Evaluation of mean arterial blood pressure, heart rate, and sympathetic nerve activity in rabbits after administration of two formulations of etomidate

Abstract

ObjectiveTo evaluate and compare the effects of the aqueous sulfobutyl ether β-cyclodextrin (SBE-CD) etomidate formulation and the commercial etomidate formulation on mean arterial pressure (MAP), heart rate, and sympathetic outflow using neuraxis-intact and baro-denervated rabbits. Study designProspective experimental study. AnimalsTwenty-seven male New Zealand white rabbits. MethodsUnder basal anesthesia (urethane) and ventilation with intermittent positive pressure (IPPV), the New Zealand white rabbits underwent surgical preparation including isolation of the left renal sympathetic nerve and, in the baro-denervated models, additional combined denervation of bilateral carotid sinus, aortic, and vagal nerves. After hemodynamic stabilization, both neuraxis-intact and baro-denervated animals received bolus intravenous (IV) injection (0.6 mg kg−1) of either the SBE-CD or commercial etomidate formulation over 5 seconds (n = 6 animals per group). ResultsMean arterial pressure decreased significantly in all four groups to the same extent. However, the rate of MAP decrease was lower in the SBE-CD-treated groups relative to the commercial formulation. Renal sympathetic nerve activity was decreased significantly less in the SBE-CD group in the baro-denervated studies. Independent pharmacokinetic evaluation demonstrated that the two formulations had comparable plasma concentration–time profiles. Conclusions and Clinical relevanceEtomidate in the commercial drug product is solubilized with propylene glycol, a cosolvent associated with adverse side effects on injection. An aqueous formulation of etomidate has been developed, which utilizes SBE-CD as a solubilizing agent. The data suggest that the SBE-CD etomidate formulation may be a safer IV induction formulation than the commercial etomidate drug product.