Michael P Eaton1, George M Alfieris, Dawn M Sweeney, Ronald E Angona, Jill M Cholette, Charles Venuto, Brian Anderson. 1. From the Departments of Anesthesiology (M.P.E., D.M.S.), Surgery (G.M.A., R.E.A.), Pediatrics (J.M.C.), and Neurology, Center for Human Experimental Therapeutics (C.V.), University of Rochester School of Medicine and Dentistry, Rochester, New York; and Department of Anaesthesiology, University of Auckland, Auckland, New Zealand (B.A.).
Abstract
BACKGROUND: Antifibrinolytic medications such as ε-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. The authors sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population. METHODS: Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70-kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/l). RESULTS: Pharmacokinetics were described using a two-compartment model plus an additional compartment for the cardiopulmonary bypass pump. First-order elimination was described with a clearance of 5.07 l/h × (WT/70). Simulation showed a dosing regimen with a loading dose of 40 mg/kg and an infusion of 30 mg · kg · h, with a pump prime concentration of 100 mg/l maintained plasma concentrations above 50 mg/l in 90% of neonates during cardiopulmonary bypass surgery. CONCLUSIONS: EACA clearance, expressed using allometry, is reduced in neonates compared with older children and adults. Loading dose and infusion dose are approximately half those required in children and adults.
BACKGROUND: Antifibrinolytic medications such as ε-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. The authors sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population. METHODS: Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70-kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/l). RESULTS: Pharmacokinetics were described using a two-compartment model plus an additional compartment for the cardiopulmonary bypass pump. First-order elimination was described with a clearance of 5.07 l/h × (WT/70). Simulation showed a dosing regimen with a loading dose of 40 mg/kg and an infusion of 30 mg · kg · h, with a pump prime concentration of 100 mg/l maintained plasma concentrations above 50 mg/l in 90% of neonates during cardiopulmonary bypass surgery. CONCLUSIONS:EACA clearance, expressed using allometry, is reduced in neonates compared with older children and adults. Loading dose and infusion dose are approximately half those required in children and adults.
Authors: Martin Ries; Richard L Easton; Colin Longstaff; Martin Zenker; Howard R Morris; Anne Dell; Patrick J Gaffney Journal: Thromb Res Date: 2002-02-01 Impact factor: 3.944
Authors: Ralph Gertler; Michael Gruber; Gunther Wiesner; Stanislas Grassin-Delyle; Saïk Urien; Peter Tassani-Prell; Klaus Martin Journal: Br J Clin Pharmacol Date: 2018-06-15 Impact factor: 4.335