Skip to main content
SpringerLink
Log in

A systematic review of the use of antifibrinolytic agents in pediatric surgery and implications for craniofacial use

  • Review Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

A systematic review aimed to evaluate the efficacy and safety of aprotinin, epsilon-aminocaproic acid (EACA), and tranexamic acid (TXA) in reducing perioperative blood loss, risk for transfusion, and total perioperative transfusion volume in major pediatric surgery. Medline, Embase, and Cochrane Reviews were searched for relevant articles published from January 1990 to January 2012. Additional studies were identified by cross-referencing citations and extracting data from recent published reviews. Data were recorded and analyzed using Cochrane’s RevMan5.1 software. Thirty-four studies were included in this review of which 21 provided level 1b evidence, 11 were level 2b, and two were level 3b. As compared to control groups, antifibrinolytics reduced perioperative blood loss by standardized mean difference (SMD) of −0.70 (−0.89, −0.50; p < 0.00001), total transfusion volume by SMD of −0.78 (−0.95, −0.61; p < 0.00001), and Odds Ratio (OR) for transfusion was 0.39 (0.23, 0.64; p = 0.002). The OR for adverse events attributable to treatment was not statistically significant across groups (OR = 0.96; p = 0.58). Antifibrinolytics are effective in reducing blood loss and transfusion requirements in major pediatric surgery. TXA and EACA also appear to have reasonable side-effect profiles. Application to craniofacial surgery is promising, though further investigation is necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Guay J, Rivard GE (1996) Mediastinal bleeding after cardiopulmonary bypass in pediatric patients. Ann ThoracSurg 62:1955–1960

    Article  CAS  Google Scholar 

  2. Williams GD, Bratton SL, Ramamoorthy C (1999) Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery. Anesth Analg 89:57–64

    PubMed  CAS  Google Scholar 

  3. Chan AK, Leaker M, Burrows FA et al (1997) Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 77:270–277

    PubMed  CAS  Google Scholar 

  4. Meert KL, Kannan S, Mooney JF (2002) Predictors of red cell transfusion in children and adolescents undergoing spinal fusion surgery. Spine 27:2137–2142

    Article  PubMed  Google Scholar 

  5. Meyer P, Renier D, Arnaud E et al (1993) Blood loss during repair of craniosynostosis. Br J Anaesth 71:854–857

    Article  PubMed  CAS  Google Scholar 

  6. Feldman JM, Roth JV, Bjoraker DG (1995) Maximum blood savings by acute normovolemic hemodilution. Anesth Analg 80:108–113

    PubMed  CAS  Google Scholar 

  7. Chauhan S, Kumar BA, Rao BH et al (2000) Efficacy of aprotinin, epsilon aminocaproic acid or combination in cyanotic heart disease. Ann Thorac Surg 70:1308–1312

    Article  PubMed  CAS  Google Scholar 

  8. Florentino-Pineda I, Thompson GH, Poe-Kochert C et al (2004) The effect of amicar on perioperative blood loss in idiopathic scoliosis: the results of a prospective, randomized, double-blind study. Spine 29:233–238

    Article  PubMed  Google Scholar 

  9. Goobie SM, Meier PM, Pereira LM et al (2011) Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind Placebo-controlled trial. Anesthesiology 114:862–871

    Article  PubMed  CAS  Google Scholar 

  10. Dadure C, Sauter M, Bringuier S et al (2011) Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 114:856–861

    Article  PubMed  CAS  Google Scholar 

  11. Fergusson DA, Hebert PC, Mazer CD et al (2008) A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358(22):2319–2331

    Article  PubMed  CAS  Google Scholar 

  12. OCEBM Levels of Evidence Working Group Oxford Centre for Evidence-Based Medicine The Oxford 2011 levels of evidence. http://www.cebm.net/index.aspx?o=5653. Accessed 19 Jan 2012 (OCEBM levels of evidence working group = Jeremy Howick, Iain Chalmers (James Lind Library), Paul Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob Phillips, Hazel Thornton, Olive Goddard and Mary Hodgkinson)

