medigraphic Artemisaen línea

E A NO D NEST A ES Mexicana de IC IO EX L M O G O I ÍA G A E L . C C O .

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Revista

A N A T Í E Anestesiología S G S O O L C IO I S ED TE A ES D M AN EXICANA DE CONFERENCIAS MAGISTRALES Vol. 30. Supl. 1, Abril-Junio 2007 pp S126-S132

Neurosurgical Does the choice of agents matter?

Piyush Patel, MD, FRCPC*

* Professor of . Department of Anesthesiology University of California, San Diego.

Staff Anesthesiologist VA Medical Center San Diego

INTRODUCTION 1) Moderate to severe intracranial hypertension 2) Inadequate brain relaxation during The anesthetic management of neurosurgical is, by 3) Evoked potential necessity, based upon our understanding of the physiology 4) Intraoperative and of the central (CNS) 5) Cerebral protection and the effect of anesthetic agents on the CNS. Consequent- ly, a great deal of investigative effort has been expended to CNS EFFECTS OF ANESTHETIC AGENTS elucidate the influence of on CNS physiology and pathophysiology. The current practice of neuroanes- It is now generally accepted that N2O is a cerebral vasodila- thesia is based upon findings of these investigations. How- tor and can increase CBF when administered alone. This ever, it should be noted that most studies in this field have can result in an increase in ICP. In addition, been conducted in laboratory animals and the applicability N2O can also increase CMR to a small extent. The simulta- of the findings to the human is debatable at best. A neous administration of intravenous anesthetics (barbitu- great deal of emphasis has been placed on the minor differ- rates, , , ) can substantially ences in anesthetic induced changes in cerebral blood flow reduce this increase in CBF and CMR. The behavior of a

(CBF), cerebral metabolic rate (CMR) and intracranial pres- combination of volatile agents and N2O is quite different. sure (ICP) that have been consistently demonstrated in a When administered in low doses, volatile agents can reduce variety of studies. Is this emphasis justified? It is not surpris- CBF and CMR. The addition of N2O to low dose volatile ing that, in the absence of controlled studies which demon- agent anesthesia increases both CBF and CMR. This N2O strate the superiority of one technique over another, inter- mediated vasodilation can be greater when higher doses of pretations of the available data differ and that opinions on volatile agents are administered. the optimal approach to the neurosurgical patient also dif- Volatile agents uniformly suppress CMR. At doses of 1.5 fer. A more important question to the practicing anesthesi- – 2.0 MAC, the commonly used agents , desflu- ologist is not whether the minor differences in CNS physiol- rane and all produce burst suppression of the ogy induced by anesthetics are relevant to all neurosurgical EEG. At burst suppression, CMR is reduced by 50-60%. patients but the identification of clinical situations in which Volatile agents are also vasodilators. Their effect on CBF is anesthetic effects might be significant. edigraphic.combiphasic. At doses of about 0.5 MAC, the suppression in In the present discussion, a brief review of the cerebrovas- CMR balances the vasodilatory effects and CBF does not cular effects of anesthetic agents will be presented. Thereaf- change significantly. In doses greater than 1.0 MAC, the ter, situations in which the anesthetic selection has been vasodilatory effect predominates and CBF increases. The suggested to be relevant will be addressed: addition of N2O to volatile anesthetic anesthesia will in-

S126 Revista Mexicana de Anestesiología Patel P. Neurosurgical anesthesia crease CBF and CMR. This increase in CBF may not neces- observation of the brain and the surgical conditions can sarily result in an increase in ICP. The effect of volatile then dictate the anesthetic regimen. agents on cerebral (CBV) parallel the CBF A similar logic may apply to the management of the acute- changes but are of a significantly lesser magnitude. ly head injured patient. Compensatory mechanisms are inad- Intravenous agents, with the exception of ket- equate to offset the rapid increase in intracranial volume and amine, all decrease CMR and CBF substantially. In appro- ICP. In such patients, brain distortion and herniation can com- priate doses, , propofol and etomidate produce promise regional brain perfusion, rendering the brain ischem- burst suppression of the EEG. ’s effect on CBF and ic. Moreover, experimental data have shown that hyperventi- CMR are regionally specific; in the limbic structures, CBF lation, which is often employed to minimize or counteract and CMR increase whereas within the cortex, reductions in volatile agent induced vasodilation, can be ineffective in CBF and CMR occur. doing so with acute head (3). A cogent argument can therefore be made that one should avoid nitrous and 1) MODERATE TO SEVERE INTRACRANIAL volatile agents in the anesthetic management. HYPERTENSION “TIGHT BRAIN” DURING SURGERY Patients with intracranial hypertension (ICH) have symp- toms of , , and visual disturbance. Adequate brain relaxation facilitates and re- Patients with severe ICH also have a reduced level of con- duces the need for excessive brain retraction. Although un- sciousness. CT scans demonstrate mass lesions, ventricular common, brain swelling can occur intraoperatively during effacement, midline shifts of the brain and full basal cis- surgery. This is most commonly seen during AVM surgery terns. The brain’s capacity to accommodate increases in CBV but it can occur during tumor surgery as well. The etiology is exhausted and even slight increases in intracranial vol- of brain swelling is not clear. Clearly, engorgement of the ume can result in dramatic increases in ICP. In patients with brain with blood plays a significant role. When brain swell- acute increases in ICP (for example, with traumatic brain ing does occur, the brain is placed at risk for ischemic inju- SUSTRAÍDODE-M.E.D.I.G.R.A.P.H.I.C injury, epidural and subdural hematomas), the effect of an ry. In addition, brain swelling interferes with surgery and on increase in CBV on ICP is even greater. It is in these patients occasion, can prevent closure of the dura. This represents an :ROP ODAROBALE FDP that the choice of anesthetic agents must be considered care- urgent problem that demands the attention of the anesthesi- fully. ologist and the neurosurgeon. The approach to this difficult VC ED AS, CIDEMIHPARG Agents that produce vasodilation can increase CBF and problem is reasonably well established and the following more importantly, CBV. The potential for a further increase maneurvers may be instituted: ARAP in ICP is therefore apparent. Minor increases in ICP can be readily treated by modest hyperventilation and the use of • Check ventilation. Moderate hypocapnia (target PaCO ACIDÉMOIB ARUTARETIL :CIHPARGIDEM 2 diuretics. Consequently, for the majority of patients, it is 25-30 mmHg) will produce cerebral vasoconstriction and unlikely that anesthetic induced increases in ICP will be the consequent reduction in brain bulk. Measurement of substantial enough to compromise the brain. For example, end-tidal CO2 tension is occasionally misleading. Arteri- in patients with intracranial tumors, there were no differenc- al blood gas analysis should be utilized judiciously to es in outcome in patients anesthetized with propofol-fenta- confirm hypocarbia. nyl, isoflurane- or -nitrous oxide(1). • Ensure normal oxygenation. Nontheless, other studies have shown that dural tension is • Control . Target is normotension (within higher with isoflurane-fentanyl and sevoflurane-fentanyl 10% of baseline blood pressure). anesthesia in comparison to propofol-fentanyl anesthesia(2). • Ensure adequate venous drainage from the brain. Neck In patients in whom the ability of the brain to compensate torsion or the placement of endotracheal tube ties around for further increases in CBV is exhausted, a technique that the neck can impede venous drainage from the brain. reduces CMR, CBV and ICP may be preferable. In such pa- • Head elevation (30° optimum) tients, it is the author’s practice to avoid nitrous oxide and • Check intrathoracic pressure. Rule out pneumothorax volatile agents until such time as the dura is opened. An (especially if central line has been placed). anesthetic technique based on the infusion of propofol and • Maintain adequate neuromuscular relaxation. narcotics may be a more prudent approch in so faredigraphic.com as the • Administer mannitol. reserve of the brain to compensate for increases in CBV is not encroached upon and may in fact be increased (reduc- If these measures are not adequate, then consideration tion in CBV). Volatile agents may be introduced once the should be given to the potential deleterious effect of anes- cranium has been opened and the dura has been reflected; thetic agents. In particular, attention should be focused on

