Anesthesia for Neurosurgery



Anesthesia for Neurosurgery


Armagan Dagal

Arthur M. Lam







Neuroanatomy

A basic knowledge of neuroanatomy is essential for all anesthesiologists, particularly those caring for patients with disease of the central nervous system (CNS). Components of the CNS, the brain and spinal cord, are protected by the bony structures that surround them. Yet by virtue of their protective nature, these structures are nondistensible. The intracranial volume is fixed, thereby providing little room for anything other than the brain, cerebrospinal fluid (CSF), and blood contained in the cerebral vasculature. Even the space in the spinal column, although not as restrictive as the cranium, is quickly exhausted by a space-occupying lesion such as an expanding hematoma or abscess. It is in the context of the restrictive nature of the cranium and vertebral column in which the CNS is housed that all interventions must be considered.

Both the brain and spinal cord have unique blood supply. The carotid artery in the neck bifurcates into the external and internal carotid arteries at the level of the third cervical vertebra, sending the internal branch through the base of the skull, giving seven branches including the ophthalmic artery, and ultimately bifurcating into the anterior and middle cerebral arteries. These vessels define the anterior cerebral circulation. The posterior circulation results from the vertebral arteries, which ascend in the posterior aspect of the neck through foramina in the cervical vertebral bodies before exiting, coursing around the brainstem, and joining the contralateral vessel to form the basilar artery. The basilar artery ascends along the brainstem before dividing into the posterior cerebral arteries. The anterior and posterior circulations anastomose through the posterior communicating arteries to provide collateral flow; collateral circulation can also occur through the anterior communicating artery connecting the bilateral anterior cerebral arteries. This system of collateralization, named the circle of Willis (Fig. 36-1), was described by Thomas Willis (1621–1675) with the recognition of its purpose “… that there may be a manifold way, and that more certain, for the blood about to go into divers Regions of the Brain.”

The spinal column is the bony structure made up of the 7 cervical, 12 thoracic, 5 lumbar vertebrae, 5 fused sacral and 3 to 5 fused coccygeal vertebrae. It is about 70 cm long in the adult male with cervical and lumbar regions which convex forward and thoracic and sacral regions that are concave. The spinal cord exits the skull through the foramen magnum and enters the canal formed by the vertebral bodies. In the adult, the cord typically ends at the lower aspect of the first lumbar vertebral body. It is around 45 cm long in men and 43 cm long in women.

Blood supply to the cord is provided by several sources. The anterior spinal artery, which arises from the vertebral arteries, supplies the anterior two-thirds of the spinal cord. This vessel runs the length of the cord, receiving contributions from radicular arteries via intercostal vessels. The artery of Adamkiewicz is the most important radicular vessel, typically joining the anterior spinal artery in the lower thoracic region and providing blood to the thoracolumbar cord. The posterior third of the cord is supplied by two posterior spinal arteries, which arise from the vertebral arteries and also receive contributions from radicular arteries (Fig. 36-2).


Neurophysiology

Cerebral metabolic rate is directly related to the number of stimulated neurons and rate of depolarization. Therefore, any activity or stimulation raises the metabolic rate. Cerebral blood flow (CBF) is tightly coupled to metabolism, on a regional as well on a global level. As an example, while visual stimulation may raise blood flow to the occipital cortex, mild hyperthermia, which raises global cerebral metabolic rate, increases flow to the entire brain.

The CSF occupies the subarachnoid space, providing a protective layer of fluid between the CNS and the tissue that surrounds it. CSF is produced by the choroid plexus in the ventricles at about 0.3 mL/min. CSF circulation follows the path from the lateral ventricles into the third ventricle via the interventricular foramina (foramina of Monro). It subsequently transits through the cerebral aqueduct of Sylvius into the fourth ventricle, and then into the space around the brain via the foramina of Magendie
(midline posteriorly) and Luschka (laterally). It bathes both the spinal cord and the brain. Absorption into the dural venous sinuses occurs through the arachnoid granulations. Although CSF volume is approximately 150 mL, more than three times this amount is produced in a 24-hour period. This continuous flow of CSF from the source to sink allows it to participate in many functions in addition to cushioning the brain. It maintains a milieu in which the brain can function by regulating pH and electrolytes, carrying away waste products, and delivering nutrients.1,2






Figure 36.1. The circle of Willis, and other blood supply to the brain and spinal cord.






Figure 36.2. Blood supply to the spinal cord. Both the single anterior spinal artery and the paired posterior spinal artery arise from the vertebral arteries. The radicular arteries and particularly the artery of Adamkiewicz are important contributors. The anterior spinal artery supplies the anterior two-thirds of the spinal cord, with the posterior spinal artery supplying the rest. (vert., vertebral; art., artery; ant., anterior)

Intracranial pressure (ICP) is low except in pathologic states. The Monro–Kellie doctrine states that in the setting of a nondistensible cranial vault, the volume of blood, CSF, and brain tissue must be in equilibrium. An increase in one of these three elements, or the addition of a space-occupying lesion, can be accommodated initially through displacement of CSF into the thecal sac, but only to a small extent. A further increase, as with significant cerebral edema or accumulation of an extradural hematoma, will quickly lead to a marked increase in ICP due to limited intracranial compliance (Fig. 36-3).






Figure 36.3. Intracranial compliance (elastance) curve. The brain has minimal compensatory capacity, and any increase in mass from hematoma or brain swelling will result in an inordinate increase in intracranial pressure.

As mentioned earlier, blood flow to the brain is tightly coupled to cerebral metabolism. As such, many factors affect CBF because of their effect on metabolism. Stimulation, arousal, nociception, and mild hyperthermia elevate metabolism and flow, while sedative–hypnotic agents and hypothermia decrease both metabolism and flow. A number of other factors govern CBF directly without changing metabolism. A potent determinant of CBF is the arterial CO2 tension (PaCO2). Within physiologic range, CBF has an approximately linear relationship with PaCO2. CBF changes by approximately 3% of baseline for each 1 mm Hg change in PaCO2 (Fig. 36-4). As CBF changes, so does cerebral blood volume (CBV), which is why hyperventilation can be used for short periods of time to relax the brain or decrease the ICP. However, this effect is thought to be short-lived. CSF pH normalizes
over time, and vessel caliber returns to baseline. The exact duration of hypocapnic vasoconstriction is uncertain; a period of minutes to hours has been found in different patient populations.3 Because the decrease in CBF occurs without a change in cerebral metabolic rate, the risk of ischemia is a theoretical concern. However, the significance of this concern is uncertain. We have no evidence of harm of moderate hyperventilation to the normal brain under general anesthesia. Early hyperventilation in traumatic brain injury (TBI) is associated with poor outcome, and the consequence of hyperventilation in TBI after the initial 24 hours is uncertain.4,5,6






Figure 36.4. Cerebrovascular response to change in PaCO2 partial pressure. The change is linear between PaCO2 of 25 and 65 mm Hg.






Figure 36.5. Cerebrovascular response to change in PaO2 partial pressure. The response of cerebral blood flow to change in PaO2 is flat until PaO2 falls below 50 mm Hg.

In contrast to CO2, O2 has little effect on CBF except at abnormally low levels (Fig. 36-5). When PaO2 falls below 50 mm Hg, CBF begins to increase sharply. A teleologic explanation for this phenomenon is that CBF needs to increase only when the O2 content of the blood begins to decrease significantly.

