10: Volatile Anesthetics

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CHAPTER 10 Volatile Anesthetics

Michelle Dianne Herren, MD

1 What are the properties of an ideal anesthetic gas?

An ideal anesthetic gas would be predictable in onset and emergence; provide muscle relaxation, cardiostability, and bronchodilation; not trigger malignant hyperthermia or other significant side effects (such as nausea and vomiting); be inflammable; undergo no transformation within the body; and allow easy estimation of concentration at the site of action.

2 What are the chemical structures of the more common anesthetic gases? Why do we no longer use the older ones?

Isoflurane, desflurane, and sevoflurane are the most commonly used volatile anesthetics. As the accompanying molecular structures demonstrate, they are substituted halogenated ethers, except halothane, a halogenated substituted alkane. Many older anesthetic agents had unfortunate properties and side effects such as flammability (cyclopropane and fluroxene), slow induction (methoxyflurane), hepatotoxicity (chloroform and fluroxene), nephrotoxicity (methoxyflurane), and the theoretic risk of seizures (enflurane) (Figure 10-1).

Figure 10-1 Molecular structures of contemporary gaseous anesthetics.

3 How are the potencies of anesthetic gases compared?

The potency of anesthetic gases is compared using minimal alveolar concentration (MAC), which is the concentration at one atmosphere that abolishes motor response to a painful stimulus (i.e., surgical incision) in 50% of patients. Of note, 1.3 MAC is required to abolish this response in 99% of patients. Other definitions of MAC include the MAC-BAR, which is the concentration required to block autonomic reflexes to nociceptive stimuli (1.7 to 2 MAC), and the MAC-awake, the concentration required to block appropriate voluntary reflexes and measure perceptive awareness (0.3 to 0.5 MAC). MAC appears to be consistent across species lines. The measurement of MAC assumes that alveolar concentration directly reflects the partial pressure of the anesthetic at its site of action and equilibration between the sites.

4 What factors may influence MAC?

The highest MACs are found in infants at 6 to 12 months of age and decrease with both increasing age and prematurity. For every Celsius degree drop in body temperature, MAC decreases approximately 2% to 5%. Hyponatremia, opioids, barbiturates, α₂-blockers, calcium channel blockers, acute alcohol intoxication, and pregnancy decrease MAC. Hyperthermia, chronic alcoholism, and central nervous system (CNS) stimulants (cocaine) increase MAC. Factors that do not affect MAC include hypocarbia, hypercarbia, gender, thyroid function, and hyperkalemia. MAC is additive. For example, nitrous oxide potentiates the effects of volatile anesthetics.

5 Define partition coefficient. Which partition coefficients are important?

A partition coefficient describes the distribution of a given agent at equilibrium between two substances at the same temperature, pressure, and volume. Thus the blood-to-gas coefficient describes the distribution of anesthetic between blood and gas at the same partial pressure. A higher blood-to-gas coefficient correlates with a greater concentration of anesthetic in blood (i.e., a higher solubility). Therefore a greater amount of anesthetic is taken into the blood, which acts as a reservoir for the agent, reducing the alveolar concentration and thus slowing the rate of induction. Equilibration is relatively quick between alveolar and brain anesthetic partial pressure. Thus alveolar concentration ultimately is the principal factor in determining onset of action.

Other important partition coefficients include brain to blood, fat to blood, liver to blood, and muscle to blood. Except for fat to blood, these coefficients are close to 1 (equally distributed). Fat has partition coefficients for different volatile agents of 30 to 60 (i.e., anesthetics continue to be taken into fat for quite some time after equilibration with other tissues) (Table 10-1).

TABLE 10-1 Physical Properties of Contemporary Anesthetic Gases

6 Review the evolution in hypothesis as to how volatile anesthetics work

At the turn of the century Meyer and Overton independently observed that an increasing oil-to-gas partition coefficient correlated with anesthetic potency. The Meyer-Overton lipid solubility theory dominated for nearly half a century before it was modified.

Franks and Lieb found that an amphophilic solvent (octanol) correlated better with potency than lipophilicity and concluded that the anesthetic site must contain both polar and nonpolar sites.

Modifications of Meyer and Overton’s membrane expansion theories include the excessive volume theory, in which anesthesia is created when a polar cell membrane components and amphophilic anesthetics synergistically create a larger cell volume than the sum of the two volumes together.

In the critical volume hypothesis, anesthesia results when the cell volume at the anesthetic site reaches a critical size. These theories rely on the effects of membrane expansion on and at ion channels.

The previous theories oversimplify the mechanism of anesthetic action and have been abandoned for the following reasons: volatile anesthetics lead to only mild perturbations in lipids, and the same changes can be reproduced by changes in temperature without leading to behavioral changes; also, variations in size, rigidity, and location of the anesthetic in the lipid bilayer are similar to those in compounds that do not have anesthetic activity, which implies that specific receptors are involved.

Newer accepted theories propose distinct molecular targets and anatomic sites of action rather than nonspecific actions on cell volume or wall. Volatile anesthetics are thought to enhance inhibitory receptors, including γ-aminobutyric acid (GABA) type A and glycine receptors.

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