.2% versus 11.9%, p = 0.02)( 20 ). Another essential advantage of on-pump CABG is the greater proficiency surgeons possess as a more traditional technique( 22 , 23 ). Due to the difficulty of vascular anastomosis on a beating heart, surgeons require a longer learning curve to master off-pump CABG surgery. In emergency situations, it is recommended to engage the CPB rather than off-pump bypass( 24 ). Off-pump CABG is required to temporarily occlude the coronary artery for vascular anastomosis, which may impose an additional load on the already ischemic heart. There is still a need to consider the patient's physical condition, the urgency of the myocardial infarction, and the expected prognosis when choosing the surgical procedure. This study still has several limitations. First, as a retrospective analysis, it is difficult to define a causation between CPB and sepsis clearly. Second, MIMIC data are derived from single center, which may limit the generalizability of our findings to other populations. Third, certain important perioperative variables—such as operative duration, surgical complexity, transfusion volume, and specific antibiotic use—were not uniformly available in the database, which may have introduced residual confounding. Moreover, this study based on the MIMIC-IV database identified a prevalence of sepsis following CABG according to the sepsis-3 criteria at 48.4%, significantly higher than previously reported rates. In a study conducted in Australia, the incidence of sepsis following elective CABG ranged from 1.3% to 2.0%( 25 ). However, the diagnosis of sepsis in this study was based on the American Healthcare Research and Quality (AHRQ) criteria rather than the sepsis-3. Even in prospective cardiac surgery cohort studies using the sepsis-3 criteria, the reported incidence of sepsis typically below 10%. Howitt et al. found that 4.7–4.8% of cardiac surgery patients met the sepsis-3 criteria during intensive care( 26 ). There may be several reasons for this situation. First, the MIMIC-IV database includes patients from intensive care units only, with a high proportion of high-risk and complex coronary artery bypass grafting cases. Second, the electronic sepsis-3 algorithm combines “suspected infection” with an acute increase in SOFA score ≥ 2 points. It is common to undertake prophylactic or empirical antibiotic therapy and routine microbiological cultures within 24 hours after CABG surgery. Meanwhile, CPB often induces transient organ dysfunction (such as hypoxemia, vasopressin-dependent hypotension, and mild renal impairment). These conditions make patients more likely to satisfy electronic diagnostic criteria, even if physicians have not formally recorded a sepsis diagnosis. Despite the accuracy of sepsis prevalence rates requiring further confirmation, the predictive factors for sepsis identified in this study retain clinical value. Conclusion This study investigated risk factors for sepsis after CABG surgery. CPB was identified as an independent risk factor for postoperative sepsis, and patients with high 24-hour postoperative serum lactate levels and comorbid pneumonia also experience higher risks. The impact of CPB on patient prognosis should be considered when CABG procedures are performed in critically ill patients. The potential mechanisms still need further investigation. Abbreviations CABG Coronary artery bypass grafting CPB Cardiopulmonary bypass MIMIC-IV Medical Information Mart for Intensive Care-IV ICU Intensive care unit LASSO Least Absolute Shrinkage and Selection Operator PCI Percutaneous coronary intervention CAD Coronary heart disease SQL Structured query language MAP Mean arterial pressure SpO2 Oxygen saturation WBC White blood cell count PT Prothrombin time PTT Partial thromboplastin time SOFA Sequential organ failure assessment score SAPS Simplified acute physiology score OASIS Oxford acute severity of illness score COPD Chronic obstructive pulmonary disease OR Odds ratio HR Hazard ratio CI Confidence interval SIRS Systemic inflammatory response syndrome ARDS Acute respiratory distress syndrome Declarations Ethics approval and consent to participate The Institutional Review Boards of the Massachusetts Institute of Technology (MIT) and Beth Israel Deaconess Medical Center (BIDMC) have approved the research resource sharing. Informed consent requirements are waived due to the retrospective the study design. Funding This study was supported by Pressure-Volume Loop Cardiac Function Monitoring and Life Support Technology (2023C-TS39) and Chinese domestic pulse contour analysis (PiCCO) cardiac function monitoring and life support technology (2023C-TS43). Author Contribution Xiaojie Yu designed the study and drafted the manuscript. Lin Wang collected the data from MIMIC-IV database. Yang Cao, Qingchun Liang, and Bing Liang proposed revisions to the manuscript. All authors made significant contributions to the study and reviewed the manuscript. Acknowledgement We would like to thank the participants and developers involved with the MIMIC-IV database. Data Availability The data was based on the publicly available MIMIC-IV database (Version 3.1), https://mimic.physionet.org/iv/. References Gu D, Qu J, Zhang H, Zheng Z. Revascularization for Coronary Artery Disease: Principle and Challenges. 