AUTHOR(S): Zentner, Josef, M.D.; Albrecht, Thomas, M.D.; Heuser, Dieter, M.D. Departments of Neurosurgery (JZ) and Anesthesiology (TA, DH), Medical School, University of Tübingen, Tübingen, Germany Neurosurgery 31; 298-305, 1992 ABSTRACT: THE INFLUENCE OF the inhalational anesthetics halothane, enflurane, and isoflurane on motor evoked potentials was studied in a total of 10 rabbits. Motor evoked potentials were recorded from the extremity muscles as well as from the epidural space of the spinal cord and cauda equina in response to electrical stimulation of the motor cortex at baseline conditions and equianesthetic concentrations (0.25 to 1.5 minimal alveolar concentration). Our results show a dose-dependent suppression of the electromyographic responses, which was similar with all anesthetics. Beyond 0.5 minimal alveolar concentration of any of the agents, electromyographic responses were absent. In contrast, spinal evoked responses representing neural activity were only slightly affected by the anesthetics. We hypothesize that the descending impulse elicited by the electrical stimulation of the motor cortex is mainly inhibited at the level of the spinal interneuronal or motoneuronal systems, because 1) electromyographic responses evoked by the stimulation of the cervical and lumbar nerve roots were only minimally affected by 1.5 minimal alveolar concentration halothane; and 2) spinal evoked responses were stable several minutes after cardiac arrest, indicating a subcortical action site of the electrical impulse. In conclusion, intraoperative monitoring of descending pathways by means of motor evoked potentials during anesthesia with the inhalational agents halothane, enflurane and isoflurane is only feasible when neural activity is evaluated. KEY WORDS: Anesthesia; Inhalational anesthetics; Intraoperative monitoring; Motor evoked potential In order to lower the risk of neurological complications during neurosurgical operations, the intraoperative monitoring of evoked potentials has become widely accepted (6). In addition to examination of ascending pathways by means of somatosensory evoked potentials (SEP), the assessment of descending pathways is now available by the transcranial electrical or magnetoelectric excitation of the motor cortex and by the recording of neural or muscular activity (motor evoked potentials [MEP]) (1,14). Although acute changes in spinal cord function usually affect both motor and sensory pathways, a few isolated cases of motor impairment despite stable SEP have been documented in the
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literature (5,11). Therefore, MEP monitoring has gained increasing interest. This is especially true because animal studies of spinal cord trauma and ischemia confirmed close relationships between changes in motor potentials and the neurological condition (4,16, 20) . However, the intraoperative evaluation of motor responses is still limited by the lack of knowledge on the influence of anesthesia. The comprehension of the anesthetic effects can be expected to improve the value of this monitoring technique by both increasing the recordability of potentials and decreasing the misinterpretation of potential findings related to nonsurgical factors. Because inhalational agents are usually applied for neuroanesthesia in spinal cord surgery, we designed this experimental study in rabbits to evaluate the effects of halothane, enflurane, and isoflurane on MEP. Our results clearly indicate a major suppressive effect of these anesthetics on muscular activity, whereas neural activity is affected to only a minor extent. Therefore, we are encouraged to report our findings. MATERIALS AND METHODS Ten male rabbits weighing between 3500 and 4500 g were used for this study. The day before the actual experiment, silver ball electrodes (2 mm in diameter) were implanted epidurally over the left motor cortex (anode at the level of the coronary suture and cathode 2 cm behind it, each 1 cm parasagittally) with intravenous analgosedation with droperidol/fentanyl (Janssen, Neuss, Germany) via an ear vein. Additionally, small cardiac pacing electrodes with an interelectrode distance of 0.5 cm were implanted epidurally over the upper and lower thoracic spinal cord as well as over the cauda equina after laminectomy. All electrode cables were placed subcutaneously by undermining the skin. The animal was allowed to wake up and to take nourishment. On the day of the actual experiment, an ear vein was cannulated and a sleeping dose of 10 mg of methohexital (Lilly, Bad Homburg, Germany) was administered. A tracheotomy was performed, and the animal was ventilated with an air/oxygen mixture (70/30 vol%). The right femoral artery was cannulated with a 22-gauge cannula. The animal was placed in the prone position. Electrode cables implanted the day before were mobilized and connected to the stimulating and recording device. Additionally, electromyograph