Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis

doi:10.1016/S2352-3026(15)00198-2

The Lancet Haematology

Volume 2, Issue 12, December 2015, Pages e543-e553

https://doi.org/10.1016/S2352-3026(15)00198-2 Get rights and content

Summary

Background

Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery.

Methods

We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality.

Findings

We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232 806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0·70 (95% CI 0·49–1·02; p=0·060) for cardiac surgical trials and 1·10 (95% CI 0·96–1·27; p=0·16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2·72, 95% CI 2·11–3·49; p<0·0001) and other morbidity, although with substantial heterogeneity and small study effects.

Interpretation

Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery.

Funding

None.

Introduction

The aim of perioperative red blood cell transfusion in cardiac surgery is to improve or preserve oxygen delivery in patients with blood loss and anaemia. The decision to transfuse is complicated by several factors; severe anaemia and excessive blood loss are common,1, 2 and patients with cardiovascular disease have different transfusion requirements to other patient groups.³ Transfusion decisions in cardiac surgery are most commonly based on the severity of perioperative anaemia: guidelines recommend (grade C recommendation) highly restrictive transfusion thresholds with haemoglobin concentrations of 60–70 g/L.4, 5 These thresholds are largely based on the results of randomised controlled trials6, 7, 8 of non-cardiac surgery patients that suggest equivalence for restrictive transfusion threshold. They are also informed by evidence from observational studies9, 10, 11 showing strong associations between the reversal of severe anaemia by red blood cell transfusion and adverse clinical outcomes, such as death, acute lung injury, acute kidney injury, stroke, myocardial infarction, sepsis, and surgical site infections.

Red blood cell transfusion has important morbidity. Haemolytic transfusion reactions and transfusion-associated lung injury account for many deaths per year¹² but a causal relationship has yet to be established between red blood cell transfusion and the adverse outcomes suggested by observational analyses. Severe anaemia, the main indication for transfusion, is an important predictor of adverse outcomes in patients undergoing cardiac surgery, who are probably already at the limits of their physiological reserve.2, 11 Clinical uncertainty as to the appropriate indications for transfusion is shown by wide variations in the number of transfusions done in cardiac surgery; ranging from 25% to 95% between hospitals according to cross-sectional studies.¹³

We systematically reviewed and critically assessed the evidence from randomised controlled trials and observational studies that are used to inform transfusion guidelines in cardiac surgery, to provide evidence to support clinical transfusion decisions and to inform the design of studies of appropriate transfusion indicators.

Section snippets

Study design and systematic review

A protocol was developed (appendix pp 21–28) that was restricted to randomised controlled trials and observational studies of transfusion in cardiac surgery, but because transfusion guidelines4, 5 are also based on randomised controlled trials of non-cardiac surgical patients, we subsequently decided to include these in this systematic review. Despite the limitations of comparing different study designs, we chose to compare randomised controlled trials and observational studies because they are

Results

We included six cardiac surgical randomised controlled trials (3352 patients),20, 21, 22, 23, 24, 25 19 non-cardiac surgical randomised controlled trials (8361 patients),3, 6, 7, 8, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 and 39 cardiac surgical observational studies (232 806 patients; figure 1).9, 10, 11, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76 All cardiac surgical

Discussion

Our meta-analysis has shown that estimated effects of red blood cell transfusion differed greatly between cardiac surgical randomised controlled trials, non-cardiac surgical randomised controlled trials, and observational studies. In randomised controlled trials of adult patients undergoing cardiac surgery, the odds ratio for mortality favoured a liberal red blood cell transfusion strategy rather than a restrictive transfusion strategy, but the difference between strategies was not

