Speed of onset and offset and mechanisms of ventilatory depression from sevoflurane: an experimental study in the cat.
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 alpha 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 0.50% 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.
Dahan
A
A
Department of Anesthesiology, Leiden University Medical Center, The Netherlands. adahan@anst.azl.nl
Olofsen
E
E
Teppema
L
L
Sarton
E
E
Olievier
C
C
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002628:Chemoreceptor Cells / Q000502:physiology; D005260:Female; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000503:physiopathology; D000077149:Sevoflurane; D013997:Time Factors
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane