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Pharmacokinetics of exogenous epinephrine in critically ill children
D G Fisher1, P H Schwartz, A L Davis
1Division of Pediatric Critical Care, Memorial Miller Children's Hospital, Long Beach, CA 90801.
Insights
Epinephrine infusions in critically ill children result in pharmacologic plasma concentrations that correlate with the dose, indicating linear pharmacokinetics. Epinephrine clearance rates are similar to dopamine and dobutamine, but lower than in healthy adults.
Area of Science:
- Pediatric Critical Care Medicine
- Clinical Pharmacology
- Pharmacokinetics
Background:
- Critically ill children often require vasoactive medications like epinephrine.
- Understanding the pharmacokinetic profile of epinephrine is crucial for optimizing its use in this population.
- Limited data exists on epinephrine pharmacokinetics specifically in pediatric intensive care unit (PICU) patients.
Purpose of the Study:
- To determine steady-state plasma concentrations and clearance rates of epinephrine in critically ill children.
- To assess if epinephrine pharmacokinetics follow a linear model in this patient group.
- To compare epinephrine clearance rates with those of dopamine and dobutamine.
Main Methods:
- Prospective study conducted in pediatric ICUs of two tertiary care teaching hospitals.
- Included hemodynamically stable children receiving continuous epinephrine infusions.
- Blood samples analyzed for epinephrine, dopamine, and dobutamine concentrations using high-pressure liquid chromatography with electrochemical detection.
Main Results:
- Plasma epinephrine concentrations ranged from 670 to 9430 pg/mL and were linearly related to the infusion dose.
- Epinephrine clearance rates varied from 15.6 to 79.2 mL/kg/min and were not concentration-dependent.
- Epinephrine clearance rates were comparable to dopamine and dobutamine and showed a linear relationship with them.
Conclusions:
- Epinephrine administration leads to pharmacologic plasma concentrations in critically ill children, supporting linear pharmacokinetics.
- Epinephrine clearance rates in critically ill children appear lower than in healthy adults.
- Significant correlations were observed between epinephrine clearance rates and those of dopamine and dobutamine.
Objectives:
This study was designed to determine the steady-state plasma concentrations and clearance rates of epinephrine in critically ill children, to examine if epinephrine pharmacokinetics conform to a linear model, and to compare epinephrine clearance rates with clearance rates of dopamine and dobutamine.
Design:
This study was prospective, without intervention or control groups.
Setting:
The pediatric ICUs of two tertiary care teaching hospitals.
Patients:
All patients who were hemodynamically stable while requiring continuous epinephrine infusions were eligible for the study.
Interventions:
Blood samples were taken at steady state and analyzed for epinephrine concentrations, as well as dopamine and dobutamine concentrations, if present, by high-pressure liquid chromatography with electrochemical detection.
Results:
Plasma epinephrine concentrations during steady-state infusions of 0.03 to 0.2 micrograms/kg/min ranged from 670 to 9430 pg/mL (3660 to 51,490 pmol/L), with a mean of 4360 +/- 3090 pg/mL (23,810 +/- 16,870 pmol/L) and were linearly related to dose. Epinephrine clearance rates ranged from 15.6 to 79.2 mL/kg/min (mean 29.3 +/- 16.1) and were not dependent on steady-state plasma concentrations. Epinephrine clearance rate was in the same range as the clearance rates of dopamine (34.1 +/- 16.6) and dobutamine (35.9 +/- 27.8) and was linearly related to them (p < .005).
Conclusions:
Epinephrine infusions produce pharmacologic plasma concentrations of epinephrine in critically ill children. The plasma concentration of epinephrine correlates with the infusion rate, suggesting linear pharmacokinetics. Epinephrine clearance rates in critically ill children appear to be lower than the reported clearance rates in healthy adults. The clearance rates of two other inotropic catecholamines, dopamine and dobutamine, are significantly correlated with the clearance rate of epinephrine.