Bleske B E, Rice T L, Warren E W, Giacherio D A, Gilligan L J, Massey K D, Chrisp C E, Tait A R
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
Pharmacotherapy. 1996 Nov-Dec;16(6):1039-45.
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.
我们在先前的研究中表明,鼻内给予肾上腺素是心肺复苏(CPR)期间一种可行的给药途径。为促进肾上腺素的吸收,我们在给予肾上腺素之前先给予酚妥拉明,并使用胆盐作为载体来溶解肾上腺素。本研究的目的是比较两种不同载体(胆盐与表面活性剂)在CPR期间促进鼻内给予肾上腺素吸收的效果,并确定它们对鼻黏膜的影响。
一项随机、盲法研究。
受控实验室环境。
11只杂种犬。
每只犬先经历3分钟无辅助心室颤动(VF),随后进行7分钟有CPR的VF。VF开始5分钟后,10只犬每侧鼻孔给予0.25 mg/kg酚妥拉明,1分钟后每侧鼻孔给予7.5 mg/kg肾上腺素。肾上腺素溶解于随机分配的载体中,载体为牛磺脱氧胆酸(A组,胆盐)或聚氧乙烯-9-月桂基醚(B组,表面活性剂)。1只动物作为对照,鼻内给予0.9%氯化钠。
纳入8只犬(1只对照)的数据进行分析。鼻腔组织学检查显示,与对照组相比,A组和B组的呼吸上皮有严重的多灶性糜烂和溃疡。两组的严重程度相似。此外,两组之间在血浆肾上腺素浓度或血压反应方面未见显著差异。
基于组织学检查,聚氧乙烯-9-月桂基醚在对鼻黏膜的影响方面并不优于牛磺脱氧胆酸。关于肾上腺素浓度和血压变化的现有数据也表明,在动物模型的CPR期间,两种载体在促进肾上腺素吸收方面没有差异。