A practical tranexamic acid dosing scheme based on population pharmacokinetics in children undergoing cardiac surgery.
BACKGROUND
Pediatric cardiac surgery patients are at high risk for bleeding, and the antifibrinolytic drug tranexamic acid (TA) is often used to reduce blood loss. However, dosing schemes remain empirical as a consequence of the absence of pharmacokinetic study in this population. The authors' objectives were thus to investigate the population pharmacokinetics of TA in pediatric cardiac surgery patients during cardiopulmonary bypass (CPB).


METHODS
Twenty-one patients were randomized to receive TA either continuously (10 mg/kg followed by an infusion of 1 mg · kg · h(-1) throughout the operation, and 10 mg/kg into the CPB) or discontinuously (10 mg/kg, then 10 mg/kg into the CPB and 10 mg · kg · h(-1) at the end of CPB). Serum concentrations were measured at eight time points with chromatography-mass spectrometry and the data were modeled using Monolix (Lixoft, Orsay, France).


RESULTS
Tranexamic acid pharmacokinetics was ascribed to a two-compartment open model. The main covariate effects were body weight and CPB. Representative pharmacokinetic parameters adjusted to a 70-kg body weight were as follows: systemic clearance, 2.45 l/h; volume of distribution in the central compartment, 14.1 l; intercompartmental clearance, 5.74 l/h; and peripheral volume, 32.8 l. In accordance with this model, the authors proposed a weight-adjusted dosing scheme to maintain effective TA concentrations in children during surgery, consisting of one loading dose followed by a continuous infusion.


CONCLUSIONS
The authors report for the first time the pharmacokinetics of TA in children undergoing cardiac surgery with CPB, and propose a dosing scheme for optimized TA administration in those children.
Laboratoire de Pharmacologie, UPRES EA220, Hôpital Foch, Suresnes, France. s.grassindelyle@hopital-foch.org
Stanislas
S
Grassin-Delyle
Roland
R
Couturier
Emuri
E
Abe
Jean Claude
JC
Alvarez
Philippe
P
Devillier
Saïk
S
Urien
D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid