Electroencephalography

Increasing concentrations of inhaled anesthetics produce a continuum of electroencephalography (EEG) changes, eventually resulting in burst suppression and a flat EEG (also see Chapter 31 ). In contrast, a ceiling effect is reached with opioids. Increasing opioid dosage, once this ceiling has been obtained, does not further affect the EEG.^[71] Problems with lead placement and signal processing need to be resolved before EEG analysis can be used as a routine monitor of opioid anesthesia depth. It was reported that emergence from isoflurane but not fentanyl anesthesia is associated with obvious changes in the overall EEG frequency power spectrum.^[72]

Although potency and rate of equilibrium between plasma and brain are different among opioids, the effects of fentanyl, alfentanil, sufentanil, and remifentanil are consistent.^[73] Small doses of fentanyl (200 µg) produce minimal EEG changes, whereas higher doses (30–70 µg/kg) result in high-voltage slow (delta) waves, suggesting a state consistent with anesthesia. Although transient isolated (usually frontotemporal) sharp wave activity can be observed after large doses of fentanyl and other opioids, it is not generalized. Sufentanil produces EEG changes similar to fentanyl ( Fig. 11-6 ).^[74] The effects of alfentanil on the EEG are slightly different from those of fentanyl or sufentanil. Alfentanil (125 µg/kg) produces less synchronization of the EEG and less change in the relative EEG power in the delta band.^[75]

As an effect site measure, EEG can be employed to assess onset of drug action and drug potency ratios. It was reported that a lag time between plasma drug concentration and change in the spectral edge is only 1 min for alfentanil and 6 min for fentanyl.^[74] The serum concentration ratio that results in a similar EEG pattern is 75:1 for alfentanil and fentanyl, ^[74] and the lag time is as short for alfentanil as it is for remifentanil ( Fig. 11-7 ). ^[76] This contrasts with the reported dose ratio in which fentanyl was only three to five times as potent as alfentanil. The serum

Figure 11-6 Electroencephalography (EEG) stages for fentanyl and alfentanil. Representative 3-second tracings of EEG recordings from fentanyl and alfentanil are shown. Awake = mixed α (8–13 Hz) and β (>13 Hz) activity. Stage 1 = slowing with α spindles. Stage 2 = more slowing, theta activity present (4–7 Hz). Stage 3 = maximal slowing, δ waves present (<4 Hz), with high amplitude. (From Scott JC, Ponganis KV, Stanski DR: EEG quantitation of narcotic effect: The comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology 62:234–241, 1985.)

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Figure 11-7 Time course of spectral edge and serum opioid concentration. Fentanyl (top panel) and alfentanil (middle panel) were infused at 150 µg/minute and 1500 µg/minute, respectively. Remifentanil (bottom panel) was administered at 3 µg/kg/minute for 10 minutes. The spectral edge changes lag behind the serum concentration changes in the case of fentanyl, whereas the spectral edge and serum concentrations are closely parallel in the cases of alfentanil and remifentanil. (From Scott JC, Ponganis KV, Stanski DR: EEG quantitation of narcotic effect: The comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology 62:234–241, 1985; and Egan TD, Minto CF, Hermann DJ, Barr J, Muir KT, Shafer SL: Remifentanil versus alfentanil: Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology 84:821–833, 1996.)