SvO₂ Response to Red Blood Cell Transfusion in Cardiovascular Surgical ICU Patients: A Retrospective Observational Study

SvO₂ Response to Red Blood Cell Transfusion in Cardiovascular Surgical ICU Patients: A Retrospective Observational Study | 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 SvO₂ Response to Red Blood Cell Transfusion in Cardiovascular Surgical ICU Patients: A Retrospective Observational Study Kentaro Okamoto, Kimito Minami, Chase Donaldson, Jean Deschamps, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9352763/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background: Hemoglobin thresholds alone may not identify cardiovascular surgical ICU patients who derive physiologic benefit from red blood cell (RBC) transfusion. Mixed venous oxygen saturation (SvO₂) reflects the balance between oxygen delivery and consumption and may help identify patients with transfusion-responsive oxygen supply-demand mismatch. Methods: We conducted a retrospective observational study of adult cardiovascular surgical ICU patients who underwent a first 2-unit RBC transfusion episode with pre-transfusion hemoglobin (Hb) ≥ 7.5 g/dL and paired pre- and post-transfusion SvO₂ measurements. The primary outcome was SvO₂ responsiveness, defined as ΔSvO₂ ≥ 5 percentage points from pre-transfusion baseline to approximately 60 minutes after transfusion initiation. Multivariable logistic regression was used to identify predictors of response, and receiver operating characteristic analysis was used to determine the optimal pre-transfusion SvO₂ cutoff. Subgroup analyses evaluated higher Hb thresholds, and sensitivity analyses included overlap-weighted transfusion-versus-no-transfusion trajectory comparisons and multivariable linear regression using continuous ΔSvO₂. Results: Among 18,117 eligible transfusion episodes, 1,352 unique patients met the final inclusion criteria. Mean Hb increased from 9.82 ± 0.92 to 10.24 ± 0.98 g/dL, whereas mean SvO₂ changed only minimally at the cohort level (73.79 ± 9.91% to 73.86 ± 9.37%). However, lower pre-transfusion SvO₂ was associated with larger increases in SvO₂ after transfusion. In multivariable logistic regression, baseline SvO₂ was the only independent predictor of SvO₂ response (adjusted OR, 0.89 per 1% increase; 95% CI, 0.86–0.91; P < 0.001). Pre-transfusion SvO₂ predicted a response with an AUC of 0.778 (95% CI, 0.74–0.816), and the optimal cutoff was 69%. The inverse association between baseline SvO₂ and ΔSvO₂ was preserved in the Hb ≥ 9 g/dL and Hb ≥ 10 g/dL subgroups. In overlap-weighted sensitivity analyses, 0–6-hour trajectories of SvO₂, Hb, and DO₂i differed significantly between transfusion and no-transfusion groups (all group-by-time interaction P < 0.001). Conclusions: In cardiovascular surgical ICU patients with Hb ≥ 7.5 g/dL, a low pre-transfusion SvO₂ identified patients more likely to show a physiologic rise in SvO₂ after RBC transfusion. Pre-transfusion SvO₂ may complement Hb when evaluating transfusion need in this population, but prospective validation is required before physiologic SvO₂-guided transfusion can be recommended. red blood cell transfusion mixed venous oxygen saturation SvO₂ cardiovascular intensive care physiologic transfusion trigger Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Red blood cell (RBC) transfusion is frequently performed in the postoperative management of cardiovascular surgery. However, recent international guidelines generally recommend a restrictive transfusion strategy with a threshold of Hb 7.5 g/dL even for cardiac surgery patients [1]. However, transfusion triggers beyond hemoglobin concentration, particularly those based on physiological indicators, remain poorly established. Mixed venous oxygen saturation (SvO₂) reflects the balance between oxygen delivery (DO₂) and oxygen consumption (VO₂) and may serve as an indicator of potential benefit from transfusion. Nevertheless, studies evaluating transfusion efficacy using venous oxygen saturation (SvO₂ or ScvO₂) are limited [2,3]. Zeroual et al., in an observational study of cardiac surgery patients with Hb ≤ 9 g/dL, reported that cases with lower pre-transfusion central venous oxygen saturation (ScvO₂) were more likely to show an increase in ScvO₂ post-transfusion [4]. Furthermore, in a randomized controlled trial (RCT), the same group demonstrated that a strategy of transfusing RBCs in patients with a Hb <9 g/dL only when ScvO₂ ≤ 65% could reduce RBC transfusion [5]. Similarly, Fischer et al. demonstrated in an RCT involving patients with Hb < 9 g/dL that compared to an intervention group receiving transfusions only when ScvO₂ < 70%, the transfusion rate was significantly reduced with no difference in clinical outcomes [6]. These prior studies demonstrate that a restrictive transfusion protocol integrating hemoglobin levels and a marker of oxygen supply and demand mismatch (ScvO2) in cardiac surgery patients reduces the number of transfused red blood cell units and the number of patients receiving at least one transfusion, without evidence of significant adverse events [7]. Based on the results of previous studies, we considered that even in patients with Hb ≥ 7.5 g/dL—a level not currently considered an indication for active transfusion—if pre-transfusion SvO₂ is low, there may be patients who exhibit an increase in SvO₂ after transfusion. In this patient group, despite Hb levels greater than those currently recommended as a potential RBC transfusion trigger, there may still be tissue oxygen supply-demand mismatch, suggesting that transfusion could provide physiological benefit. Objective To describe the physiologic change in SvO₂ after a 2-unit RBC transfusion in CVICU patients with pre-transfusion Hb ≥ 7.5 g/dL, identify predictors of SvO₂ response (ΔSvO₂ ≥5%), and determine the optimal pre-transfusion SvO₂ cutoff. Methods Study Design and Setting This retrospective observational study utilized electronic medical record data from patients admitted to the Cardiovascular Intensive Care Unit (CVICU) at the National Cerebral and Cardiovascular Center between July 1, 2019, and December 31, 2024. The study was approved by the Ethics Review Committee (Approval No. R24108). Given the retrospective design, consent was obtained using an opt-out approach, and the requirement for individual written informed consent was waived. Subjects Inclusion criteria were: (1) age ≥18 years, (2) receipt of one standard 2-unit RBC product during CVICU admission, (3) pre-transfusion Hb ≥ 7.5 g/dL, (4) obtainable pre- and post-transfusion SvO₂ values, and (5) SvO₂ monitoring via pulmonary artery catheterization. Exclusion criteria were cases where multiple blood products were administered simultaneously and blood product records were deemed inaccurate (e.g., massive transfusion for postoperative bleeding) and cases of refusal to participate in this study. Furthermore, for patients receiving multiple transfusions, only the first transfusion was included in the analysis. In our institution, red blood cells were routinely administered as a leukoreduced RBC product derived from a 400-mL whole-blood donation. In Japan, this product is labeled as 2 units in the Japanese system; its approximate volume is approximately 280 mL, making it roughly comparable to 1 unit of packed red blood cells in the United States, and it is commonly infused over approximately 1 hour in routine adult practice. Data Acquisition and Variable Definition The following variables were extracted: transfusion time, Hb from blood gas analysis, SvO₂, SpO₂, heart rate, blood pressure, cardiac index, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance from ACSYS® monitor records. The pulmonary artery catheter used was the thermal filament pulmonary artery catheter (Edwards Lifesciences). Pre-transfusion values were defined as the closest recorded value (immediate value) to the transfusion start time. Post-transfusion values were defined as the closest recorded value (immediate value) to approximately 60 minutes after transfusion start. ΔSvO₂ was calculated as post-transfusion SvO₂ minus pre-transfusion SvO₂. Outcomes The primary outcome was SvO₂ responsiveness, defined a priori as ΔSvO₂ ≥5% after transfusion. This cutoff was selected based on previous work by Zeroual et al.[4], which used a ≥5% increase in ScvO₂ after RBC transfusion as a marker of transfusion response, allowing comparison with the existing literature. In addition, we evaluated the predictive performance of pre-transfusion SvO₂ for SvO₂ responsiveness and performed prespecified subgroup and sensitivity analyses. Statistical Analysis Continuous variables were presented as mean ± standard deviation or median (interquartile range). Categorical variables were presented as number (%) or proportion (%). To examine factors associated with SvO₂ responsiveness, multivariate logistic regression analysis was performed using variables related to oxygen supply (age, sex, pre-transfusion Hb, pre-transfusion SvO₂, SpO₂, cardiac index, left ventricular ejection fraction) as explanatory variables. The predictive ability of pre-transfusion SvO₂ for SvO₂ responsiveness was evaluated using ROC curves. As a subgroup analysis, ΔSvO₂ was described by pre-transfusion SvO₂ category in populations with lower limits of pre-transfusion Hb set at 9, 10, 11, and 12 g/dL. As a sensitivity analysis, we constructed a risk set anchored at transfusion initiation to compare the transfusion and no-transfusion groups. To adjust for confounding, we evaluated propensity score matching, inverse probability of treatment weighting (IPTW), and overlap weighting, and selected overlap weighting because it provided the best covariate balance (Table S1). Trajectories of SvO₂, Hb, and DO₂i over 0–6 hours were analyzed using models that included group, time, and a group-by-time interaction term. Furthermore, to reinforce the results of the main analysis, a multivariate linear regression analysis was also performed using ΔSvO₂ as a continuous variable. Statistical analyses were performed using R version 4.5.2 (R Foundation for Statistical Computing, Vienna, Austria). This study is reported in accordance with the STROBE statement for observational studies. Results Identification of Subject Patients Among patients aged 18 years or older admitted to the CVICU, 18,117 transfusion episodes with Hb ≥7.5 g/dL were identified. Of these, 6,962 episodes had paired pre- and post-transfusion SvO₂ values. After excluding repeated transfusions beyond the first transfusion per patient (n = 5,555) and transfusions other than 2 units of RBCs (n = 55), 1,352 patients were included in the analysis population (Figure 1). Patient background and pre- and post-transfusion parameters The patient’s background is shown in Table 1. A total of 1,352 patients were included. The mean age at ICU admission was 66.6 ± 15.2 years, and 822 (60.8%) patients were male. Mean body mass index was 23.0 ± 4.0 kg/m². The median ICU length of stay was 4 [3–7] days, and ICU mortality was 48 (3.6%). Preoperative cardiac function showed a left ventricular ejection fraction of 49.8 ± 17.4% using the visual method (n = 776) and 45.9 ± 15.0% using the modified Simpson method (n = 602). Regarding procedure types (mutually exclusive), 377 (27.9%) underwent isolated valve surgery, 218 (16.1%) isolated open aortic/vascular surgery, 202 (14.9%) isolated CABG/coronary surgery, 154 (11.4%) isolated endovascular procedures (EVAR/TEVAR), and 76 (5.6%) isolated heart transplant/VAD. Combined procedures included CABG + valve surgery (48 [3.6%]), valve + open aortic surgery (35 [2.6%]), and CABG + open aortic surgery (14 [1.0%]). Other combined procedures accounted for 24 (1.8%), and unclassified cases accounted for 204 (15.1%). Table 2 shows circulatory and respiratory parameters before and after transfusion. The median time from transfusion initiation to post-transfusion SvO₂ measurement was 70 minutes (interquartile range [IQR], 58–86 minutes; range, 45–120 minutes; mean, 72.3 minutes). Pre-transfusion Hb was 9.82 ± 0.92 g/dL, and post-transfusion Hb was 10.24 ± 0.98 g/dL. SvO₂ was 73.79 ± 9.91% (median 75%, IQR 68–80) before transfusion and 73.86 ± 9.37% (median 74%, IQR 68–80) after transfusion, showing a small change as a group average. However, the response was not uniform. When stratified by pre-transfusion SvO₂ category, lower pre-transfusion SvO₂ was associated with larger ΔSvO₂ and a greater likelihood of post-transfusion SvO₂ elevation (Figure 2). Prediction of SvO₂ Response The predictive ability of pre-transfusion SvO₂ for SvO₂ responsiveness was an AUC of 0.778 (95% confidence interval 0.74–0.816) (Figure 3). ROC analysis identified an optimal cutoff value of SvO₂ 69%, with a sensitivity of 0.68 and specificity of 0.75. For reference, applying the 65% cutoff used in the prior study by Zeroual et al. using ScvO₂ guidance to this dataset yielded a sensitivity of 0.52 and a specificity of 0.86 [4]. Multivariate Analysis In a multivariate logistic regression analysis with SvO₂ responsiveness as the outcome, only pre-transfusion SvO₂ was independently associated with SvO₂ responsiveness (Table 3, Figure 4). Subgroup Analysis and Sensitivity Analysis Subgroup analyses were performed by modifying the lower limit of pre-transfusion Hb (Hb ≥ 9, Hb ≥ 10, Hb ≥ 11, Hb ≥ 12 g/dL), and ΔSvO₂ was evaluated by pre-transfusion SvO₂ category within each stratum (Figure S1). In the Hb ≥ 9 g/dL (n = 1,153) and Hb ≥ 10 g/dL (n = 520) groups, the visual trend observed in the entire cohort—where lower pre-transfusion SvO₂ was associated with greater ΔSvO₂—was largely maintained. However, in the Hb ≥ 11 g/dL (n = 119) and Hb ≥ 12 g/dL (n = 28) groups, the number of cases was limited, particularly in the low pre-transfusion SvO₂ category, leaving uncertainty in verifying the trend. In the overlap-weighted sensitivity analysis, trajectories of SvO₂, Hb, and DO₂i over 0–6 hours differed significantly between the transfusion and no-transfusion groups (all group-by-time interaction P<0.001). The transfusion group showed clear increases in Hb and DO₂i and maintained or slightly increased SvO₂, whereas the no-transfusion group showed minimal change in Hb and no comparable increase in SvO₂ or DO₂i (Figure S2). Furthermore, in multivariate linear regression analyzing ΔSvO₂ as a continuous variable, CI and SpO₂ were significantly associated with ΔSvO₂, in addition to baseline SvO₂, consistent with the primary analysis (Table S2, Figure S3). Discussion This study demonstrated that in intensive care patients following cardiovascular surgery, even with Hb ≥ 7.5 g/dL, if pre-transfusion SvO₂ is low, post-transfusion SvO₂ increases significantly, with a high likelihood of showing ΔSvO₂ ≥ 5%. This trend persisted in subgroup analyses restricted to cases with higher Hb thresholds, remaining consistent at least up to Hb 10 g/dL. ROC analysis indicated that pre-transfusion SvO₂ around 69% contributed to distinguishing SvO₂ responsiveness. Pre-transfusion SvO₂ also remained an independent predictor in a multivariate model adjusting for age, sex, and DO₂ components. Sensitivity analysis results suggested that the increase in SvO₂, accompanied by elevated Hb levels and increased DO₂ after RBC transfusion, was maintained for up to 6 hours post-transfusion.Compared to previous studies using ScvO₂ in cardiac surgery patients with Hb < 9 g/dL, this study, conducted against the backdrop of recent recommendations for restricted transfusion, targeted transfusions performed at Hb ≥ 7.5 g/dL. It complements existing research by demonstrating the reproducibility of “responsiveness” based on SvO₂, while simultaneously presenting new findings. Both SvO₂ and ScvO₂ reflect the balance between systemic oxygen delivery (DO₂) and oxygen consumption (VO₂). SvO₂ is measured in the pulmonary artery and represents mixed venous blood from the whole circulation, whereas ScvO₂ is typically obtained from a central venous catheter in the superior vena cava. Although ScvO₂ is often used as a less invasive surrogate, the two measures are not interchangeable [8,9], and SvO₂ may better reflect whole-body oxygen supply-demand balance [10]. Since DO₂ is primarily determined by cardiac output, arterial oxygen saturation, and Hb, it is theoretically expected that, if VO₂ remains constant, an increase in Hb due to transfusion will increase DO₂, resulting in an observable rise in SvO₂. In this study, cases with lower pre-transfusion SvO₂ showed greater increases in SvO₂ post-transfusion. This finding aligns with the concept that low SvO₂ suggests insufficient DO₂ and supports the physiological rationale for transfusion. Conversely, the group with higher pre-transfusion SvO₂ showed minimal change in SvO₂ post-transfusion. Elevated SvO₂ values may indicate either (i) that oxygen supply already sufficiently meets tissue oxygen demand, making additional increases in DO₂ unlikely to enhance oxygen extraction, or (ii) that peripheral oxygen extraction and utilization capacity is impaired, leading to residual oxygen in the venous system [11]. As a pathophysiological explanation for (ii), vasoplegic syndrome may develop in the acute postoperative period after cardiovascular surgery requiring initial transfusion, in the setting of cardiopulmonary bypass exposure and ischemia-reperfusion–related inflammation. This may lead to circulatory abnormalities mediated by excessive nitric oxide (NO) production, as well as impaired oxygen utilization due to mitochondrial dysfunction [12–14]. This study was conducted in a high-volume cardiovascular surgical ICU in Japan, where the ICU mortality rate was 3.6% and patient severity was high. Given the high pre-transfusion SvO₂ in all enrolled patients, it remains possible that many patients had vasoplegic syndrome. Furthermore, stored RBCs may exhibit a leftward shift in the oxygen dissociation curve (decreased P50) and reduced peripheral oxygen release due to decreased 2,3-DPG levels. Scott et al. reported that stored RBCs exhibit a marked decrease in 2,3-DPG and a reduction in P50, and that it takes several days for the patient's blood 2,3-DPG to recover after transfusion with stored RBCs [15]. These findings represent one potential mechanism by which elevated Hb does not necessarily directly improve tissue oxygenation. Additionally, circulatory changes associated with transfusion (attenuated compensatory tachycardia and cardiac output) may prevent Hb elevation from leading to increased DO₂. Overall, this study also shows a slight downward trend in HR, CO, and CI before and after transfusion. However, sensitivity analysis indicates that SvO₂, Hb, and DO₂ tend to increase after RBC transfusion. This study is the first large-scale investigation examining SvO₂ as a physiological indicator in RBC transfusion for cardiovascular surgery patients. A key strength is the use of directly measured hemodynamic data, including SvO₂ obtained from pulmonary artery catheter monitoring in routine clinical practice across a broad pre-transfusion Hb range (Hb ≥ 7.5 g/dL). While restrictive transfusion is recommended in many situations [1], randomized controlled trials in acute myocardial infarction patients have not completely ruled out potential disadvantages of restrictive transfusion strategies [16]. Rather than applying a uniform threshold based solely on Hb, the concurrent use of SvO₂, which reflects the oxygen supply-demand balance, may enable the identification of cases where transfusion could be physiologically meaningful. Future prospective studies based on physiological triggers, including SvO₂, are needed to verify the impact on transfusion optimization and patient-centered outcomes. Limitations This study is a single-center retrospective observational study, and the influence of unmeasured confounding and selection bias cannot be excluded. In particular, because the analysis was limited to patients in whom a pulmonary artery catheter was placed and paired SvO₂ measurements were available, the generalizability of the findings is limited. Moreover, post-transfusion SvO₂ measurements were not obtained at a strictly standardized time point after transfusion initiation (median, 70 minutes [IQR, 58–86 minutes]), which may have affected the estimation of acute SvO₂ changes. Furthermore, because the primary outcome was defined as ΔSvO₂, the observed association between pre-transfusion SvO₂ and outcome may have been influenced by regression to the mean or mathematical coupling. In addition, no standardized transfusion protocol was in place, and decisions regarding the indication and timing of transfusion were left to the treating clinicians, which may have introduced additional residual confounding. Finally, this study was primarily intended to characterize the physiologic response to transfusion rather than to demonstrate definitive clinical benefit. Accordingly, whether the observed changes in SvO₂ and DO₂i translate into improved patient-centered outcomes remains unclear. Conclusions In this population of cardiovascular surgical ICU patients with pre-transfusion Hb ≥ 7.5 g/dL, lower pre-transfusion SvO₂ was associated with a greater increase in SvO₂ after a 2-unit RBC transfusion, and this relationship was preserved up to Hb ≥ 10 g/dL. Pre-transfusion SvO₂ showed moderate discriminative ability for predicting SvO₂ responsiveness, with an optimal cutoff of 69%. These findings suggest that pre-transfusion SvO₂ may help identify patients with physiologic responsiveness to transfusion, although prospective studies are needed to determine whether this approach improves clinical outcomes. Abbreviations CABG: Coronary artery bypass grafting CI: Cardiac index CVICU: Cardiovascular intensive care unit DO₂: Oxygen delivery DO₂i: Oxygen delivery index EVAR: Endovascular aneurysm repair Hb: Hemoglobin ICU: Intensive care unit IQR: Interquartile range IPTW: Inverse probability of treatment weighting OR: Odds ratio OW: Overlap weighting PAC: Pulmonary artery catheter PSM: Propensity score matching RBC: Red blood cell ROC: Receiver operating characteristic ScvO₂: Central venous oxygen saturation SpO₂: Peripheral oxygen saturation SvO₂: Mixed venous oxygen saturation TEVAR: Thoracic endovascular aortic repair VAD: Ventricular assist device VO₂: Oxygen consumption Declarations Ethics approval and consent to participate This retrospective observational study was approved by the Ethics Review Committee of the National Cerebral and Cardiovascular Center (Approval No. R24108). Given the retrospective design, consent was obtained using an opt-out approach, and the requirement for individual written informed consent was waived. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are not publicly available because they contain potentially identifiable clinical information, but are available from the corresponding author on reasonable request and with the permission of the National Cerebral and Cardiovascular Center. Competing interests The authors declare that they have no competing interests. Funding No specific funding was received for this study. Authors’ contributions KO conceived and designed the study, analyzed and interpreted the data, and drafted the manuscript. KM, TS, and MT contributed to data acquisition and interpretation. CD, JD, and MGD contributed to interpretation of the data and critical revision of the manuscript. SF, TN, and MT contributed to study supervision, interpretation of the data, and critical revision of the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable. Authors’ information Not applicable. References Carson JL, Stanworth SJ, Guyatt G, Valentine S, Dennis J, Bakhtary S, et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA. 2023;330:1892–902. https://doi.org/10.1001/jama.2023.12914 Magruder JT, Weiss SJ, DeAngelis KG, Haddle J, Desai ND, Szeto WY, et al. Correlating oxygen delivery on cardiopulmonary bypass with Society of Thoracic Surgeons outcomes following cardiac surgery. J Thorac Cardiovasc Surg. 2022;164:997–1007. https://doi.org/10.1016/j.jtcvs.2020.12.008 Ranucci M, Castelvecchio S, Ditta A, Brozzi S, Boncilli A, Baryshnikova E, et al. Transfusions during cardiopulmonary bypass: better when triggered by venous oxygen saturation and oxygen extraction rate. 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Characteristic Overall Demographics Age at ICU admission, years 66.6 ± 15.2 Male sex, n (%) 822 (60.8) Body mass index, kg/m² 23.0 ± 4.0 ICU length of stay, days 4 [3–7] Preoperative echocardiography Left ventricular ejection fraction (visual), % (n = 776) 49.79 ± 17.38 Left ventricular ejection fraction (modified Simpson), % (n = 602) 45.89 ± 15.02 Mortality outcomes ICU mortality, n (%) 48 (3.6) In-hospital mortality, n (%) 213 (15.8) Procedure type (mutually exclusive) Isolated valve surgery, n (%) 377 (27.9) Isolated open aortic/vascular surgery, n (%) 218 (16.1) Isolated CABG/coronary surgery, n (%) 202 (14.9) Isolated endovascular procedure (EVAR/TEVAR), n (%) 154 (11.4) Isolated heart transplant/VAD, n (%) 76 (5.6) CABG + valve surgery, n (%) 48 (3.6) Valve + open aortic surgery, n (%) 35 (2.6) CABG + open aortic surgery, n (%) 14 (1.0) Other combined, n (%) 24 (1.8) Unclassified, n (%) 204 (15.1) Values are presented as mean ± SD, median [interquartile range], or n (%), as appropriate. Percentages are based on the total cohort (N = 1352). ICU, intensive care unit; CABG, coronary artery bypass grafting; EVAR, endovascular aneurysm repair; TEVAR, thoracic endovascular aortic repair; VAD, ventricular assist device. Table 2. Hemodynamic and respiratory variables before and after red blood cell transfusion. Variable Pre-transfusion Post-transfusion Hemoglobin, g/dL 9.82 ± 0.92 10.24 ± 0.98 Oxygen saturation (SpO₂), % 98.54 ± 1.64 98.34 ± 2.97 Arterial blood pressure, systolic, mmHg 102.39 ± 16.53 103.25 ± 16.89 Arterial blood pressure, diastolic, mmHg 53.69 ± 9.92 53.72 ± 10.03 Mean arterial pressure, mmHg 68.98 ± 11.16 69.06 ± 9.06 Heart rate, beats/min 94.82 ± 14.09 93.84 ± 14.52 Respiratory rate, breaths/min 14.85 ± 4.98 14.88 ± 5.02 Blood temperature, °C 37.04 ± 0.89 37.30 ± 1.23 Mixed venous oxygen saturation (SvO₂), % 73.79 ± 9.91 73.86 ± 9.37 Pulmonary artery pressure, systolic, mmHg 27.04 ± 6.96 27.01 ± 6.71 Pulmonary artery pressure, diastolic, mmHg 17.17 ± 4.71 17.09 ± 4.53 Pulmonary artery pressure, mean, mmHg 21.09 ± 7.21 20.94 ± 5.22 Mean right atrial pressure, mmHg 11.58 ± 16.62 12.37 ± 21.68 Cardiac index, L/min/m² 3.01 ± 2.66 2.86 ± 1.15 Cardiac output, L/min 4.77 ± 1.58 4.66 ± 1.50 Systemic vascular resistance, dyn·s·cm⁻5 1262.70 ± 535.46 1281.56 ± 496.70 Values are presented as mean ± SD. SpO₂ indicates oxygen saturation measured by pulse oximetry. Table 3. Multivariable logistic regression analysis for SvO₂ response (ΔSvO₂ ≥ 5%). Variable Adjusted OR 95% CI P value Age (per year) 1.00 0.99–1.02 0.86 Male sex 0.86 0.56–1.33 0.49 Hemoglobin (g/dL) 0.97 0.74–1.26 0.83 Baseline SvO₂ (per 1% increase) 0.89 0.86–0.91 <0.001 SpO₂ (%) 0.95 0.84–1.09 0.45 Cardiac index (L/min/m²) 0.95 0.90–1.08 0.17 Ejection fraction (%) 1.00 0.98–1.01 0.83 The outcome variable was post-transfusion SvO₂ response (ΔSvO₂ ≥ 5%). All covariates were measured pre-transfusion (baseline). Left ventricular ejection fraction was obtained from the most recent transthoracic or transesophageal echocardiogram (n = 1204/1352). Additional Declarations No competing interests reported. Supplementary Files SupplementaryAppendix20260408.