CBF remains approximately constant despite modest swings in arterial blood pressure. The mechanism by which CBF is maintained, originally described by Lassen,7 is called autoregulation of CBF, or at times, pressure autoregulation of CBF. As cerebral perfusion pressure (CPP), defined as the difference of mean arterial pressure (MAP) and ICP, changes, cerebrovascular resistance adjusts to maintain stable flow. The resistance is varied at the arteriolar level. The range of CPP over which autoregulation is maintained is termed the autoregulatory plateau. Although this range is frequently quoted as a MAP range of 60 to 150 mm Hg, there is significant variability between individuals, and these numbers are only approximate. At the low end of the plateau, cerebrovascular resistance is at a minimum, and any further decrease in CPP will compromise CBF. At the high end of the plateau, cerebrovascular resistance is at a maximum, and any further increase in CPP will result in hyperemia (Fig. 36-6). Various mechanisms have been proposed to account for autoregulation, including myogenic, neurogenic, and local metabolic mediators. However, the exact mechanism remains undefined.

There is interaction between CO2 reactivity and pressure autoregulation, although the molecular mechanism is likely different for these two homeostatic processes. When blood pressure is low, CO2 reactivity is reduced. In contrast, under hypercapnic conditions, autoregulatory capacity is lost because of the concurrent vasodilation.






Figure 36.6. Cerebral autoregulation. It is generally accepted that cerebral blood flow is maintained constant between 60 and 160 mm Hg. However, these are average values, and there is considerable variation in both the lower and the upper limit of cerebral autoregulation among normal individuals.

Other factors affect CBF as well. Anemia increases CBF via higher cardiac output, CPP and lower blood viscosity, as well as induced cerebral vasodilatation.8,9,10 Proposed mechanisms underlying this dilatation may include upregulation of nitric oxide (NO) production, sympathetic β2-receptor stimulation and upregulation of vascular endothelial growth factor, hypoxia-inducible factor 1α, and erythropoietin that contributes to vasodilatation and maintenance of CBF. Although it seems likely that these mediators are neuroprotective, it remains possible that they could also have harmful pathophysiologic effects.11,12,13


Anesthetic Influences

Anesthetic agents have variable influence on CBF and metabolism, CO2 reactivity, and autoregulation.14 Inhalation anesthetics tend to cause vasodilation in a dose-related manner, but do not per se uncouple flow and metabolism. Thus the vasodilatory influence is opposed by metabolism-mediated decrease in flow. The resultant effect is that during low doses of inhalation anesthesia, CBF is either unchanged or slightly increased. Higher doses result in dominance of the vasodilatory effect and an increase in CBF. Compared to other inhaled agents, sevoflurane in clinically relevant doses does not increase CBF, although propofol at comparable doses results in more profound cerebral vasoconstriction, and sevoflurane does not appear to impair cerebrovascular autoregulation.15,16 Furthermore, sevoflurane anesthesia is associated with profound regional and global reduction in cerebral metabolic rate.17 Intravenous agents including thiopental and propofol cause vasoconstriction coupled with a reduction in metabolism.18 Ketamine, on the other hand, increases flow and metabolism.19 CO2 reactivity is a robust mechanism and is preserved under all anesthetic conditions.

Dexmedetomidine is a pure α2 agonist that is increasingly utilized to provide a state of “conscious sedation” associated with minimal respiratory depression and some analgesia. It may create an ideal state to facilitate procedures such as awake craniotomy, carotid endarterectomy (CEA) under regional anesthesia, carotid angioplasty and stenting, and other neurointerventional procedures. It appears to preserve flow–metabolism coupling in healthy volunteers,20 although its effects on the injured brain still
need to be determined. It has been reported to have little effect on static cerebrovascular autoregulation (sCA) in healthy volunteers (unpublished observation), but it may weaken dynamic cerebrovascular autoregulation (dCA) and delay restoration of CBF velocity to normal with reduction in blood pressure.21


Pathophysiology

The homeostatic mechanisms that ensure protection of the brain and spinal cord, removal of waste, and delivery of adequate O2 and substrate to the tissue can be interrupted through a multitude of mechanisms. Traumatic insults may result in contusion with subsequent edema formation, direct injury from depressed skull fractures or spine fractures, diffuse injury to neurons from rapid deceleration, and disruption of the vasculature, resulting in ischemia or hemorrhage. All of these insults may ultimately compromise CNS perfusion.

Mass lesions, such as tumors, may compress adjacent structures, raise ICP, and obstruct normal flow of CSF. Hemorrhage may be spontaneous or traumatic. Depending on its location, this may cause a mass effect, impair CSF circulation, or, in the case of subarachnoid blood, breakdown of the blood may lead to further ischemic injury by causing cerebral vasospasm.

Hydrocephalus is caused by an imbalance between CSF production and removal. It frequently results in the elevation of ICP. Hydrocephalus is commonly divided into two categories: Communicating hydrocephalus and obstructive hydrocephalus. The former is characterized by a failure to absorb CSF, typically because of dysfunctional arachnoid granulations. The latter may be caused by any direct obstruction or extrinsic compression of a passageway through which CSF must pass, such as the cerebral aqueduct. This obstruction, for example, may result from a clot within the space or from a tumor adjacent to it. Depending on the circumstances, hydrocephalus can have a subtle or dramatic presentation. For example, acute hydrocephalus following an intraventricular hemorrhage may result in a rapidly progressive obtundation that improves dramatically with external ventricular drainage. In contrast, normal pressure hydrocephalus may evolve over years, resulting in barely perceptible changes in cognition and gait.


Monitoring

Anesthesia for neurosurgery and spine surgery requires the standard American Society of Anesthesiologists monitoring for physiologic parameters. However, the risk imposed to the CNS by these surgical procedures may warrant more extensive monitoring. For many procedures, adequate oxygenation, ventilation, and systemic blood pressure do not ensure the well being of the brain and spinal cord. Instead, the integrity of the CNS needs to be evaluated intraoperatively with monitors that specifically detect CNS function, perfusion, or metabolism. At times, the monitoring modalities can be combined to provide greater information regarding the well being of the CNS.


Central Nervous System Function


Electroencephalogram

The electroencephalogram (EEG) is the quintessential cerebral function monitor. It records the electrical activity generated by the depolarization of cortical neurons that can be detected by surface electrodes placed on the scalp. Typically the activity is measured between two points on the scalp (bipolar), as there is no electrically neutral place from which to reference the signal. Other sources of electrical activity, such as that from the heart and muscles, must be filtered from the signal, otherwise they would overwhelm the small voltages generated by the cortical activity. Common-mode rejection, that is, rejection of signals common to both electrodes, allows interference from cardiac and muscle activity to be minimized.

The EEG can be used for intraoperative monitoring (IOM) and diagnosis. Monitoring provides information regarding functional assessment of the brain, the occurrence of ischemia, seizure activity, burst-suppression pattern, and potentially, depth of anesthesia. Several standardized systems of electrode placement have been developed to facilitate reliable and consistent EEG monitoring, the most common of which is the International 10–20 System. In brief, artificial meridians are generated on the scalp running front to back and side to side, where the 10 to 20 refers to the percentage of the distance across the scalp, either from the tragus to tragus or the nasion to inion, that defines the meridian (Fig. 36-7). Electrodes can be placed at the intersection of each meridian. Each such intersection or point is given a name—either a combination of letters and a number or two letters, where the final letter is Z. The letters are F for frontal, C for central, P for parietal, T for temporal, O for occipital, A for auricular, and Fp for frontal pole. A letter followed by an odd number is a point on the left hemisphere, while a letter followed by an even number is a point on the right hemisphere. Two letters, with the second letter a Z, indicate a point along the midline.

Although sophisticated EEG monitoring for epilepsy evaluation may require recording of multiple channels, providing information on the activity between numerous points, EEG monitoring during anesthesia frequently uses a broad montage with fewer channels (two or four) to evaluate hemispheric activity. Once the signal is recorded, it can be evaluated in several ways. Viewing raw EEG may be appropriate at times, but subtle changes are difficult to detect, particularly for the infrequent user. However, the EEG can be processed to yield readily interpretable information. A common method used is frequency domain analysis. Using Fourier analysis, the apparent random activity of raw EEG can be broken down into a series of wave frequencies, the summation
of which gives the overall EEG pattern. The range of frequencies seen in EEG is described in Table 36-1. The power (amplitude squared) at each frequency can then be plotted as a spectral array, whereby the effect of various influences such as anesthetic agents or an ischemic insult can be detected by how they modify the spectral analysis. A common parameter to include in the analysis of EEG is the spectral edge frequency, which is the frequency below which 95% of the power resides.






