Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis
Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, College of Medicine, Korea University, Seoul 02841, Republic of Korea
*
Authors to whom correspondence should be addressed.
†
The authors contributed equally to this work.
J. Clin. Med. 2025, 14(8), 2662; https://doi.org/10.3390/jcm14082662
Submission received: 27 February 2025
/
Revised: 2 April 2025
/
Accepted: 5 April 2025
/
Published: 13 April 2025
(This article belongs to the Special Issue Clinical Advances in Cardiac Anesthesia and Critical Care)
Abstract
:Background/Objectives: The impact of different coronary artery bypass grafting (CABG) strategies, particularly on-pump versus off-pump techniques, on red blood cell (RBC) transfusions and their associated outcomes has not been fully investigated. This study aims to evaluate the association between RBC transfusion and survival in CABG patients, focusing on-pump strategy. Methods: Data from CABG patients were retrieved from the National Health Insurance Service database (2003 to 2019). Perioperative RBC transfusions were classified into three groups: no transfusion, RBC 1, and RBC ≥ 2 units. The primary endpoint was all-cause mortality rate. Subgroup analysis assessed the impact of RBC transfusion on mortality across the conventional on-pump (CCAB) and off-pump (OPCAB) groups. Results: Among the 6150 participants who underwent CABG, 2028 underwent CCAB and 4122 underwent OPCAB. The mean age was 66.2 ± 9.7 years, with a mean follow-up of 2.9 (2.53–3.35) years. Multivariable analysis showed a significant association between transfusion of ≥2 RBC units and increased mortality risk (HR 2.34 [1.65–3.32], p < 0.001). Subgroup analysis showed a similar trend in both CCAB and OPCAB groups (p for interaction = 0.2). Transfusion of ≥2 units significantly increased mortality in OPCAB (HR 2.28 [1.55–3.37], p < 0.001) but not in CCAB (HR 2.96 [0.97–9.06], p = 0.057). OPCAB and surgery at large volume center was associated with a reduced risk of RBC transfusion (p < 0.01). Conclusions: Increased RBC transfusion is associated with higher long-term mortality in patients undergoing CABG. Based on a large cohort predominantly consisting of OPCAB patients, OPCAB is associated with decreased RBC transfusion requirements.
1. Introduction
Coronary artery bypass grafting (CABG) is commonly performed during cardiac surgery to treat ischemic heart disease and acute coronary syndrome [1]. Patients undergoing cardiac surgery, including CABG, occasionally need transfusion [2,3]. Transfusion is aimed at enhancing oxygen delivery to tissues by increasing hemoglobin levels [4]. However, perioperative transfusion is associated with worse outcomes [5,6,7,8]. These outcomes include increased morbidity in critically ill patients, as well as an increased risk of renal failure and respiratory, cardiac, and neurologic complications [9,10,11].
Despite efforts to reduce their incidence in patients undergoing surgery, transfusions commonly occur during CABG. Conventional on-pump coronary artery bypass grafting (CCAB) utilizes cardiopulmonary bypass (CPB) to temporarily take over heart and lung function during surgery. In contrast, off-pump coronary artery bypass grafting (OPCAB) is performed on a beating heart without the use of CPB, potentially reducing complications related to extracorporeal circulation [8,12]. The initiation of CPB necessitates a higher level of anticoagulation, significant manipulation of major vessels (such as the aorta and vena cava), and depletion of coagulation factors, all of which may contribute to an increased tendency for bleeding. However, the impact of CABG strategy, whether conventional on-pump or off-pump, on red blood cell (RBC) transfusion and clinical outcomes has not been thoroughly investigated.
Therefore, this study aimed to investigate the effects of RBC transfusion during CABG, specifically utilizing the OPCAB-dominant approach, on long-term mortality using a large administrative population-based database.
2. Materials and Methods
2.1. Study Participants
The data were obtained from the National Health Insurance Service (NHIS). Individuals possessing Korean nationality residing in Korea were mandated to participate in the NHIS. Consequently, the NHIS patient database epitomizes the medical practices prevalent in Korea and constitutes the largest repository of claims data in the country. The claims data utilized for this investigation encompassed patients’ demographic details, diagnoses, procedures, and prescription records pertaining to both inpatient and outpatient services. Between 2002 and 2019 (available in the NHIS), 76,233 patients underwent their first cardiac surgeries. Among these, 12,290 patients underwent isolated CABG. To obtain laboratory data collected before surgery, patients with health screening data within two years before the index surgery were included (n = 6140). The Institutional Review Board approved this study (IRB no. 2022AN0011), and the requirement for informed consent was waived.
2.2. Surgical Techniques
All the patients included in this study underwent isolated CABG. CPB strategies were classified into two groups for subgroup analysis: CCAB and OPCAB.