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 May, 2026 Reviews received at journal 04 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviews received at journal 27 Apr, 2026 Reviews received at journal 25 Apr, 2026 Reviews received at journal 22 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 15 Apr, 2026 Reviewers agreed at journal 15 Apr, 2026 Reviewers invited by journal 15 Apr, 2026 Editor assigned by journal 10 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 08 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-9352763","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":627882087,"identity":"316bcc64-0ad5-4d29-b865-2abc117e24eb","order_by":0,"name":"Kentaro Okamoto","email":"data:image/png;base64,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","orcid":"","institution":"St. Marianna University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Okamoto","suffix":""},{"id":627882088,"identity":"cef3c69b-e978-4bc5-9f1d-a3239cc43aa5","order_by":1,"name":"Kimito Minami","email":"","orcid":"","institution":"National Cerebral and Cardiovascular Center","correspondingAuthor":false,"prefix":"","firstName":"Kimito","middleName":"","lastName":"Minami","suffix":""},{"id":627882090,"identity":"61f3e9ce-4a55-4b01-83db-0238063f4179","order_by":2,"name":"Chase Donaldson","email":"","orcid":"","institution":"Cleveland Clinic Main Campus Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chase","middleName":"","lastName":"Donaldson","suffix":""},{"id":627882091,"identity":"513b69ca-579a-4cb3-841f-1ffa235b42b8","order_by":3,"name":"Jean Deschamps","email":"","orcid":"","institution":"Cleveland Clinic Main Campus Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jean","middleName":"","lastName":"Deschamps","suffix":""},{"id":627882096,"identity":"3a1fd745-9935-486d-afd0-a620a5ec09d9","order_by":4,"name":"Marcelo Gama de Abreu","email":"","orcid":"","institution":"Cleveland Clinic Main Campus Hospital","correspondingAuthor":false,"prefix":"","firstName":"Marcelo","middleName":"Gama","lastName":"de Abreu","suffix":""},{"id":627882099,"identity":"cc27b23c-7da1-4f41-8587-4af82c28fcee","order_by":5,"name":"Shigeki Fujitani","email":"","orcid":"","institution":"St. Marianna University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shigeki","middleName":"","lastName":"Fujitani","suffix":""},{"id":627882101,"identity":"9684e87b-2dcf-45df-b9d9-00d5a0f21abb","order_by":6,"name":"Takaki Naito","email":"","orcid":"","institution":"St. Marianna University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takaki","middleName":"","lastName":"Naito","suffix":""},{"id":627882104,"identity":"f8b4bb6a-4c46-459f-8df9-3377221e5656","order_by":7,"name":"Tatsutoshi Shimatani","email":"","orcid":"","institution":"National Cerebral and Cardiovascular Center","correspondingAuthor":false,"prefix":"","firstName":"Tatsutoshi","middleName":"","lastName":"Shimatani","suffix":""},{"id":627882106,"identity":"7bbb1905-7a27-43f3-94d8-9122e96ab992","order_by":8,"name":"Muneyuki Takeuchi","email":"","orcid":"","institution":"National Cerebral and Cardiovascular Center","correspondingAuthor":false,"prefix":"","firstName":"Muneyuki","middleName":"","lastName":"Takeuchi","suffix":""}],"badges":[],"createdAt":"2026-04-08 06:54:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9352763/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9352763/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107675504,"identity":"d2ba1adc-5a1c-4240-90a8-ed35ccc5c024","added_by":"auto","created_at":"2026-04-24 00:43:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":393295,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow diagram.\u003c/p\u003e\n\u003cp\u003eAmong 18,117 RBC transfusion episodes with hemoglobin ≥ 7.5 g/dL identified in the CVICU between July 1, 2019 and December 31, 2024, 6,962 had paired pre- and post-transfusion SvO₂ measurements. After exclusion of repeated transfusions beyond the first transfusion per patient (n = 5,555) and transfusions other than 2 units of RBCs (n = 55), 1,352 unique patients were included in the final analysis.\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/ad3275ea15fef5afadd4e056.png"},{"id":107675507,"identity":"757571bd-7a2b-4d1e-8ee8-aeead59578b8","added_by":"auto","created_at":"2026-04-24 00:43:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":132757,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eΔSvO₂ (Hb ≥ 7.5 g/dL) by pre-transfusion SvO₂ category.\u003c/p\u003e\n\u003cp\u003eBoxplots with overlaid individual observations are shown across pre-transfusion SvO₂ categories. The dashed horizontal line indicates ΔSvO₂ = 5%.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/2f56bfbd919b1ec8def971b5.png"},{"id":107675505,"identity":"503c99b7-947d-4bec-b1ae-a5962f7b0d59","added_by":"auto","created_at":"2026-04-24 00:43:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":177710,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve predicting SvO₂ response (ΔSvO₂ ≥ 5%) based on pre-transfusion SvO₂.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe area under the curve (AUC) was 0.778 (95% CI, 0.74–0.816). The plotted cut-off of 69% corresponded to a sensitivity of 0.68 and a specificity of 0.75.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/e9690e61b1e079f997608a7c.png"},{"id":107706395,"identity":"976e3038-dd95-479e-96fa-d1bab2e544c5","added_by":"auto","created_at":"2026-04-24 09:18:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":207346,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of multivariable logistic regression with SvO₂ response (ΔSvO₂ ≥ 5%) as the target variable.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003ePoints indicate adjusted odds ratios and whiskers indicate 95% confidence intervals. Continuous variables are shown as odds ratios per unit increase.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/da4567a8f83d47ba3ff37aa9.png"},{"id":107709408,"identity":"37b2456a-1212-4731-9135-e9e192ef545b","added_by":"auto","created_at":"2026-04-24 09:35:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1116797,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/686ac547-c09a-46c9-85c5-f90fa32d2d22.pdf"},{"id":107708019,"identity":"fbea2b95-ecc5-48dc-bb07-e379a9bfa0eb","added_by":"auto","created_at":"2026-04-24 09:21:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":730254,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryAppendix20260408.docx","url":"https://assets-eu.researchsquare.com/files/rs-9352763/v1/304d54480acfe1767acfbe9e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"SvO₂ Response to Red Blood Cell Transfusion in Cardiovascular Surgical ICU Patients: A Retrospective Observational Study","fulltext":[{"header":"Background","content":"\u003cp\u003eRed blood cell (RBC) transfusion is frequently performed in the postoperative management of cardiovascular surgery. However, recent international guidelines generally recommend a restrictive transfusion strategy with a threshold of Hb 7.5 g/dL even for cardiac surgery patients [1]. However, transfusion triggers beyond hemoglobin concentration, particularly those based on physiological indicators, remain poorly established. Mixed venous oxygen saturation (SvO₂) reflects the balance between oxygen delivery (DO₂) and oxygen consumption (VO₂) and may serve as an indicator of potential benefit from transfusion. Nevertheless, studies evaluating transfusion efficacy using venous oxygen saturation (SvO₂ or ScvO₂) are limited [2,3].\u003c/p\u003e\n\u003cp\u003eZeroual et al., in an observational study of cardiac surgery patients with Hb \u0026le; 9 g/dL, reported that cases with lower pre-transfusion central venous oxygen saturation (ScvO₂) were more likely to show an increase in ScvO₂ post-transfusion [4]. Furthermore, in a randomized controlled trial (RCT), the same group demonstrated that a strategy of transfusing RBCs in patients with a Hb \u0026lt;9 g/dL only when ScvO₂ \u0026le; 65% could reduce RBC transfusion [5]. Similarly, Fischer et al. demonstrated in an RCT involving patients with Hb \u0026lt; 9 g/dL that compared to an intervention group receiving transfusions only when ScvO₂ \u0026lt; 70%, the transfusion rate was significantly reduced with no difference in clinical outcomes [6].\u003c/p\u003e\n\u003cp\u003eThese prior studies demonstrate that a restrictive transfusion protocol integrating hemoglobin levels and a marker of oxygen supply and demand mismatch (ScvO2) in cardiac surgery patients reduces the number of transfused red blood cell units and the number of patients receiving at least one transfusion, without evidence of significant adverse events [7]. Based on the results of previous studies, we considered that even in patients with Hb \u0026ge; 7.5 g/dL\u0026mdash;a level not currently considered an indication for active transfusion\u0026mdash;if pre-transfusion SvO₂ is low, there may be patients who exhibit an increase in SvO₂ after transfusion. In this patient group, despite Hb levels greater than those currently recommended as a potential RBC transfusion trigger, there may still be tissue oxygen supply-demand mismatch, suggesting that transfusion could provide physiological benefit.\u003c/p\u003e\n\u003ch1\u003eObjective\u003c/h1\u003e\n\u003cp\u003eTo describe the physiologic change in SvO₂ after a 2-unit RBC transfusion in CVICU patients with pre-transfusion Hb \u0026ge; 7.5 g/dL, identify predictors of SvO₂ response (\u0026Delta;SvO₂ \u0026ge;5%), and determine the optimal pre-transfusion SvO₂ cutoff.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy Design and Setting\u003c/h2\u003e\n\u003cp\u003eThis retrospective observational study utilized electronic medical record data from patients admitted to the Cardiovascular Intensive Care Unit (CVICU) at the National Cerebral and Cardiovascular Center between July 1, 2019, and December 31, 2024. The study was approved by the Ethics Review Committee (Approval No. R24108). Given the retrospective design, consent was obtained using an opt-out approach, and the requirement for individual written informed consent was waived.\u003c/p\u003e\n\u003ch2\u003eSubjects\u003c/h2\u003e\n\u003cp\u003eInclusion criteria were: (1) age \u0026ge;18 years, (2) receipt of one standard 2-unit RBC product during CVICU admission, (3) pre-transfusion Hb \u0026ge; 7.5 g/dL, (4) obtainable pre- and post-transfusion SvO₂ values, and (5) SvO₂ monitoring via pulmonary artery catheterization.