Volumen 30, Suplemento 1, abril-junio 2007 S127 Patel P. Neurosurgical anesthesia those agents that can increase brain bulk by producing cere- results in a very good signal is a total intravenous anesthet- bral vasodilation. The manipulation of anesthetic adminis- ic technique. The combination of propofol and a tration can effect dramatic reductions in brain bulk: infusion results in excellent signals in most patients(7). In addition, the variability in the amplitude of the evoked po-

• Make sure that the concentration of volatile agent is less tential is reduced by this technique in comparison to a N2O than 0.5 MAC -volatile agent-narcotic technique. This is an important con-

• Discontinue the administration of N2O sideraton in those patients with CNS abnormalities in whom • Discontinue the administration of volatile anesthetics the EP is already compromised by the primary . If the • Switch to an intravenous anesthetic technique. A combi- signal does not improve, then it is highly unlikely that the nation of propofol and narcotic infusion is ideal. cause of the problem is the anesthetic. • If the brain swelling does not abate, then the probability Etomidate is unique among anesthetic agents in that it that the patient will have protracted intracranial hyper- actually increases the amplitude of somatosensory evoked tension in the post-operative period is high. In that event, potentials. Clinicians often administer etomidate by infusion barbiturates (pentobarbital) may be administered until to improve the quality of the recording. However, it is diffi- either the swelling is reduced or until burst suppression cult to determine what exactly an improvement in the signal of the EEG is attained. On rare occasions, the that is induced by etomidate means to the transmission of the may elect to amputate brain or to close the without signal from the peripheral to the brain. In addition, the replacing the bone flap. usual criteria for determining a change in the evoked poten- tial (amplitude reduction by 50% and latency delay by 10%) 2) INADEQUATE SIGNAL QUALITY DURING may not apply when etomidate is administered. Nonetheless, EVOKED POTENTIAL MONITORING in patients with significant sensory abnormalities, an anes- thetic technique based on an etomidate infusion may be con- Somatosensory evoked potentials sidered. Such a technique may allow reasonable EP recording which otherwise may not be possible(8). All volatile agents attenuate evoked potentials in a dose related manner (see an excellent review by Banoub et al)(4). 3) MOTOR EVOKED POTENTIALS Somatosensory evoked potential (SSEP) amplitude can be attenuated at 1.0 MAC concentrations and can be abolished Motor evoked potential (MEP) monitoring is a relatively new with higher concentrations. Simultaneously, a dose depen- technique that is being increasingly employed during spine dent increase is latency is also observed. The newer volatile surgery that entails a significant risk of injury to the motor agents sevoflurane and desflurane appear to depress the tracts. In many instances, the ability to reliably monitor the amplitude of the SSEP to a lesser extent and their use may motor tracts has replaced the intraoeprative wake-up test. In permit the delivery of a higher concentration (~1 – 1.5 the OR, transcranial electrical rather than magnetic stimula- MAC)(5). Auditory evoked potentials are relatively robust tion, applied to the scalp, is used to depolarize cortical pyra- but even their waveforms will be affected at volatile anes- midal tracts and to evoke a motor response in the upper and thetic concentrations that exceed 1.5 MAC. N2O can also lower extremities. MEP are exquisitely sensitive to anesthet- reduce the amplitude of the SSEP(6). Intravenous agents, on ic agents. Volatile agents (in concentrations as low as 0.2-0.3 the other hand, have a modest impact on evoked potentials; MAC), barbiturates, propofol and all significant- in fact, evoked potentials can be detected even with doses ly suppress MEP(9,10). It is therefore apparent that the anes- of barbiturates that produce burst suppression of the EEG. thetic technique for MEP monitoring has to be substantially Given that anesthetic agents suppress EPs, the choice of modified. In addition, the administration of muscle relaxants anesthetic agents for the maintenance of anesthesia becomes has to be strictly titrated to ensure that muscle contraction in an important consideration. Although volatile agents and the monitored limb is possible(11).