electrodes were fixed to the proximal muscles of the right fore and hind legs as well as to the paraspinal muscles adjacent to the epidural recording sites after the skin was shaved. Single doses of droperidol and fentanyl (5 mg and 240 µg, respectively) were administered repeatedly as required. Bipolar anodal stimulation of the motor cortex was achieved by constant-voltage condenser discharges with a Digitimer D 180 stimulator (Digitimer, Hertfordshire, England). Stimulus strength was gradually increased until a clear response was obtained at all recording sites. After that, stimulus strength was kept constant throughout the experiment. In some animals, the cervical and lumbar nerve roots were stimulated additionally with a stimulus strength of 20 to 30 V. EMG responses
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Neurosurgery 1992-98 August 1992, Volume 31, Number 2 298 Influence of Halothane, Enflurane, and Isoflurane on Motor Evoked Potentials Experimental Study
RESULTS In all animals, distinct baseline values were obtained from all recording sites. Latencies of EMG responses recorded from the fore leg ranged from 4.8 to 5.6 milliseconds (average, 5.1 ms), and those obtained from the hind leg ranged from 11.3 to 12.7 milliseconds (average, 11.8 ms). EMG amplitudes varied between 800 µV and 3.5 mV. Latencies of spinal responses recorded from the upper thoracic cord ranged from 1.8 to 2.2 milliseconds (average, 2.1 ms), and those obtained from the lower thoracic cord ranged from 3.9 to 4.6 milliseconds (average, 4.3 ms). Cauda equina potentials showed latencies of 4.9 to 5.6 milliseconds (average, 5.2 ms). Amplitudes of epidurally recorded potentials varied between 8 and 76 µV (average, 26 µV) and decreased with increasing distance of the recording site from the motor cortex. Halothane, enflurane, and isoflurane showed a similar effect on EMG responses obtained from the fore and hind legs. Evaluating results on an equianesthetic concentration basis, we found amplitudes to be reduced to 41% (range, 13-61%) of the baselines with 0.25 MAC of one of the agents, whereas latencies increased by an average of 0.3 milliseconds. With 0.5 MAC, EMG responses were obtained in only 3 of 10 animals and ranged from 3 to 12% (average, 6%) of the baseline values. At the same time, latencies increased by an average of 0.5
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milliseconds. EMG responses were absent in all animals with concentrations of 1.0 and 1.5 MAC. Spinal responses were obtained at all concentrations of the various agents. Halothane, enflurane, and isoflurane showed a similar dosedependent effect on the amplitudes of potentials at the different recording sites. Amplitudes were reduced to 95% (range, 78-99%), with 0.25 MAC, to 91% (range, 75-101%) with 0.5 MAC, and to 81% (range, 40-95%) with 1.0 MAC. A MAC of 1.5 of either agent caused a reduction in the amplitudes of spinal responses to 77% on the average (range, 3197%). At the same time, latencies increased by 0.2 milliseconds with 0.5 MAC and 0.3 milliseconds with 1.5 MAC. Figures 1, 4, and 7 present the potential findings in single animals. Figures 2, 3, 5, 6, 8, and 9 provide a summary of the results in our animals. Complete temporary paralyzation of the animals achieved by the administration of 15 mg of succinylcholine did not show any changes of epidurally recorded responses, with respect to neither amplitudes nor latencies. Only later waves of the potentials representing myogenic activity of the paraspinal muscles were abolished (Figs. 1, 4, and 7). In three animals, the cervical (by upward and lateral movement of the proximal thoracic electrode) and the lumbar nerve roots were also stimulated. Evaluating EMG responses of the fore and hind legs, we found amplitudes to be slightly reduced to an average of 92% at 1.5 MAC halothane as compared with the baseline values. There were no changes in the latencies of the potentials (Fig. 10). In four animals, spinal responses were recorded from the upper thoracic spinal cord and the cauda equina after the intracardial injection of potassium chloride, which caused cardiac arrest. All of these animals showed stable potentials at both recording sites 2 minutes after cardiac arrest, whereas potentials were noticeably reduced in amplitude after 6 minutes with a slight increase in latencies. Eight minutes after cardiac arrest, potentials were abolished. In every case, primary changes in potentials were observed at the cauda equina (Fig. 11). DISCUSSION The examination of descending pathways by means of MEP seems to be a promising tool for monitoring the functional state of the central nervous system. To date, some reports on the application of MEP during orthopedic, vascular, and neurosurgical operations exist (2,8,12,17,21). Stimulation can be performed transcranially or directly to the motor cortex with single or repeated stimuli. Responses can be recorded from the extremity muscles, peripheral nerves, or the epidural space along the spinal cord and cauda equina. However, although there is no consensus on the most suitable stimulation and recording technique, all authors dealing with motor monitoring agree that MEP in addition to SEP might represent a useful tool for lowering postoperative morbidity. A major problem involved with MEP monitoring is the influence of anesthesia. Especially in spinal cord surgery, inhalational agents such as halothane, enflurane, and isoflurane are widely used for
