Anesthesiology
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Comparative Study
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. ⋯ 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.
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To determine the effects of cardiopulmonary bypass (CPB) and hypothermia on the neuromuscular blockade produced by pancuronium, this relaxant was infused intravenously into 10 anesthetized patients to produce and maintain 90% depression of the twitch tension of the adductor pollicis muscle following supramaximal ulnar nerve stimulation. Infusion rates, plasma concentration of pancuronium, and adductor pollicis temperature were measured every 15 min. During the normothermic period preceding the start of CPB, the pancuronium requirement, the pancuronium plasma concentration, and muscle temperature were mean (mean +/- SEM): 238 +/- 12 micrograms . m-2 . 15 min-1, 0.31 +/- 0.01 microgram/ml, and 33.9 +/- 0.1 degrees C, respectively. ⋯ After the muscle temperature was returned to 34 +/- 0.6 degrees C, the plasma pancuronium concentration and requirements increased to 0.35 +/- 0.05 microgram/ml and 392 +/- 32 micrograms . m-2 . 15 min-1 (P less than 0.001), respectively. After CPB, these values were 0.39 +/- 0.04 microgram/ml and 239 +/- 25 microgram . m-2 . 15 min-1. These results demonstrate that pancuronium requirements are increased at the beginning of CPB because of circulatory volume changes and again during rewarming of the patient once muscle temperature reaches about 34 degrees C.