Neuroanesthesia

Handbook of Clinical Neurology, Vol. 121 (3rd series) Neurologic Aspects of Systemic Disease Part III Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 106

Neuroanesthesia W. SCOTT JELLISH* AND STEVEN EDELSTEIN Department of Anesthesiology, Loyola University Medical Center, Maywood, IL, USA

HISTORY One of the most important influences in the development of neurosurgery in the 19th century was the introduction of anesthesia. The discovery of carbon dioxide, hydrogen and nitrogen and experiments by Joseph Priestley on several other gases including nitrous oxide and oxygen created an interest in exploring possible uses for these agents. Sir Humphrey Davy, one of the founders of the Pneumatic Institute of Bristol, suggested that nitrous oxide be used to alleviate pain after surgical operations. The advent of tracheal intubation and controlling ventilation was the next major step in the development of neuroanesthesia. Pierre Desault observed in the late 18th century that foreign bodies such as tubes could be tolerated by the larynx in conscious individuals. William Macewen, a professor from Glasgow, mandated practical instruction and certification in anesthesia. His attention to detail was well known and he tenaciously reported physical signs including pupillary changes associated with the response to anesthetics, cerebral injury, and intoxication. He was one of the first to notice that in acute inflammatory cerebral disease, anesthesia use should be minimized as deeper levels could increase the edema that may already be present. Victor Horsley found that ether caused a blood pressure rise, increased blood viscosity, and prompted excessive bleeding, vomiting, and excitement. He concluded that this drug should never be used in neurosurgery. During craniotomy Horsley felt that chloroform administration should be reduced to 0.5% or less after bone removal. Exact determination of the percentage delivered was particularly important in patients with raised intracranial pressure since a safe concentration in normal patients was found to be fatal in patients with intracranial pathology.

A pioneer in neurosurgery, Dr. Harvey Cushing, became involved early in his career with the practice of anesthesia and was one of the first to devise charts that followed pulse, respiration and temperature. These charts were soon incorporated as part of the anesthetic record. Cushing also was the first to recognize the association between blood pressure and elevated intracranial pressure (ICP). He incorporated continuous blood pressure recording as part of the anesthesia record. In addition, Cushing used local anesthesia and employed cocaine infiltration of the scalp and experimented with the use of several other local anesthetics. Advances in the early 20th century contributed to the development of neuroanesthesia. Instead of open drop methods, ether anesthesia pumping devices were attached with tubes between the patient and the inhaler, moving the sources of anesthesia away from the head. In 1909 Elsberg advocated intratracheal insufflation anesthesia with ether and O2. By the 1930s endotracheal anesthesia was recommended for neurosurgery. Other anesthetics such as tribromo methanol were developed and administered rectally to reduce ICP. Thiopental also was synthesized and gained popularity around 1940. Its use in reducing ICP became well known and it is still used to this day. Halothane was synthesized by Raventos and Sundling in 1956 and introduced into clinical practice the following year. It was used as a neuroanesthetic, but its propensity to increase ICP by cerebrovasodilation concerned many anesthetists and neurosurgeons. Most of the major neuroanesthesia principles were developed over the last 60 years. In 1942 it was noted that spontaneous ventilation produced hypoxia and hypoventilation making it difficult to reduce ICP. Cannon was the first to recognize the dependency of cerebral blood flow on carbon dioxide and oxygen tension. Intracranial

*Correspondence to: W. Scott Jellish, M.D., Ph.D., Professor and Chairman, Department of Anesthesiology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA. Tel: þ1-708-216-4016, Fax: þ1-708-216-8941, E-mail: [email protected]

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dynamics were further defined in 1919 and pressure/volume curves for intracranial compliance were identified. New and novel anesthetic agents were produced and investigators studied the cerebral vascular effects of these agents which will be discussed in subsequent sections of this chapter. A large variety of drugs surfaced as possible cerebroprotective agents and a much clearer pathway for cell damage was achieved. In addition, monitoring has seen major advances in the past 20 years. Air embolism, a potential complication of open cranium procedures, can be easily detected by the use of a precordial Doppler. Neurophysiologic monitors have seen major advances in their ability to monitor the integrity of the central nervous system, and their development has evolved only by close cooperation among basic scientists, neurosurgeons, and anesthesiologists.

NEUROANESTHESIA FUNDAMENTALS The goal for any neurosurgical anesthetic is to maintain cerebral perfusion and oxygen delivery to the central nervous system while surgical manipulation occurs. Physical manipulation by the surgeon (or mechanical manipulation by retraction), adverse venous drainage due to positioning of the patient, sympathetic stimulation, intravascular fluid shifts and variations in respiratory physiology all impact cerebral blood flow (CBF) and ultimately tissue viability. During anesthesia there is a balance between oxygen demand and delivery that is quite complex and requires an understanding of the neurophysiologic effects of medications administered to maintain amnesia, immobility, and analgesia.

