• CEA is a surgical procedure designed to prevent ischemic stroke by removing the atheromatous lesion at the carotid bifurcation (a high-grade stenosis of 70-99%), and restoring the patency of the carotid vessels to an almost normal level.

• CEA surgery remains the most commonly performed non-cardiac, vascular surgery in the United States (US), with more than 1 million performed in the last 40 years at a current annual cost of $1.2 billion.

• Asymptomatic Carotid Atherosclerosis Study (ACAS) finding -  50% risk reduction of ipsilateral stroke in asymptomatic patients with greater than 60%carotid narrowing.

• Currently, it is estimated that 170,000 CEAs are performed per year in the US and rising due to the aging of our society.

• Concern about adequate cerebral perfusion and embolism during CEAsurgery has made IOM more common during this surgery than with any other type of cerebrovascular procedure.

A variety of techniques have been utilized to monitor for adequate cerebral circulation and neural function, and detection of embolism, particularly for routine and selective shunting during CEA surgery.

1. Electrical activity of the brain (e. g., rEEG and qEEG, and median nerve somatosensory evoked potentials (MN SSEPs )

2. Intracranial, cerebral circulation measures (e. g., subjective estimation of carotid artery back-bleeding, internal carotid artery "stump" pressure, regional cerebral blood flow (rCBF) using "washout" techniques, and cerebral blood flow velocity measurements of the middle cerebral artery (MCA) using transcranial Doppler (TCD)

3. Oxygen saturation evaluation (e. g., jugular bulb oxygenation and noninvasive cerebral oximetry).

No single method has proven entirely reliable and flawless for detecting both cerebral ischemia and embolization and a multimodality strategy may be employed to improve outcomes.

Perioperative Stroke Rate for CEA Surgery

• The literature has indicated that 2-21% of patients having CEA surgery experienced a stroke.

• Studies evaluating the operative morbidity and mortality rates associated with CEA surgery are usually retrospective, and the differentiation between intraoperative and postoperative stroke is often unclear. In fact, many authors simply describe a neurological deficit in relation to CEA surgery as perioperative.

• However, Jansen et al. [19] have categorized the time of stroke. Sixty-eight percent of perioperative strokes occurred intraoperatively. Fifty percent of the intra-operative strokes were probably caused by hemodynamic factors. The remaining half was probably of thrombo-embolic origin and primarily occurred during surgical manipulation of the carotid arteries.

   

The main factors contributing to outcomes include:

1) hypoperfusion during crossclamping

2) air or particulate emboli occurring during shunting procedures and reperfusion of the carotid

3) reperfusion cerebral hyperemia

4) postoperative emboli (debris remaining in the vessel or clot formation at the operative site)

5) postoperative hypotension and hypertension

Electrode Montages for CEA Surgery

Controversy has ensued over the electrode montage used (bipolar versus referential) and the number of channels (2, 4, 8, 16, or 21) deemed adequate for IOM.

• The primary argument for multi-channel recordings (greater than 8-12) in the diagnostic setting is the need “…..to ensure that EEG activity having a small area of representation on the scalp is recorded and to analyze accurately the distribution of more diffuse activity”.

• AEEGS concluded that a “minimum” of 8 channels of simultaneous recordings are required to show cortical areas which produce “most normal and abnormal EEG patterns,” however, “16 channels are now found to be necessary.

• Traditionally for intraoperative recordings, a bipolar, anterior-posterior, 16-channel, montage was proposed since this derivation "is less prone to artifact and electrical interference, and gives easily appreciated inter-hemispheric comparative data".

• American Academy of Neurology (1990) stated that ".....monitoring should be carried out at least at the anterior and the posterior regions over each hemisphere. Sixteen channels are preferable to identify occasional embolic complications".

•  According to the ACNS’s (2000) intraoperative guidelines, “using less than 8-12 channels is insufficient. Displaying the EEG in the form of bipolar montages is preferred in most cases”.

• ASET says: for EEG surgical monitoring (e. g., carotid endarterectomy) where a baseline has been obtained and outcomes at critical times are compared to that baseline, there is some evidence that 4-channel recordings may be adequate if a lateralized change is the only desired information. When only 4 channels are visualized, it is imperative to understand that the selection of electrode sites is crucial, and that localized changes may not be detected.

A recent evaluation of 2-, 4-, and 16-channel monitoring using rEEG and qEEG for detection of cerebral ischemia led Edmonds et al. to conclude that 8 scalp-recording electrodes may be sufficient to detect cortical ischemia in both the anterior and posterior watershed areas. A previous report by some of the same proponents who have traditionally advocated many channels (>8) have suggested that a minimum of two may be appropriate, yielding a high degree of sensitivity and specificity if the appropriate montage is used. This particular montage selectively recorded rEEG from the area of cortical hemisphere where blood supply is most compromised by CEA surgery, specifically the middle cerebral artery (MCA) distribution.

Significant changes in rEEG were defined as a >50% decrease in amplitude of 8-15 Hz activity. Using this alarm criteria, the channel pair combinations shown in the Table 3. yielded 100% sensitivity and 100% specificity for detection of an ischemic episode within the cortical areas perfused by the MCA.

The channel pair combinations shown in Table 3. provide a frontoparietal plus a frontotemporal coverage,which correlates with the distribution of the blood supply of the superior and inferior M2 branches of the MCA, respectively. However, it should be noted that using combinations of these montages, even with experienced personnel, does not necessarily guarantee perfect sensitivity and specificity, and an uneventful outcome.

Bipolar montages for CEA surgical monitoring which yielded a 100% sensitivity and 100% specificity for detection of cerebral ischemia

Shunting and rEEG

What clinically optimal event should occur following carotid cross-clamping and during the period of plaque removal?

1) the use of universal temporary carotid shunting, 2) selective shunting, or 3) no shunting.

The potential consequences of cerebral ischemia and/or embolism appear unavoidable regardless of the technique employed, and thus can only beminimized at best. Although in principle, the routine use of shunting may eliminate the need for neuromonitoring and measurement of collateral cerebral circulation, the risk of iatrogenic problems associated with shunting ranged from0.5-3%.

The inherent risks associated with shunting can be attributed to:

 1) technical problems which limit the surgeons ability to expose and dissect the atheroma, especially the distal segment

2) shunt kinking or occlusion due to improper placementwhich results in ischemia

3) intraoperative thrombosis

4) increased risk of cerebral embolization of atherosclerotic debris and air into the distal cerebral circulation

5) potential intimal damage resulting in postoperative thrombosis at the operative site.

Selective shunting is considered by many to offer the optimal surgical management of CEA surgery, tailoring to the needs of the individual patient and thus minimizing the above risks. However, there remains a lack of universal selection criteria for its use and the type(s) of neuromonitoring required.

Although the routine practice of shunting varies among surgeons, intraoperative cerebral ischemia is an inevitable consequence of temporary mechanical carotid occlusion, requiring shunting in at least 9-20% of patients based on rEEG criteria. Others have reported a higher incidence of 20-35% for the occurrence of ipsilateral ischemia that required shunting.

Lastly, selective shunting based on neuromonitoring, particularly major changes in the rEEG, may reduce the incidence of stroke 10-fold, and even "close to an irreducible minimum" (0%, 0.3%, and 1.1%). However, it should be noted that some authors have reported good outcomes when all patients were shunted without the use of intraoperative neuromonitoring .

Incidence of Ischemia Detected by rEEG During CEA Surgery

• "gold standard" is conventional, multichannel rEEG.

• Changes in the rEEG are typically characterized by alterations in both frequency and amplitude. These changes have been reported in 9.8-35% of patients after mechanical occlusion of the carotid artery prior to arteriotomy, with the majority of these clamp-related changes occurring within one minute following cross-clamping.

• Of patients exhibiting any clamp-related changes in the rEEG, 80% appear within the first minute with 69% appearing within 20 seconds.

• Major changes begin earlier, with more than 80%of these occurring within the first 20 seconds

Establishing Intraoperative Baselines and Recording Strategies for Optimizing the Detection of Cerebral Ischemia

• Artifactual contamination must always be a concern in interpretation of the intraoperative rEEG and qEEG.

• A preinduction, premedicated baseline should be recorded in order to assess any pre-existing asymmetries or abnormalities.

• "at least a 10-minute baseline pre-clamp recording while anesthetized is essential to appreciate any clamp-associated changes".Similarly, a 10-minute period following restoration of blood flow upon clamp release is also required to ensure that any intraoperative changes have resolved.

• In patients with significant stenosis of the carotid arteries, the development of ischemia as a result of minor blood pressure fluctuations may occur prior to clamping and the endarterectomy.

• For rEEG, recording strategies altering the display sensitivity and/or paper speed (if digital EEG, the computer display time base or sweep speed) have been suggested in order to optimize the visual detection of an ischemic event.