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The Adherence to an Intraoperative Blood Product Transfusion Algorithm Is Associated With Reduced Blood Product Transfusions in Cardiac Surgical Patients Undergoing Coronary Artery Bypass Grafts and Aortic and/or Valve Replacement Surgery: A Single-Center, Observational Study
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To demonstrate the value of a viscoelastic-based intraoperative transfusion algorithm to reduce non-RBC product administration in adult cardiac surgical patients.
A prospective observational study.
At a quaternary academic teaching hospital.
Cardiac surgical patients.
Viscoelastic-based intraoperative transfusion algorithm.
The study authors compared intraoperative blood product transfusion rates in 184 cardiac surgical patients to 236 historic controls after implementing a viscoelastic-based algorithm. The authors found a non-significant reduction in transfusion of 23.8% for fresh frozen plasma (FFP) units (0.84 ± 1.4 v 0.64 ± 1.38; p = ns), 33.4% for platelet units (0.90 ± 1.39 v 0.60 ± 131; p = ns), and 15.8% for cryoprecipitate units (0.19 ± 0.54 v 0.16 ± 0.50; p = ns). They found a 43.9% reduction in red blood cell (RBC) units transfused (1.98 ± 2.24 v 0.55 ± 1.36; p = 0.008). There were no statistically significant differences in time to extubation (8.0 hours (4.0-21.0) v 8.0 (4.0-22.3), reoperation for bleeding (15 [12.3%] v 10 [10.6%]), intensive care unit length of stay (ICU LOS) (51.0 hours [28.0-100.5] v 53.5 [33.3-99.0]) or hospital LOS (9.0 days [6.0-15.0] v 10.0 [7.0-17.0]). Deviation from algorithm adherence was 32.7% (48/147). Packed RBC, FFP, platelets, cryoprecipitate, and cell saver were significantly reduced in the Algorithm Compliant Cohort compared with historic controls, whereas times to extubation, ICU LOS, and hospital LOS did not reach significance.
After the implementation of a viscoelastic-based algorithm, patients received fewer packed RBC, FFP, platelets, cryoprecipitate, and cell saver. Algorithm-compliant patients received fewer transfusions; however, reductions in times to extubation, ICU LOS, and hospital LOS were not statistically significant compared with historic controls.
Red Blood Cell Transfusion and Pulmonary Complications: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis
2024, Annals of Thoracic Surgery
Intraoperative packed red blood cell (PRBC) transfusion during cardiac surgery is associated with increased postoperative morbidity and mortality; however, data on the association between PRBC transfusion and postoperative pulmonary complications (PPCs) are somewhat conflicting. Using The Society of Thoracic Surgeons Adult Cardiac Surgery Database, we sought to determine whether intraoperative PRBC transfusion was associated with PPCs as well as with longer intensive care unit (ICU) stay after isolated coronary artery bypass grafting (CABG) surgery.
A registry-based cohort study was performed on 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score–weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of PPCs (hospital-acquired pneumonia [HAP], mechanical ventilation for >24 hours, or reintubation), ICU length of stay, and ICU readmission.
Transfusion of 1, 2, 3, and ≥4 units of PRBCs was associated with increased odds for HAP (odds ratios [ORs], 1.24 [95% CI, 1.21-1.26], 1.28 [95% CI, 1.26-1.32], 1.36 [95% CI, 1.33-1.39], 1.31 [95% CI, 1.28-1.34]), reintubation (ORs, 1.23 [95% CI, 1.21-1.25], 1.38 [95% CI, 1.35-1.40], 1.57 [95% CI, 1.55-1.60], 1.70 [95% CI, 1.67-1.73]), prolonged ventilation (ORs, 1.34 [95% CI, 1.33-1.36], 1.56 [95% CI, 1.53-1.58], 1.97 [95% CI, 1.94-2.00], 2.27 [95% CI, 2.24-2.30]), initial ICU length of stay (mean difference in hours, 6.79 [95% CI, 6.00-7.58], 9.55 [95% CI, 8.71-10.38], 17.26 [95% CI, 16.38-18.15], 22.14 [95% CI, 21.22-23.06]), readmission to ICU (ORs, 1.14 [95% CI, 1.12-1.64], 1.15 [95% CI, 1.12-1.17], 1.15 [95% CI, 1.13-1.18], 1.32 [95% CI, 1.29-1.35]), and additional ICU length of stay (mean difference in hours, 0.55 [95% CI, 0.18-0.92], 0.38 [95% CI, 0.00-0.77], 1.02 [95% CI, 0.61-1.43], 1.83 [95% CI, 1.40-2.26]), respectively.
Intraoperative PRBC transfusion was associated with increased incidence of PPCs, prolonged ICU stay, and ICU readmissions after isolated CABG surgery.
Coagulation Tests and Bleeding Classification After Cardiopulmonary Bypass: A Prospective Study
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No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB.
A prospective observational study.
At a single-center academic hospital.
Patients ≥18 years of age undergoing elective cardiac surgery.
Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values.
A total of 816 patients were included in the study—358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021).
Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.
Timing of Blood Transfusions and 30-Day Patient Outcomes After Coronary Artery Bypass Graft Surgery
2023, Journal of Cardiothoracic and Vascular Anesthesia
Packed red blood cell transfusion during coronary artery bypass graft surgery is known to be associated with adverse outcomes. However, the association of the timing between transfusions in relation to discharge and 30-day postoperative outcomes has not been studied. The study authors investigated the impact of transfusion timing on 30-day surgical outcomes.
A retrospective review.
At a single tertiary-care academic hospital.
A total of 2,481 adult patients underwent primary coronary artery bypass graft surgery between January 2014 and December 2020.
The relationship between the timing of packed red blood cell transfusion (intraoperative, postoperative, or both) and 30-day postoperative outcome variables was calculated as an odds ratio. The influence of timing of transfusion on adjusted probability of postoperative complications was plotted against the lowest intraoperative hematocrit. The median age of the population was 67 years (60.0-74.0), body mass index was 28.5 (25.6-32.3) kg/m², and 497 (20.0%) were female. A total of 1,588 (36%) patients received packed red blood cell transfusions; 182 (7.3%) received intraoperative transfusions, 489 (19.7%) received postoperative transfusions, and 222 (9.0%) received both (intraoperative and postoperative transfusions). Postoperative transfusion was associated with significantly higher odds of readmission (1.83 [1.32-2.54], p = 0.002) and heart failure (1.64 [1.2-2.23], p = 0.008) compared to patients with no transfusions; whereas intraoperative transfusions were not.
