Blood Transfusions in Elective Cardiac Surgery: The Debate Continues

Abstract

In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Sanaiha et al presented a manuscript entitled “Morbidity and Mortality Associated with Blood Transfusions in Elective Adult Cardiac Surgery.” The authors looked at the association between transfusions of stored packed red blood cells (pRBC) or coagulation products (CP), and the increased risk of 30 day mortality, prolonged mechanical ventilation, acute kidney injury and stroke in patients undergoing elective cardiac surgery. Case types included isolated coronary artery bypass grafting (CABG), isolated valve, CABG and single valve, and multivalve surgeries. They hypothesized that transfusion of pRBC or CP would be associated with an increased mortality and morbidity. As outlined by the authors, they identified 2 main objectives: to present an independent association between preoperative transfusion and outcomes of interest and to develop Machine Learning (ML) models that could both be used to predict 30 day mortality and rank variables related to transfusion risk. The authors did find a dose dependent association between the amount of pRBC and CP transfusion and their outcomes of interest. Using their developed ML models they were able to rank transfusion related variables of anemia, transfusions and mortality. The authors argue that even though anemia is a well-accepted and significant contributor to morbidity and mortality, outcomes are greatly affected by the addition of transfusions despite the starting hemoglobin levels. The investigators were able to recruit 7,762 patients to their study, with more than half receiving transfusions. Analysis of the authors’ results demonstrate that certain populations, comorbidities, and surgical aspects were associated with increased transfusion rates including old age, female gender and low BMI. These findings are in accordance with previous studies [1Nolan H.R. Ramaiah C. Effect of body mass index on postoperative transfusions and 24-hour chest-tube output.Int J Angiol. 2011; 20: 81-86Crossref PubMed Scopus (5) Google Scholar, 2Stammers A.H. et al.Gender and intraoperative blood transfusion: analysis of 54,122 non-reoperative coronary revascularization procedures.Perfusion. 2019; 34: 236-245Crossref PubMed Scopus (1) Google Scholar, 3Ad N. et al.Effect of patient age on blood product transfusion after cardiac surgery.J Thorac Cardiovasc Surg. 2015; 150: 209-214Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 4Arora R.C. et al.Identifying patients at risk of intraoperative and postoperative transfusion in isolated CABG: toward selective conservation strategies.Ann Thorac Surg. 2004; 78: 1547-1554Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. The authors state patients with peripheral vascular disease, dialysis dependence and liver dysfunction also demonstrated increased prevalence of transfusions. The increased mortality associated with transfusion in these patients is confounded by the fact that these patient populations have been clearly demonstrated to have higher risk of perioperative mortality and poor long-term survival following cardiac surgery [5Kogan A. et al.Cardiac surgery in patients on chronic hemodialysis: short and long-term survival.Thorac Cardiovasc Surg. 2008; 56: 123-127Crossref PubMed Scopus (28) Google Scholar, 6Rahmanian P.B. et al.Early and late outcome of cardiac surgery in dialysis-dependent patients: single-center experience with 245 consecutive patients.J Thorac Cardiovasc Surg. 2008; 135: 915-922Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 7Zimmet A.D. et al.The outcome of cardiac surgery in dialysis-dependent patients.Heart Lung Circ. 2005; 14: 187-190Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 8Hayashida N. et al.Clinical outcome after cardiac operations in patients with cirrhosis.Ann Thorac Surg. 2004; 77: 500-505Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 9Jacob K.A. et al.Mortality after cardiac surgery in patients with liver cirrhosis classified by the Child-Pugh score.Interact Cardiovasc Thorac Surg. 2015; 20: 520-530Crossref PubMed Scopus (37) Google Scholar, 10Macaron C. et al.Safety of cardiac surgery for patients with cirrhosis and Child-Pugh scores less than 8.Clin Gastroenterol Hepatol. 2012; 10: 535-539Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. Increased rates of transfusions were also reported in patients who had longer cross clamp times and underwent more complex surgeries such as CABG and single valves or multivalve. Again, this is not a new finding.[11Iino K. et al.Prolonged Cross-Clamping During Aortic Valve Replacement Is an Independent Predictor of Postoperative Morbidity and Mortality: Analysis of the Japan Cardiovascular Surgery Database.Ann Thorac Surg. 2017; 103: 602-609Abstract Full Text Full Text PDF PubMed Google Scholar, 12Al-Sarraf N. et al.Cross-clamp time is an independent predictor of mortality and morbidity in low- and high-risk cardiac patients.Int J Surg. 2011; 9: 104-109Crossref PubMed Scopus (167) Google Scholar, 13Cheng Y.Y. et al.Outcomes Following Triple Cardiac Valve Surgery Over 17-years: A Multicentre Population-Linkage Study.Heart Lung Circ. 2022; Google Scholar, 14Nissinen J. et al.Safe time limits of aortic cross-clamping and cardiopulmonary bypass in adult cardiac surgery.Perfusion. 