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Hospital variability of postoperative sepsis and sepsis-related mortality after elective coronary artery bypass grafting surgery. J Crit Care. 2018;47:232–7. Howitt SH, Herring M, Malagon I, McCollum CN, Grant SW. Incidence and outcomes of sepsis after cardiac surgery as defined by the Sepsis-3 guidelines. Br J Anaesth. 2018;120(3):509–16. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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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-8416630","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":609902260,"identity":"64b55bbc-292c-4497-a73b-ecd3f10c9568","order_by":0,"name":"Xiaojie Yu","email":"","orcid":"","institution":"Guangzhou Red Cross Hospital, Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojie","middleName":"","lastName":"Yu","suffix":""},{"id":609902261,"identity":"bbee206d-ace0-448a-90b9-af876dcc43e9","order_by":1,"name":"Yang Cao","email":"","orcid":"","institution":"Guangzhou Red Cross Hospital, Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Cao","suffix":""},{"id":609902262,"identity":"273be4d2-3d72-4fd6-b4f3-52011727d9a1","order_by":2,"name":"Qingchun Liang","email":"","orcid":"","institution":"The Third Affiliated Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qingchun","middleName":"","lastName":"Liang","suffix":""},{"id":609902263,"identity":"e633ddf7-f1e2-498b-85f0-1f84161f2a1e","order_by":3,"name":"Lin Wang","email":"","orcid":"","institution":"Guangzhou Red Cross Hospital, Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Wang","suffix":""},{"id":609902264,"identity":"9d9311e6-7a4f-4c88-b0e6-9a23c1776a74","order_by":4,"name":"Bing Liang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYBACfvnHBx8k/Phfz0+0FsmGtGSDhz3MCZINxGoxOJBjJvmAjTnB4ADR1hw4YCaRwMOWZ3w8eQPDj4pthHUwNjYkWyRY8BSbnXlWwNhz5jZhLczMDAdvJPBIMG67kWPAzNhGhBY2NsYGiQQ2A8bNM4jVwsPDzATUkpC4QYJYLRISbMwGiT0HjCWAfjlIlF/sb/B/fPjjxwE5/vbkjQ9+VBChBQmQEjVwLaTqGAWjYBSMghECAA1sPepRmEIpAAAAAElFTkSuQmCC","orcid":"","institution":"Guangzhou Red Cross Hospital, Jinan University","correspondingAuthor":true,"prefix":"","firstName":"Bing","middleName":"","lastName":"Liang","suffix":""}],"badges":[],"createdAt":"2025-12-21 10:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8416630/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8416630/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105351909,"identity":"91f265b8-064b-40a5-a127-8043e5a4086f","added_by":"auto","created_at":"2026-03-25 06:00:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125601,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patients selection.\u003c/p\u003e\n\u003cp\u003eNotes: ICU: intensive care unit; CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8416630/v1/d7038d8a9f278bd9005ce405.jpg"},{"id":105351906,"identity":"364914e3-92d9-4131-a03f-847d7aa5c915","added_by":"auto","created_at":"2026-03-25 06:00:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28688,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves of sepsis-free within 15 days after ICU admission.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8416630/v1/e54afba73980542a8bfead4a.jpg"},{"id":105351908,"identity":"5683364e-c37c-4e36-afde-95a980ef4e36","added_by":"auto","created_at":"2026-03-25 06:00:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":148044,"visible":true,"origin":"","legend":"\u003cp\u003eSelection of the demographic and clinical features by using the Lasso regression model. (a) Coefficient path plot illustrates the coefficients' variation according to log(lambda). (b) Cross-validation curve shows three variables selected using the 1 standard error of the minimum criterion (lambda.1se).\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8416630/v1/16b0d98769910188f424213f.jpg"},{"id":105569769,"identity":"323ca566-39e9-47a1-9ed4-46f9d374d539","added_by":"auto","created_at":"2026-03-27 13:13:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":791323,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8416630/v1/37433992-4c82-4269-86b8-3bc40e10323a.pdf"},{"id":105565288,"identity":"971b0ca1-dbfe-4bae-8372-19d94d67cf07","added_by":"auto","created_at":"2026-03-27 12:52:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28099,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8416630/v1/92a50bea2e44f033235c022e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sepsis Risk after On-pump vs Off-pump Coronary Artery Bypass Surgery: A MIMIC-IV Database Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCoronary artery bypass grafting (CABG) is the most effective treatment for coronary heart disease and the most commonly performed cardiac surgery worldwide(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Patients treated with CABG showed a significant lower long-term mortality rate compared to those receiving drug therapy or percutaneous coronary intervention (PCI), especially for high-risk patients with coronary heart disease (CAD)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). There are two types of CABG surgery: using cardiopulmonary bypass (CPB) and without cardiopulmonary bypass (on-pump CABG and off-pump CABG). The debate over the