Intraosseous versus intravenous epinephrine infusions in lambs: pharmacokinetics and pharmacodynamics

Intraosseous and intravenous administrations of epinephrine were compared in newborn lambs. Plasma epinephrine levels were measured during each route of drug administration and used to calculate steady-state epinephrine clearance rate and to compare cardiovascular responses with plasma levels. Epinephrine was administered at a dose of 0.5 to 5 micrograms/kg/min. We observed first-order (linear) clearance kinetics by both routes of drug administration. The plasma epinephrine clearance rate was 186 +/- 17 ml/kg/min by the intraosseous route versus 174 +/- 11 ml/kg/min by the intravenous route. Dose responses were analyzed by computerized fit to a threshold model. The plasma epinephrine threshold, or lowest plasma level beyond which discernible increases in blood pressure occur, was slightly lower after intravenous than after intraosseous drug administration, 2.0 +/- 0.6 ng/ml versus 4.0 +/- 0.9 ng/ml of epinephrine. Both thresholds were within the ranges of plasma epinephrine levels that would be achieved at doses of 0.4 to 0.6 microgram/kg/min by either route. Other hemodynamic responses, including the maximum systolic blood pressure and degree of reflex bradycardia, were comparable. These results support the effectiveness of the intraosseous route for epinephrine administration.