Factors Affecting the Rate of Development of Anesthetic Concentration in the Lung
Gases diffuse from areas of high partial pressure to ar-eas of low partial pressure; thus, the tension of anes-thetic in the alveoli provides the driving force to estab-lish brain tension. In fact, the tension of anesthetic in all body tissue will tend to rise toward the lung tension as equilibrium is approached. Consequently, factors that control or modify the rate of accumulation of anesthetic in the lung (e.g., rate of gas delivery, uptake of gas from the lung into the pulmonary circulation) will simultane-ously influence the rate at which tension equilibria in other body compartments is established.
Graphs of the alveolar tension plotted against time are used here to illustrate the changes in lung partial pressure as anesthetic is inhaled. Only a fraction of total lung gases are exchanged during one breathing cycle. Therefore, the volume of gases already in the lung dilutes the first breath of anesthetic (breathing cycle 1 in Fig. 25.3). In subsequent breathing cycles, the alveo-lar tension will continue to rise toward the inspired level along an exponentially declining curve. The net change of anesthetic tension becomes smaller with each breathing cycle, and the curve of alveolar tension will approach the inspired level more slowly.
The alveolar tension–time curve always declines in an exponential manner, but the position of the curve can be greatly affected by the rate of delivery of anes-thetic gases and the rate of their uptake into the pul-monary circulation. For this reason, it is important to consider factors that modify or regulate delivery and uptake.
Tissues, including the brain, that have a high blood flow per unit mass (Fig. 25.1) equilibrate with the alveolar tension of anesthetic gases first. Tissues with lower blood flow require a longer time and continue to accu-mulate anesthetic gas during the maintenance phase of individuals, essentially equivalent to the cardiac output) also affects the rate of induction of anesthesia.
Since more blood will pass through the pulmonary capillary bed when the cardiac output is high, it follows that a greater total transfer of any anesthetic agent across the alveolus will anesthesia, that is, after patients become unconscious.
As body tissues become saturated with anesthetic mol-ecules, blood returning to the lung will have increas-ingly high anesthetic tension, and the alveolar–arterial tension gradient will be reduced. Since the gradient controls the rate of diffusion across the alveolar capil-lary membrane, uptake is also reduced and the rate of rise of the alveolar tension of anesthetic is accelerated.
The inhalational anesthetics have distinctly different solubility (affinity) characteristics in blood as well as in other tissues. These solubility differences are usually expressed as coefficients and indicate the number of volumes of a particular agent distributed in one phase, as compared with another, when the partial pressure is at equilibrium (Table 25.3). For example, isoflurane has a blood-to-gas partition coefficient (often referred to as the Ostwald solubility coefficient) of approximately 1.4. Thus, when the partial pressure has reached equi-librium, blood will contain 1.4 times as much isoflurane as an equal volume of alveolar air. The volume of the various anesthetics required to saturate blood is similar to that needed to saturate other body tissues (Table 25.3); that is, the blood–tissue partition coefficient is usually not more than 4 (that of adipose tissue is higher).
The solubility of anesthetic agents is a major factor for the rate of induction of anesthesia, or the time re-quired to establish a level of unconsciousness adequate for surgery. Agents with limited plasma solubility and a low rate of uptake (e.g., N2O, cyclopropane, sevoflurane, and desflurane) will equilibrate rapidly with tissues. For an agent that is highly soluble in plasma (e.g., methoxyflurane), the rate of rise of alveolar tension to the inspired level and the equilibration of the gas with brain will be delayed by a higher initial uptake into plasma from the alveoli. This phenomenon is often counterintuitive to students. However, with gases, par-tial pressure is the controlling factor for equilibration between tissues, and even though uptake is high, partial pressure in the tissues and lung rises slowly, as large quantities of a highly soluble gas must be accumulated to establish the desired tension (Henry’s law).
To illustrate the effect of solubility on the rate of induction of anesthesia, we can consider a situation in which individual agents are delivered to patients at their equivalent MAC values. Under these conditions, regardless of the agent being employed, a similar level of anesthesia will be achieved. In contrast, induction rates, illustrated as the time required for the alveolar tension to rise to the inspired level (Fig. 25.3), can be seen to be quite different. A patient receiving a MAC of N2O, desflurane, or sevoflurane will be unconscious within 3 minutes. However, halothane, enflurane, and isoflurane, which have significant blood and tissue solubilities, will require at least 30 minutes before surgical anesthesia is established. Methoxyflurane, a highly soluble agent, requires several hours and may be clinically impractical if administered in this way.
The rate of pulmonary perfusion (in healthy individuals, essentially equivalent to the cardiac output) also affects the rate of induction of anesthesia. Since more blood will pass through the pulmonary capillary bed when the cardiac output is high, it follows that a greater total transfer of any anesthetic agent across the alveolus will occur in these conditions. Also, tissues normally receiv-ing a smaller proportion of the total cardiac output re-ceive a greater amount when cardiac output is high and will accumulate a larger proportion of the anesthetic crossing the alveolar membrane. Ultimately, greater up-take will slow the rate of rise of the alveolar tension– time curve, and anesthetic induction with an individual agent may be slower when the cardiac output and per-fusion of the lung are high. In low cardiac output states, the reverse is true. The rate of uptake will be lower, and the alveolar tension will rise toward the inspired tension more quickly. To minimize the effect of cardiac output on the rate of induction of anesthesia, agents of lower solubility would be preferred clinically.
Frequently it is desirable to overcome the slow rate of rise of alveolar tension associated with such factors as the high blood solubility of some anesthetics and in-creased pulmonary blood flow. Since both of these fac-tors retard tension development by increasing the up-take of anesthetic, the most effective way to alleviate the problem is to accelerate the input of gas to the alve-oli. A useful technique to increase the input of anes-thetic to the lung is to elevate the minute alveolar ven-tilation. This maneuver, which causes a greater quantity of fresh anesthetic gas to be delivered to the patient per unit of time, is most effective with highly soluble agents (Fig. 25.4).
Increasing the inspired tension of an anesthetic gas above the maintenance tension (i.e., near the MAC value) is also an effective means of quickly establishing effective alveolar tension. This maneuver, frequently re-ferred to as overpressure, parallels the concept of load-ing dose. As the desired depth of anesthesia or level of alveolar tension is achieved, the delivered tension of anesthetic must be returned to the maintenance (MAC) level to avoid overdosing the patient.
Special factors influence the rate of rise of the alveolar tension to the inspired level when anesthetics are deliv-ered in high concentration. These factors particularly significant when N2O is used, since it is often required in concentrations exceeding 25% in the inspired air.
When anesthetics are delivered in high concentra-tion, the alveolar tension will rise rapidly. Thus, if 75% N2O is being delivered in the inspired air, the 75% ten-sion in blood will be established more quickly than if 40% N2O were being inhaled and a 40% N2O tension were desired in blood.
The alveolar tension of other anesthetic gases also rises more rapidly (second gas effect) when an anes-thetic such as N2O is present in high concentration. These gases are also subject to the increased inflow (pulling in of fresh gases) as N2O is taken up into the blood.
Diffusion hypoxia may be encountered at the end of an anesthetic administration with N2O. The mechanism underlying diffusion hypoxia is essentially the reverse of the concentration effect; that is, when anesthetic ad-ministration is stopped, large volumes of N2O move from the blood into the alveolus, diluting oxygen and expanding lung expiratory volume. To avoid diffusion hypoxia, the anesthesiologist may employ 100% oxygen rather than room air after discontinuing administration of the anesthetic gas mixture.