EEG Basics and Changes During Anaesthesia

1. What the EEG Measures

• Amplitude: 5-500 µV (roughly 1/1000th of the ECG)
• Frequency range: 0.5-30 Hz (traditional range), up to 600 Hz for some fast oscillations
• Excellent temporal resolution (milliseconds) but poor spatial resolution (~6 cm² per electrode)
• Decreases in amplitude with normal aging (neuronal loss)

2. Electrode Placement: The 10-20 System

• F = Frontal, P = Parietal, T = Temporal, O = Occipital, C = Central
• Odd numbers = left hemisphere, even numbers = right hemisphere, Z = midline
• Standard diagnostic EEG: at least 16 channels
• Intraoperative recordings: 1-32 channels; processed EEG monitors (BIS, SedLine) typically use 4 frontal channels

3. EEG Frequency Bands: Nomenclature

4. The Normal EEG (Awake Baseline)

• Eyes open, alert: Low amplitude, high frequency beta activity (>13 Hz) from frontal regions - the hallmark of an alert, attentive brain
• Eyes closed, relaxed: Higher amplitude alpha activity (8-13 Hz), largest over occipital and posterior parietal regions; waxes and wanes spontaneously. This "eyes-closed resting pattern" is the accepted baseline when describing anesthetic effects
• Eye opening immediately suppresses alpha - the "alpha block" or desynchronization response
• Normal sleep: Alpha rhythm slows and is replaced by vertex sharp waves, sleep spindles (8-14 Hz), and K complexes. Small theta activity may appear over temporal regions (more in patients >60 years)
• Delta activity is absent in the normal waking adult

5. From Raw EEG to the Spectrogram

• X-axis = time
• Y-axis = frequency (Hz)
• Color = power (red = high power; blue = low power)

6. EEG Changes During Anaesthesia: The Sequential Pattern

A. Induction (GABAergic agents - propofol or volatile agents)

B. Maintenance: The "Alpha-Delta" Pattern

• Marked decrease in beta and gamma power
• EEG becomes dominated by slow-wave (0.1-2 Hz) and delta (0.5-4 Hz) oscillations, combined with an alpha (8-12 Hz) oscillation - the characteristic "alpha-delta pattern"
• In the spectrogram, this appears as two horizontal red bands (high power) in the delta and alpha frequency ranges, persisting throughout maintenance

• The primary target for titration of anaesthesia in almost all cases
• Easily recognized in the spectrogram
• Correlated with loss of responsiveness and suppression of cortical responses to noxious stimuli
• Similar to natural sleep patterns, reflecting thalamocortical hyperpolarization
• Associated with a "resilient brain" unlikely to suffer postoperative cognitive disturbances

C. Burst Suppression

• EEG alternates between low-amplitude suppression periods (<5 µV, isoelectric) and high-amplitude bursts
• This is burst suppression (BS)
• With increasing dose, the suppression periods lengthen until the EEG becomes fully isoelectric
• All EEG monitors display a Suppression Ratio (SR): the fraction of time spent in suppression over a 30-60 second window

• High anesthetic doses
• Hypothermia
• Hypoxia / ischemia
• Toxic metabolic states

D. Isoelectric (Flat) EEG

• Complete suppression at maximal anesthetic doses
• Also seen in deep hypothermia (used deliberately in some cardiac surgery), profound ischemia/hypoxia, and brain death
• Important diagnostic distinction: anesthetic-induced isoelectric EEG is reversible, whereas brain death EEG suppression is permanent

7. Emergence

1. Power in slow-delta and alpha bands decreases
2. Peak frequency of the alpha oscillation increases before alpha power fully dissipates
3. During late emergence: a period of absent delta and alpha where the patient is unresponsive but in disconnected consciousness (often dreaming)
4. ~1/3 of patients abruptly lose high delta power and transition directly to responsiveness
5. Immediately on return of responsiveness: occipital alpha reappears (with eyes closed)
6. Beta power increases and the power spectrum slope flattens

Neural Inertia

8. EEG Responses to Noxious Stimulation

• Beta arousal: Increased high-frequency power suggesting cortical arousal (seen with low-dose hypnosis, inadequate opioid)
• Alpha dropout: Decreased alpha band power (seen with balanced techniques)
• Delta arousal: Increased delta power following painful stimulus (paradoxical arousal pattern)
• Shift to higher-frequency desynchronized activity resembling emergence
• Abrupt onset of burst suppression (paradoxical effect)

