Anesthetics concentrations

In inhalation exposures, the arterial blood concentration of chloroform is directly proportional to the concentration in inhaled air. At anesthetic concentrations (8,000-10,000 ppm), steady-state arterial blood concentrations of chloroform were 7-16.2 mg/mL (Smith et al. 1973). Total body equilibrium with inspired chloroform concentration required at least two hours in normal humans at resting ventilation and cardiac output (Smith et al. 1973). 

Stewart RD, Erley DS, Schaffer AW, Gay HH Accidental vapor exposure to anesthetic concentrations of a solvent containing tetrachloroethylene. Ind Med Surg 30 327-330, 1961... 

The increase in membrane fluidity at clinically relevant anesthetic concentrations is quite small. In tact, it is mimicked by a one degree increase in temperature (Franks Lieb 1994). Clearly consciousness is not lost in states ot low-grade tever. 

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. 

Factors Affecting the Rate of Development of Anesthetic Concentration in the Lung... 

MAC is the anesthetic concentration that produces immobility in 50% of patients exposed to a noxious stimulus. 

The concentration of an inhaled anesthetic in a mixture of gases is proportional to its partial pressure (or tension). These terms are often used interchangeably in discussing the various transfer processes involving anesthetic gases within the body. Achievement of a brain concentration of an inhaled anesthetic necessary to provide an adequate depth of anesthesia requires transfer of the anesthetic from the alveolar air to the blood and from the blood to the brain. The rate at which a therapeutic concentration of the anesthetic is achieved in the brain depends primarily on the solubility properties of the anesthetic, its concentration in the inspired air, the volume of pulmonary ventilation, the pulmonary blood flow, and the partial pressure gradient between arterial and mixed venous blood anesthetic concentrations. 

The concentration of an inhaled anesthetic in the inspired gas mixture has direct effects on both the maximum tension that can be achieved in the alveoli and the rate of increase in its tension in arterial blood. Increases in the inspired anesthetic concentration increase the rate of induction of anesthesia by increasing the rate of transfer into the blood according to Fick s law (see Chapter 1). Advantage is taken of this effect in anesthetic practice with inhaled anesthetics that possess moderate blood solubility (eg, enflurane, isoflurane, and halothane). For example, a 1.5% concentration of isoflurane may be administered initially to increase the rate of rise in the brain concentration the inspired concentration is subsequently reduced to 0.75-1% when an adequate depth of anesthesia is achieved. In addition, these moderately soluble anesthetics are often administered in combination with a less soluble agent (eg, nitrous oxide) to reduce the time required for loss of consciousness and achievement of a surgical depth of anesthesia. 

During the induction phase of anesthesia (and the initial phase of the maintenance period), the tissues that exert greatest influence on the arteriovenous anesthetic concentration gradient are those that are highly perfused (eg, brain, heart, liver, kidneys, and splanchnic bed). These tissues receive over 75% of the resting cardiac output. In the case of volatile anesthetics with relatively high solubility in highly perfused tissues, venous blood concentration will initially be very low, and equilibrium with the arterial blood is achieved slowly. 

Dose-Response Characteristics The Concept of Minimum Alveolar Anesthetic Concentration the Continuum of CNS Depression... 

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... 

Eger El II, Saidman U, Brandstater B Minimum alveolar anesthetic concentration A standard of anesthetic potency. Anesthesiology 1965 26 756. [PMID 5844267]... 

Sonner JM, Antognini JF, Dutton RC, et al. Inhaled anesthetics and immobility mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg. 2003 97 718-740. 

The oxygen consumption of nerve is decreased by cocaine, procaine, and urethane, approximately in the ratio of their anesthetic concentrations. 

Dose-Response Characteristics The Minimum Alveolar Anesthetic Concentration (MAC)... 

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. 

Bilayer order decreases with increasing anesthetic concentration, as indicated by decreasing S>n values. (Reprinted from Fig. 1.2 of ref. 65 with permission from Wiley-Liss.)... 

Wolfson et al. (1972) recommended brain anesthetic concentration for construction of anesthetic indices. 

Wolfson B, Dorsch SE, Kuo TS, Siker ES (1972) Brain anesthetic concentration - a new concept. Anesthesiol 36 176-179... 

After determination of the heart rate effect and the lethal effect, the rats are sacrificed for determinations of brain tissue concentrations. The whole brain is removed and tissue anesthetic concentration is determined by gas chromatography. 

The term minimum alveolar anesthetic concentration (MAC) was coined by Merkel and Eger (1963) as an index to compare various anesthetic agents. 

Issues in the design and interpretation of minimum alveolar anesthetic concentration studies were discussed by Sonner (2002). 

Fang et al. (1997) found that maturation decreases ethanol minimum alveolar anesthetic concentration more than desflurane MAC in rats. 

Doquier et al. (2003) studied the minimum alveolar anesthetic concentration of volatile anesthetics in rats as tools to assess antinociception in animals. 

Ide et al. (1998) used airway occlusion in cats as a noxious respiratory stimulus that induces a visceral sensation of choking for determination of minimum alveolar anesthetic concentrations during halothane, isoflurane, and sevoflurane anesthesia. These values were compared with MAC values for somatic noxious stimuli such as toe pinch or tetanic stimulus. The authors recommended this method as a new concept for MAC determination. 

Eger El II, Saidman LJ, Brandstater B (1965) Minimum alveolar anesthetic concentration a standard of anesthetic potency. Anesthesiol 26 756-763... 

Eger El II, Ionescu P, Laster MJ et al. (1999) Minimum alveolar anesthetic concentration of fluorinated alkanols in rats relevance to theories of narcosis. Anesth Analg 88 867-876... 

Eger El II, Xing Y, Laster M et al. (2003) Halothane and isofluroane have additive minimum alveolar concentration (MAC) effects in rats. Anesth Analg 96 1350-1353 Fang Z, Gong D, Ionescu P et al. (1997) Maturation decreases ethanol minimum alveolar anesthetic concentration (MAC) more than desflurane MAC in rats. Anaesth Analg 84 852-858... 

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