Cardiovascular Safety and Actions of High Concentrations of I-653 and Isoflurane in Swine

Abstract

The ratio of lethal-to-anesthetic concentration can be used to define the margin of safety of an inhaled anesthetic. In mechanically ventilated swine the fatal concentration of I-653, a new inhaled anesthetic, was 23.9 .+-. 0.06% (mean .+-. SE), and of isoflurane, 6.22 .+-. 0.23%. The ratio of fatal anesthetic concentration-to-MAC for I-653 (2.45 .+-. 0.11) was less than that determined for isoflurane (3.02 .+-. 0.13; P < 0.01) but relatively greater than that reported previously for other inhaled anesthetics. As with other inhaled anesthetics, the concentration of I-653 causing cardiovascular collapse exceeds that producing apnea, making cardiovascular collapse during spontaneous ventilation unlikely. Mean aortic blood pressure and cardiac output decreased as linear functions of anesthetic concentration. Values for these variables for isoflurane were greater than those for I-653 at concentrations exceeding 1.5 MAC. Heart rate, blood lactate concentration, and base-deficit did not change with anesthetic depth.Mixed venous PO2, mixed venous oxyhemoglobin saturation, and the ratio of oxygen transport to oxygen consumption remained at or above values in conscious swine but decreased similarly with both anesthetics when anesthetic concentration increased to within 0.5 MAC of the fatal concentration. Thus, the latter three variables, reflecting the fraction of delivered oxygen that is consumed, and "mean" tissues PO2 appear to be useful indices of anesthetic concentrations approaching those producing cardiovascular collapse.