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The concentration and second gas effects are two interesting phenomena that are pertinent in understanding the uptake and distribution of the potent inhalation anesthetics. With the possible exception of nitrous oxide (N2O), the clinical significance, however, is limited.


Increasing the fraction of inspired concentration (FI) of an inhalation anesthetic will more rapidly increase the fraction of alveolar concentration (FA) of that agent. However, increasing the FI will also increase the rate at which the FA approaches the FI (FA/FI ratio).

As shown in Figure 10-1, the administration of 65% nitrous oxide produces a more rapid rise in its FA/FI ratio as compared to the administration of 5% nitrous oxide. To help explain this concentration effect, we will examine the hypothetical scenario of nitrous oxide delivered at 100% FI. Recall that the FA of N2O is determined by the balance between its delivery to the alveoli and its uptake by the blood. At a hypothetical 100% FI, uptake of N2O creates a void that draws gas down the trachea to replace the gas taken up by the blood. Because the replacement gas concentration is 100% N2O, uptake cannot modify the FA. As the FI decreases, blood uptake will be replaced with a lower concentration of nitrous oxide. As a result, the rate at which the FA approaches the FI slows down. Remember that the curve of FA/FI versus time rises more quickly with nitrous oxide than with desflurane despite their nearly equal blood–gas partition coefficients (see Chapter 9, Figure 9-8). Note that in this comparison, N2O was given at an FI of 70%, whereas desflurane was given in a concentration of 2%. If two agents with identical blood–gas partition coefficients were delivered at identical FIs, their FA/FI ratio would be identical.


Concentration (continuous curves) and second gas effect (dashed curves). (Reproduced with permission from Miller RD, Miller’s Anesthesia, 7th ed. Philadelphia, PA: Churchill Livingstone/Elsevier; 2010.)

This concentration effect has two components:

  1. Concentrating effect—Consider the administration of 80% (80 volumes per 100 volumes) nitrous oxide to a patient. If 50% of the nitrous oxide is taken up by the blood from the lungs, the remaining 40 volumes will exist in a total of 60 volumes, yielding a concentration of 67%. In other words, the uptake of half the nitrous oxide does not simply halve the concentration because the remaining gases are concentrated in a smaller volume. Now consider the administration of 20% nitrous oxide (20 volumes per 100 volumes) with the same 50% uptake. In this scenario, 10 volumes will be taken up by the blood while 10 volumes remain in the lungs in a total of 90 volumes, yielding an 11% concentration. Therefore, ...

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