Pharmacokinetics of dexmedetomidine in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass.
Paediatr Anaesth
; 33(4): 303-311, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36594749
ABSTRACT
BACKGROUND:
Cardiopulmonary bypass can affect the pharmacokinetics of anesthetic agents.AIMS:
We aimed to evaluate the pharmacokinetics of dexmedetomidine for infants and small children undergoing cardiac surgery with cardiopulmonary bypass based on population pharmacokinetics.METHODS:
We enrolled 30 pediatric cardiac surgical patients in this study. After anesthetic induction with atropine (0.02 mg/kg), thiopental sodium (5 mg/kg), and fentanyl (2-3 µg/kg), we administered 1 µg/kg of dexmedetomidine for 10 min, followed by administration of 0.5 µg/kg of dexmedetomidine per hour during surgery. At the initiation of cardiopulmonary bypass, 1 µg/kg of dexmedetomidine was infused over 5 min. Arterial blood was obtained at predefined time points. A pharmacokinetic model was developed using NONMEM. Theory-based allometric scaling with fixed exponents was applied. Weight, age, post-menstrual age, fat-free mass, whether to implement cardiopulmonary bypass and temperature were explored as covariates.RESULTS:
A total of 376 blood samples were obtained from 29 children (age 20.3 ± 19.3 months, weight 9.7 ± 4.1 kg). A two-compartment mammillary model with third compartment associated cardiopulmonary bypass procedure best explained the pharmacokinetics of dexmedetomidine. The pharmacokinetic parameter estimates (95% CI) standardized to a 70-kg person were as follows V1 (L) = 31.6 (17.9-39.5), V2 (L) = 90.1 (44.0-330), Cl (L/min) = 1.08 (0.70-1.25), Q (L/min) = 2.0 (1.05-3.46). Volume for third compartment associated cardiopulmonary bypass procedure (L) = 39.4 (19.3-50.9). Clearance was not influenced by the presence of cardiopulmonary bypass in this model.CONCLUSION:
When cardiopulmonary bypass is applied, the plasma concentration of dexmedetomidine decreases due to an increase in the volume of distribution, so a loading dose is required to maintain the previous concentration.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article