In this month's Anesthesia & Analgesia, Hendrickx and co-workers  report that two paradigms of inhaled anesthetic uptake and distribution may lead to incorrect conclusions. Hendrickx et al. find that after an initial period of washin of desflurane or isoflurane in patients, the uptake of each anesthetic (as defined by the input of liquid anesthetic required to reach and maintain a constant alveolar anesthetic concentration) is "virtually constant" and does not differ with spontaneous versus controlled ventilation. The finding of a constant uptake conflicts with: 1) the square root of time rule , and 2) the concept of progressive equilibration of anesthetics with tissue compartments having successively longer time constants. Hendrickx et al. add that "these findings may greatly simplify closed-circuit anesthesia." The authors generously shared their raw data with me, and my comments rely on those data.
The finding of a constant uptake depends on the definition of constancy. Hendrickx et al. correctly argue that during their early period of measurement, washin of the gaseous phase (circuit, bag, or ventilator, and lungs) is the primary determinant of the input of liquid anesthetic required to obtain and sustain a constant alveolar concentration of anesthetic. Input of liquid anesthetic during the first 5 min of anesthesia reflects the need to provide a gaseous phase washin and, to a smaller extent, to replace uptake by the patient. Input of liquid anesthetic thereafter reflects uptake alone. Considering the data of Hendrickx et al. in the light of these notions indicates that uptake is not constant during the first hour of anesthesia. Uptake per minute for the 10- to 20-min decade is 86% +/- 11% (mean +/- SD) of uptake during the 5- to 10-min period. Uptake per minute for the 39- to 49-min period (the last decade in which data are available for all subjects) is 70% +/- 12% of uptake during the 5- to 10-min period. Thus, uptake is not constant, decreasing by 30% over the 5 to 49-min period of observation.
Still, the 30% decrease is less than would be predicted by the square root of time rule. Uptake at the 49th min should be 43% of uptake at the 9th min (i.e., 3/7 mg = 0.43), a 57% decrease. Similarly, the decrease might be less than would be predicted from simulations of uptake that make use of mammillary models . Why? Do the square root of time and the mammillary models err, or will these models correctly describe anesthetic uptake if they apply additional factors?
Consider the traditional paradigm of anesthetic uptake. After anesthetic washes into the lungs, uptake is the algebraic sum of uptake by four tissue groups: the vessel rich group (VRG), the muscle group (MG), the fat group (FG), and fat that draws anesthetic from well-perfused tissues by intertissue diffusion (the intertissue diffusion group or ITDG) . Most equilibration with the VRG occurs in the first 5 min of anesthesia, and this tissue group figures little or not at all in the uptake Equation after5 min. The FG and ITDG have time constants for equilibration that exceed the time in question (5-49 min) by 10-fold or more. Thus, uptake to these tissue groups continues at a virtually constant level for the first 49 min of anesthesia. Uptake to the MG does decline during this period, and it is this decline that the measurements of Hendrickx et al. reveal.
But why is the decline less than might be predicted? Suppose uptake proceeds normally during the initial phase of anesthesia. The lungs and VRG equilibrate with the alveolar anesthetic partial pressure during the first few minutes of anesthesia. Uptake thereafter is sustained by the normal distribution of anesthetic to the MG, FG, and ITDG. Uptake during the 5- to 10-min period should be considerably greater than uptake at 49 min unless additional factors intervene to sustain uptake at a higher level. Perhaps they do. Sometime after 10 min, surgery begins, and the stimulus of surgery increases cardiac output and perfusion to all tissue groups. The increased perfusion increases uptake and produces a slowing or transient reversal of the declining uptake . Consistent with this thought, for the average data from each of the four groups studied by Hendrickx et al., the decrease in uptake from the 10- to 20-min decade to the 20- to 30-min decade is 4% +/- 8% (not a significant decrease). As surgery proceeds, the surface area of the wound increases, and increasing amounts of anesthetic are lost through the wound . This, too, would tend to sustain uptake, as would an increasing percutaneous loss of anesthetic .
If uptake were virtually constant, one could make good use of this constancy to deliver anesthetic at a predetermined rate without reference to complex equations (of either the square root of time type or those describing mammillary models). One could dispense with anesthetic analyzers. However, we have seen that uptake is not constant, that it decreases with time. Furthermore, uptake differs among patients in a less-than-predictable manner. At 49 min of equilibration, the highest cumulative uptake in each of the groups studied by Hendrickx et al. exceed the lowest cumulative uptake by nearly 50%. Thus, it is our good fortune to have available anesthetic analyzers that permit us to deliver closed-circuit anesthetic in a precisely controlled manner.
Hendrickx et al.  bring to us data suggesting that anesthetic uptake may be more stable than we had considered. We are indebted to Hendrickx et al. for calling our attention to the complexities of inhaled anesthetic uptake and distribution. Paradoxically, it may be complexities that provide constancy and simplicity.
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