2.3. Variables in Analysis
Perioperative red blood cell (RBC) transfusion is operationally defined as the administration of transfused blood occurring both prior to and subsequent to the indexed coronary artery bypass grafting (CABG) procedure. Regarding the RBC transfusion categorization, the volume of transfused red blood cells during the perioperative period was stratified for analytical purposes into the following groups: 0 (no transfusion), 1 (RBC 1), and ≥2 (RBC ≥ 2) units. Anemia is clinically defined as a hemoglobin concentration of less than 13 g/dL in male patients or less than 12 g/dL in female patients.
2.4. Outcomes of Interest
The primary outcome of interest was the overall all-cause mortality during the postoperative follow-up period. Secondary study outcomes included identifying the risk factors associated with RBC transfusion in patients undergoing CABG.
2.5. Statistical Analysis
The risk of incident events based on the number of RBC transfusions was analyzed using the Kaplan–Meier method and log-rank test. Cox proportional hazards models were applied to evaluate the relationship between RBC transfusions and mortality, employing a backward elimination method for variable selection. The final model retained variables with a significance level of p > 0.2. In the multivariable analysis, the covariates that were adjusted for encompassed age, sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), hypertension, diabetes mellitus, dyslipidemia, ischemic stroke, congestive heart failure, liver cirrhosis, a history of malignancy, atrial fibrillation, myocardial infarction, peripheral artery disease, the utilization of antiplatelet agents, admission via the emergency department, the application of extracorporeal membrane oxygenation (ECMO), surgical procedures conducted at high-volume centers (defined as centers performing more than 50% of surgical interventions; median cases: 324 [IQR, 290.5–474.5] for high-volume centers vs. 26 [IQR, 7–46] for low-volume centers), the volume of red blood cell (RBC) transfusions, and the comparative analysis between coronary artery bypass grafting (CCAB) and off-pump coronary artery bypass grafting (OPCAB). Individuals with incomplete datasets were excluded from the analysis. In order to evaluate the proportional hazard assumption, an interaction term involving RBC transfusion and temporal factors was incorporated into the Cox regression model. The findings indicated that the interaction term did not achieve statistical significance (p = 0.953), suggesting that the influence of RBC transfusion on survival remained consistent over time, thereby fulfilling the criteria for the assumption of proportional hazards.
A subgroup analysis utilizing various pump strategies was executed through Cox proportional hazards models to investigate the correlation between mortality and red blood cell transfusions within both the CCAB and OPCAB cohorts. The variables included in the multivariate analysis were consistent with those described above. The p-value for the interaction was calculated to assess the differential impact of RBC transfusions on mortality between the CCAB and OPCAB groups.
The transfusion risk was evaluated using a logistic regression model. In the multivariate model, the variables included in the analysis were consistent with those described above.
All statistical analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC, USA) and R software version 4.0.5 (R Foundation, Vienna, Austria). Statistical significance was defined as a two-tailed p < 0.05.
3. Results
The study population included 6150 patients. The patient demographics are shown in Table 1. CCAB and OPCAB were performed in 2028 and 4122 patients, respectively. The mean follow-up duration was 2.9 (2.53–3.35) years. A total of 927 (15.07%) patients had anemia preoperatively and 4809 (78.2%) patients underwent RBC transfusions. Compared to CCAB, OPCAB patients had a significantly lower proportion of congestive heart failure, atrial fibrillation, myocardial infarction, and emergency admission. The mean number of transfused RBC units in the study population was 1.64 (±1.71). Although the proportion of patients with preoperative anemia did not differ according to CABG strategy, patients who underwent OPCAB received fewer transfusions than those who underwent CCAB (69.77% vs. 95.32%) (Table 1). The mean RBC transfusion volume during CCAB was also significantly higher than that during OPCAB (2.49 [±2.08] vs. 1.22 [±1.30]).
3.1. RBC Transfusion and Overall Mortality
During the follow-up period, the overall mortality rate was 16.0% (983 of 6150 patients). In univariate analysis, preoperative anemia and transfusion volume were associated with an increased risk of mortality. In the multivariable analysis, transfusion volume remained an independent risk factor for mortality (RBC 1: hazard ratio [HR] 1.4 (0.97–2.01), p = 0.071; red blood cell [RBC] ≥ 2: HR 2.34 (1.65–3.32), p < 0.0001), while preoperative anemia did not show a statistically significant association (p = 0.8) (Table 2 and Figure 1 and Figure 2).
In subgroup analysis, the mortality rates for OPCAB and CCAB were 13.31% and 21.40%, respectively. A similar association was observed in both CCAB and OPCAB groups (p for interaction = 0.2). Transfusion of ≥2 units (RBC ≥ 2) was associated with an increased risk of mortality; however, this association was not statistically significant in the CCAB group (CCAB group: HR 2.96 (0.97–9.06), p = 0.057); (OPCAB group: HR 2.28 (1.55–3.37), p < 0.0001) (Table 3). All variables and statistical analyses of the subgroups are presented in Supplementary Tables S1 and S2.