  13. Review Manager (RevMan) [Computer program]. Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011

  14. Rao BH, Saxena S, Chauhan S et al (2000) Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss. Indian J Med Res 111:57–61

    PubMed  CAS  Google Scholar 

  15. Williams GD, Bratton SL, Riley EC et al (1999) Efficacy of e-aminocaproic acid in children undergoing cardiac surgery. J Cardiothorac Vasc Anesth 13:304–308

    Article  PubMed  CAS  Google Scholar 

  16. Chauhan S, Bisoi A, Modi R et al (2003) Tranexamic acid in paediatric cardiac surgery. Indian J Med Res 118:86–89

    PubMed  CAS  Google Scholar 

  17. Levin E, Wu J, Devine DV et al (2000) Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid. Thromb Haemost 83:54–59

    PubMed  CAS  Google Scholar 

  18. Reid RW, Zimmerman A, Laussen PC et al (1997) The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 84:990–996

    PubMed  CAS  Google Scholar 

  19. Zonis Z, Seear M, Reichert C et al (1996) The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 111:982–987

    Article  PubMed  CAS  Google Scholar 

  20. Carrel TP, Schwanda M, Vogt PR et al (1998) Aprotinin in pediatric cardiac operations: a benefit in complex malformations and with high-dose regimen only. Ann Thorac Surg 66:153–158

    Article  PubMed  CAS  Google Scholar 

  21. Chiravuri SD, Voepel-Lewis T, Devaney EJ et al (2008) The use of aprotinin in children undergoing operative repair of isolated atrial septal defects. Pediatr Anesth 18:145–150

    Google Scholar 

  22. Costello JM, Backer CL, de Hoyos A et al (2003) Aprotinin reduces operative closure time and blood product use after pediatric bypass. Ann Thorac Surg 75:1261–1266

    Article  PubMed  Google Scholar 

  23. Davies MJ, Allen A, Kort H et al (1997) A prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations. Ann Thorac Surg 63:497–503

    Article  PubMed  CAS  Google Scholar 

  24. D’Errico CC, Shayevitz JR, Martindale SJ et al (1996) Efficacy and cost of aprotinin in children undergoing operative open heart surgery. Pediatr Anesth 83:1193–1199

    Google Scholar 

  25. Herynkopf F, Lucchese F, Pereira E et al (1994) Aprotinin in children undergoing correction of congenital heart defects: a double-blind pilot study. J Thorac Cardiovasc Surg 108:517–521

    PubMed  CAS  Google Scholar 

  26. Miller BE, Tosone SR, Tam VK et al (1998) Hematologic and economic impact of aprotinin in reoperative pediatric operations. Ann Thorac Surg 66:535–540

    Article  PubMed  CAS  Google Scholar 

  27. Mossinger H, Dietrich W, Braun SL et al (2003) High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery. Ann Thorac Surg 75:430–437

    Article  PubMed  Google Scholar 

  28. Penkoske PA, Entwistle LM, Marchak BE et al (1995) Aprotinin in children undergoing repair of congenital heart defects. Ann Thorac Surg 60:529–532

    Article  Google Scholar 

  29. Williams GD, Ramamoorthy C, Pentcheva K et al (2008) A randomized, controlled trial of aprotinin in neonates undergoing open-heart surgery. Pediatr Anesth 18:812–819

    Article  Google Scholar 

  30. Chauhan S, Das SN, Bisoi A et al (2004) Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 18:141–143

    Article  PubMed  CAS  Google Scholar 

  31. Martin K, Gertler R, Sterner A et al. (2011) Comparison of blood-sparing efficacy of e-aminocaproic acid and tranexamic acid in newborns undergoing cardiac surgery. J Thorac Cardiovasc Surg

  32. Bulutcu FS, Ozbek U, Polat B et al (2005) Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Pediatr Anesth 15:41–46

