Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Abstract

Received from the Department of General Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio.EVOKED potentials (EPs) are the electrophysiologic responses of the nervous system to sensory or motor stimulation. 1,2Stimulating the nervous system initiates the transmission of neural signals that may be recorded as EPs from various points along the stimulated pathway. Intraoperative monitoring (IOM) of EP has gained popularity because EPs reflect the functional integrity of neural pathways in anesthetized patients undergoing surgical procedures that place nervous system structures in jeopardy. EPs monitored intraoperatively include somatosensory evoked potentials (SSEPs), brainstem auditory evoked potentials (BAEPs; also referred to as auditory brainstem responses), visual evoked potentials (VEPs), and motor evoked potentials. Additional EP modalities include dermatomal sensory evoked potentials, electrocochleography, and electromyography.Intraoperative EP changes may result from surgical injury or ischemia of the specific neural pathway, or they may be due to nonspecific physiologic or pharmacologic influences. Physiologic factors that may influence EPs include temperature, blood pressure, hematocrit, acid–base balance, and oxygen and carbon dioxide tensions. Anesthetic drugs and sedatives are the most common pharmacologic causes of nonspecific EP changes.This review discusses the physiologic and pharmacologic factors (including newer anesthetic agents and adjuncts) that influence sensory evoked potentials (SEPs), focussing on SSEPs, BAEPs, and VEPs. For ease of reference and to allow better comparisons between anesthetic agents, the discussion of anesthetic effects is separated from physiologic effects. The review intends to help clinicians recognize the important confounding perturbations so that intraoperative changes in SEPs can be interpreted optimally. It also aims to guide anesthetic planning so that reliable intraoperative EP monitoring can be accomplished during effective and safe anesthesia.The single cortical sensory evoked response has a low amplitude (1–2 μV) compared with the much larger electroencephalogram waves (50–100 μV). Therefore, the EP wave has to be extracted from concurrent spontaneous electroencephalogram activity by repetitive stimulation and computer-signal averaging techniques. 3The EP waveform consists of a series of peaks and valleys presented as a graph of voltage over time and described in terms of amplitude, latency, and morphology. For IOM, amplitude is commonly measured as the waves’ peak-to-peak voltage difference. Latency is the time from stimulus to the peak of the response. Interpeak latency is the interval between the peaks of interest (fig. 1).Evoked potential waves can have either negative or positive polarity. A negative wave occurring at a latency of approximately 20 ms would be indicated as N-20. Generally, negative waves are shown as upward deflections, while positive waves are shown as downward deflections. Evoked potentials can be of cortical or subcortical origin. Responses recorded by electrodes located within 3–4 cm of the neural generator are termed near-field potentials (e.g. , cortical SSEP waves recorded from scalp electrodes), whereas those recorded from electrodes farther from the neural generator are called far-field potentials (e.g. , BAEP recorded over the vertex). 4,5SEPs are also classified as short latency (< 30 ms), intermediate latency (30–75 ms), or long latency (> 75 ms). 6For the purposes of this review, SEPs are considered recordable when reproducible waveforms are reported. An anesthetic regimen is described as compatible with IOM when it results in consistently recordable waveforms. Reliability of SEPs refers to their ability to detect potentially injurious conditions intraoperatively.The SSEP represents the reproducible electrical activity of cortical and subcortical structures time-locked to a peripheral nerve stimulus. For perioperative applications, electrical impulses are commonly delivered to the median nerve or posterior tibial nerves using needle or surface electrodes. The impulse propagates peripherally (resulting in muscle twitches) and centrally via the peripheral nerve