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were recorded from the proximal muscles of the right fore and hind legs. Furthermore, potentials were recorded from the upper and lower thoracic spinal cord and the cauda equina. Onset latencies of the potentials and peak-to-peak amplitudes were measured. Only single shocks applied with an interval of at least 3 seconds were evaluated. Filter settings ranged between 20 Hz and 3 kHz. The time base was 20 microseconds with a gain ranging from 10 µV to 1 mV per division (electrophysiological system, Compact 4; Nicolet, Madison, WI). MEP were recorded under baseline conditions (analgosedation with droperidol/fentanyl during breathing of an oxygen/air mixture) as well as at 0.25, 0.5, 1.0, and 1.5 minimal alveolar concentration (MAC) of halothane (Hoechst, Frankfurt, Germany), enflurane, and isoflurane (both from Abbot, Wiesbaden, Germany), respectively. Each concentration was maintained for 20 minutes. In most animals, more than one inhalational anesthetic was tested. However, in every case, baseline values were obtained before the next trial was started. Electrocardiogram, heart rate, and blood pressure were monitored continuously via the femoral artery. Body temperature was registered and kept constant by warming the animal with red light irradiation. Blood gases were controlled at regular intervals and kept constant. After the experiment, the animals were killed by an intracardial injection of 50 mg of potassium chloride (Boehringer, Mannheim, Germany), which caused cardiac arrest. When the blood pressure was at the zero level, spinal responses were recorded at regular intervals until they were completely abolished.
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general agreement that anesthesia with either inhalational agent is suitable for SEP monitoring if used in moderate concentrations. In accordance, our results show compatibility of inhalational anesthetics with the intraoperative recording of neural activity along the descending pathways, whereas muscular activity is abolished at concentrations beyond 0.5 MAC. The small number of animals used for this study prohibits the statistical analysis of our data. However, it was the aim of this study to provide comprehensive data indicating the possibilities and limits of intraoperative MEP monitoring during anesthesia with these inhalational agents in humans. One may speculate about the neuropharmacological mechanisms of the essential suppression of EMG responses. Larsen (10) observed a slight reduction of EMG amplitudes obtained in response to peripheral nerve stimulation with halothane that was attributed to a dampening effect on central pathways. In accordance, EMG amplitudes in our animals were reduced only to 92% of the baselines by 1.5 MAC halothane after stimulation of the cervical and lumbar nerve roots. Moreover, spinal evoked responses were stable several minutes after cardiac arrest. This clearly indicates a deep action site of the electrical impulse, activating axons rather than dendrites of nerve cells and thus providing D waves (3) . Therefore, the suppression of EMG responses after central stimulation as observed in our experiments cannot be explained by an effect of the anesthetics at the cortical or neuromuscular level. We hypothesize that the descending impulse may be affected at the level of the spinal interneuronal or motoneuronal system. Further neurophysiological analysis should be able to explain in more detail the mechanism that is involved in the alleged interaction of inhalational agents with the descending motor system. In conclusion, the intraoperative monitoring of descending pathways by means of MEP during anesthesia with the inhalational agents halothane, enflurane, and isoflurane is feasible only when neural activity is evaluated. Similar to monitoring with SEP, the evaluation of descending neural activity is compatible at even 1.5 MAC of any of the three anesthetics. With regard to amplitudes of the potentials, proximal recording sites along the spinal cord are preferable to recording from the cauda equina. However, it is not advisable to record muscular activity when concentrations of more than 0.25 MAC are applied. Received, June 12, 1991. Accepted, February 14, 1992. Reprint requests: J. Zentner, M.D., Department of Neurosurgery, Sigmund-Freud-Str. 25, D-5300 Bonn 1, Germany. REFERENCES: (1-22) 1. 2.