Figure 36.7. The international 10–20 system for electroencephalogram electrode montage. The odd numbers denote the left (L) hemisphere whereas the even numbers represent the right (R) hemisphere. See text for details.








Table 36-1. Electroencephalogram Frequencies






















Wave Range (Hz) Description
Delta 0–3 Low frequency, high amplitude; present in deep coma, encephalopathy, and deep anesthesia
Theta 4–7 Not prominent in adults, although may be seen in encephalopathy
Alpha 8–12 Prominent in the posterior region during relaxation with eyes closed
Beta >12 High frequency, low amplitude; the dominant frequency during arousal








Table 36-2. Indications for Electroencephalogram Monitoring








During anesthesia

  1. Carotid endarterectomy
  2. Cardiopulmonary bypass procedures
  3. Cerebrovascular surgery

    1. Aneurysm surgery involving temporary clipping
    2. Vascular bypass procedures

  4. When burst suppression is desired for cerebral protection
In the intensive care unit

  1. Barbiturate coma for patients with traumatic brain injury
  2. When subclinical seizures are suspected

A progressive reduction in CBF will produce a reliable pattern change in the EEG, consisting of a loss of high-frequency activity, a loss of power, and the eventual progression to EEG silence. The monitor is therefore useful when surgical procedures jeopardize perfusion to the brain, such as when the carotid artery is cross-clamped during CEA. The EEG is particularly useful in this setting because the spectral analysis on the at-risk side can be compared in real time with the unaffected side, thus facilitating detection of ischemia by the resultant asymmetry of the spectral edge frequency.

However, the changes in the EEG spectrum seen with ischemia can occur as a result of other influences. Intravenous anesthetic agents such as propofol and thiopental, as well as inhaled agents such as isoflurane, will cause a similar decrease in the spectral edge frequency, with eventual progression to a drug-induced isoelectric EEG in a dose-related manner. During certain surgical procedures, such as extracranial-to-intracranial arterial bypass procedures, maximal suppression of cerebral metabolic rate is desirable to protect the brain during an ischemic insult. Under such circumstances, the anesthetic agent can be titrated against the EEG until the desired effect is achieved. Typically, instead of an isoelectric EEG, the goal is a state called burst suppression. In this state, periods of isoelectric EEG are punctuated by “bursts” of EEG activity. When burst suppression is the goal, a suppression ratio can be calculated as the percentage of an epoch in which the patient’s EEG is isoelectric. The suppression ratio allows one to achieve near-complete suppression (>90%) of EEG activity, while remaining certain that regular EEG activity will return in a short while with cessation of administration of the drug. In contrast, when complete isoelectric EEG is achieved, time to arousal becomes unpredictable. Other settings in which EEG monitoring and burst suppression may be useful are listed in Table 36-2.

Using a proprietary algorithm based on probabilistic analysis, a computer-processed EEG has been used to derive a dimensionless number to monitor the degree of hypnosis or the “depth of anesthesia.” The most commonly used monitor is the Bispectral index (BIS) where a number between 40 and 60 is considered optimal for the prevention of intraoperative awareness. However, a recent study failed to demonstrate the superiority of a BIS protocol over a protocol based on end-tidal anesthetic agent concentration monitoring in the prevention of intraoperative awareness.22


Evoked Potential Monitoring

Although EEG is a cerebral function monitor that detects spontaneous activity, evoked potential (EP) modalities detect signals that are the result of specific stimuli applied to the patient. These include somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP), visual evoked potential (VEP), and motor evoked potential (MEP).

The proposed benefit of EP monitoring is to identify the deterioration of neuronal function, thus enabling the opportunity to correct offending factors before becoming irreversible. Such factors include positioning of the patient (e.g., neck position, shoulder position), hypotension, hypothermia, and surgical intervention. In elective spinal surgery without EP monitoring, iatrogenic neurologic injuries have been estimated to be 0.46% for anterior cervical discectomy, 0.23% to 3.2% with scoliosis correction, and between 23.8% and 65.4% with intramedullary spinal cord tumor resection. A recent systematic review indicated that, although there is a high level of evidence that multimodal neurophysiologic monitoring is sensitive and specific for detecting intraoperative neurologic injury during spine surgery, there is very little evidence that an intraoperative response to a neuromonitoring alert reduces the rate of perioperative neurologic deterioration. Consequently there is a low level of evidence that it reduces the rate of new or worsening perioperative neurologic deficits.23,24


Somatosensory Evoked Potential

SSEP is a signal that is detectable on EEG and is generated in a time-locked fashion in response to a specific applied sensory input, typically a cutaneous electrical stimulation (i.e., of a peripheral sensory nerve, but also of a cranial nerve with a sensory pathway). As a result, an intact neural pathway from the periphery to the cerebral sensory cortex is essential for a signal to be generated. This monitoring modality has application in any surgical procedure that may jeopardize this pathway. Specifically, spine surgery in which the dorsal column of the spinal cord may be placed at risk is a particularly appropriate application, but it may also be used during other procedures such as craniotomy
and carotid surgery where any part of the pathway may be subjected to ischemia or surgical retraction.

Because of the presence of spontaneous EEG activity, a single peripheral stimulus, which generates cortical activity of relatively low amplitude, would not be detectable amidst the background noise. Summation followed by signal averaging of repetitive stimuli is therefore necessary in order to extract meaningful signals.

Stimulation is typically done in the regions of the median nerve, ulnar nerve, and posterior tibial nerve to generate predictable and reliable signals. However, in theory, any sensory nerve could be used to generate SSEP. The SSEP is described by its polarity (the direction of the wave deflection) and its latency (the time required for a signal to be detected after the stimulus has been applied), and is quantified by both the amplitude of that signal and its latency. For example, N20 is the SSEP generated via stimulation of the median nerve that is expected to have a latency of approximately 20 ms and a negative displacement (Fig. 36-8).

Disruption of the neural pathway at any point will result in complete loss of SSEP. More commonly, ischemia, not mechanical disruption, is the intraoperative insult. As a result of ischemia, the amplitude of the signal decreases and the latency increases. A 50% decrease in signal amplitude is generally accepted as clinically significant, as is a 10% increase in latency.






Figure 36.8. Representative tracings of multiple modalities of sensory evoked potential. BAEP, brainstem auditory evoked potential; ms, millisecond; n, nerve; SSEP, somatosensory evoked potential; VEP, visual evoked potential.


Brainstem Auditory Evoked Potential

BAEP is a specialized type of sensory evoked potential. Instead of an electrical stimulus applied to a somatosensory nerve, a standardized sound (click) is applied to the eighth cranial nerve via the auditory apparatus. A recognized series of peaks are generated with this technique, where the latency of each peak has significance with respect to the integrity of various parts of the auditory pathway. Although this monitoring modality is specific to cranial nerve VIII, and is particularly useful in acoustic neuroma surgery, it may be used during any surgical procedure around the brainstem to infer its integrity, although such use is associated with both low sensitivity and specificity.


Visual Evoked Potential

VEP signals are generated via light stimulation of the retina. Typically, goggles that emit LED lights are worn. Although this modality is particularly appealing to monitor the integrity of the optic nerve in settings in which visual loss is a concern, such as in prone spine surgery, the signals are not robust. They are difficult to record in a consistent fashion during anesthesia, although it appears to be more stable during propofol compared to inhalation anesthesia. Research is ongoing with respect to its intraoperative use, particularly with regard to its interpretation.