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were cases where multiple blood products were administered simultaneously and blood product records were deemed inaccurate (e.g., massive transfusion for postoperative bleeding) and cases of refusal to participate in this study. Furthermore, for patients receiving multiple transfusions, only the first transfusion was included in the analysis. In our institution, red blood cells were routinely administered as a leukoreduced RBC product derived from a 400-mL whole-blood donation. In Japan, this product is labeled as 2 units in the Japanese system; its approximate volume is approximately 280 mL, making it roughly comparable to 1 unit of packed red blood cells in the United States, and it is commonly infused over approximately 1 hour in routine adult practice.\u003c/p\u003e\n\u003ch2\u003eData Acquisition and Variable Definition\u003c/h2\u003e\n\u003cp\u003eThe following variables were extracted: transfusion time, Hb from blood gas analysis, SvO₂, SpO₂, heart rate, blood pressure, cardiac index, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance from ACSYS\u0026reg; monitor records. The pulmonary artery catheter used was the thermal filament pulmonary artery catheter (Edwards Lifesciences). Pre-transfusion values were defined as the closest recorded value (immediate value) to the transfusion start time. Post-transfusion values were defined as the closest recorded value (immediate value) to approximately 60 minutes after transfusion start. \u0026Delta;SvO₂ was calculated as post-transfusion SvO₂ minus pre-transfusion SvO₂.\u003c/p\u003e\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003cp\u003eThe primary outcome was SvO₂ responsiveness, defined a priori as \u0026Delta;SvO₂ \u0026ge;5% after transfusion. This cutoff was selected based on previous work by Zeroual et al.[4], which used a \u0026ge;5% increase in ScvO₂ after RBC transfusion as a marker of transfusion response, allowing comparison with the existing literature.\u0026nbsp;In addition, we evaluated the predictive performance of pre-transfusion SvO₂ for SvO₂ responsiveness and performed prespecified subgroup and sensitivity analyses.\u003c/p\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eContinuous variables were presented as mean \u0026plusmn; standard deviation or median (interquartile range). Categorical variables were presented as number (%) or proportion (%). To examine factors associated with SvO₂ responsiveness, multivariate logistic regression analysis was performed using variables related to oxygen supply (age, sex, pre-transfusion Hb, pre-transfusion SvO₂, SpO₂, cardiac index, left ventricular ejection fraction) as explanatory variables. The predictive ability of pre-transfusion SvO₂ for SvO₂ responsiveness was evaluated using ROC curves. As a subgroup analysis, \u0026Delta;SvO₂ was described by pre-transfusion SvO₂ category in populations with lower limits of pre-transfusion Hb set at 9, 10, 11, and 12 g/dL. As a sensitivity analysis, we constructed a risk set anchored at transfusion initiation to compare the transfusion and no-transfusion groups. To adjust for confounding, we evaluated propensity score matching, inverse probability of treatment weighting (IPTW), and overlap weighting, and selected overlap weighting because it provided the best covariate balance (Table S1). Trajectories of SvO₂, Hb, and DO₂i over 0\u0026ndash;6 hours were analyzed using models that included group, time, and a group-by-time interaction term. Furthermore, to reinforce the results of the main analysis, a multivariate linear regression analysis was also performed using \u0026Delta;SvO₂ as a continuous variable. Statistical analyses were performed using R version 4.5.2 (R Foundation for Statistical Computing, Vienna, Austria). This study is reported in accordance with the STROBE statement for observational studies.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eIdentification of Subject Patients\u003c/h2\u003e\n\u003cp\u003eAmong patients aged 18 years or older admitted to the CVICU, 18,117 transfusion episodes with Hb \u0026ge;7.5 g/dL were identified. Of these, 6,962 episodes had paired pre- and post-transfusion SvO₂ values. After excluding repeated transfusions beyond the first transfusion per patient (n = 5,555) and transfusions other than 2 units of RBCs (n = 55), 1,352 patients were included in the analysis population (Figure 1).\u003c/p\u003e\n\u003ch2\u003ePatient background and pre- and post-transfusion parameters\u003c/h2\u003e\n\u003cp\u003eThe patient\u0026rsquo;s background is shown in Table 1. A total of 1,352 patients were included. The mean age at ICU admission was 66.6 \u0026plusmn; 15.2 years, and 822 (60.8%) patients were male. Mean body mass index was 23.0 \u0026plusmn; 4.0 kg/m\u0026sup2;. The median ICU length of stay was 4 [3\u0026ndash;7] days, and ICU mortality was 48 (3.6%). Preoperative cardiac function showed a left ventricular ejection fraction of 49.8 \u0026plusmn; 17.4% using the visual method (n = 776) and 45.9 \u0026plusmn; 15.0% using the modified Simpson method (n = 602).\u003c/p\u003e\n\u003cp\u003eRegarding procedure types (mutually exclusive), 377 (27.9%) underwent isolated valve surgery, 218 (16.1%) isolated open aortic/vascular surgery, 202 (14.9%) isolated CABG/coronary surgery, 154 (11.4%) isolated endovascular procedures (EVAR/TEVAR), and 76 (5.6%) isolated heart transplant/VAD. Combined procedures included CABG + valve surgery (48 [3.6%]), valve + open aortic surgery (35 [2.6%]), and CABG + open aortic surgery (14 [1.0%]). Other combined procedures accounted for 24 (1.8%), and unclassified cases accounted for 204 (15.1%).\u003c/p\u003e\n\u003cp\u003eTable 2 shows circulatory and respiratory parameters before and after transfusion. The median time from transfusion initiation to post-transfusion SvO₂ measurement was 70 minutes (interquartile range [IQR], 58\u0026ndash;86 minutes; range, 45\u0026ndash;120 minutes; mean, 72.3 minutes). Pre-transfusion Hb was 9.82 \u0026plusmn; 0.92 g/dL, and post-transfusion Hb was 10.24 \u0026plusmn; 0.98 g/dL. SvO₂ was 73.79 \u0026plusmn; 9.91% (median 75%, IQR 68\u0026ndash;80) before transfusion and 73.86 \u0026plusmn; 9.37% (median 74%, IQR 68\u0026ndash;80) after transfusion, showing a small change as a group average. However, the response was not uniform. When stratified by pre-transfusion SvO₂ category, lower pre-transfusion SvO₂ was associated with larger \u0026Delta;SvO₂ and a greater likelihood of post-transfusion SvO₂ elevation (Figure 2).\u003c/p\u003e\n\u003ch2\u003ePrediction of SvO₂ Response\u003c/h2\u003e\n\u003cp\u003eThe predictive ability of pre-transfusion SvO₂ for SvO₂ responsiveness was an AUC of 0.778 (95% confidence interval 0.74\u0026ndash;0.816) (Figure 3). ROC analysis identified an optimal cutoff value of SvO₂ 69%, with a sensitivity of 0.68 and specificity of 0.75. For reference, applying the 65% cutoff used in the prior study by Zeroual et al. using ScvO₂ guidance to this dataset yielded a sensitivity of 0.52 and a specificity of 0.86 [4].\u003c/p\u003e\n\u003ch2\u003eMultivariate Analysis\u003c/h2\u003e\n\u003cp\u003eIn a multivariate logistic regression analysis with SvO₂ responsiveness as the outcome, only pre-transfusion SvO₂ was independently associated with SvO₂ responsiveness (Table 3, Figure 4).\u003c/p\u003e\n\u003ch2\u003eSubgroup Analysis and Sensitivity Analysis\u003c/h2\u003e\n\u003cp\u003eSubgroup analyses were performed by modifying the lower limit of pre-transfusion Hb (Hb \u0026ge; 9, Hb \u0026ge; 10, Hb \u0026ge; 11, Hb \u0026ge; 12 g/dL), and \u0026Delta;SvO₂ was evaluated by pre-transfusion SvO₂ category within each stratum (Figure S1). In the Hb \u0026ge; 9 g/dL (n = 1,153) and Hb \u0026ge; 10 g/dL (n = 520) groups, the visual trend observed in the entire cohort\u0026mdash;where lower pre-transfusion SvO₂ was associated with greater \u0026Delta;SvO₂\u0026mdash;was largely maintained. However, in the Hb \u0026ge; 11 g/dL (n = 119) and Hb \u0026ge; 12 g/dL (n = 28) groups, the number of cases was limited, particularly in the low pre-transfusion SvO₂ category, leaving uncertainty in verifying the trend.\u003c/p\u003e\n\u003cp\u003eIn the overlap-weighted sensitivity analysis, trajectories of SvO₂, Hb, and DO₂i over 0\u0026ndash;6 hours differed significantly between the transfusion and no-transfusion groups (all group-by-time interaction P\u0026lt;0.001). The transfusion group showed clear increases in Hb and DO₂i and maintained or slightly increased SvO₂, whereas the no-transfusion group showed minimal change in Hb and no comparable increase in SvO₂ or DO₂i (Figure S2). Furthermore, in multivariate linear regression analyzing \u0026Delta;SvO₂ as a continuous variable, CI and SpO₂ were significantly associated with \u0026Delta;SvO₂, in addition to baseline SvO₂, consistent with the primary analysis (Table S2, Figure S3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that in intensive care patients following cardiovascular surgery, even with Hb\u0026thinsp;\u0026ge;\u0026thinsp;7.5 g/dL, if pre-transfusion SvO₂ is low, post-transfusion SvO₂ increases significantly, with a high likelihood of showing ΔSvO₂ \u0026ge; 5%. This trend persisted in subgroup analyses restricted to cases with higher Hb thresholds, remaining consistent at least up to Hb 10 g/dL. ROC analysis indicated that pre-transfusion SvO₂ around 69% contributed to distinguishing SvO₂ responsiveness. Pre-transfusion SvO₂ also remained an independent predictor in a multivariate model adjusting for age, sex, and DO₂ components. Sensitivity analysis results suggested that the increase in SvO₂, accompanied by elevated Hb levels and increased DO₂ after RBC transfusion, was maintained for up to 6 hours post-transfusion.Compared to previous studies using ScvO₂ in cardiac surgery patients with Hb\u0026thinsp;\u0026lt;\u0026thinsp;9 g/dL, this study, conducted against the backdrop of recent recommendations for restricted transfusion, targeted transfusions performed at Hb\u0026thinsp;\u0026ge;\u0026thinsp;7.5 g/dL. It complements existing research by demonstrating the reproducibility of \u0026ldquo;responsiveness\u0026rdquo; based on SvO₂, while simultaneously presenting new findings.