PDF herunterladen
Semin Thromb Hemost 2021; 47(05): 538-568
DOI: 10.1055/s-0040-1721736
Review Article

Efficacy and Safety of Antifibrinolytic Drugs in Pediatric Surgery: A Systematic Review

Nadia Thrane Hovgesen
1   Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
,
Julie Brogaard Larsen
1   Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
,
Christian Fenger-Eriksen
2   Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark
,
Anne Kirkeby Hansen
3   Neonatal Intensive Care Unit, Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
,
Anne-Mette Hvas
1   Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
4   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
› Institutsangaben Funding The work was supported by Aarhus University Research Foundation.
› Weitere Informationen
    Lizenzen und Reprints

Abstract

Antifibrinolytic drugs are used to reduce blood loss and subsequent transfusions during surgery and following trauma, but the optimal dosing regimen in the pediatric population is still unresolved. The aim of this systematic review was to evaluate efficacy and safety of antifibrinolytic drugs in pediatric surgery and trauma to determine the optimal dosing regimen. A literature search was performed in PubMed, Embase, Cochrane, and Web of Science on May 3, 2020. We included randomized controlled studies investigating the effect of tranexamic acid (TXA), aprotinin, and epsilon-aminocaproic acid, in terms of reducing blood loss, blood transfusions, reoperations, and rebleeds in pediatric patients aged 0 to 18 years undergoing cardiac surgery, noncardiac surgery, or trauma. Fifty randomized controlled trials (RCTs) were included; 28 RCTs investigated cardiac surgery and 22 investigated noncardiac surgery. No RCTs regarding trauma met the inclusion criteria. All antifibrinolytic drugs reduced postoperative blood loss and transfusions when used in pediatric surgery. The dosing regimen varied between studies, but similar effect sizes were found in terms of reduced blood loss regardless of the cumulative dose used. Few studies found adverse events, and no difference in incidence or type of adverse events was seen between the antifibrinolytic and the placebo group. In conclusion, use of antifibrinolytics is efficient and safe in children undergoing surgery. We propose TXA as the drug of choice based on its level of evidence and safety profile; we recommend a dosing regimen composed of a loading dose of 10 to 15 mg/kg prior to surgery followed by 1 to 5 mg/kg/h as continuous infusion throughout surgery.

Keywords

Antifibrinolytic agents - Tranexamic acid - Aprotinin - Aminocaproic acid - pediatric surgery - blood loss - surgical