and the dorsal root to the spinal cord. The nerve cell body of the first-order neuron lies in the dorsal root ganglion. Impulses then ascend primarily in the dorsal column fibers of the spinal cord, which synapse (fig. 2) in the lower medulla near the nucleus gracilis and cuneatus, respectively. Axons of the second-order neurons cross the midline at the cervicomedullary junction, from where they regroup to form the medial lemniscus and synapse in the ventroposterior–lateral nucleus of the contralateral thalamus. Third-order neurons from the ventroposterior–lateral leave the thalamus and travel through the posterior limb of the internal capsule as the thalamocortical radiation to synapse in the primary somatosensory cortex in the postcentral gyrus of the parietal lobe. The spinocerebellar pathways, located anteriorly in the spinal cord, contribute to the rostral conduction of SSEP signals. Therefore, SSEPs can assess the sensory system from the peripheral nerves through the spinal cord and brainstem to the cerebral cortex.Somatosensory evoked potential waveform activity can be recorded at the popliteal fossa after posterior tibial nerve stimulation and at Erb's point above the clavicle after median nerve stimulation. Spinal potentials recorded over the cervical and lumbar spinous processes confirm the delivery of the stimulus to the central neural axis, after it is delivered in the arm or leg, respectively. The subcortical component of the SSEP is recorded over the second cervical vertebra as a negative deflection (N-14) 14 ms after median nerve stimulation. The earliest cortical (midlatency) component of the SSEP wave is generated by the primary somatosensory cortex and occurs approximately 20 ms after median nerve and 40 ms after posterior tibial nerve stimulation. Cortical SSEPs are recorded from scalp overlying the contralateral primary sensory cortex (fig. 3). A spinal sensory EP may be stimulated or recorded from epidural electrodes placed percutaneously or in the surgical field. The central conduction time (CCT) is the time needed for the signal to travel from the cervicomedullary junction to the contralateral cerebral cortex (CCT = N-20 to N-14 latency difference after median nerve stimulation).The subcortical SSEP recorded over the second cervical vertebra can be very useful intraoperatively because it is not very susceptible to anesthetic effects. 7Assuming an electromyography artifact is eliminated and technical problems are solved, the cervical response has a shorter acquisition time that allows faster feedback to the surgical team, which enhances its usefulness in surgical procedures that may jeopardize the spinal cord. The midlatency cortical SSEP is moderately sensitive to anesthetic depression, but clinically useful recordings can be obtained in most patients with modifications in anesthetic technique. Longer latency SSEP waves, which represent further neural processing of sensory inputs into the association cortex, are exquisitely sensitive to anesthetic drugs, and therefore, are not useful to monitor the integrity of the sensory pathway. 8Diagnostic criteria to evaluate intraoperative waveform changes diagnostic of spinal cord dysfunction have been difficult to establish. Latency changes of 7–10% and amplitude decreases of 45–50% may occur without changes in postoperative neurologic function. 9–11The criteria for determining which event-related changes 10should be considered significant are still empiric. 12In patients undergoing surgical correction of neuromuscular scoliosis, sensitivity and specificity of IOM in the detection of new postoperative neurologic deficits was maximized with the use of a 50% amplitude reduction criterion. 13An alternate criterion for sounding the alarm intraoperatively has been loss of cortical baseline amplitude greater than 30–40%. 14–16Most, however, consider a decrease in amplitude of 50% or greater, an increase in latency of 10% or greater, or both to be significant changes reflecting loss of integrity of a neural pathway, provided these changes are not caused by anesthetics or temperature. 17–20At least one study suggests that the use of amplitude criteria is associated with better sensitivity for detecting neurologic injury than latency criteria. 