Barker AT, Jalinous R, Freeston IL: Noninvasive magnetic stimulation of the human cortex. Lancet 1:1106-1107, 1985. Boyd SG, Rothwell JC, Cowan JMA, Webb PJ, Morley T: A method of monitoring
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anesthesia. Therefore, this study was designed to provide more data on the influence of these anesthetics on both muscular and neural activity. It was the aim of our work to compare these agents on an equianesthetic basis, while physiological parameters such as blood pressure, temperature, and blood gases were kept constant throughout the procedure. This was achieved by continuous and discontinuous monitoring of these parameters during ventilation with an oxygen/air/anesthetic mixture with increasing anesthetic concentrations (0.25 to 1.5 MAC). Baseline values were obtained under analgosedation with droperidol/fentanyl, which have been shown to have only a minor effect on MEP (22). Our results clearly indicate a major suppressive effect of halothane, enflurane, and isoflurane on the EMG responses elicited by the electrical stimulation of the motor cortex. This effect was similar for all agents tested in this study. With 0.25 MAC of any of the agents, EMG amplitudes were reduced to an average of 41% of the baseline values. At the same time, latencies increased by 0.3 milliseconds. With 0.5 MAC, EMG responses were obtained in only 3 of 10 animals with amplitudes of an average of 6% of the baselines and an increase in latencies by an average of 0.5 milliseconds. EMG responses were absent in all animals at concentrations of 1.0 and 1.5 MAC. In accordance with our findings, Haghighi et al. (7) observed a dose-dependent decrease in amplitudes and an increase in latencies of muscle responses in rats during isoflurane anesthesia. On the other hand, spinal evoked responses were obtained at all concentrations of halothane, enflurane, and isoflurane. With all of the anesthetics, we found amplitudes of spinal responses to be slightly reduced, depending on their concentration. With 0.25 MAC, amplitudes were an average of 95% of the baselines and decreased to 91% with 0.5 MAC and to 81% with 1.0 MAC. However, with 1.5 MAC of any of the agents, potentials were also obtained although amplitudes were reduced to an average of 77% with an increase in latencies by an average of 0.3 milliseconds. Complete temporary paralyzation of the animals as achieved by the administration of 15 mg of succinylcholine did not show any changes in epidurally recorded potentials. However, muscle potentials recorded simultaneously from the paraspinal muscles adjacent to the epidural recording sites were abolished after the succinylcholine block. Thus, it is clearly shown that spinal responses represent neural activity. The effect of inhalational anesthetics on spinal evoked motor responses is similar to that described for cortical and spinal evoked somatosensory potentials. It is well known that amplitudes and latencies of SEP are influenced in a dose-related fashion. Salzmann et al. (18) studied SEP monitoring in 116 patients undergoing surgery for spinal fusion and found that halothane (0.5%) slightly increased latencies and variably decreased the amplitudes of the potentials. This corresponds with Koht's study (9) of 395 spinal cord patients. Isoflurane and enflurane cause a similar dose-dependent increase in latencies and a decrease in SEP amplitudes (13,15,19). There is
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spinal potentials to trancranial motor cortex stimulation: intraoperative recording, in Rossini PM, Marsden CD (eds): Non-invasive Stimulation of Brain and Spinal Cord. New York, Alan R Liss, 1988, pp 297-304. Salzmann SK, Beckman AL, Marks HG, Naidu R, Bunnell WP, MacEwen GD: Effects of halothane on intraoperative scalp-recorded somatosensory evoked potentials to posterior tibial nerve stimulation in man. Electroencephalogr Clin Neurophysiol 65:3645, 1988. Sebel PS, Ingram DA, Flynn PJ, Rutherford CF, Rogers H: Evoked potentials during isoflurane anaesthesia. Br J Anaesth 58:580585, 1986. Simpson RK, Baskin DS: Corticomotor evoked potentials in acute and chronic blunt spinal cord injury in the rat: Correlation with neurological outcome and histological damage. Neurosurgery 20:131-137, 1987. Tsubokawa T, Yamamoto T, Hirayama T, Maejima S, Katayama Y: Clinical application of corticospinal evoked potentials as a monitor of pyramidal function. Nihon Univ J Med 28:27-37, 1986a. Zentner J, Kiss I, Ebner A: Influence of anesthestics--nitrous oxide in particular--on electromyographic response evoked by transcranial electrical stimulation of the cortex. Neurosurgery 24:253-256, 1989.
