Alveolar concentration

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Potency is described by the minimum alveolar concentration (MAC) of an agent and lipid solubility by the oil gas solubility coefficient. 

The minimum alveolar concentration of an anaesthetic vapour at equilibrium is the concentration required to prevent movement to a standardized surgical stimulus in 50% of unpremedicated subjects studied at sea level... 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

Gion El, Saidman LJ The minimum alveolar concentration in man. Anesthesiology 35 361-364, 1971... 

Nitrous oxide is the only inhalation anesthetic that is a gas. It is chemically inert. Nitrous oxide has little effect on overall cardiovascular function. Disadvantages are that it has no muscle relaxing effect and that it cannot be used on its own because of high Minimal Alveolar Concentration values needed for adequate anesthesia. During recovery there is a risk for hypoxia and anesthesia should be slowly tapered off to prevent this event. 

A Concept of Anesthetic Dose Based on Partial Pressure-Minimum Alveolar Concentration... 

The rate at which the alveolar concentration of a vapour or gas approaches the inspired concentration is directly proportional to its inspired concentration. This is sometimes referred to as the concentration effect. It states that the higher the inspired anaesthetic concentration, the more rapid the rise in alveolar concentration and hence the more quickly equilibrium is attained between tensions in the alveoli and the brain. In practice, it is necessary to strike a balance to avoid irritation of the airway, or other unwanted phenomena, due to excessively high inspired concentrations of vapour. 

An increase in alveolar ventilation will cause an increase in the alveolar concentration of inhaled agent when semi-closed or open breathing circuits are employed. The effect is most noticeable with a highly soluble anaesthetic, such as diethyl ether. With modern, relatively insoluble agents, such as isoflurane and desflurane, the effects of changes in alveolar ventilation are less pronounced. 

Anesthetic Blood Gas Partition Coefficient1 Brain Blood Partition Coefficient1 Minimal Alveolar Concentration (MAC) (°/o)2 Metabolism Comments... 

During inhalation anesthesia, the partial pressure of the inhaled anesthetic in the brain equals that in the lung when steady-state conditions are achieved. Therefore, at a given level (depth) of anesthesia, measurements of the steady-state alveolar concentrations of different anesthetics provide a comparison of their relative potencies. The volatile anesthetic concentration is the percentage of the alveolar gas mixture, or partial pressure of the anesthetic as a percentage of 760 mm Hg (atmospheric pressure at sea level). The minimum alveolar anesthetic concentration (MAC ) is defined as the... 

Flalothane, desflurane, enflurane, sevoflurane, and isoflurane all decrease mean arterial pressure in direct proportion to their alveolar concentration. With halothane and enflurane, the reduced arterial pressure appears to be caused by a reduction in cardiac output because there is little change in systemic vascular resistance despite marked changes in individual vascular beds (eg, an increase in cerebral blood flow). In contrast, isoflurane, desflurane, and sevoflurane have a depressant effect on arterial pressure as a result of a decrease in systemic vascular resistance with minimal effect on cardiac output. 

Therefore, when Pco = 1/220 XP02 the hemoglobin in the blood will be 50% saturated with carbon monoxide. Since air contains 21% oxygen, approximately 0.1% carbon monoxide will give this level of saturation. Hence, carbon monoxide is potentially very poisonous at low concentrations. The rate at which the arterial blood concentration of carbon monoxide reaches an equilibrium with the alveolar concentration will depend on other factors such as exercise and the efficiency of the lungs. Other factors will also affect the course of the poisoning. 

Depth of anesthesia is determined by the concentration of anesthetic agent that reaches the brain. Brain concentration, in turn, depends on the solubility and transport of the anesthetic agent in the bloodstream and on its partial pressure in inhaled air. Anesthetic potency is usually expressed as a minimum alveolar concentration (MAC), defined as the percent concentration of anesthetic in inhaled air that results in anesthesia in 50% of patients. As shown in Table 9.6, nitrous oxide, N2O, is the least potent of the common anesthetics. Fewer than 50% of patients are immobilized by breathing an 80 20 mix of nitrous oxide and oxygen. Methoxyflurane is the most potent agent a partial pressure of only 1.2 mm Hg is sufficient to anesthetize 50% of patients, and a partial pressure of 1.4 mm Hg will anesthetize 95%. 

Interferon- gamma (INF-y) Antitumor Human (Phase I trial) Inhalation Inhalation increases alveolar concentration of INF-y without major side effects [99]... 

The slope of the regression line implies that the MAC (minimal alveolar concentration effective in 50 percent of animals) is inversely proportional to partition coefficient or potency is directly proportional to partition coefficient. The Meyer-Overton correlation suggests that the site at which anesthetics bind is primarily a hydrophobic environment. Although a wide variety of compounds lie on the Meyer-Overton correlation line, there are many compounds that do not. This suggests that the chemical properties of the anesthetic site differ from those of olive oil. 

Petrenko AB, Tsujita M, Kohno T et al. (2007) Mutation of alG T-type calcium channels in mice does not change anesthetic requirements for loss of the righting reflex and minimum alveolar concentration but delays the onset of anesthetic induction. Anesthesiology 106 1177-1185... 

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... 

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