21General anesthesia has an inhibitory effect on neurotransmission and, therefore, on the EP. The effect of anesthetics is greater on synaptic transmission than on axonal conduction. 22For this reason, responses recorded from polysynaptic pathways (e.g. , cortical recordings) are affected by anesthesia to a much greater extent than those recorded from oligosynaptic pathways (e.g. , spinal cord and subcortical recordings). 23For example, VEPs (which represent cortical activity) are very sensitive to the effects of anesthetics while BAEPs (representing brainstem and subcortical activities) are the least sensitive to drug effects.All volatile anesthetics produce a dose-dependent increase in SSEP latency, an increase in CCT, and a decrease in amplitude 23–29(table 1). They may also cause morphologic changes, such as contraction of early cortical waveforms (N-20) into a simple monophasic wave under deep isoflurane 30,31or sevoflurane 32,33anesthesia (fig. 4). The later cortical waveform components are most sensitive to volatile anesthetics, with marked attenuation at concentrations exceeding 0.5 minimum alveolar concentration (MAC). 30Satisfactory monitoring of early cortical SSEPs is possible with 0.5–1.0 MAC halothane, enflurane, or isoflurane without nitrous oxide. 24,26At 0.67 MAC halothane or less, SSEPs were recordable in 96% of cases but only in 91% with higher concentrations. 34During deep (1.6 MAC) isoflurane anesthesia, however, the early cortical N-20 wave was recordable 35in 94%, and amplitude decreased severely (table 1). 30Yet, the later N-35 wave, which is also important in IOM, could only be recorded in 47%. 35The effect of volatile anesthetics on cortical SSEP amplitude is compounded by nitrous oxide. Increasing isoflurane concentration from 0.5 to 1.0 MAC in the presence of nitrous oxide resulted in a 75% decrease in the cortical SSEP (from 1.2 μV to 0.3 μV). 36The newer volatile anesthetics desflurane and sevoflurane affect SSEPs not unlike isoflurane but may permit the use of higher inhaled concentrations (table 1). Increases in cortical latency and decreases in amplitude occur at doses of 1.5 MAC sevoflurane and desflurane or less, with minimal effects on subcortical SSEP components. 37,38Desflurane up to 1.0 MAC without nitrous oxide is compatible with cortical median nerve SSEP monitoring during scoliosis surgery. 38Even at 1.5 MAC (without nitrous oxide), the amplitude of cortical SSEPs was preserved at 60% of baseline. 39However, nitrous oxide added to desflurane 40or sevoflurane 41severely depresses amplitude. At 1.7–2.5 MAC sevoflurane, a high-amplitude early cortical SSEP waveform is found with absence of all later waves. 32,33How volatile anesthetics differ quantitatively in their effects on the SSEP is not completely settled. Pathak et al. 26showed that halothane had a greater effect on both amplitude and latency of the SSEP at equipotent concentrations than either isoflurane or enflurane. On the other hand, Peterson et al. 24found that isoflurane and enflurane reduced SSEP amplitude and prolonged CCT more than halothane did. Sevoflurane and desflurane are associated with less amplitude reduction than isoflurane at a MAC range of 0.7–1.3. 29In contrast to their effects on the cortical SSEP, all volatile anesthetics, even at concentrations above 1.0 MAC, only minimally affect the subcortical waveform, resulting in high recordability 35and reliability (table 2).Nitrous oxide (60–70%) generally diminishes cortical SSEP amplitude by approximately 50% while leaving cortical latency and subcortical waves unaffected. 36,42Nitrous oxide potentiates the depressant effect of volatile anesthetics 24,41and most intravenous anesthetics, 12,43,44producing greater amplitude depression than an equipotent concentration of volatile anesthetics administered alone 24,45,46(table 1). For example, adding 50% (0.5 MAC) nitrous oxide to a fentanyl-based anesthetic resulted in a greater decrease in amplitude than adding 1% (0.8 MAC) isoflurane, especially in patients with abnormal preoperative SSEP. 25Likewise, during opioid-based anesthetics, nitrous oxide depressed cortical SSEP amplitude to a greater extent than did propofol when substituted for nitrous oxide. 