Advertisement

Patient Blood Management for Neonates and Children Undergoing Cardiac Surgery: 2019 NATA Guidelines

      Pediatric cardiac surgery is associated with a substantial risk of bleeding, frequently requiring the administration of allogeneic blood products. Efforts to optimize preoperative hemoglobin, limit blood sampling, improve hemostasis, reduce bleeding, correct coagulopathy, and incorporate blood sparing techniques (including restrictive transfusion practices) are key elements of patient blood management (PBM) programs, and should be applied to the pediatric cardiac surgical population as across other disciplines. Many guidelines for implementation of PBM in adults undergoing cardiac surgery are available, but evidence regarding the implementation of PBM in children is limited to systematic reviews and specific guidelines for the pediatric cardiac population are missing. The objective of the task force from the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA, www.nataonline.com) is to provide evidence-based recommendations regarding anemia management and blood transfusion practices in the perioperative care of neonates and children undergoing cardiac surgery, and to highlight potential areas where additional research is urgently required.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiothoracic and Vascular Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Despotis G.J.
        • Gravlee G.
        • Filos K.
        • et al.
        Anticoagulation monitoring during cardiac surgery: A review of current and emerging techniques.
        Anesthesiology. 1999; 91: 1122-1151
        • Paparella D.
        • Brister S.J.
        • Buchanan M.R.
        Coagulation disorders of cardiopulmonary bypass: A review.
        Intensive Care Med. 2004; 30: 1873-1881
        • Osthaus W.A.
        • Boethig D.
        • Johanning K.
        • et al.
        Whole blood coagulation measured by modified thrombelastography (ROTEM) is impaired in infants with congenital heart diseases.
        Blood Coagul Fibrinolysis. 2008; 19: 220-225
        • Cholette J.M.
        • Faraoni D.
        • Goobie S.M.
        • et al.
        Patient blood management in pediatric cardiac surgery: A review.
        Anesth Analg. 2018; 127: 1002-1016
        • New H.V.
        • Berryman J.
        • Bolton-Maggs P.H.
        • et al.
        Guidelines on transfusion for fetuses, neonates and older children.
        Br J Haematol. 2016; 175: 784-828
        • Boer C.
        • et al.
        • Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Society
        • the European Association of Cardiothoracic Anaesthesiology
        2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery.
        J Cardiothorac Vasc Anesth. 2018; 32: 88-120
        • Siemens K.
        • Sangaran D.P.
        • Hunt B.J.
        • et al.
        Strategies for prevention and management of bleeding following pediatric cardiac surgery on cardiopulmonary bypass: A scoping review.
        Pediatr Crit Care Med. 2018; 19: 40-47
        • Mustafa R.A.
        • Santesso N.
        • Brozek J.
        • et al.
        The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses.
        J Clin Epidemiol. 2013; 66: 736
        • O'Brien S.M.
        • Clarke D.R.
        • Jacobs J.P.
        • et al.
        An empirically based tool for analyzing mortality associated with congenital heart surgery.
        J Thorac Cardiovasc Surg. 2009; 138: 1139-1153
        • Jacobs M.L.
        • O'Brien S.M.
        • Jacobs J.P.
        • et al.
        An empirically based tool for analyzing morbidity associated with operations for congenital heart disease.
        J Thorac Cardiovasc Surg. 2013; 145 (e1): 1046-1057
        • Goobie S.M.
        • Faraoni D.
        • Zurakowski D.
        • et al.
        Association of preoperative anemia with postoperative mortality in neonates.
        JAMA Pediatr. 2016; 170: 855-862
        • Faraoni D.
        • DiNardo J.A.
        • Goobie S.M.
        Relationship between preoperative anemia and in-hospital mortality in children undergoing noncardiac surgery.
        Anesth Analg. 2016; 123: 1582-1587
        • Mulaj M.
        • Faraoni D.
        • Willems A.
        • et al.
        Predictive factors for red blood cell transfusion in children undergoing noncomplex cardiac surgery.
        Ann Thorac Surg. 2014; 98: 662-667
        • Park S.K.
        • Hur M.
        • Kim E.
        • et al.
        Risk factors for acute kidney injury after congenital cardiac surgery in infants and children: A retrospective observational study.
        PLoS One. 2016; 11e0166328
        • Oski F.A.
        Iron deficiency in infancy and childhood.
        N Engl J Med. 1993; 329: 190-193
        • Hassan N.
        • Boville B.
        • Reischmann D.
        • et al.
        Intravenous ferumoxytol in pediatric patients with iron deficiency anemia.
        Ann Pharmacother. 2017; 51: 548-554
        • Shimpo H.
        • Mizumoto T.
        • Onoda K.
        • et al.
        Erythropoietin in pediatric cardiac surgery: Clinical efficacy and effective dose.
        Chest. 1997; 111: 1565-1570
        • Sonzogni V.
        • Crupi G.
        • Poma R.
        • et al.