INDUCTION AGENTS Induction agents rapidly alter the level of consciousness. When administered intravenously, each of these agents results in the patient going from an “awake state” to a state where awareness and responses to surgical stimulation are ablated. The pharmacokinetic characteristic shared by each of these medications is their rapid ability to redistribute from the vessel-rich areas of the central nervous system, thus terminating their pharmacodynamic effects on consciousness. Typical redistribution occurs within 10 minutes, even though the elimination half-life of many medications may be over several hours. Ultrashort-acting barbiturates have for years been the mainstay of intravenous induction agents. They are hypnotically active derivates of barbituric acid and are divided into thiobarbiturates (thiopental) and oxybarbiturates (methohexital). Barbituates act on the g-aminobutyric acid (GABAA ) receptor that is a chloride ion channel composed of five subunits, one of which is specific to barbiturates. Activation of the channel mimics the action of GABA increasing chloride

conductance and subsequently hyperpolarizing the cell membrane (Tanelian et al., 1993). Barbiturates cause a dose-dependent decrease in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) that occurs until the electroencephalogram (EEG) becomes isoelectric. The CMRO2 and CBF are coupled but ICP is markedly reduced by these agents. The reduction of ICP may be through reduction of blood flow and cerebral blood volume (CBV). There is also some evidence suggesting neuroprotective effects of barbiturates in the presence of focal ischemia (Warner et al., 1996). Propofol is an isopropyl phenol hypnotic dissolved in a lipid emulsion. The onset of the hypnotic effect is rapid (within seconds of administration) and duration is approximately 8–10 minutes. There is a significant decrease in CMRO2 via interference with the GABAchloride channel. The coupling of CBF and CMRO2 is maintained. However, some studies have suggested that there is a vasoconstrictive effect of propofol since there is a observed larger decrease in CBF compared to CMRO2 (McCulloch et al., 2007). Propofol has significant effects on the cardiovascular system, mostly as a result of vasodilation that leads to decreases in preload. In addition, propofol interferes with calcium influx in the cardiac system resulting in decreased contractility. Finally, there is inhibition of baroreceptors that typically respond to decreases in preload; this ultimately results in the lack of reflex tachycardia and more profound hypotension. As a neuroprotective agent, propofol has been used successfully for burst-suppression and metabolic suppression during episodes of surgically induced cerebral hypoperfusion. Possible reasons for its effectiveness may be related to the GABA activation, prevention of mitronchrondrial swelling, and attenuation of glutamate excitotoxicity (Adembri et al., 2007). There is little accumulation of the drug over time and this is the result of a very high plasma clearance and extensive extrahepatic clearance. Ketamine is a phencyclidine derivate that is frequently used for induction of anesthesia. With the administration of ketamine there is a notable depression of cortical and thalamic structures while stimulating the limbic and hippocampus. Several reflexes are maintained and it is common to see pupillary dilatation, nystagmus, lacrimation, salivation, emergence delirium, and increased skeletal muscle tone (Reves et al., 2010). Ketamine is known to increase CBF and CMRO2 with vasodilation probably related to its metabolic stimulator, direct dilating and cholinergic mechanisms (Sakabe and Matsumoto, 2010). Intracranial pressure is adversely affected with a marked increase in ICP with ketamine administration. This effect can be blunted by the

