Blood gas partition coefficient

Sevoflurane. Sevoflurane, l,l,l,3,3,3-hexafluoro-2-propyl fluromethyl ether [28523-86-6] is nonpungent, suggesting use in induction of anesthesia. The blood/gas partition coefficient is less than other marketed products (Table 1) yet similar to nitrous oxide, suggesting fast onset and recovery. In animal studies, recovery was faster for sevoflurane than for isoflurane, enflurane, or halothane (76). Sevoflurane is stable to light, oxygen, and metals (28). However, the agent does degrade in soda lime (77). 

Nitrous oxide is rapidly absorbed through inhalation, and it is distributed predominantly in blood with a blood/gas partition coefficient of 0.5 (Sten-qvist 1994). It is rapidly eliminated through the lungs, with small amounts being eliminated through the skin (Stenqvist 1994). 

Absorption of trichloroethylene in humans is very rapid upon inhalation exposure. Trichloroethylene has a blood/gas partition coefficient that is comparable to some other anesthetic gases (i.e., chloroform, diethylether, and methoxyfluorene), but it is much more lipophilic than these gases. As a consequence of these properties, the initial rate of uptake of inhaled trichloroethylene in humans is quite high, with the rate leveling off after a few hours of exposure (Fernandez et al. 1977). The absorbed dose is proportional to the inhaled trichloroethylene concentration, duration of exposure, and alveolar ventilation rate at a given inhaled air concentration (Astrand and Ovrum 1976). Several studies indicate that 37-64% of inhaled trichloroethylene is taken up from the lungs (Astrand and Ovrum 1976 Bartonicek 1962 Monster et al. 1976). 

After drawing and labelling the axis draw a series of build-up negative exponential curves with different gradients as shown. The order of the curves is according to the blood gas partition coefficients. The more insoluble the agent, the steeper the curve and the faster the rate of onset. The exceptions to this are the N20 and desflurane curves, which are the opposite way round. This is because of the concentration effect when N20 is administered at... 

Agent bp ( C) Blood gas Partition Coefficient Muscular Coordination Recuperation Time (min) Metabohsm %... 

Four highly fluorinated ethers with low boiling points are currently used in anesthesia enflurane, isoflurane, sevoflumne, and desflurane (Figure 8.89). Des-flurane and sevoflurane are now the most used (sevoflurane is especially used in pediatrics). They exhibit the lowest blood-gas partition coefficients, the lowest ratio of toxic metabolites, and the lowest solubilities in lipids. These features limit the retention and, consequently, the metabolism is delayed (Table 8.2). 

Halothane was introduced into clinical practice in 1956. It was not the first fluorinated anaesthetic— fluoroxene (Fluoromar) holds that distinction—but it was the first to achieve widespread acceptability. Halothane is a fluorinated alkane 1-bromo, 1-chloro -2,2,2-trifluoroethane (Figure 3.2). It has a characteristic odour, similar to chloroform, and requires a stabiliser, thymol (0.01%), to prevent degradation by light. Halothane has a blood/gas partition coefficient of 2.4 able 3.2) but its lack of irritant qualities makes possible the use of relatively high inspired concentrations (2-4%). For that reason, inhalation induction is characteristically smooth and rapid. Compared to sevoflurane, and possibly isoflurane, recovery from halothane anaesthesia is delayed. 

These are shown in Table 3.3. Xenon (MAC 70%) has a potency of about twice that of nitrous oxide (MAC 104%). Thus, it can be given in anaesthetic concentrations in o> gen with less risk of hypoxia. It is highly insoluble in all body tissues with a blood/gas partition coefficient of 0.14 (nitrous oxide, 0.47 sevoflurane, 0.65 desflurane, 0.42). 

One of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood is its solubility characteristics (Table 25-2). The blood gas partition coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood compared with that of inspired gas. The partition coefficients for desflurane and nitrous oxide, which are relatively insoluble in blood, are extremely low. When an anesthetic with low blood solubility... 

Tensions of three anesthetic gases in arterial blood as a function of time after beginning inhalation. Nitrous oxide is relatively insoluble (blood gas partition coefficient = 0.47) methoxyflurane is much more soluble (coefficient = 12) and halothane is intermediate (2.3). 

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. 

The newer volatile anesthetics, desflurane and sevoflurane, have physicochemical characteristics (ie, low blood gas partition coefficients) that are favorable to a more rapid onset and shorter duration of anesthetic actions compared with isoflurane and halothane. However, both of these newer agents also have certain limitations. The low volatility of desflurane necessitates the use of a specialized heated vaporizer, and the pungency of the drug leads to a high incidence of coughing and sympathomimetic side effects that make it less than ideally suited for induction of anesthesia. 

A rapid onset of anesthetic action is also characteristic of desflurane and sevoflurane, compounds that also have a low blood gas partition coefficient. 

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. 

The ratio of the blood/gas partition coefficients was assumed to be 1. The concentration was adjusted for intermittent exposure by multiplying the LOAEL (10.2 ppm) by 6/24 to correct for less than a full day of exposure. The resulting number (adjusted LOAEL) is 2.50 ppm. 

Disposition in the Body. Absorbed into the circulation after inhalation the blood gas partition coefficient is high (about 12). About 90% of a dose is slowly exhaled unchanged and very little is metabolised a small amount may be excreted unchanged in the urine. Acetaldehyde is believed to be a minor metabolite. 

Disposition in the Body. Rapidly absorbed upon inhalation blood gas partition coefficient about 2.4. It accumulates in adipose tissue. About 60 to 80% of an absorbed dose is exhaled unchanged from the lungs in 24 hours and smaller amounts continue to be exhaled for several days or weeks. A variable amount is metabolised in the liver by debromination and dechlorination replacement of a fluorine atom by a methoxy group followed by glucuronic acid conjugation occurs to a limited extent. Other metabolites which have been detected in expired air and in blood are 2-chloro-1,1,1-trifluoroethane and 2-chloro-l, 1-difluoroethylene. Up to about 20% of a dose may be excreted in the urine as trifluoroacetic acid and its salts. Bromide ion is slowly excreted in the urine. 

An anaesthetic that has high solubility in blood, i.e., a high blood/gas partition coefficient, will provide a slow induction and adjustment of the depth of anaesthesia. This is because the blood acts as a reservoir (store) for the drug so that it does not enter the brain easily imtil the blood reservoir has been filled. A rapid induction can be obtained by increasing the concentration of drug inhaled initially and by hyperventilating the patient. 

Agents that have low solubility in blood, i.e., a low blood/gas partition coefficient (nitrous oxide, sevoflurane), provide a rapid induction of anaesthesia because the blood reservoir is small and agent is available to pass into the brain sooner. 

Desflurane has the lowest blood/gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and caimot be administered with conventional vaporisers. It has a very pimgent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia. 

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe and is second choice to sevoflurane for inhalational induction of anaesthesia. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 363). 

Rgure 2.13 Postprandial and fasting effects on blood/gas partition coefficients (A) the broken line represents the situation in which the values of the two blood/gas partition coefficients are identical. 

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