ET-26 hydrochloride (ET-26 HCl) has similar hemodynamic stability to that of etomidate in normal and uncontrolled hemorrhagic shock (UHS) rats

OBJECTIVE: ET-26 HCl is a promising sedative–hypnotic anesthetic with virtually no effect on adrenocortical steroid synthesis. However, whether or not ET-26 HCl also has a sufficiently wide safety margin and hemodynamic stability similar to that of etomidate and related compounds remains unknown. In this study, the effects of ET-26 HCl, etomidate and propofol on therapeutic index, heart rate (HR), mean arterial pressure (MAP), maximal rate for left ventricular pressure rise (D(max)/t), and maximal rate for left ventricular pressure decline (D(min)/t) were investigated in healthy rats and a rat model of uncontrolled hemorrhagic shock (UHS). METHODS: 50% effective dose (ED(50)) and 50% lethal dose (LD(50)) were determined after single bolus doses of propofol, etomidate, or ET-26 HCl using the Bliss method and the up and down method, respectively. All rats were divided into either the normal group and received either etomidate, ET-26 HCl or propofol, (n = 6 per group) or the UHS group and received either etomidate, ET-26 HCl or propofol, (n = 6 per group). In the normal group, after preparation for hemodynamic and heart-function monitoring, rats were administered a dose of one of the test agents twofold-higher than the established ED(50), followed by hemodynamic and heart-function monitoring. Rats in the UHS group underwent experimentally induced UHS with a target arterial pressure of 40 mmHg for 1 hour, followed by administration of an ED(50) dose of one of the experimental agents. Blood-gas analysis was conducted on samples obtained during equilibration with the experimental setup and at the end of the experiment. RESULTS: In the normal group, no significant differences in HR, MAP, D(max)/t and D(min)/t (all P > 0.05) were observed at any time point between the etomidate and ET-26 HCl groups, whereas HR, MAP and D(max)/t decreased briefly and D(min)/t increased following propofol administration. In the UHS group, no significant differences in HR, MAP, D(max)/t and D(min)/t were observed before and after administration of etomidate or ET-26 HCl at ED(50) doses (all P > 0.05). Administration of propofol resulted in brief, statistically significant reductions in HR and D(max)/t, with a brief increase in D(min)/t (P ˂ 0.05), while no significant differences in MAP were observed among the three groups. The blood-lactate concentrations of rats in the ET-26 HCl group were significantly lower than those in etomidate and propofol groups (P ˂ 0.05). CONCLUSIONS: ET-26 HCl provides a similar level of hemodynamic stability to that obtained with etomidate in both healthy rats, and rat models of UHS. ET-26 HCl has the potential to be a novel induction anesthetic for use in critically ill patients.