The authors’ data suggested that the postoperative timing of transfusion in patients undergoing coronary artery bypass graft surgery may be associated with an increased incidence of 30-day heart failure and readmission. Prospective research is needed to conclusively confirm these findings.
Enhanced recovery after cardiac surgery under CPB or off-pump 2021
2022, Anesthesie et Reanimation
Éditer des recommandations pour un programme de Réhabilitation améliorée après chirurgie cardiaque (RAACC), reposant sur une approche multimodale de la médecine périopératoire des patients adultes opérés d’une chirurgie cardiaque, ayant pour objectifs d’améliorer la satisfaction du patient, de réduire la morbidité et la mortalité postopératoires et les durées de séjour.
Un groupe composé de 20 experts des Sociétés françaises d’anesthésie-réanimation (SFAR) et de la Société française de chirurgie thoracique et cardiovasculaire (SFCTCV) a été réuni. D’éventuels conflits d’intérêts ont été officiellement déclarés dès le début du processus d’élaboration des recommandations et ce dernier a été conduit indépendamment de tout financement de l’industrie. Les auteurs ont suivi la méthode GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer le niveau de preuve de la littérature.
Six champs ont été définis : 1) la sélection du parcours patient et son information ; 2) la gestion et la réhabilitation préopératoire ; 3) l’anesthésie et analgésie pour chirurgie cardiaque ; 4) la stratégie chirurgicale et la gestion de la circulation extracorporelle (CEC) ; 5) la gestion personnalisée du capital sanguin, et 6) la réhabilitation postopératoire. Pour chaque champ, l’objectif des recommandations était de répondre à un certain nombre de questions formulées selon le modèle PICO (Population, Intervention, Comparison, Outcome). À partir de ces questions, une recherche bibliographique extensive a été réalisée, et analysée selon la méthode GRADE. Les recommandations ont été formulées selon la méthode GRADE, puis votées par tous les experts selon la méthode GRADE grid.
Trente-trois recommandations sur la prise en charge des patients opérés d’une chirurgie cardiaque sous CEC ou à cœur battant ont été formulées par le panel d’experts SFAR/SFCTCV. Après trois tours de votes et plusieurs amendements, un accord fort a été obtenu pour 33 recommandations. Parmi ces recommandations, 10 ont un niveau de preuve élevé (7 GRADE 1+ et 3 GRADE 1-), 19 ont un niveau de preuve faible (15 GRADE 2+ et 4 GRADE 2-) et 4 sont des avis d’experts. Enfin, pour 3 questions, aucune recommandation n’a pu être formulée.
Un accord fort a été obtenu parmi les experts afin de fournir des recommandations visant à optimiser la prise en charge périopératoire des patients opérés d’une chirurgie cardiaque sous CEC ou à cœur battant.
To provide recommendations for Enhanced Recovery After Cardiac Surgery (ERACS) based on a multimodal approach of perioperative medicine of adult cardiac surgery patients with the aim of improving patient satisfaction, reducing postoperative mortality and morbidity and reducing length of hospital stays.
A consensus committee of 20 experts from the French society of anaesthesiology and critical care medicine (Société française d’anesthésie-réanimation, SFAR) and the French society of thoracic and cardio-vascular surgery (Société française de chirurgie thoracique et cardiovasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence.
Six fields were defined: 1) selection of the patient pathway and their information; 2) preoperative management and rehabilitation; 3) anaesthesia and analgesia for cardiac surgery; 4) surgical strategy for cardiac surgery and bypass management; 5) Patient Blood Management; and 6) postoperative enhanced recovery. For each field, the objective of the recommendations was to answer questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). Based on these questions, an extensive bibliographic search was carried out and analysed using the GRADE approach. The recommendations were formulated according to the GRADE methodology, and then voted by all the experts according to the GRADE grid method.
The SFAR/SFCTCV guideline panel provided 33 recommendations on the management of patients undergoing pulmonary lobectomy. After three rounds of voting and several amendments, a strong agreement was reached for 33 recommendations. Of these recommendations, 10 have a high level of evidence (7 GRADE 1+ and 3 GRADE 1-); 19 have a moderate level of evidence (15 GRADE 2+ and 4 GRADE 2-); and 4 are expert judgments. Finally, no recommendation was provided for 3 questions.
Strong agreement exists among the experts to provide recommendations to optimize the whole perioperative management of patients undergoing cardiac surgery.
Perioperative blood transfusion in major abdominal cancer surgery: a multi-centre service evaluation and national survey
2022, BJA Open
Anaemia is associated with complications and death after surgery. Perioperative red-cell transfusion triggers are not well defined in patients having oncological surgery, or with cardiovascular disease.
We carried out a prospective multicentre cohort study and a clinician survey of UK transfusion practice in adult patients undergoing surgery for abdominal malignancy. The primary outcome was red cell transfusion. Secondary outcomes were transfusion trigger haemoglobin, incidence of complications, length of hospital stay, and acute hospital mortality.
In this prospective cohort study, data were collected on 412 patients undergoing surgery for intrabdominal malignancy in 14 NHS hospitals. Twenty-two (5.2%) patients received preoperative, 42 (10.2%) intraoperative, and 52 (12.2%) postoperative red blood cell transfusion. The mean postoperative transfusion trigger was 75.3 g L⁻¹, and the mean number of units of red blood cells transfused was 1.5 (standard deviation, 1.1). Seventeen (4.0%) patients had a documented postoperative troponin elevation. Five (1.2%) patients died within 30 days of surgery. In the survey, 117 clinicians submitted complete responses, of whom 62 (53%) indicated that a transfusion threshold of 70 g L⁻¹ was appropriate: however, this decreased to six (5.1%) if there was evidence of recent cardiac ischaemia. There were 100 (86%) respondents who indicated equipoise for a trial of restrictive vs liberal transfusion, decreasing to 56% if there was coexisting cardiovascular disease.
Many patients having oncological surgery receive red cell transfusion, the majority being given postoperatively. Restrictive transfusion practice is generally followed; however, variability exists especially in cardiovascular disease. Equipoise exists for a study of transfusion thresholds in this group.

