Speed of onset and offset and mechanisms of ventilatory depression from sevoflurane: An experimental study in the cat

Abstract

Background: Inhalational anesthetics depress breathing dose dependently. The authors studied the dynamics of ventilation on changes in end-tidal sevoflurane partial pressure. To learn more about the mechanisms of sevoflurane-induced respiratory depression, the authors also studied its influence on the dynamic ventilatory response to carbon dioxide. Methods: Experiments were performed in cats anesthetized with α chloralose-urethane. For protocol 1, step changes in end-tidal sevoflurane partial pressure were applied and inspired ventilation was measured. Breath-to-breath inspired ventilation was related to the sevoflurane concentration in a hypothetical effect compartment based on an inhibitory sigmoid Emax model. For protocol 2, step changes in the end-tidal partial pressure of carbon dioxide were applied at 0, 0.5, and 1% end-tidal sevoflurane. The inspired ventilation-end-tidal partial pressure of carbon dioxide data were analyzed using a two- compartment model of the respiratory controller, which consisted of a fast peripheral and slow central compartment. Values are the mean ± SD. Results: In protocol 1, the effect-site half-life of respiratory changes caused by alterations in end-tidal sevoflurane partial pressure was 3.6 ± 1.0 min. In protocol 2, at 0.5% sevoflurane, the central and peripheral carbon dioxide sensitivities decreased to 43 ± 20% and 36 ± 18% of control. At 1% sevoflurane, the peripheral carbon dioxide sensitivity decreased further, to 12 ± 13% of control, whereas the central carbon dioxide sensitivity showed no further decrease. Conclusions: Steady state inspired ventilation is reached after 18 min (i.e., 5 half-lives) on stepwise changes in end-tidal sevoflurane. Anesthetic concentrations of sevoflurane have, in addition to an effect on pathways common to the peripheral and central chemoreflex loops, a selective effect on the peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory control in humans and cats.