The inhalational anesthetics have distinctly different solubility (affinity) characteristics in blood as well as in other tissues. These solubility differences are usually expressed as coefficients and indicate the number of volumes of a particular agent distributed in one phase, as compared with another, when the partial pressure is at equilibrium (Table 25.3). For example, isoflurane has a blood-to-gas partition coefficient (often referred to as the Ostwald solubility coefficient) of approximately 1.4. Thus, when the partial pressure has reached equilibrium, blood will contain 1.4 times as much isoflurane as an equal volume of alveolar air. The volume of the various anesthetics required to saturate blood is similar to that needed to saturate other body tissues (Table 25.3); that is, the blood-tissue partition coefficient is usually not more than 4 (that of adipose tissue is higher).
The solubility of anesthetic agents is a major factor for the rate of induction of anesthesia, or the time required to establish a level of unconsciousness adequate for surgery. Agents with limited plasma solubility and a low rate of uptake (e.g., N2O, cyclopropane, sevoflurane, and desflurane) will equilibrate rapidly with tissues. For an agent that is highly soluble in plasma (e.g., methoxyflurane), the rate of rise of alveolar tension to the inspired level and the equilibration of the gas with brain will be delayed by a higher initial uptake into plasma from the alveoli. This phenomenon is often counterintuitive to students. However, with gases, partial pressure is the controlling factor for equilibration between tissues, and even though uptake is high, partial pressure in the tissues and lung rises slowly, as large quantities of a highly soluble gas must be accumulated to establish the desired tension (Henry's law).
To illustrate the effect of solubility on the rate of induction of anesthesia, we can consider a situation in which individual agents are delivered to patients at their equivalent MAC values. Under these conditions, regardless of the agent being employed, a similar level of anesthesia will be achieved. In contrast, induction rates, illustrated as the time required for the alveolar tension to rise to the inspired level (Fig. 25.3), can be seen to be quite different. A patient receiving a MAC of N2O, desflurane, or sevoflurane will be unconscious within 3 minutes. However, halothane, enflurane, and isoflurane, which have significant blood and tissue solubilities, will require at least 30 minutes before surgical anesthesia is established. Methoxyflurane, a highly soluble agent, requires several hours and may be clinically impractical if administered in this way.
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