ABSTRACT
Background
Postoperative bleeding is a major concern in cardiac surgery, often leading to significant transfusion requirements. Despite this high transfusion demand, the use of postoperative autologous blood transfusion (PABT) remains underexplored.
Methods and Results
This large-scale, single-blind randomized controlled trial with a 30-day follow-up enrolls patients undergoing elective on- or off-pump coronary artery bypass grafting. Patients with shed mediastinal blood volumes over 500 mL within the first 6 hours postoperatively are randomly assigned 1:1 to either the PABT group or the standard care group. The PABT group receives postoperative autotransfusion and additional allogeneic RBC transfusions if needed, while the standard care group receives allogeneic RBC transfusions only when clinically necessary, without postoperative autotransfusion. The primary efficacy endpoint is the postoperative allogeneic RBC transfusion volume, defined as the cumulative amount transfused from the day of surgery to discharge. Secondary efficacy endpoints include postoperative allogeneic RBC and non-RBC transfusion rates, perioperative hematologic recovery, drainage volume, mechanical ventilation duration, ICU and hospital length of stay. The primary safety endpoint is the incidence of a composite of postoperative infections (pneumonia, bloodstream infections, and surgical site infections). Secondary safety endpoints include a composite of other postoperative complications (renal dysfunction, myocardial infarction, stroke, deep vein thrombosis, and all-cause mortality), individual components of these composites, and 30-day mortality and morbidity. The estimated sample size is 1,232 participants. Patient recruitment is planned from January 2026 to December 2029 and is currently in the preparatory phase. The study is registered at the Chinese Clinical Trial Registry (ChiCTR2500103269, https://www.chictr.org.cn/ ) and was registered on May 27, 2025.
Conclusions
The study is designed to identify the efficacy and safety of PABT after cardiac surgery. We hypothesize that PABT has superior efficacy and noninferior safety to the standard care.
Background
Cardiac surgery accounts for 10% to 15% of national blood use in both the United States and the United Kingdom, representing the highest consumption among all surgical specialties. ,, According to the Universal Definition of Perioperative Bleeding (UDPB), approximately 49.6% of patients undergoing cardiac surgery require blood transfusions due to postoperative bleeding. Despite the substantial volume of postoperative bleeding, the absence of standardized postoperative cell salvage process leads to significant wastage of autologous blood, higher allogeneic transfusion rates, increased financial burden for patients, and mounting strain on national blood supplies.
Efforts to recover and reinfuse postoperative shed mediastinal blood in cardiac surgery date back to the 1970s. Early reinfusion techniques involved unwashed blood collected from surgical drains, filtered and reinfused directly. However, subsequent evidence revealed that unwashed shed blood carries a significant risk of complications, including microemboli, hemolysis, coagulopathy and infection. Consequently, major guidelines have classified unwashed shed blood reinfusion as a Class III intervention, not recommended for routine use.
In contrast, washed cell salvage systems, commonly used intraoperatively, have gained recognition for producing high-purity, functionally viable red blood cells by removing plasma proteins, cell debris, and inflammatory mediators. However, the use of washed cell salvage in the postoperative setting of cardiac surgery has received limited attention. Among the available studies, a large 2011 retrospective analysis of 623 patients by Folkersen et al. demonstrated that postoperative autotransfusion significantly reduced allogeneic blood transfusion rates (36.5% vs 54.9%), without increasing complications or mortality. Similarly, other studies have reported consistent findings, indicating that postoperative autologous blood transfusion (PABT) may effectively reduce allogeneic transfusion requirements. Prior studies were limited by small single-center designs, absence of adequately powered multicenter trials, lack of comprehensive systematic reviews or meta-analyses, and insufficient statistical power to provide convincing safety assessments. In addition, postoperative blood salvage in cardiac surgery is typically initiated in the intensive care unit (ICU), where shed blood is collected over an extended period at ambient temperature. Consequently, concerns about potential bacterial contamination due to prolonged drainage collection remain a key barrier to broader clinical adoption. However, such concerns have only been partially explored in the literature, and high-quality data evaluating associated risks remain limited. This paucity of evidence may, in part, explain why international patient blood management (PBM) guidelines have yet to assign a recommendation grade or establish implementation protocols, limiting standardized practice.
To address these limitations, we initiated the RESCUE trial ( RE infusion of S alvaged mediastinal blood after C ardiac s U rg E ry), a prospective, multicenter, randomized controlled trial (RCT) with a 30-day follow-up to evaluate efficacy and safety of postoperative autologous blood transfusion. This large-scale, single-blind RCT was designed by investigators from Fuwai Shenzhen Hospital, a branch of the National Center for Cardiovascular Diseases and the National Clinical Research Center of Cardiovascular Diseases in China. Patient enrollment began in January 2026 across 3 high-volume cardiac centers. The primary objective of the RESCUE trial is to evaluate the clinical efficacy and safety of PABT in patients undergoing coronary artery bypass grafting (CABG). We hypothesize that, compared with standard postoperative clinical care, PABT will reduce the volume of postoperative allogeneic red blood cell transfusion (efficacy) and will be noninferior in safety, as measured by the postoperative incidence of a composite of postoperative pneumonia, bloodstream infection, and surgical site infection in Chinese patients undergoing CABG.