Supplementary Material



Publikationsverlauf

Artikel online veröffentlicht:
30. Juni 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Guzzetta NA, Allen NN, Wilson EC, Foster GS, Ehrlich AC, Miller BE. Excessive postoperative bleeding and outcomes in neonates undergoing cardiopulmonary bypass. Anesth Analg 2015; 120 (02) 405-410
    CrossrefPubMedGoogle Scholar
  • 2 Meyer P, Renier D, Arnaud E. et al. Blood loss during repair of craniosynostosis. Br J Anaesth 1993; 71 (06) 854-857
    CrossrefPubMedGoogle Scholar
  • 3 Meert KL, Kannan S, Mooney JF. Predictors of red cell transfusion in children and adolescents undergoing spinal fusion surgery. Spine 2002; 27 (19) 2137-2142
    CrossrefPubMedGoogle Scholar
  • 4 Stainsby D, Jones H, Wells AW, Gibson B, Cohen H. SHOT Steering Group. Adverse outcomes of blood transfusion in children: analysis of UK reports to the serious hazards of transfusion scheme 1996-2005. Br J Haematol 2008; 141 (01) 73-79
    CrossrefPubMedGoogle Scholar
  • 5 Lavoie J. Blood transfusion risks and alternative strategies in pediatric patients. Paediatr Anaesth 2011; 21 (01) 14-24
    CrossrefPubMedGoogle Scholar
  • 6 Redlin M, Kukucka M, Boettcher W. et al. Blood transfusion determines postoperative morbidity in pediatric cardiac surgery applying a comprehensive blood-sparing approach. J Thorac Cardiovasc Surg 2013; 146 (03) 537-542
    CrossrefPubMedGoogle Scholar
  • 7 Schouten ES, van de Pol AC, Schouten AN, Turner NM, Jansen NJ, Bollen CW. 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 (02) 182-190
    CrossrefPubMedGoogle Scholar
  • 8 Henry DA, Carless PA, Moxey AJ. et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011; (03) CD001886
    PubMedGoogle Scholar
  • 9 Shakur H, Roberts I, Bautista R. et al; CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376 (9734): 23-32
    CrossrefPubMedGoogle Scholar
  • 10 Faraoni D, Goobie SM. The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature. Anesth Analg 2014; 118 (03) 628-636
    CrossrefPubMedGoogle Scholar
  • 11 McNicol ED, Tzortzopoulou A, Schumann R, Carr DB, Kalra A. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev 2016; 9 (09) CD006883
    PubMedGoogle Scholar
  • 12 Basta MN, Stricker PA, Taylor JA. A systematic review of the use of antifibrinolytic agents in pediatric surgery and implications for craniofacial use. Pediatr Surg Int 2012; 28 (11) 1059-1069
    CrossrefPubMedGoogle Scholar
  • 13 Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol) 1980; 14: 41-47
    CrossrefPubMedGoogle Scholar
  • 14 Davis R, Whittington R. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery. Drugs 1995; 49 (06) 954-983
    CrossrefPubMedGoogle Scholar
  • 15 Karkouti K, Beattie WS, Dattilo KM. et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46 (03) 327-338
    CrossrefPubMedGoogle Scholar
  • 16 Mangano DT, Tudor IC, Dietzel C. Multicenter Study of Perioperative Ischemia Research Group, Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354 (04) 353-365
    CrossrefPubMedGoogle Scholar
  • 17 Manufacturer removes remaining stocks of Trasylol [press release]. . May 8, 2008. Accessed February 6, 2021 at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116895.htm
    PubMedGoogle Scholar
  • 18 Fergusson DA, Hébert PC, Mazer CD. et al; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358 (22) 2319-2331
    CrossrefPubMedGoogle Scholar
  • 19 Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: a meta-analysis. Seizure 2016; 36: 70-73
    CrossrefPubMedGoogle Scholar
  • 20 Maeda T, Michihata N, Sasabuchi Y. et al. Safety of tranexamic acid during pediatric trauma: a nationwide database study. Pediatr Crit Care Med 2018; 19 (12) e637-e642
    CrossrefPubMedGoogle Scholar
  • 21 Martin K, Breuer T, Gertler R. et al. Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg 2011; 39 (06) 892-897
    CrossrefPubMedGoogle Scholar
  • 22 Goobie SM, Faraoni D. Tranexamic acid and perioperative bleeding in children: what do we still need to know?. Curr Opin Anaesthesiol 2019; 32 (03) 343-352
    CrossrefPubMedGoogle Scholar
  • 23 Moher D, Shamseer L, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4 (01) 1
    CrossrefPubMedGoogle Scholar
  • 24 National Institutes of Health. 2014 Quality assessment tool for observational cohort and cross-sectional studies. Accessed July 22, 2020 at: https://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/cohort
    PubMedGoogle Scholar