9. Drug-Specific EEG "Fingerprints"

Propofol (and Volatile Agents - GABAergic)

Nitrous Oxide (N₂O)

• Different mechanism from GABAergic drugs (NMDA antagonism)
• Given alone at atmospheric pressure: minimal, inconsistent EEG changes (rarely produces full unconsciousness)
• Large abrupt concentration changes: large short-lived delta waves + loss of alpha waves
• This pattern can occur with sudden withdrawal (in the wakeful patient) or sudden introduction on a background of ether-based anesthesia
• Most EEG indices (including BIS) are insensitive to N₂O, making its contribution to anesthesia difficult to detect

Xenon

• Dominated by delta power with reductions in all other frequency bands
• Not commonly used clinically

Ketamine (NMDA antagonist)

• Sub-hypnotic doses: Loss of alpha power, increased theta and gamma activity
• Full hypnotic doses: Large slow waves alternating with gamma bursts
• In clinical supplemental doses (25-50 mg bolus/infusion): Decreases alpha oscillatory activity; may increase beta/gamma power
• Mechanism: thalamocortical depolarization secondary to cholinergic, aminergic, and glutamatergic dysregulation
• Important: Ketamine causes spurious elevation of depth-of-anaesthesia indices (e.g., BIS reads higher = apparently "lighter") despite providing real antinociception

Dexmedetomidine (α₂-agonist)

• Most closely replicates natural sleep EEG patterns of all agents
• Mechanism: suppresses aminergic arousal → thalamocortical hyperpolarization (primarily subcortical action)
• EEG shows sleep spindles (9-15 Hz) superimposed on delta background
• More easily awakened than equivalent propofol sedation (propofol has both subcortical AND direct cortical inhibitory actions)
• Does NOT reliably produce alpha-delta pattern of GABAergic agents
• Spindles are the distinguishing hallmark

10. Processed EEG (pEEG) Monitors

• Power in different frequency bands (weighted)
• Burst suppression ratio
• Coherence between channels
• Autoregressive parameters

1. Artifacts processed along with true signal (can give false readings)
2. Only 4 or fewer channels = limited cerebral territory
3. Cannot distinguish unilateral from bilateral changes unless bilateral leads placed
4. Validated on young, healthy populations - may not apply to all surgical patients
5. A BIS of 50 in one patient ≠ BIS of 50 in another; patients become aware at BIS values from 40-90
6. Ketamine, dexmedetomidine, and N₂O can give misleading index values
7. Index values lag behind real-time EEG changes (time delay of ~30-60 seconds)

11. Intraoperative Uses of EEG

1. Monitor for cerebral ischemia - e.g., during carotid endarterectomy (regional EEG slowing with preserved, then lost voltage indicates progressing ischemia); reduction in CBF by 50% causes EEG slowing; reduction by 75% causes complete suppression
2. Guide anesthetic-induced cerebral metabolic reduction - burst suppression or isoelectric EEG for neuroprotection during anticipated ischemia or raised ICP
3. Predict neurologic outcome after brain insult
4. Optimize anesthetic delivery - depth of anesthesia monitoring, prevention of awareness and over-sedation

12. Key Summary Table: EEG Stages During Anaesthesia

• Miller's Anesthesia, 2-Volume Set, 10th ed., Chapter 35 (Neuromonitoring) pp. 5214-5222; Chapter 36 (EEG Monitoring of Anaesthesia) pp. 5363-5410
• Adams and Victor's Principles of Neurology, 12th ed., Chapter 2 (EEG) pp. 40-45
• Neuroscience: Exploring the Brain, 5th ed., Chapter 19 (EEG Rhythms) pp. 1710-1712

BIS (Bispectral Index) Monitoring - Detailed

1. Background and Development

• Relatively robust to noise
• Capable of reliably detecting burst suppression
• Capable of detecting and rejecting artifacts
• Showed reasonable correlation with commonly used GABAergic anesthetic drugs
• Made routine EEG monitoring accessible to operating room practitioners without specialist training

