title: Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing cardiac surgery with cardiopulmonary bypass.
abstract: BACKGROUND
  Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic medications in children undergoing repair of congenital heart defects. However, a pharmacokinetics analysis of TXA has never been performed in neonates or young children undergoing complex cardiac surgeries using cardiopulmonary bypass, hypothermia, circulatory arrest, and ultrafiltration. A comprehensive pharmacokinetics study was performed in this patient population.
  
  
  METHODS
  Fifty-five patients ranging from 2 days through 4 yr old were categorized into three groups: children less than 2 months old, infants 2 months to 1 yr old, and children greater than 1 yr old and weighing up to 20 kg. TXA was given as a bolus of 100 mg/kg followed by an infusion of 10 mg · kg · h throughout the surgery. A dose of 100 mg/kg was placed in the cardiopulmonary bypass prime. A total of 16 to 18 samples were obtained from all patients throughout surgery. Plasma TXA concentrations were measured by high-performance liquid chromatography and modeled under a nonlinear mixed-effects framework with a two-compartment structural model.
  
  
  RESULTS
  Cardiopulmonary bypass had a statistically significant impact on all pharmacokinetic parameters. Age was a better covariate than body weight, affecting both the distribution and the elimination of TXA. However, weight performed well in some cases. Other covariates including body surface area, pump prime volume, ultrafiltrate volume, and body temperature did not improve the model.
  
  
  CONCLUSIONS
  This TXA pharmacokinetic analysis is reported for the first time in neonates and young children undergoing complex cardiac surgeries with cardiopulmonary bypass. Dosing recommendations are provided as guidance for maintaining desired target concentrations.
authors.affiliation: From the Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts (M.C.W., L.M.P., J.A.D.); Boston Children's Hospital, Boston, Massachusetts (L.A.S.); Department of Cardiac Surgery, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts (S.M.E.); and Department of Anesthesiology and Critical Care, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania (F.X.M.).
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wesley
authors.forename: Luis M
authors.initials: LM
authors.lastname: Pereira
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Scharp
authors.forename: Sitaram M
authors.initials: SM
authors.lastname: Emani
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
authors.forename: James A
authors.initials: JA
authors.lastname: DiNardo
mesh_terms: D000933:Antifibrinolytic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006348:Cardiac Surgical Procedures / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000379:methods; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D014148:Tranexamic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid