Section 2: Scientific Principles
Part A: Inhaled Anesthetics
Chapter 4: Uptake and Distribution

Closed-Circuit Anesthesia

The use of a closed circuit represents an extreme of anesthetic administration, one that is infrequently accomplished because few systems completely eliminate leakage of gas from the circuit. Indeed, anesthetists often apply a deliberate leak of approximately 200 mL/min by sampling gases for oxygen, carbon dioxide, and anesthetic analyses.

Usually, closed-circuit anesthesia requires replacement of three gases: (1) oxygen, (2) nitrous oxide, and (3) a potent volatile anesthetic. Each replacement implies somewhat different considerations. Oxygen replacement remains constant unless metabolism changes as a consequence of sympathetic response to stimulation, alteration in body temperature, or shivering. Replacement of nitrous oxide follows a fairly predictable course, in part because the concentration applied does not usually vary. Furthermore, it is the least soluble of anesthetics, especially in fat, and is the most prone to percutaneous loss (a constant value). Of most interest and potential variability are the uptakes of the potent inhaled anesthetics.

Uptake of potent anesthetics may be estimated from the values (constants) obtained by Yasuda et al 4, 5  in human volunteers. These values may be applied to obtain uptake at a constant alveolar concentration. To provide an appropriate level for comparison, I have assumed an alveolar concentration equal to the minimum alveolar concentration (MAC). The resulting figure (Fig. 4–16) reveals parallel shapes for each anesthetic, shapes dictated by the perfusion and solvent characteristics of the three major tissue compartments (plus intertissue diffusion). Thus, a large initial uptake rapidly decreases to a much lower level in 5 to 10 minutes, reflecting the high initial uptake of the VRG (high because of its large perfusion) and the rapid decrease in uptake imposed by a short time constant. The subsequent slower decrease primarily results from the longer time constant of the muscle group, which dominates this period until its uptake declines below that provided by fourth compartment and fat groups.

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FIGURE 4–16 The uptake (in milliliters per minute), as illustrated in this graph, resulted from the application of the constants calculated by Yasuda et al4, ,5  from their measurements in human volunteers. The application also assumes that the alveolar concentration equals maximum alveolar concentration (MAC). Uptake is a function of both MAC and solubility of the anesthetic in blood and tissues. Thus, the fivefold higher MAC for desflurane versus isoflurane is offset by a threefold lower solubility, producing less than a twofold difference in uptake at any point in time. Uptake for all anesthetics initially declines rapidly as a function of the rate at which the vessel-rich group equilibrates. The further decline after 5 to 10 minutes is a function of the approach to equilibration of the muscle group. (Data from Yasuda et al4, ,5

Although the curves for each anesthetic do not differ in shape, they differ in position. The height of each curve (i.e., uptake) is directly proportional to two factors: (1) solubility and (2) MAC. This relationship tends to minimize differences among anesthetics because solubility and MAC tend to move inversely. For example, although the MAC for desflurane is five times that for isoflurane, its uptake is less than twice that of isoflurane because of its lower solubility in both blood and tissues.

Uptake may be estimated from the “square-root-of-time rule,” first proposed by Severinghaus 63  and expanded greatly by Lowe and associates 64, 65  in their classic descriptions of closed-circuit anesthesia. This rule states that uptake at any point in time may be estimated as uptake during the first minute of anesthesia divided by the square root of time in minutes. Making certain assumptions permits an estimate of uptake during the first minute. In general, uptake equals the product of blood solubility, cardiac output, and alveolar to venous anesthetic partial pressure difference. Several sources supply standard values for solubility and cardiac output, and alveolar to venous anesthetic partial pressure difference may be estimated if we determine what alveolar partial pressure we wish and assume that venous anesthetic partial pressure is inconsequential. An inconsequential venous partial pressure is reasonable because no anesthetic can appear in venous blood before recirculation (about a half a minute) and even the anesthetic that appears is small because tissue uptake is maximal during the first minute. Thus, we might estimate isoflurane uptake in a normal adult as 1.4 times 5,400 times 0.0115, or 87 mL, where 1.4 is the blood/gas partition coefficient; 5,400 is a reasonable cardiac output, and 0.0115 is MAC as a fraction of one atmosphere (1 atm). By 4 minutes, uptake would equal 87 mL/2; by 9 minutes 87 mL/3; and by 64 minutes 87 mL/8.