NEUROANESTHESIA coadministration of a benzodiazepine or thiopental or pre-existing hypocapnia. Ketamine use for intracranial procedures is usually contraindicated. Ketamine has been shown to be of possible benefit in patients undergoing electroconvulsive therapy (ECT) for major depression. Krystal and colleagues (2003) compared seizure duration, ictal EEG and cognitive side-effects of ketamine and methohexital anesthesia with ECT. It was noted that ketamine was well tolerated and prolonged seizure duration, particularly in those who had a seizure duration shorter than 25 seconds with methohexital at maximum stimulus intensity. Ketamine also increased mid-ictal EEG slow wave amplitude. They concluded that ketamine may be useful when it is difficult to elicit a robust seizure. The faster post-treatment reorientation also suggests a low level of associated cognitive sideeffects. Etomidate is a carboxylated imidiazole hypnotic that also activates the GABA-chloride channels and decreases CMRO2 and CBF in a parallel manner. It is also effective in burst-suppression but its neuroprotective effects have come into question due to the observation of injury-enhancing effects of the drug in the presence of middle cerebral artery occlusion (Annane, 2005). Hemodynamic stability is the main reason that etomidate is utilized as an induction agent. There is no significant change in heart myocardial contractility and systemic vascular resistance, thus cardiac output and blood pressure are maintained. There are other significant side-effects associated with etomidate including an increased incidence of postoperative nausea, pain on injection, myoclonus, and adrenocortical suppression. In fact, many practitioners have advised against the use of etomidate in the presence of high adrenal states such as sepsis (Annane, 2005). Unlike other agents utilized for the induction of anesthesia, benzodiazepines are not ultrashort-acting in duration but do interact with the GABAA receptor and affect the chloride channel. Typically, only one benzodiazepine plays a potential role as an induction agent during anesthesia, this being midazolam. Midazolam will reduce CMRO2 and CBF while producing a decrease or no change in ICP. It has been reported that midazolam may have a protective effect against hypoxia or cerebral ischemia (Lei et al., 2009). A summary of the cerebral effects of intravenous induction agents can be found in Table 106.1.

INHALATIONAL AGENTS Inhalational agents are the only true anesthetic agents used in practice. Each agent provides all of the key aspects of anesthesia. The pharmacologic basis of most is that of fluorinated ethers that have a propensity to

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Table 106.1 Cerebral effects of intravenous induction agents

Agent

Cerebral blood flow

Cerebral metabolic rate

Intracranial pressure

Thiopental Etomidate Propofol Midazolam Ketamine

### ## ## # ""

### ## ## # "

### ## ## # or ! " or ""

# Decrease, " increase, ! no change. (Adapted from Kass et al., 2010.)

vaporize. As the name implies, these drugs must be administered via the respiratory system and are unbound gases that translocate from the alveolus to the blood and ultimately the brain where their effect on consciousness occurs. A unique feature of these agents, compared with intravenous agent, is that the less soluble the agent, the faster the clinical effect. Inhalational agents utilized today are very insoluble, thus are “fast on” and “fast off.” This feature makes them very desirable in neuroanesthesia when rapid postoperative assessment of neurologic function is required. As with all medication, inhalational agents have implications due to their effects on CBF and CMRO2. These agents have the benefit of reducing CMRO2 on a global perspective. However, inhalational agents cause a dose-dependent increase in CBF due to their profound vasodilatory properties. This uncoupling of supply and demand may result in deleterious increases in intracranial pressure. In addition, there are significant systemic effects of these agents that must be taken into account. All inhalational agents result in a dose-dependent decrease in both myocardial contractility and systemic vascular resistance along with, in some agents, significant reflex tachycardia. Some other effects include shifting the respiratory responsiveness to carbon dioxide to the left (higher resting carbon dioxide (CO2) levels required to trigger respiration), decreases in tidal volume, and an increase in respiratory rate. Halothane is a very potent bromide-based ether that, as noted earlier, has a long history of use in anesthesia but recently has fallen out of favor because of its slower onset of action due to increased blood:gas solubility. Halothane is known to increase cerebral blood flow and decrease cerebral vascular resistance provided that the systemic blood pressure is maintained (Sakabe and Matsumoto, 2010). Isoflurane, which has a lower potency and lower blood:gas solubility than halothane (thus faster onset),

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is known to decrease CVR and CMRO2 while increasing CBF. Even though it has been reported that there is more significant cerebral vasodilation as compared with halothane, the effect of isoflurane on CMRO2 is more pronounced. There appear to be some neuroprotective effects of isoflurane that may be explained by its profound effects on global reduction of CMRO2. Isoflurane has also been demonstrated to be effective in the control of status epilepticus that is refractory to conventional anticonvulsant therapy (Kofke et al., 1989). It has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans. This drug was noted to be an effective rapidly titratable anticonvulsant, does not reverse the underlying cause of the refractory seizures and this therapy usually necessitates hemodynamic support with fluids and/or pressures. Sevoflurane is a poorly soluble agent that has a benefit of being easy to administer during inhalational inductions. Sevoflurane has been shown to cause a dose-dependent decrease in CMRO2. The effects on cerebral blood flow are similar to those of isoflurane, but it has been reported that CBF may be decreased, unchanged or increased during administration. Sevoflurane also appears to be weaker in its effects on CBF than isoflurane (Sakabe and Matsumoto, 2010). Of note, there is little to no increases in ICP seen with the administration of sevoflurane. A potential disadvantage of sevoflurane is the fact that it may be metabolized and degraded into compound A, a vinyl halide associated with renal dysfunction in animal models. Desflurane, the most insoluble inhalational agent available, has similar effects of CMRO2 and CBF as other agents. There is a reported dose-dependent increase in CBF and decrease in CMRO2 with its administration. The most valuable feature regarding desflurane is its extremely low solubility which allows for rapid titration and awakening of individuals. This is exceptionally important when thorough neurologic examinations are required in a timely fashion. Nitrous oxide is a weakly potent inhalational anesthetic that is poorly soluble. Its role is mainly as an additive agent that allows the administration of lower concentrations of other inhalational agents, thus abating their adverse cardiovascular side-effects. It is noted that nitrous oxide can increase CBF, ICP, and unlike other inhalational agents, CMRO2. The degree of these elevations is questioned because of the inconsistencies of minimum alveolar concentration levels administered during studies that measured the effects (Sakabe and Matsumoto, 2010) (Table 106.2).

