Emergence from general anesthesia and the sleep-manifold

Abstract

The electroencephalogram (EEG) during the re-establishment of consciousness after general anesthesia and surgery varies starkly between patients. Can the EEG during this emergence period provide a means of estimating the underlying biological processes underpinning the return of consciousness? Can we use a model to infer these biological processes from the EEG patterns? A frontal EEG was recorded from 84 patients. Ten patients were chosen for state-space analysis. Five showed archetypal emergences; which consisted of a progressive decrease in alpha power and increase peak alpha frequency before return of responsiveness. The five non-archetypal emergences showed almost no spectral EEG changes (even as the volatile general anesthetic decreased) and then an abrupt return of responsiveness. We used Bayesian methods to estimate the likelihood of an EEG pattern corresponding to the position of the patient on a 2-dimensional manifold in a state space of excitatory connection strength vs. change in intrinsic resting neuronal membrane conductivity. We could thus visualize the trajectory of each patient in the state-space during their emergence period. The patients who followed an archetypal emergence displayed a very consistent pattern; consisting of progressive increase in conductivity, and a temporary period of increased connection strength before return of responsiveness. The non-archetypal emergence trajectories remained fixed in a region of phase space characterized by a relatively high conductivity and low connection strength throughout emergence. This unexpected progressive increase in conductivity during archetypal emergence may be due to an abating of the surgical stimulus during this period. Periods of high connection strength could represent forays into dissociated consciousness, but the model suggests all patients reposition near the fold in the state space to take advantage of bi-stable cortical dynamics before transitioning to consciousness.

Keywords: connection strength; emergence; general anesthesia; resting membrane conductivity; sleep-manifold.

Figure 1

Example power spectral density estimate showing absolute delta (∗) and alpha (◦) power. Oscillatory alpha power is the difference between maximal alpha power (◦) and the alpha power at the linear regression estimate (△).

Figure 2

Sleep-manifold showing the folding state-space surface (folded area is bi-stable) over a two dimensional parameter space (adapted from Dadok et al., 2014).

Figure 3

Oscillatory alpha power against alpha frequency for each of 82 patients for the 15 min prior to the start of emergence. Green diamonds are the centroid and red ellipsoids the area of 80% of the closest points from the centroid. Four patients are displayed in either blue (WH19 and WH42, “archetypal” transitions) or black (WH9 and WH57, “non-archetypal” transition).

Figure 4

Patient WH19: Archetypal emergence (alpha frequency increase, alpha loss, delta loss). (A) Spectrogram of the observation period. Start of emergence shown as a vertical green line at 900 s, time of patient response as a vertical red line. (B) Frequency of maximal oscillatory alpha power. (C) Concentration of anesthetic gas (C_eMAC), blue line, left vertical axis, and opioid levels as equivalent Fentanyl (C_eFentanyl, ng/ml), green line, right vertical axis. (D) Absolute alpha power (dB) against absolute delta power (dB) for prior to start of emergence (black circles), during emergence period (blue circles), and following recovery of response (ROR).

Figure 5

Patient WH19, Sleep Manifold. (A) Spectrogram as in Figure 4. (B) Excitatory connection strength (L-parameter) over period of observation. (C) Change in resting membrane impedance (Δh^rest_e) over period of observation. (D) Resultant positioning on the sleep-manifold, with a black cross being the start of, and a white cross being the end of the observation period, with intermediate shades on the gray-scale representing the time progression between these time-points.

Figure 6

Patient WH42. Archetypal emergence. (alpha frequency increase, alpha loss, persistent delta). (A) Spectrogram of the observation period. Start of emergence shown as a vertical green line at 900 s, time of patient response as a vertical red line. (B) Frequency of maximal oscillatory alpha power. (C) Concentration of anesthetic gas (C_eMAC), blue line, left vertical axis, and opioid levels as equivalent Fentanyl (C_eFentanyl, ng/ml), green line, right vertical axis. (D) Absolute alpha power (dB) against absolute delta power (dB) for prior to start of emergence (black circles), during emergence period (blue circles), and following recovery of response (ROR).

Figure 7

Patient WH42, Sleep-Manifold. (A) Spectrogram as in Figure 6. (B) Excitatory connection strength (L-parameter) over period of observation. (C) Change in resting membrane impedance (Δh^rest_e) over period of observation. (D) Resultant positioning on the sleep-manifold, with a black cross being the start of, and a white cross being the end of the observation period, with intermediate shades on the gray-scale representing the time progression between these time-points.

Figure 8

Patient WH9: Non-archetypal emergence: minimal alpha loss, persistent theta and delta. (A) Spectrogram of the observation period. Start of emergence shown as a vertical green line at 900 s, time of patient response as a vertical red line. (B) Frequency of maximal oscillatory alpha power. (C) Concentration of anesthetic gas (C_eMAC), blue line, left vertical axis, and opioid levels as equivalent Fentanyl (C_eFentanyl, ng/ml), green line, right vertical axis. (D) Absolute alpha power (dB) against absolute delta power (dB) for prior to start of emergence (black circles), during emergence period (blue circles), and following recovery of response (ROR).

Figure 9

Patient WH9, Sleep manifold. (A) Spectrogram as in Figure 8. (B) Excitatory connection strength (L-parameter) over period of observation. (C) Change in resting membrane impedance (Δh^rest_e) over period of observation. (D) Resultant positioning on the sleep-manifold, with a black cross being the start of, and a white cross being the end of the observation period, with intermediate shades on the gray-scale representing the time progression between these time-points.

Figure 10

Patient WH57: Non-archetypal emergence (no alpha, persistent delta, periods of high frequency activity). (A) Spectrogram of the observation period. Start of emergence shown as a vertical green line at 900 s, time of patient response as a vertical red line. (B) Frequency of maximal oscillatory alpha power. (C) Concentration of anesthetic gas (C_eMAC), blue line, left vertical axis, and opioid levels as equivalent Fentanyl (C_eFentanyl, ng/ml), green line, right vertical axis. (D) Absolute alpha power (dB) against absolute delta power (dB) for prior to start of emergence (black circles), during emergence period (blue circles), and following recovery of response (ROR).

Figure 11

Patient WH57, Sleep Manifold. (A) Spectrogram as in Figure 10. (B) Excitatory connection strength (L-parameter) over period of observation. (C) Change in resting membrane impedance (Δh^rest_e) over period of observation. (D) Resultant positioning on the sleep-manifold, with a black cross being the start of, and a white cross being the end of the observation period, with intermediate shades on the gray-scale representing the time progression between these time-points.

Figure 12

Change in resting membrane impedance (Δh^rest_e, blue line, left axis), and excitatory connection strength (L-parameter, green line, right axis) plotted against decreasing anesthetic concentrations (C_eMAC) for the entire observation period for 10 patients. The five patients in the upper-half of the figure show “archetypal” emergences, those in the lower-half display “non-archetypal” emergences.