3.2. Risk Factors for RBC Transfusion
In the multivariable analysis, factors associated with an increased prevalence of RBC transfusion included older age, reduced estimated glomerular filtration rate (eGFR), congestive heart failure, myocardial infarction, emergency admission, perioperative ECMO use, surgery performed at low-volume centers, preoperative anemia, and the conventional coronary artery bypass grafting (CCAB) technique compared to OPCAB (p < 0.05) (Table 4). These findings underscore the importance of hospital surgical volume, perioperative critical illness, and surgical technique in determining RBC transfusion rates.
4. Discussion
Based on our findings, RBC transfusion is associated with an increased risk of death. However, we did not observe any association between preoperative anemia and death. In the subgroup analysis, this relationship was observed in both the CCAB and OPCAB groups, but statistical significance was only observed in the OPCAB group. Additionally, the prevalence of RBC transfusions was higher in the CCAB group than in the OPCAB group.
RBC transfusions can increase oxygen delivery to tissues, which is helpful in myocardial ischemia [4]. Thus, RBC transfusion could be effective treatment, especially in surgery with hemorrhage, such as cardiac surgery or hemorrhagic shock. However, it is also associated with increase morbidity and mortality [5,6,7,13,14]. Therefore, all efforts should be made to minimize exposure.
Patients undergoing cardiac surgery who receive packed RBC transfusions have worse outcomes, including ischemic stroke, renal injury, and mortality, than non-transfused patients, even after adjusting for a variety of risk factors [14]. The adverse effects of RBC transfusion on outcomes can be explained by systemic inflammation [15]. This is because stored RBCs can lead to increased red blood cell aggregation and diminished microvascular autoregulatory ability. In addition, pro-inflammatory cytokines and potentially toxic microparticles are observed [9,16,17].
Patients with anemia are prone to tissue hypoxia; consequently, physicians tend to manage this condition by administering RBC transfusions perioperatively. This study also found that preoperative anemia was associated with RBC transfusion [13,18]. Because of this finding, many studies have suggested that anemia and RBC transfusion can independently affect outcomes [18,19,20,21,22]. Conversely, other studies have suggested that preoperative anemia itself may not be an independent risk factor for worse outcomes [23,24]. The current study found that the impact of RBC transfusion on survival was more pronounced than that of preoperative anemia.
Regarding the CPB strategy during CABG, OPCAB is associated with fewer RBC transfusions than CCAB [25,26]. This tendency could be attributed to the differences in the CPB strategies and the invasiveness of the techniques. Many studies have reported that OPCAB yields better short-term outcomes compared with those of CCAB [12,27]. However, OPCAB poses some potential hazards to survival, including technical difficulties, instrument issues, and anastomosis strategies. Thus, long-term survival according to the CPB strategy has not yet been clarified [28,29,30]. In the current study, the mortality rate in the OPCAB group was lower than that in the CCAB group (13.31% vs. 21.4%, respectively). This result can be attributed to the preference for OPCAB in Korea and its association with high-performance medical centers. In addition, the multivariable analysis indicated that the relationship between the RBC transfusion volume and increased mortality was not significantly affected by the operative technique.
In terms of risk factors associated with RBC transfusion, OPCAB procedures, treatment at high-volume hospitals, and the absence of ECMO support were identified as significant protective factors. However, these relationships are nuanced. OPCAB procedures were predominantly conducted at high-volume centers, which typically employ advanced patient blood management protocols and have more experienced medical teams compared to lower-volume centers [31]. Furthermore, aside from the inherent demands of extracorporeal support (such as CPB or ECMO), targeted training and implementation of effective patient blood management practices could significantly reduce the necessity for RBC transfusions [32].
Limitation
Our investigation is subject to numerous constraints. Initially, notwithstanding its classification as a substantial population-based study, it possesses a retrospective design. Furthermore, the transfusion methodologies and technical interventions aimed at minimizing hemorrhage exhibited considerable variability across the 104 medical institutions offering cardiothoracic surgical programs in Korea. Due to the large number of hospitals during long period involved, factors such as blood transfusion thresholds and technical details, including pump operation, bypass conduit choice, and specific blood management protocols, were not investigated or incorporated into the analysis. These factors are significant considerations that can influence transfusion practices and outcomes, highlighting the need for further studies.
Second, our study could not definitively establish causality between RBC transfusion and associated outcomes due to its retrospective design and the lack of hemoglobin data at the time of transfusion or details regarding bleeding events. Without information on hemoglobin levels maintained during transfusion, the precise impact of RBC transfusion on mortality remains uncertain.
Third, our study was susceptible to selection bias due to the preference for off-pump CABG, which is widely performed in Korea. Consequently, the demographics of the patients who underwent conventional on-pump CABG in our cohort were worse than those reported in other studies. To mitigate this limitation, we incorporated numerous variables into our analysis, although some limitations persist.