OPIOIDS AND MUSCLE RELAXANTS Opioids are commonly administered during anesthesia for their beneficial analgesic effects both intraoperatively and postoperatively. The majority of their beneficial effects are mediated via m1-receptors that are known to impart supraspinal and spinal analgesia. The problem with these medications is that they are also associated with gender-specific, dose-dependent ventilatory depression, decreased responsiveness of ventilatory centers to CO2 (rightward shift of the CO2 response curve), increased nausea/vomiting, constipation, urinary retention, delayed gastric emptying and miosis. In neuroanesthesia, the respiratory depressant effects can be worrisome especially since this may lead to higher resting CO2 levels resulting in cerebral vasodilation, increased cerebral blood flow and increased ICP (Stoelting and Hillier, 2006). Morphine, a naturally occurring opioid, also has a long history of use in anesthesia. Today, due to its slow onset, it is rarely used intraoperatively, but it does play a role in the postoperative pain management of individuals undergoing neuroanesthesia procedures. The administration of morphine is also complicated by the fact that it is associated with histamine release and has an active metabolite, morphine-6-glucoronide that may accumulate in patients with impaired renal function. Fentanyl and sufentanil are highly potent phenylpiperidine-derviative opioids. Both agents have analgesic potency that is far in excess of that associated with morphine. The onset times for fentanyl and sufentanil are faster than morphine, with duration of action of a single bolus being shorter than morphine. Both opioids are known to decrease CBF and CMRO2, but transient increases in ICP have been seen, especially with fentanyl, in acute head trauma patients with and without preserved cerebral autoregulation (de Nadal et al., 2000). Other effects related to sufentanil and fentanyl include the fact that skeletal muscle tone has been noted to be increased in the presence of rapid opioid administration and has been associated with difficult ventilation. This has been found to be the result of vocal cord closure induced by the opioid (Bennett et al., 1997). Exact mechanism of action has yet to be determined. Remifentanil is an ultrashort-acting opioid that has the unique ability of being metabolized by plasma esterases allowing for prolonged administration with limited accumulation. Due to its nature, remifentanil must be administered as a constant infusion and is associated with significant hypotension and bradycardia due to its inhibition of sympathetic outflow. Remifentanil, like other opioids, displays a dose-dependent decrease in CMRO2, CBF, has limited effect on neurophysiologic monitoring such as somatosensory evoked potentials,

Table 106.2 Circulatory and cerebral effects of inhaled anesthetic agents

Agent

BP

CO

SV

HR

Contract

SVR

Peripheral vasodilation

Cerebral blood flow

CSF formation

CSF resorb

Right atrial pressure

Nitrous oxide Halothane Isoflurane Sevoflurane Desflurane

! # ## # #

! ## ! ! !

" # # # #

# ! "" " ""

" # # # #

" ! ## ## ##

! " """ " ""

" """ " " "

! # # # !*

! " # " !

"" "" " ! "

BP, blood pressure; SV, stroke volume; HR, heart rate; SVR, systemic vascular resistance; CSF, cerebral spinal fluid; " increase; # decrease; ! no change. *Can see increase in formation during hypocapnia combined with increase CSF pressure. (Adapted from: Stoelting and Hillier, 2006; Sakabe and Matsumoto, 2010.)

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and minimal increases in ICP. Discontinuation of remifentanil after surgical procedures results in an increase in blood pressure, tachycardia, and sympathetic outflow due to the removal of the analgesic effects of the opioid. Neuromuscular relaxing agents are routinely administered during neuroanesthesia procedures to insure immobilization during critical portions of surgery or to enhance surgical exposure. In addition, these agents are more frequently utilized to facilitate intubation of the trachea at the start of the procedure. Clinically nondepolarizing muscle relaxants have no effect on CBF, CMRO2, and ICP; however, this cannot be said of depolarizing agents such as succinylcholine. Succinylcholine has a long list of complications associated with its administration including fasciculations, myalgias, hyperkalemia, bradyarrhythmias, myoglobinuria, masseter spasm, and malignant hyperthermia. In addition, succinylcholine is known to increase ICP in the presence or absence of space occupying lesions (Minton et al., 1986).

DISEASE STATES AFFECTING THE DELIVERY OF NEUROANESTHESIA Myasthenic syndromes When discussing the utilization of muscle relaxants during anesthesia it is important to briefly discuss the role of myasthenic syndromes and their effect of the function and duration of action of neuromuscular blocking agents. Frequently anesthesiologists will consult with neurology to discuss the management of these complex individuals especially in regards to perioperative medication optimization. Since a thorough discussion of myasthenic syndromes is beyond the scope of this chapter we will focus on myasthenia gravis. Myasthenia gravis is an autoimmune disorder that exerts an effect on the postsynaptic membrane of the neuromuscular junction. Typically it is associated with an IgG antibody to the postsynaptic acetylcholine receptor resulting in a reduction in the number of effective receptors as well as damage to the site. These changes result in a decrease in the generation of action potentials and decreased muscle contraction (Hirsch, 2007). It has been observed that patients with myasthenia gravis exhibit a resistance to the effects of succinylcholine, a depolarizing muscle relaxant, but are very sensitive to the pharmacologic effects of nondepolarizing muscle relaxants. The resistance to succinylcholine may result in a larger administration of the drug and the development of a phase II block, making the duration of action unpredictable (Baraka et al., 1993). The utilization of oral acetylcholinesterase inhibitors, the mainstay of medical therapy for myasthenia gravis, may also inhibit pseudocholinesterase, again leading to a

prolongation of the depolarizing effect of succinylcholine. In addition, acetylcholinesterase inhibition is frequently utilized to “reverse” the competitive inhibition of nondepolarizing muscle relaxants. As such, the coadministration of oral medications such as pyridostigmine (a drug that enhances the concentration of synaptic acetylcholine) can make the perioperative utilization of nondepolarizing muscle relaxants problematic. As such, it is a common recommendation that nondepolarizing agent be avoid if at all possible.

Traumatic brain injury The principles developed in neuroanesthesia are designed to specifically treat the central brain where perfusion and control of intracranial pressure are key parameters in predicting survival with good neurologic outcome. Blood pressure management in these patients is controversial with hypertension after trauma due to elevated intracranial pressure and the body’s physiologic attempt to maintain cerebral perfusion. Hypertension and hypoxia have been proven to correlate with poor outcomes. Postoperatively these patients often remain intubated as ICP must be controlled and they often times have reduced airway protection. Medical management of increased ICP entails elevation of the head of the bed to increase venous drainage. Doses of intravenous (IV) mannitol or hyperosmolar therapy will help reduce brain tissue volume and decrease ICP (Fisher et al., 1984). If the patient is intubated, hyperventilation will decrease CO2 and reduce vascular volume. Barbiturate coma may be indicated as a way of reducing intravascular volume and ICP while still maintaining cerebral blood flow and oxygenation (Wilberger and Cantella, 1988). Hypothermia has been shown to lower ICP and may improve outcomes after severe head injury (Marion et al., 1997). There are, however, significant toxicities associated with hypothermia including coagulopathies and reduced cardiac contractility. Thus, extremely low temperatures must be used with caution. Mild hypothermia is associated with significantly higher Glasgow outcome scale scores compared to normothermic patients. Anticonvulsants should also be administered in patients with traumatic brain injury. Phenytoin 15–18 mg/kg and 5 mg/kg thereafter within 24 hours of injury has been shown to be effective in reducing neurologic injury and improving survivability (Temkin et al., 1990).

Intracranial masses Another aspect of neuroanesthesia involves the clinical care of a patient with a large intracranial mass secondary to a primary or metastatic tumor. These patients are subject to changes in intracranial compliance and ICP. They may spontaneously hemorrhage and have an incidence

