Uptake

The solubility of the inhalation anesthetic agent, the patient’s cardiac output, and the partial pressure difference of the gas between the alveoli and pulmonary vein are the three major factors affecting uptake and distribution. Their relationship is expressed by the formula:

< ?xml:namespace prefix = "mml" />Uptake= λ ·Q·PA–Pv_PB

where λ is solubility, Q is the cardiac output, PA – P is the alveolar-venous partial pressure difference, and PB is the barometric pressure.

Solubility

The solubility of an anesthetic agent is defined by its blood-gas partition coefficient. It describes the relative affinity of an inhaled anesthetic agent for the blood. For example, isoflurane has a blood-gas partition coefficient of 1.4. This means that, at equilibrium, the isoflurane concentration in the blood would be 1.4 times the concentration in the gas (alveolar) phase. By definition, the partial pressures of the agent in blood and gas are identical at equilibrium, but the blood would contain more isoflurane. The blood-gas partition coefficients of commonly used inhalation anesthetic agents are listed in Table 61-1.

The higher the blood-gas partition coefficient, the greater the amount of anesthetic agent dissolved in blood at equilibrium, and onset of anesthesia is delayed because it is not the total amount of drug in the blood, but the partial pressure of inhalation agent in the blood and, therefore, in the brain that induces anesthesia. For agents with a high coefficient, it takes a relatively long time to “fill the tank” before the partial pressure begins to rise high enough to induce anesthesia. Gases with a high coefficient, because the gas diffuses so quickly into blood, have a relatively low alveolar/inspired gas ratio (FA/FI) (Figure 61-1), which also delays onset. Uptake of the more soluble inhalation agents can be increased by anesthetic overpressuring, that is, delivering a concentration of inspired gas two to four times the MAC (minimum alveolar concentration).

Cardiac output

As cardiac output increases, more blood travels through the lungs, thereby removing more anesthetic from the gas phase and resulting in a lower FA and a slower rate of FA increase. Changes in cardiac output have the most pronounced effect on the uptake of more soluble anesthetic gases. The alveolar-venous anesthetic gradient results from tissue uptake. As this gradient approaches 0 and tissues are fully saturated, uptake of anesthetic by the blood ceases, and the FA/FI ratio more rapidly approaches unity.

With decreased cardiac output, less blood flows through the lungs. Less anesthetic agent is taken up by the blood, and alveolar concentration increases more rapidly. Again, highly soluble agents are most affected. With a less soluble anesthetic, the rate of FA/FI increase is rapid regardless of the cardiac output and, thus, is little affected by a decrease in cardiac output. With highly soluble agents, a potentially dangerous positive feedback exists in that anesthetic-induced cardiac depression decreases uptake, increases alveolar concentration, and further depresses cardiac output.

The anesthetic agent in the blood is initially distributed to the vessel-rich tissues (Table 61-2). Soon after blood returns to the lungs, depending on its blood-gas partition coefficient, it has the same partial pressure that it had on leaving the lungs. As the gradient for the uptake of anesthetic approaches 0, less agent is taken up, and alveolar concentration rises (PI ∼ PA ∼ PBLOOD). Because children have greater perfusion of the vessel-rich group than do adults, FA/FI rises more rapidly in children, so anesthesia is achieved more rapidly in these patients.

An increased functional residual capacity results in slower uptake of the inhalation agent simply because there is a greater volume of lung that must be filled. This volume dilutes the concentration of inhalation agent, therefore slowing induction. Conversely, uptake is more rapid for patients with disease conditions that reduce functional residual capacity.

A ventilation-perfusion mismatch tends to increase the alveolar anesthetic partial pressure and decrease the arterial anesthetic partial pressure. With the less soluble anesthetic agents, the arterial partial pressure of the agent decreases markedly because of mixing with blood from areas with inadequate ventilation. With more highly soluble anesthetic agents, blood from the relatively hyperventilated alveoli contains more anesthetic agent, which compensates for blood emerging from underventilated alveoli, resulting in less effect on the arterial partial pressure.