Motor Evoked Potential

MEP monitoring is different from the other evoked potential modalities described thus far. Whereas SSEP, BAEP, and VEP provide information about ascending sensory neural pathways (i.e., from the periphery to the cerebral cortex), MEP evaluates descending motor pathways (i.e., from the cerebral cortex, past the neuromuscular junction, to peripheral muscle groups). This difference allows MEP to complement SSEP, particularly in the setting of spine surgery, in which the two modalities provide information about the integrity of anatomically different areas of the spinal cord. With MEP, the stimulus is applied in a transcranial fashion over the motor cortex. The deflection, essentially an electromyographic signal, is then detected by electrodes embedded in the muscle belly. Although theoretically the stimulus can be delivered with either a magnetic or electrical source, transcranial magnetic stimulation is obliterated under anesthesia. The transcranial electrical signal is usually delivered as a rapid train of four or more stimuli, the voltage of which is adjusted to achieve adequate signals in both the upper and lower extremities. The MEP is typically detected at the thenar eminence and the abductor hallucis muscle. Transcranial electrical MEP is of substantially greater magnitude compared with SSEP, and signal averaging with repetitive stimuli is therefore not required. However, it is very sensitive to anesthetic agents, particularly inhalation anesthetics. Its amplitude can be augmented by increasing the transcranial voltage, or the number of stimuli in the train. The stimulus can cause patient movement, so MEP signals are typically obtained intermittently at points during the surgery when slight patient movements are not problematic. A bite block is mandatory to prevent injury to the tongue during transcranial stimulation.

With MEP, latency of the signal is somewhat unreliable, and not typically used to make clinical decisions. Decision making is based on amplitude alone, where a 50% decrease is considered significant (Fig. 36-9). Although MEP can be used during any spine or intracranial surgical procedure, it is becoming increasingly used during cervical spine surgery.

MEP signals are much more sensitive to volatile anesthesia than SSEP. Although there is some evidence that MEP signals are adequate during desflurane anesthesia, more research on
the efficacy of this technique is required, and total intravenous anesthesia is the preferred technique when MEP monitoring is required.25 Some centers use partial neuromuscular blockade, but most centers avoid muscle relaxants altogether with MEP in order to avoid compromise of the signal.26






Figure 36.9. Representative tracing of motor evoked potential (MEP) recorded from the thenar muscles in response to transcranial electrical stimulation.


Spontaneous Electromyography

Spontaneous electromyography (EMG) is different from other evoked potentials in that a signal is not intentionally generated through stimulation at some point in a known neural pathway. Instead, it is a continuous recording of EMG activity in the muscle of regions innervated by nerve roots around which surgeons are working. Its purpose is to detect injury to those nerve roots by the surgical procedure. Impingement on a nerve root by an instrument will cause immediate motor activity that is easily detectable, which may allow the surgeon to modify his or her technique. Although spontaneous EMG is a robust signal that is tolerant of various anesthetic techniques, muscle relaxant must be avoided. Spontaneous EMG is frequently used during cervical and lumbar spine surgery where the brachial plexus and lumbosacral plexus are encountered.


Cranial Nerve Monitoring

Surgery in the posterior cranial fossa and adjacent to the brainstem places the surgeon in close proximity to cranial nerves. Although cranial nerve VIII can be monitored with BAEP as discussed earlier, several other cranial nerves can be monitored as well. Generally, only the integrity of nerves with motor components can be detected, either through spontaneous EMG or through EMG evoked by local electrical stimulation. These include cranial nerves V, VII, IX, X, XI, and XII. Cranial nerve X is usually monitored via special monitoring endotracheal tubes embedded with electrodes near the cuff.


Influence of Anesthetic Technique

As mentioned previously, anesthetic agents can have a profound influence on the amplitude and latency of evoked potentials. For instance, the quality of signals obtained with SSEP monitoring depends on the anesthetic agents used. Signals are obtainable under volatile anesthesia, but the anesthetic is typically kept at sub-MAC (minimum alveolar concentration) doses to avoid degradation in quality (increase in latency and decrease in amplitude), as amplitude of SSEP signals are depressed by volatile agents in a dose-related manner; they are recordable during low dose and obliterated with high doses. Potent volatile anesthetics should not be combined with nitrous oxide, as this technique will further compromise quality. The signals are unaffected by opioids, and opioid infusions are frequently used to facilitate low-dose volatile anesthesia. Signal quality is also excellent under intravenous anesthesia with propofol. Ketamine has been shown to enhance evoked potential monitoring. Dexmedetomidine infusion has also been used as an adjunct, allowing a reduction in propofol dose, but its effects on MEP remain controversial, with some studies reporting a lack of effect while some reports suggest a deleterious effect.27,28

To summarize the influence of anesthetic agents on evoked potential monitoring, general statements can be made.



  • Inhalation agents including nitrous oxide generally have more depressant effects on EP monitoring than intravenous agents.


  • Cortical EP with long latency involving multiple synapses are exquisitely sensitive to the influence of anesthetic while short latency brainstem and spinal components are resistant to anesthetic influence. Thus, BAEP can be recorded under any anesthetic technique, whereas VEP and SSEP are very sensitive.


  • Monitoring of MEP and cranial nerve EMG in general preclude the use of muscle relaxants, although the use of a short-acting neuromuscular blocking agent for the purpose of tracheal intubation is not contraindicated as its effect usually wears off before monitoring and surgery begins.


  • MEP is exquisitely sensitive to the depressant effects of inhalation anesthetics including nitrous oxide. Although it can be recorded with low-dose agents, the signals are so severely attenuated that this practice is generally not advisable. Total intravenous anesthesia without nitrous oxide is the ideal anesthetic technique for monitoring of MEP. Ketamine may enhance the amplitude of MEP, while dexmedetomidine may have either negligible or some depressant effects.


  • Opioids and benzodiazepines have negligible effects on recording of EP.


  • Propofol and thiopental attenuate the amplitude of virtually all modalities of EP but do not obliterate them. SSEP and MEP can be monitored even during burst suppression induced by these agents. BAEP can be recorded with any anesthetic technique.


  • During crucial events in which part of the central neural pathway is specifically placed at risk by surgical manipulation, as in placement of a temporary clip during aneurysm surgery, change in “anesthetic depth” should be minimized to avoid misinterpretation of the changes in EP recorded.


  • Ketamine and etomidate have been reported to enhance the quality of signals in patients with weak baseline SSEP signals, although the clinical significance and interpretation of signals obtained under these circumstances remain unclear.


Cerebral Perfusion

Although adequate CBF does not guarantee the well being of the CNS, it is one factor that is essential to its integrity. Measuring CBF is therefore an attractive method of monitoring the
CNS. Currently available techniques for quantitative measurement of CBF are not practical as an intraoperative monitor, but other methods for looking at relative changes in CBF do lend themselves to use in the operating room. Transcranial Doppler ultrasonography (TCD) and laser Doppler flowmetry are examples. Furthermore, as adequate CBF depends on an appropriate CPP, measuring ICP may be useful in certain patients to ensure conditions are adequate for sufficient CBF. Finally, numerous other modalities that evaluate CBF and that may not be practical in the operating room are used commonly in the perioperative setting.


Laser Doppler Flowmetry

Laser Doppler flowmetry is a technique that measures cortical blood flow in a small region of the brain adjacent to the placement of the device. Although it is useful for detecting relative changes in CBF, its utility is limited by several factors. First, it requires a burr hole for placement, which prevents its use in most patients. Second, it measures flow in only a small region of the brain; it could miss hypoperfusion in any area of the brain not directly monitored. Accuracy is also affected by movement and the presence of underlying major vessels. Because of these limitations, laser Doppler flowmetry has found limited applications.


