The human burst suppression electroencephalogram of deep hypothermia

Abstract

Objective: Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity.

Methods: We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis.

Results: Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant.

Conclusions: These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures.

Significance: These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression.

Keywords: Burst suppression; Electroencephalogram; Hypothermia.

Figure 1. Typical Electroencephalogram of Deep Hypothermia, Example 1

(A) EEG voltage trace (Fp1). (B) Segmentation of the EEG into periods of suppression (white), non-suppression (‘burst’ state’) in black, and periods of artifact (red). (C) Spectrogram of the EEG. (D) Burst suppression probability (BSP), with overbars in red indicating periods of isoelectricity (two or more minutes with EEG voltage continuously less than 2 microvolts). (D) Temperature. (F) Representative examples of burst EEG voltage traces and (G) corresponding burst spectrograms at three different temperatures. (H) All bursts that occurred throughout surgery and had duration 30 seconds or less are shown, with temperature indicated by color. Burst amplitude and duration tend to decrease with temperatures.

Figure 1. Typical Electroencephalogram of Deep Hypothermia, Example 1

(A) EEG voltage trace (Fp1). (B) Segmentation of the EEG into periods of suppression (white), non-suppression (‘burst’ state’) in black, and periods of artifact (red). (C) Spectrogram of the EEG. (D) Burst suppression probability (BSP), with overbars in red indicating periods of isoelectricity (two or more minutes with EEG voltage continuously less than 2 microvolts). (D) Temperature. (F) Representative examples of burst EEG voltage traces and (G) corresponding burst spectrograms at three different temperatures. (H) All bursts that occurred throughout surgery and had duration 30 seconds or less are shown, with temperature indicated by color. Burst amplitude and duration tend to decrease with temperatures.

Figure 2. Typical Electroencephalogram of Deep Hypothermia, Example 2

See legend for Figure 1 for explanation of the subpanels.

Figure 2. Typical Electroencephalogram of Deep Hypothermia, Example 2

See legend for Figure 1 for explanation of the subpanels.

Figure 3. Typical Electroencephalogram of Deep Hypothermia, Example 3

See legend for Figure 1 for explanation of the subpanels

Figure 3. Typical Electroencephalogram of Deep Hypothermia, Example 3

See legend for Figure 1 for explanation of the subpanels

Figure 4. Temperature vs Suppression Probability

(A) The burst suppression probability (BSP) is plotted against the corresponding temperature at 3 minute intervals throughout the case, for the entire study cohort (black asterisks). A strong relationship is evident, with decreased brain temperatures correlating deeper levels of burst suppression, i.e. increased BSP. A regression line (straight red line) is fit to the data to show the overall trend, and a Gaussian curve was fit to the 95% interquantile range as a function of temperature using bins of width 1°C (dashed red lines). (B) A Gaussian curve (red dashed lines) provided a good fit (R²=0.83) through the interquantile difference measurements (black asterisks).

Figure 5. Burst and Suppression Lengths vs Temperature

Empirical cumulative distribution functions (CDFs) are shown for suppression lengths (A) and burst lengths (B), together with parametric fits (C and D). The fitted models are Weibull cumulative distribution functions with exponentially decreasing (for suppressions) or increasing (for bursts) scale parameters, as described in the Supplementary Table 1. The median suppression and burst lengths derived from the fitted models are shown as superimposed dashed black lines.

Figure 6. Burst Amplitudes vs Temperature

Empirical cumulative distribution functions (CDFs) are shown for suppression amplitudes in mild hypothermia (27-32°, red curve) and deep hypothermia (17-22°, blue curve). The Kolmogorov-Smirnov (KS) statistic value, D, and associated p-value are also shown.

Figure 7. Comparison of Power Spectra at Different Temperatures

Estimated power spectra for 3 cases and for all cases pooled together in deep (15-22°C) and mild (27-34°C) hypothermia are shown before (A) and after (B) normalization. Regions of the power spectra accepted as statistically indistinguishable are indicated by black bars.

Figure 8. Model explaining how deep hypothermia leads to shorter, weaker bursts

As the rate of substrate recovery decreases (with decreasing metabolic rate), fewer cells are recruited before precipitous depletion leads to suppression. In essence, the equivalent amount of neuronal activity leads to progressively more rapid depletion. Consequently, bursts become shorter and manifest less power. The intrinsic circuit mechanisms within each bursts, however, do not fundamentally change.