NEUROANESTHESIA 1629 of seizures as high as 85% depending on the grade of the neural injury exist, but usually the focus is on neurotumor. The goals of the neuroanesthesiologist during praxia with subsequent issues being those of axonotmthese procedures are to minimize changes in cerebral esis and neurotmesis. Axonotmesis and neurotmesis blood flow, monitor hemodynamic stability, provide are more severe with limited recovery, but most periopfor a stable operative field with a slack brain, and facilerative events result in neuropraxia. Typically these injuitate a rapid awakening for a prompt neurologic exam at ries are associated with the brachial plexus, lumbar the end of the procedure. In many instances intracranial plexus, or peroneal nerves and are a result of excessive tumors will produce changes in the blood–brain barrier stretch on the nerve. producing cerebral edema. The neuroanesthesiologist Neurosurgical approaches, especially those for lateral can control this edema with the use of steroids, hyperapproaches to the skull base (translabrynthine and retroventilation or diuretics such as mannitol or furosemide sigmoid), require that the patient’s head be turned to the to reduce extracellular free water. contralateral side of the surgery with the ipsalateral The principles for blood pressure control and reducshoulder pushed downward. This places the patient at tion of increased intracranial pressure are also important risk for brachial plexus injury, and the neuroanesthesiolin patients after subarachnoid hemorrhage. The goal in ogist must have a sound knowledge of anatomy to detertreating these patients includes preventing large changes mine the correct neck and shoulder position to facilitate in blood pressure, facilitating surgical exposure with tumor removal, while preventing plexus damage. hyperventilation and diuresis, ensuring adequate cereThough the mechanism of occurrence is not fully bral perfusion and preventing vasospasm. The neuroaunderstood, the careful positioning of patients, frequent nesthesiologist must also recognize the physiologic examination of final location of extremities and neck changes that could accompany a subarachnoid hemorand thorough documentation of pre-existing defects rhage. The two most problematic are neurogenic pulmoassist in the management of these events. Frequently nary edema and vasospasm (Hasan et al., 1988). A person patients will undergo EMG examination to clarify the with pulmonary edema or pneumonia may not survive existence of the condition followed by intensive rehabilthe surgery if oxygenation is poor and they cannot be itation. Overall, the long-term recovery is quite promisventilated. In many instances, the surgery may have to ing for most neuropraxias; however, this requires be delayed to improve lung function or diurese the reassurance and education of the patient and family. patient to reduce pulmonary edema. Judicious use of In some instances, the approach to the posterior fossa positive end expiratory pressure (PEEP) along with or skull base may require the patient be placed in a sitting diuretics may improve lung function sufficiently to position. This is used to provide a better surgical view allow the patient to proceed to surgery for the craniotand access. This position is also associated with several omy and possible aneurysm clipping. complications, of which venous air embolism could also In addition to intracranial pathology, neuroanesthesia be produced. The neuroanesthesia care provider must be practitioners must also deal with spinal cord pathology aware of these possible complications and safeguard and the physiologic considerations that occur with such against them. The diagnosis of venous air embolism injury. The area of the lesion is the first variable that and air entrainment is important since unrecognized must be considered when caring for a patient with spinal entrainment of air could produce cardiovascular colcord pathology. Cervical cord injury may require fiber lapse or neurologic injury with stroke (Byrick et al., optic intubation with minimal head movement to pre2001). The use of a precordial Doppler device to monitor serve neurologic function and reduce the incidence of for air embolism is imperative to prevent its occurrence. secondary injuries during placement of the endotracheal A thorough knowledge of the therapeutic measures to tube (Fuchs et al., 1999). Thus, stabilization of the neck is treat a venous air embolism, neck compression, volume a key priority. If the cervical pathology is traumatic, spiloading, and aspiration of air from a multiorifice central nal shock may be present with subsequent hypotension venous catheter is important in salvaging patients from and bradycardia. Treatment with vasopressors and this event (Jellish et al., 2002). fluids is important in maintaining normal hemodynamic Prone positioning of patients is routinely used for physiology. neurosurgical procedures involving the spine and posterior fossa. Again, care must be taken to avoid damage to the brachial plexus due to overextension of the arms and PERIPHERAL NEUROPATHIES AND neck. In addition, prolonged prone positioning could POSITIONING INJURIES produce an increase in intraocular pressure which, if Occasionally neurologists will be consulted by anesthenot corrected, or if prolonged hypotension and blood sia and surgery for consultations regarding the onset loss are present, could produce a condition known as of peripheral neuropathies. Several classifications of posterior ischemic optic neuropathy (PION) with

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subsequent blindness (Warner et al., 2006). This possibility increases with prolonged prone positioning, large blood loss with fluid replacement, hypotension and multiple units of blood administered. The discipline of neuroanesthesia requires that the physician know the risks and complications of the unique position in which many of these patients are placed to provide ample space for the surgical approach. Prevention of the complications that occur secondary to position reduces the incidence of postoperative morbidity observed in these patients.

