EFFECTS OF SUBANESTHETIC HALOTHANE ON THE VENTILATORY RESPONSES TO HYPERCAPNIA AND ACUTE-HYPOXIA IN WEALTHY VOLUNTEERS

Background: The peripheral chemoreceptors are responsible for the ventilatory response to hypoxia (acute hypoxic response) and for 30% of the normoxic hypercapnic ventilatory response. To quantify the effects of subanesthetic concentrations of halothane on the respiratory control system, in particular on the peripheral chemoreceptors, we studied the response of humans to carbon dioxide and oxygen at two subanesthetic concentrations of halothane. Methods: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.3 mmHg) and step decreases in end-tidal oxygen tension (arterial hemoglobin oxygen saturation 82 +/- 2%; duration of hypoxia 5 min) were performed in nine healthy male subjects during 0, 0.05 (HA-1), and 0.1 minimum alveolar concentration (HA-2) halothane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set. Results: Fifty-six carbon dioxide responses and 27 oxygen-responses were obtained. The peripheral carbon dioxide sen- sitivities averaged to 0.76 +/- 0.14 1.min(-1).mmHg(-1) (control), 0.50 +/- 0.12 1.min(-1).mmHg(-1) (HA(-1)), and 0.30 +/- 0.08 1.min(-1).mmHg(-1) (HA-2; P < 0.01 vs. control). The central carbon dioxide sensitivity did not differ significantly among treatment groups (control, 1.47 +/- 0.22 1.min(-1).mmHg(-1); HA-1, 1.41 +/- 0.51 1.min(-1).mmHg(-1); and HA-2, 1.23 +/- 0.30 1.min(-1).mmHg(-1)). The time constants of the central chemoreflex loop showed a large decrease during the administration of 0.1 minimum alveolar concentration halothane. The acute hypoxic response declined from 15.0 +/- 3.91.min(-1) to 10.9 +/- 2.91.min(-1) (HA-1) and 4.8 +/- 1.41.min(-1) (HA-2; P < 0.01 vs. control and HA-1). All values are means +/- SEM. Conclusions: The results show depression of the ventilatory responses to hypoxia and hypercapnia during inhalation of subanesthetic concentrations of halothane. The depression is attributed to a selective effect of halothane on the peripheral chemoreflex loop. The oxygen and carbon dioxide responses mediated by the peripheral chemoreceptors are affected proportionally. It is argued that the decrease in central time constants is caused by an effect of halothane on central neuronal dynamics.