ELECTROPHYSIOLOGIC MONITORING

Spontaneous Electroencephalogram

The realization that anesthetic drugs alter the EEG dates back to the discovery that the brain produces electrical activity (see Chapter 38 ).^[127] In 1875, Caton^[128] used chloroform to convince himself that the electrical oscillations from the brain were indeed biologic in origin. During the 1920s and 1930s, when electronic amplifiers allowed recording of these small voltages through the skull, Berger^[129] measured the influence of chloroform on the EEG. In 1937, Gibbs and coauthors^[130] reported that anesthetics changed EEG activity from low-voltage fast waves to high-voltage slow waves and postulated that the EEG could be used to measure the effects of anesthesia. In 1952, Faulconer^[131] demonstrated with ether that the depth of anesthesia, based on recognition of EEG patterns, correlated with the arterial concentration of ether. He also demonstrated that the presence of nitrous oxide lowered the arterial concentration of ether necessary to produce a given EEG effect.

The EEG can be considered a measure of the depth of anesthesia for several reasons. It represents cortical electrical activity derived from summated excitatory and inhibitory postsynaptic activity, which is controlled and paced by subcortical thalamic nuclei. This electrical activity has direct physiologic correlates relevant to the depth of anesthesia. Cerebral blood flow and cerebral metabolism are related to the degree of EEG activity.^[132] Anesthetic drugs affect both cerebral physiology and EEG patterns. The EEG is a noninvasive indicator of cerebral function when the patient is unconscious and unresponsive. Although recording of the raw EEG involves accumulating a large amount of information and EEG tracings, new computer analysis techniques can summarize and distill the EEG into a condensed, descriptive format (the "processed" EEG).^{[133] [134]} Rampil^[135] reviewed the value of the processed EEG in the clinical practice of anesthesia.

Inadequate anesthesia generally causes EEG activation. Peripheral noxious stimuli reach the brain through afferent systems that pass through the ascending reticular activating systems of the brainstem. These systems regulate corticocerebral function and thus affect the underlying EEG pattern. Noxious stimuli can cause three types of changes in the EEG: (1) desynchronization with the appearance of 20- to 60-Hz fast rhythms (EEG activation), (2) the appearance of 6- to 10-Hz spindles, and (3) bursts of 1- to 3-Hz slow waves.^[136] These patterns vary with individual anesthetics and with the nature of the stimulation. ^[137] For example, during light levels of thiopental anesthesia in dogs (steady-state plasma concentrations of 15 to 27 µg/mL),

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The EEG is a valuable tool because it reflects cerebral physiology, it is a continuous and noninvasive measure, and it changes markedly on administration of anesthetic drugs.^[139] However, early studies concluded that the EEG was not a meaningful measure of the depth of anesthesia. Galla and colleagues^[140] examined raw EEG signals for 43 patients and correlated EEG patterns with clinical signs of anesthesia. A discrepancy seemed to exist between the clinical signs and EEG patterns, especially during induction and emergence. During induction, clinical signs indicated that the patients were more lightly anesthetized than the EEG patterns suggested, whereas on emergence, clinical signs indicated greater anesthetic depth. Levy^[141] investigated processed EEG signals during induction and before bypass in patients undergoing cardiac surgery who were given potent inhaled anesthetics and opioids. He examined a series of univariate descriptors, including median frequency (the frequency below which 50% of the EEG power is located) and spectral edge (the frequency below which 95% of the EEG power is located). He concluded that the multimodal EEG activity observed in 64% of cases precluded the use of single univariate parameters to describe the anesthetic state. Berezowskyj and coworkers^[142] had similar findings with the use of power spectral analysis in patients given nitrous oxide, opioid, and halothane for anesthesia. Clinical assessment of the depth of anesthesia did not correlate well with EEG patterns.

Two studies attempted to correlate univariate EEG parameters to the clinical end point of awakening from anesthesia. Drummond and colleagues^[143] examined five numeric descriptors derived from the processed EEG during imminent arousal (spontaneous movement, coughing, or eye opening) from isoflurane/nitrous oxide anesthesia. These authors determined the threshold value for each parameter that best served to predict imminent arousal. Although several parameters (median frequency, spectral edge 90% frequency, total power, and frequency band ratio) predicted imminent arousal with sensitivities of 90% and specificities of 82% to 90%, none of the EEG descriptors could serve as a completely reliable, sole predictor of imminent arousal. Long and coworkers^[144] undertook a similar analysis using either isoflurane or fentanyl anesthesia. For isoflurane anesthesia, these investigators found that awakening was always presaged by an abrupt decrease in power in the 1- to 4-Hz frequency range (decrease in delta power). During emergence from fentanyl/nitrous oxide anesthesia, obvious change in the overall EEG power spectrum was noted; however, the same numeric EEG descriptors that were predictive of awakening from isoflurane also occurred during emergence from fentanyl. These two studies concluded that consistent trends in the EEG can be expected to occur with changing depth of anesthesia, with the available EEG descriptors providing potentially useful trend information regarding the changing depth of anesthesia. However, the sensitivity and specificity of the available parameters are such that none can serve as the sole indicator of anesthetic depth.

Dwyer and colleagues^[145] examined the power spectrum of the EEG in surgical patients receiving 0.6 to 1.4 MAC isoflurane-only anesthesia with skin incision. A second group of volunteers received 0.15 to 0.45 MAC isoflurane with memory testing. Different time-dependent EEG frequency parameters (e.g., spectral edge, median frequency) were examined relative to the clinical measures. The authors found that isoflurane caused some decrease in EEG activity. However, no difference in EEG parameters was found between subjects who moved and those who did not move with skin incision. In volunteers receiving low-dose isoflurane, memory of the information presented did not correlate with values of any EEG parameter. The authors concluded that the examined EEG parameters did not predict depth of anesthesia as defined by response to surgical skin incision, response to verbal command, or development of memory.

The previously described clinical research attempting to relate EEG effects to clinical anesthetic depth has resulted in inconclusive findings. When single anesthetic drugs are examined under defined conditions, it has been possible to demonstrate unambiguous relationships between EEG parameters and anesthetic drug concentrations and to use pharmacokinetic and pharmacodynamic modeling concepts to link drug concentrations to EEG drug effects.^[146] Different EEG waveform data analysis approaches have been used to define different univariate EEG parameters as measures of anesthetic drug effect. The most powerful application has been to further understand the fundamental clinical pharmacology of the anesthetic drugs. By using a statistical approach called "semilinear canonic correlation," drug-specific EEG measures have been identified for opioids,^[147] midazolam,^[148] and propofol^[149] and have proved robust when prospectively tested.^[150]

Application of the EEG to measure clinical depth of anesthesia failed previously for several reasons: a lack of understanding of the effects of interactions of several concurrently administered anesthetic drugs on the EEG, no standard approach to choosing an optimal EEG parameter, and finally, no clear definition of a "gold standard" for measurement and assessment of the clinical depth of anesthesia. Attempts to apply the MAC concept of inhaled anesthetics (i.e., movement responses to skin incision) have been inconclusive, as reflected in the previously discussed studies because the spinal-versus-cortical mechanisms of purposeful movement were not understood until recently.^{[29] [30] [31]}