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Pharmacokinetics of ε-Aminocaproic Acid in Neonates Undergoing Cardiac Surgery with Cardiopulmonary Bypass.
- Source :
-
Anesthesiology [Anesthesiology] 2015 May; Vol. 122 (5), pp. 1002-9. - Publication Year :
- 2015
-
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.<br />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).<br />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.<br />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.
- Subjects :
- Aminocaproic Acid administration & dosage
Aminocaproic Acid pharmacology
Antifibrinolytic Agents administration & dosage
Antifibrinolytic Agents pharmacology
Female
Fibrinolysis drug effects
Humans
Infant, Newborn
Infusion Pumps
Infusions, Intravenous
Male
Models, Statistical
Nonlinear Dynamics
Aminocaproic Acid pharmacokinetics
Antifibrinolytic Agents pharmacokinetics
Cardiac Surgical Procedures
Cardiopulmonary Bypass
Subjects
Details
- Language :
- English
- ISSN :
- 1528-1175
- Volume :
- 122
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Anesthesiology
- Publication Type :
- Academic Journal
- Accession number :
- 25723765
- Full Text :
- https://doi.org/10.1097/ALN.0000000000000616