        Erythropoietin therapy and preoperative autologous blood donation in children undergoing open heart surgery.
        Br J Anaesth. 2001; 87: 429-434
        • Williams G.D.
        • Bratton S.L.
        • Riley E.C.
        • et al.
        Coagulation tests during cardiopulmonary bypass correlate with blood loss in children undergoing cardiac surgery.
        J Cardiothorac Vasc Anesth. 1999; 13: 398-404
        • Williams G.D.
        • Bratton S.L.
        • Ramamoorthy C.
        Factors associated with blood loss and blood product transfusions: A multivariate analysis in children after open-heart surgery.
        Anesth Analg. 1999; 89: 57-64
        • Moganasundram S.
        • Hunt B.J.
        • Sykes K.
        • et al.
        The relationship among thromboelastography, hemostatic variables, and bleeding after cardiopulmonary bypass surgery in children.
        Anesth Analg. 2010; 110: 995-1002
        • Hayashi T.
        • Sakurai Y.
        • Fukuda K.
        • et al.
        Correlations between global clotting function tests, duration of operation, and postoperative chest tube drainage in pediatric cardiac surgery.
        Paediatr Anaesth. 2011; 21: 865-871
        • Roberts I.
        • Shakur H.
        • et al.
        • CRASH-2 Collaborators
        The importance of early treatment with tranexamic acid in bleeding trauma patients: An exploratory analysis of the CRASH-2 randomised controlled trial.
        Lancet. 2011; 377 (1101.e1-2): 1096-1101
        • WOMAN Trial Collaborators
        Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): An international, randomised, double-blind, placebo-controlled trial.
        Lancet. 2017; 389: 2105-2116
        • Zonis Z.
        • Seear M.
        • Reichert C.
        • et al.
        The effect of preoperative tranexamic acid on blood loss after cardiac operations in children.
        J Thorac Cardiovasc Surg. 1996; 111: 982-987
        • Reid R.W.
        • Zimmerman A.A.
        • Laussen P.C.
        • et al.
        The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery.
        Anesth Analg. 1997; 84: 990-996
        • Chauhan S.
        • Kumar B.A.
        • Rao B.H.
        • et al.
        Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease.
        Ann Thorac Surg. 2000; 70: 1308-1312
        • Rao B.H.
        • Saxena N.
        • Chauhan S.
        • et al.
        Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss.
        Indian J Med Res. 2000; 111: 57-61
        • Chauhan S.
        • Bisoi A.
        • Modi R.
        • et al.
        Tranexamic acid in paediatric cardiac surgery.
        Indian J Med Res. 2003; 118: 86-89
        • Chauhan S.
        • Bisoi A.
        • Kumar N.
        • et al.
        Dose comparison of tranexamic acid in pediatric cardiac surgery.
        Asian Cardiovasc Thorac Ann. 2004; 12: 121-124
        • Chauhan S.
        • Das S.N.
        • Bisoi A.
        • et al.
        Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery.
        J Cardiothorac Vasc Anesth. 2004; 18: 141-143
        • Bulutcu F.S.
        • Ozbek U.
        • Polat B.
        • et al.
        Which may be effective to reduce blood loss after cardiac operations in cyanotic children: Tranexamic acid, aprotinin or a combination?.
        Paediatr Anaesth. 2005; 15: 41-46
        • Shimizu K.
        • Toda Y.
        • Iwasaki T.
        • et al.
        Effect of tranexamic acid on blood loss in pediatric cardiac surgery: A randomized trial.
        J Anesth. 2011; 25: 823-830
        • Sarupria A.
        • Makhija N.
        • Lakshmy R.
        • et al.
        Comparison of different doses of epsilon-aminocaproic acid in children for tetralogy of Fallot surgery: Clinical efficacy and safety.
        J Cardiothorac Vasc Anesth. 2013; 27: 23-29
        • Faraoni D.
        • Willems A.
        • Melot C.
        • et al.
        Efficacy of tranexamic acid in paediatric cardiac surgery: A systematic review and meta-analysis.
        Eur J Cardiothorac Surg. 2012; 42: 781-786
        • Eaton M.P.
        Antifibrinolytic therapy in surgery for congenital heart disease.
        Anesth Analg. 2008; 106: 1087-1100
        • Eaton M.P.
        • Alfieris G.M.
        • Sweeney D.M.
        • et al.
        Pharmacokinetics of epsilon-aminocaproic acid in neonates undergoing cardiac surgery with cardiopulmonary bypass.
        Anesthesiology. 2015; 122: 1002-1009
        • Wesley M.C.
        • Pereira L.M.
        • Scharp L.A.
        • et al.
        Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing cardiac surgery with cardiopulmonary bypass.
        Anesthesiology. 2015; 122: 746-758
        • Yurka H.G.
        • Wissler R.N.
        • Zanghi C.N.
        • et al.
        The effective concentration of epsilon-aminocaproic acid for inhibition of fibrinolysis in neonatal plasma in vitro.
