Alveolar concentration, minimal

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. 

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. 

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

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. 

Salmempera et al. (1992) studied in dogs the potency of remifentanil, a short acting opioid analgesic, which is used as anesthetic adjunct by variable-rate infusion. Enfluorane minimal alveolar concentration was measured by the tail-clamp method in dogs before and after sequential infusion of various doses of remifentanil. The plasma concentration causing a 50% reduction of enfluorane minimal alveolar concentration was determined. 

Davis et al. (1975) Determination of the minimal alveolar concentration of halothane in the white New Zealand rabbit was published. 

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 nitrous oxide must be inhaled in high concentrations, much smaller concentrations are required in the case of the more lipophilic halothane. 

The effects of desflurane and sevoflurane on bronchial smooth muscle reactivity have been compared in a randomized study of 40 patients (36). Anesthesia was induced with thiopental, followed by muscle relaxation and ventilation. Airway pressures were recorded during administration of desflurane or sevoflurane at one minimal alveolar concentration (MAC). Airway resistance increased by 5% in the desflurane group and fell by 15% in the sevoflurane group. The increase in airways resistance was greater in smokers and with desflurane, but did not differ with sevoflurane. The result was a surprise, given that desflurane stimulates the sympathetic nervous system. Thiopental also increased airways resistance by 10%. The result is important, because induction of anesthesia can cause bronchospasm and desflurane can exacerbate this. 

MAC minimal alveolar concentration NCAM neural cell adhesion molecule... 

Muir W W III, Sams R 1992 Effects of ketamine infusion on halothane minimal alveolar concentration in horses. American Journal of Veterinary Research 53 1802-1806... 

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. 

Current anesthesia protocols usually include several agents in combinations that vary according to the depth of anesthesia required for specific procedures. Inhalational anesthetics, which include nitrous oxide and six halogenated hydrocarbons, have varying potency in proportion to their lipid solubilities. MAC value, a measure of anesthetic potency, is defined as the minimal alveolar anesthetic concentration (% of inspired air) at which 50% of patients do not respond to a surgical stimulus. MAC values are additive, lower in elderly patients, and lower in the presence of opioid analgesics and sedative hypnotics. 

Kumar et al. (1994) exposed mice to an average CR concentration of 1008 mg m 3 daily for 15 minaday for lOdays. At5days, lungs demonstrated minimal alveolar haemorrhage and after 10 days there was moderate alveolar haemorrhage and alveolar capillary congestion and a few foci of renal cortical necrosis. 

A MAC (minimal alveolar anesthetic concentration) is defined as the concentration of inhaled anesthetic, as a % of inspired air, at which 50% of patients do not respond to a surgical stimulus. 

Minimal alveolar anesthetic concentration (MAC) The alveolar concentration of an anesthetic that is required to prevent a response to a standardized painful stimulus in 50% of patients... 

Anesthetic Blood Gas Partition Coefficient Minimal Alveolar Anesthetic Concentration (%)... 

In an intermediate-duration inhalation study of nickel sulfate in rats (Dunnick et al. 1989 NTP 1996c), alveolar macrophage hyperplasia was observed at all concentrations (0, 0.03, 0.06, 0.11, 0.22, and 0.44 mg nickel/m ), and chronic active inflammation of the lungs and olfactory epithelial atrophy were noted at 0.6 mg/m. Macrophage hyperplasia tends to be an inconsistent or perhaps reversible effect that showed an increase after 7 months of exposure but not at 2 years in the chronic study. In addition to being a minimal or reversible effect, alveolar macrophage hyperplasia can be attributed to the physical stimulus of particulate treatment and is not necessarily speciflc for nickel. Therefore use of 0.03 mg/m as a LOAEL for macrophage hyperplasia to derive an intermediate MRL is questionable. Because the NOAEL identified in the chronic study (0.03 mg/m ) is at the level of a minimal LOAEL in the intermediate-duration study, the chronic MRL should be protective of both chronic- and intermediate-duration exposures. 

Body weights of female rats were 6-9% lower than controls during the second year. Hematology examinations completed at a 15 month interim sacrifice showed no effects. The only treatment-related changes noted were in the respiratory tract. Minimal to mild chronic active inflammation was observed at all concentrations at the 7 month interim sacrifice, but only at the two higher concentrations at two years. The inflammation was described as multifocal, minimal to mild accumulations of macrophages, neutrophils and cell debris within alveolar spaces. Fibrosis was observed in 2/54, 6/53, 35/53 and 43/53 male rats, and 8/52, 7/53, 45/53, and 49/53 female rats at 0, 0.03, 0.06, and 0.11 mg/m, respectively. Hyperplasia of the bronchial lymph nodes and atrophy of the olfactory epithelium were observed at the high dose. 

Eger II, E. I., Koblin, D. D., Laster, M. J., Schurig, V., Juza, M., Ionescu, P., and Gong. D. (1997) Minimum alveolar anesthetic concentration values for the enantiomers of isoflurane differ minimally. Anesth, Analg. 85, 188-192. 

Gong D, Fang Z, Ionescu P et al. (1998) Strain minimally influences anesthetic and convulsant requirements of inhaled compounds in rats. Anesth Analg 87 963-966 Hall RI, Murphy MR, Hug CC (1987) The enfluorane sparing effect of sufentanyl in dogs. Anesthesiol 67 518-525 Ide T, Sakurai Y, Aono M, Nishino T (1998) Minimum alveolar anesthetic concentrations for airway occlusion in cats A new concept of minimum alveolar anesthetic concentration-airway occlusion response. Anaesth Analg 86 191-197... 

Minimal information is available on the half life of Stoddard solvent in the body. One study showed that levels of aliphatic and aromatic components in alveolar air dropped substantially within 20 minutes of exposure (Astrand et al. 1975). However, measurable amounts remained in the blood for at least 100 minutes post-exposure. In the second study, the rate of inhalation absorption of the alkane components was fairly constant over the different exposure intervals (5 days, 6 hours/day) that were measured. The mean blood concentration of white spirits was 2 mg/L on day I and 2.54 mg/L on day 5, showing accumulation of white spirits in the blood (Pedersen et al. 1984,... 

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