Transcranial Doppler Ultrasonography

TCD is a noninvasive monitor for evaluating relative changes in flow through the large basal arteries of the brain (i.e., the circle of Willis). TCD does not measure flow directly, and therefore cannot provide information regarding absolute CBF. TCD measures flow velocity (Fig. 36-10), which is directly proportional to the flow if the diameters of these large vessels are constant. Except in well-known circumstances such as cerebral vasospasm following aneurysmal subarachnoid hemorrhage, these vessels are thought to be conductance vessels, where diameters of the basal arteries are stable.29 Pressure autoregulation and CO2 reactivity of CBF occurs via changes in arteriolar diameter distal to these large vessels.

Although the vessels that can be evaluated with TCD include the middle cerebral artery, internal carotid artery, anterior cerebral artery, posterior cerebral artery, ophthalmic artery, vertebral artery, and basilar artery, not all of these vessels can be monitored continuously during surgical procedures. Many of these vessels can only be evaluated with a hand-held TCD probe, which is useful for providing a brief snapshot of flow velocity in that vessel. A commercially available device for fixation of the TCD probe is essential for continuous monitoring. These devices are available either as a headband or as a rack that remains attached via fixation points on the bridge of the nose and in bilateral auditory canals. With these devices, flow velocity in the middle cerebral artery can be continuously evaluated.

In addition to the measurement of flow velocity, TCD is useful for detecting emboli. Microembolic signals can be generated by the passage of either gas or particulate matter (Fig. 36-11). The former is likely to occur as a result of venous air embolism (VAE), particularly if the patient has a patent foramen ovale, while the latter may occur during the manipulation of an atheroma in a neck vessel or as the result of thrombus formation and dislodgement on a vascular dissection.

Specific applications for intraoperative use of TCD include CEA, nonneurologic surgery in patients with TBI, and surgical procedures requiring cardiopulmonary bypass. There are also numerous indications for TCD in the perioperative setting.

Perhaps the most important use of TCD is in the neurocritical care unit, where it is used to monitor the development of vasospasm in patients who have suffered a subarachnoid hemorrhage. It has also been used for the measurement of cerebral autoregulation in patients with TBI, vasomotor reactivity in patients with occlusive vascular disease, noninvasive measurement of ICP, determination of intracranial circulatory arrest and confirmation of brain death.30,31,32,33


Intracranial Pressure Monitoring

Although monitoring ICP does not provide direct information about CBF, it allows the derivation of CPP, which must be in an appropriate range in order for CBF to be adequate. CPP is defined as the difference between MAP and ICP. In other words, it is the net pressure acting to move blood through the cerebral vasculature (assuming ICP is greater than right atrial pressure). CPP and CBF are not expected to be proportional, as there are other factors
determining CBF (discussed elsewhere). In fact, within a physiologic range of CPP, CBF should remain approximately constant. However, a CPP that is too low will result in cerebral ischemia and CPP that is too high will cause hyperemia.






Figure 36-10. Transcranial Doppler tracing with release of cross-clamp during carotid endarterectomy. The resultant hyperemia is accompanied with evidence of air emboli (vertical streaks on the tracing). MCA, middle cerebral artery; ICA, internal carotid artery.






Figure 36.11. Particulate emboli seen on transcranial Doppler in a patient with symptoms of transient ischemic attacks consistent with right carotid artery territory embolization. The emboli are denoted by the arrows. MCA, middle cerebral artery; PW, pulse wave.

ICP monitoring is recommended in all salvageable patients with severe TBI (GCS ≤ 8) and an abnormal CT scan (hematomas, contusions, swelling, herniation, or compressed basal cistern), and in patients with severe TBI with a normal CT scan if two or more of the following features are noted at the admission: Age >40 years, unilateral or bilateral motor posturing, or SBP <90 mm Hg. However, patients who present to the operating room in the acute stage of injury will seldom have an ICP monitor in place, and the presence of elevated ICP must be inferred from the medical history, physical examination, and CT scan.

When ICP is high and CPP is low, interventions can target either ICP or MAP in order to restore a favorable balance of the two. Ideally, ICP should be maintained under 20 mm Hg. Interventions to lower ICP include suppression of cerebral metabolic activity, positional changes to decrease cerebral venous blood volume, drainage of CSF, removal of brain water with osmotic agents such as mannitol, and if absolutely essential, mild-to-moderate hyperventilation to further decrease CBV. MAP is raised via adequate intravascular resuscitation and with a vasopressor as needed. The goal CPP in TBI is >50 to 60 mm Hg.34


Other Modalities

Although seldom employed in the intraoperative setting, CT perfusion, single-photon emission computed tomography, positron emission tomography, and cerebral angiography all have roles, experimental or clinical, in the evaluation of CBF. However, these techniques are frequently used preoperatively and postoperatively in neurosurgical patients. On the other hand, intraoperative angiography is frequently used during neurovascular surgery to confirm placement of an aneurysm clip or to verify complete obliteration of an arteriovenous malformation (AVM). More recently, this has been superseded by indocyanine green videoangiography, as this obviates the need for radiation.35



Cerebral Oxygenation/Metabolism Monitors

A number of invasive and noninvasive monitors provide insight into the metabolic state of the brain and the level of tissue oxygenation of the brain, both of which reveal the balance between blood supply and metabolic demands.


Near-infrared Spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive method of detecting the oxygenation of cerebral tissue. It is based on reflectance spectroscopy; it measures the light reflected from chromophobes in the brain (hemoglobin) to derive the regional oxygen saturation. In this manner, it provides an indication of the balance between flow and metabolism. Typically, a sensor is applied to the forehead (over hairless skin). A light signal is transmitted through the skin, skull, and meninges into the cerebral cortex. A complex analysis of the reflected light allows calculation of the oxygenation of blood in the cortex, which is a mix of venous and arterial blood. Falling saturation indicates a decline in cerebral perfusion. Exact thresholds for concern relate to the specific device used for this purpose.

Bilateral monitoring is particularly attractive for procedures that place a single hemisphere at risk for ischemia, such as CEA carotid surgery. In this setting, the development of significant asymmetry in cerebral oxygenation could be used as an indicator for the need for a shunt.

Individual variations in extracranial tissue (hence contamination), arterial to venous blood volume ratio, systemic blood pressure, PaCO2, hematocrit, and regional CBV are factors that can influence cerebral tissue oxygenation, and this creates potential difficulties when attempting to establish a consensus value for NIRS-derived “thresholds” for ischemia/hypoxia.36 It is generally accepted that normal range varies between 60% and 75%, with a coefficient of variation of almost 10%.36,37

The applicability of NIRS in brain injury monitoring is as yet to be defined and there are no data to support the widespread application of NIRS to monitor cerebral oxygenation routinely during anesthesia and surgery. Ironically NIRS has found most acceptance in cardiac anesthesia, where access to the forehead for placement of the sensor is less of a problem than in neuroanesthesia. Nevertheless, it is a promising technology that, as advances in design are made, may find increasing application in the field of neuroanesthesia.


Brain Tissue PO2

The brain tissue PO2 (PbtO2) monitor is an invasive probe that is inserted through a burr hole into the brain parenchyma, typically in conjunction with a fiberoptic ICP monitor. As a result, this monitor is used most commonly in patients with TBI. It measures oxygen tension in the surrounding brain. An adequate CPP in such a patient is encouraging, but it does not guarantee adequate blood supply to meet the metabolic needs of the brain. PbtO2 complements ICP information in that it provides insight into oxygen delivery. A low PbtO2 is indicative of inadequate oxygen delivery to that area of brain. A level of 15 mm Hg is concerning for cerebral hypoxia, and warrants intervention in TBI.38,39 In patients with TBI, PbtO2 has been shown to correlate well with the treatment effects and outcome.40

Its major limitation is that the information it provides reflects oxygenation at the local level—in proximity to the probe—meaning that an adequate PbtO2 at that location may not guarantee adequate oxygen delivery to other regions of the brain.