        Anesth Analg. 2010; 111: 180-184
        • Yee B.E.
        • Wissler R.N.
        • Zanghi C.N.
        • et al.
        The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro.
        Anesth Analg. 2013; 117: 767-772
        • Rozen L.
        • Faraoni D.
        • Sanchez Torres C.
        • et al.
        Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator induced hyperfibrinolysis in children with congenital heart disease: A prospective, controlled, in-vitro study.
        Eur J Anaesthesiol. 2015; 32: 844-850
        • Martin K.
        • Breuer T.
        • Gertler R.
        • et al.
        Tranexamic acid versus e-aminocaproic acid: Efficacy and safety in paediatric cardiac surgery.
        Eur J Cardiothoracic Surg. 2011; 39: 892-897
        • Breuer T.
        • Martin K.
        • Wilhelm M.
        • et al.
        The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery.
        Eur J Cardiothorac Surg. 2009; 35: 167-171
        • Kratzer S.
        • Irl H.
        • Mattusch C.
        • et al.
        Tranexamic acid impairs gamma-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: A potential mechanism for drug-induced seizures?.
        Anesthesiology. 2014; 120: 639-649
        • Lecker I.
        • Wang D.S.
        • Romaschin A.D.
        • et al.
        Tranexamic acid concentrations associated with human seizures inhibit glycine receptors.
        J Clin Invest. 2012; 122: 4654-4666
        • Schouten E.S.
        • van de Pol A.C.
        • Schouten A.N.
        • et al.
        The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: A meta-analysis.
        Pediatr Crit Care Med. 2009; 10: 182-190
        • Pasquali S.K.
        • Li J.S.
        • He X.
        • et al.
        Comparative analysis of antifibrinolytic medications in pediatric heart surgery.
        J Thorac Cardiovasc Surg. 2012; 143: 550-557
        • Faraoni D.
        • Rahe C.
        • Cybulski K.A.
        Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?.
        Paediatr Anaesth. 2018; ([Epub ahead of print])https://doi.org/10.1111/pan.13533
        • Elliott M.
        Minimizing the bypass circuit: A rational step in the development of paediatric perfusion.
        Perfusion. 1993; 8: 81-86
        • Bockeria L.A.
        • Kim A.
        • Averina T.
        • et al.
        ICVTS on-line discussion A. Minimizing CPB circuit and reducing use of homologous blood products.
        Interact Cardiovasc Thorac Surg. 2007; 6: 339
        • Charette K.
        • Hirata Y.
        • Bograd A.
        • et al.
        180 ml and less: Cardiopulmonary bypass techniques to minimize hemodilution for neonates and small infants.
        Perfusion. 2007; 22: 327-331
        • Hickey E.
        • Karamlou T.
        • You J.
        • et al.
        Effects of circuit miniaturization in reducing inflammatory response to infant cardiopulmonary bypass by elimination of allogeneic blood products.
        Ann Thorac Surg. 2006; 81: S2367-S2372
        • Durandy Y.
        Usefulness of low prime perfusion pediatric circuit in decreasing blood transfusion.
        ASAIO J. 2007; 53: 659-661
        • Koster A.
        • Huebler M.
        • Boettcher W.
        • et al.
        A new miniaturized cardiopulmonary bypass system reduces transfusion requirements during neonatal cardiac surgery: Initial experience in 13 consecutive patients.
        J Thorac Cardiovasc Surg. 2009; 137: 1565-1568
        • Bojan M.
        • Constanza Basto Duarte M.
        • Lopez Lopez V.
        • et al.
        Use of a miniaturized cardiopulmonary bypass circuit in neonates and infants is associated with fewer blood product transfusions.
        ASAIO J. 2011; 57: 527-532
        • Redlin M.
        • Huebler M.
        • Boettcher W.
        • et al.
        Minimizing intraoperative hemodilution by use of a very low priming volume cardiopulmonary bypass in neonates with transposition of the great arteries.
        J Thorac Cardiovasc Surg. 2011; 142: 875-881
        • Boettcher W.
        • Sinzobahamvya N.
        • Miera O.
        • et al.
        Routine application of bloodless priming in neonatal cardiopulmonary bypass: A 3-year experience.
        Pediatr Cardiol. 2017; 38: 807-812
        • Jonas R.A.
        • Wypij D.
        • Roth S.J.
        • et al.
        The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: Results of a randomized trial in infants.
        J Thorac Cardiovasc Surg. 2003; 126: 1765-1774
        • Newburger J.W.
        • Jonas R.A.
        • Soul J.
        • et al.
        Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery.
        J Thorac Cardiovasc Surg. 2008; 135 (354.e1-4): 347-354
        • Wypij D.
        • Jonas R.A.
        • Bellinger D.C.
        • et al.
        The effect of hematocrit during hypothermic cardiopulmonary bypass in infant heart surgery: Results from the combined Boston hematocrit trials.