advantages and disadvantages of the two procedures has been going on for over 30 years(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Although on-pump CABG offers a stable surgical field and consistent vascular patency, it is associated with potential adverse effects of extracorporeal circulation, including hemodilution, microembolic phenomena, and activation of systemic inflammation(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Conversely, off-pump CABG is thought to reduce postoperative complications such as bleeding, renal dysfunction, and sepsis(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite extensive comparisons between on-pump and off-pump CABG, important knowledge gaps remain regarding infection-related outcomes in the ICU. Large randomized trials such as CORONARY and GOPCABE primarily focused on major cardiovascular events and mortality(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), yet excluded sepsis. Actually, sepsis is a severe and relatively common complication of postoperative cardiac surgery(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Previous studies on postoperative sepsis following cardiac surgery have often been limited by small sample sizes and inconsistent definitions of sepsis. Furthermore, clinically predictive indicators for early sepsis detection in high-risk subgroups\u0026mdash; on-pump CABG patients\u0026mdash;remain inadequately established.\u003c/p\u003e \u003cp\u003eWith the emergence of large-scale critical care databases, researchers can now explore clinical issues with greater statistical power and external validity. The Medical Information Mart for Intensive Care IV (MIMIC-IV) database, developed by the Massachusetts Institute of Technology and the Beth Israel Deaconess Medical Center, provides comprehensive ICU data from more than 70,000 admissions between 2008 and 2019(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This publicly available database includes detailed information on patient demographics, comorbidities, laboratory findings, vital signs, and clinical outcomes, enabling robust retrospective analyses.\u003c/p\u003e \u003cp\u003eThis study based on the MIMIC-IV database and aimed to investigate whether CPB is an independent risk factor for postoperative sepsis and to identify early warning indicators for sepsis in on-pump CABG patients. The findings are expected to contribute to the selection of CABG procedures and postoperative management, thereby advancing individualized perioperative risk assessment and precision treatment.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 3.1) database, a large, freely accessible critical care database jointly developed by the Massachusetts Institute of Technology and the Beth Israel Deaconess Medical Center. It contains detailed clinical data for over 50,000 ICU admissions, including demographic information, vital signs, laboratory results, medication use, diagnoses, and procedural data. Data use was authorized after completion of the required training. All patient data are de-identified for privacy protection and the study proceeded in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003ePatients included in the study were required to have undergone coronary artery bypass grafting (CABG). Those patients who were aged less than 18 years and whose ICU admission duration was less than 24 hours were excluded. For patients with multiple admissions, only the first ICU admission was extracted. Based on whether cardiopulmonary bypass (CPB) was used during surgery, these patients were then categorized into an on-pump group and an off-pump group. The procedure for selecting patients enrolled in the study is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eClinical variables were extracted from the MIMIC-IV (version 3.1) database using Structured Query Language (SQL). Demographic characteristics were collected along with vital signs and laboratory tests within 24 hours of ICU admission including: age, gender, heart rate, mean arterial pressure (MAP), oxygen saturation (SpO2), white blood cell count (WBC), hemoglobin, hematocrit, platelet, glucose, anion gap, lactate, prothrombin time (PT) and partial thromboplastin time (PTT). To assess illness severity, Sequential Organ Failure Assessment (SOFA) score, Simplified Acute Physiology Score (SAPS) II and Oxford Acute Severity of illness Score (OASIS) at admission were also collected. Comorbidities including sepsis, acute kidney injury, Hypertension, type 2 diabetes, heart failure, myocardial infarction, acute renal failure, pneumonia, stroke, hyperlipidemia and chronic obstructive pulmonary disease (COPD). The Medications used including dobutamine, dopamine, epinephrine, norepinephrine, phenylephrine, milrinone, vasopressin. Length of hospital stays, length of ICU stays, Hospital mortality, ICU mortality, 28-day mortality and ventilation hours are also collected.