The acute hypoxic ventilatory response under halothane, isoflurane, and sevoflurane anaesthesia in rats*

Background: Hypoxia is a potent respiratory stimulus that evokes hypoxic ventilatory response, (HVR) in mammals. Volatile anesthetics alter the magnitude and pattern of breathing. The basic respiratory behavior of anesthetized animals can be described by observing the phrenic nerve activity recorded as the phrenic neurogram (PNG). The relative order of potency of anesthetic agents on hypoxic ventilatory response was tested in humans, but has not been shown directly in an animal model. We tested the hypothesis that the relative order of potency on the phrenic nerve response to acute normocapnic hypoxia in rats was halothane > isoflurane > sevoflurane monoanesthesia. Methods: Studies were performed in adult male Sprague-Dawley rats, bilaterally vagotomized and mechanically ventilated. PNG was recorded with a bipolar electrode. We examined the effects of 1.4, 1.6, 1.8, and 2.0 minimum alveolar concentration (MAC) of halothane, isoflurane, and sevoflurane on the baseline phrenic nerve activity, as well as during acute normocapnic hypoxia, induced by mixture of 9% oxygen in balance nitrogen. Results: Halothane monoanesthesia made all animals apneic and HVR was abolished at all studied levels. During 1.4 MAC isoflurane monoanesthesia, 5/14 animals were above apneic threshold and in 10/14 animals hypoxia evoked marked increase in the peak amplitude of PNG by 200± 27% (mean± SE ; P=0.003). At 1.6, 1.8, and 2.0 MAC of isoflurane all animals were apneic at baseline and the HVR was abolished. During the sevoflurane monoanesthesia, at 1.4, and 1.6 MAC, there were 7/13 and 9/13, apneic animals, respectively. Hypoxia evoked PNG in all animals tested. An increase in the peak amplitude of PNG was 282± 48% P=0.030, and 161± 25% ; P=0.038, respectively. At 1.8 MAC, HVR was still induced in 8/13, and at 2.0 MAC in 6/13 animals. Conclusion: The results of the study confirmed in animals the hypothesis that the relative order of potency of volatile anesthetic agents regarding hypoxic ventilatory response (HVR) was halothane>isoflurane>sevoflurane monoanesthesia on the phrenic nerve response to acute normocapnic hypoxia in rats. HVR was still preserved in about one half of the animals at 2.0 MAC sevoflurane monoanesthesia.