\u003c/p\u003e \u003cp\u003eBoth SvO₂ and ScvO₂ reflect the balance between systemic oxygen delivery (DO₂) and oxygen consumption (VO₂). SvO₂ is measured in the pulmonary artery and represents mixed venous blood from the whole circulation, whereas ScvO₂ is typically obtained from a central venous catheter in the superior vena cava. Although ScvO₂ is often used as a less invasive surrogate, the two measures are not interchangeable [8,9], and SvO₂ may better reflect whole-body oxygen supply-demand balance [10]. Since DO₂ is primarily determined by cardiac output, arterial oxygen saturation, and Hb, it is theoretically expected that, if VO₂ remains constant, an increase in Hb due to transfusion will increase DO₂, resulting in an observable rise in SvO₂. In this study, cases with lower pre-transfusion SvO₂ showed greater increases in SvO₂ post-transfusion. This finding aligns with the concept that low SvO₂ suggests insufficient DO₂ and supports the physiological rationale for transfusion. Conversely, the group with higher pre-transfusion SvO₂ showed minimal change in SvO₂ post-transfusion. Elevated SvO₂ values may indicate either (i) that oxygen supply already sufficiently meets tissue oxygen demand, making additional increases in DO₂ unlikely to enhance oxygen extraction, or (ii) that peripheral oxygen extraction and utilization capacity is impaired, leading to residual oxygen in the venous system [11]. As a pathophysiological explanation for (ii), vasoplegic syndrome may develop in the acute postoperative period after cardiovascular surgery requiring initial transfusion, in the setting of cardiopulmonary bypass exposure and ischemia-reperfusion\u0026ndash;related inflammation. This may lead to circulatory abnormalities mediated by excessive nitric oxide (NO) production, as well as impaired oxygen utilization due to mitochondrial dysfunction [12\u0026ndash;14]. This study was conducted in a high-volume cardiovascular surgical ICU in Japan, where the ICU mortality rate was 3.6% and patient severity was high. Given the high pre-transfusion SvO₂ in all enrolled patients, it remains possible that many patients had vasoplegic syndrome. Furthermore, stored RBCs may exhibit a leftward shift in the oxygen dissociation curve (decreased P50) and reduced peripheral oxygen release due to decreased 2,3-DPG levels. Scott et al. reported that stored RBCs exhibit a marked decrease in 2,3-DPG and a reduction in P50, and that it takes several days for the patient's blood 2,3-DPG to recover after transfusion with stored RBCs [15]. These findings represent one potential mechanism by which elevated Hb does not necessarily directly improve tissue oxygenation. Additionally, circulatory changes associated with transfusion (attenuated compensatory tachycardia and cardiac output) may prevent Hb elevation from leading to increased DO₂. Overall, this study also shows a slight downward trend in HR, CO, and CI before and after transfusion. However, sensitivity analysis indicates that SvO₂, Hb, and DO₂ tend to increase after RBC transfusion. This study is the first large-scale investigation examining SvO₂ as a physiological indicator in RBC transfusion for cardiovascular surgery patients. A key strength is the use of directly measured hemodynamic data, including SvO₂ obtained from pulmonary artery catheter monitoring in routine clinical practice across a broad pre-transfusion Hb range (Hb\u0026thinsp;\u0026ge;\u0026thinsp;7.5 g/dL). While restrictive transfusion is recommended in many situations [1], randomized controlled trials in acute myocardial infarction patients have not completely ruled out potential disadvantages of restrictive transfusion strategies [16]. Rather than applying a uniform threshold based solely on Hb, the concurrent use of SvO₂, which reflects the oxygen supply-demand balance, may enable the identification of cases where transfusion could be physiologically meaningful. Future prospective studies based on physiological triggers, including SvO₂, are needed to verify the impact on transfusion optimization and patient-centered outcomes.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study is a single-center retrospective observational study, and the influence of unmeasured confounding and selection bias cannot be excluded. In particular, because the analysis was limited to patients in whom a pulmonary artery catheter was placed and paired SvO₂ measurements were available, the generalizability of the findings is limited. Moreover, post-transfusion SvO₂ measurements were not obtained at a strictly standardized time point after transfusion initiation (median, 70 minutes [IQR, 58\u0026ndash;86 minutes]), which may have affected the estimation of acute SvO₂ changes. Furthermore, because the primary outcome was defined as ΔSvO₂, the observed association between pre-transfusion SvO₂ and outcome may have been influenced by regression to the mean or mathematical coupling. In addition, no standardized transfusion protocol was in place, and decisions regarding the indication and timing of transfusion were left to the treating clinicians, which may have introduced additional residual confounding. Finally, this study was primarily intended to characterize the physiologic response to transfusion rather than to demonstrate definitive clinical benefit. Accordingly, whether the observed changes in SvO₂ and DO₂i translate into improved patient-centered outcomes remains unclear.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this population of cardiovascular surgical ICU patients with pre-transfusion Hb\u0026thinsp;\u0026ge;\u0026thinsp;7.5 g/dL, lower pre-transfusion SvO₂ was associated with a greater increase in SvO₂ after a 2-unit RBC transfusion, and this relationship was preserved up to Hb\u0026thinsp;\u0026ge;\u0026thinsp;10 g/dL. Pre-transfusion SvO₂ showed moderate discriminative ability for predicting SvO₂ responsiveness, with an optimal cutoff of 69%. These findings suggest that pre-transfusion SvO₂ may help identify patients with physiologic responsiveness to transfusion, although prospective studies are needed to determine whether this approach improves clinical outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCABG: Coronary artery bypass grafting\u003c/p\u003e\n\u003cp\u003eCI: Cardiac index\u003c/p\u003e\n\u003cp\u003eCVICU: Cardiovascular intensive care unit\u003c/p\u003e\n\u003cp\u003eDO₂: Oxygen delivery\u003c/p\u003e\n\u003cp\u003eDO₂i: Oxygen delivery index\u003c/p\u003e\n\u003cp\u003eEVAR: Endovascular aneurysm repair\u003c/p\u003e\n\u003cp\u003eHb: Hemoglobin\u003c/p\u003e\n\u003cp\u003eICU: Intensive care unit\u003c/p\u003e\n\u003cp\u003eIQR: Interquartile range\u003c/p\u003e\n\u003cp\u003eIPTW: Inverse probability of treatment weighting\u003c/p\u003e\n\u003cp\u003eOR: Odds ratio\u003c/p\u003e\n\u003cp\u003eOW: Overlap weighting\u003c/p\u003e\n\u003cp\u003ePAC: Pulmonary artery catheter\u003c/p\u003e\n\u003cp\u003ePSM: Propensity score matching\u003c/p\u003e\n\u003cp\u003eRBC: Red blood cell\u003c/p\u003e\n\u003cp\u003eROC: Receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eScvO₂: Central venous oxygen saturation\u003c/p\u003e\n\u003cp\u003eSpO₂: Peripheral oxygen saturation\u003c/p\u003e\n\u003cp\u003eSvO₂: Mixed venous oxygen saturation\u003c/p\u003e\n\u003cp\u003eTEVAR: Thoracic endovascular aortic repair\u003c/p\u003e\n\u003cp\u003eVAD: Ventricular assist device\u003c/p\u003e\n\u003cp\u003eVO₂: Oxygen consumption\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective observational study was approved by the Ethics Review Committee of the National Cerebral and Cardiovascular Center (Approval No. R24108). Given the retrospective design, consent was obtained using an opt-out approach, and the requirement for individual written informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are not publicly available because they contain potentially identifiable clinical information, but are available from the corresponding author on reasonable request and with the permission of the National Cerebral and Cardiovascular Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKO conceived and designed the study, analyzed and interpreted the data, and drafted the manuscript. KM, TS, and MT contributed to data acquisition and interpretation. CD, JD, and MGD contributed to interpretation of the data and critical revision of the manuscript. SF, TN, and MT contributed to study supervision, interpretation of the data, and critical revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCarson JL, Stanworth SJ, Guyatt G, Valentine S, Dennis J, Bakhtary S, et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA. 2023;330:1892\u0026ndash;902. https://doi.org/10.1001/jama.2023.12914\u003c/li\u003e\n\u003cli\u003eMagruder JT, Weiss SJ, DeAngelis KG, Haddle J, Desai ND, Szeto WY, et al. Correlating oxygen delivery on cardiopulmonary bypass with Society of Thoracic Surgeons outcomes following cardiac surgery. J Thorac Cardiovasc Surg. 2022;164:997\u0026ndash;1007. https://doi.org/10.1016/j.jtcvs.2020.12.008\u003c/li\u003e\n\u003cli\u003eRanucci M, Castelvecchio S, Ditta A, Brozzi S, Boncilli A, Baryshnikova E, et al. Transfusions during cardiopulmonary bypass: better when triggered by venous oxygen saturation and oxygen extraction rate. Perfusion. 