The concept of the so-called “minimum”—but actually median—alveolar concentration (MAC) required to prevent movement to a surgical stimulus was the original yardstick that advanced mechanistic anesthesia research by allowing comparisons between agents and species. Understanding the processes underlying MAC was the original “holy grail” of research into anesthetic drug actions, but it appeared to be uncrackable. Funding for laboratories to systematically look into mechanisms of immobility dried up as interest moved toward mechanisms of memory suppression and hypnosis, commonly referred to with the trendy but poorly defined term “unconsciousness.” This pitiful paucity of basic science investigation into mechanisms of MAC is unfortunate because of its biologic complexity and obvious clinical relevance. All clinicians will at some time have experienced the frustration of having a patient who is apparently overanesthetized, requires vasoconstrictors for blood pressure support, and...

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