2. Solubility—As described above, the rate of rise of FA/FI is an important determinant of the speed of induction, but is opposed by the uptake of anesthetic into the blood. Uptake is determined by pharmacokinetic characteristics of each anesthetic agent as well as patient factors.
One of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood is its solubility characteristics (Table 25–1). As described above, the blood:gas partition coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood compared to the affinity for inspired gas. Desflurane and nitrous oxide, which are relatively insoluble in blood, display low partition coefficients. When an anesthetic with low blood solubility partitions between gas in the lung and pulmonary capillary blood, equilibrium is quickly established and the blood concentration rises rapidly (Figure 25–4, top; nitrous oxide, desflurane, sevoflurane). Conversely, for anesthetics with greater solubility (Figure 25–4, bottom; halothane, isoflurane), more molecules dissolve in the blood before partial pressure changes significantly, and arterial concentration of the gas increases less rapidly. A blood:gas partition coefficient of 0.47 for nitrous oxide means that at equilibrium, the concentration in blood is less than half the concentration in the alveolar space (gas). A larger blood:gas partition coefficient causes a greater uptake of anesthetic into the pulmonary blood flow and therefore increases the time required for FA/FI to approach equilibrium (Figure 25–4).
0.5
FIGURE 25–4 The alveolar anesthetic concentration (FA) approaches the inspired anesthetic concentration (FI) fastest for the least soluble agents.
3.
Cardiac output—Changes in the flow rate of blood through the lungs also affect the uptake of anesthetic gases from the alveolar space. An increase in pulmonary blood flow (ie, increased cardiac output) will increase the uptake of anesthetic, thereby slowing the rate by which FA/FI rises and decreasing the rate of induction of anesthesia. Furthermore, one should consider the effect of cardiac output in combination with the tissue distribution and uptake of anesthetic into other tissue compartments. The increased uptake of anesthetic into the blood caused by increased cardiac output will be distributed to all tissues. Since cerebral blood flow is well regulated, the increased anesthesia uptake caused by increased cardiac output will predominantly be distributed to tissues that are not involved in the site of action of the anesthetic.
4.
Alveolar-venous partial pressure difference—The anesthetic partial pressure difference between alveolar and mixed venous blood is dependent mainly on uptake of the anesthetic by the tissues, including nonneural tissues. Depending on the rate and extent of tissue uptake, venous blood returning to the lungs may contain significantly less anesthetic than arterial blood Anesthetic uptake into tissues is influenced by factors similar to those that determine transfer of the anesthetic from the lung to the intravascular space, including tissue:blood partition coefficients (Table 25–1), rates of blood flow to the tissues, and concentration gradients. The greater this difference in anesthetic gas concentrations, the more time it will take to achieve equilibrium with brain tissue.
During the induction phase of anesthesia (and the initial phase of the maintenance period), the tissues that exert greatest influence on the arteriovenous anesthetic concentration gradient are those that are highly perfused (eg, brain, heart, liver, kidneys, and splanchnic bed). Combined, these tissues receive over 75% of the resting cardiac output. In the case of volatile anesthetics with relatively high solubility in highly perfused tissues, venous blood concentration initially is very low, and equilibrium with the alveolar space is achieved slowly.