Another limitation of our study was the higher transfusion rate observed compared with the other study groups. This discrepancy may be attributed to the relatively recent development of blood transfusion regulations and recommendations in Korea, primarily driven by referral medical centers and government initiatives. As a result, there exists a possibility of bias arising from disparities in transfusion methodologies when contrasted with practices in other nations. Additional investigation is essential to rectify these constraints and to furnish more thorough understandings regarding the correlation between red blood cell transfusion and patient prognoses.
Groups were categorized based on transfusion volume to achieve balanced case numbers across three groups. Because the number of cases with no transfusion or more than three units was limited, the threshold for categorization was set at one unit of transfusion.
In conclusion, our study reinforces the notion that RBC transfusion volume is an independent risk factor for survival, regardless of preoperative anemia. Additionally, OPCAB and higher surgery volume were associated with reduced RBC transfusion rates compared to CCAB. Reducing RBC transfusions during CABG may improve patient survival.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm14082662/s1, Supplemental Table S1. Multivariable analysis for overall death in conventional on-pump coronary artery bypass grafting group; Supplemental Table S2. Multivariable analysis for overall death in off-pump coronary artery bypass grafting.
Author Contributions
Conceptualization, J.S.J. and H.-J.K.; methodology, H.-J.K.; validation, J.H.L., J.S.J., J.E.K. and H.-J.K.; formal analysis, H.-J.K.; data curation, H.-J.K.; writing—original draft preparation, H.-J.K. and S.H.L.; writing—review and editing, H.-J.K. and S.H.L.; supervision, H.-J.K. and H.S.S.; funding acquisition, H.-J.K. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by the National Research Foundation (NRF) grant funded by the Korean government (MSIT) (no. RS-2023-00247757).
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Korea University Anam Hospital (protocol code 2022AN0011 and Jan-01-2022).
Informed Consent Statement
Patient consent was waived due to nature of retrospective study design.
Data Availability Statement
Restrictions apply to the availability of these data. Data were obtained from Korea National Health Insurance Service and are available at https://nhiss.nhis.or.kr/bd/ay/bdaya001iv.do with the permission of Korea National Health Insurance Service (accessed on 30 December 2024).
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
The following abbreviations are used in this manuscript:
| BMI | Body mass index |
| CABG | Coronary artery bypass rafting |
| CCAB | Conventional on-pump coronary artery bypass |
| CI | Confidence interval |
| CPB | Cardiopulmonary bypass |
| ECMO | Extracorporeal membrane oxygenation |
| eGFR | Estimated glomerular filtration rate |
| HR | Hazard ratio |
| OPCAB | Off-pump coronary artery bypass |
| PBM | Patient blood management |
| RBC | Red blood cell |
References
- Byrne, R.A.; Fremes, S.; Capodanno, D.; Czerny, M.; Doenst, T.; Emberson, J.R.; Falk, V.; Gaudino, M.; McMurray, J.J.V.; Mehran, R.; et al. 2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG. Eur. J. Cardiothorac. Surg. 2023, 64, ezad286. [Google Scholar] [CrossRef]
- Woldendorp, K.; Manuel, L.; Srivastava, A.; Doane, M.; Bassin, L.; Marshman, D. Perioperative transfusion and long-term mortality after cardiac surgery: A meta-analysis. Gen. Thorac. Cardiovasc. Surg. 2023, 71, 323–330. [Google Scholar] [CrossRef]
- Oh, T.K.; Song, I.A. Perioperative Transfusion and Mortality for Cardiovascular Surgery: A Cohort Study Based on Population in Republic of Korea. J. Clin. Med. 2024, 13, 2328. [Google Scholar] [CrossRef]