COMMENTS Dr. Zentner and associates report the effects of halothane, enflurane, and isoflurane on the transmission of the motor evoked potential. Bipolar epidural motor cortex stimulation was performed on 10 rabbits, and responses were recorded epidurally over the upper and lower thoracic spine and the proximal limb muscles. Their results, in agreement with the findings of our laboratory, show that these agents significantly suppress the motor evoked potentials as recorded from the muscle. In addition, the authors found that the signal as recorded over the spine is more resistant to suppression and suggest that this site can be used for monitoring. However, because the spinal motor evoked potential is known to be more resistant to interventions, it remains to be seen whether spinal recording will be sensitive enough to serve as a reliable monitor of motor function. John Oro Columbia, Missouri The work is an important step in defining the characteristics of motor evoked potentials. The effect of volatile anesthetics on the motor pathways at the level of the anterior horn is clearly demonstrated. In addition to providing additional information about the physiology of the action of these anesthetic
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3.
functions in corticospinal pathways during scoliosis surgery with a note on motor conduction velocities. J Neurol Neurosurg Psychiatry 49:251-257, 1986. Day BL, Thompson PD, Dick JP, Nakashima K, Marsden CD: Different sites of action of electrical and magnetic stimulation of the human brain. Neurosci Lett 75:101-106, 1987. Fehlings MG, Tator CH, Linden RD, Piper IR: Motor evoked potentials recorded from normal and spinal cord-injured rats. Neurosurgery 20:125-130, 1987. Ginsburg HH, Shetter AG, Raudzens PA: Postoperative paraplegia with preserved intraoperative somatosensory evoked potentials. J Neurosurg 63:296-300, 1985. Grundy B: Intraoperative monitoring of sensory-evoked potentials. Anesthesiology 58:72-87, 1983. Haghighi SS, Green D, Oro JJ, Drake RK, Kracke GR: Depressive effect of isoflurane anesthesia on motor evoked potentials. Neurosurgery 26:993-997, 1990. Katayama Y, Tsubokawa T, Yamamoto T, Maejima S: Spinal cord potentials to direct stimulation of the exposed motor cortex in humans: Comparison with data from trancranial motor cortex stimulation, in Rossini PM, Marsden CD (eds): Non-invasive Stimulation of Brain and Spinal Cord. New York, Alan R Liss, 1988, pp 305-311. Koht A: Anesthesia and evoked potentials: an overview. Int J Clin Monit Comput 5:167173, 1988. Larsen R: Anaesthesie. Baltimore, Urban and Schwarzenberg, 1985, p 135. Lesser RP, Raudzens PA, Lueders H, Nuwer MR, Goldie WD, Morris HH, Dinner DS, Klemm G, Hahn JF, Shetter AG, Ginsburg HH, Gurd AR: Postoperative neurological deficits may occur despite unchanged intraoperative somatosensory evoked potentials. Ann Neurol 19:22-25, 1986. Levy WJ: Clinical experience with motor and cerebellar evoked potential monitoring. Neurosurgery 20:169-182, 1987. McPherson RW, Mahla M, Johnson R, Traystman RJ: Effects of enflurane, isoflurane and nitrous oxide on somatosensory evoked potentials during fentanyl anesthesia. Anesthesiology 62:626-633, 1985. Merton PA, Morton HB: Stimulation of the motor cortex in the intact human subject. Nature 285:227, 1980. Nogueira MC, Brunko E, Vandesteen A, De Rood M, Zegers de Beyl D: Differential effects of isoflurane on SEP recorded over parietal and frontal scalp. Neurology 39:12101215, 1989. Patil AA, Nagaray MP, Mehta R: Cortically evoked motor action potentials in spinal cord injury research. Neurosurgery 16:473- 476, 1985. Pelosi L, Caruso G, Balbi P: Characteristics of
agents, this work also explains many of the difficulties that have been reported of using motor evoked potentials to monitor neural function during surgery. Reliable monitoring of motor evoked potentials will likely require either anesthesia without volatile agents or recording of the spinal cord potentials.
