Inhaled anesthetics elimination

Inhalational anesthetics are administered in and, for the most part, eliminated via respired air. They serve to maintain anesthesia Pertinent substances are considered on p. 218. 

The rates of onset and cessation of action vary widely between different inhalational anesthetics and also depend on the degree of lipophilicity. In the case of N2O, there is rapid elimination from the body when the patient is ventilated with normal air. Due to the high partial pressure in blood, the driving force for transfer of the drug into expired air is large and, since tissue uptake is minor, the body can be quickly cleared of N2O. 

The use of inhalational anesthetics is generally reserved for maintenance of anesthesia. The development of an anesthetic concentration in the brain occurs more slowly with inhalational anesthetics than with IV drugs. Once an anesthetic level has been achieved, however, it is easily adjusted by controlling the rate or concentration of gas delivery from the anesthesia machine. The rate of recovery from a lengthy procedure in which inhalational agents are used is reasonably rapid, since inhalational anesthetics are eliminated by the lungs and do not depend on a slow rate of metabolism for their tissue clearance. Thus, inhalational drugs meet the requirement for a relatively prompt return of the patient s psychomotor competence. 

Inhaled anesthetics that are relatively insoluble in blood (ie, possess low blood gas partition coefficients) and brain are eliminated at faster rates than the more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, leading to a more rapid recovery from their anesthetic effects compared with halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane- and isoflurane-based anesthesia is predictably less rapid. 

Inhaled anesthetics that are relatively insoluble in blood (low blood gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, which leads to a more rapid recovery from their anesthetic effects compared to halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane anesthesia is predictably less rapid. The duration of exposure to the anesthetic can also have a marked effect on the time of recovery, especially in the case of more soluble anesthetics. Accumulation of anesthetics in tissues, including muscle, skin, and fat, increases with continuous inhalation (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is gradually eliminated from these tissues. Thus, if exposure to the anesthetic is short, recovery may be rapid even with the more soluble agents. However, after prolonged anesthesia, recovery may be delayed even with anesthetics of moderate solubility such as isoflurane. 

Clearance of inhaled anesthetics by the lungs into the expired air is the major route of their elimination from the body. However, metabolism by enzymes of the liver and other tissues may also contribute to the elimination of volatile anesthetics. For example, the elimination of halothane during recovery is more rapid than that of enflurane, which would not be predicted from their... 

Inhaled gases are the mainstay of anesthesia and are primarily used for the maintenance of anesthesia after administration of an intravenous agent. Inhalation anesthetics have a benefit that is not available with intravenous agents, since the depth of anesthesia can be rapidly altered by changing the concentration of the inhaled anesthetic. Because most of these agents are rapidly eliminated from the body, they do not cause postoperative respiratory depression. 

The potency of inhaled anesthetics is defined quantitatively as the minimum alveolar concentration (MAC), which is the concentration of anesthetic gas needed to eliminate movement among 50% of patients challenged by a standardized skin incision. The MAC is... 

Answer D. Saturation of the blood with inhaled anesthetics is more rapid if they have a low blood-gas partition coefficient. This results in the more rapid achievement of a partial pressure of the dissolved anesthetic molecules commensurate with their movement out of the blood into the alveolar spaces of the lung, where they are eliminated. Note that the same physicochemical characteristic is responsible for the rapid onset of the anesthetic action of sevoflurane. Although redistribution of anesthetics between tissues occurs, it is not responsible for rapid recovery. MAC values are a measure, of anesthetic potency. With the exception of halothane (and methoxyflurane), inhaled anesthetics are not metabolized to a significant extent. Naloxone is an opioid receptor antagonist. 

Although not widely reported in the scientific literature, other organs in the body are capable of drug excretion. The primary route of elimination of some inhalation anesthetics (e.g., isoflurane) is exhalation. 

C. Minimum Alveolar Anesthetic Concentration (MAC) The potency of inhaled anesthetics is best measured by the minimum alveolar anesthetic concentration (MAC), defined as the alveolar concentration required to eliminate the response to a standardized painful stimulus in 50% of patients. Each anesthetic has a defined MAC (see Table 25-2), but tWs value may vary among different patients depending on age, cardiovascular status, and use of adjuvant drugs. Estimations of MAC value suggest a relatively steep dose-response relationship for inhaled anesthetics. MACS for infants and elderly patients are lower than those for adolescents and young adults. When several anesthetic agents are used simultaneously, their MAC values are additive. 

Biological Elimination Reactions Trichloroethylene (a solvent) Halothane (an inhaled anesthetic) Dichlorodifluoromethane (a refrigerant) Bromomethane (a fumigant)... 

Figure 7.28 Halothane is an inhalation anesthetic that undergoes metabolism by oxidative dehalogenation. Oxygen inserts into the C-H bond and bromide is eliminated to form an acid chloride. This reacts with water to form trifluoroacetic acid.

Gases that do not react irreversibly with epithelial tissue, such as anesthetic gases, may diffuse into the bloodstream and will ultimately be eliminated from the body. A different and earlier model developed by DuBois and Rogers estimates the rate of uptake of inhaled gas from the tracheobronchial tree in terms of diffusion through the epithelial tissue, rate of blood flow, and solubility of the gas in blood. The rate of uptake from the airway lumen is determined by the equation ... 

Because of its volatility, the most likely route of exposure to diethyl ether is by inhalation. About 80% of this compound that gets into the body is eliminated unmetabolized as the vapor through the lungs. Diethyl ether is a central nervous system depressant, and for many years was the anesthetic of choice for surgery. At low doses, it causes drowsiness, intoxication, and stupor. Higher exposures result in unconsciousness and even death. 

The distribution of carbon disulfide following inhalation exposure has been studied in rabbits and rats (Toyama and Kusano 1953). In rabbits, blood equilibrium concentrations of carbon disulfide were reached after exposure to 20-150 ppm for 1.5-2.0 hours. In rats exposed to 60-350 ppm carbon disulfide, distribution was primarily to the brain, kidney, and liver. In contrast to rabbits, blood equilibrium concentrations for various carbon disulfide exposures in rats were not determined. Although carbon disulfide was rapidly eliminated from rat tissues during the first 6-8 hours after exposure, low concentrations of carbon disulfide were still detected in the tissues 20 hours after exposure. A separate study reported that equilibrium concentrations of carbon disulfide in blood were attained in dogs after 0.5-2.0 hours of exposure to 25-60 ppm carbon disulfide (McKee et al. 1943). Desaturation was largely complete within the first 30-60 minutes after inhalation exposure. Anesthetized male Sprague-Dawley... 

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