Anesthesia and analgesia
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Anesthesia and analgesia · Jun 1999
ReviewHypothesis: volatile anesthetics produce immobility by acting on two sites approximately five carbon atoms apart.
All series of volatile and gaseous compounds contain members that can produce anesthesia, as defined by the minimum alveolar anesthetic concentration (MAC) required to produce immobility in response to a noxious stimulus. For unhalogenated n-alkanes, cycloalkanes, aromatic compounds, and n-alkanols, potency (1 MAC) increases by two-to threefold with each carbon addition in the series (e.g., ethanol is twice as potent as methanol). Total fluorination (perfluorination) of n-alkanes essentially eliminates anesthetic potency: only CF4 is anesthetic (MAC = 66.5 atm), which indicates that fluorine atoms do not directly influence sites of anesthetic action. Fluorine may enhance the anesthetic action of other moieties, such as the hydrogen atom in CHF3 (MAC = 1.60 atm), but, consistent with the notion that the fluorine atoms do not directly influence sites of anesthetic action, adding -(CF2)n moieties does not further increase potency (e.g., CHF2-CF3 MAC = 1.51 atm). Similarly, adding -(CF2)n moieties to perfluorinated alkanols (CH2OH-[CF2]nF) does not increase potency. However, adding a second terminal hydrogen atom (e.g., CHF2-CHF2 or CH2OH-CHF2) produces series in which the addition of each -CF2- "spacer" in the middle of the molecule increases potency two- to threefold, as in each unhalogenated series. This parallel stops at four or five carbon atom chain lengths. Further increases in chain length (i.e., to CHF2[CF2]4CHF2 or CHF2[CF2]5CH2OH) decrease or abolish potency (i.e., a discontinuity arises). This leads to our hypothesis that the anesthetic moieties (-CHF2 and -CH2OH) interact with two distinct, spatially separate, sites. Both sites must be influenced concurrently to produce a maximal anesthetic (immobility) effect. We propose that the maximal potency (i.e., for CHF2[CF2]2CHF2 and CHF2[CF2]3CH2OH) results when the spacing between the anesthetic moieties most closely matches the distance between the two sites of action. This reasoning suggests that a distance equivalent to a four or five carbon atom chain, approximately 5 A, separates the two sites. ⋯ Volatile anesthetics may produce immobility by a concurrent action on two sites five carbon atom lengths apart.
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Anesthesia and analgesia · Jun 1999
Multicenter Study Clinical TrialMiddle latency auditory evoked responses and electroencephalographic derived variables do not predict movement to noxious stimulation during 1 minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia.
The electroencephalogram (EEG) and middle latency auditory evoked responses (MLAER) have been proposed for assessment of the depth of anesthesia. However, a reliable monitor of the adequacy of anesthesia has not yet been defined. In a multicenter study, we tested whether changes in the EEG and MLAER after a tetanic stimulus applied to the wrist could be used to predict subsequent movement in response to skin incision in patients anesthetized with 1 minimum alveolar anesthetic concentration (MAC) isoflurane in N2O. We also investigated whether the absolute values of any of these variables before skin incision was able to predict subsequent movement. After the induction of anesthesia with propofol and facilitation of tracheal intubation with succinylcholine, 82 patients received 1 MAC isoflurane (0.6%) in N2O 50% without an opioid or muscle relaxant. Spontaneous EEG and MLAER to auditory click-stimulation were recorded from a single frontoparietal electrode pair. MLAER were severely depressed at 1 MAC isoflurane. At least 20 min before skin incision, a 5-s tetanic stimulus was applied at the wrist, and the changes in EEG and MLAER were recorded. EEG and MLAER values were evaluated before and after skin incision for patients who did not move in response to tetanic stimulation. Twenty patients (24%) moved after tetanic stimulation. The changes in the EEG or MLAER variables were unable to predict which patients would move in response to skin incision. Preincision values were not different between patients who did and did not move in response to skin incision for any of the variables. MLAER amplitude increased after skin incision. We conclude that it is unlikely that linear EEG measures or MLAER variables can be of practical use in titrating isoflurane anesthesia to prevent movement in response to noxious stimulation. ⋯ Reliable estimation of anesthetic adequacy remains a challenge. Changes in spontaneous or auditory evoked brain activity after a brief electrical stimulus at the wrist could not be used to predict whether anesthetized patients would subsequently move at the time of surgical incision.