Carbon Dioxide Response Curves

Inspiration of carbon dioxide in normal subjects increases minute ventilation by approximately 3 L/min per 1 mm Hg of arterial carbon dioxide tension. This observation demonstrates a high gain from the central chemoreceptor in response to variations in arterial carbon dioxide tension. The slope of the relationship between minute ventilation and arterial carbon dioxide tension is an index of ventilatory drive provided that hypoxic conditions are avoided to minimize peripheral chemoreceptor stimulation. NO is increased in the carotid bodies during hypoxia,^[304] plays an inhibitory role in the peripheral and central chemoreflex pathways during hypoxia,^[305] and may act as a respiratory stimulant under normoxic conditions.^[306] Experiments determining the relationship between minute ventilation and arterial carbon dioxide tension should be interpreted with these potential confounding variables in mind. All inhaled anesthetics depress the ventilatory response to hypercarbia in a dose-dependent fashion.^{[224] [225] [226] [231] [232] [307]} High concentrations of volatile anesthetics may almost

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The effects of small doses of inhaled anesthetics on ventilatory responses to hypercarbia remain somewhat controversial despite intense investigation. Several studies have demonstrated that subanesthetic concentrations (e.g., 0.1 MAC) of inhaled anesthetics (with the exception of desflurane and nitrous oxide) depress the peripheral chemoreflex loop by approximately 30% to inhibit the ventilatory response to hypercarbia.^{[309] [310] [311] [312] [313]} The response was also attenuated during administration of desflurane when a level of sedation comparable with sleep was achieved.^[309] At higher concentrations of volatile agents, other sites, including the central chemoreceptors, may also be affected. In marked contrast, results from Pandit and coworkers^[314] showed that subanesthetic sevoflurane did not affect the response to acute or sustained hypercapnia.^[314] The discrepancies in these results may be related to the sustained nature of the hypercapnic responses or, more likely, to differences in the state of central nervous system arousal under baseline conditions.^[312] Unlike the effects of small doses of inhaled anesthetics on peripheral chemoreceptors, the intravenous agent propofol depresses the hypercapnic-induced ventilatory response at the level of the central chemoreceptors.^[315]

Depression of ventilatory responsiveness to inhaled carbon dioxide is clinically important. Carbon dioxide accumulation and concomitant acidemia may cause dysfunction in several organs, including the heart, where this condition may produce potentially dangerous arrhythmias. The attenuation of the normal ventilatory responses to elevated arterial carbon dioxide tension makes clinical diagnosis of hypercarbia difficult independent of actual measurement of arterial blood gases or end-tidal carbon dioxide concentration. The respiratory system is less able to compensate for elevations in carbon dioxide tensions that occur in response to rebreathing carbon dioxide from malfunctioning anesthetic circuits or resulting from increased metabolic production of this gas during anesthesia. Reduced ventilatory drive to hypercapnia may also occur in the immediate postoperative period and contribute to significant morbidity. Pietak and associates^[297] showed that patients with chronic obstructive pulmonary disease demonstrated a reduced ability to respond to increased arterial carbon dioxide tension during anesthesia.

Experimental studies have shown that carbon dioxide rebreathing recruits expiratory respiratory muscles, including the internal intercostals, but does not reverse the profound depression of parasternal intercostal muscle activity produced by halothane.^[316] There is a prolongation of expiration leading to a decrease in respiratory rate during the course of rebreathing. These alterations in individual respiratory muscle control of ventilation during breathing are different in halothane-anesthetized dog than in humans,^[317] but these species differences do not necessarily imply that other systems responsible for respiratory control are also dissimilar between species. Halothane depressed the peripheral chemoreceptor transduction (i.e., phrenic nerve response) to an acute, severe carbon dioxide stimulation of the peripheral chemoreceptors in paralyzed, vagotomized dogs in a dose-related manner.^[318] Carbon dioxide sensitivity was diminished but not abolished by doses of halothane typically required for surgical anesthesia. It appears that halothane depresses peripheral and central carbon dioxide sensitivities to similar degrees,^[319] but the peripheral chemoreceptors contribute only approximately 15% of the total carbon dioxide sensitivity. The response of peripheral chemoreceptors may not initially appear to be of less clinical significance. However, if the peripheral chemoreceptor response to hypoxia is abolished by low concentrations of inhaled anesthetics, this action may contribute to a marked respiratory impairment during the concomitant episodes of hypercarbia and hypoxia that are known to occur in the perioperative period.