Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial

Published:December 19, 2017DOI:


      To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity.


      Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design ( number, NCT02042898).


      Eligible patients were randomized prior to surgery in a 1:1 ratio.


      Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more.


      Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward.

      Measurements and Main Results

      The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy.


      By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

      Key Words

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      1. STS Adult Cardiac Surgery Database. Available at: Accessed September 2017.

        • Hung M.
        • Ortmann E.
        • Besser M.
        • et al.
        A prospective observational cohort study to identify the causes of anaemia and association with outcome in cardiac surgical patients.
        Heart. 2015; 101: 107-112
        • Karkouti K.
        • Wijeysundera D.N.
        • Beattie W.S.
        Risk associated with preoperative anemia in cardiac surgery: A multicenter cohort study.
        Circulation. 2008; 117: 478-484
        • Miceli A.
        • Romeo F.
        • Glauber M.
        • et al.
        Preoperative anemia increases mortality and postoperative morbidity after cardiac surgery.
        J Cardiothorac Surg. 2014; 9: 137
        • Delaney M.
        • Wendel S.
        • Bercovitz R.S.
        • et al.
        Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Transfusion reactions: Prevention, diagnosis, and treatment.
        Lancet. 2016; 388: 2825-2836
        • Shehata N.
        • Burns L.A.
        • Nathan H.
        • et al.
        A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery.
        Transfusion. 2012; 52: 91-99
      2. Transfusion Requirements in Cardiac Surgery II. Available at:

        • Nashef S.A.
        • Roques F.
        • Hammill B.G.
        • et al.
        Validation of European System for Cardiac Operative Risk Evaluation (EuroSCORE) in North American cardiac surgery.
        Eur J Cardiothorac Surg. 2002; 22: 101-105
        • Geissler H.J.
        • Holzl P.
        • Marohl S.
        • et al.
        Risk stratification in heart surgery: Comparison of six score systems.
        Eur J Cardiothorac Surg. 2000; 17: 400-406
        • Surgenor S.D.
        • Kramer R.S.
        • Olmstead E.M.
        • et al.
        • Northern New England Cardiovascular Disease Study Group
        The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery.
        Anesth Analg. 2009; 108: 1741-1746
        • Covin R.
        • O'Brien M.
        • Grunwald G.
        • et al.
        Factors affecting transfusion of fresh frozen plasma, platelets, and red blood cells during elective coronary artery bypass graft surgery.
        Arch Pathol Lab Med. 2003; 127: 415-423
        • Shehata N.
        • Wilson K.
        • Mazer C.D.
        • et al.
        Factors affecting perioperative transfusion decisions in patients with coronary artery disease undergoing coronary artery bypass surgery.
        Anesthesiology. 2006; 105: 19-27
        • Arora R.C.
        • Legare J.-F.
        • Buth K.J.
        • et al.
        Identifying patients at risk of intraoperative and postoperative transfusion in isolated CABG: Toward selective conservation strategies.
        Ann Thor Surg. 2004; 78: 1547-1555
        • Shehata N.
        • Naglie G.
        • Alghamdi A.A.
        • et al.
        Risk factors for red cell transfusion in adults undergoing coronary artery bypass surgery: A systematic review.
        Vox Sang. 2007; 93: 1-11
        • Deans K.J.
        • Minneci P.C.
        • Suffredini A.F.
        • et al.
        Randomization in clinical trials of titrated therapies: Unintended consequences of using fixed treatment protocols.
        Crit Care Med. 2007; 35: 1509-1516
        • Schulz K.F.
        • Altman D.G.
        • Moher D.
        • et al.
        CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials.
        Ann Intern Med. 2010; 152: 726-732
        • Ferraris V.A.
        • Ferraris S.P.
        • et al.
        • Society of Thoracic Surgeons Blood Conservation Guideline Task Force
        Perioperative blood transfusion and blood conservation in cardiac surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.
        Ann Thorac Surg. 2007; 83: S27-S86
        • Weiskopf R.B.
        • Viele M.K.
        • Feiner J.
        • et al.
        Human cardiovascular and metabolic response to acute severe isovolemic anemia.
        JAMA. 1998; 279: 217-221
        • Hébert P.C.
        • Yetisir E.
        • Martin C.
        • et al.
        Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?.
        Crit Care Med. 2001; 29: 227-234
        • Thygesen K.
        • Alpert J.S.
        • Jaffe A.S.
        • et al.
        Third universal definition of myocardial infarction.
        Circulation. 2012; 126: 2020-2035
      3. KDIGO Clinical Practice Guideline for Acute Kidney Injury.
        Kidney Int Suppl. 2012; 2: 1-138
      4. Confusion Assessment Method for the ICU (CAM-ICU) Available at: Accessed August 2017.