  • Following carotid artery cross-clamping, one of the most common initial changes in the rEEG is a reduction of relatively low- amplitude, beta activity. A sensitivity change to 3 or 5 μV/mm, or a pre-clamp sensitivity setting which achieves an average pen deflection of at least 1 cm aids in the detection of such amplitude decreases.

  • Decreasing paper speeds (or time bases) to 5, 10 or 15 mm/sec for intraoperative monitoring of the rEEG may also visually enhance the detection of an ischemic episode by accentuating slow-wave asymmetries and voltage changes. However, it should be noted that these time bases (or paper speeds) will most often make it difficult to appreciate the complete morphology of the pre-event, baseline rEEG.

• The type of anesthetic agent, as well as controlling its maintenance level to a steady-state, are also important for optimizing conditions for the detection of cerebral ischemia during routine and criticalanesthetic and surgical events.

• For example, a bolus of intravenous (IV) drugs such as barbiturates, propofol, or etomidate, or increasing inhalational agents at critical times during surgery (e. g., before cross-clamping of the carotid arteries) should be avoided. Such maneuvers can cause moderate to severe rEEG depression, making detection of ischemia impossible or difficult at best.

rEEG: Ischemic Effects Associated with CEA Surgery

• The characteristic alterations in rEEG due to ischemia range from subtle changes, such as a mild loss of beta/alpha activity and a minimal increase in slower frequencies, to a complete loss of all detectable electrical activity.

• The most common and sensitive analog EEG change is attenuation of anesthetic-induced, fast activity (low beta, high alpha), which occurs in 14-47% of the patients following carotid cross-clamping.

• Increased delta activity is almost always associated with decreased amplitudes of higher frequency activity. The amplitude of the rEEG may increase (e. g., high-amplitude, slowing phenomenon) or decrease.

• A major loss of amplitude and the appearance of delta waves for longer than 30 minutes have been associated with postoperative deficits.

• Frequency and amplitude changes are usually ipsilateral to the occlusion, although bilateral changes may occur with severely compromised collateral circulation.

• Unilateral changes occur more than twice as often as bilateral changes.

• After shunt placement, focal changes in the rEEG typically resolve in 2-7 minutes, although longer times may be required.

• In the event of amplitude and frequency changes, it has been suggested that an abrupt change, particularly focal, may be associated with embolic causes, whereas a more gradual decline is probably due to hemodynamic causes . Furthermore, severe changes not associated with cross-clamping during conditions of stable anesthesia and blood pressure control are likely a result of embolic complications.

Alarm Criteria for Ischemic Thresholds Using rEEG

• Jenkins et al. proposed that a loss of 75-80% or more in amplitude should be treated as a complete loss of all electroencephalographic activity.

• At the Mayo Clinic,major clamp related changes were defined as changes producing at least a 75% alteration of all activity, and/or a

• two-fold or greater increase of <1 Hz delta activity.

• A moderate change was attenuation of non delta activity to about 50% of pre-clamp levels, and/or an obvious and persistent increase of delta activity at >1 Hz.

• Although gradations of changes in the rEEG occur, augmentation of delta activity reflects a less severe ischemic episode than does attenuation of all encephalographic activity.

• Others have defined significant changes as a >50%decrease in the amplitude of the 8-15Hz bandwidth (fast alpha/slow beta).

• One of the more detailed alarm criteria for classifying electroencephalogically-determined ischemia during CEA surgery was outlined by Kearse and colleagues (1993). These authors defined three distinct categories which included mild,moderate, and severe ischemic changes in the rEEG from an anesthetic-induced baseline established 5 minutes before carotid artery cross-clamping. Each category was defined by three components.

•  Mild if there was a minimal diminution of alpha (8-13 Hz) and beta (14-30 Hz) activities, a less than 50% increase in theta activity (4-7 Hz), and no detectable change in amplitude or increase in delta activity (0.5-3 Hz).

• Moderate ischemia was defined by easily detectable loss or absence of fast activity, a more than 50% increase in theta and/or delta activity, and a 30% or less increase or decrease in amplitude.

• Severe or major ischemia was characterized by a marked loss or complete absence of alpha and beta frequencies, a pre-dominance of delta activity with little or no theta frequencies, and a greater than 30% increase or decrease in amplitude. In each severity category, the ischemic pattern could be focal or generalized.

• Others have classified amajor change in the analog EEGusing a 50% criterion: a > 50% loss of overall amplitude or fast activity, or > 50% increase in slow activity. Using such criteria, the incidence of major changes in rEEG has been reported to range from 3-12.5%.

