FACTORS MODIFYING THE RATIO OF ALVEOLAR ANESTHETIC CONCENTRATION TO INSPIRED ANESTHETIC CONCENTRATION

Alteration of factors that govern the rate of delivery of anesthetic to the lungs or its removal from the lungs changes the alveolar concentration of anesthetic. We have seen the importance of differences in solubility (see Fig. 5-2 ). The following sections examine the impact of differences in ventilation and circulation and the interaction of these differences with factors such as solubility.

Effect of Ventilatory Changes

By augmenting delivery of anesthetic to the lungs, an increased ventilation accelerates the rate of rise of FA/FI ( Fig. 5-5 ).^{[1] [33] [34]} A change in ventilation produces a greater relative change in FA/FI with a more soluble anesthetic.

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Figure 5-5 The alveolar concentration of anesthetic/concentration of inspired anesthetic (FA/FI ratio) rises more rapidly if ventilation is increased. Solubility modifies this impact of ventilation; the effect on the anesthetizing partial pressure is greatest with the most soluble anesthetic (ether) and least with the least soluble anesthetic (nitrous oxide). (Adapted from Eger EI II: Ventilation, circulation and uptake. In Eger EI II [ed]: Anesthetic Uptake and Action. Baltimore, Williams & Wilkins, 1974, pp 122–145.)

The impact of solubility may be explained as follows. With a poorly soluble agent, such as nitrous oxide, the rate of rise of FA/FI is rapid, even with hypoventilation. Because FA normally cannot exceed FI, augmentation of ventilation can increase FA/FI but slightly. With a highly soluble agent, such as ether and methoxyflurane, most of the anesthetic delivered to the lungs is taken up, so that if the uptake at 2 L/min ventilation equaled X, the uptake at 4 L/min would approach 2X. If cardiac output is held constant, ventilation of 4 L/min produces an arterial ether concentration that is nearly twice the concentration produced by a ventilation of 2 L/min. Because arterial and alveolar concentrations are in equilibrium, this example suggests that doubling ventilation must nearly double the concentration of a highly soluble anesthetic in lung or blood.

These observations imply that imposed alterations in ventilation (e.g., an increase produced by conversion from spontaneous to controlled ventilation) produce greater changes in anesthetic effect with more soluble agents. Because such effects include anesthetic depth and depression of circulation, greater caution must be exercised when ventilation is augmented during anesthesia produced with a highly soluble agent.

Anesthetics themselves may alter ventilation and thereby alter their own uptake.^{[10] [35]} Modern potent agents (e.g., desflurane, enflurane, halothane, isoflurane, sevoflurane) can profoundly depress respiration, doing so in a dose-related manner.^{[36] [37] [38] [39] [40]} At some dose, all inhaled anesthetics produce apnea, a feature that limits the MAC that can be obtained if ventilation is spontaneous.

Anesthetic-induced respiratory depression significantly decreases delivery of anesthetic to the alveoli.^{[10] [41]} Doubling the inspired concentration does not double the alveolar concentration attained at a given point in time. At high inspired concentrations, further increases in inspired concentration produce little absolute change in the alveolar concentration ( Fig. 5-6 ). Anesthetics thereby exert a negative feedback effect on their own alveolar concentration, an effect that increases the safety of spontaneous ventilation by limiting the maximum concentration attained in the alveoli.

Figure 5-6 An increase in the inspired halothane concentration does not produce a proportional increase in the alveolar concentration because of the progressively greater depression of ventilation that occurs as alveolar halothane is increased. The initial "overshoot" seen with 10% to 20% inspired halothane results from the delay in the transfer of alveolar halothane partial pressure to the brain. FA/FI is the alveolar concentration of anesthetic/concentration of inspired anesthetic. (Adapted from Munson ES, Eger EI II, Bowers DL: Effects of anesthetic-depressed ventilation and cardiac output on anesthetic uptake. Anesthesiology 38:251–259, 1973.)