        J Thorac Cardiovasc Surg. 2008; 135: 355-360
        • Hornykewycz S.
        • Odegard K.C.
        • Castro R.A.
        • et al.
        Hemostatic consequences of a non-fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants.
        Paediatr Anaesth. 2009; 19: 854-861
        • Miao X.
        • Liu J.
        • Zhao M.
        • et al.
        Evidence-based use of FFP: The influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients.
        Perfusion. 2015; 30: 140-147
        • Miao X.
        • Liu J.
        • Zhao M.
        • et al.
        The influence of cardiopulmonary bypass priming without FFP on postoperative coagulation and recovery in pediatric patients with cyanotic congenital heart disease.
        Eur J Pediatr. 2014; 173: 1437-1443
        • McCall M.M.
        • Blackwell M.M.
        • Smyre J.T.
        • et al.
        Fresh frozen plasma in the pediatric pump prime: A prospective, randomized trial.
        Ann Thorac Surg. 2004; 77: 983-987
        • Bianchi P.
        • Cotza M.
        • Beccaris C.
        • et al.
        Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: The APPEAR randomized trial.
        Br J Anaesth. 2017; 118: 788-796
        • Mou S.S.
        • Giroir B.P.
        • Molitor-Kirsch E.A.
        • et al.
        Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants.
        N Engl J Med. 2004; 351: 1635-1644
        • Gruenwald C.E.
        • McCrindle B.W.
        • Crawford-Lean L.
        • et al.
        Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: A randomized controlled trial.
        J Thorac Cardiovasc Surg. 2008; 136: 1442-1449
        • Riegger L.Q.
        • Voepel-Lewis T.
        • Kulik T.J.
        • et al.
        Albumin versus crystalloid prime solution for cardiopulmonary bypass in young children.
        Crit Care Med. 2002; 30: 2649-2654
        • Hanart C.
        • Khalife M.
        • De Ville A.
        • et al.
        Perioperative volume replacement in children undergoing cardiac surgery: Albumin versus hydroxyethyl starch 130/0.4.
        Crit Care Med. 2009; 37: 696-701
        • Van der Linden P.
        • De Ville A.
        • Hofer A.
        • et al.
        Six percent hydroxyethyl starch 130/0.4 (Voluven) versus 5% human serum albumin for volume replacement therapy during elective open-heart surgery in pediatric patients.
        Anesthesiology. 2013; 119: 1296-1309
        • Van der Linden P.
        • Dumoulin M.
        • Van Lerberghe C.
        • et al.
        Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven) for perioperative volume replacement in children undergoing cardiac surgery: A propensity-matched analysis.
        Crit Care. 2015; 19: 87
        • Miao N.
        • Yang J.
        • Du Z.
        • et al.
        Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery.
        Perfusion. 2014; 29: 462-468
        • Patel J.
        • Prajapati M.
        • Solanki A.
        • et al.
        Comparison of albumin, hydroxyethyl starch and ringer lactate solution as priming fluid for cardiopulmonary bypass in paediatric cardiac surgery.
        J Clin Diagn Res. 2016; 10: UC01-UC04
        • Perner A.
        • Haase N.
        • Guttormsen A.B.
        • et al.
        Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.
        N Engl J Med. 2012; 367: 124-134
        • Myburgh J.A.
        • Finfer S.
        • Bellomo R.
        • et al.
        Hydroxyethyl starch or saline for fluid resuscitation in intensive care.
        N Engl J Med. 2012; 367: 1901-1911
        • Friesen R.H.
        • Tornabene M.A.
        • Coleman S.P.
        Blood conservation during pediatric cardiac surgery: Ultrafiltration of the extracorporeal circuit volume after cardiopulmonary bypass.
        Anesth Analg. 1993; 77: 702-707
        • Journois D.
        • Pouard P.
        • Greeley W.J.
        • et al.
        Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components.
        Anesthesiology. 1994; 81: 1181-1189
        • Naik S.K.
        • Knight A.
        • Elliott M.
        A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery.
        Circulation. 1991; 84: III422-III431
        • Friesen R.H.
        • Campbell D.N.
        • Clarke D.R.
        • et al.
        Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open heart operations.
        Ann Thorac Surg. 1997; 64: 1787-1789
        • Williams G.D.
        • Ramamoorthy C.
        • Totzek F.R.
        • et al.
        Comparison of the effects of red cell separation and ultrafiltration on heparin concentration during pediatric cardiac surgery.
        J Cardiothorac Vasc Anesth. 1997; 11: 840-844
        • Bando K.
        • Turrentine M.W.
        • Vijay P.
        • et al.
        Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease.
        Ann Thorac Surg. 1998; 66: 821-827
        • Gurbuz A.T.
        • Novick W.M.
        • Pierce C.A.
        • et al.
        Impact of ultrafiltration on blood use for atrial septal defect closure in infants and children.
        Ann Thorac Surg. 1998; 65: 1105-1108
        • Elliott M.
