INFLUENCES OF SUBANESTHETIC ISOFLURANE ON VENTILATORY CONTROL IN HUMANS

Background: The purpose of this study was to quantify in humans the ef fects of subanesthetic isoflurane on the ventilatory control system, i n particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isof lurane wash-in upon sustained hypoxic steady-state ventilation, and th e ventilatory response at the onset of 20 min of isocapnic hypoxia. Me thods: Study 1: Square-wave changes in end-tidal carbon dioxide tensio n (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, c entral component, characterized by a time constant, carbon dioxide sen sitivity, time delay, and off-set (apneic threshold). Study 2: The ven tilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min afte r the induction of isocapnic hypoxia, were studied in 11 healthy volun teers. Study 3: The ventilatory responses to a step decrease in end-ti dal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 br eaths; duration of hypoxia 20 min) were assessed in eight healthy volu nteers at 0, 0.1, and 0.2 MAC isoflurane. Results: Values are reported as means +/- SE. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 1 . min(-1). mmHg( -1) (isoflurane; P < 0.01). The central carbon dioxide sensitivities ( control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 1 . min(-1). mmHg(- 1)) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0. 2 mmHg) did not differ between treatments. Study 2: Within 30 s of exp osure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 1 . min(-1) (hypoxia, i soflurane). Study 3: At the initiation of hypoxia ventilation increase d by 7.7 +/- 1.4 (control), 4.1 + 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) 1 . min(-1). The subs equent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0. 5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) 1 . min(-1). There was a good correla tion between the acute hypoxic response and the hypoxic ventilatory de crease (r = 0.9; P < 0.001). Conclusions: The results of all three stu dies indicate a selective and profound effect of subanesthetic isoflur ane on the peripheral chemoreflex loop at the site of the peripheral c hemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.