12,47–49Intravenous anesthetics generally affect SSEPs less than inhaled anesthetics (table 3). This is easily seen from the fact that the human SSEP is preserved even at high doses of narcotics and barbiturates (table 3) but abolished at high volatile anesthetic concentrations. Intravenous agents only modestly affect early and intermediate (< 40 ms for median nerve stimulation and < 80 ms for posterior tibial nerve stimulation) SSEP components. Low doses of intravenous agents have minimal effects on SSEPs, whereas high doses of most agents cause slight to moderate decreases in amplitude and increases in latency. With very few exceptions, subcortical potentials are unaffected (table 3).Barbiturates produce a dose-dependent increase in latency and decrease in early cortical SSEP amplitude that does not preclude IOM. Changes in long-latency cortical waves are affected more than subcortical and midlatency waveforms. This is consistent with the notion that barbiturates, like volatile anesthetics, affect synaptic transmission more than axonal conduction. An induction dose of thiopental (5 mg/kg) increases latency 10–20% and decreases amplitude 20–30%, an effect that lasts less than 10 min. 43,50,51Similar changes occur with thiamylal. 40Even at much higher doses, such as those used for barbiturate coma, barbiturates allow recording of cortical SSEPs. 52–55Unlike the barbiturates, etomidate dramatically increases cortical SSEP amplitude (N-20), up to 400% above preinduction baseline in some patients. 50,43Subcortical amplitude is decreased by up to 50% (table 3). 50,56Etomidate is associated with a high incidence of myoclonic movements. 57Patients with familial myoclonic epilepsy are also known to have abnormally large EPs, 58especially noted during myoclonic jerking episodes. It is tempting to speculate that myoclonus is an indication that sensory signals are being synchronized (pathologically or by etomidate), which then result in enhanced SSEP amplitude. However, Kochs et al. 59observed amplitude enhancement after etomidate whether or not myoclonic movements occurred. Based on careful electrophysiologic experiments in cats, SSEP amplitude enhancement with etomidate is thought to result from an altered balance between inhibitory and excitatory influences at the level of the cerebral cortex, 60resulting in increased signal synchronization at the thalamic level. 56Like etomidate, ketamine increases cortical SSEP amplitude, with the maximum effect occurring within 2–10 min of bolus administration. 61No effect on cortical latency 61or subcortical waveforms 62was evident. However, the addition of nitrous oxide 44or 1.0 MAC enflurane 61to a ketamine background anesthetic depressed SSEP amplitude by approximately 50%. Ketamine, 3 mg/kg, followed by 2 mg · kg−1· h−1combined with 0.15 mg · kg−1· h−1midazolam and 60% nitrous oxide was compatible with satisfactory recordings during major spine surgery. 63Propofol's effect on SSEPs is similar to that of the barbiturates. This is important because propofol can be infused in anesthetic concentrations during prolonged central nervous system (CNS) surgery and still effect rapid emergence for timely postoperative neurologic assessment. A dose of 2.5 mg/kg propofol produced no changes in the amplitude of the cortical (N-20) and subcortical (N-14) waves after median nerve stimulation. 62Cortical latency and CCT increased by 8 and 20%, respectively. In scoliosis surgery, total intravenous anesthesia with propofol and sufentanil (table 3) prolonged cortical latency 10–15% and reduced the amplitude of the cortical posterior tibial nerve SSEP by 50%. However, SSEP waveforms stabilized within 30 min after anesthetic administration and were compatible with IOM. 48When used as a sedative hypnotic in combination with opioids, propofol reduces SSEP amplitude less than nitrous oxide or midazolam. Cortical SSEP amplitude is approximately 50% lower during sufentanil–nitrous oxide 47,48or alfentanil–nitrous oxide anesthesia 49compared with sufentanil-propofol-opioid–based regimens. 47,48Propofol was associated with higher cortical SSEP amplitude despite the use of anesthetic concentrations equivalent to nitrous oxide or sevoflurane. 64Average cortical SSEP amplitude was higher and within-patient amplitude variability was less during propofol–alfentanil than during nitrous oxide–alfentanil anesthesia. 