EPINEPHRINE PHARMACOKINETICS AND PHARMACODYNAMICS FOLLOWING ENDOTRACHEAL ADMINISTRATION IN DOGS - THE ROLE OF VOLUME OF DILUENT

Objective: to define the optimal volume of dilution for endotracheal ( ET) administration of epinephrine (EPI). Design: prospective, randomiz ed, laboratory comparison of four different volumes of dilution of end otracheal epinephrine (1, 2, 5, and 10 mi of normal saline). Setting: large animal research facility of a university medical center. Subject s and interventions: epinephrine (0.02 mg/kg) diluted with four differ ent volumes (1, 2, 5, and 10 mi) of normal saline was injected into th e ET tube of five anesthetized dogs. Each dog served as its own contro l and received all four volumes in different sequences at least 1 week apart. Arterial blood samples for plasma epinephrine concentration an d blood gases were collected before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5 , 10, 15, 20, 25, 30 and 60 min after drug administration. Heart rate and arterial blood pressure were continuously monitored with a polygra ph recorder. Measurements and main results: higher volumes of diluent (5 and 10 mi) caused a significant decrease of PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of diluent (1 and 2 mi), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects persi sted for over 30 min. Mean plasma epinephrine concentrations significa ntly increased within 15 s following administration for all the volume s of diluent. Mean plasma epinephrine concentrations, maximal epinephr ine concentration (C-max) and the coefficient of absorption (K-a) were higher in the 5 and 10 mi groups. The time interval to reach maximal concentration (T-max) was shorter in the 5 and 10 mi groups. Yet these results were not significantly different. Heart rate, systolic and di astolic blood pressures did not differ significantly between the group s throughout the study. Conclusions: Dilution of endotracheal epinephr ine into a 5 mi volume with saline optimizes drug uptake and delivery without adversely affecting oxygenation and ventilation. (C) 1997 Else vier Science Ireland Ltd.