Interventions to raise the PbtO2 must either target oxygen delivery or oxygen consumption. In order to improve oxygen delivery, FIO2-inspired oxygen can be increased, but treating anemia makes more sense from a physiologic perspective. Decompressive craniectomy may improve perfusion. Decreasing oxygen requirements can be accomplished by metabolic suppression with propofol or a barbiturate, as well as by treating hyperthermia with external cooling, acetaminophen, and when appropriate, nonsteroidal anti-inflammatory medications.


Jugular Venous Oximetry

Although PbtO2 gives a local view of the balance of oxygen supply and demand, jugular venous oximetry provides that same information for a larger portion, if not the complete, brain. For this monitor, a catheter is inserted into the jugular vein in a retrograde fashion so that its tip sits at the base of the skull in the jugular bulb. This allows continuous pressure monitoring as well as intermittent withdrawal of a jugular venous blood sample for gas analysis. Continuous monitoring can be achieved using an oximetry catheter inserted via a conduit sheath. Confirmation of location can be made with a lateral cervical spine film.

For best representation of the metabolic state of the brain, the catheter should be placed in the dominant jugular vein, most commonly the right side. In patients who have had a cerebral angiogram, the venous phase of the study will provide information on dominant venous drainage. Often the intra-arterial contrast will drain almost exclusively through one jugular vein, regardless of the side of injection. Side dominance can also be predicted using ultrasound where the dominant vein may be larger. In the absence of this information, the right side is preferred.

Pressure transduction of the jugular bulb catheter allows comparison with the central venous pressure to rule out potential venous obstruction. In a supine patient with a neutral neck position, there should be no pressure gradient between the tip of the jugular bulb and the central venous catheter. Although rare, a significant gradient (>4 mm Hg) can occasionally develop during positioning if there is significant twisting or bending of the neck. This gradient indicates venous obstruction, potentially causing brain edema, or ischemia. The head should be repositioned until the gradient resolves.

Blood gas analysis of the sample provides several useful parameters. The saturation of jugular venous blood (SjvO2) demonstrates whether CBF is sufficient to meet the cerebral metabolic rate for oxygen (CMRO2) of the brain. A normal value is in the 65% to 75% range. In TBI, SjvO2 below 50% for more than 10 minutes is undesirable and associated with poor outcome.41 However, it has low sensitivity, and a study using PET scan indicates that a relatively large volume of tissue must be affected, approximately 13%, before SjvO2 levels decreased below 50%.42 Intraoperative hyperventilation will lower SjvO2 as it decreases CBF. In the setting of a nontraumatized brain that is exposed to moderate hyperventilation for the duration of a neurosurgical procedure, the acceptable level for SjvO2 is unknown. In the absence of other demands, it is reasonable to guide intraoperative hyperventilation by maintaining SjvO2 >50%. It is essential that blood samples from the retrograde catheter be drawn slowly to avoid contamination from noncerebral venous blood.43

Measurement of simultaneous arterial and jugular venous samples allows the determination of lactate output from the brain, the presence of which indicates occurrence of anaerobic metabolism. The obvious disadvantage to jugular venous oximetry is precisely the opposite of the shortcoming for PbtO2, in that it is a global monitor that could easily miss small areas of regional ischemia. The two monitors may be complementary in the setting
of TBI. Intraoperatively, jugular venous oximetry is used routinely in some centers that specialize in neurosurgical procedures.


Cerebral Protection

Cerebral ischemia and/or hypoxia leads to neuronal death in multiple settings. For example, ischemic stroke, TBI, and cerebral vasospasm following subarachnoid hemorrhage. Efforts to avert neurologic insult, using medications or through the manipulation of physiologic parameters, have met with meager results. In the setting of ischemic stroke, for example, thrombolysis may restore perfusion and decrease infarct size, but it may also lead to expansion of the infarct, edema, and even hemorrhage as a result of ischemia-reperfusion injury. In general, a protective strategy that is effective in experimental cerebral ischemia has not been found to be useful in the clinical setting. Of recent advances that are intriguing and controversial, none matches that generated by the concept of cerebral protection by mild or moderate hypothermia.

Persons suffering out-of-hospital cardiac arrest have been shown to have improved neurologic outcome if they are made mildly hypothermic following resuscitation.44,45 Therefore, it would seem that mild hypothermia is protective against global ischemia/hypoxia at least in the setting of cardiac arrest.

One problem with most settings in which cerebral ischemia is encountered is that the therapeutic intervention can be applied only after the insult has occurred, that is, during the reperfusion phase. Little opportunity exists to intervene before the ischemic event. However, the operating room is a unique environment in this respect. Many ischemic insults that patients suffer in the operating room are iatrogenic and anticipated. A temporary aneurysm clip on the middle cerebral artery is an example of a focal ischemic insult that could be predicted, and a brief period of circulatory arrest induced with adenosine to facilitate clipping of a basilar artery aneurysm is an example of a global insult. The value of anticipating such events is that it allows the anesthesiologist to intervene in advance.

Despite the luxury of planning the intervention for the ischemic insult, the options anesthesiologists have for cerebral protection are few and the evidence for benefit is modest; much of this evidence has been extrapolated from animal research. Each technique will be examined in detail here.


Ischemia and Reperfusion

Ischemic insult to the brain results in energy failure. The brain depends on a continuous supply of glucose and O2 to support aerobic metabolism, generation of adenosine triphosphate (ATP), and maintenance of cellular function. When this nutrient supply is interrupted, ATP is depleted. Cellular processes, such as those that maintain cellular membrane integrity, fail. It is reasonable then to attempt to minimize ischemic insult by lowering cerebral metabolic rate, thus decreasing the likelihood of exhausting ATP reserves during the period of ischemia. This has been the traditional paradigm for approaching the subject of intraoperative neuroprotection.

Unfortunately, further damage occurs as a result of processes that are initiated during the reperfusion stage. The reperfusion injury may be mediated via the generation of toxic oxygen species, release of excitotoxic amino acids such as glutamate, up-regulation of nitric oxide synthase, and initiation of cellular apoptosis. Further therapeutic interventions would need to target these pathways as well to provide protection. A shift in the focus of neuroprotection from metabolic suppression to targeting ischemic cascades has recently been advocated.46


Hypothermia

It is important to distinguish mild/moderate and profound hypothermia, as they have very different practical considerations and they likely modify cerebral function in different ways.

Profound hypothermia is well known for its neuroprotective effects. Anecdotes of successful resuscitation of hypothermic drowning and avalanche victims with good neurologic recovery have been reported.47,48 Furthermore, extensive use of deep hypothermia with circulatory arrest has been used intraoperatively for the repair of aneurysms of the thoracic aorta and for cerebral aneurysms.49,50 When core body temperature is <20°C, and the brain is <15°C, circulatory arrest of <30 minutes appears to be well tolerated. This level of hypothermia not only decreases cerebral activity, but it also decreases the energy required for cellular housekeeping. The practical constraints against using deep hypothermia in settings in which cerebral ischemia is anticipated are numerous. Foremost is the need for cardiopulmonary bypass during the cooling and warming portion of the procedure. Hypothermia-induced coagulopathy is another concern during surgical procedures in the cold patient. Despite the drawbacks to this technique, it remains a reasonable anesthetic option to provide protection for the brain and other organs when the surgical procedure necessitates circulatory arrest.

