PHARMACOKINETICS OF EXOGENOUS EPINEPHRINE IN CRITICALLY ILL CHILDREN

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 mug/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 2 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 2 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.