  • 25 Centre for Evaluation and Monitoring (CEM). Effect size calculator. Accessed August 15, 2020 at: https://www.cem.org/effect-size-calculator
    PubMedGoogle Scholar
  • 26 Higgins JPT, Li T, Deeks JJ. Choosing effect measures and computing estimates of effect (Section 6.5.2.2). In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. eds. Cochrane Handbook for Systematic Reviews of Interventions, Version 6.0 (updated July 2019). Welch VA: ed. Cochrane; 2019. . Available at: www.training.cochrane.org/handbook
    Google Scholar
  • 27 Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. Accessed August 15, 2020 at: http://www.math.hkbu.edu.hk/~tongt/papers/median2mean.html
    PubMedGoogle Scholar
  • 28 Brum MR, Miura MS, Castro SF, Machado GM, Lima LH, Lubianca Neto JF. Tranexamic acid in adenotonsillectomy in children: a double-blind randomized clinical trial. Int J Pediatr Otorhinolaryngol 2012; 76 (10) 1401-1405
    CrossrefPubMedGoogle Scholar
  • 29 Sarupria A, Makhija N, Lakshmy R, Kiran U. Comparison of different doses of ε-aminocaproic acid in children for tetralogy of Fallot surgery: clinical efficacy and safety. J Cardiothorac Vasc Anesth 2013; 27 (01) 23-29
    CrossrefPubMedGoogle Scholar
  • 30 D'Errico CC, Munro HM, Buchman SR, Wagner D, Muraszko KM. Efficacy of aprotinin in children undergoing craniofacial surgery. J Neurosurg 2003; 99 (02) 287-290
    CrossrefPubMedGoogle Scholar
  • 31 Dadure C, Sauter M, Bringuier S. et al. Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 2011; 114 (04) 856-861
    CrossrefPubMedGoogle Scholar
  • 32 Eldaba AA, Amr YM, Albirmawy OA. Effects of tranexamic acid during endoscopic sinsus surgery in children. Saudi J Anaesth 2013; 7 (03) 229-233
    CrossrefPubMedGoogle Scholar
  • 33 Fenger-Eriksen C, D'Amore Lindholm A, Nørholt SE. et al. Reduced perioperative blood loss in children undergoing craniosynostosis surgery using prolonged tranexamic acid infusion: a randomised trial. Br J Anaesth 2019; 122 (06) 760-766
    CrossrefPubMedGoogle Scholar
  • 34 Goobie SM, Meier PM, Pereira LM. et al. Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind, placebo-controlled trial. Anesthesiology 2011; 114 (04) 862-871
    CrossrefPubMedGoogle Scholar
  • 35 Goobie SM, Zurakowski D, Glotzbecker MP. et al. Tranexamic acid is efficacious at decreasing the rate of blood loss in adolescent scoliosis surgery: a randomized placebo-controlled trial. J Bone Joint Surg Am 2018; 100 (23) 2024-2032
    CrossrefPubMedGoogle Scholar
  • 36 Kim EJ, Kim YO, Shim KW, Ko BW, Lee JW, Koo BN. Effects of tranexamic acid based on its population pharmacokinetics in pediatric patients undergoing distraction osteogenesis for craniosynostosis: rotational thromboelastometry (ROTEM™) analysis. Int J Med Sci 2018; 15 (08) 788-795
    CrossrefPubMedGoogle Scholar
  • 37 Mössinger H, Dietrich W, Braun SL, Jochum M, Meisner H, Richter JA. High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery. Ann Thorac Surg 2003; 75 (02) 430-437
    CrossrefPubMedGoogle Scholar
  • 38 Neilipovitz DT, Murto K, Hall L, Barrowman NJ, Splinter WM. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg 2001; 93 (01) 82-87
    CrossrefPubMedGoogle Scholar
  • 39 Saleh AN, Mostafa RH. Increased nociception following administration of different doses of tranexamic acid in adolescent idiopathic scoliosis surgery. Open Anesthesiol J 2018; 12 (01) 61-68
    CrossrefPubMedGoogle Scholar
  • 40 Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 2005; 102 (04) 727-732
    CrossrefPubMedGoogle Scholar
  • 41 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 (06) 823-830
    CrossrefPubMedGoogle Scholar
  • 42 Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 1996; 111 (05) 982-987
    CrossrefPubMedGoogle Scholar
  • 43 Aggarwal V, Kapoor PM, Choudhury M, Kiran U, Chowdhury U. Utility of Sonoclot analysis and tranexamic acid in tetralogy of Fallot patients undergoing intracardiac repair. Ann Card Anaesth 2012; 15 (01) 26-31
    CrossrefPubMedGoogle Scholar
  • 44 Bulutcu FS, Ozbek U, Polat B, Yalçin Y, Karaci AR, Bayindir O. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination?. Paediatr Anaesth 2005; 15 (01) 41-46
    CrossrefPubMedGoogle Scholar
  • 45 Ahmed Z, Stricker L, Rozzelle A, Zestos M. Aprotinin and transfusion requirements in pediatric craniofacial surgery. Paediatr Anaesth 2014; 24 (02) 141-145
    CrossrefPubMedGoogle Scholar
  • 46 Chauhan S, Kumar BA, Rao BH. et al. Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease. Ann Thorac Surg 2000; 70 (04) 1308-1312