Mild hypothermia (33° to 35°C) not only decreases cerebral metabolism, but likely modulates the immune and inflammatory response to ischemia, thus affecting the reperfusion portion of the injury as well. Animal studies have shown improved neurologic function following resuscitation from arrest.51 This promising result in animals was later confirmed by two independent studies in humans, demonstrating that induction of hypothermia in cardiac arrest patients improved the outcome.44,45

Although mild hypothermia is clearly beneficial in the setting of cardiac arrest, cerebral ischemia due to an arrest is an uncommon occurrence in patients under anesthesia. In contrast, the cerebral ischemia frequently encountered by the anesthesiologist is focal in nature because of the temporary occlusion of a cerebral vessel. Although there is considerable evidence in rats that mild hypothermia is beneficial here too, there is a paucity of evidence in humans. In fact, a large multicenter study (IHAST II—Intraoperative Hypothermia for Aneurysm Surgery Trial) evaluating patients undergoing cerebral aneurysm surgery found no benefit with mild intraoperative hypothermia.52 However, the study was not designed to study patients at the highest risk—that is, those who had undergone temporary occlusion for more than 20 minutes. Although the sample size is small, a post-hoc analysis of these at-risk patients suggest that there is a trend for either hypothermia or metabolic suppression to improve outcome.53

Nevertheless, hypothermia remains our most promising intervention for cerebral protection. There is a compelling physiologic rationale for its use, a clearly demonstrated effect in animals, and human data showing benefit in the setting of cardiac arrest. Unfortunately, inadequate evidence exists in humans outside cardiac arrest to recommend its routine use in the neurosurgical patient.

Despite the lack of evidence to support hypothermia in humans for cerebral protection, there is ample evidence that hyperthermia is associated with worse outcome in the setting of ischemic stroke, subarachnoid hemorrhage, cardiac arrest, and TBI.54,55,56,57 A common extrapolation from these studies is the belief
that concomitant hyperthermia and cerebral ischemia is deleterious. However, it is important to consider that these studies demonstrate an association, not a causation, of poor outcome from fever. Nevertheless, it would seem reasonable to avoid hyperthermia and treat fever aggressively in any setting in which the brain is at risk.58

In the operating room, during neurosurgical procedures in which the brain is at risk for ischemic insult, a goal temperature of 35° to 36°C is reasonable. Mild hypothermia (33° to 35°C) may be appropriate in many patients with a planned period of temporary focal ischemia (as in temporary occlusion for aneurysm clipping) even recognizing that there is currently a lack of solid evidence to support this therapy. Finally, deep hypothermia (<20°C) is appropriate in any situation in which a prolonged cardiac arrest is required.


Medical Therapy for Cerebral Protection

Volatile and intravenous anesthetic agents decrease cerebral metabolism, and thus seem like appropriate candidates for cerebral protection. However, evidence that the level of metabolic suppression does not correlate with the degree of protection has eroded the traditional belief in the mechanism of protection.59 Nevertheless, numerous animal studies have found protective effects of volatile anesthetics, particularly isoflurane, in mitigating mild-to-moderate ischemic insult, although this effect may only be short-lived.60,61,62,63 This effect may exist when applied during the insult, but also may be effective when administered prior to the insult as a preconditioning therapy.64,65

Barbiturates, such as thiopental, have been extensively researched in regard to cerebral protection. They have been shown to have at least short-term benefit on focal cerebral ischemia, while benefit in global ischemia remains controversial.66,67,68,69,70,71,72,73,74 This effect may be mediated through a reduction in glutamate activity and intracellular calcium, an increase in γ-aminobutyric acid (GABA) activity, as well as N-methyl-D-aspartate (NMDA) antagonism.75,76 Propofol likely has similar protective effects through its action on GABA receptors, as well as via free radical scavenging and limiting lipid peroxidation.77,78 Again, the durability of this protection is unknown.

Current opinion is that anesthetic neuroprotection is primarily mediated through prevention of excitotoxic injury, not through termination of apoptotic pathways; it thus delays neuronal death and leaves a greater temporal window for intervention.61 Without other therapeutic options to prevent eventual cell death, outcome is unlikely to be improved, save for perhaps the setting of mild ischemic insult in which apoptotic pathways are not initiated. Sufficient evidence in humans to guide clinical interventions, apart from modest hypothermia in cardiac arrest, is difficult to obtain.45,79 Clinically, barbiturates and propofol are used intraoperatively to achieve metabolic depression as evidenced by a burst suppression EEG pattern, and although not statistically significant, results from IHAST II suggest that patients undergoing temporary occlusion for >20 minutes may benefit from metabolic suppression therapy.53


Glucose and Cerebral Ischemia

Although hyperglycemia has long been recognized as a frequent occurrence in critically ill patients, it was commonly viewed as benign or even beneficial.80 Hyperglycemia could facilitate cellular uptake of glucose through noninsulin-dependent mechanisms, and thus may benefit cellular metabolism. A subsequent recognition of its association with worse outcome in many settings, including acute coronary syndrome, stroke, TBI, and critical illness, forced the medical community to reconsider the burden of hyperglycemia.81,82,83,84,85,86 Furthermore, animal studies suggested that hyperglycemia in the setting of both cerebral and myocardial ischemia increased infarct size.87,88

Although considerable evidence accumulated suggesting harm associated with hyperglycemia, evidence for benefit with normalization of serum glucose using insulin has been somewhat controversial. The most influential literature is from the intensive care unit (ICU) setting, not the operating room. A prospective study in surgical ICU patients (predominantly after cardiac surgery) showed that mortality and morbidity benefit with tight glycemic control (80 to 110 mg/dL).89 This study spurred an unfettered enthusiasm for aggressive treatment of hyperglycemia, changing practice not only in the surgical ICU but the medical ICU, and in many cases, the operating room. However, a subsequent study evaluating this therapy in a much sicker medical ICU population showed no overall mortality benefit.90 In fact, subgroup analysis revealed increased mortality in patients who stayed in the ICU <3 days, with an improvement only in those who had a longer ICU stay. In the heterogeneous patient population who present for neurologic surgery, with operative times of several hours, not several days, it is inappropriate to extrapolate conclusions from a body of controversial ICU literature to the anesthetic environment, particularly when there is evidence for harm with short durations of therapy. Furthermore, a prospective study of intraoperative insulin therapy in cardiac surgery patients further eroded the basis for translating this ICU literature to the operating room; the insulin group had a higher incidence of death and stroke.91

Despite our reluctance to embrace intraoperative tight glycemic control given the current literature, it is worthwhile to consider the patient undergoing cerebrovascular surgery in particular. Given the preponderance of evidence that hyperglycemia and cerebral ischemia in combination are harmful, changing practice in these patients may be warranted. Hyperglycemia on the day of surgery for CEA is associated with worse outcome.92 And, patients who suffer from an ischemic stroke have an improved outcome if their glucose is treated aggressively.93 Therefore, it may be appropriate to treat neurosurgical patients who will have a period of cerebral ischemia due to temporary vascular occlusion differently from other neurosurgical patients. Better glycemic control is a reasonable goal in these patients, aiming for a range of 140 to 180 mg/dL however, we cannot state at this time that this intervention is neuroprotective.


Promising Areas of Research

Continued research in the various excitotoxic and apoptotic pathways that lead to cell death with cerebral ischemia is essential to bring promising interventions to the clinical arena. It is likely that only a multimodality approach will create durable meaningful cerebral protection.61 Mild to moderate hypothermia continues to hold promise, given its efficacy in experimental focal ischemia. Several additional medical interventions show potential as well. Statins, which inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have nonlipid lowering effects such as improved endothelial function, as well as antithrombotic and anti-inflammatory activity, which may be neuroprotective.94 Furthermore, the nonhematopoietic effects of erythropoietin include mitigation of lipid peroxidation and prevention of apoptosis.95 Whether these medications will offer any benefit to neurosurgical patients remains to be determined.