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eA normality check on the continuous variables showed that all continuous variables in this study showed non-normal distribution. Therefore, these non-normally distributed variables were reported as median interquartile ranges (IQRs) and compared using the Mann-Whitney U test. Categorical variables are presented as numbers and proportions and were compared using the Pearson chi-square or Fisher exact test. Variables with missing rates greater than 5% were excluded. Of the remaining variables, continuous and categorical variables were interpolated using means and modes, respectively. Kaplan-Meier curves for the sepsis incidence within 15 days of ICU admission in on-pump and off-pump groups was constructed and compared by log-rank test. Risk factors for sepsis following coronary artery bypass grafting were identified using multivariate logistic regression analysis with odds ratios (ORs) and 95% confidence interval (CI). On-pump group patients were categorized into sepsis and non-sepsis cohorts to detect variables showing significant inter-cohort differences by Mann-Whitney U test and Pearson chi-square test. Then the Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to screen risk factors among these variables. Multivariate Cox proportional hazards analysis which incorporated the selected variables from the Lasso regression was used to calculate the hazard ratios (HRs) and 95% CI of these remaining risk factors. All statistical analyses were performed using R studio (version R4.4.3). A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was regarded as statistically significant. The diagnosis of sepsis is based on The Third International Consensus Definitions for Sepsis and Septic Shock (sepsis-3)(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), which identified by suspected or documented infection together with an acute increase in the SOFA score of \u0026ge;\u0026thinsp;2 points from baseline.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003ch3\u003ePatient Characteristics\u003c/h3\u003e\n\u003cp\u003eOverall, 6,509 patients in the ICU were included in the study, comprising 2,889 in on-pump group (44.4%) and 3,620 in off-pump group (55.6%). The median age of the study population was 69 years, and off-pump group had a higher proportion of males (79.6% versus 75.6%). On-pump group patients had generally higher SAPS II and OASIS scores than off-pump group patients and longer ventilation durations. There were no statistically significant differences between the two groups in Length of ICU stays or in-hospital mortality. However, compared to on-pump group patients, off-pump group patients were admitted with a higher prevalence of comorbidities such as type 2 diabetes and myocardial infarction. The baseline characteristics of these two groups are shown in\u0026nbsp;Table 1. Of the 6509 patients, 772 had sepsis diagnoses documented in their medical records somewhat earlier than the ICU admission time while other data were not missing. These cases were included in the baseline profiles and multivariate\u0026nbsp;binary logistic regression analysis\u0026nbsp;but excluded from the Multivariate Cox proportional hazard analysis.\u003c/p\u003e\n\u003ch3\u003eAssociation between CPB and postoperative sepsis incidence\u003c/h3\u003e\n\u003cp\u003eA total of 3,152 patients (48.4%) developed sepsis after admission to ICU following CABG, with on-pump group patients showing a significantly higher sepsis incidence than off-pump group patients (74.1% vs. 27.9%, P\u0026lt;0.001). The Kaplan-Meier curves depicted in\u0026nbsp;Figure 2\u0026nbsp;illustrate the distribution of postoperative sepsis within 15 days of ICU admission for patients in on-pump group and off-pump group. The cumulative incidence curve for on-pump group consistently remained below that of off-pump group (log-rank test, p\u0026lt;0.05), indicating that patients undergoing CABG with cardiopulmonary bypass experienced a significantly poorer sepsis-free probability within 15 days postoperatively. We employed logistic regression to assess the impact of each variable on sepsis in all patients. CPB demonstrated a significant positive effect on sepsis prevalence (OR = 6.822, 95% CI 5.883-7.922, P\u0026lt;0.001) (Table 2).\u003c/p\u003e\n\u003ch3\u003eFeature selection in on-pump group\u003c/h3\u003e\n\u003cp\u003eWe screened for variables other than CPB that could lead to postoperative sepsis in on-pump group patients, who had a higher incidence of sepsis. On-pump group patients were divided into two subgroups based on occurrence of sepsis, and the characteristics of the two groups were compared. Continuous variables were analyzed using the Mann-Whitney U test, while categorical variables were compared using the chi-square test. Significant intergroup differences are shown in\u0026nbsp;Table 3. After univariate analysis, variables with P\u0026lt;0.05 were retained for further Lasso-Cox regression analysis for feature selection. The Lasso regression model with 10-fold cross-validation was then applied to these candidate variables to select the most informative predictors. The optimal penalty parameter (\u0026lambda;) was determined using the one standard error rule (\u0026lambda;\u003csub\u003e1se\u003c/sub\u003e), at which the model demonstrated good balance between accuracy and simplicity. At \u0026lambda;\u003csub\u003e1se\u003c/sub\u003e, three variables with non-zero coefficients were identified: comorbid pneumonia, serum lactate level in 24 hours after ICU admission, and length of ICU stays were associated