Hendrickx et al 66  questioned the accuracy of the square root of time rule, suggesting that the rule overestimates the decrease in uptake with the passage of time. Eger 67  considered whether the evidence provided by Hendrickx overturns the square root of time rule, and the matter continues to be debated.

Replacement of anesthetic taken up may be accomplished by infusion of liquid anesthetic directly into the anesthetic circuit, either continuously or as boluses. A continuous infusion requires a pump of some sort, and an elegant solution uses a computer to direct a progressive decrease in infusion rate as a function of time. Bolus injection from a syringe has an elegant simplicity but has two disadvantages: (1) the circuit concentration modestly oscillates, and (2) the anesthetist is required to remember when and how much to inject. A further disadvantage accrues to the injection of desflurane by either pump or syringe. The high vapor pressure of desflurane (about 1 atm at room temperature) results in the unpredictable formation of bubbles of desflurane gas and a potential for a marked variability in the rate of infusion or injection, especially when smaller volumes of liquid are to be injected.

An alternative solution to injection of liquid applies a variable bypass (Tec-type) vaporizer, one capable of accurate delivery of a range of concentrations at low inflow rates (e.g., 200 mL/min). This solution may not be applicable in the initial delivery of anesthesia, because the demand for vapor may exceed the capability of presently available vaporizers. For example, the maximum output of a conventional isoflurane vaporizer is 5 percent, and at a 200 mL/min flow of oxygen, only approximately 10 mL of isoflurane vapor can be produced per minute, far less than the 87 mL estimated earlier. Even after 1 hour of anesthesia, an isoflurane vaporizer is barely capable of meeting the demand for anesthetic (Fig. 4–17 A). This difficulty may be overcome in several ways. If a concentration less than MAC is acceptable, a lesser delivery of vapor is required. Thus, the concurrent use of nitrous oxide decreases the demand on the vaporizer. In addition, the use of nitrous oxide also increases the total fresh gas flow to compensate for the considerable uptake of nitrous oxide. If the fresh gas flow increases to 1,500 mL/min, 79 mL of isoflurane vapor can be produced. Another solution is to select an anesthetic having a vaporizer capability closer to demand. Such a solution tends to be available for less soluble anesthetics. For example, we calculate the uptake for desflurane in the first minute of anesthesia to be 0.45 × 5,400 × 0.06, or 146 mL. At a 200-mL/min flow of oxygen, the 18 percent maximum output of a desflurane vaporizer permits delivery of 44 mL. Although still inadequate to meet demand in the first minute, this figure is 2.6 times closer to meeting that demand than the isoflurane vaporizer, and within 10 minutes, the desflurane vaporizer can supply the required volume (see Fig.4–17 A).

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FIGURE 4–17 (A–D) The ratio of delivered to alveolar concentrations (FD/FA) required to sustain the alveolar concentration constant at, for example, MAC, is a function of several factors. First, it is determined by uptake (see Fig. 4–16). Second, it is determined by rebreathing. Thus, the ratio decreases with increasing inflow rates. Although these graphs have the same shape, notice the progressive decrease in the scale on the ordinate as inflow rate increases. The lowest values for any anesthetic result from a nonrebreathing system (i.e., when the inflow rate equals minute ventilation).

Figure 4–17 A suggests one of the major difficulties associated with the closed-circuit approach, namely, control. Clearly, there is an enormous difference between delivered (i.e., vaporizer dial) and alveolar concentrations. The differences decrease with less soluble anesthetics, but even with an anesthetic such as desflurane and even after the initial high-uptake period is passed, the dialed concentration markedly exceeds the alveolar concentration that it sustains. This means that changes in uptake (e.g., secondary to the increase in cardiac output that may result from surgical stimulation) can cause considerable alterations in alveolar concentration unless the delivered concentration is altered. The alveolar concentration changes for two reasons: (1) assuming a constant ventilation, the difference between the alveolar and inspired concentrations varies directly with uptake (e.g., a greater uptake increases the difference), and (2) because of the rebreathing, the inspired concentration varies inversely with the uptake (e.g., an increased uptake lowers the inspired concentration). Thus, the sum of these effects either decreases or increases the alveolar concentration. A closed circuit has an inherent element of instability not present in an open circuit.