        Modified ultrafiltration and open heart surgery in children.
        Paediatr Anaesthesia. 1999; 9: 1-5
        • Williams G.D.
        • Ramamoorthy C.
        • Chu L.
        • et al.
        Modified and conventional ultrafiltration during pediatric cardiac surgery: Clinical outcomes compared.
        J Thorac Cardiovasc Surg. 2006; 132: 1291-1298
        • Kuratani N.
        • Bunsangjaroen P.
        • Srimueang T.
        • et al.
        Modified versus conventional ultrafiltration in pediatric cardiac surgery: A meta-analysis of randomized controlled trials comparing clinical outcome parameters.
        J Thorac Cardiovasc Surg. 2011; 142: 861-867
        • Turkoz A.
        • Tuncay E.
        • Balci S.T.
        • et al.
        The effect of modified ultrafiltration duration on pulmonary functions and hemodynamics in newborns and infants following arterial switch operation.
        Pediatr Crit Care Med. 2014; 15: 600-607
        • Meybohm P.
        • Choorapoikayil S.
        • Wessels A.
        • et al.
        Washed cell salvage in surgical patients: A review and meta-analysis of prospective randomized trials under PRISMA.
        Medicine. 2016; 95: e4490
        • Carless P.A.
        • Henry D.A.
        • Moxey A.J.
        • et al.
        Cell salvage for minimising perioperative allogeneic blood transfusion.
        Cochrane Database Syst Rev. 2010; CD001888
        • Wang G.
        • Bainbridge D.
        • Martin J.
        • et al.
        The efficacy of an intraoperative cell saver during cardiac surgery: A meta-analysis of randomized trials.
        Anesth Analg. 2009; 109: 320-330
        • Golab H.D.
        • Takkenberg J.J.
        • van Gerner-Weelink G.L.
        • et al.
        Effects of cardiopulmonary bypass circuit reduction and residual volume salvage on allogeneic transfusion requirements in infants undergoing cardiac surgery.
        Interact Cardiovasc Thorac Surg. 2007; 6: 335-339
        • Cholette J.M.
        • Powers K.S.
        • Alfieris G.M.
        • et al.
        Transfusion of cell saver salvaged blood in neonates and infants undergoing open heart surgery significantly reduces RBC and coagulant product transfusions and donor exposures: Results of a prospective, randomized, clinical trial.
        Pediatr Crit Care Med. 2013; 14: 137-147
        • Durandy Y.
        Perfusionist strategies for blood conservation in pediatric cardiac surgery.
        World J Cardiol. 2010; 2: 27-33
        • Cholette J.M.
        • Henrichs K.F.
        • Alfieris G.M.
        • et al.
        Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.
        Pediatr Crit Care Med. 2012; 13: 290-299
        • Van der Linden P.
        The physiology of acute isovolaemic anaemia.
        Acta Anaesthesiol Belg. 2002; 53: 97-103
        • Jamnicki M.
        • Kocian R.
        • van der Linden P.
        • et al.
        Acute normovolemic hemodilution: Physiology, limitations, and clinical use.
        J Cardiothorac Vasc Anesth. 2003; 17: 747-754
        • Friesen R.H.
        • Perryman K.M.
        • Weigers K.R.
        • et al.
        A trial of fresh autologous whole blood to treat dilutional coagulopathy following cardiopulmonary bypass in infants.
        Paediatr Anaesth. 2006; 16: 429-435
        • Naguib A.N.
        • Winch P.D.
        • Tobias J.D.
        • et al.
        A single-center strategy to minimize blood transfusion in neonates and children undergoing cardiac surgery.
        Paediatr Anaesth. 2015; 25: 477-486
        • Crescini W.M.
        • Muralidaran A.
        • Shen I.
        • et al.
        The use of acute normovolemic hemodilution in paediatric cardiac surgery.
        Acta Anaesthesiol Scand. 2018; 62: 756-764
        • Laliberte B.D.
        • Nath D.S.
        • Costello J.P.
        • et al.
        Normovolemic hemodilution using hydroxyethyl starch 130/0.4 (Voluven) in a Jehovah's Witness child requiring cardiopulmonary bypass for ventricular septal defect repair.
        J Clin Anesth. 2014; 26: 402-406
        • Winch P.D.
        • Naguib A.N.
        • Bradshaw J.R.
        • et al.
        Decreasing the need for transfusion: Infant cardiac surgery using hemodilution and recombinant factor VIIa.
        Pediatr Cardiol. 2013; 34: 119-124
        • Guzzetta N.A.
        • Miller B.E.
        • Todd K.
        • et al.
        An evaluation of the effects of a standard heparin dose on thrombin inhibition during cardiopulmonary bypass in neonates.
        Anesth Analg. 2005; 100: 1276-1282
        • Ignjatovic V.
        • Lai C.
        • Summerhayes R.
        • et al.
        Age-related differences in plasma proteins: How plasma proteins change from neonates to adults.
        PLoS One. 2011; 6: e17213
        • Heying R.
