INFLUENCE OF 0.1 MINIMUM ALVEOLAR CONCENTRATION OF SEVOFLURANE, DESFLURANE AND ISOFLURANE ON DYNAMIC VENTILATORY RESPONSE TO HYPERCAPNIA INHUMANS

To assess the effects and site of action of a subanaesthetic concentra tion of isoflurane, desflurane and sevoflurane (0.1 minimum alveolar c oncentration (MAC)) on respiratory control, we measured the ventilator y response to square wave changes in PECO2' against a background of no rmoxia. Using the computer steered ''end-tidal forcing system'', 2 min of steady state ventilation were followed by a step increase in PECO2 ' (1-1.5 kPa). This level was maintained for 8 min, followed by a step decrease to the original value for another 8 min. Each hypercapnic re sponse was separated into a fast, peripheral component and a slow, cen tral component, characterized by a time constant, carbon dioxide sensi tivity, time delay and off-set. We studied 25 healthy volunteers; they performed 2-3 studies without and 23 studies during inhalation of the anaesthetic agent. Level of sedation was scored using a subjective se ven-point scale from 0 (= alert and awake) to 6 (unrousable). In the i soflurane (16 subjects, 33 control, 37 drug studies) and sevoflurane ( 15 subjects, 40 control, 41 drug studies) studies, peripheral carbon d ioxide sensitivity was reduced by approximately 45% and approximately 27% (ANOVA, P < 0.05 vs control), respectively, without affecting cent ral carbon dioxide sensitivity or apnoeic threshold. In the desflurane study (16 subjects, 36 control, 37 drug studies), no significant effe ct was observed for any of the variables measured. A significant relat ion was observed between sedation score and change from control in cen tral carbon dioxide sensitivities in the isoflurane and desflurane stu dies and in the change in the ratio peripheral carbon dioxide sensitiv ity over total carbon dioxide sensitivity in the sevoflurane studies. At the highest level of sedation observed (score 3-arousal state compa rable with ''light sleep''-in three subjects) these latter variables d iffered significantly from those in the other observed sedation levels (scores 1 and 2-a state of drowsiness). We conclude that 0.1 MAC of i soflurane and sevoflurane depressed the peripheral chemoreflex loop, w ithout affecting the central chemoreflex loop. Desflurane at the same MAC showed no effect on peripheral and central carbon dioxide sensitiv ity. When the level of sedation was considered, our data suggested tha t at levels of sedation comparable with sleep, a depressive effect of all three anaesthetics was observed on the central chemoreflex loop.