Determinants of Alveolar Partial Pressure. The Pa and ultimately the P_BRAIN of inhaled anesthetics are determined by input (delivery) into alveoli minus uptake (loss) of the drug from alveoli into arterial blood (Table 4-2).

1. Inhaled Partial Pressure (PI). A high PI delivered from the anesthetic machine is required during initial administration of the anesthetic.

   1. A high initial input offsets the impact of uptake, accelerating induction of anesthesia as reflected by the rate of rise in the Pa and thus the P_BRAIN.

   2. With time, as uptake into the blood decreases, the PI should be decreased to match the decreased anesthetic uptake and therefore maintain a constant and optimal P_BRAIN.

2. Concentration Effect. The impact of PI on the rate of rise of the Pa of an inhaled anesthetic is known as the concentration effect (Fig. 4-4).

3. Second gas effect reflects the ability of high-volume uptake of one gas (first gas) to accelerate the rate of increase of the Pa of a concurrently administered “companion” gas (second gas) (Fig. 4-5).

4. Spontaneous versus Mechanical Ventilation. Inhaled anesthetics influence their own uptake by virtue of dose-dependent depressant effects on alveolar ventilation. This, in effect, is a negative-feedback protective mechanism that prevents establishment of an excessive depth of anesthesia (delivery of anesthesia is decreased when ventilation is decreased) when a high PI is administered during spontaneous breathing (Fig. 4-6).

5. Impact of Solubility. The impact of changes in alveolar ventilation on the rate of increase in the Pa toward the PI depends on the solubility of the anesthetic in blood. For example, changes in alveolar ventilation influence the rate of increase of the Pa of a soluble anesthetic (halothane, isoflurane) more than a poorly soluble anesthetic (nitrous oxide, desflurane, sevoflurane). Indeed, the rate of increase in the Pa of nitrous oxide is rapid regardless of the alveolar ventilation.

6. Anesthetic Breathing System. Characteristics of the anesthetic breathing system that influence the rate of increase of the Pa are the (a) volume of the external breathing system, (b) solubility of the inhaled anesthetics in the rubber or plastic components of the breathing system, and (c) gas inflow from the anesthetic machine.

Solubility. The solubility of the inhaled anesthetics in blood and tissues is denoted by the partition coefficient (Table 4-3). A partition coefficient is a distribution ratio describing how the inhaled anesthetic distributes itself between two phases at equilibrium (partial pressures equal in both phases).

1. Blood:Gas Partition Coefficients. The rate of increase of the Pa toward the PI (maintained constant by mechanical ventilation of the lungs) is inversely related to the solubility of the anesthetic in blood (see Fig. 4-3).

2. Tissue:blood partition coefficients determine uptake of anesthetic into tissues and the time necessary for equilibration of tissues with the Pa.

   1. The time for equilibration can be estimated by calculating a time constant (amount of inhaled anesthetic that can be dissolved in the tissue divided by tissue blood flow) for each tissue.

   2. One time constant on an exponential curve represents 63% equilibration. Three time constants are equivalent to 95% equilibration. For volatile anesthetics, equilibration between the Pa and P_BRAIN depends on the anesthetic’s blood solubility and requires 5 to 15 minutes (three time constants).

3. Nitrous Oxide Transfer to Closed Gas Spaces. The blood:gas partition coefficient of nitrous oxide (0.46) is about 34 times greater than that of nitrogen (0.014). This differential solubility means that nitrous oxide can leave the blood to enter an air-filled cavity 34 times more rapidly than nitrogen can leave the cavity to enter blood.

   1. As a result of this preferential transfer of nitrous oxide, the volume or pressure of an air-filled cavity increases.

   2. Passage of nitrous oxide into an air-filled cavity surrounded by a compliant wall (intestinal gas, pneumothorax, pulmonary blebs, air bubbles) causes the gas space to expand (Fig. 4-7). Conversely, passage of nitrous oxide into an air-filled cavity surrounded by a noncompliant wall (middle ear, cerebral ventricles, supratentorial space) causes an increase in intracavitary pressure.

Cardiac Output. Cardiac output (pulmonary blood flow) influences uptake and therefore Pa by carrying away either more or less anesthetic from the alveoli. An increased cardiac output results in more rapid uptake, so the rate of increase in the Pa and thus the induction of anesthesia is slowed. A decreased cardiac output speeds the rate of increase of the Pa because there is less uptake to oppose input.

1. Conceptually, a change in cardiac output is analogous to the effect of a change in solubility.

2. As with alveolar ventilation, changes in cardiac output mostly influence the rate of increase of the Pa of a soluble anesthetic. Conversely, the rate of increase of the Pa of a poorly soluble anesthetic, such as nitrous oxide, is rapid regardless of physiologic deviations of the cardiac output around its normal value (Fig. 4-8).

Alveolar-to-Venous Partial Pressure Differences (Table 4-4)

Recovery from Anesthesia (Fig. 4-8)

1. Context-Sensitive Half-Time. The pharmacokinetics of the elimination of inhaled anesthetics depends on the length of administration and the blood-gas solubility of the inhaled anesthetic.

2. Diffusion hypoxia occurs when inhalation of nitrous oxide is discontinued abruptly, leading to a reversal of partial pressure gradients such that nitrous oxide leaves the blood to enter alveoli.