A left-to-right cardiac shunt in the presence of normal tissue perfusion does not affect anesthetic uptake. With a right-to-left shunt, a fraction of blood does not pass through the lungs and cannot take up anesthetic. This type of shunt results in a slower rate of increase in arterial concentration of anesthetic agent and slower induction of anesthesia, with the least soluble agents affected most.

Ventilation

The PA of an anesthetic agent influences the partial pressure in the brain. The FI of the anesthetic gases and alveolar ventilation are the two factors influencing the rate at which the alveolar concentration of the anesthetic agent increases. Increasing the FI of an inhalation agent or increasing alveolar ventilation facilitates the rate of increase of the anesthetic gas in the alveoli. The rate of FA increase is also influenced by the concentration effect and the second-gas effect.

Concentration effect describes how increasing the FI of a gas produces a more rapid rise in alveolar concentration of that gas. This phenomenon is the sum of two components. The first is confusingly termed the concentrating effect; the second is an effective increase in alveolar ventilation.

As the inhalation agent is taken up by the blood, the total lung volume is decreased by the amount of gas taken up by the blood, concentrating (hence, the concentrating effect) the agent remaining within the lung. The magnitude of this effect is influenced by the initial concentration of gas within the lung—the higher the concentration, the greater the effect. For example, when the lung is filled with 1% N₂O, if one half is taken up, then the remaining concentration is 0.5% (0.5 part in 99.5 parts). If the same lung is filled with 80% N₂O and one half is taken up, then the remaining concentration is 67%, not 40% (40 parts in a total of 60).

The effective increase in alveolar ventilation occurs as uptake of N₂O into the blood causes a decrease in volume within the lung, causing additional gas to be drawn in via the trachea to replace N₂O lost by uptake. This decreases the FI/FA concentration difference because inspired gas (as in the second example earlier) contains 80% N₂O, thus further raising the alveolar concentration of N₂O from 67% to 72%.

Second-gas effect

The phenomenon known as the second-gas effect results from large volumes of a first gas (usually N₂O) being taken up from alveoli, as described in the concentrating effect, increasing the rate of increase in alveolar concentration of the second gas given concomitantly. Factors responsible for the concentration effect also govern the second-gas effect. The effective increase in alveolar ventilation should increase the alveolar concentration of all concomitantly inspired gases regardless of their inspired concentration. Moreover, uptake of the first gas reduces the total gas volume, thereby increasing the concentration of the second gas (Figure 61-2).

The fractional uptake of the second gas determines the relative importance of increased ventilation versus the concentrating effect. Increased ventilation plays the greater role in raising the second-gas concentration when the fraction of the second gas removed by uptake into the blood is large (i.e., with more soluble second gases). The concentrating effect plays the greater role when uptake into the blood is small (i.e., with less soluble agents).

Both the concentration and second-gas effects speed inhalation inductions (i.e., increase the rate of FA/FI increase). Uptake of large volumes of anesthetic agent, usually N₂O, concentrates the remaining gases regardless of whether they are N₂O (concentration effect) or a second gas concomitantly administered (second-gas effect). Uptake of large volumes also increases the effective alveolar ventilation. The concentrating action plus the increase in alveolar ventilation tend to increase the concentration of both N₂O and a second gas.

During hyperventilation, more anesthetic agent is delivered to the lungs, increasing the rate of FA/FI increase. This change is more pronounced with more soluble anesthetic agents because a large portion of highly soluble anesthetic agent delivered to the lungs is taken up by the blood. During hypoventilation, the rate of increase in the alveolar concentration is slowed because of decreased delivery of anesthetic gas to the lungs.

Although acknowledging the usefulness of the original description of the concentration and second-gas effects for teaching purposes, Korman and Mapleson suggested that these explanations are too simplistic and do not consider alternative volume effects of gas uptake. A study by Carette and colleagues in 2007 suggests that the second-gas effect may persist well past the phase of uptake of large volumes of N₂O. It should also be pointed out that a 1999 study by Sun and associates reported that N₂O did not affect the alveolar or blood concentrations of a second gas (enflurane) under controlled constant-volume ventilation (leading the authors to conclude that the second-gas effect is not a valid concept), whereas another study by Taheri and Eger in the same year using N₂O and desflurane effectively demonstrated the predicted effects of the concentration and second-gas effects.