with the occurrence of postoperative sepsis. The coefficient path plot shown in\u0026nbsp;Figure 3a\u0026nbsp;demonstrated gradual shrinkage of regression coefficients with increasing \u0026lambda;, and the cross-validation curve in\u0026nbsp;Figure 3b\u0026nbsp;indicated that the optimal \u0026lambda; was achieved at \u0026lambda;\u003csub\u003e1se\u003c/sub\u003e =0.032. Multivariate Cox regression analysis revealed that after adjusting for the above three variables selected by Lasso method, high serum lactate levels and comorbid pneumonia were risk factors for developing sepsis within 15 days postoperatively, with hazard ratios (HR) of 1.096 (95% CI 1.038-1.157, p\u0026lt;0.001) and 1.221 (95% CI 1.091-1.367, p\u0026lt;0.001) respectively. However, the length of ICU stays had no significant association with sepsis (HR=1.002, 95% CI 0.989-1.014, p=0.812)[shown in Table 4].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large retrospective cohort study based on the MIMIC-IV database, we found that among patients admitted to the ICU after CABG, the rate of sepsis was significantly higher in on-pump group compared to off-pump group. Multivariate logistic regression analysis indicated that the use of CPB was an independent predictor of sepsis. Kaplan-Meier curves likewise demonstrated that during the high-risk window for surgery-related sepsis\u0026mdash;specifically within 15 days postoperatively(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u0026mdash;the incidence of sepsis was notably higher in the on-pump group than in the off-pump group. Then we attempted to identify other factors responsible for the dramatic sepsis prevalence in on-pump group. Using Lasso-Cox regression analysis, we found that comorbid pneumonia and serum lactate levels within 24 hours of ICU admission were significantly associated with the occurrence of sepsis. This study revealed that the different surgical procedures of CAGB impact patients' short-term prognosis. It is important to evaluate postoperative serum lactate levels and lung function to assess the risk of postoperative sepsis.\u003c/p\u003e \u003cp\u003eRegarding the potential increased risk of sepsis associated with CPB, its mechanism may involve multiple complex inflammatory pathways. The blood contacting the artificial tubing during CPB which triggers complement activation, cytokine release, and leukocyte adhesion, leading to systemic inflammatory response and transient immunosuppression[14]. These immune disturbances may increase susceptibility to postoperative infection and sepsis. Previous studies have demonstrated that levels of interleukin-8, interleukin-6, and tumor necrosis factor receptors 1 and 2 released were higher in the off-pump group compared to the on-pump group[5]. The increase of these pro-enflammatory factors may be one of the causes for the postoperative complications in the on-pump group.\u003c/p\u003e \u003cp\u003eAs a severe inflammatory response affecting millions of patients worldwide, sepsis contributing to one-third to one-half of all hospital deaths, especially in intensive care units(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The sepsis-3 proposed in 2016 no longer relies on systemic inflammatory response syndrome (SIRS) as the diagnostic criterion. Instead, it is based on the Sequential Organ Failure Assessment (SOFA) score, emphasizing that organ failure is the central symptom of sepsis(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The new definition of sepsis is more suitable for clinical practice and promotes early recognition and intervention of sepsis. According to sepsis-3 guidelines, higher serum lactate levels usually indicate tissue hypoxia, suggesting potential organ dysfunction. The lung is also generally the first organ injured during sepsis(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A prospective study conducted in 40 intensive care units across 16 countries found that among patients with sepsis, the respiratory system usually reached highest SOFA scores in the shortest time during the progression of multiple organ failure(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Acute respiratory distress syndrome (ARDS) is the late stage of acute lung injury, and its symptoms of hypoxemia and respiratory distress are also typically the earliest clinical manifestations in patients with sepsis(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Therefore, early postoperative monitoring of pulmonary function could assist in promptly recognizing and intervening in sepsis.