Effect of vehicle on the nasal absorption of epinephrine during cardiopulmonary resuscitation

• Published in: Pharmacotherapy Vol. 16; no. 6; p. 1039
• Main Authors: Bleske, B E, Rice, T L, Warren, E W, Giacherio, D A, Gilligan, L J, Massey, K D, Chrisp, C E, Tait, A R
• Format: Journal Article
• Language: English
• Published: United States 01.11.1996
• Subjects: Administration, Intranasal; Adrenergic Agonists - administration & dosage; Animals; Blood Pressure - drug effects; Cardiopulmonary Resuscitation; Detergents; Dogs; Drug Carriers; Drug Delivery Systems; Epinephrine - administration & dosage; Epinephrine - blood; Nasal Mucosa - drug effects; Nasal Mucosa - pathology; Phentolamine - administration & dosage; Polyethylene Glycols; Single-Blind Method; Taurodeoxycholic Acid; Ventricular Fibrillation - therapy
• ISSN: 0277-0008
• DOI: 10.1002/j.1875-9114.1996.tb03030.x

We have shown in previous studies that epinephrine administered intranasally is a feasible route of administration during cardiopulmonary resuscitation (CPR). To promote the absorption of epinephrine we administered phentolamine prior to epinephrine and used a bile salt as a vehicle to dissolve the epinephrine. The purpose of this study was to compare the effect of two different vehicles (bile salt vs surfactant) in promoting the absorption of nasally administered epinephrine during CPR and to determine their effects on the nasal mucosa. A randomized, blinded study. A controlled laboratory environment. Eleven mongrel dogs. Each dog underwent 3 minutes of unassisted ventricular fibrillation (VF) followed by 7 minutes of VF with CPR. Five minutes after the start of VF, 10 dogs received intranasal phentolamine 0.25 mg/kg/nostril followed 1 minute later by intranasal epinephrine 7.5 mg/kg/nostril. The epinephrine was dissolved in a randomly assigned vehicle consisting of either taurodeoxycholic acid (group A, bile salt) or polyoxyethylene-9-lauryl ether (group B, surfactant). One animal acted as a control and received 0.9% sodium chloride nasally. Data from eight dogs (one control) were included for analysis. Histology of the nasal cavity demonstrated severe multifocal erosion and ulceration of the respiratory epithelium for groups A and B compared with the control. The severity was similar between the two groups. In addition, no significant differences in plasma epinephrine concentrations or blood pressure responses were seen between the groups. Based on histology, polyoxyethylene-9-lauryl ether offered no advantage over taurodeoxycholic acid in its effect on the nasal mucosa. The data available for changes in epinephrine concentration and pressure also suggest no difference between the two vehicles in promoting the absorption of epinephrine during CPR in an animal model.