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The state of general anesthesia is a drug-induced absence of perception of all sensations. Depths of anesthesia appropriate for surgical procedures can be achieved with a wide variety of drugs. General anesthetics are administered primarily by inhalation and intravenous (IV) injection. These routes of administration allow control of the dosage and time course of action.

For these drugs, understanding the principles of uptake, distribution, and elimination are the major focus, particularly for the inhaled anesthetics. The mechanism of action of most of the anesthetics is unknown. You should be able to recognize the names of the general anesthetics and know a few specific facts about these drugs (Figure 25–1).


Structures of some of the inhalational drugs. Notice the very simple structures and the presence of fluoride.

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Inhaled Drugs IV Drugs












The tension of a gas in a mixture is proportional to its concentration. Therefore, the terms tension and concentration are often used interchangeably. The term partial pressure is also used interchangeably with tension.

When a constant tension (concentration) of anesthetic gas is inhaled, the tension (concentration) in arterial blood approaches that of the agent in the inspired mixture. The tension (concentration) in the brain is always approaching the tension (concentration) in arterial blood.

The level of general anesthesia is dependent on the concentration of anesthetic in the brain.

The solubility of an agent is expressed as the blood–gas partition coefficient.

The blood–gas partition coefficient represents the ratio of anesthetic concentration in blood to the concentration in the gas phase. The blood–gas coefficient is high for very soluble agents and low for relatively insoluble anesthetics such as nitrous oxide.

The more soluble an anesthetic is in blood, the more of it must be dissolved in blood to raise its partial pressure in the blood.

The potential reservoir for relatively soluble gases is large and will be filled more slowly. Therefore, for soluble gases the rate at which the tension (partial pressure) in the arterial blood approaches the inspired partial pressure is slow. Also, the rate at which the brain partial pressure approaches the arterial partial pressure is slow. The opposite is true for more insoluble anesthetics.

The speed of onset of anesthesia is inversely related to the solubility of the gas in blood:

  • More soluble (high blood–gas partition coefficient) = Slower onset

  • Less soluble (low blood–gas partition coefficient) = Faster onset

Onset of anesthesia is also related to pulmonary ventilation, rate of pulmonary blood flow, tissue blood flow, and ...

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