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Jasper R. Daube Rochester, Minnesota
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Figure 2. Influence of halothane (0.25 to 1.5 MAC) on MEP amplitudes as found in eight animals. Mean values and mean square errors are shown.
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Figure 1. Influence of halothane on MEP recorded from the fore leg (FL), hind leg (HL), lower thoracic spinal cord (LTSC), and cauda equina (CE) in a single animal. Potentials with 0.25 to 1.5 MAC halothane as well as those after complete paralyzation with 15 mg of succinylcholine are shown. Two to three recordings are superimposed.
Figure 4. Influence of enflurane on MEP recorded from the fore leg (FL), hind leg (HL), upper thoracic spinal cord (UTSC), and lower thoracic spinal cord (LTSC) in a single animal. Potentials with 0.25 to 1.5 MAC enflurane as well as those after complete paralyzation with 15 mg of succinylcholine are shown. Two to three recordings are superimposed.
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Figure 3. Influence of halothane (0.25 to 1.5 MAC) on MEP latencies as found in eight animals. Mean values and mean square errors are shown.
Figure 6. Influence of enflurane (0.25 to 1.5 MAC) on MEP latencies as found in six animals. Mean values and mean square errors are shown.
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Figure 5. Influence of enflurane (0.25 to 1.5 MAC) on MEP amplitudes as found in six animals. Mean values and mean square errors are shown.
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Figure 7. Influence of isoflurane on MEP recorded from the fore leg (FL), hind leg (HL), upper thoracic spinal cord (UTSC), and cauda equina (CE) in a single animal. Potentials with 0.25 to 1.5 MAC isoflurane as well as those after complete paralyzation with 15 mg succinylcholine are shown. Two to three recordings are superimposed.
Figure 9. Influence of isoflurane (0.25 to 1.5 MAC) on MEP latencies as found in seven animals. Mean values and mean square latencies are shown.
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Figure 8. Influence of isoflurane (0.25 to 1.5 MAC) on MEP amplitudes as found in seven animals. Mean values and mean square errors are shown.
Figure 11. Influence of cardiac arrest, achieved by the intravenous administration of 50 mg of potassium chloride, on MEP recorded from the upper thoracic spinal cord (UTSC) and cauda equina (CE) in a single animal. Potential findings 2 to 8 minutes after depression of blood pressure to the zero level are shown.
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Figure 10. Influence of 1.5 MAC halothane on EMG responses recorded from the fore leg (FL) and hind leg (HL) in response to stimulation of the cervical and lumbar nerve roots, respectively. Two recordings are superimposed.
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literature (5,11). Therefore, MEP monitoring has gained increasing interest. This is especially true because animal studies of spinal cord trauma and ischemia confirmed close relationships between changes in motor potentials and the neurological condition (4,16, 20) . However, the intraoperative evaluation of motor responses is still limited by the lack of knowledge on the influence of anesthesia. The comprehension of the anesthetic effects can be expected to improve the value of this monitoring technique by both increasing the recordability of potentials and decreasing the misinterpretation of potential findings related to nonsurgical factors. Because inhalational agents are usually applied for neuroanesthesia in spinal cord surgery, we designed this experimental study in rabbits to evaluate the effects of halothane, enflurane, and isoflurane on MEP. Our results clearly indicate a major suppressive effect of these anesthetics on muscular activity, whereas neural activity is affected to only a minor extent. Therefore, we are encouraged to report our findings. MATERIALS AND METHODS Ten male rabbits weighing between 3500 and 4500 g were used for this study. The day before the actual experiment, silver ball electrodes (2 mm in diameter) were implanted epidurally over the left motor cortex (anode at the level of the coronary suture and cathode 2 cm behind it, each 1 cm parasagittally) with intravenous analgosedation with droperidol/fentanyl (Janssen, Neuss, Germany) via an ear vein. Additionally, small cardiac pacing electrodes with an interelectrode distance of 0.5 cm were implanted epidurally over the upper and lower thoracic spinal cord as well as over the cauda equina after laminectomy. All electrode cables were placed subcutaneously by undermining the skin. The animal was allowed to wake up and to take nourishment. On the day of the actual experiment, an ear vein was cannulated and a sleeping dose of 10 mg of methohexital (Lilly, Bad Homburg, Germany) was administered. A tracheotomy was performed, and the animal was ventilated with an air/oxygen mixture (70/30 vol%). The right femoral artery was cannulated with a 22-gauge cannula. The animal was placed in the prone position. Electrode cables implanted the day before were mobilized and connected to the stimulating and recording device. Additionally, electromyograph electrodes were fixed to the proximal muscles of the right fore and hind legs as well as to the paraspinal muscles adjacent to the epidural recording sites after the skin was shaved. Single doses of droperidol and fentanyl (5 mg and 240 µg, respectively) were administered repeatedly as required. Bipolar anodal stimulation of the motor cortex was achieved by constant-voltage condenser discharges with a Digitimer D 180 stimulator (Digitimer, Hertfordshire, England). Stimulus strength was gradually increased until a clear response was obtained at all recording sites. After that, stimulus strength was kept constant throughout the experiment. In some animals, the cervical and lumbar nerve roots were stimulated additionally with a stimulus strength of 20 to 30 V. EMG responses
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Neurosurgery 1992-98 August 1992, Volume 31, Number 2 298 Influence of Halothane, Enflurane, and Isoflurane on Motor Evoked Potentials Experimental Study
RESULTS In all animals, distinct baseline values were obtained from all recording sites. Latencies of EMG responses recorded from the fore leg ranged from 4.8 to 5.6 milliseconds (average, 5.1 ms), and those obtained from the hind leg ranged from 11.3 to 12.7 milliseconds (average, 11.8 ms). EMG amplitudes varied between 800 µV and 3.5 mV. Latencies of spinal responses recorded from the upper thoracic cord ranged from 1.8 to 2.2 milliseconds (average, 2.1 ms), and those obtained from the lower thoracic cord ranged from 3.9 to 4.6 milliseconds (average, 4.3 ms). Cauda equina potentials showed latencies of 4.9 to 5.6 milliseconds (average, 5.2 ms). Amplitudes of epidurally recorded potentials varied between 8 and 76 µV (average, 26 µV) and decreased with increasing distance of the recording site from the motor cortex. Halothane, enflurane, and isoflurane showed a similar effect on EMG responses obtained from the fore and hind legs. Evaluating results on an equianesthetic concentration basis, we found amplitudes to be reduced to 41% (range, 13-61%) of the baselines with 0.25 MAC of one of the agents, whereas latencies increased by an average of 0.3 milliseconds. With 0.5 MAC, EMG responses were obtained in only 3 of 10 animals and ranged from 3 to 12% (average, 6%) of the baseline values. At the same time, latencies increased by an average of 0.5