      5. Intensive Care Delirium Screening Checklist (ICDSC). Available at: Accessed August 2017.

        • Tuman K.J.
        • McCarthy R.J.
        • March R.J.
        • et al.
        Morbidity and duration of ICU stay after cardiac surgery. A model for preoperative risk assessment.
        Chest. 1992; 102: 36-44
        • Higgins T.L.
        • Estafanous F.G.
        • Loop F.D.
        • et al.
        Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. A clinical severity score.
        JAMA. 1992; 267: 2344-2348
        • Curley G.F.
        • Shehata N.
        • Mazer C.D.
        • et al.
        Transfusion triggers for guiding RBC transfusion for cardiovascular surgery: A systematic review and meta-analysis.
        Crit Care Med. 2014; 42: 2611-2624
        • Whitlock R.P.
        • Whitlock R.P.
        • Devereaux P.J.
        • et al.
        Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): A randomised, double-blind, placebo-controlled trial.
        Lancet. 2015; 386: 1243-1253
        • Scott B.H.
        • Seifert F.C.
        • Grimson R.
        Blood transfusion is associated with increased resource utilisation, morbidity and mortality in cardiac surgery.
        Annals Cardiac Anesth. 2008; 11: 15-19
        • Surgenor S.D.
        • Kramer R.S.
        • Olmstead E.M.
        • et al.
        The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery.
        Anesth Analg. 2009; 108: 1741-1746
        • Bracey A.W.
        • Radovancevic R.
        • Riggs S.A.
        • et al.
        Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: Effect on patient outcome.
        Transfusion. 1999; 39: 1070-1077
        • Blumberg N.
        • Heal J.M.
        • Gettings K.F.
        • et al.
        An association between decreased cardiopulmonary complications (transfusion-related acute lung injury and transfusion-associated circulatory overload) and implementation of universal leukoreduction of blood transfusions.
        Transfusion. 2010; 50: 2738-2744
        • Gøtzsche P.C.
        Lessons from and cautions about noninferiority and equivalence randomized trials.
        JAMA. 2006; 295: 1172-1174
        • Hébert P.C.
        • Wells G.
        • Blajchman M.A.
        • et al.
        A multicenter, randomized controlled clinical trial of transfusion requirements in critical care.
        N Engl J Med. 1999; 340: 409-417
        • Carson J.L.
        • Terrin M.L.
        • Noveck H.
        • et al.
        Liberal or restrictive transfusion in high-risk patients after hip surgery.
        N Engl J Med. 2011; 365: 2453-2462
        • Brunskill S.J.
        • Millette S.L.
        • Shokoohi A.
        • et al.
        Red blood cell transfusion for people undergoing hip fracture surgery.
        Cochrane Database of Systematic Reviews. 2015; (CD009699): 4
        • Murphy G.J.
        • Pike K.
        • Rogers C.A.
        • et al.
        Liberal or restrictive transfusion after cardiac surgery.
        N Engl J Med. 2015; 372: 997-1008
        • Loor G.
        • Li L.
        • Sabik 3rd, J.F.
        • et al.
        Nadir hematocrit during cardiopulmonary bypass: End-organ dysfunction and mortality.
        J Thorac Cardiovasc Surg. 2012; 144: 654-662