Comparison of isoflurane and halothane safety margins in rats.

In rat experiments, the dose-effect curves for three different end points of anesthesia [loss of righting reflex (RR), prevention of movement (PM), and heart rate response (HR) to noxious stimuli] and for the lethal effect (LE) due to cardiovascular depression were determined with isoflurane and halothane. The obtained data were used to calculate LD50/ED50 ratios and standard safety margins (SSM) for assessment of each agent's safety. It was found that isoflurane provides an equal degree of separation between dose-effect curves for different end points of anesthesia as halothane does. However, isoflurane provides greater margins of safety. The margin between the highest of anesthetic doses--the loss of HR response--and the lethal dose for isoflurane was twice that for halothane (LD50/HR ED50 4.3 vs. 2.2, P less than 0.01). The standard safety margin for the loss of HR response was also greater with isoflurane (142 vs. 43, P less than 0.05). These results agreed that isoflurane may provide greater cardiovascular safety for anesthesia than halothane does.