\u003c/p\u003e \u003cp\u003eDespite the prevalence of postoperative inflammatory responses in the on-pump group, there was no significant mortality difference between the two groups during hospitalization in this study. And the main advantage of on-pump CABG is more complete revascularization. Robertson et al. found that the frequency of complete revascularization was significantly higher in the on-pump group than in the off-pump group(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Two famous large randomized controlled trials, ROOBY and CORONARY, also proved this point(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In terms of five-year mortality, the on-pump group also had a significant benefit in survival rates (15.2% versus 11.9%, p\u0026thinsp;=\u0026thinsp;0.02)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Another essential advantage of on-pump CABG is the greater proficiency surgeons possess as a more traditional technique(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Due to the difficulty of vascular anastomosis on a beating heart, surgeons require a longer learning curve to master off-pump CABG surgery. In emergency situations, it is recommended to engage the CPB rather than off-pump bypass(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Off-pump CABG is required to temporarily occlude the coronary artery for vascular anastomosis, which may impose an additional load on the already ischemic heart. There is still a need to consider the patient's physical condition, the urgency of the myocardial infarction, and the expected prognosis when choosing the surgical procedure.\u003c/p\u003e \u003cp\u003eThis study still has several limitations. First, as a retrospective analysis, it is difficult to define a causation between CPB and sepsis clearly. Second, MIMIC data are derived from single center, which may limit the generalizability of our findings to other populations. Third, certain important perioperative variables\u0026mdash;such as operative duration, surgical complexity, transfusion volume, and specific antibiotic use\u0026mdash;were not uniformly available in the database, which may have introduced residual confounding.\u003c/p\u003e \u003cp\u003eMoreover, this study based on the MIMIC-IV database identified a prevalence of sepsis following CABG according to the sepsis-3 criteria at 48.4%, significantly higher than previously reported rates. In a study conducted in Australia, the incidence of sepsis following elective CABG ranged from 1.3% to 2.0%(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). However, the diagnosis of sepsis in this study was based on the American Healthcare Research and Quality (AHRQ) criteria rather than the sepsis-3. Even in prospective cardiac surgery cohort studies using the sepsis-3 criteria, the reported incidence of sepsis typically below 10%. Howitt et al. found that 4.7\u0026ndash;4.8% of cardiac surgery patients met the sepsis-3 criteria during intensive care(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). There may be several reasons for this situation. First, the MIMIC-IV database includes patients from intensive care units only, with a high proportion of high-risk and complex coronary artery bypass grafting cases. Second, the electronic sepsis-3 algorithm combines \u0026ldquo;suspected infection\u0026rdquo; with an acute increase in SOFA score\u0026thinsp;\u0026ge;\u0026thinsp;2 points. It is common to undertake prophylactic or empirical antibiotic therapy and routine microbiological cultures within 24 hours after CABG surgery. Meanwhile, CPB often induces transient organ dysfunction (such as hypoxemia, vasopressin-dependent hypotension, and mild renal impairment). These conditions make patients more likely to satisfy electronic diagnostic criteria, even if physicians have not formally recorded a sepsis diagnosis. Despite the accuracy of sepsis prevalence rates requiring further confirmation, the predictive factors for sepsis identified in this study retain clinical value.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study investigated risk factors for sepsis after CABG surgery. CPB was identified as an independent risk factor for postoperative sepsis, and patients with high 24-hour postoperative serum lactate levels and comorbid pneumonia also experience higher risks. The impact of CPB on patient prognosis should be considered when CABG procedures are performed in critically ill patients. The potential mechanisms still need further investigation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCABG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoronary artery bypass grafting\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCardiopulmonary bypass\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMIMIC-IV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMedical Information Mart for Intensive Care-IV\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLASSO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeast Absolute Shrinkage and Selection Operator\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePercutaneous coronary intervention\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoronary heart disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSQL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStructured query language\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean arterial pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSpO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOxygen saturation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWhite blood cell count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePartial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSequential organ failure assessment score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSimplified acute physiology score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOASIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOxford acute severity of illness score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSIRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSystemic inflammatory response syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The Institutional Review Boards of the Massachusetts Institute of Technology (MIT) and Beth Israel Deaconess Medical Center (BIDMC) have approved the research resource sharing. Informed consent requirements are waived due to the retrospective the study design.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by Pressure-Volume Loop Cardiac Function Monitoring and Life Support Technology (2023C-TS39) and Chinese domestic pulse contour analysis (PiCCO) cardiac function monitoring and life support technology (2023C-TS43).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXiaojie Yu designed the study and drafted the manuscript. Lin Wang collected the data from MIMIC-IV database. Yang Cao, Qingchun Liang, and Bing Liang proposed revisions to the manuscript. All authors made significant contributions to the study and reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank the participants and developers involved with the MIMIC-IV database.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data was based on the publicly available MIMIC-IV database (Version 3.1), https://mimic.physionet.org/iv/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGu D, Qu J, Zhang H, Zheng Z. Revascularization for Coronary Artery Disease: Principle and Challenges. Adv Exp Med Biol. 2020;1177:75\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVervoort D, Lee G, Ghandour H, Guetter CR, Adreak N, Till BM, et al. Global Cardiac Surgical Volume and Gaps: Trends, Targets, and Way Forward. Ann Thorac Surg Short Rep. 2024;2(2):320\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344(8922):563\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaudino M, Angelini GD, Antoniades C, Bakaeen F, Benedetto U, Calafiore AM, et al. Off-Pump Coronary Artery Bypass Grafting: 30 Years of Debate. J Am Heart Assoc. 2018;7(16):e009934.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStr\u0026uuml;ber M, Cremer JT, Gohrbandt B, Hagl C, Jankowski M, V\u0026ouml;lker B, et al. Human cytokine responses to coronary artery bypass grafting with and without cardiopulmonary bypass. Ann Thorac Surg. 1999;68(4):1330\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrasil LA, Gomes WJ, Salom\u0026atilde;o R, Buffolo E. Inflammatory response after myocardial revascularization with or without cardiopulmonary bypass. Ann Thorac Surg. 1998;66(1):56\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoff SJ, Ball SK, Coltharp WH, Glassford DM Jr., JWt L, Petracek MR. Coronary artery bypass in patients 80 years and over: is off-pump the operation of choice? Ann Thorac Surg. 2002;74(4):S1340\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirose H, Amano A, Takahashi A. Off-pump coronary artery bypass grafting for elderly patients. Ann Thorac Surg. 2001;72(6):2013\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, et al. Off-pump or on-pump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366(16):1489\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiegeler A, B\u0026ouml;rgermann J, Kappert U, Breuer M, B\u0026ouml;ning A, Ursulescu A, et al. Off-pump versus on-pump coronary-artery bypass grafting in elderly patients. N Engl J Med. 2013;368(13):1189\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBateman RM, Sharpe MD, Jagger JE, Ellis CG, Sol\u0026eacute;-Viol\u0026aacute;n J, L\u0026oacute;pez-Rodr\u0026iacute;guez M et al. 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15\u0026ndash;18 March 2016. Crit Care. 2016;20(Suppl 2):94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson AEW, Bulgarelli L, Shen L, Gayles A, Shammout A, Horng S, et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci Data. 2023;10(1):1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinger M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlemayehu MA, Azene AG, Mihretie KM. Time to development of surgical site infection and its predictors among general surgery patients admitted at specialized hospitals in Amhara region, northwest Ethiopia: a prospective follow-up study. BMC Infect Dis. 2023;23(1):334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1):90\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim GO, Park DH, Bae JS. Procyanidin B2 Attenuates Sepsis-Induced Acute Lung Injury via Regulating Hippo/Rho/PI3K/NF-κB Signaling Pathway. Int J Mol Sci. 2023;24(9).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVincent JL, de Mendon\u0026ccedil;a A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on sepsis-related problems of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiao X, Yin J, Zheng Z, Li L, Feng X. Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications. Cell Commun Signal. 2024;22(1):241.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobertson MW, Buth KJ, Stewart KM, Wood JR, Sullivan JA, Hirsch GM, et al. Complete revascularization is compromised in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2013;145(4):992\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShroyer AL, Hattler B, Grover FL. Five-Year Outcomes after On-Pump and Off-Pump Coronary-Artery Bypass. N Engl J Med. 2017;377(19):1898\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Straka Z, et al. Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting. N Engl J Med. 2016;375(24):2359\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026eacute;gar\u0026eacute; JF, Hirsch G. Off-pump coronary artery bypass graft surgery is standard of care: where do you stand? Can J Cardiol. 2006;22(13):1107\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamy A, Devereaux PJ, Prabhakaran D, Hu S, Piegas LS, Straka Z, et al. Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery. Am Heart J. 2012;163(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan MS, Islam MY, Ahmed MU, Bawany FI, Khan A, Arshad MH. On pump coronary artery bypass graft surgery versus off pump coronary artery bypass graft surgery: a review. Glob J Health Sci. 2014;6(3):186\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOu L, Chen J, Flabouris A, Hillman K, Parr M, Bellomo R. Hospital variability of postoperative sepsis and sepsis-related mortality after elective coronary artery bypass grafting surgery. J Crit Care. 2018;47:232\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowitt SH, Herring M, Malagon I, McCollum CN, Grant SW. Incidence and outcomes of sepsis after cardiac surgery as defined by the Sepsis-3 guidelines. Br J Anaesth. 2018;120(3):509\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\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":"","lastPublishedDoi":"10.21203/rs.3.rs-8416630/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8416630/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aims to compare the differences in postoperative sepsis between patients treated with coronary artery bypass grafting (CABG) with and without cardiopulmonary bypass (CPB), and investigate the related risk factors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e6509 patients treated with CABG from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were categorized into on-pump and off-pump groups according to whether CPB was used. Binary logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select factors associated with sepsis occurrence in all patients and in on-pump group. Multivariate Cox proportional hazards analysis was used to assess the association between selected variables and postoperative sepsis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the Baseline Characteristics, the prevalence of sepsis was significantly higher in the on-pump group than in the off-pump group. Multivariate logistic regression analysis indicates CPB is a risk factor for sepsis (OR\u0026thinsp;=\u0026thinsp;6.822, 95% CI 5.883\u0026ndash;7.922, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In on-pump group, three variables were selected using the Lasso method: comorbid pneumonia, serum lactate level in 24 hours after ICU admission, and length of ICU stays. Multivariate Cox regression analysis suggested that serum lactate levels (HR\u0026thinsp;=\u0026thinsp;1.096, 95% CI 1.038\u0026ndash;1.157, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and comorbid pneumonia (HR\u0026thinsp;=\u0026thinsp;1.221, 95% CI 1.091\u0026ndash;1.367, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) are independent risk factors for postoperative sepsis, apart from CPB.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCPB, high serum lactate levels and comorbid pneumonia are independent risk factors for postoperative sepsis in patients receiving CABG surgery.\u003c/p\u003e","manuscriptTitle":"Sepsis Risk after On-pump vs Off-pump Coronary Artery Bypass Surgery: A MIMIC-IV Database Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-25 06:00:03","doi":"10.21203/rs.3.rs-8416630/v1","editorialEvents":[{"type":"communityComments","content":1},{"type":"decision","content":"Revision requested","date":"2026-04-06T09:20:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-05T15:12:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212843646186761225228840419291724488640","date":"2026-03-31T15:02:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143184502956480586141506806226872230232","date":"2026-03-30T06:23:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27171712252671717773451617854232909477","date":"2026-03-28T14:27:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-26T09:28:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190566355498516004428179363380849161744","date":"2026-03-19T14:58:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T14:23:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-04T06:27:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-26T11:39:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-26T11:37:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-12-21T10:25:19+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":"257ad333-8edd-48d1-a7ec-adae1c8d0ddc","owner":[],"postedDate":"March 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T09:25:31+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-25 06:00:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8416630","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8416630","identity":"rs-8416630","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}