    Article  Google Scholar 

  33. D’Errico CC, Munro HM, Buchman SR et al (2003) Efficacy of aprotinin in children undergoing craniofacial surgery. J Neurosurg 99:287–290

    Article  PubMed  Google Scholar 

  34. Thompson GH, Florentino-Pineda I, Poe-Kochert C et al (2008) The role of amicar in same-day anterior and posterior spinal fusion for idiopathic scoliosis. Spine 33:2237–2242

    Article  PubMed  Google Scholar 

  35. Thompson GH, Florentino-Pineda I, Poe-Kochert C et al (2008) Role of amicar in surgery for neuromuscular scoliosis. Spine 33:2623–2629

    Article  PubMed  Google Scholar 

  36. Florentino-Pineda I, Blakemore LC, Thompson GH et al (2001) The effect of e-aminocaproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion. Spine 26:1147–1151

    Article  PubMed  CAS  Google Scholar 

  37. Grant JA, Howard J, Luntley J et al (2009) Perioperative blood transfusion requirements in pediatric scoliosis surgery: the efficacy of tranexamic acid. J Pediatr Orthop 29:300–304

    Article  PubMed  Google Scholar 

  38. Neilipovitz DT, Murto K, Hall L et al (2001) A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg 93:82–87

    Article  PubMed  CAS  Google Scholar 

  39. Sethna NF, Zurakowski D, Brustowicz RM et al (2005) Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 102:727–732

    Article  PubMed  CAS  Google Scholar 

  40. Shapiro F, Zurakowski D, Sethna NF (2007) Tranexamic acid diminishes intraoperative blood loss and transfusion requirements in spinal fusions for duchenne muscular dystrophy scoliosis. Spine 32:2278–2283

    Article  PubMed  Google Scholar 

  41. Kasimian S, Skaggs DL, Sankar WN et al (2008) Aprotinin in pediatric neuromuscular scoliosis surgery. Eur Spine J 17:1671–1675

    Article  PubMed  Google Scholar 

  42. Khoshhal K, Mukhtar I, Clark P et al (2003) Efficacy of aprotinin in reducing blood loss in spinal fusion for idiopathic scoliosis. J Pediatr Orthop 23:661–664

    Article  PubMed  Google Scholar 

  43. Cole JW, Murray DJ, Snider RJ et al (2003) Aprotinin reduces blood loss during spinal surgery in children. Spine 28:2482–2485

    Article  PubMed  Google Scholar 

  44. Smith PK, Muhlbaier LH (1996) Aprotinin: safe and effective only with the full-dose regimen. Ann Thoracic Surg 62:1575–1577

    Article  CAS  Google Scholar 

  45. Tzortzopoulou A, Cepeda MS (2008) Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children (review). Cochrane Libr 4:1–34

    Google Scholar 

  46. Schouten E, van de Pol AC, Schouten A et al (2009) 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 10:182–190

    Article  PubMed  Google Scholar 

  47. Carrier M, Denault A, Lavoie J, Perrault LP (2006) Randomized controlled trial of pericardial blood processing with a cell-saving device on neurologic markers in elderly patients undergoing coronary artery bypass graft surgery. Ann Thorac Surg 82(1):51–55

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, 100 Stemmler Hall, Philadelphia, PA, 19104, USA

    Marten N. Basta

  2. The Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Room 9307, Philadelphia, PA, 19104, USA

    Paul A. Stricker

  3. Children’s Hospital of Philadelphia, 3400 Spruce Street, 10 Penn Tower, Philadelphia, PA, 19104, USA

    Jesse A. Taylor

Authors
  1. Marten N. Basta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul A. Stricker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jesse A. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jesse A. Taylor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basta, M.N., Stricker, P.A. & Taylor, J.A. A systematic review of the use of antifibrinolytic agents in pediatric surgery and implications for craniofacial use. Pediatr Surg Int 28, 1059–1069 (2012). https://doi.org/10.1007/s00383-012-3167-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-012-3167-6

Keywords

Search

Navigation