49Amplitude was also greater than during midazolam–alfentanil anesthesia. 65The typical W-shaped morphology of the cortical posterior tibial nerve SSEP was better preserved with propofol than with midazolam.Benzodiazepines have only mild-to-moderate depressant effects on SSEPs (table 3). Diazepam, 0.1–0.25 mg/kg, produced mild and moderate decreases in N-20 and later wave cortical amplitude, respectively. Very long latency peaks (200–400 ms) were abolished. 66In a dose of 0.2–0.3 mg/kg, midazolam is associated with modest 67or no 43reduction in amplitude and slight prolongation of median nerve SSEP latency (table 3). Adding opioids 43,68or nitrous oxide 43to midazolam or propofol 65preserves the cortical SSEP better when compared to adding nitrous oxide or opioids to thiopental, etomidate, 43or ketamine. 44Benzodiazepines affect sensory pathways differentially. The significant decrease in the amplitude of the evoked electromyelogram response (a spinal cord response to somatosensory stimulation) after diazepam 69indicates a peripheral action. Conversely, sedative doses of midazolam (60–70 μg/kg), while leaving the early cortical waveform (N-20) unaffected, depress late cortical waves generated in the association cortex. 69This is consistent with the notion that sedative doses of benzodiazepines might blunt the emotional response to pain perception. 70Most authors report clinically unimportant changes in SSEP latency and amplitude after the administration of opioids, whether given in analgesic or anesthetic doses (table 3).McPherson et al. 50found minimal SSEP changes after 25 μg/kg fentanyl for induction of anesthesia in adults. A small increase (5–6%) in cortical median nerve SSEP latency and a variable decrease (0–30%) in amplitude resulted after 36–71 μg/kg fentanyl, which was compatible with IOM. 71No significant effects on SSEP from fentanyl up to 130 μg/kg were observed during hypothermic cardiopulmonary bypass. The effect of fentanyl was greater with boluses compared to a continuous infusion 72during maintenance of anesthesia.A bolus dose of 5 μg/kg sufentanil produced 5% increases in early cortical SSEP latency and a 15% increase in CCT. 73The 40% decrease in cortical amplitude did not interfere with waveform acquisition. 73Sufentanil, 0.5–1.0 μg/kg, followed by 0.25–0.5 μg · kg−1· h−1with 50% nitrous oxide and 0.5% isoflurane prompted a 50% reduction in cortical amplitude and a 5–10% increase in cortical latency and CCT but no changes in subcortical waves. 74Alfentanil is associated with only modest SSEP amplitude depression while leaving latency unchanged 43,75(table 3). Three doses of remifentanil (table 3) combined with 0.4 MAC isoflurane produced a 20–30% decrease in early cortical amplitude that was not dose dependant. By contrast, late cortical waves showed a 10–30% increase in amplitude. 76Compared with the combination of fentanyl and nitrous oxide, remifentanil reduces cortical amplitude less, with lower amplitude variability. 77Pathak et al. 72reported posterior tibial nerve SSEP latency to increase by approximately 10–15% and amplitude to decrease by 20% after induction of anesthesia with 0.25 mg/kg morphine. Amplitude continued to decrease to approximately 10% of control during subsequent morphine infusion. This study could not isolate the effect of morphine from residual effects of the barbiturate used for induction and the effect of a background nitrous oxide anesthetic, but it shows that this regimen is not desirable for IOM. As with fentanyl, the magnitude of morphine's effect was greater with bolus administration than with continuous infusion.The administration of subarachnoid meperidine produced a 60% decrease in cortical posterior tibial nerve SSEP amplitude and a 10% increase in latency. The response was abolished in 40% of patients. 78This is attributed to the local anesthetic-like effect of meperidine in blocking voltage-dependent sodium channels. In contrast, subarachnoid fentanyl (25 μg), 78morphine (20 μg/kg) combined with sufentanil (50 μg), 79or morphine alone (15 μg/kg) 80produced no significant changes in latency or amplitude of cortical posterior tibial nerve SSEPS in the awake or anesthetized states, nor did the lumbar epidural administration of 0.1 mg/kg diamorphine in adolescents undergoing corrective surgery for idiopathic scoliosis. 81Droperidol is an acceptable anesthetic adjunct with minimal effects of SSEPs. 8Clonidine, an α2receptor agonist, reduces anesthetic requirements. 82,83However, clonidine administered alone 84or added to 1 MAC isoflurane 85did not change latency or amplitude of the cortical SSEP. At a dose of 10 μg/kg, subcortical amplitude decreased by 10%, and latency increased 2%. 86Clonidine can be used as an anesthetic adjuvant without compromising SSEP monitoring. Dexmedetomidine affects SSEP amplitude minimally at sedative doses. During isoflurane anesthesia, it blunts isoflurane's effect on SSEP amplitude. 87In two patients undergoing spinal surgery, dexmedetomidine maintained good conditions for SSEP monitoring. 88During isoflurane–nitrous oxide anesthesia, adenosine triphosphate does not affect human SSEPs. 89Neuromuscular blocking drugs do not directly influence SSEP, BAEP, or VEP. 90However, they may improve waveform quality by favorably increasing the signal-to-noise ratio through elimination of the electromyography artifact, 90which introduces noise at higher frequencies, especially when EPs are acquired at lower stimulation frequency and higher frequency cutoffs. 90Complete local anesthetic block of the sensory pathway abolishes SSEPs. Local infiltration of lidocaine eliminates the cortical evoked response to painful dental stimulation 91,92as does bupivacaine 93or lidocaine subarachnoid block. 78On the other hand, epidural administration of bupivacaine 93,94or clonidine 95variably affects the lower-extremity SSEP depending on dose and dermatome stimulated. The SSEP response to L1dermatome stimulation is reliably abolished by bupivacaine epidural blockade. By contrast, because the S1 nerve root is often incompletely blocked during epidural anesthesia, posterior tibial nerve stimulation can still generate an SSEP response. Thoracic epidural anesthesia (to T7) with 1.5% etidocaine was associated with decreased cortical amplitude (by 60–80%) and increased cortical SSEP latency, while 1% etidocaine resulted in less pronounced changes. 96Similarly, bupivacaine (0.5–0.75%) injected into the lumbar epidural space significantly prolonged latency and decreased amplitude of posterior tibial nerve SSEPs, contrasted with only slight latency prolongation with 0.25% bupivacaine. 97Therefore, neuraxial administration of local anesthetics at higher concentrations is not suitable to supplement general anesthesia in scoliosis surgery if SSEPs are to be monitored. 97Intravenously administered lidocaine affects cortical SSEPs but is unlikely to interfere with IOM. Systemically administered lidocaine at therapeutic plasma concentrations (3–6 μg/dl) in patients anesthetized with sufentanil–nitrous oxide–low dose (< 0.5%) isoflurane further decreased amplitude of the cortical SSEP by approximately 25–30% and produced a small (5%) latency prolongation. 74The volume of information about effects of anesthetics on SEP waveform morphology and metrics is daunting. Ideally, reliable multicenter evidence should be available for each major anesthetic and anesthetic technique to assess the specificity and sensitivity of SEPs in the identification of impending neural injury to allow prompt and successful intervention. Yet, much of the published data of anesthetic effects on SEPs were gathered in neurologically normal patients or were obtained before surgical trespass on the nervous system. Data such as those presented in tables 1–4represent merely a proxy for assessment of the reliability of IOM in identifying and predicting neural injury during various anesthetics.It stands to reason that an identifiable, reproducible waveform (which we refer to as recordable) must persist during the anesthetic for critical events to be detectable with IOM. Anesthetic regimens during which even a small number of neurologically normal patients’ waveforms disappear are not suitable for successful IOM. Similarly unsuitable are anesthetics that result in amplitude depression and latency prolongation on the order that would confuse the interpretation of SSEP changes and potentially risk either not detecting a critical event or providing excessive false-negative