- Rao, S.V.; Sherwood, M.W. Isn’t it about time we learned how to use blood transfusion in patients with ischemic heart disease? J. Am. Coll. Cardiol. 2014, 63, 1297–1299. [Google Scholar] [CrossRef] [PubMed]
- Murphy, G.J.; Reeves, B.C.; Rogers, C.A.; Rizvi, S.I.A.; Culliford, L.; Angelini, G.D. Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery. Circulation 2007, 116, 2544–2552. [Google Scholar] [CrossRef]
- Goodnough, L.T.; Bach, R.G. Anemia, Transfusion, and Mortality. N. Engl. J. Med. 2001, 345, 1272–1274. [Google Scholar] [CrossRef] [PubMed]
- Vlot, E.A.; Verwijmeren, L.; van de Garde, E.M.W.; Kloppenburg, G.T.L.; van Dongen, E.P.A.; Noordzij, P.G. Intra-operative red blood cell transfusion and mortality after cardiac surgery. BMC Anesthesiol. 2019, 19, 65. [Google Scholar] [CrossRef] [PubMed]
- Schwann, T.A.; Vekstein, A.M.; Engoren, M.; Grau-Sepulveda, M.; O’Brien, S.; Engelman, D.; Lobdell, K.W.; Gaudino, M.F.; Salenger, R.; Habib, R.H. Perioperative Anemia and Transfusions and Late Mortality in Coronary Artery Bypass Patients. Ann. Thorac. Surg. 2023, 115, 759–769. [Google Scholar] [CrossRef]
- Karkouti, K. Transfusion and risk of acute kidney injury in cardiac surgery. Br. J. Anaesth. 2012, 109, i29–i38. [Google Scholar] [CrossRef]
- Raphael, J.; Chae, A.; Feng, X.; Shotwell, M.S.; Mazzeffi, M.A.; Bollen, B.A.; Pfeil, D.; Feduska, E.; Shah, A.S.; Kertai, M.D. Red Blood Cell Transfusion and Pulmonary Complications: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis. Ann. Thorac. Surg. 2024, 117, 839–846. [Google Scholar] [CrossRef]
- De La Vega-Mendez, F.M.; Estrada, M.I.; Zuno-Reyes, E.E.; Gutierrez-Rivera, C.A.; Oliva-Martinez, A.E.; Diaz-Villavicencio, B.; Calderon-Garcia, C.E.; Gonzalez-Barajas, J.D.; Arizaga-Napoles, M.; Garcia-Pena, F.; et al. Blood transfusion reactions and risk of acute kidney injury and major adverse kidney events. J. Nephrol. 2024, 37, 951–960. [Google Scholar] [CrossRef] [PubMed]
- Shaefi, S.; Mittel, A.; Loberman, D.; Ramakrishna, H. Off-Pump Versus On-Pump Coronary Artery Bypass Grafting—A Systematic Review and Analysis of Clinical Outcomes. J. Cardiothorac. Vasc. Anesth. 2019, 33, 232–244. [Google Scholar] [CrossRef]
- Meybohm, P.; Westphal, S.; Ravn, H.B.; Ranucci, M.; Agarwal, S.; Choorapoikayil, S.; Spahn, D.R.; Ahmed, A.B.; Froessler, B.; Zacharowski, K. Perioperative Anemia Management as Part of PBM in Cardiac Surgery—A Narrative Updated Review. J. Cardiothorac. Vasc. Anesth. 2020, 34, 1060–1073. [Google Scholar] [CrossRef]
- Koch, C.G.; Li, L.; Duncan, A.I.; Mihaljevic, T.; Cosgrove, D.M.; Loop, F.D.; Starr, N.J.; Blackstone, E.H. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit. Care Med. 2006, 34, 1608–1616. [Google Scholar] [CrossRef]
- Warltier, D.C.; Laffey, J.G.; Boylan, J.F.; Cheng, D.C. The Systemic Inflammatory Response to Cardiac Surgery: Implications for the Anesthesiologist. Anesthesiology 2002, 97, 215–252. [Google Scholar] [CrossRef] [PubMed]
- Almac, E.; Ince, C. The impact of storage on red cell function in blood transfusion. Best. Pract. Res. Clin. Anaesthesiol. 2007, 21, 195–208. [Google Scholar] [CrossRef]
- Fransen, E.; Maessen, J.; Dentener, M.; Senden, N.; Buurman, W. Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery. Chest 1999, 116, 1233–1239. [Google Scholar] [CrossRef] [PubMed]
- Arias-Morales, C.E.; Stoicea, N.; Gonzalez-Zacarias, A.A.; Slawski, D.; Bhandary, S.P.; Saranteas, T.; Kaminiotis, E.; Papadimos, T.J. Revisiting blood transfusion and predictors of outcome in cardiac surgery patients: A concise perspective. F1000Res 2017, 6, 168. [Google Scholar] [CrossRef]
- Muñoz, M.; Gómez-Ramírez, S.; Campos, A.; Ruiz, J.; Liumbruno, G.M. Pre-operative anaemia: Prevalence, consequences and approaches to management. Blood Transfus. 2015, 13, 370–379. [Google Scholar] [CrossRef]