2009; 24: 297-305Crossref PubMed Scopus (109) Google Scholar, 15Shahian D.M. et al.The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 3–valve plus coronary artery bypass grafting surgery.Ann Thorac Surg. 2009; 88 (Suppl): S43-S62Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar] While the authors readily acknowledge that preoperative anemia is a known independent risk factor for mortality and morbidity following cardiac surgery; they did aim to examine the impact of transfusions in the setting of preoperative anemia[16-19]. Perhaps the most interesting finding in this regard is that transfusions in subjects with low preoperative HCT attenuated mortality. This relationship between preoperative anemia and transfusions warrants further investigations as other studies have presented conflicting relationships. Padmanabhan et al aimed to investigate the association between preoperative anemia and red blood cell (RBC) transfusion following cardiac surgery. Over a 64 month period they found no interaction between preoperative anemia and RBC transfusion[20]. Engoren et al, also aimed to evaluate the relationship between anemia and transfusion on mortality on patient undergoing CABG. Their study reaffirmed that perioperative anemia was associated with increased mortality. They, however, found that RBC transfusions administered in anemia patients increased their mortality, refuting findings in the Padmanabhan paper. [21Engoren M. et al.The independent effects of anemia and transfusion on mortality after coronary artery bypass.Ann Thorac Surg. 2014; 97: 514-520Abstract Full Text Full Text PDF PubMed Google Scholar]. The authors set out to build upon the associated increase in morbidity and mortality and complications associated with perioperative transfusions. They found a dose dependent relationship between the transfusion of RBC and CP and 30 day mortality, renal failure and prolonged mechanical ventilation. Using their ML model they demonstrated that 30 day mortality was, to a large degree, driven by the administration of blood products. The findings and study design were very similar to a study conducted by Ad et al. Ad et al also demonstrated a dose dependent relationship between increased mortality and administration of each additional blood product albeit RBC or non-RBCs. They found a 9% greater odds for 30 day mortality for each additional unit of total blood products transfused, 7% greater odds for stroke, renal failure and major infection and 4% greater odds for extended hospital, new onset atrial fibrillation and readmission within 30 days[22]. These findings illustrate an increased mortality with each additional administered unit, and further support a continuous restrictive transfusion strategy as recommended by the Society of Thoracic Surgeons[23]. The authors used a ML model to aid in predicting 30-day mortality and rank transfusion related outcomes. The use of risk stratification models is not new to cardiac surgery. Models such as the European Cardiac Operative Risk Evaluation (EuroSCORE), EUROSCORE II and The Society of Thoracic Surgeons short term risk calculator (STS risk calculator) have all aided clinicians in their decision making[24-27]. While risk models to predict mortality and complications are in practice, an enormous opportunity exists for ML and continuous prediction models that aid in decision making as the clinical picture evolves. ML models to address this gap are being developed and utilized with more and more frequency in medicine. The authors should be commended, as manuscripts like this pave the way for these developments. The study presented by Sanaiha et al demonstrates that transfusions of products whether pRBC or CP increase a patient's 30 day mortality, prolonged mechanical ventilation, acute kidney injury and stroke in patients undergoing elective cardiac surgery. This study adds to the growing evidence supporting a restrictive transfusion approach. Their development and use of a ML model to predict 30 day mortality addresses gaps in current prediction models and how ML can enhance medical management. [16Bolliger D. Mauermann E. Buser A. Preoperative anaemia in cardiac surgery: preoperative assessment, treatment and outcome.Br J Anaesth. 2022; 128: 599-602Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,17Hazen Y. et al.Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis.Br J Anaesth. 2022; 128: 636-643Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,18Miceli A. et al.Preoperative anemia increases mortality and postoperative morbidity after cardiac surgery.J Cardiothorac Surg. 2014; 9: 137Crossref PubMed Google Scholar,19Padmanabhan H. et al.Preoperative Anemia and Outcomes in Cardiovascular Surgery: Systematic Review and Meta-Analysis.Ann Thorac Surg. 2019; 108: 1840-1848Abstract Full Text Full Text PDF PubMed Google Scholar,20Padmanabhan H. et al.Association Between Anemia and Blood Transfusion With Long-term Mortality After Cardiac Surgery.Ann Thorac Surg. 2019; 108: 687-692Abstract Full Text Full Text PDF PubMed Google Scholar,22Ad N. et al.Number and Type of Blood Products Are Negatively Associated With Outcomes After Cardiac Surgery.Ann Thorac Surg. 2022; 113: 748-756Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,23Tibi P. et al.STS/SCA/AmSECT/SABM Update to the Clinical Practice Guidelines on Patient Blood Management.J Cardiothorac Vasc Anesth. 2021; 35: 2569-2591Abstract Full Text Full Text PDF PubMed Google Scholar,24Nashef S.A. et al.European system for cardiac operative risk evaluation (EuroSCORE).Eur J Cardiothorac Surg. 1999; 16: 9-13Crossref PubMed Scopus (2747) Google Scholar,25Nashef S.A. et al.EuroSCORE II.Eur J Cardiothorac Surg. 2012; 41 (discussion 744-5): 734-744Crossref PubMed Scopus (1858) Google Scholar,26O'Brien S.M. et al.The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2–isolated valve surgery.Ann Thorac Surg. 2009; 88 (Suppl): S23-S42Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,27Shahian D.M. et al.The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 1–coronary artery bypass grafting surgery.Ann Thorac Surg. 2009; 88 (Suppl): S2-22Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar] The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Morbidity and Mortality Associated With Blood Transfusions in Elective Adult Cardiac SurgeryJournal of Cardiothoracic and Vascular AnesthesiaPreviewPerioperative transfusion thresholds have garnered increasing scrutiny as restrictive strategies have been shown to be noninferior. The study authors used data from a statewide academic collaborative to test the association between transfusion and 30-day mortality. Full-Text PDF Open Access