Chapter 48

### CHEMICAL STRUCTURE

The most commonly used volatile anesthetics are desflurane, sevoflurane, and isoflurane. The chemical structures can be classified as substituted halogenated ethers. Additionally, halothane is a substituted halogenated alkane, a derivative of ethane. Isoflurane and enflurane are isomers that are methyl ethyl ethers. Desflurane differs from isoflurane in the substitution of fluorine for a chlorine atom, and sevoflurane is a methyl isopropyl ether.

### MECHANISM OF ACTION

The mechanism of action of inhalational anesthetics has not been completely elucidated. Broadly, they are postulated to enhance inhibitory receptors (GABAAand glycine) while dampening excitatory pathways (nicotinic and glutamate). Unspecified mechanisms also include suppression of nociceptive motor responses within the spinal cord, as well as supraspinal suppression causing amnesia and hypnotic state.

### PHYSICAL CHARACTERISTICS

The end goal of administering inhaled gases is to create an anesthetic state by reaching effective concentrations within the central nervous system (Table 48-1). To arrive at this end point, effective partial pressures must be established within the lung’s alveoli, allowing the gases to equilibrate in the pulmonary vasculature and ultimately within the CNS. At equilibrium, the partial pressure of the gases in the alveoli will be equivalent with the partial pressures in the patient’s blood and brain. Inhaled anesthetics reach equilibrium due to the following: rapid bidirectional transfer of gases between alveoli, blood, and CNS; the low capacity of tissue and plasma to absorb inhaled anesthetics; and the low metabolism, excretion, and redistribution of volatile agents relative to the rate at which they are removed or added to the lungs. Simply put, inhaled agent levels in the brain are heavily dependent on the anesthetic gas concentrations in the alveoli.

Palveoli = Pblood = Pbrain

### MINIMUM ALVEOLAR CONCENTRATION

One minimum alveolar concentration (MAC) of a volatile anesthetic is the alveolar concentration of the gas, at 1 atmosphere, for which 50% of patients will not have a motor response to painful stimulus (ie, surgical incision). A MAC of 1.3 will eliminate motor response in 99% of patients. MAC was developed to compare potencies of inhaled agents, and the potency is inversely proportional to MAC. For example, the MAC of the most common agents, desflurane, sevoflurane, and isoflurane, are roughly 6, 2, and 1, respectively. Isoflurane has the lowest MAC, requiring the lowest alveolar concentration to abolish motor response, and is the most potent agent of the three mentioned. In contrast, desflurane is the least potent and requires the highest concentration to abolish motor response, as it has the largest MAC of the three agents considered.

MAC increases (decreases in potency) with the following: hyperthermia, stimulants (cocaine, amphetamines), and chronic alcoholism. The highest MAC values are in infants aged 6-12 months.

MAC decreases (increases in potency) with the following: hypothermia, hyponatremia, opioids, barbiturates, alpha-2 blockers, Ca2+...

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