• These latter changes have been typically reported when regional rCBF decreased below 10-15 mL/100gm/min. The critical rCBF threshold needed to maintain a relatively normal EEG is 18-20mL/100g/min (about 35-40%of normal. However, these thresholds may vary with the type of maintenance anesthesia: the threshold is least under isoflurane (about 10 mL/100g/min) and most under halothane (20 mL/100g/min).

• Lastly, the ACNS’s intraoperative EEG guidelines (2000) defined three degrees of EEG changes caused by ischemia:

• 1) the first degree--a decrease in background fast activity,most apparent when using anesthetic agents that generate such fast activity (the diminution is considered significant if it exceeds 50-60 % of baseline)

  2) the second degree--an increase in slow (delta-theta) which should be considered clinically significant if it exceeds 50% of baseline (a decrease in fast activity may be simultaneous)

  3) the third degree--all rEEG activity progressively diminishes in amplitude and approaches bioelectricity.

• Controlled intraoperative hypertension is commonly used during the anesthetic and surgical management of CEA surgery in order to prevent cerebral ischemic insult (an incidence of 61%).

• Although target blood pressures (e. g., preoperative baseline mean arterial pressure (MAP), 10 or 20% above preoperative baseline MAP, or MAP = 90 or 100mm Hg) have been commonly used, these strategies can be tailored to the individual patient using neuromonitoring. Changes in rEEG and other neural measures (e. g., cerebral blood flow velocity of the MCA as measured by TCD and cerebral oximetry) have been utilized to determine the appropriate blood pressure requirement .

Analog EEG criteria for determination of critical, cerebral, ischemic thresholds associated with CEA surgery, particularly during carotid artery cross-clamping.

Multimodality Neuromonitoring: Other Computer-Processed Modalities

• Multi-channel, rEEG is considered bymost as the gold standard for intraoperative neuromonitoring during CEA surgery; however, several disadvantages should be recognized.

• Conventional rEEG can be technically laborious, difficult to interpret,requires experienced personnel, does not provide direct information about subcortical structures, and, as the only intraoperative monitoring modality, can have a lower sensitivity (50%) and specificity (92%) as compared to MN SSEPs in detecting postoperative neurological deficits.

• In comparison, Lam et al. reported sensitivity and specificity rates of 100%and 94%, respectively,

• for MN SSEPs. For example, neuromonitoring using TCD of the MCA provides a beat-by-beat

• detection of cerebral blood flow velocity, which can be used for the detection of ischemia, and air or

• particulate embolism.

• Cerebral oximetry is a very inexpensive, noninvasive technique, although

• currently the critical ischemic thresholds are not firmly established.

Anesthetic Effects on the rEEG During CEA Surgery

• There is still no universal adoption of a monitoring technique or criteria for its neural end-point(s) by anesthesiologists and neurophysiologist.

• "balanced" anesthesia produces hypnosis, analgesia, amnesia, and muscle relaxation .

• "Polypharmacy" the electroencephalographic effects often observed and assessed are not necessarily the effects on background rhythms typically associated with each drug alone, but often in combination.

• Selection of anesthetic agents for induction and maintenance of a steady-state are important for optimizing the detection of cerebral ischemia.

• The effects of pre-medication and anesthetic induction are typically bilateral and

• symmetrical.

• Induction is usually with IV drugs such as thiopental, propofol, or etomidate, and then steady-state anesthesia is maintained by inhalational agents, most commonly halogenated agents (e. g., isoflurane) and nitrous oxide.

• Blume and Sharbrough's characterization of typical rEEG patterns prevalent during sub-minimal alveolar concentrations (sub-MAC concentrations) of anesthetic agents, particularly during steady-state anesthesia include:

• Widespread anteriorly maximum rhythm (WAR) - This pattern is characterized by a rhythmic lower beta or alpha (8-14 Hz) activity which appears as the dominant activity over the anterior hemispheric region with induction using inhalational agents such as halothane, enflurane, and isoflurane, and IV drugs such as thiopental. During lighter levels of steady state anesthesia the WAR pattern becomes widespread and is essentially generalized. This pattern does slow with increasing level of anesthetic agent. In addition, the EEG typically shows intermittent delta wave (usually 1 sec or less in duration), which is often sharply contoured and commonly biphasic, and best expressed as transients or in a brief train.

• Frontal intermittent rhythmic delta activity (FIRDA) - This pattern is characterized by a a high-amplitude, intermittent, rhythmic, delta activity which is usually maximal frontally. It is typically seen with a rapid induction with thiopental as a burst intermixed with the faster alpha/beta activity.

  Anterior intermittent slow waves (AIS) - This pattern is characterized by an anteriorly, maximum, intermittent, slow-wave activity which is commonly diphasic, triangular in morphology, and may occur either singly or in brief trains lasting about 1 second.

  Widespread persistent slow activity (WPS) - This polymorphic pattern is characterized by a widespread, persistent, slow-wave activity with low amplitude, expressed maximally over the temporal and posterior regions, and lasts about 1 second. This pattern is more prevalent when higher concentrations of isoflurane anesthesia are used, particularly in conjunction with 50-60% nitrous oxide.

   

• At sub-MAC concentrations of the inhalational anesthetics or at lighter levels of steady-state anesthesia, the dominant rEEG activity is characteristized by theWAR pattern, as described above. This is a preferred, anesthetic-induced, rEEG pattern which would optimize the detection of cerebral ischemia. At supra-MAC concentrations of the inhalational anesthetics, unique rEEG patterns may develop.

• Since isoflurane is typically used, its patterns will be further reviewed.

• At sufficiently higher levels approaching about 1.0-1.5MAC for this inhalational agent, the rEEG emerges into a burst-suppression pattern, or becomes isoelectric.

  Frequently, all activity is lost between 2.0-3.0 MAC. This is clearly a pattern of activity which is undesirable for evaluating ischemia, particularly during carotid cross-clamping. In addition, during inhalational anesthesia with nitrous oxide, a WPS activity with lower amplitude may become more prominent. Again, this is not preferred during neuromonitoring since it typically produces a pattern that is not optimal for the detection of ischemia.

   

  Although most patients undergoing CEA surgery show diffuse anesthetic-related EEG changes, one third may show focal abnormalities in their pre-clamp rEEG. These abnormalities consist of unilateral attenuation of WAR patterns and prominent polymorphic delta on the same side. In many cases, these abnormalities seen under anesthesia are present in the waking traces, and probably reflect a pre-existing focal area that is ischemic and dysfunctional, such as an infarction or an area of vascular insufficiency. Furthermore, anesthesia may influence the detection of preoperative focal abnormalities in the rEEG by either activating or obscuring them.

Alarm Criteria for Ischemia Using qEEG During CEA Surgery

In general, ischemia is associated with a shift of the power spectrum to the lower frequency range, and concomitant loss of amplitude in the power spectrumfor selected frequencies or across the entire frequency spectrum. As stated above, proper interpretation of any computer-processed display or derived measures of the rEEG should always include selected segments of concurrent analog or digitally-recorded EEG to verify the validity of the interpretation of the reduced and simplified computer-processed data. Like anesthetic effects, the display techniques for power spectral analysis using either the CSA or DSA can afford the user a remarkable neural fingerprint of the effects of cerebral ischemia during CEA surgery [80-82]. One major advantage of these computer processed transformations of the rEEG is that the alarm criteria for intervention during ischemia can be more easily quantified. For example, several quantitative criteria have been applied which have accurately predicted postoperative neurological outcome.

1) Rampil et al. [83] defined a significant ischemic period as a rapid (<1 min) decrease in SEF to < 50% of the prior baseline, which persisted for longer than 10 minutes.

2) Using power spectral analysis, Ivanovic et al. [80] defined three broad frequency bandwidths: low (delta and theta, 0.25 to 6.0 Hz, middle (alpha, 6.0 to 10.5 Hz), and high (sigma to beta, 10.5 to 16.0 Hz).

Changes in the qEEG during carotid crossclamping were assigned to one of three categories based on the magnitude of the changes in the power spectrum of each bandwidth:

1) mild or no power reduction in which the changes in the power spectrum did not exceed 50% for any frequency bandwidth

2) marked power reduction characterized by a >50% reduction in one or two frequency bandwidths

3) global or profound reduction that reflected at least a 50% reduction in the power of the qEEG in all three frequency bands.

In their series, the percentage of patients falling into each category was 78%, 11%, and 11%respectively.

3) Tempelhoff et al. used the criterion of either a decrease in SEF > 50% or a decrease in total spectral power > 30%.

In contrast, however, others have criticized these computer-enhanced techniques for their unreliability in detecting mild ischemia, which was claimed to be more easily recognized with greater sensitivity and specificity when using conventional, analog, multi-channel EEG recordings