N2O suppress EPs, stable and robust EP recording can be The recent introduction of a multiple stimulation device obtained provided the concentration of the volatile agent is has simplified to some extent the anesthetic management. kept to 0.5 MAC or less and the nitrous oxide concentration Multiple stimuli, from 2 to 5, with about 75 msec interval is maintained in 50-60% range. Without N2O, the volatile between the stimuli, significantly improves the amplitude anesthetic concentration can be increased to aboutedigraphic.com 1 MAC. of the MEP. Moreover, this MEP is less susceptible to anes- Opiate infusion in addition will provide, in most circum- thetic induced suppression(12). Accordingly, low doses of stances, stable anesthetic conditions that permit EP moni- volatile agent (~0.3 MAC), propofol- N2O, propofol-remifen- (13) (14) toring. If the quality of the signals is not adequate, then the tanil and isoflurane- N2O – techniques may be anesthetic technique has to be modified. The technique that compatible with adequate MEP monitoring. However, it

S128 Revista Mexicana de Anestesiología Patel P. Neurosurgical anesthesia should be noted that the administration of isoflurane reduc- is increased to at least 65%. Once the volatile agent is elim- es the percentage of patients in whom reliable MEP record- inated, ECOG can be performed. During this time, the pa- ing is possible and it increases the variability in the ampli- tient will be lightly anesthetized and there is a significant tude of the MEP. Accordingly, it may be prudent to establish risk of movement or coughing. It is therefore very important robust MEP monitoring before volatile agents are added to to ensure that the patient is paralyzed. If the spike waves are the anesthetic regimen. not detectable, spike activity can be induced by the admin- istration of one of the following: 4) INTRAOPERATIVE ELECTROCORTICOGRAPHY (ECOG) i) , 0.3-0.5 mg/kg(16). Methohexital results in spike wave activity that emanates primarily from the In patients undergoing for resection of seizure focus. producing foci, intraoperative ECoG is often employed. ii) Etomidate, 0.1-0.2 mg/kg(17). The resulting spike wave ECoG is used to precisely identify the location of the lesion activity is more generalized that with methohexital. and the margins of safe brain resection. Seizure foci are iden- iii) , 50 µg/kg(18). tified by characteristic spike waves that are elicited by elec- trical stimulation of the surrounding brain region. Once the 5) EPILEPTOGENESIS foci are identified, they are removed. ECoG is then used to confirm the removal of the relevant focus – a lack of spike Of the currently used anesthetics, two agents have been im- waves will confirm this. plicated in the genesis of . Etomidate can activate surgery can be performed in an awake or anes- seizure foci (see above) and can increase spike activity in thetized patient. is usually reserved for the brain. However, overt seizure activity with the use of cooperative adult patients. Uncooperative patients or pedi- this agent has not been demonstrated. In fact, etomidate has atric patients are generally anesthetized for the procedure. been used to treat refractory status epilepticus. Nonetheless, During awake craniotomy, patients are usually sedated the possibility of activating the EEG in patients with pre- SUSTRAÍDODE-M.E.D.I.G.R.A.P.H.I.C with an infusion of propofol during the craniotomy. There- existing epilepsy should be considered before it is used in after, the propofol infusion is discontinued and the patient such patients. :ROP ODAROBALE FDP is allowed to awaken. Upon resumption of , Sevoflurane administration has been shown to cause frank ECoG mapping is started. Propofol is an ideal agent to use seizure activity in patients. In healthy volunteers, sevoflu- VC ED AS, CIDEMIHPARG because its pharmacokinetic properties permit rapid emer- rane in 1-2 MAC doses has been associated with the devel- gence from a state of anesthesia. However, it should be re- opment of encephalographic seizure activity. In addition, ARAP membered that propofol can have a profound effect on the seizures have been observed in patients who awaken from a ECoG. Residual propofol in the brain can result in EEG sevoflurane anesthetic. Accordingly, caution should be ex- ACIDÉMOIB ARUTARETIL :CIHPARGIDEM activation in the 18 Hz range(15). This activation can ob- ercised with respect to the administration of sevoflurane to scure spike waves from the seizure foci, thereby making patients with epilepsy. precise localization of the foci difficult. The EEG activa- tion can occur even when the patient appears to be fully 6) ANESTHETIC NEUROTOXICITY awake! EEG activation is generally short lived and lasts about 20 min. It is therefore important to discontinue the The adverse impact exposure on the developing administration of propofol at least 30 min before the start of brain was reported two decades ago by Levin and col- ECoG. More recently, the addition of remifentanil to a pro- leagues(19). These investigators demonstrated that long-term pofol infusion has permitted a reduction in the dose of pro- exposure to halothane, beginning in utero and continuing pofol; a more rapid emergence (within 10 min) is therefore for several days in the post-natal period, led to impaired possible. Anesthetics that suppress seizure foci (benzodiaz- synaptogenesis, reduced dendritic branching, suppressed epine, volatile agents) should, in general, be avoided. axonal growth and reduced myelination in rodents. More- ECoG during general anesthesia is more challenging. over, halothane exposure during development resulted in Volatile anesthetics, intravenous and benzodiaz- impaired neurocognitive function in adulthood. These stud- epines can suppress spike waves. Therefore, during ECoG, ies did not achieve notoriety because the manifestation of the use of these agents must be minimized or avoidededigraphic.com alto- CNS toxicity required prolonged exposure to halothane, a gether. An anesthetic technique that is commonly used for situation not encountered in clinical practice. this procedure is a combination of N2O, low dose volatile Interest in anesthetic neurotoxicity was renewed by the agent and a narcotic infusion. Shortly before ECoG, the demonstration that drugs that have antagonist activity at volatile agent is discontinued and the concentration of N2O NMDA receptors and agonist activity at GABA-A receptors

Volumen 30, Suplemento 1, abril-junio 2007 S129 Patel P. Neurosurgical anesthesia produce widespread in the developing tivation (phosphorylation) or a number of signal transduc- brain(20). These data led to a re-evaluation of anesthetic neu- tion mechanisms, many of which are important in dendritic rotoxicity because commonly used anesthetic agents have growth, synaptic stabilization and neuronal survival(26). these effects on NMDA and GABA-A receptors(21). In a sem- During the critical period of synaptogenesis, inhibition of inal investigation, Jevtovic-Todorovic and colleagues dem- NMDA receptor signaling would be expected to be detri- onstrated that isoflurane (0.75% to 1.5%) resulted in sub- mental to brain development. Indeed, other agents, such as stantial neurodegeneration in a number of structures of the MK801, which are potent NMDA antagonists also produce brain, including the and neocortex(22). The a pattern of neurodegeneration that is similar to that pro- addition of midazolam or N2O to isoflurane increased neu- duced by ketamine. ronal death to a greater extent that either of the agents alone. What is surprising is that GABA-A receptor agonists also Electrophysiologic function in the hippocampus was sig- produce neuronal death. Anesthetics that are agonists at this nificantly reduced in the hippocampus by the anesthetics. receptor include the volatile anesthetics, propofol, barbitu- In rats that were exposed to anesthetics on post-natal day 7, rates and benzodiazepines. Each of these is associated with neurocognitive deficits were apparent at 4-5 weeks of age in neuronal toxicity. In the adult, GABA-A receptor activation comparison to control animals. Collectively, these data in- leads to an influx of Cl- into the cell. This results in hyper- dicated that anesthetic agents injure the brain and that this polarization of the cell and in many models of hypoxia and injury results in a long-term impairment of cognitive func- ischemia, this can be neuroprotective. However, in the de- tion. Such neurotoxicity has now been demonstrated for veloping brain, especially during synaptogenesis, intracel- ketamine, midazolam(23), diazepam, pentobarbital(20) and lular concentration of Cl- is high; activation of GABA-A (22) N2O . While the potential toxicity of propofol has not yet receptor results in Cl- efflux and depolarization of the neu- been investigated in detail, it is probable that it too produc- ron(27). Consequently, intracellular calcium concentration es neuronal death given its potent activity at GABA-A re- reaches levels that can be harmful to the cell. This action of ceptors(24). GABA may contribute to neuronal injury. Although the data from rodent studies are convincing, Based on the above discussion, it has been proposed that its relevance to humans is debatable and it is difficult to an imbalance between excitatory and inhibitory input in extrapolate these findings to the clinical setting. Data from the CNS during synaptogenesis produces neuronal injury. sub-human primates would be expected to have greater rel- According to this model, the imbalance leads to the activa- evance to humans. To that end, Slikker et al have evaluated tion of processes in the neuron that lead to programmed cell the toxicity of ketamine in frontal cortical neurons cultured death or apoptosis(28). Apoptosis occurs normally in the de- from 3 day old monkeys. When exposed to ketamine for 24 veloping brain and it is an essential means by which excess hours, these neurons underwent both apoptotic and necrot- cells in the CNS are removed. Apoptosis is the end result of ic cell death. The extent of this injury was reduced by agents the activation of a cascade of enzymes called caspases. The that reduced NMDA receptor number(25). In addition, more final caspase in this cascade is caspase-3. This enzyme pro- recent (yet unpublished data) from this group has shown teolytically cleaves a variety of cellular substrates that are that ketamine also increases neuronal death in vivo in neo- essential for survival. Neuronal death by apoptosis is an natal monkeys. Of importance is the observation that the orderly process that is characterized by membrane blebbing nature of neuronal degeneration was similar to that observed and cleavage of the nucleus to produce apoptotic bodies. in rodents. These data demonstrate clearly that anesthetic The apoptotic cell is then removed by phagocytosis. It is agents in common use in patients have the potential to in- important to note that apoptosis does not result in inflam- jure the developing brain. mation, which in itself can produce a substantial amount of The mechanisms by which anesthetics produce neuronal collateral damage(29). death are under intense investigation. It is clear that the In order to reveal neurodegeneration induced by anes- brain is most susceptible during the period of synaptogene- thetic agents, neonatal pups have to be exposed to anesthet- sis(26). In rodents, this occurs during the first two weeks of ics for a prolonged period of time, usually about 6 hours, post-natal . Cell death results in impaired or aberrant during the period of synaptogenesis. In rats, synaptogenesis synaptic connections and it is readily apparent why cell occurs mainly over a period of about 12 days(30). Therefore, death leads to impaired cognitive function later in life. a 6 h period of anesthesia represents a substantial fraction of Many of the agents that produce neurodegenerationedigraphic.com are the synaptogenesis time. In humans, synaptogenesis occurs antagonists of the NMDA receptor. These include ketamine during the third trimester and continues until about the age and nitrous oxide. It is clear that glutamate signaling via the of four(31). To achieve a similar exposure in humans, neo- NMDA receptor plays a crucial role in synaptic develop- nates would have to be anesthetized for several weeks(32). ment and neuronal survival. This signaling initiates the ac- This does not occur in the operating room. However, such