2. The BIS Number: What It Is

3. The BIS Algorithm: How It Works

Three Core Mathematical Components

• The raw EEG undergoes Fourier transformation, converting the voltage-vs-time signal into frequency components
• The power in different frequency bands is quantified
• As depth of anaesthesia increases, there is progressive slowing of the EEG (shift from beta/gamma to alpha/delta)
• The relative beta ratio - comparing power in the 30-47 Hz range to the 11-20 Hz range - is a key sub-component. As anaesthesia deepens, beta power falls relative to lower frequencies

• The standard power spectrum captures the amplitude (power) of each frequency component but discards phase information - it cannot detect whether different frequency components are synchronized with each other
• Bispectral analysis measures the phase coupling (synchrony) between different EEG frequencies - i.e., whether two different frequencies interact to produce a third frequency (e.g., f1 + f2 = f3)
• The degree of this cross-frequency coupling (called bicoherence) changes markedly with anaesthetic depth
• In the awake state, EEG frequencies are largely independent (low bicoherence)
• During anaesthesia, EEG frequencies become highly coupled (high bicoherence), particularly the synchronization between slow and fast oscillations in the alpha-delta pattern
• This is the unique feature that differentiates BIS from simple spectral analysis

• The algorithm detects and quantifies burst suppression via the QUAZI suppression sub-algorithm
• It calculates a Suppression Ratio (SR): the percentage of time in the last 63 seconds where the EEG amplitude is less than 5 µV (i.e., in suppression)
• SR is incorporated into the final BIS number (increasing SR drives BIS towards 0)
• A "forme fruste" pre-burst-suppression state is also detected where power at all frequencies above ~2 Hz abruptly decreases for short periods

• High-frequency (70-110 Hz) electromyographic (EMG) activity is also incorporated into the BIS calculation
• This has been controversial: EMG activity (from facial/frontalis muscle contraction) increases the BIS value
• The system partially uses EMG as a marker of cortical arousal, but it also means that muscular artifact causes falsely elevated BIS values

4. Hardware: The BIS System

Components

Electrode Placement

• A single strip placed on the forehead (frontal) and temple (frontotemporal)
• 4 electrode contacts: reference, 2 active EEG channels, ground
• The placement uses the frontotemporal region because GABAergic drugs cause anteriorization of EEG activity into frontal areas, maximizing the signal detectable at these sites
• Skin impedance must be < 5 kΩ (ideally similar at all electrodes) for reliable signal

Displayed Parameters on the BIS Monitor

5. How BIS Is Used in Clinical Practice

During Induction

• BIS starts at ~90-100 (awake)
• At mild sedation: BIS 70-85
• At loss of consciousness: typically BIS drops to 60-70
• Note: There is a time delay of up to 104 seconds between actual EEG changes and the displayed BIS value due to the signal processing algorithm. This lag means the displayed BIS during induction often underestimates the depth already achieved

During Maintenance

• Target: BIS 40-60 for general anaesthesia
• In this range, the underlying EEG typically shows the alpha-delta pattern (appropriate thalamocortical hyperpolarization)
• BIS-guided titration allows drug dose reduction: studies show ~25% reduction in volatile agent consumption and faster recovery times when BIS is used
• A BIS consistently < 40 warrants reducing anaesthetic dose to prevent burst suppression
• A BIS consistently > 60 during surgical stimulation warrants increasing the anaesthetic

During Emergence

• BIS begins rising as drug effect wears off
• Return of responsiveness typically occurs at BIS 60-70, though with wide inter-individual variation (patients have been known to emerge at BIS values from 40 to 90)
• The neural inertia phenomenon means patients emerge at lower drug concentrations than required for induction - so emergence BIS correlates with emergence but not with induction pharmacology

6. Validation: The Major Clinical Trials

7. Clinical Applications

1. Prevention of Awareness with Recall (AWR)

• The primary indication
• Especially valuable in TIVA cases, cardiac surgery (reduced volatile due to haemodynamic compromise), obstetric anaesthesia, major trauma surgery
• Incidence of awareness is higher in: women, cardiac surgery, caesarean section, patients on chronic opioids/benzodiazepines, emergency cases

2. Prevention of Excessive (Deep) Anaesthesia

• Deep anaesthesia (BIS <40, burst suppression) is associated with:
  • Postoperative delirium (POD)
  • Postoperative neurocognitive dysfunction (PNCD)
  • Possible excess mortality (though the Balanced Anaesthesia Study failed to show mortality benefit from BIS titration)
• BIS guidance reduces total drug consumption, facilitating faster recovery and reducing PACU time

3. Fast-tracking and Efficiency

• BIS-guided anaesthesia associated with shorter time to eye opening, faster PACU discharge
• Particularly useful in ambulatory surgery with propofol and desflurane

4. Detection of Cerebral Ischaemia (Intraoperative)

• During carotid endarterectomy or cardiac surgery: sudden unilateral or bilateral EEG slowing may indicate ischaemia
• BIS is less sensitive for this application than multichannel raw EEG; it monitors primarily frontal regions only
• However, sudden EEG changes during CPB can signal correctable problems (SVC obstruction, severe CO reduction)

5. ICU Sedation

• BIS can guide sedation in critically ill/ventilated patients
• Target range: 60-70 for light sedation; 40-60 for deeper sedation

8. Factors That Falsely INCREASE BIS (Falsely "Light")

9. Factors That Falsely DECREASE BIS (Falsely "Deep")

10. Drug-Specific BIS Behaviour

11. Limitations of BIS Monitoring

Technical Limitations

1. Proprietary algorithm - exact weightings unknown; cannot be independently validated or modified
2. Time delay: up to 104 seconds lag between actual brain state change and displayed value (due to epoch-based processing, typically 30-second smoothing window)
3. Only 4 frontal channels - monitors a very small fraction of total brain tissue; misses posterior cortex (where consciousness may partially reside) and subcortical structures
4. Cannot detect unilateral ischaemia unless bilateral leads placed
5. Validated on young healthy populations - application to elderly, paediatric, neurologically impaired patients requires caution

Clinical Limitations

1. A BIS of 50 in one patient ≠ BIS of 50 in another - significant inter-individual variability; patients become aware at BIS values from 40 to 90
2. Cannot predict response to surgical incision - poor correlation of EEG indices with movement response to incision
3. No opioid information - BIS reflects only the hypnotic component of anaesthesia; does not measure antinociception
4. "Graded consciousness" problem - binary classification of "aware/not aware" does not reflect the reality of graded, continuous states of consciousness
5. Not a gold standard for awareness - as Miller's states: "a single number is analogous to getting only the heart rate from the ECG"
6. Neural inertia asymmetry - BIS values during emergence do not mirror induction values due to pharmacodynamic hysteresis

Specific Conditions

1. Hypothermia, ischaemia, and hypoxia produce changes identical to deep anaesthesia - extremely important in cardiac surgery and neurosurgery
2. EMG contamination - the most common cause of falsely elevated BIS in clinical practice; neuromuscular blockade artificially lowers BIS
3. Paediatric limitations - immature EEG patterns in neonates and infants; BIS values less reliable

12. EEG Artifacts Affecting BIS (with illustration)

13. Alternatives to BIS

14. The "Deep Anaesthesia Is Harmful" Debate

• Observational studies consistently show an association between deep anaesthesia (low BIS, burst suppression) and:
  • Postoperative delirium
  • Postoperative neurocognitive dysfunction/decline
  • Possible increased 1-year mortality (observational)

• These associations may reflect confounding - patients with more comorbidities and older/frailer brains naturally require less drug to achieve low BIS (they're more sensitive) AND are more prone to poor outcomes
• The Balanced Anaesthesia Study (large RCT): randomised patients to deep (BIS 35-45) vs light (BIS 50-60) anaesthesia and found no mortality difference
• EEG monitoring may simply reveal "sensitive" brains rather than causing harm through deep anaesthesia itself

Summary

BIS monitoring provides an objective, real-time measure of the hypnotic component of anaesthesia by processing frontal EEG into a 0-100 dimensionless index. It is most useful in TIVA, high-risk patients, and situations where end-tidal monitoring is unavailable or unreliable. The optimal target is BIS 40-60 during surgery. Its principal limitations are: single-number reductionism, time lag, EMG artifact, drug-specific unreliability (especially ketamine and N₂O), and significant inter-individual variability. It should always be interpreted alongside the raw EEG, clinical signs, and haemodynamic data - not used as a standalone depth monitor.

• Miller's Anesthesia, 10th ed., Chapters 35 (pp. 5214-5222) and 36 (pp. 5398-5413)
• Miller's Anesthesia, Cardiac Chapter 20 (pp. 7421-7422)
• Morgan & Mikhail's Clinical Anesthesiology, 7th ed., pp. 2347-2348
• StatPearls: Bispectral Index