Pharmacologic and Physiologic Influences Affecting Sensory Evoked Potentials

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 ( 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 ( patients and those with scoliosis, scoliosis, spinal spinal or other neurologic the negative between cortical SSEP amplitude and within-patient amplitude the possible SSEP amplitude be reduced cortical SSEP amplitude variability in patients undergoing spine surgery and amplitude. nitrous anesthesia, surgical stimulation may increase cortical amplitude by more than to amplitude variability. of propofol for nitrous oxide increases cortical SSEP amplitude by up to during an opioid-based nitrous oxide from the background anesthetic has been shown to cortical amplitude to IOM more of remifentanil for fentanyl and nitrous oxide during a isoflurane anesthetic also decreased SSEP waveform which nitrous oxide is to be used in in which amplitude to be it be used in combination with where it depresses amplitude the least with with or no effect on SSEPs, such as and opioids (table may also be effect allow lower doses of anesthetics to be with less depression of SSEP using agents known to increase the EP amplitude, such as etomidate or can be to use etomidate to IOM in patients with abnormally small SSEP waves due to preoperative administration of etomidate, mg/kg, followed by the infusion of mg · kg−1· waveforms and monitoring that would not have been increases in the amplitude of SSEP may represent an early of etomidate could interfere with early detection of et al. to detect intraoperative to spinal cord in patients in etomidate had been used to the SSEP that etomidate did not neural the volatile anesthetic concentration in an to IOM may be associated with Low concentrations of volatile anesthetics are used during IOM, and anesthesia may be to and consider using or that in the of anesthetic Adding etomidate or propofol is to nitrous oxide or volatile anesthetic concentrations when anesthetic is anesthetics are also used to control blood and and may to be substituted