- Kulier, A.; Levin, J.; Moser, R.; Rumpold-Seitlinger, G.; Tudor, I.C.; Snyder-Ramos, S.A.; Moehnle, P.; Mangano, D.T. Impact of Preoperative Anemia on Outcome in Patients Undergoing Coronary Artery Bypass Graft Surgery. Circulation 2007, 116, 471–479. [Google Scholar] [CrossRef]
- LaPar, D.J.; Hawkins, R.B.; McMurry, T.L.; Isbell, J.M.; Rich, J.B.; Speir, A.M.; Quader, M.A.; Kron, I.L.; Kern, J.A.; Ailawadi, G. Preoperative anemia versus blood transfusion: Which is the culprit for worse outcomes in cardiac surgery? J. Thorac. Cardiovasc. Surg. 2018, 156, 66–74.e62. [Google Scholar] [CrossRef] [PubMed]
- Karkouti, K.; Wijeysundera, D.N.; Beattie, W.S. Risk associated with preoperative anemia in cardiac surgery: A multicenter cohort study. Circulation 2008, 117, 478–484. [Google Scholar] [CrossRef]
- Tauriainen, T.; Koski-Vähälä, J.; Kinnunen, E.-M.; Biancari, F. The Effect of Preoperative Anemia on the Outcome After Coronary Surgery. World J. Surg. 2017, 41, 1910–1918. [Google Scholar] [CrossRef]
- Miles, L.F.; Kunz, S.A.; Na, L.H.; Braat, S.; Burbury, K.; Story, D.A. Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and iron-deficient patients—An exploratory study. Anaesthesia 2018, 73, 450–458. [Google Scholar] [CrossRef]
- Chen, J.W.; Hsu, R.B. Impact of surgeon experience on the rate of blood transfusion in off-pump coronary artery bypass. J. Formos. Med. Assoc. 2016, 115, 145–151. [Google Scholar] [CrossRef]
- Walczak, M.; Urbanowicz, T.K.; Tomczyk, J.; Camacho, E.; Ligowski, M.; Stefaniak, S.; Jemielity, M. Transfusion of blood products in off-pump coronary artery bypass and conventional coronary artery revascularization. A prospective randomized study. Kardiochir. Torakochirurgia Pol. 2014, 11, 136–139. [Google Scholar] [CrossRef] [PubMed]
- Kowalewski, M.; Pawliszak, W.; Malvindi, P.G.; Bokszanski, M.P.; Perlinski, D.; Raffa, G.M.; Kowalkowska, M.E.; Zaborowska, K.; Navarese, E.P.; Kolodziejczak, M.; et al. Off-pump coronary artery bypass grafting improves short-term outcomes in high-risk patients compared with on-pump coronary artery bypass grafting: Meta-analysis. J. Thorac. Cardiovasc. Surg. 2016, 151, 60–77.e58. [Google Scholar] [CrossRef] [PubMed]
- Diegeler, A.; Börgermann, J.; Kappert, U.; Breuer, M.; Böning, A.; Ursulescu, A.; Rastan, A.; Holzhey, D.; Treede, H.; Rieß, F.-C.; et al. Off-Pump versus On-Pump Coronary-Artery Bypass Grafting in Elderly Patients. N. Engl. J. Med. 2013, 368, 1189–1198. [Google Scholar] [CrossRef]
- Sheikhy, A.; Fallahzadeh, A.; Sadeghian, S.; Forouzannia, K.; Bagheri, J.; Salehi-Omran, A.; Tajdini, M.; Jalali, A.; Pashang, M.; Hosseini, K. Mid-term outcomes of off-pump versus on-pump coronary artery bypass graft surgery; statistical challenges in comparison. BMC Cardiovasc. Disord. 2021, 21, 412. [Google Scholar] [CrossRef]
- Lamy, A.; Devereaux, P.J.; Prabhakaran, D.; Taggart, D.P.; Hu, S.; Straka, Z.; Piegas, L.S.; Avezum, A.; Akar, A.R.; Lanas Zanetti, F.; et al. Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting. N. Engl. J. Med. 2016, 375, 2359–2368. [Google Scholar] [CrossRef]
- Chervu, N.; Verma, A.; Sakowitz, S.; Bakhtiyar, S.S.; Hadaya, J.; Sanaiha, Y.; Benharash, P. Association of Hospital Volume and Outcomes Following Off-Pump Coronary Artery Bypass Grafting. Heart Lung Circ. 2023, 32, 1128–1135. [Google Scholar] [CrossRef] [PubMed]
- Magruder, J.T.; Blasco-Colmenares, E.; Crawford, T.; Alejo, D.; Conte, J.V.; Salenger, R.; Fonner, C.E.; Kwon, C.C.; Bobbitt, J.; Brown, J.M.; et al. Variation in Red Blood Cell Transfusion Practices During Cardiac Operations Among Centers in Maryland: Results From a State Quality-Improvement Collaborative. Ann. Thorac. Surg. 2017, 103, 152–160. [Google Scholar] [CrossRef] [PubMed]
Figure 1.
Incidence of mortality according to preoperative anemia.
Figure 2.
Incidence of mortality according to the RBC transfusion volume. RBC, red blood cell.
Table 1.