        • van Oeveren W.
        • Wilhelm S.
        • et al.
        Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity.
        Crit Care. 2006; 10: R165
        • Manlhiot C.
        • Gruenwald C.E.
        • Holtby H.M.
        • et al.
        Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin activity.
        J Thorac Cardiovasc Surg. 2016; 151: 444-450
        • Guzzetta N.A.
        • Bajaj T.
        • Fazlollah T.
        • et al.
        A comparison of heparin management strategies in infants undergoing cardiopulmonary bypass.
        Anesth Analg. 2008; 106: 419-425
        • Gruenwald C.E.
        • Manlhiot C.
        • Chan A.K.
        • et al.
        Randomized, controlled trial of individualized heparin and protamine management in infants undergoing cardiac surgery with cardiopulmonary bypass.
        J Am Coll Cardiol. 2010; 56: 1794-1802
        • Machovec K.A.
        • Jooste E.H.
        • Walczak R.J.
        • et al.
        A change in anticoagulation monitoring improves safety, reduces transfusion, and reduces costs in infants on cardiopulmonary bypass.
        Paediatr Anaesth. 2015; 25: 580-586
        • Codispoti M.
        • Ludlam C.A.
        • Simpson D.
        • et al.
        Individualized heparin and protamine management in infants and children undergoing cardiac operations.
        Ann Thorac Surg. 2001; 71: 922-927
        • Nakamura S.
        • Honjo O.
        • Crawford-Lean L.
        • et al.
        Predicting heparin responsiveness in children before cardiopulmonary bypass: A retrospective cohort study.
        Anesth Analg. 2018; 126: 1617-1623
        • Guzzetta N.A.
        • Monitz H.G.
        • Fernandez J.D.
        • et al.
        Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass.
        Anesth Analg. 2010; 111: 173-179
        • Guzzetta N.A.
        • Amin S.J.
        • Tosone A.K.
        • et al.
        Change in heparin potency and effects on the activated clotting time in children undergoing cardiopulmonary bypass.
        Anesth Analg. 2012; 115: 921-924
        • Gruenwald C.E.
        • Manlhiot C.
        • Abadilla A.A.
        • et al.
        Heparin brand is associated with postsurgical outcomes in children undergoing cardiac surgery.
        Ann Thorac Surg. 2012; 93: 878-882
        • Wong T.E.
        • Nguyen T.
        • Shah S.S.
        • et al.
        Antithrombin concentrate use in pediatric extracorporeal membrane oxygenation: A multicenter cohort study.
        Pediatr Crit Care Med. 2016; 17: 1170-1178
        • Koster A.
        • Faraoni D.
        • Levy J.H.
        Argatroban and bivalirudin for perioperative anticoagulation in cardiac surgery.
        Anesthesiology. 2018; 128: 390-400
        • Hasija S.
        • Talwar S.
        • Makhija N.
        • et al.
        Randomized controlled trial of heparin versus bivalirudin anticoagulation in acyanotic children undergoing open heart surgery.
        J Cardiothorac Vasc Anesth. 2018; 32: 2633-2640
        • Zaleski K.L.
        • DiNardo J.A.
        • Nasr V.G.
        Bivalirudin for pediatric procedural anticoagulation: A narrative review.
        Anesth Analg. 2019; 128: 43-55
        • Toulon P.
        • Ozier Y.
        • Ankri A.
        • et al.
        Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery. A multicenter study.
        Thromb Haemost. 2009; 101: 394-401
        • Kozek-Langenecker S.A.
        • Ahmed A.B.
        • Afshari A.
        • et al.
        Management of severe perioperative bleeding: Guidelines from the European Society of Anaesthesiology: First update 2016.
        Eur J Anaesthesiol. 2017; 34: 332-395
        • American Society of Anesthesiologists Task Force on Perioperative Blood Management
        Practice guidelines for perioperative blood management: An updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management.
        Anesthesiology. 2015; 122: 241-275
        • Perez-Ferrer A.
        • Vicente-Sanchez J.
        • Carceles-Baron M.D.
        • et al.
        Early thromboelastometry variables predict maximum clot firmness in children undergoing cardiac and non-cardiac surgery.
        Br J Anaesth. 2015; 115: 896-902
        • Pekelharing J.
        • Furck A.
        • Banya W.
        • et al.
        Comparison between thromboelastography and conventional coagulation tests after cardiopulmonary bypass surgery in the paediatric intensive care unit.
        Int J Lab Hematol. 2014; 36: 465-471
        • Faraoni D.
        • Willems A.
        • Savan V.
        • et al.
        Plasma fibrinogen concentration is correlated with postoperative blood loss in children undergoing cardiac surgery. A retrospective review.
        Eur J Anaesth. 2014; 31: 317-326
        • Rizza A.
        • Ricci Z.
        • Pezzella C.
        • et al.
        Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: A prospective cohort study.
        Paediatr Anaesth. 2017; 27: 170-180
        • Miller B.E.
        • Guzzetta N.A.
        • Tosone S.R.
        • et al.
        Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography.
        Anesth Analg. 2000; 90: 1324-1330
        • Miller B.E.
        • Guzzetta N.A.
        • Tosone S.R.
        • et al.
        Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: Baseline values and comparisons.
        Anesth Analg. 2003; 97: 1289-1293
        • Straub A.
        • Schiebold D.
        • Wendel H.P.
        • et al.
        Using reagent-supported thromboelastometry (ROTEM) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest.
        Eur J Cardiothorac Surg. 2008; 34: 641-647
        • Andreasen J.B.
        • Hvas A.M.
        • Christiansen K.
        • et al.
        Can RoTEM analysis be applied for haemostatic monitoring in paediatric congenital heart surgery?.
        Cardiol Young. 2011; 21: 684-691
        • Niebler R.A.
        • Gill J.C.
        • Brabant C.P.
        • et al.
        Thromboelastography in the assessment of bleeding following surgery for congenital heart disease.
        World J Pediatr Congenit Heart Surg. 2012; 3: 433-438
        • Romlin B.S.
        • Wahlander H.
        • Berggren H.
        • et al.
        Intraoperative thromboelastometry is associated with reduced transfusion prevalence in pediatric cardiac surgery.
        Anesth Analg. 2011; 112: 30-36
        • Kane L.C.
        • Woodward C.S.
        • Husain S.A.
        • et al.
        Thromboelastography—Does it impact blood component transfusion in pediatric heart surgery?.
        J Surg Res. 2016; 200: 21-27
        • Nakayama Y.
        • Nakajima Y.
        • Tanaka K.A.
        • et al.
        Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery.
        Br J Anaesth. 2015; 114: 91-102
        • Mazine A.
        • Rached-D'Astous S.
        • Ducruet T.
        • et al.
        Blood transfusions after pediatric cardiac operations: A North American multicenter prospective study.
        Ann Thorac Surg. 2015; 100: 671-677
        • Wilkinson K.L.
        • Brunskill S.J.
        • Doree C.
        • et al.
        Red cell transfusion management for patients undergoing cardiac surgery for congenital heart disease.
        Cochrane Database Syst Rev. 2014; CD009752
        • Willems A.
        • Van Lerberghe C.
        • Gonsette K.
        • et al.
        The indication for perioperative red blood cell transfusions is a predictive risk factor for severe postoperative morbidity and mortality in children undergoing cardiac surgery.
        Eur J Cardiothorac Surg. 2014; 45: 1050-1057
        • Willems A.
        • Datoussaid D.
        • Tucci M.
        • et al.
        Impact of on-bypass red blood cell transfusion on severe postoperative morbidity or mortality in children.
        Anesth Analg. 2016; 123: 420-429
        • Salvin J.W.
        • Scheurer M.A.
        • Laussen P.C.
        • et al.
        Blood transfusion after pediatric cardiac surgery is associated with prolonged hospital stay.
        Ann Thorac Surg. 2011; 91: 204-210
        • Szekely A.
        • Cserep Z.
        • Sapi E.
        • et al.
        Risks and predictors of blood transfusion in pediatric patients undergoing open heart operations.
        Ann Thorac Surg. 2009; 87: 187-197
        • Lacroix J.
        • Hebert P.C.
        • Hutchison J.S.
        • et al.
        Transfusion strategies for patients in pediatric intensive care units.
        N Engl J Med. 2007; 356: 1609-1619
        • Willems A.
        • Harrington K.
        • Lacroix J.
        • et al.
        Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: A subgroup analysis.
        Crit Care Med. 2010; 38: 649-656
        • de Gast-Bakker D.H.
        • de Wilde R.B.P.
        • Hazekamp M.G.
        • et al.
        Safety and effects of two cell transfusion strategies in pediatric cardiac surgery patients: A randomized controlled trial.
        Intensive Care Med. 2013; 39: 2011-2019
        • Cholette J.M.
        • Rubenstein J.S.
        • Alfieris G.M.
        • et al.
        Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: Results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy.
        Pediatr Crit Care Med. 2011; 12: 39-45
        • Cholette J.M.
        • Swartz M.F.
        • Rubenstein J.
        • et al.
        Outcomes using a conservative versus liberal red blood cell transfusion strategy in infants requiring cardiac operation.
        Ann Thorac Surg. 2017; 103: 206-214
        • Du Pont-Thibodeau G.
        • Harrington K.
        • Lacroix J.
        Anemia and red blood cell transfusion in critically ill cardiac patients.
        Ann Intensive Care. 2014; 4: 16
        • Dhabangi A.
        • Ainomugisha B.
        • Cserti-Gazdewich C.
        • et al.
        Effect of transfusion of red blood cells with longer vs shorter storage duration on elevated blood lactate levels in children with severe anemia: The TOTAL randomized clinical trial.
        JAMA. 2015; 314: 2514-2523
        • Vallet B.
        • Robin E.
        • Lebuffe G.
        Venous oxygen saturation as a physiologic transfusion trigger.
        Crit Care. 2010; 14: 213
        • Orlov D.
        • O'Farrell R.
        • McCluskey S.A.
        • et al.
        The clinical utility of an index of global oxygenation for guiding red blood cell transfusion in cardiac surgery.
        Transfusion. 2009; 49: 682-688
        • Barr P.J.
        • Bailie K.E.
        Transfusion thresholds in FOCUS.
        N Engl J Med. 2011; 365: 2532-2533
        • Bonding Andreasen J.
        • Hvas A.-M.
        • Ravn H.B.
        Marked changes in platelet count and function following pediatric congenital heart surgery.
        Paediatr Anaesth. 2014; 24: 386-392
        • Romlin B.S.
        • Soderlund F.
        • Wahlander H.
        • et al.
        Platelet count and function in paediatric cardiac surgery: A prospective observational study.
        Br J Anaesth. 2014; 113: 847-854
        • Gertler R.
        • Hapfelmeier A.
        • Tassani-Prell P.
        • et al.
        The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery.
        Eur J Cardiothorac Surg. 2015; 48: 301-307
        • Romlin B.S.
        • Soderlund F.
        • Wahlander H.
        • et al.
        Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry?.
        Br J Anaesth. 2016; 116: 822-828
        • Galas F.R.B.G.
        • de Almeida J.P.
        • Fukushima J.T.
        • et al.
        Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: A randomized pilot trial.
        J Thorac Cardiovasc Surg. 2014; 148: 1647-1655
        • Guzzetta N.A.
        • Szlam F.
        • Kiser A.S.
        • et al.
        Augmentation of thrombin generation in neonates undergoing cardiopulmonary bypass.
        Br J Anaesth. 2014; 112: 319-327
        • Franklin S.W.
        • Szlam F.
        • Fernandez J.D.
        • et al.
        Optimizing thrombin generation with 4-factor prothrombin complex concentrates in neonatal plasma after cardiopulmonary bypass.
        Anesth Analg. 2016; 122: 935-942
        • Giorni C.
        • Ricci Z.
        • Iodice F.
        • et al.
        Use of Confidex to control perioperative bleeding in pediatric heart surgery: Prospective cohort study.
        Pediatr Cardiol. 2014; 35: 208-214
        • Jooste E.H.
        • Machovec K.A.
        • Einhorn L.M.
        • et al.
        3-Factor prothrombin complex concentrates in infants with refractory bleeding after cardiac surgery.
        J Cardiothorac Vasc Anesth. 2016; 30: 1627-1631
        • Keshava S.
        • Sundaram J.
        • Rajulapati A.
        • et al.
        Pharmacological concentrations of recombinant factor VIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice.
        J Thromb Haemost. 2016; 14: 546-550
        • Ekert H.
        • Brizard C.
        • Eyers R.
        • et al.
        Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: A randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy.
        Blood Coagul Fibrinolysis. 2006; 17: 389-395
        • Pychynska-Pokorska M.
        • Moll J.J.
        • Krajewski W.
        • et al.
        The use of recombinant coagulation factor VIIa in uncontrolled postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass.
        Pediatr Crit Care Med. 2004; 5: 246-250
        • Pychynska-Pokorska M.
        • Pagowska-Klimek I.
        • Krajewski W.
        • et al.
        Use of recombinant activated factor VII for controlling refractory postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass.
        J Cardiothorac Vasc Anesth. 2011; 25: 987-994
        • Agarwal H.S.
        • Bennett J.E.
        • Churchwell K.B.
        • et al.
        Recombinant factor seven therapy for postoperative bleeding in neonatal and pediatric cardiac surgery.
        Ann Thorac Surg. 2007; 84: 161-168
        • Niles S.D.
        • Burkhart H.M.
        • Duffey D.A.
        • et al.
        Use of recombinant factor VIIa (NovoSeven) in pediatric cardiac surgery.
        J Extra Corpor Technol. 2008; 40: 241-248
        • Downey L.
        • Brown M.L.
        • Faraoni D.
        • et al.
        Recombinant factor VIIa is associated with increased thrombotic complications in pediatric cardiac surgery patients.
        Anesth Analg. 2017; 124: 1431-1436
        • Seear M.D.
        • Wadsworth L.D.
        • Rogers P.C.
        • et al.
        The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children.
        J Thorac Cardiovasc Surg. 1989; 98: 217-219
        • Oliver W.C.
        • Santrach P.J.
        • Danielson G.K.
        • et al.
        Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations.
        Ann Thorac Surg. 2000; 70: 1923-1930
        • Reynolds L.M.
        • Nicolson S.C.
        • Jobes D.R.
        • et al.
        Desmopressin does not decrease bleeding after cardiac operation in young children.
        J Thorac Cardiovasc Surg. 1993; 106: 954-958