A Practical Approach

In the absence of compelling evidence in humans regarding the benefit of one practice over another, it is difficult to present firm guidelines with respect to the prevention of intraoperative ischemic insult. Maintaining optimal systemic and cerebral hemodynamics, as well as oxygenation, remain the most important principles. Beyond these, for patients undergoing surgical procedures with an anticipated period of temporary focal cerebral ischemia such as cerebral aneurysm surgery or cerebrovascular bypass procedures, either volatile anesthesia or an intravenous technique can be used. It is reasonable to administer additional propofol or thiopental prior to vessel occlusion. Optimally this intervention should be guided by EEG monitoring with the goal of achieving burst suppression nearing a 50% ratio. A total intravenous anesthetic technique is preferred when maximal brain “relaxation” is desired. Euglycemia, or near euglycemia prior to vessel occlusion is desirable (140 to 180 mg/dL), but frequent glucose checks are essential throughout the anesthetic to avoid episodes of hypoglycemia if insulin is administered. Finally, hyperthermia should be avoided during this time, with the temperature kept at or below 36°C.


Anesthetic Management


Preoperative Evaluation

Risk stratification is indicated for neurologic or spine surgery to assess the patient’s neurologic condition, as well as the inherent risk of the surgical procedure. For a smooth transition from patient referral to surgical intervention, dynamic communication between neurosurgeons, anesthesiologists, the preanesthesia clinic, neurophysiologists, and the laboratory is essential.96,97

Preoperative assessment allows identification of modifiable risk factors, optimization of the patient’s condition, explanation of the risks and formulating the best possible anesthetic plan to improve patient safety, optimize resource utilization and increased patient satisfaction. A thorough history may be difficult to obtain from patients whose disease has resulted in a neurologic decline, such as those obtunded from TBI. Prior medical records, discussion with family physicians and family members are both helpful in this context.

Perioperative cardiac outcome is influenced by urgency, magnitude, type, duration of surgery, associate blood loss, fluid shifts, and change in body temperature. The 2007 American College of Cardiology/American Heart Association guidelines has a simplified algorithm for considering whether a patient needs preoperative cardiac testing, such as stress echocardiography, or a nuclear medicine evaluation of myocardial perfusion.98 Spine and neurosurgical surgery fall into the intermediate-risk procedure category. The decision to perform a noninvasive cardiac test in patients with risk factors for coronary disease and poor functional status hinges on whether findings from that evaluation will affect management of the patient in the time before surgery. For neurologic patients with significant cardiac disease, current guidelines include delaying surgery for at least 2 weeks following simple balloon angioplasty, 1 month for a bare metal stent, and a full year for a drug-eluting stent. However, it is generally not feasible to delay most of the spine and neurosurgical procedures. For these patients joint consultation with cardiologists is essential. As for beta-blockers, the results of the POISE trial indicated that perioperative beta-blockade is recommended primarily in two types of patients undergoing intermediate-risk surgical procedures: Those already receiving a beta-blocker, and those who are at high risk for perioperative myocardial infarction due to documented reversible ischemia from a noninvasive study.99,100 Furthermore, patients previously receiving a statin should continue their statin in the perioperative period.

Further considerations in the preoperative visit should include issues that will affect choice of medications and anesthetic agents. Many patients presenting for spine surgery have weakness or paralysis that may present a contraindication to the use of succinylcholine. In addition, some neurosurgical patients may have suffered from a stroke resulting in a similar contraindication. Finally, many neurosurgical patients have been exposed to antiepileptic medications, which are known to induce liver enzymes and alter drug metabolism. Previous allergies or reactions to these medications, especially phenytoin, should be elucidated.


Induction and Airway Management

With the exception of some minimally invasive spine surgery procedures and awake craniotomies, placement of an endotracheal tube is essential for most surgical procedures of the brain and spinal cord.

During induction of anesthesia, hypotension, hypertension, and prolonged apnea should be avoided. A brief period of mild hypotension is frequently encountered following induction of anesthesia. Although most patients tolerate this transient phenomenon well, it should be aggressively avoided and/or treated in patients with brain injury in which any episode of hypotension may be associated with unfavorable outcome.101 Hypertension due to laryngoscopy, in contrast, is poorly tolerated by patients following aneurysmal subarachnoid hemorrhage, as systolic hypertension is thought to be a cause of recurrent hemorrhage from the aneurysm.102 Finally, apnea results in a predictable increase in PaCO2, and corresponding cerebral vasodilation. Although most patients tolerate the increase in CBV, patients with poor intracranial compliance may develop severe intracranial hypertension and decompensate from apnea, as well as suffer a decrease in cerebral perfusion.

TBI patients in particular are frequently intolerant of apnea. Unfortunately, many of these patients require a rapid-sequence induction. To further complicate matters, the presence of a cervical collar for known or suspected cervical spine injury may make intubation more difficult. Careful preparation for a difficult airway is essential. Furthermore, these patients may have concomitant injuries with significant blood loss that may predispose to systemic hypotension. Vigorous resuscitation with isotonic fluid and/or blood should be administered prior to induction and continued until the patient is euvolemic. A conservative dose of thiopental, propofol, or etomidate is appropriate for induction, with succinylcholine a reasonable choice as the muscle relaxant in the setting of acute injury.

Because patients with subarachnoid hemorrhage are at risk of rebleeding from hypertension, it is reasonable to place an arterial catheter for hemodynamic monitoring prior to induction. Unacceptable increases in blood pressure during laryngoscopy should result in discontinuing the attempt, returning to mask ventilation, and deepening the anesthesia. The latter can be accomplished either with a higher concentration of inspired volatile anesthetic, or a bolus of an intravenous agent such as propofol or remifentanil. In addition, esmolol (0.5 mg/kg) can be given prior to laryngoscopy to blunt the hypertensive response.

Most intravenous anesthetic agents (propofol, thiopental, and etomidate) are indirect cerebral vasoconstrictors, reducing
cerebral metabolism (CMR) leading to a corresponding reduction of CBF while preserving autoregulation and CO2 reactivity. In contrast, ketamine has sympathomimetic properties. Its cerebral effects include an increase in CBF and ICP, but these are usually attenuated by the actions of other concurrently administered drugs.103,104,105 Etomidate decreases the cerebral metabolic rate, CBF, and ICP. At the same time, because of minimal cardiovascular effects, CPP is well maintained. However, it has been reported to reduce brain tissue oxygen tension, but the mechanism is unclear. Although changes in the EEG resemble those associated with barbiturates, etomidate enhances SSEPs and causes less reduction of MEP amplitudes than thiopental or propofol.106,107 The major limitation of etomidate is its known adrenal suppression effects. Even after a single induction dose etomidate has been shown to prolong hospital and ICU length of stay.108,109,110

The choice of muscle relaxant for use during induction deserves some consideration. Succinylcholine is contraindicated in patients with muscle denervation from stroke, myelopathy, or spinal cord injury (SCI) which results in up-regulation of acetylcholine receptor isoforms on myocyte membranes.111 In these patients, profound hyperkalemia may result from the use of succinylcholine which has the potential to lead to a cardiac arrest.112 However, it is generally safe to use succinylcholine in the first 24 to 72 hours after an injury, as well as, although controversial, after the spasticity is well established in about 9 months. In general a nondepolarizing muscle relaxant is appropriate for most neurosurgical patients to achieve acceptable conditions for tracheal intubation. Duration of action should be considered if MEP, spontaneous EMG, or cranial nerve monitoring is planned when adequate reversal is not possible. When used in appropriate doses, rocuronium (1.2 mg/kg) is comparable to succinylcholine (1 mg/kg) for rapid sequence induction.113 When available, profound neuromuscular blockade from rocuronium can be reversed with sugammadex, which currently awaits approval in the United States.114,115

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Jul 5, 2016 | Posted by in ANESTHESIA | Comments Off on Anesthesia for Neurosurgery
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