Demographic characteristics of the study cohort.
| Variable | Total Cohort (N = 6150) | Conventional CABG Group (N = 2028) | Off-pump CABG Group (N = 4122) | p-Value |
|---|---|---|---|---|
| Age (year, mean, SD) | 66.20 (9.72) | 66.36 (9.63) | 66.11 (9.76) | 0.341 |
| Sex (Female population, %) | 1385 (22.54) | 507 (25.02) | 878 (21.32) | 0.001 |
| BMI | 24.76 (3.01) | 24.74(3.05) | 24.77 (2.99) | 0.697 |
| Hypertension | 5269 (85.67) | 1735 (85.55) | 3534 (85.74) | 0.847 |
| Diabetes | 4131 (67.17) | 1371 (67.60) | 2760 (66.96) | 0.612 |
| Dyslipidemia | 5509 (89.58) | 1772 (87.38) | 3737 (90.66) | <0.0001 |
| Ischemic stroke | 1259 (20.47) | 413 (20.36) | 846 (20.52) | 0.884 |
| Congestive heart failure | 1959 (31.85) | 721 (35.55) | 1238 (30.03) | <0.0001 |
| Liver cirrhosis | 148 (2.41) | 55 (2.71) | 93 (2.26) | 0.273 |
| Malignancy history | 815 (13.25) | 244 (12.03) | 571 (13.85) | 0.048 |
| Atrial fibrillation | 448 (7.28) | 192 (9.47) | 256 (6.21) | <0.0001 |
| Myocardial infarction | 1618 (26.31) | 608 (29.98) | 1010 (24.50) | <0.0001 |
| Peripheral artery disease | 1215 (19.76) | 375 (18.49) | 840 (20.38) | 0.081 |
| Anti-platelet agent | 4285 (69.67) | 1361 (67.11) | 2924 (70.94) | 0.0021 |
| Emergency admission | 1777 (28.89) | 798 (39.35) | 979 (23.75) | <0.0001 |
| ECMO use | 265 (4.31) | 174 (8.58) | 91 (2.21) | <0.0001 |
| Surgery at high volume center | 2830 (46.02) | 484 (23.87) | 2346 (56.91) | <0.0001 |
| Hemoglobin | 0.403 | |||
| Normal | 5223 (84.93) | 1715 (84.57) | 3508 (85.10) | |
| Mild anemia (men 11–12.9 g/dL; women 11–11.9 g/dL) | 692 (11.25) | 226 (11.14) | 466 (11.31) | |
| Moderate and severe (men < 10.9 g/dL; women < 10.9 g/dL) | 235 (3.82) | 87 (4.29) | 148 (3.59) | |
| eGFR (mL/min) | 0.042 | |||
| eGFR ≥ 90 | 1376 (26.23) | 435 (25.89) | 941 (26.40) | |
| eGFR < 90 and ≥60 | 2821 (53.78) | 888 (52.86) | 1933 (54.22) | |
| eGFR < 60 and ≥30 | 827 (15.77) | 267 (15.89) | 560 (15.71) | |
| eGFR < 30 | 221 (4.21) | 90 (5.36) | 131 (3.67) | |
| Mean transfusion unit (count, SD) | 1.64 (1.71) | 2.49 (2.08) | 1.22 (1.30) | <0.0001 |
| Patients by transfusion volume | <0.0001 | |||
| No transfusion | 1341 (21.80) | 95 (4.68) | 1246 (30.23) | |
| RBC 1 unit | 2204 (35.84) | 576 (28.40) | 1628 (39.50) | |
| RBC ≥ 2 units | 2605 (42.36) | 1357 (66.91) | 1248 (30.28) | |
SD, standard deviation; CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; BMI, body mass index; high volume center, index surgery performed at large cases center (performing 50% of total cases); RBC, red blood cell.
Table 2.
Multivariable analysis for overall death in the total cohort.
| Variable | Hazard Ratio (95% CI) | p-Value |
|---|---|---|
| Age (years) | ||
| 20–40 | Reference | |
| 60–80 | 2.83 (0.62–13.00) | 0.181 |
| 80≤ | 5.55 (1.19–25.95) | 0.03 |
| Female sex | 0.78 (0.61–0.98) | 0.034 |
| eGFR (mL/min) | ||
| eGFR ≥ 90 | Reference | |
| eGFR < 60 and ≥30 | 1.73 (1.28–2.34) | <0.0001 |
| eGFR < 30 | 3.56 (2.43–5.23) | <0.0001 |
| Congestive heart failure | 1.57 (1.29–1.92) | <0.0001 |
| Ischemic stroke | 1.32 (1.08–1.63) | 0.008 |
| Malignancy history | 1.56 (1.22–1.98) | <0.0001 |
| Atrial fibrillation | 1.57 (1.19–2.08) | 0.002 |
| Peripheral artery disease | 1.40 (1.14–1.73) | 0.002 |
| Emergency admission | 1.22 (1.00–1.50) | 0.053 |
| ECMO use | 10.81 (7.98–14.64) | <0.0001 |
| Surgery at high volume center | 0.64 (0.52–0.79) | <0.0001 |
| RBC transfusion | ||
| Number of RBC, 0 | Reference | |
| Number of RBC, 1 | 1.40 (0.97–2.01) | 0.071 |
| Number of RBC, 2≤ | 2.34 (1.65–3.32) | <0.0001 |
eGFR, estimated glomerular filtration rate; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; RBC, red blood cell; OPCAB, off-pump coronary artery bypass grafting; surgery at high-volume centers (defined as centers performing more than 50% of surgery cases).
