During maintenance of anesthesia with inhaled anesthetics, the drug continues to be transferred between various tissues at rates dependent on the solubility of the agent, the concentration gradient between the blood and the respective tissue, and the tissue blood flow. Although muscle and skin constitute 50% of the total body mass, anesthetics accumulate more slowly in these tissues than in highly perfused tissues (eg, brain) because they receive only one fifth of the resting cardiac output. Although most anesthetic agents are highly soluble in adipose (fatty) tissues, the relatively low blood perfusion to these tissues delays accumulation, and equilibrium is unlikely to occur with most anesthetics during a typical 1to 3-hour operation.
The combined effect of ventilation, solubility in the different tissues, cardiac output, and blood flow distribution determines the rate of rise of FA/FI characteristic of each drug. Figure 25–5 schematically compares how uptake and distribution proceed with two widely different agents. The anesthetic state is achieved when the partial pressure of the anesthetic in the brain reaches a threshold concentration determined by its potency (MAC; see Table 25–1 and Box: What Does Anesthesia Represent & Where Does It Work?). For an insoluble agent like desflurane, the alveolar partial pressure can quickly equilibrate through the blood and brain compartments to reach anesthetizing concentrations. However, for an agent like halo-thane, its greater solubility in blood and other tissue compartments (higher partition coefficients) produces a steeper decline in the concentration gradient from lung to brain, causing a delayed onset of anesthesia. Therefore, administering a larger concentration of halothane and increasing alveolar ventilation are the two strategies that can be used by anesthesiologists to speed the rate of induction with halothane.
B. Elimination
Recovery from inhalation anesthesia follows some of the same principles in reverse that are important during induction. The time to recovery from inhalation anesthesia depends on the rate of elimination of the anesthetic from the brain. One of the most important factors governing rate of recovery is the blood:gas partition coefficient of the anesthetic agent. When the anesthesiologist discontinues the administration of the anesthetic agent to the lung, the alveolar concentration falls rapidly. Insoluble anesthetics that prefer the gas phase over blood will then rapidly diffuse into the alveolus and be removed from the body by the process of lung ventilation. Other factors controlling rate of recovery include pulmonary blood flow and tissue solubility of the anesthetic.
Two features differentiate the recovery phase from the induction phase. First, transfer of an anesthetic from the lungs to blood during induction can be enhanced by increasing its concentration in inspired air, but the reverse transfer process cannot be enhanced because the concentration in the lungs cannot be reduced below zero. Second, at the beginning of the recovery phase, the anesthetic gas tension in different tissues throughout the body may be quite variable, depending on the specific agent and the duration of anesthesia. In contrast, at the start of induction of anesthesia, the initial anesthetic tension is zero in all tissues.
Inhaled anesthetics that are relatively insoluble in blood (ie, possess low blood:gas partition coefficients) and brain are eliminated faster than the more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, leading to a more rapid recovery from their anesthetic effects compared with halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane; its elimination therefore takes place more slowly, and recovery from halothaneand isoflurane-based anesthesia is predictably less rapid.