Minimum Alveolar Concentration (MAC)
The first stimulus-response test devised for assessing anesthetic potency was Minimum Alveolar Concentration (MAC), developed by Edmund Eger and colleagues at UCSF in 1965. Here, the stimulus is a small skin incision and the response is "purposeful movement." For an individual subject, MAC is the minimum concentration at which no movement is observed in response to an incision. When applied to a group of test subjects, MAC (or MAC-immobility) really refers to the Median Alveolar Concentration that at which half of the subjects do not move in response to a skin incision. The value of MAC-immobility is that it helps predict how much anesthetic will be required to keep patients from moving during surgery, which is obviously important to the surgeon.
A related stimulus response test for awareness was introduced in the 1970s. MAC-awake is the minimum alveolar concentration at which an anesthetized patient responds appropriately to spoken commands. Commands such as "open your mouth" and "squeeze my hand" are frequently given at the end of an anesthetic to establish whether the patient is awake. The importance of MAC-awake is that it helps predict how much anesthetic is required to ensure that patients are unaware. This is a particularly important concept in cases where muscle relaxants are used to prevent movement during surgery. In this circumstance, patients who receive inadequate anesthetic may be awake, but unable to move and thereby communicate with caregivers. In general, it takes less anesthetic to prevent awareness than to prevent movement in response to pain. For volatile anesthetics, MAC-awake is generally about one third of MAC, but for nitrous oxide, MAC-awake is about 2/3 x MAC.
MAC-blockade of adrenergic responses (MAC-BAR) is another scale devised to test the potency of anesthetics for ablating tachycardia and hypertension in response to noxious stimuli during anesthesia. It is mentioned here mostly for historical and illustrative purposes, because it has questionable value as a clinical measure. It takes more anesthetic to block adrenergic responses than to block movement. At these concentrations, many patients will suffer hypotension and hypoventilation due to anesthetic suppression of brainstem circuits and reflexes.
Amnesia is the absence of memory, and while it is a goal of anesthesia, it is impossible to assess intra-operatively. By definition, we can only establish whether memories were formed after the anesthetic is turned off and the patient is awake and able to respond to questions. It is also difficult to assess memory in a controlled way unless one devises specific stimuli (like test-word lists) to be read to patients during an exposure to the anesthetic to see if they can recall any of test-words afterwards. Explicit (conscious) memory is when the patient can remember and recite test-words. Implicit (unconscious) memories can also form during exposure to anesthetics?this can be established by showing that patients who lack explicit memory of test-words are more likely to pick those words from another list or to complete word stems with the test-words. Anesthetics block explicit memory formation at concentrations that are lower than MAC-awake. Thus, it is a rare occurrence when a patient reports that they were awake during an anesthetic and can recite noises or conversation from the operating room. More frequently, patients recall vague feelings or sensations that are difficult to confirm were actual experiences during a period of intra-operative wakefulness.
Analgesia is frequently listed as a goal of general anesthesia, but this is a philosophical premise that is difficult to defend. Pain is a subjective experience, requiring awareness. Therefore an anesthetized unaware patient cannot experience pain. It is more universally acceptable to assert that post-operative analgesia is a goal of an anesthetic if post-operative pain is anticipated, but that is clearly not achieved using a general anesthetic agent. What is certain is that analgesic drugs like opioids reduce the amount of general anesthetic required to block responses to noxious stimuli. That is, analgesics will reduce MAC-immobility and MAC-BAR. Analgesics will also reduce MAC-awake if noxious stimulation (like surgery) is occurring simultaneously with spoken commands to test for awareness. This effect has also been shown in patients receiving epidural or spinal block together with a general anesthetic.
An important point to reiterate is that the various behavioral effects of general anesthetics are not produced at the same drug concentrations (Figure 3). This fact implies that anesthetics affect distinct circuits in the nervous system in different ways and perhaps by more than one mechanism. In fact, there is experimental evidence demonstrating that the immobilizing action of anesthetics is mediated almost entirely through spinal mechanisms. Blocking communication between the spinal cord and brainstem does not affect MAC-immobility. In contrast, awareness and memory are associated primarily with brain circuits.
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