title: Effect of dose on the nasal absorption of epinephrine during cardiopulmonary resuscitation.
abstract: Delay in epinephrine administration during cardiopulmonary resuscitation (CPR) due to technical difficulties in obtaining an access site may be detrimental. To avoid this potential delay, we have previously shown that intranasal administration of phentolamine and epinephrine is a rapidly obtainable and feasible route of administration during CPR. A randomized blinded dose ranging study was performed in a controlled laboratory environment. Thirty mongrel dogs were randomized to one of the following dosage regimens: phentolamine, 0.25 or 2.5 mg/kg/nostril; epinephrine, 0.075, 0.75, or 7.5 mg/kg/nostril. Phentolamine was administered intranasally 1 minute before the intranasal administration of epinephrine to improve absorption. Each dog underwent 3 minutes of ventricular fibrillation followed by 7 minutes of closed chest CPR. Epinephrine was administered was administered at 3 minutes of CPR. Data from 26 dogs were included for analysis. Treatment B (0.25 and 7.5 mg/kg/nostril of phentolamine and epinephrine, respectively) produced the greatest elevation in coronary perfusion pressure (17 +/- 11 vs. 4 +/- 3 mm Hg for the next highest group, P < .003) and in epinephrine plasma concentrations (1,403 +/- 1,400 vs 290 +/- 182 ng/mL for the next highest group, P > .05). In addition, treatment B had the highest resuscitation rate, 100% (5/5) versus 0% to 50% for the other groups (P < .05). These data show that there is a dose response effect, with 0.25 and 7.5 mg/kg/nostril of phentolamine and epinephrine being the optimal dose studied. In addition, when administered in appropriate doses, intranasal epinephrine reaches the systemic circulation and increases coronary perfusion pressure and successful resuscitation during CPR in this canine model.
authors.affiliation: University of Michigan College of Pharmacy, Ann Arbor 48109-1065, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Bleske
authors.forename: T L
authors.initials: TL
authors.lastname: Rice
authors.forename: E W
authors.initials: EW
authors.lastname: Warren
authors.forename: D A
authors.initials: DA
authors.lastname: Giacherio
authors.forename: L J
authors.initials: LJ
authors.lastname: Gilligan
authors.forename: K D
authors.initials: KD
authors.lastname: Massey
authors.forename: A R
authors.initials: AR
authors.lastname: Tait
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D001794:Blood Pressure; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006439:Hemodynamics; D013566:Sympathomimetics / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D001993:Bronchodilator Agents; D013566:Sympathomimetics; D004837:Epinephrine