2011;26:327\u0026ndash;33. https://doi.org/10.1177/0267659111407539, PubMed PMID: 21558300\u003c/li\u003e\n\u003cli\u003eZeroual N, Samarani G, Gallais J, Culas G, Saour M, Mourad M, et al. ScvO\u003csub\u003e2\u003c/sub\u003e changes after red‐blood‐cell transfusion for anaemia in cardiothoracic and vascular ICU patients: an observational study. Vox Sang. 2018;113:136\u0026ndash;42. https://doi.org/10.1111/vox.12610\u003c/li\u003e\n\u003cli\u003eZeroual N, Blin C, Saour M, David H, Aouinti S, Picot MC, et al. Restrictive transfusion strategy after cardiac surgery. Anesthesiology. 2021;134:370\u0026ndash;80. https://doi.org/10.1097/ALN.0000000000003682\u003c/li\u003e\n\u003cli\u003eFischer MO, Guinot PG, Debroczi S, Huette P, Beyls C, Babatasi G, et al. Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial. Br J Anaesth. 2022;128:37\u0026ndash;44. https://doi.org/10.1016/j.bja.2021.09.037\u003c/li\u003e\n\u003cli\u003ePutaggio A, Tigano S, Caruso A, La Via L, Sanfilippo F. Red blood cell transfusion guided by hemoglobin only or integrating perfusion markers in patients undergoing cardiac surgery: A systematic review and meta-analysis with trial sequential analysis. J Cardiothorac Vasc Anesth. 2023;37:2252\u0026ndash;60. https://doi.org/10.1053/j.jvca.2023.08.001\u003c/li\u003e\n\u003cli\u003eMotazedian P, Beauregard N, Letourneau I, Olaye I, Syed S, Lam E, et al. Central venous oxygen saturation for estimating mixed venous oxygen saturation and cardiac index in the ICU: A systematic review and meta-analysis. Crit Care Med. 2024;52:e568\u0026ndash;77. https://doi.org/10.1097/CCM.0000000000006398\u003c/li\u003e\n\u003cli\u003eLanning KM, Erkinaro TM, Ohtonen PP, Vakkala MA, Liisanantti JH, Ylikauma LA, et al. Accuracy, precision, and trending ability of perioperative central venous oxygen saturation compared to mixed venous oxygen saturation in unselected cardiac surgical patients. J Cardiothorac Vasc Anesth. 2022;36:1995\u0026ndash;2001. https://doi.org/10.1053/j.jvca.2021.08.103\u003c/li\u003e\n\u003cli\u003eTymen R, Dos Santos EC, Taccone FS, Aubron C. Physiological determinants and the red blood cells transfusion decision-making process in non-bleeding critically ill patients: a comprehensive narrative review. Intensive Care Med. 2026;52:309\u0026ndash;23. https://doi.org/10.1007/s00134-026-08304-w, PubMed PMID: 41586889, PubMed Central PMCID: PMC12971815\u003c/li\u003e\n\u003cli\u003eBloos F, Reinhart K. Venous oximetry. Intensive Care Med. 2005;31:911\u0026ndash;3. https://doi.org/10.1007/s00134-005-2670-9\u003c/li\u003e\n\u003cli\u003eBusse LW, Barker N, Petersen C. Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options. Crit Care. 2020;24:36. https://doi.org/10.1186/s13054-020-2743-8\u003c/li\u003e\n\u003cli\u003eBrown GC. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta. 2001;1504:46\u0026ndash;57. https://doi.org/10.1016/S0005-2728(00)00238-3\u003c/li\u003e\n\u003cli\u003eGnoni A, Ballini A, Trentadue R, Taurino F, Santacroce L, Ferrara P, et al. Induction of mitochondrial dysfunction in patients under cardiopulmonary by-pass: preliminary results. Eur Rev Med Pharmacol Sci. 2019;23:8115\u0026ndash;23. https://doi.org/10.26355/eurrev_201909_19030, PubMed PMID: 31599439\u003c/li\u003e\n\u003cli\u003eScott AV, Nagababu E, Johnson DJ, Kebaish KM, Lipsitz JA, Dwyer IM, et al. 2,3-diphosphoglycerate concentrations in autologous salvaged versus stored red blood cells and in surgical patients after transfusion. Anesth Analg. 2016;122:616\u0026ndash;23. https://doi.org/10.1213/ANE.0000000000001071, PubMed PMID: 26891388, PubMed Central PMCID: PMC4770563\u003c/li\u003e\n\u003cli\u003eCarson JL, Brooks MM, H\u0026eacute;bert PC, Goodman SG, Bertolet M, Glynn SA, et al. Restrictive or liberal transfusion strategy in myocardial infarction and anemia. N Engl J Med. 2023;389:2446\u0026ndash;56. https://doi.org/10.1056/NEJMoa2307983\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eBaseline characteristics of the study population (N = 1352).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 662px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eAge at ICU admission, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e66.6 \u0026plusmn; 15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e822 (60.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eBody mass index, kg/m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e23.0 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eICU length of stay, days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e4 [3\u0026ndash;7]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 662px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative echocardiography\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eLeft ventricular ejection fraction (visual), % (n = 776)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e49.79 \u0026plusmn; 17.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eLeft ventricular ejection fraction (modified Simpson), % (n = 602)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e45.89 \u0026plusmn; 15.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 662px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eICU mortality, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e48 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIn-hospital mortality, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e213 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 662px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProcedure type (mutually exclusive)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIsolated valve surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e377 (27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIsolated open aortic/vascular surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e218 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIsolated CABG/coronary surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e202 (14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIsolated endovascular procedure (EVAR/TEVAR), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e154 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eIsolated heart transplant/VAD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e76 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eCABG + valve surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e48 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eValve + open aortic surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e35 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eCABG + open aortic surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e14 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eOther combined, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e24 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003eUnclassified, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 331px;\"\u003e\n \u003cp\u003e204 (15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eValues are presented as mean \u0026plusmn; SD, median [interquartile range], or n (%), as appropriate.\u003c/p\u003e\n\u003cp\u003ePercentages are based on the total cohort (N = 1352). ICU, intensive care unit; CABG, coronary artery bypass grafting; EVAR, endovascular aneurysm repair; TEVAR, thoracic endovascular aortic repair; VAD, ventricular assist device.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eHemodynamic and respiratory variables before and after red blood cell transfusion.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-transfusion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-transfusion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eHemoglobin, g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e9.82 \u0026plusmn; 0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e10.24 \u0026plusmn; 0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eOxygen saturation (SpO₂), %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e98.54 \u0026plusmn; 1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e98.34 \u0026plusmn; 2.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eArterial blood pressure, systolic, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e102.39 \u0026plusmn; 16.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e103.25 \u0026plusmn; 16.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eArterial blood pressure, diastolic, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e53.69 \u0026plusmn; 9.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e53.72 \u0026plusmn; 10.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eMean arterial pressure, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e68.98 \u0026plusmn; 11.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e69.06 \u0026plusmn; 9.