C. Physical Characteristics of Inhaled Anesthetics (Tables 17-1 and 17-2)

1. The goal of delivering inhaled anesthetics is to produce the anesthetic state by establishing a specific concentration (partial pressure) in the central nervous system (CNS). This is achieved by establishing the desired partial pressure in the lungs that ultimately equilibrates with the brain and spinal cord.

2. At equilibrium, the CNS partial pressure equals the blood partial pressure, which equals alveolar partial pressure.

D. Gases in Mixtures. For any mixture of gases in a closed container, each gas exerts a pressure proportional to its fractional mass (partial pressure).

E. Gases in Solutions

1. The concentration of any one gas in a mixture of gases in solution depends on (i) its partial pressure in the gas phase in equilibrium with the solution and (ii) its solubility within that solution.

2. The concentration of anesthetic in the target tissue depends on the partial pressure at equilibrium and the target tissue solubility.

3. Because inhaled anesthetics are gases and because partial pressures of gases equilibrate throughout a system, monitoring the alveolar concentration of inhaled anesthetics provides an index of their effects on the brain.

F. Anesthetic Transfer: Machine to Central Nervous System (Table 17-3)

G. Uptake and Distribution

1. FA/FI. A common way to assess anesthetic uptake is to follow the ratio of the alveolar anesthetic concentration (F_A) to the inspired anesthetic concentration (F_I) over time (F_A/F_I) (Fig. 17-2).

2. Distribution (Tissue Uptake). Factors that increase or decrease the rate of increase of F_A/F_I determine the speed of induction of anesthesia (see Fig. 17-2 and Table 17-3).

3. Metabolism plays little role in opposing induction but may have some significance in determining the rate of recovery.

H. Overpressurization and Concentration Effect

1. Overpressurization (delivering a higher F_I than the F_A actually desired for the patient) is analogous to an intravenous bolus and thus speeds the induction of anesthesia.

2. Concentration effect (the greater the F_I of an inhaled anesthetic, the more rapid the rate of increase of the F_A/F_I) is a method used to speed the induction of anesthesia (Fig. 17-3).

I. Second Gas Effect

1. A special case of the concentration effect is administration of two gases simultaneously (nitrous oxide and a potent volatile anesthetic) in which the high volume uptake of nitrous oxide increases the F_A (concentrates) of the volatile anesthetic.

J. Ventilation Effects

1. Inhaled anesthetics with low blood solubility have a rapid rate of increase in the F_A/F_I with induction of anesthesia such that there is little room to improve this rate of increase by increasing or decreasing ventilation (see Fig. 17-3).

2. To the extent that inhaled anesthetics depress ventilation with an increasing F_I, alveolar ventilation decreases, as does the rate of increase of F_A/F_I (negative feedback that results in apnea and may prevent an overdose).

K. Perfusion Effects

1. As with ventilation, cardiac output does not greatly affect the rate of increase of the F_A/F_I for poorly soluble anesthetics.

2. Cardiovascular depression caused by a high F_I results in depression of anesthetic uptake from the lungs and increases the rate of increase of F_A/F_I (positive feedback that may result in profound cardiovascular depression).

L. Exhalation and Recovery

1. Recovery from anesthesia, similar to induction of anesthesia, depends on the drug’s solubility (primary determinant of the rate of decrease in F_A), ventilation, and cardiac output (Fig. 17-4).

2. The “reservoir” of anesthetic in the body at the conclusion of anesthesia is determined by the solubility of the inhaled anesthetic and the dose and duration of the drug’s administration (can slow the rate of decrease in the F_A).

3. Pharmacokinetic differences between recovery and induction of anesthesia include the absence of overpressurization (cannot give less than zero) during recovery and the presence of tissue anesthetic concentrations present at the start of recovery (tissue concentration of zero at the start of anesthesia induction).

II. CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS (see Table 17-1 and Fig. 17-1)

A. Isoflurane

1. Isoflurane is a halogenated methyl ethyl ether that has a high degree of stability and has become the “gold standard” anesthetic since its introduction in the 1970s.

2. Coronary vasodilation is a characteristic of isoflurane, and in patients with coronary artery disease, there has been concern that coronary steal could occur (rare occurrence).

B. Desflurane

1. Desflurane is a completely fluorinated methyl ethyl ether that differs from isoflurane only by replacement of a chlorine with a fluorine atom.

2. Compared with isoflurane, fluorination of desflurane results in low tissue and blood solubility (similar to nitrous oxide), greater stability (near-absent metabolism to trifluoroacetate), loss of potency, and a high vapor pressure (decreased intermolecular attraction). A heated and pressurized vaporizer requiring electrical power is necessary to deliver desflurane.

3. Disadvantages of desflurane include its pungency (it cannot be administered by face mask to an awake patient), transient sympathetic nervous system stimulation when F_I is abruptly increased, and degradation to carbon monoxide when exposed to dry carbon dioxide absorbents (more so than isoflurane).

4. Desflurane has the lowest blood:gas solubility of the potent volatile anesthetics permitting rapid emergence even with prolonged surgical procedures and in obese patients.

C. Sevoflurane

1. Sevoflurane is completely fluorinated methyl isopropyl ether with a vapor pressure similar to that of isoflurane. It can be used in a conventional vaporizer.

2. Compared with isoflurane, sevoflurane is less soluble in blood and tissues (it resembles desflurane), is less potent, and lacks coronary artery vasodilating properties.

3. Sevoflurane has minimal odor and pungency (it is useful for mask induction of anesthesia) and is a potent bronchodilator.

4. Similar to enflurane, the metabolism of sevoflurane results in fluoride, but unlike enflurane, this has not been associated with renal concentrating defects.

5. Unlike other volatile anesthetics, sevoflurane is not metabolized to trifluoroacetate but rather to hexafluoroisopropanol, which does not stimulate formation of antibodies and immune-mediated hepatitis.

6. Sevoflurane does not decompose to carbon monoxide or to dry carbon dioxide absorbents but rather is degraded to a vinyl halide (compound A), which is a dose-dependent nephrotoxin in rats. Renal injury has not been shown to occur in patients even when fresh gas flows are ≤1 L/min.

D. Xenon

1. This inert gas has many characteristics of an “ideal” inhaled anesthetic (blood gas partition coefficient of 0.14, provides some analgesia, nonpungent, does not produce myocardial depression or alter coronary blood flow).

2. The principal disadvantages of xenon are its expense (difficult to obtain) and high minimum alveolar concentration (MAC) (71%).

E. Nitrous Oxide

1. Nitrous oxide is a sweet-smelling, nonflammable gas of low potency and limited blood and tissue solubility that is most often administered as an adjuvant in combination with other volatile anesthetics or opioids.

2. Controversy surrounding the use of nitrous oxide is related to its unclear role in postoperative nausea and vomiting, potential toxicity related to inactivation of vitamin B₁₂, effects on embryonic development, and adverse effects related to its absorption into air-filled cavities and bubbles. (Compliant spaces such as a pneumothorax expand, and noncompliant spaces such as the middle ear experience increased pressure.)

a. Inhalation of 75% nitrous oxide may expand a pneumothorax to double its size in 10 minutes.

b. Accumulation of nitrous oxide in the middle ear may diminish hearing after surgery.

III. NEUROPHARMACOLOGY OF INHALED ANESTHETICS

A. Minimum Alveolar Concentration

1. MAC is the F_A of an anesthetic at 1 atm and 37°C that prevents movement in response to a surgical stimulus in 50% of patients (analogous to an ED50 for injected drugs; Table 17-1). Clinical experience is that 1.2 to 1.3 MAC consistently prevents patient movement during surgical stimulation. Although these MAC levels do not absolutely ensure the defining criteria for brain anesthesia (absence of self-awareness and recall), it is unlikely for a patient to be aware of or to recall the surgical incision at these anesthetic concentrations unless other conditions exist so that MAC is increased (Table 17-4). Self-awareness and recall are prevented by 0.4 to 0.5 MAC.

2. Standard MAC values are roughly additive (0.5 MAC of a volatile anesthetic and 0.5 MAC of nitrous oxide is equivalent to 1 MAC of the volatile anesthetic).

3. A variety of factors may increase or decrease MAC (see Table 17-4).

B. Other Alterations in Neurophysiology. The currently used volatile anesthetics have qualitatively similar effects on cerebral metabolic rate, the electroencephalogram (EEG), cerebral blood flow (CBF), and flow–metabolism coupling. There are differences in effects on intracerebral pressure, cerebrospinal fluid (CSF) production and resorption, CO₂ reactivity, CBF autoregulation, and cerebral protection. Nitrous oxide departs from the more potent agents in several respects.

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