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).


METHODS
prospective, randomized, laboratory comparison of four different volumes of dilution of endotracheal epinephrine (1, 2, 5, and 10 ml of normal saline).


METHODS
large animal research facility of a university medical center.


METHODS
epinephrine (0.02 mg/kg) diluted with four different volumes (1, 2, 5, and 10 ml) of normal saline was injected into the ET tube of five anesthetized dogs. Each dog served as its own control and received all four volumes in different sequences at least 1 week apart. Arterial blood samples for plasma epinephrine concentration and 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 polygraph recorder.


RESULTS
higher volumes of diluent (5 and 10 ml) caused a significant decrease of PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of diluent (1 and 2 ml), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects persisted for over 30 min. Mean plasma epinephrine concentrations significantly increased within 15 s following administration for all the volumes of diluent. Mean plasma epinephrine concentrations, maximal epinephrine concentration (Cmax) and the coefficient of absorption (Ka) were higher in the 5 and 10 ml groups. The time interval to reach maximal concentration (Tmax) was shorter in the 5 and 10 ml groups. Yet these results were not significantly different. Heart rate, systolic and diastolic blood pressures did not differ significantly between the groups throughout the study.


CONCLUSIONS
Dilution of endotracheal epinephrine into a 5 ml volume with saline optimizes drug uptake and delivery without adversely affecting oxygenation and ventilation.
Paret
G
G
Pediatric ICU, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Vaknin
Z
Z
Ezra
D
D
Peleg
E
E
Rosenthal
T
T
Vardi
A
A
Mayan
H
H
Barzilay
Z
Z
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D016887:Cardiopulmonary Resuscitation; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007442:Intubation, Intratracheal; D008297:Male; D010100:Oxygen / Q000097:blood; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D002245:Carbon Dioxide; D012965:Sodium Chloride; D010100:Oxygen; D004837:Epinephrine