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ArticlesIndications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and systematic review

Results

Discussion

Ann Thorac Surg

Ann Thorac Surg

Am J Cardiol

Am J Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Blood

Ann Thorac Surg

Ann Thorac Surg

Am Heart J

Am J Cardiol

J Cardiothorac Vasc Anesth

Semin Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Chest

Ann Thorac Surg

Am Heart J

Advance targeted transfusion in anemic cardiac surgical patients for kidney protection: an unblinded randomized pilot clinical trial

Anesthesiology

Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study

Circulation

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?

Crit Care Med

Clinical practice guideline: red blood cell transfusion in adult trauma and critical care

Crit Care Med

Transfusion strategies for patients in pediatric intensive care units

N Engl J Med

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group

N Engl J Med

Liberal or restrictive transfusion in high-risk patients after hip surgery

N Engl J Med

Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery

Circulation

Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on operative outcome

Crit Care Med

The annual SHOT report

Variation in use of blood transfusion in coronary artery bypass graft surgery

JAMA

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

BMJ

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

BMJ

Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group

JAMA

Quantifying heterogeneity in a meta-analysis

Stat Med

Methods for trend estimation from summarized dose-response data, with applications to meta-analysis

Am J Epidemiol

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data

BMC Med Res Methodol

A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery

Transfusion

Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial

JAMA

Rationalizing blood transfusion in cardiac surgery: preliminary findings with a red cell volume-based model

Vox Sang

Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome

Transfusion

A pilot randomized controlled trial of the effect of transfusion-threshold reduction on transfusion rates and morbidity after cardiac surgery

Transfus Altern Transfus Med

Liberal or restrictive transfusion after cardiac surgery

N Engl J Med

Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease

Am Heart J

Articles
Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis