The solubility of anaesthetic gases in blood and tissues

Blood solubility and anaesthetic action

Anaesthetic gases such as ether which have a high blood solubility (Ostwald solubility coefficient in blood is 12) are transported away from the lungs more rapidly than those such as halothane (Ostwald coefficient = 2.3) and nitrous oxide (Ostwald coefficient = 0.47). As a consequence, the concentration of ether in alveolar air builds up more slowly than that of the more poorly soluble anaesthetic gases and is only slightly above the level in the tissues. Figure 2.12 shows the way in which the alveolar concentrations of anaesthetic gases with a range of blood solubilities (expressed as a percentage of their final values) change with time after administration. We can see that soluble anaesthetics such as ether are very slow to approach their equilibrium value compared with those of lower solubility; nitrous oxide, for example, reaches an equilibrium value in 10-15 minutes. Because the concentrations of anaesthetics in the blood and brain are close to the alveolar concentrations, there is a rapid onset of anaesthesia in the case of nitrous oxide and a relatively slow induction of anaesthesia with ether.

Increases in blood solubility without corresponding increases in tissue solubility slow the rate at which halothane increases in the alveoli. Because of the increased content of this anaesthetic in the blood flowing through the tissues, however, the halothane partial pressure in the tissues approaches equilibrium more rapidly than in the alveoli. The net consequence is that the time for induction with halothane is not greatly affected by changes in blood solubility, although the depth of anaesthesia achieved after 10-30 minutes may be considerably affected.

Influence of blood and tissue composition on solubility

The solubility of an anaesthetic gas in the blood is mainly a consequence of its higher solubility in the lipids and proteins than in aqueous solution. Consequently, changes in the amounts of these components in the blood can alter the anaesthetic solubility in this solvent. The influence of the composition of the blood on the solubility of anaesthetic gases has been studied by several workers;9 we will consider a few examples here. In many cases anaemia leads to a decrease in blood solubility through a reduction in haemoglobin and in the protein and lipids which form the red cells. Changes in the concentration and type of plasma proteins have been reported to affect the solubility of halothane.10 Some workers have correlated the solubility of halothane with the concentration of plasma triglycerides in the blood of dogs and humans11,12 and also of horses.13 Changes in serum constituents with age lead to concomitant changes in the blood/gas partition coefficient, Ablood/gas. A patient who has recently eaten will have a higher blood lipid content than a fasting patient, and this results

Figure 2.12 Graph of alveolar concentration of anaesthetic gases against time during anaesthetic uptake.

Time (min)

Figure 2.12 Graph of alveolar concentration of anaesthetic gases against time during anaesthetic uptake.

in a greater concentration of anaesthetic in the blood (Fig. 2.13).

The high lipid solubility of anaesthetics is an important factor in determining their solubility in tissue fluids. The solubility of xenon and krypton in human liver tissue has been found to be proportional to its triglyceride content.14 Halothane solubility has been correlated with the fat content of the muscles of horses.13 This relationship between solubility and fat content implies a greater muscle solubility in adults than in children because of a greater infiltration of fat in adult muscles. The consequence of increased tissue solubility on the depth and rate of onset of anaesthesia is different from that caused by increased blood solubility. Although a similar slowing of the rate of rise of anaesthetic in the alveoli is observed, the increased capacity of the tissues for the anaesthetic leads to an increase in the time required for the partial pressure in the tissues to approach that in the alveoli. The resultant effect of increased tissue solubility is a delayed onset of anaesthesia and also a decreased eventual depth of anaesthesia produced by a given inspired concentration.

Influence of pressure

It is perhaps not surprising, bearing in mind the complexity of blood and tissue fluids, that Henry's law is frequently disobeyed. For example, departures of the solubility versus pressure relationships from Henry's law have been reported for cyclopropane in blood,15 which have been attributed to the binding of the cyclopropane by the haemoglobin molecule. An increase in pressure at low partial pressures of cyclopropane simply results in an increase in the proportion of cyclopropane-binding sites on the haemoglobin molecule that are occupied. At higher pressures, however, nearly all the sites become occupied and further pressure increases cannot further increase the extent of cyclopropane binding, and a deviation from Henry's law becomes apparent. Similar deviations from Henry's law have been reported for xenon in the presence of myoglobin.16 In contrast, a study of the solubility of isoflurane and halothane in rabbit blood and human or rabbit brain has shown Henry's law to be obeyed over a wide range of partial pressures.17 The authors have concluded that there was no evidence of saturable binding sites for these anaesthetic gases.

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