POSTOPERATIVE COGNITIVE DYSFUNCTION Recently it has been recognized that postoperative cognitive dysfunction (POCD) occurs with surgical patients for all age groups. It has been described by subjective symptoms such as memory loss and reduction in ability to handle complex intellectual tasks and initially was recognized in patients undergoing cardiopulmonary bypass. The symptoms may last for months and it has been implicated in the inability to handle normal activities of daily living in the postsurgical patient. Currently the only univocal risk factor is increasing age and extent of surgical trauma (Krenk et al., 2010). There is some concern that inhalational agents may be implicated in POCD with animal studies implicating long exposure to neurodegenerative changes such as cell damage and apoptosis (Brambrink et al., 2010). However, to date, these observations cannot be applied to human subjects. Further research is warranted on this subject with a focus on other contributing factors (e.g., inflammatory response, change in environment, length of hospital stay).

NEUROPROTECTION Many anesthetic agents are also considered to have properties that can protect neurons during times of hypoxia or reduced blood flow. There is a general consensus that volatile agents, barbiturates, and propofol reduce ischemic injury after a short postischemia recovery period. This effect, however, is short lived and not apparent after a long postischemia recovery period. A number of investigators have demonstrated that volatile anesthetics reduce ischemic cerebral injury. Their neuroprotective effects are similar with all agents offering evidence for reduced infarct volume after focal cerebral ischemia (Warner et al., 1993). The precise mechanism by which volatile anesthetics reduce brain injury is not clearly defined. They can attenuate excitotoxicity by inhibiting glutamate release and postsynaptic glutamate receptor responses. The influence of anesthetics on reducing sympathetic tone is also a significant mechanism for volatile anesthetic neuroprotection. In most instances, though infarction is not apparent after

the initial ischemic event, in the presence of inhalational agents, a long-term reduction in neurologic injury is not realized. Investigators have noted that the increase in size of cerebral infarction in isoflurane-treated animals parallels the appearance of markers of apoptosis such as TUNEL, caspase 3 and caspase 9 (Kawaguchi et al., 2004). It appears that neuroprotection with inhalational agents occurs when the severity of the injury is mild. Thus volatile agent-mediated neuroprotection can be sustained if the ischemic insult is mild, while moderate to severe infarcts are not protected by inhalational anesthetics. Barbiturates were initially thought to produce neuroprotection by their ability to reduce cerebral metabolism; however, recent evidence suggests that the metabolic depression produced by barbiturates does not play a significant role. This has been suggested by a recent investigation demonstrating that the reduction in infarct volume in rats subjected to focal ischemia was similar whether pentobarbital was administered to EEG burst suppression or in doses one-third of that required (Warner et al., 1996). Barbiturate neuroprotection has been attributed to redistribution of cerebral blood flow to injured areas, sodium channel and glutamate receptor blockade, inhibition of calcium influx, and potentiation of GABAergic activity. Propofol may be the ideal neuroanesthetic since it has beneficial effects on cerebral physiology and protects the brain against ischemic injury. Numerous reports have demonstrated reduced infarct volumes in animals administered propofol with results similar to those obtained with pentobarbital (Pittman et al., 1997). Propofol’s neuroprotective effect is attributed to its antioxidant properties and potentiation of GABAA-mediated inhibition of synaptic transmission. It is also noted to inhibit glutamate release and directly scavenge free radicals. The long-term protection afforded by propofol after an ischemic neurologic event may be similar to that of inhalational anesthetics. Propofol may delay ischemic injury, but does not prevent cerebral infarction after ischemia. It may be neuroprotective over a long postischemic interval if the ischemic insult is mild. It is not sustained with moderate to severe injury.

ANESTHETICS AND NEUROPHYSIOLOGIC MONITORING Neurophysiologic monitoring has become an important aspect when planning the anesthetic for a neurosurgical procedure. General anesthesia has an inhibiting effect on neurotransmission and therefore evoked potentials. The effect of anesthetics is greater on synaptic transmission than compared to axonal conduction. Therefore, cortical responses are affected to a much greater extent than those from oligosynaptic pathways. All volatile

NEUROANESTHESIA

1631

+

+

1.25mV 1.5 MAC, NO N2O

1.25mV 1.5 MAC, NO N2O

1.5 MAC, 60% N2O

1.5 MAC, 60% N2O 1.0 MAC, 60% N2O 0.5 MAC, 60% N2O

1.0 MAC, 60% N2O 0.5 MAC, 60% N2O

Pre-Induction

Pre-Induction

0

8

A Halothane

16 24 Milliseconds

32

40

0

8

B Enflurane

16 24 Milliseconds

32

40

+ 1.25mV 1.5 MAC, NO N2O 1.5 MAC, 60% N2O 1.0 MAC, 60% N2O 0.5 MAC, 60% N2O

Pre-Induction

0

8

C Isoflurane

16 24 Milliseconds

32

40

Fig. 106.1. Cortical somatosensory evoked potential response at various minimum alveolar concentrations of halothane (A), enflurane (B) and isoflurane (C) (Reproduced from Peterson et al., 1986.)