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eHeart rate, beats/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e94.82 \u0026plusmn; 14.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e93.84 \u0026plusmn; 14.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eRespiratory rate, breaths/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e14.85 \u0026plusmn; 4.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e14.88 \u0026plusmn; 5.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eBlood temperature, \u0026deg;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e37.04 \u0026plusmn; 0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e37.30 \u0026plusmn; 1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eMixed venous oxygen saturation (SvO₂), %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e73.79 \u0026plusmn; 9.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e73.86 \u0026plusmn; 9.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003ePulmonary artery pressure, systolic, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e27.04 \u0026plusmn; 6.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e27.01 \u0026plusmn; 6.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003ePulmonary artery pressure, diastolic, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e17.17 \u0026plusmn; 4.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e17.09 \u0026plusmn; 4.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003ePulmonary artery pressure, mean, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e21.09 \u0026plusmn; 7.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e20.94 \u0026plusmn; 5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eMean right atrial pressure, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e11.58 \u0026plusmn; 16.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e12.37 \u0026plusmn; 21.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eCardiac index, L/min/m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e3.01 \u0026plusmn; 2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e2.86 \u0026plusmn; 1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eCardiac output, L/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e4.77 \u0026plusmn; 1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e4.66 \u0026plusmn; 1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003eSystemic vascular resistance, dyn\u0026middot;s\u0026middot;cm⁻5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e1262.70 \u0026plusmn; 535.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 221px;\"\u003e\n \u003cp\u003e1281.56 \u0026plusmn; 496.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eValues are presented as mean \u0026plusmn; SD.\u003c/p\u003e\n\u003cp\u003eSpO₂ indicates oxygen saturation measured by pulse oximetry.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eMultivariable logistic regression analysis for SvO₂ response (\u0026Delta;SvO₂ \u0026ge; 5%).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted OR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eAge (per year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.99\u0026ndash;1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eMale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.56\u0026ndash;1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.74\u0026ndash;1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eBaseline SvO₂ (per 1% increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.86\u0026ndash;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eSpO₂ (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.84\u0026ndash;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eCardiac index (L/min/m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.90\u0026ndash;1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eEjection fraction (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.98\u0026ndash;1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe outcome variable was post-transfusion SvO₂ response (\u0026Delta;SvO₂ \u0026ge; 5%). All covariates were measured pre-transfusion (baseline).\u003c/p\u003e\n\u003cp\u003eLeft ventricular ejection fraction was obtained from the most recent transthoracic or transesophageal echocardiogram (n = 1204/1352).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\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":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"red blood cell transfusion, mixed venous oxygen saturation, SvO₂, cardiovascular intensive care, physiologic transfusion trigger","lastPublishedDoi":"10.21203/rs.3.rs-9352763/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9352763/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eHemoglobin thresholds alone may not identify cardiovascular surgical ICU patients who derive physiologic benefit from red blood cell (RBC) transfusion. Mixed venous oxygen saturation (SvO₂) reflects the balance between oxygen delivery and consumption and may help identify patients with transfusion-responsive oxygen supply-demand mismatch.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a retrospective observational study of adult cardiovascular surgical ICU patients who underwent a first 2-unit RBC transfusion episode with pre-transfusion hemoglobin (Hb) ≥ 7.5 g/dL and paired pre- and post-transfusion SvO₂ measurements. The primary outcome was SvO₂ responsiveness, defined as ΔSvO₂ ≥ 5 percentage points from pre-transfusion baseline to approximately 60 minutes after transfusion initiation. Multivariable logistic regression was used to identify predictors of response, and receiver operating characteristic analysis was used to determine the optimal pre-transfusion SvO₂ cutoff. Subgroup analyses evaluated higher Hb thresholds, and sensitivity analyses included overlap-weighted transfusion-versus-no-transfusion trajectory comparisons and multivariable linear regression using continuous ΔSvO₂.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eAmong 18,117 eligible transfusion episodes, 1,352 unique patients met the final inclusion criteria. Mean Hb increased from 9.82 ± 0.92 to 10.24 ± 0.98 g/dL, whereas mean SvO₂ changed only minimally at the cohort level (73.79 ± 9.91% to 73.86 ± 9.37%). However, lower pre-transfusion SvO₂ was associated with larger increases in SvO₂ after transfusion. In multivariable logistic regression, baseline SvO₂ was the only independent predictor of SvO₂ response (adjusted OR, 0.89 per 1% increase; 95% CI, 0.86–0.91; P \u0026lt; 0.001). Pre-transfusion SvO₂ predicted a response with an AUC of 0.778 (95% CI, 0.74–0.816), and the optimal cutoff was 69%. The inverse association between baseline SvO₂ and ΔSvO₂ was preserved in the Hb ≥ 9 g/dL and Hb ≥ 10 g/dL subgroups. In overlap-weighted sensitivity analyses, 0–6-hour trajectories of SvO₂, Hb, and DO₂i differed significantly between transfusion and no-transfusion groups (all group-by-time interaction P \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eIn cardiovascular surgical ICU patients with Hb ≥ 7.5 g/dL, a low pre-transfusion SvO₂ identified patients more likely to show a physiologic rise in SvO₂ after RBC transfusion. Pre-transfusion SvO₂ may complement Hb when evaluating transfusion need in this population, but prospective validation is required before physiologic SvO₂-guided transfusion can be recommended.\u003c/p\u003e","manuscriptTitle":"SvO₂ Response to Red Blood Cell Transfusion in Cardiovascular Surgical ICU Patients: A Retrospective Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 00:43:46","doi":"10.21203/rs.3.rs-9352763/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-05T05:33:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T21:25:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22060121917605388458271702902065495555","date":"2026-05-04T21:24:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-27T10:52:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-25T06:13:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-22T15:43:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151991203195817784398340678702838651882","date":"2026-04-17T14:39:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329857077913560479550013247316739282218","date":"2026-04-16T06:25:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78903667793658610195623447582929198506","date":"2026-04-15T15:25:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35743352045247517387828705741830884928","date":"2026-04-15T13:36:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-15T12:59:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T12:59:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T12:58:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Critical Care","date":"2026-04-08T06:40:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cb225847-5bac-4a76-944b-c29e1933fcfb","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-05T05:33:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T21:25:30+00:00","index":23,"fulltext":""},{"type":"reviewerAgreed","content":"22060121917605388458271702902065495555","date":"2026-05-04T21:24:23+00:00","index":22,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-16T09:55:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 00:43:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9352763","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9352763","identity":"rs-9352763","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}