Pharmacological support for children with myocardial dysfunction

Booker, Peter D.

doi:10.1046/j.1460-9592.2002.00682.x

Cited by 19 publications

(1 citation statement)

References 164 publications

(186 reference statements)

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“…However, postnatal development of cardiac contractility is associated with major changes in the modulatory effect of β-adrenoreceptor signaling. Moreover, differential maturation of the transduction pathways within the cardiomyocyte contributes to age-dependent changes in cardiac responsiveness and sensitivity to agonists [7]. Although much is known regarding the adult physiological and pharmacological effects of Ep, there are very few pediatric studies on Ep pharmacodynamics.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children

et al. 2014

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IntroductionThe response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors.MethodsThirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested.ResultsEp dosing infusions ranged from 0.01 to 0.23 μg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply.ConclusionsAccording to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.

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Section: Introductionmentioning

confidence: 99%