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

Abstract

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 À1 followed by 5 mg kg À1 h À1 ) or low TXA (10 mg kg À1 followed by 5 mg kg À1 h À1 ). 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 e20 ml kg À1 . 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 À1 [difference¼0.9; 95% CI: e14.2, 15.9]) and blood transfusion (21.3 [1.6] vs 23.6 [1.5] ml kg À1 [difference¼2.3; 95% CI: e2.1, 6.7]) between high-dose (n¼32) and low-dose (n¼34) groups, respectively. The TXA plasma concentrations during surgery averaged 50.2 (8.0) and 29.6 (7.6) mg ml À1 . There was no difference in fibrinolytic and inflammatory biological marker concentrations. No adverse events were observed. Conclusions: Tranexamic acid 10 mg kg À1 followed by 5 mg kg À1 h À1 is not less effective than a higher dose of 50 mg kg À1 and 5 mg kg À1 h À1 in reducing blood loss and transfusion in paediatric craniosynostosis surgery. Clinical trial registration: NCT02188576.

Efficacy of Tranexamic Acid in Pediatric Craniofacial and Orthognathic Surgery: A Meta-Analysis

“…Two studies calculated the cost associated with TXA use per patient versus the cost of blood product transfusions. 17,18 The Risk of Bias (RoB) for 5 studies was judged to be low and one was judged to be probably low. The details of the RoB for the studies included are shown in Table 1.…”

“…Two studies calculated the cost associated with TXA use per patient versus the cost of blood product transfusions. 17,18…”

Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomised, parallel-group, placebo control, non-inferiority trial

“…A few randomised studies reported the difference in postoperative seizure fit in TXA treated patients and placebo-treated patients. Hooda et al 3 reported lower incidence in the TXA group compared with the placebo group in intracranial meningioma (3.3% vs 6.7%) patients while in other randomised controlled trials of paediatric craniosynostosis and tumour resection, no seizures were observed 9 10 26. Nevertheless, the incidence of seizure attacks was measured as the secondary outcome and the sample size of both studies was relatively small.…”

“…Tranexamic acid (TXA), an antifibrinolytic drug widely used for haemostasis, inhibits plasminogen activation and stabilises the blood clot by reversibly binding to the lysine residues on plasminogen, hence reducing intraoperative bleeding 7. TXA is used as a bolus ranging from 10 to 50 mg/kg, followed by a continuous infusion ranging from 1 to 5 mg/kg/hour until the end of the procedures in a variety of neurosurgical procedures 3 8–10. Unfortunately, the risk of postoperative seizures remains uncertain, and restricts the routine use of TXA in neurosurgery, though it is a safe and effective means to reduce operative blood loss and blood transfusion rates in cardiac, pulmonary, trauma, obstetric, spinal and orthopaedic surgery 11–14…”

“…History of epilepsy, tumour recurrence, frontoparietal location and peritumoral oedema was reported to be associated with EPS 20 22 23. However, there is no prospective study focusing on the effect of tranexamic acid on EPS in patients undergoing meningioma resections, though TXA was proved of reducing intraoperative haemorrhage volume in traumatic brain injury surgery, paediatric craniosynostosis surgery and meningioma resection 10 24 25…”