A. Factors Controlling Uptake 1. Inspired concentration and ventilation—The driving force for uptake of an inhaled anesthetic into the body is the ratio between inspired and alveolar concentration. The most important
FIGURE 25–2 Chemical structures of inhaled anesthetics.
parameter that can be controlled by the anesthesiologist to change alveolar concentration quickly is the inspired concentration or partial pressure. The partial pressure is the fraction of a gas mixture that a particular component comprises. For example, a mixture of gases that may be delivered by an anesthesia machine—70% nitrous oxide, 29% oxygen, and 1% isoflurane at normal barometric pressure (760 mm Hg)—contains partial pressures of 532 mm Hg nitrous oxide, 220 mm Hg oxygen, and 7.6 mm Hg isoflurane. The partial pressure of anesthetic in the inspired gas mixture determines the maximum partial pressure that can be achieved in the alveoli as well as the rate of rise of the partial pressure in the alveoli. To accelerate induction, the anesthesiologist increases the inspired anesthetic partial pressure to create a steeper gradient between inspired and alveolar partial pressure. This fractional rise of anesthetic partial pressure during induction is usually expressed as a ratio of alveolar concentration (FA) over inspired concentration (FI); the faster FA/FI approaches 1 (representing inspired-toalveolar equilibrium), the faster anesthesia onset will be during an inhaled induction.
The other parameter under control of the anesthesiologist that directly determines the rate of rise of FA/FI is alveolar ventilation. The anesthesiologist can increase the tidal volume and respiratory rate to deliver larger amounts of anesthetic agent faster. The magnitude of the effect is much greater for inhaled anesthetics with high blood solubility than for those with low blood solubility. The tendency for a given inhaled anesthetic to pass from the gas phase of the alveolus into the pulmonary capillary blood is determined by the blood:gas partition coefficient (see following section on Solubility and Table 25–1). As increased ventilation supplies more anesthetic molecules to the alveolus, a more soluble anesthetic (blood:gas partition coefficient > 1) will traverse the alveolar capillary membrane more readily, preventing a rise in its alveolar partial pressure. Thus, increased ventilation will replenish the alveolar anesthetic concentration for a highly soluble anesthetic but is not necessary for an anesthetic with low solubility. Therefore, an increase in ventilation produces only a small change in alveolar partial pressure of an anesthetic with low blood solubility, but can significantly increase the partial pressure of agents with moderate to high blood solubility such as halothane. As seen in Figure 25–3, a fourfold increase in the ventilation rate almost doubles the FA/FI ratio for halothane during the first 10 minutes
TABLE 25–1 Pharmacologic properties of inhaled anesthetics.
Halothane 2.30 2.9 0.75 >40% Medium rate of onset and recovery 1Partition coefficients (at 37°C) are from multiple literature sources. 2MAC is the anesthetic concentration that produces immobility in 50% of patients exposed to a noxious stimulus.
1.0 0.5
FIGURE 25–3 Effect of ventilation on FA/FI and induction of anesthesia. Increased ventilation (8 L/min versus 2 L/min) accelerates the rate of rise toward equilibration of both halothane and nitrous oxide but results in a larger percentage increase for halothane in the first few minutes of induction.
of administration but increases the FA/FI ratio for nitrous oxide by only 15%. Thus, hyperventilation increases the speed of induction of anesthesia with inhaled anesthetics that would normally have a slow onset.