Population pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children.
Br J Clin Pharmacol
; 78(4): 886-97, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24802558
ABSTRACT
AIM:
The aim of the study was to investigate the pharmacokinetics and pharmacodynamics of norepinephrine in hypotensive critically ill children, including associated variability factors.METHODS:
This was a prospective study in an 18-bed neonatal and paediatric intensive care unit. All children were aged less than 18 years, weighed more than 1500 g and required norepinephrine for systemic arterial hypotension. The pharmacokinetics and haemodynamic effects were described using the non-linear mixed effect modelling software MONOLIX.RESULTS:
Norepinephrine dosing infusions ranging from 0.05 to 2 µg kg(-1) min(-1) were administered to 38 children whose weight ranged from 2 to 85 kg. A one compartment open model with linear elimination adequately described the norepinephrine concentration-time courses. Bodyweight (BW) was the main covariate influencing norepinephrine clearance (CL) and endogenous norepinephrine production rate (q0) via an allometric relationship CL(BWi) = θCL × (BWi)(3/4) and q0(BWi) = θq0 × (BWi)(3/4) . The increase in mean arterial pressure (MAP) as a function of norepinephrine concentration was well described using an Emax model. The effects of post-conceptional age (PCA) and number of organ dysfunctions were significant on basal MAP level (MAP0i = MAP0 × PCA/9i (0.166) ) and on the maximal increase in MAP (32 mmHg and 12 mmHg for a number of organ dysfunctions ≤3 and ≥4, respectively).CONCLUSION:
The pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children highlight the between-subject variability which is related to the substantial role of age, BW and severity of illness. Taking into account these individual characteristics may help clinicians in determining an appropriate initial a priori dosing regimen.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Norepinefrina
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Hemodinâmica
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Hipotensão
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article