    CrossrefPubMedGoogle Scholar
  • 47 Cole JW, Murray DJ, Snider RJ, Bassett GS, Bridwell KH, Lenke LG. Aprotinin reduces blood loss during spinal surgery in children. Spine 2003; 28 (21) 2482-2485
    CrossrefPubMedGoogle Scholar
  • 48 D'Errico CC, Shayevitz JR, Martindale SJ, Mosca RS, Bove EL. The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery. Anesth Analg 1996; 83 (06) 1193-1199
    CrossrefPubMedGoogle Scholar
  • 49 Davies MJ, Allen A, Kort H. et al. Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations. Ann Thorac Surg 1997; 63 (02) 497-503
    CrossrefPubMedGoogle Scholar
  • 50 Durga P, Raavula P, Gurajala I. et al. Evaluation of the efficacy of tranexamic acid on the surgical field in primary cleft palate surgery on children-a prospective, randomized clinical study. Cleft Palate Craniofac J 2015; 52 (05) e183-e187
    CrossrefPubMedGoogle Scholar
  • 51 Ezhevskaya AA, Prusakova ZB, Zagrekov VI, Sosnin AV, Milenovic M. Efficacy assessment of epidural blockade and tranexamic acid application in idiopathic scoliosis surgery. Sovremennye Tehnologii V Medicine 2018; 10 (04) 164-172
    CrossrefPubMedGoogle Scholar
  • 52 Flaujac C, Pouard P, Boutouyrie P, Emmerich J, Bachelot-Loza C, Lasne D. Platelet dysfunction after normothermic cardiopulmonary bypass in children: effect of high-dose aprotinin. Thromb Haemost 2007; 98 (02) 385-391
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 53 Florentino-Pineda I, Thompson GH, Poe-Kochert C, Huang RP, Haber LL, Blakemore LC. The effect of amicar on perioperative blood loss in idiopathic scoliosis: the results of a prospective, randomized double-blind study. Spine 2004; 29 (03) 233-238
    CrossrefPubMedGoogle Scholar
  • 54 Khoshhal K, Mukhtar I, Clark P, Jarvis J, Letts M, Splinter W. Efficacy of aprotinin in reducing blood loss in spinal fusion for idiopathic scoliosis. J Pediatr Orthop 2003; 23 (05) 661-664
    CrossrefPubMedGoogle Scholar
  • 55 Murugesan C, Banakal SK, Garg R, Keshavamurthy S, Muralidhar K. The efficacy of aprotinin in arterial switch operations in infants. Anesth Analg 2008; 107 (03) 783-787
    CrossrefPubMedGoogle Scholar
  • 56 Reid RW, Zimmerman AA, Laussen PC, Mayer JE, Gorlin JB, Burrows FA. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997; 84 (05) 990-996
    CrossrefPubMedGoogle Scholar
  • 57 Rupinder S, Manimozhi V, Nagaraj G. et al. Aprotinin for open cardiac surgery in cyanotic heart disease. Asian Cardiovasc Thorac Ann 2001; 9 (02) 101-104
    CrossrefPubMedGoogle Scholar
  • 58 Soliman R, Alshehri A. Assessment of the effect of tranexamic acid on perioperative bleeding in pediatric patients undergoing tonsillectomy. Egypt J Anaesth 2015; 31 (04) 297-301
    CrossrefPubMedGoogle Scholar
  • 59 Swarup I, Nguyen J, Edmonds C, Dodwell E, Scher D. Effect of intravenous aminocaproid acid on blood loss and transfusion requirements after bilateral varus rotational osteotomy: a double-blind, placebo-controlled randomized trial. J Pediatr Orthop 2020; 40 (06) e454-e459
    CrossrefPubMedGoogle Scholar
  • 60 Teboul BK, Jacob JL, Barsoum-Homsy M. et al. Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children. Ophthalmology 1995; 102 (11) 1646-1653
    CrossrefPubMedGoogle Scholar
  • 61 Williams GD, Ramamoorthy C, Pentcheva K, Boltz MG, Kamra K, Reddy VM. A randomized, controlled trial of aprotinin in neonates undergoing open-heart surgery. Paediatr Anaesth 2008; 18 (09) 812-819
    CrossrefPubMedGoogle Scholar
  • 62 Boldt J, Knothe C, Zickmann B, Wege N, Dapper F, Hempelmann G. Aprotinin in pediatric cardiac operations: platelet function, blood loss, and use of homologous blood. Ann Thorac Surg 1993; 55 (06) 1460-1466
    CrossrefPubMedGoogle Scholar
  • 63 Boldt J, Knothe C, Zickmann B, Wege N, Dapper F, Hempelmann G. Comparison of two aprotinin dosage regimens in pediatric patients having cardiac operations. Influence on platelet function and blood loss. J Thorac Cardiovasc Surg 1993; 105 (04) 705-711
    CrossrefPubMedGoogle Scholar
  • 64 Boldt J, Zickmann B, Schindler E, Welters A, Dapper F, Hempelmann G. Influence of aprotinin on the thrombomodulin/protein C system in pediatric cardiac operations. J Thorac Cardiovasc Surg 1994; 107 (05) 1215-1221
    CrossrefPubMedGoogle Scholar
  • 65 Chauhan S, Bisoi A, Kumar N. et al. Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovasc Thorac Ann 2004; 12 (02) 121-124
    CrossrefPubMedGoogle Scholar
  • 66 Chauhan S, Bisoi A, Modi R, Gharde P, Rajesh MR. Tranexamic acid in paediatric cardiac surgery. Indian J Med Res 2003; 118: 86-89
    PubMedGoogle Scholar
  • 67 Chauhan S, Das SN, Bisoi A, Kale S, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2004; 18 (02) 141-143
    CrossrefPubMedGoogle Scholar
  • 68 Couturier R, Rubatti M, Credico C. et al. Continuous or discontinuous tranexamic acid effectively inhibits fibrinolysis in children undergoing cardiac surgery with cardiopulmonary bypass. Blood Coagul Fibrinolysis 2014; 25 (03) 259-265
    CrossrefPubMedGoogle Scholar
  • 69 Dietrich W, Mössinger H, Spannagl M. et al. Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations. J Thorac Cardiovasc Surg 1993; 105 (04) 712-720
    CrossrefPubMedGoogle Scholar
  • 70 Herynkopf F, Lucchese F, Pereira E, Kalil R, Prates P, Nesralla IA. Aprotinin in children undergoing correction of congenital heart defects. A double-blind pilot study. J Thorac Cardiovasc Surg 1994; 108 (03) 517-521
    CrossrefPubMedGoogle Scholar
  • 71 Huang H, Ding W, Su Z, Zhang W. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg 1993; 106 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 72 Levin E, Wu J, Devine DV. et al. Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid. Thromb Haemost 2000; 83 (01) 54-59
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 73 McClure PD, Izsak J. The use of epsilon-aminocaproic acid to reduce bleeding during cardiac bypass in children with congenital heart disease. Anesthesiology 1974; 40 (06) 604-608
    CrossrefPubMedGoogle Scholar
  • 74 Rao BH, Saxena N, Chauhan S, Bisoi AK, Venugopal P. Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss. Indian J Med Res 2000; 111: 57-61
    PubMedGoogle Scholar
  • 75 Santosh UP, Prashanth KB, Abhilash S. A comparative study to verify the efficacy of preoperative intravenous tranexamic acid in control of tonsillectomy bleeding. Otorhinolaryngology Clinics. 2016; 8 (01) 22-25
    CrossrefPubMedGoogle Scholar
  • 76 Seghaye MC, Duchateau J, Grabitz RG. et al. Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children. Ann Thorac Surg 1996; 61 (04) 1205-1211
    CrossrefPubMedGoogle Scholar
  • 77 Verstraete M, Tyberghein J, De Greef Y, Daems L, Van Hoof A. Double-blind trials with ethamsylate, batroxobin or tranexamic acid on blood loss after adenotonsillectomy. Acta Clin Belg 1977; 32 (02) 136-141
    CrossrefPubMedGoogle Scholar
  • 78 Howie SR. Blood sample volumes in child health research: review of safe limits. Bull World Health Organ 2011; 89 (01) 46-53
    CrossrefPubMedGoogle Scholar
  • 79 CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019; 394 (10210): 1713-1723
    CrossrefPubMedGoogle Scholar
  • 80 Yokobori S, Yatabe T, Kondo Y, Kinoshita K. Japan Resuscitation Council (JRC) Neuroresuscitation Task Force and the Guidelines Editorial Committee. Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis. J Intensive Care 2020; 8 (01) 46
    CrossrefPubMedGoogle Scholar
  • 81 Weng S, Wang W, Wei Q, Lan H, Su J, Xu Y. Effect of tranexamic acid in patients with traumatic brain injury: a systematic review and meta-analysis. World Neurosurg 2019; 123: 128-135
    CrossrefPubMedGoogle Scholar
  • 82 Delaney JW, Moltedo JM, Dziura JD, Kopf GS, Snyder CS. Early postoperative arrhythmias after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2006; 131 (06) 1296-1300
    CrossrefPubMedGoogle Scholar
  • 83 Rękawek J, Kansy A, Miszczak-Knecht M. et al. Risk factors for cardiac arrhythmias in children with congenital heart disease after surgical intervention in the early postoperative period. J Thorac Cardiovasc Surg 2007; 133 (04) 900-904
    CrossrefPubMedGoogle Scholar
  • 84 Yuan SM. Acute kidney injury after pediatric cardiac surgery. Pediatr Neonatol 2019; 60 (01) 3-11
    CrossrefPubMedGoogle Scholar
  • 85 Jafri SK, Ehsan L, Abbas Q, Ali F, Chand P, Ul Haque A. Frequency and outcome of acute neurologic complications after congenital heart disease surgery. J Pediatr Neurosci 2017; 12 (04) 328-331
    CrossrefPubMedGoogle Scholar
  • 86 Sharma V, Katznelson R, Jerath A. et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia 2014; 69 (02) 124-130
    CrossrefPubMedGoogle Scholar
  • 87 Manji RA, Grocott HP, Leake J. et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth 2012; 59 (01) 6-13
    CrossrefPubMedGoogle Scholar
  • 88 Hodgson S, Larvin JT, Dearman C. What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery?. Interact Cardiovasc Thorac Surg 2015; 21 (03) 384-388
    CrossrefPubMedGoogle Scholar