Methods
The Independent Ethics Committee of Fuwai Shenzhen Hospital Chinese Academy of Medical Sciences approved the study design of this protocol (Ethics number: SP2025045(01)). All participating sites accepted the central ethics approval. All participants will provide written informed consent. The study is registered at https://www.chictr.org.cn/ (ChiCTR2500103269).
Study objective
The objective of this study is to evaluate the clinical efficacy, safety, and cost-effectiveness of PABT in patients undergoing CABG surgery. The primary efficacy endpoint is the total volume of postoperative allogeneic RBC transfusion, and the primary safety endpoint is the incidence of a composite of postoperative pneumonia, bloodstream infection, and surgical site infection. Secondary efficacy endpoints include the rate of postoperative allogeneic RBC and non-RBC transfusion, postoperative hemoglobin (Hb) levels, drainage volume, mechanical ventilation duration, ICU stay, and total hospital length of stay. Secondary safety endpoints include the incidence of a composite of postoperative complications (renal dysfunction, myocardial infarction, ischemic stroke, deep vein thrombosis, respiratory insufficiency, and all-cause mortality) and individual incidence of each complication, and the 30-day follow-up mortality and morbility. An exploratory objective is to compare transfusion-related medical costs between the PABT group and the standard care group. We hypothesize that PABT is superior in reducing allogeneic RBC use and noninferior in safety to the standard care.
Study design
This is a multicenter, prospective, single-blinded RCT, with a 30-day follow-up to evaluate the efficacy and safety of PABT. Form January 2026 to December 2029, patients undergoing CABG (both on-pump and off-pump) and meeting the eligibility criteria will be enrolled in this study. This trial will be conducted at 3 academic centers in China. A total of 1,232 participants will be randomized in a 1:1 ratio to receive 2 postoperative blood management strategies: postoperative autotransfusion or standard care without postoperative autotransfusion. Data collection will start from the accumulation of basic data to the end of follow-up. All participants will provide written informed consent ( Figure 1 ).
Study Flowchart of the RESCUE trial. CABG, coronary artery bypass graft; Hb, hemoglobin; RBC, red blood cell; ICU, intensive care unit.
Study population
Inclusion criteria
Aged ≥18 years.
Undergoing isolated CABG (on-pump or off- pump)
Shed mediastinal blood exceeding 500 mL within 6 hours postoperatively.
Exclusion criteria
Undergoing CABG combined with other procedures.
Clinically diagnosed preoperative pleural effusion.
Clinically diagnosed preoperative malignant tumor.
Sepsis, bacteriaemia, or hematological disease during the perioperative period.
Shed mediastinal blood samples contaminated.
Patient considered unsuitable for enrolment in the present trial due to the surgeon’s clinical judgment, severe comorbidities, or refusal to participate in the study.
All patients must be willing to give informed consent to participate in the study and may withdraw from the study at any time at their own request.
Intervention
Patients in the intervention group underwent postoperative autologous blood transfusion (PABT group) if they met the inclusion criterion of mediastinal drainage volume ≥500 mL within the first 6 postoperative hours. Shed mediastinal blood was collected in the reservoir via mediastinal drainage and processed using a standard cell salvage device, with the salvaged blood reinfused immediately into the patient. As shown in Figure 2 , all shed blood was subject to a strict 6-hour storage limit from the time it entered the collection reservoir; if blood exceeded this 6-hour storage window without being processed, it was discarded and not reinfused. For patients requiring multiple rounds of cell salvage, a new 6-hour storage clock was initiated upon completion of the previous salvage cycle. Additional rounds of cell salvage were performed if the drainage volume again exceeded 500 mL within 6 hours of the previous washing cycle. This process could be repeated until one of the following termination criteria was met: continuous drainage volume < 500 mL for 6 hours or reaching a maximum of 12 hours postoperatively. Following each reinfusion, the attending physician determined the need for additional allogeneic RBC transfusion based on standard clinical transfusion criteria.
Workflow of the postoperative autologous blood salvage.
Patients in the control group (standard care group) had their shed mediastinal blood discarded without processing, in line with routine clinical practice. Allogeneic RBC transfusion, including the decision to transfuse and transfusion volume, was determined by the attending physician using the same clinical criteria as the intervention group.
Autologous blood transfusion was performed once the drainage criterion was met, regardless of the postoperative Hb level, as the intervention aimed to evaluate the safety and efficacy of PABT itself rather than to replace standard transfusion triggers. Postoperative allogeneic RBC transfusion was guided by predefined uniform criteria: Hb <80 g/L or mixed venous oxygen saturation (SvO₂) <65%.
Randomization, allocation concealment, and blinding
Stratified block randomization will be used, with study center and preoperative anemia status as stratification factors. Preoperative anemia will be stratified as Hb <100 g/L vs Hb ≥100 g/L based on the most recent preoperative laboratory assessment. Within each stratum, patients will be randomly assigned in a 1:1 ratio to the intervention or control group randomly permuted block sizes (varying among 4, 6, and 8 patients). The randomization sequence will be generated by a web-based interactive web response system (IWRS), which ensures dynamic allocation concealment and real-time assignment.
Due to the nature of the intervention, a single-blind design (patient-blinded) will be implemented: patients will be blinded to group assignment, while the attending physician administering the intervention will remain unblinded, as knowledge of group allocation is necessary to determine postoperative transfusion strategies based on laboratory results and hemodynamic status. Laboratory personnel and data analysts will remain blinded throughout the study.
To ensure rigorous blinding during data collection and analysis, a tiered data management strategy will be employed. Case report forms (CRFs) will be separated into primary and supplemental forms. The primary CRF, completed by blinded staff, will document objective clinical parameters such as Hb levels and allogeneic transfusion volume, without revealing group allocation. The supplemental CRF, completed by unblinded personnel, will record intervention-specific parameters such as the volume of salvaged blood. Both datasets will be stored separately. During analysis, group labels will be masked using neutral codes (Group A/B), and analysts will only access deidentified, coded datasets to ensure full blinding during statistical evaluation.
Study endpoints
Primary efficacy endpoint
The primary efficacy endpoint is the allogeneic RBC transfusion volume administered postoperatively, defined as the cumulative amount of allogeneic RBC transfused from operation day to discharge. For patients who do not receive any postoperative RBC transfusion, a value of “0″ will be recorded.
Secondary efficacy endpoints
The secondary efficacy endpoints include postoperative allogeneic RBC and non-RBC transfusion rate, perioperative hematologic recovery parameters, drainage volume, duration of mechanical ventilation, length of ICU stay, and length of hospital stay.
The definitions of secondary efficacy endpoints are as below:
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1.
Postoperative allogeneic RBC transfusion rate: Defined as the number (%) of patients who will receive at least one RBC unit from operation day to discharge.
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2.
Non-RBC blood transfusion rate: Defined as the proportion of patients who receive transfusion of fresh frozen plasma, platelets, and cryoprecipitate from the day of postoperation to discharge.
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3.
Perioperative hematologic recovery parameters: The levels of Hb, hematocrit (Hct), white blood cell (WBC) counts, inflammatory markers on the 1st, 3rd, 5th postoperative day and the discharge day.
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4.
Drainage volume: Record the hourly and total drainage volumes within 24 hours postoperation for the 2 groups.
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5.
Duration of mechanical ventilation: Defined as the time interval between the end of the operation and extubation.
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6.
Length of ICU stay: Defined as the time interval between the end of the operation and discharge from the ICU.
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7.
Length of hospital stay: Defined as the number of days between the operation and discharge from the hospital.
Primary safety endpoint
The primary safety endpoint is defined as the incidence of a composite of postoperative infection events (%) from surgery until discharge, including pneumonia, bloodstream infections, and surgical site infections (SSIs).
The definitions of primary safety endpoint are as below:
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1.
Pneumonia: Defined according to the CDC/NHSN criteria for clinically defined pneumonia ( Table 1 ). In the standardized follow-up questionnaire, clinical symptoms and signs suggestive of pneumonia include cough, purulent sputum, fever (≥38.0°C), dyspnea, and pleuritic chest pain. Patients presenting with these symptoms undergo physical examination and imaging evaluation (eg, chest X-ray or CT scan).
Table 1
Algorithms for clinically defined pneumonia
Radiology Signs/Symptoms Two or more serial chest radiographs with at least 1 of the following: -
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New or progressive and persistent infiltrate
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Consolidation
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Cavitation
For any patient,at least 1 of the following: -
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Fever (>38 °C) with no other recognized cause
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Leukopenia (<4 × 10⁹/L) or leukocytosis (>12×10⁹/L) and at least 2 of the following:
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New onset of purulent sputum or change in character of sputum or increased respiratory secretions or increased suctioning requirements
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New onset or worsening cough, or dyspnea, or tachypnea
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Rales or bronchial breath sounds
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Worsening gas exchange (eg, O 2 desaturations [eg, PaO 2 /FiO 2 ≤ 240], increased oxygen requirements, or increased ventilator demand)
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