Inhalational Anesthetics

Structures of the currently used inhalational anesthetics are shown in Figure 13-3. One of the troublesome properties of the inhalational anesthetics is their low safety margin. The inhalational anesthetics have therapeutic indices (LD50/ED50) that range from 2-4, making these among the most dangerous drugs in clinical use. The toxicity of these drugs is largely a function of their side effects, and each of the inhalational anesthetics has a unique side-effect profile. Hence, the selection of an inhalational anesthetic often is based on matching a patient's pathophysiology with drug side-effect profiles. The inhalational anesthetics also vary widely in their physical properties (Table 13-1), which govern the pharmacokinetics of the inhalational agents. Ideally, an inhalational agent would produce a rapid induction of anesthesia and a rapid recovery following discontinuation.

Pharmacokinetic Principles

The fact that these agents behave as gases rather than as liquids requires that different pharmacoki-netic constructs be used in analyzing their uptake and distribution. Inhalational anesthetics distribute between tissues (or between blood and gas) such that equilibrium is achieved when the partial pressure of anesthetic gas is equal in the two tissues. When a person has breathed an inhalational anesthetic for a sufficiently long time that all tissues are equilibrated with the anesthetic, the partial pressure of the anesthetic in all tissues will be equal to the partial pressure of the anesthetic in inspired gas. However, while the partial pressure of the anesthetic may be equal in all tissues, the concentration of anesthetic in each tissue will be different; indeed, anesthetic partition coefficients are defined as the ratio of anesthetic concentrations in two tissues when the partial pressures of anesthetic are equal in the two tissues. Blood:gas, brain:blood, and fat:blood partition coefficients (Table 13-1) show that inhalational anesthetics are more soluble in some tissues (e.g., fat) than they are in others (e.g., blood), and that there is significant range in the solubility of the various inhalational agents.

In clinical practice, one can monitor the equilibration of a patient with anesthetic gas. Equilibrium is achieved when the partial pressure in inspired gas is equal to the partial pressure in end-tidal (alveolar) gas. This defines equilibrium because it is the point at which there is no net uptake of anesthetic from the alveoli into the blood. For inhalational agents that are not very soluble in blood or any other tissue, equilibrium is achieved quickly (e.g., nitrous oxide, Figure 13-4). If an agent is more soluble in a tissue such as fat, equilibrium may take many hours to reach. This occurs because fat represents a huge anesthetic reservoir that will be filled slowly because of the modest blood flow to fat (e.g., halothane, Figure 13-4).

In considering the pharmacokinetics of anesthetics, one important parameter is the speed of anesthetic induction. Anesthesia is produced when anesthetic partial pressure in brain is >MAC. Because the brain is well perfused, anesthetic partial pressure in brain becomes equal to the partial pressure in alveolar gas (and in blood) over the course of several minutes. Therefore, anesthesia is achieved shortly after alveolar partial pressure reaches MAC. While the rate of rise of alveolar partial pressure will be slower for anesthetics that are highly soluble in blood and other tissues, this limitation on speed of induction can be overcome largely by delivering higher inspired partial pressures of the anesthetic.

Elimination of inhalational anesthetics is largely the reverse process of uptake. For agents with low blood and tissue solubility, recovery from anesthesia should mirror anesthetic induction, regardless of the duration of administration. For inhalational agents with high blood and tissue solubility, recovery will be a function of the duration of administration, because anesthetic accumulated in the fat reservoir will prevent blood (and therefore alveolar) partial pressures from falling rapidly. Patients will be arousable when alveolar partial pressure reaches MACawake, a partial pressure somewhat lower than MAC (Table 13-1).

Desflurane Nitrous Mac

FIGURE 13-4 Uptake of inhalational general anesthetics. The rise in end-tidal alveolar (FA) anesthetic concentration toward the inspired (F:) concentration is most rapid with the least soluble anesthetics, nitrous oxide and desflurane, and slowest with the most soluble anesthetic, halothane.

Minutes

FIGURE 13-4 Uptake of inhalational general anesthetics. The rise in end-tidal alveolar (FA) anesthetic concentration toward the inspired (F:) concentration is most rapid with the least soluble anesthetics, nitrous oxide and desflurane, and slowest with the most soluble anesthetic, halothane.

Halothane

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Responses

  • katharina luft
    How do inhalational anesthetics affects blood pressure?
    9 months ago

Post a comment