CO2 response curve
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The chemical control of breathing is based on a negative feedback loop and chemoreflex. Thus, when the central and peripheral chemoreceptors sense an increase in [H+], breathing is stimulated by a chemoreflex that includes the central nervous system, respiratory muscles, and changes in alveolar ventilation, resulting in correction of the [H+], hence the negative feedback designation of the system. However, in addition to chemical stimuli, non-chemical drives to breathe also contribute to the level of ventilation, independently of the chemoreflexes. These drives include the central nervous system "state" of the subject, which is referred to as the "waking neural drive," because it is withdrawn during sleep.
Inspiration of carbon dioxide in healthy, awake subjects increases minute ventilation by approximately 3 L/min per 1 mm Hg of arterial carbon dioxide tension. All inhaled anesthetics depress the ventilatory response to hypercarbia in a dose-dependent fashion. High concentrations of volatile anesthetics may almost entirely eliminate hypercarbia-induced increases in ventilatory drive. The slope of the minute ventilation-arterial carbon dioxide tension relation returns toward normal after 6 hours of halothane anesthesia, but ventilatory responsiveness to carbon dioxide remains profoundly depressed despite this observation.
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. The response was also attenuated during administration of desflurane when a level of sedation comparable with sleep was achieved. At higher concentrations of volatile agents, other sites, including the central chemoreceptors, may also be affected.
The response of two common classes of IV anesthetics are subtly different - opioids create a right-shift in the CO2 response curves, whereas benzodiazepines and propofol decrease the slope
Hypoxemia (paO2 < 65 mm Hg) leads to a left-shift in the CO2 response curve. The other two causes of left-shift are metabolic acidemia and central etiologies
CO2 Response Curve
- Volatile Anesthetics: decrease the response (slope AND right-shift) to CO2 (although low doses ~ 0.1 MAC controversial)
- Opioids: right-shift the ventilatory response curves (slope may change at high doses)
- Benzodiazepines: decrease the slope of the ventilatory response curves
- Propofol: decrease the slope of the ventilatory response curves (58% reduction at 100 ucg/kg/min)
- Hypoxemia: at less than 65 mm Hg paO2, the CO2 response curve is left-shifted
Miller, RD et al. Miller's Anesthesia, 7th ed, Churchill Livingstone: Chapters 22, 26. 2009 (ISBN 9780443069598)
Barash, PG. Clinical Anesthesia, 6th ed, LWW: p. 242, 2009 (ISBN 9780781787635)