High-dose versus low-dose tranexamic acid for paediatric craniosynostosis surgery: a double-blind randomised controlled non-inferiority trial

Br J Anaesth. 2020 Sep;125(3):336-345. doi: 10.1016/j.bja.2020.05.054. Epub 2020 Jun 30.


Background: Tranexamic acid (TXA) reduces blood loss and transfusion in paediatric craniosynostosis surgery. The hypothesis is that low-dose TXA, determined by pharmacokinetic modelling, is non-inferior to high-dose TXA in decreasing blood loss and transfusion in children.

Methods: Children undergoing craniosynostosis surgery were enrolled in a two-centre, prospective, double-blind, randomised, non-inferiority controlled trial to receive high TXA (50 mg kg-1 followed by 5 mg kg-1 h-1) or low TXA (10 mg kg-1 followed by 5 mg kg-1 h-1). Primary outcome was blood loss. Low dose was determined to be non-inferior to high dose if the 95% confidence interval (CI) for the mean difference in blood loss was above the non-inferiority margin of -20 ml kg-1. Secondary outcomes were transfusion, TXA plasma concentrations, and biological markers of fibrinolysis and inflammation.

Results: Sixty-eight children were included. Values were non-inferior regarding blood loss (39.4 [4.4] vs 40.3 [6.2] ml kg-1 [difference=0.9; 95% CI: -14.2, 15.9]) and blood transfusion (21.3 [1.6] vs 23.6 [1.5] ml kg-1 [difference=2.3; 95% CI: -2.1, 6.7]) between high-dose (n=32) and low-dose (n=34) groups, respectively. The TXA plasma concentrations during surgery averaged 50.2 (8.0) and 29.6 (7.6) μg ml-1. There was no difference in fibrinolytic and inflammatory biological marker concentrations. No adverse events were observed.

Conclusions: Tranexamic acid 10 mg kg-1 followed by 5 mg kg-1 h-1 is not less effective than a higher dose of 50 mg kg-1 and 5 mg kg-1 h-1 in reducing blood loss and transfusion in paediatric craniosynostosis surgery.

Clinical trial registration: NCT02188576.

Keywords: anti-fibrinolytics; blood loss; blood transfusion; craniosynostosis surgery; paediatric anaesthesia; pharmacokinetics; tranexamic acid.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifibrinolytic Agents / therapeutic use*
  • Blood Loss, Surgical / prevention & control
  • Child, Preschool
  • Craniosynostoses / surgery*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Male
  • Prospective Studies
  • Tranexamic Acid / therapeutic use*


  • Antifibrinolytic Agents
  • Tranexamic Acid

Associated data

  • ClinicalTrials.gov/NCT02188576