interpretations. Such regimens include volatile anesthetics alone at a dose greater than 1–1.3 MAC and volatile anesthetics at greater than 0.5 MAC in combination with nitrous oxide (table 1). Therefore, volatile anesthetics alone at up to 1.0 MAC can be used. Desflurane or sevoflurane may allow successful IOM at even higher (1.5–1.75) MAC. Some intravenous anesthetic regimens, such as propofol–sufentanil, reduce amplitude sufficiently to be of concern (table 3). In general, however, intravenous anesthetic techniques result in less amplitude and latency perturbation than volatile anesthetics.Somatosensory evoked potential waveform reproducibility is directly related to amplitude and inversely related to amplitude variability. 10,12The smaller the amplitude of the SSEP waveform, the more is it subject to baseline variation, electrical noise, and other confounding influences. Therefore, amplitude preservation should be one of the important goals of the intraoperative monitoring team. This is particularly important when baseline amplitude is low and variability is high, as occurs in elderly (> 50 yr) patients and those with congenital scoliosis, paralytic scoliosis, spinal stenosis, spinal tumor, or other preexisting neurologic deficits. 9,10,18Given the negative correlation between cortical SSEP amplitude and within-patient amplitude variability, the highest possible SSEP amplitude should be maintained. High-pass 30-Hz digital filtering significantly reduced cortical SSEP amplitude variability in patients undergoing spine surgery and improved amplitude. 12During nitrous oxide–isoflurane anesthesia, intense surgical stimulation may increase cortical amplitude by more than 45%, contributing to amplitude variability. 98The substitution of propofol for nitrous oxide increases cortical SSEP amplitude by up to 100% during an opioid-based anesthetic. 47–49Eliminating nitrous oxide from the background anesthetic has been shown to improve cortical amplitude sufficiently to make IOM more reliable. 25,42Substitution of remifentanil for fentanyl and nitrous oxide during a low-dose isoflurane anesthetic also decreased SSEP waveform variability, which should improve reliability. If nitrous oxide is to be used in situations in which amplitude needs to be maximized, it should be used in combination with midazolam, where it depresses amplitude the least (16 vs. 40–50% with opioids). 43Anesthetic adjuncts with little or no effect on SSEPs, such as dexmedetomidine, clonidine, and neuroaxial opioids (table 3), may also be considered. Their MAC-reducing effect should allow lower doses of anesthetics to be used, with less depression of SSEP waveforms.Alternatively, using agents known to increase the EP amplitude, such as etomidate or ketamine, can be beneficial. 99,44Several investigators 99,100were able to use etomidate to improve IOM in patients with abnormally small SSEP waves due to preoperative pathology. Bolus administration of etomidate, 0.5–1 mg/kg, followed by the infusion of 20–30 mg · kg−1· min−1augmented waveforms and allowed clinical monitoring that otherwise would not have been possible. Transient increases in the amplitude of SSEP (“injury current”) may represent an early warning sign of CNS hypoxia, 101,102and etomidate theoretically could interfere with early detection of CNS hypoxia. 50Nevertheless, Sloan et al. 99were able to detect intraoperative events leading to spinal cord compromise in patients in whom etomidate had been used to enhance the SSEP recordings, indicating that etomidate did not mask neural tissue ischemia.Limiting the inspired volatile anesthetic concentration in an attempt to optimize IOM may be associated with undesirable consequences. Low concentrations of volatile anesthetics are often used during IOM, and anesthesia may be insufficient to prevent awareness and recall. Practitioners should consider using strategies or devices that assist in the assessment of anesthetic depth. Adding etomidate or propofol is preferable to beginning nitrous oxide or increasing volatile anesthetic concentrations when anesthetic depth is inadequate. Volatile anesthetics are also used to control blood pressure and myocardial stress. Vasodilator and β-adrenergic receptor blocker therapy may need to be substituted w