S130 Revista Mexicana de Anestesiología Patel P. Neurosurgical anesthesia prolonged CNS suppression does occur in the intensive care stance of extremely mild ischemic insults, such as those that units. Furthermore, during anesthetic exposure, food and are likely to occur with brain retraction, anesthetics might nutrition, not to mention pup-maternal bonding, are not pro- produce sustained neuroprotection. However, with such mild vided. Whether this period of “malnutrition” produces neu- insults, it is highly unlikely that differences in the neuro- ronal injury is not known. In addition, the potential con- protective efficacy for individual anesthetics will be mani- founding influences of prolonged anesthesia on respiration fest. Accordingly, the available data do not support the se- (maintenance of normoxia and normocarbia) cannot be prop- lection of any given agent for purposes of neuroprotection. erly controlled in neonatal animals. Finally, the doses of Adequate anesthesia, regardless of how it is produced, will drugs used in neonatal rat pups (especially for ketamine) are increase the tolerance of the brain to ischemia in compari- considerably greater than the doses that are used in pa- son to the awake state. Barbiturates may be used for purpos- tients(32). Collectively, the available data suggest that there es of neuroprotection in rare situations (such as prolonged are sufficient differences between species and in the manner temporary clipping during surgery). in which anesthetics are administered to patients under strict Among intravenous hypnotics, the only agent who use monitoring to render the animal data less relevant to hu- might be considered controversial is etomidate. Etomidate mans. On a more pragmatic level, most of the currently used can reduce CMR, CMF and ICP. These effects are similar to anesthetic agents have been implicated in neurotoxicity; those produced by barbiturates and propofol. Unlike the lat- given the necessity of anesthesia for surgical procedures, ter agents, etomidate does not produce . Given anesthetic exposure is unavoidable. this favorable pharmacologic profile, the use of etomidate The available data do provide sufficient evidence for a during neurosurgical procedures that entail a risk of cerebral change in current practice. However, pre-clinical experimen- ischemia has been advocated. Unfortunately, it is quite clear tal data are of serious concern and as such, further intense from laboratory studies and studies in patients(34) that etomi- investigation is necessary. At the present time, there is little date does not possess neuroprotective efficacy. In fact, it can to recommend a change in practice. Nonetheless, prolonged increase ischemic neuronal injury. The administration of eto- anesthesia should be avoided in so far as it is possible. In midate for the purposes of neuroprotection therefore cannot SUSTRAÍDODE-M.E.D.I.G.R.A.P.H.I.C addition, decision to proceed with anesthesia and surgery be advocated. Single doses of etomidate for purposes of anes- in at risk neonates and infants should be made with due thetic induction are unlikely to adversely affect neurons and :ROP ODAROBALE FDP consideration of the possibility of anesthetic neurotoxicity. its use in this manner is entirely appropriate. VC ED AS, CIDEMIHPARG 7) BRAIN PROTECTION SUMMARY ARAP There is a considerable risk of cerebral ischemia during neu- In the vast majority of neurosurgical patients, the choice of rosurgical procedures and a substantial investigative effort anesthetic agent is not relevant; the choice of anesthetic ACIDÉMOIB ARUTARETIL :CIHPARGIDEM has focused upon the identification of agents that might agents is unlikely to affect either the surgical field or the reduce ischemic brain injury. Given their propensity to re- patient outcome. The best results are often obtained by the duce CMR, anesthetics appear to be logical candidates. use of a technique with which the anesthesia care provider Volatile agents, barbiturates, propofol and ketamine have is familiar. In certain situations, however, the choice of the all shown neuroprotective efficacy in the laboratory. Unfor- anesthetic agent can directly impact the surgical field and tunately, this neuroprotection is short lived and is not sus- may have an impact on patient outcome. It is during these tained beyond a period of 2 weeks(33). Neurons continue to situations that a solid command of physiology and the patho- die for a long time after the initial ischemic insult and anes- physiology of the CNS and the impact that anesthetic agents thetics to do mitigate ongoing neuronal loss. In the circum- have on the brain is essential.

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