anesthetics produce a dose-dependent increase in evoked potential latency, an increase in conduction times and a decrease in amplitudes (Richard, 1983). This effect is compounded by nitrous oxide (Fig. 106.1). The newer volatile agents, desflurane and sevoflurane, affect SSEPs like isoflurane but may permit the use of higher overall concentrations. Intravenous anesthetic agents affect evoked potentials less than inhaled anesthetics and will modestly alter early and intermediate SSEP components. Barbiturates produce a dose-dependent increase in latency and decrease in cortical SSEP amplitude but do not preclude intraoperative monitoring. This is consistent with the fact that barbiturates, like volatile agents, affect synaptic transmission more than axonal conduction. Propofol’s effect on SSEP waveforms is similar to barbiturates. This is an important property since propofol can be infused in anesthetic concentrations during prolonged central nervous system surgery and still produce a rapid emergence with appropriate neurologic assessment. With the use of an opioid infusion in combination with propofol, SSEP amplitudes are affected less than the use of N2O and midazolam. Other hypnotics such as etomidate and ketamine increase cortical SSEP amplitude. Etomidate is associated with a high incidence of myoclonic movements. This enhancement in amplitude is thought to result from an altered balance between inhibiting and exciting influences at the cerebral cortex which results in signal synchronization at the thalamic level (Ganes and Lundar, 1983).

Opioids are noted to produce clinically unimportant changes in both evoked potentials and EEG. Benzodiazepines, like opioids, produce only mild to moderate depressant effects on evoked potentials. The effects of neuromuscular blocking agents must also be assessed during the neuroanesthetic, especially when EMG is contemplated or there is a need to monitor motor evoked potentials. Though numerous reports have noted that EMG and motor evoked potentials can be obtained with partial paralysis, newer neuroanesthesia techniques make the use of muscle relaxants unnecessary. Physiologic conditions may also affect the different monitoring techniques employed. Hypothermia may affect the electroencephalogram by causing a shift to lower frequencies and possible burst suppression. It will also affect the latency of evoked potential waveforms Hyperthermia has the opposite effect, producing a decrease in latency and an increase in conduction velocity. Hypotension, especially to arterial pressures below the autoregulatory threshold, progressively decreases SSEP amplitude, eventually producing a complete loss of waveform. Hypoxia does not affect EPs if it is mild. However, severe progressive hypoxia or cerebral ischemia is associated with both an increase in latency and a decreased amplitude resulting in a complete loss of waveforms. Changes in carbon dioxide levels with induced hypocapnia will shorten EP latency by 2–4%. Hypercapnia to a PACO2 of 100 mmHg was associated with an increase in latency by 15–30% and a decrease in amplitude of 60–80%. PACO2 levels of 50 mmHg had no effect on neurophysiologic monitoring.

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The known effects of anesthetics and anesthetic agents on neurophysiologic monitoring are an important aspect of neuroanesthesia. The influences of body temperature, blood gas tension, blood pressure and hematocrit are also important considerations and reflect the importance of the neuroanesthetic on the ability to reliably monitor neurologic pathways at risk during neurosurgical procedures.

CONCLUSIONS In conclusion, the field of neuroanesthesiology is broad with the main objective being the treatment and care of the patient with neurologic pathology. The primary concern of neuroanesthesia is the regulation of brain volume and pressure, whether it be achieved by controlling the respiratory pattern and blood gas tensions of CO2, administering diuretics, or giving hypertensive agents, all of which will produce physiologic changes critical to the successful outcome of the case. The other major problem is to control blood loss which may be influenced through the choice of anesthetic, control of blood pressure, and ventilation. Finally, the last critical task is to protect nervous tissue. The field of neuroanesthesiology requires the practitioner have an intimate knowledge of neurophysiologic principles, understand neuroanatomy, and be able to cope with the effects temperature, fluids, and electrolyte control have on maintaining cellular physiology during iatrogenic injury caused by surgery. Neuroanesthesia requires meticulous attention to detail and adherence to certain principles of practice that rest on three factors: the use of rapid onset and reversible agents, maintenance of a stable intraoperative environment, and control of intracranial pressure. These factors will salvage neurologic tissue and produce optimal outcomes after surgery for intracranial pathology or traumatic injury.

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