Table 3.
Multivariable analysis of long-term mortality in subgroup (conventional coronary artery bypass grafting (CCABG) versus off-pump coronary artery bypass grafting (OPCAB).
Table 3.
Multivariable analysis of long-term mortality in subgroup (conventional coronary artery bypass grafting (CCABG) versus off-pump coronary artery bypass grafting (OPCAB).
| Conventional CABG | OPCAB | |||
|---|---|---|---|---|
| HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
| Anemia | ||||
| Normal | Reference | Reference | ||
| Anemia | 0.84 (0.47–1.51) | 0.565 | 1.21 (0.76–1.92) | 0.429 |
| Transfusion | ||||
| No transfusion | Reference | Reference | ||
| RBC 1 unit | 1.72 (0.55–5.46) | 0.354 | 1.34 (0.90–2.00) | 0.152 |
| RBC ≥ 2 units | 2.96 (0.97–9.06) | 0.057 | 2.28 (1.55–3.37) | <0.0001 |
RBC, red blood cell; CI, confidence interval; HR, hazard ratio.
Table 4.
Multivariable analysis for the risk of RBC transfusion.
| Variable | Odd Ratio (95% CI) | p-Value |
|---|---|---|
| Age (years) | ||
| 20–40 | Reference | |
| 40~60 | 2.23 (0.90–5.54) | 0.083 |
| 60~80 | 3.02 (1.22–7.48) | 0.017 |
| 80≤ | 7.75 (2.82–21.28) | <0.0001 |
| Female sex | 1.90 (1.50–2.42) | 1.90 (1.50–2.42) |
| eGFR (mL/min) | ||
| eGFR ≥ 90 | Reference | |
| eGFR < 90 and ≥60 | 0.95 (0.79–1.14) | 0.567 |
| eGFR < 60 and ≥30 | 1.44 (1.07–1.93) | 0.015 |
| eGFR < 30 | 4.43 (1.72–11.40) | 0.002 |
| Anemia | 4.34 (2.95–6.38) | <0.0001 |
| BMI (kg/m2) | ||
| <18.5 | Reference | |
| 18.5–23 | 0.59 (0.20–1.79) | 0.355 |
| 23–25 | 0.49 (0.16–1.50) | 0.211 |
| 25–30 | 0.39 (0.13–1.22) | 0.105 |
| 30< | 0.26 (0.08–0.90) | 0.033 |
| Hypertension | 1.05 (0.82–1.34) | 0.696 |
| Diabetes | 1.08 (0.89–1.31) | 0.457 |
| Dyslipidemia | 0.91 (0.66–1.26) | 0.587 |
| Congestive heart failure | 1.30 (1.07–1.57) | 0.008 |
| Ischemic stroke | 0.87 (0.70–1.08) | 0.214 |
| Liver cirrhosis | 1.05 (0.59–1.84) | 0.875 |
| Malignancy history | 0.99 (0.78–1.27) | 0.938 |
| Atrial fibrillation | 1.19 (0.83–1.70) | 0.351 |
| Myocardial infarction | 0.76 (0.62–0.93) | 0.007 |
| Peripheral artery disease | 1.08 (0.87–1.34) | 0.480 |
| Anti-platelet agent medication | 0.98 (0.80–1.20) | 0.844 |
| Emergency admission | 1.28 (1.05–1.57) | 0.017 |
| ECMO use | 7.49 (2.71–20.72) | <0.0001 |
| Surgery at high volume center | 0.78 (0.66–0.93) | 0.005 |
| OPCAB | 0.12 (0.09–0.15) | <0.0001 |
eGFR, estimated glomerular filtration rate; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; RBC, red blood cell; OPCAB, off-pump coronary artery bypass grafting; surgery at high-volume centers (defined as centers performing more than 50% of surgery cases).
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Lee, S.H.; Kim, J.E.; Lee, J.H.; Jung, J.S.; Son, H.S.; Kim, H.-J. Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis. J. Clin. Med. 2025, 14, 2662. https://doi.org/10.3390/jcm14082662
AMA Style
Lee SH, Kim JE, Lee JH, Jung JS, Son HS, Kim H-J. Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis. Journal of Clinical Medicine. 2025; 14(8):2662. https://doi.org/10.3390/jcm14082662
Chicago/Turabian StyleLee, Seung Hyung, Ji Eon Kim, Jun Ho Lee, Jae Seung Jung, Ho Sung Son, and Hee-Jung Kim. 2025. "Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis" Journal of Clinical Medicine 14, no. 8: 2662. https://doi.org/10.3390/jcm14082662
APA StyleLee, S. H., Kim, J. E., Lee, J. H., Jung, J. S., Son, H. S., & Kim, H.-J. (2025). Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis. Journal of Clinical Medicine, 14(8), 2662. https://doi.org/10.3390/jcm14082662
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