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milliseconds. EMG responses were absent in all animals with concentrations of 1.0 and 1.5 MAC. Spinal responses were obtained at all concentrations of the various agents. Halothane, enflurane, and isoflurane showed a similar dosedependent effect on the amplitudes of potentials at the different recording sites. Amplitudes were reduced to 95% (range, 78-99%), with 0.25 MAC, to 91% (range, 75-101%) with 0.5 MAC, and to 81% (range, 40-95%) with 1.0 MAC. A MAC of 1.5 of either agent caused a reduction in the amplitudes of spinal responses to 77% on the average (range, 3197%). At the same time, latencies increased by 0.2 milliseconds with 0.5 MAC and 0.3 milliseconds with 1.5 MAC. Figures 1, 4, and 7 present the potential findings in single animals. Figures 2, 3, 5, 6, 8, and 9 provide a summary of the results in our animals. Complete temporary paralyzation of the animals achieved by the administration of 15 mg of succinylcholine did not show any changes of epidurally recorded responses, with respect to neither amplitudes nor latencies. Only later waves of the potentials representing myogenic activity of the paraspinal muscles were abolished (Figs. 1, 4, and 7). In three animals, the cervical (by upward and lateral movement of the proximal thoracic electrode) and the lumbar nerve roots were also stimulated. Evaluating EMG responses of the fore and hind legs, we found amplitudes to be slightly reduced to an average of 92% at 1.5 MAC halothane as compared with the baseline values. There were no changes in the latencies of the potentials (Fig. 10). In four animals, spinal responses were recorded from the upper thoracic spinal cord and the cauda equina after the intracardial injection of potassium chloride, which caused cardiac arrest. All of these animals showed stable potentials at both recording sites 2 minutes after cardiac arrest, whereas potentials were noticeably reduced in amplitude after 6 minutes with a slight increase in latencies. Eight minutes after cardiac arrest, potentials were abolished. In every case, primary changes in potentials were observed at the cauda equina (Fig. 11). DISCUSSION The examination of descending pathways by means of MEP seems to be a promising tool for monitoring the functional state of the central nervous system. To date, some reports on the application of MEP during orthopedic, vascular, and neurosurgical operations exist (2,8,12,17,21). Stimulation can be performed transcranially or directly to the motor cortex with single or repeated stimuli. Responses can be recorded from the extremity muscles, peripheral nerves, or the epidural space along the spinal cord and cauda equina. However, although there is no consensus on the most suitable stimulation and recording technique, all authors dealing with motor monitoring agree that MEP in addition to SEP might represent a useful tool for lowering postoperative morbidity. A major problem involved with MEP monitoring is the influence of anesthesia. Especially in spinal cord surgery, inhalational agents such as halothane, enflurane, and isoflurane are widely used for
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were recorded from the proximal muscles of the right fore and hind legs. Furthermore, potentials were recorded from the upper and lower thoracic spinal cord and the cauda equina. Onset latencies of the potentials and peak-to-peak amplitudes were measured. Only single shocks applied with an interval of at least 3 seconds were evaluated. Filter settings ranged between 20 Hz and 3 kHz. The time base was 20 microseconds with a gain ranging from 10 µV to 1 mV per division (electrophysiological system, Compact 4; Nicolet, Madison, WI). MEP were recorded under baseline conditions (analgosedation with droperidol/fentanyl during breathing of an oxygen/air mixture) as well as at 0.25, 0.5, 1.0, and 1.5 minimal alveolar concentration (MAC) of halothane (Hoechst, Frankfurt, Germany), enflurane, and isoflurane (both from Abbot, Wiesbaden, Germany), respectively. Each concentration was maintained for 20 minutes. In most animals, more than one inhalational anesthetic was tested. However, in every case, baseline values were obtained before the next trial was started. Electrocardiogram, heart rate, and blood pressure were monitored continuously via the femoral artery. Body temperature was registered and kept constant by warming the animal with red light irradiation. Blood gases were controlled at regular intervals and kept constant. After the experiment, the animals were killed by an intracardial injection of 50 mg of potassium chloride (Boehringer, Mannheim, Germany), which caused cardiac arrest. When the blood pressure was at the zero level, spinal responses were recorded at regular intervals until they were completely abolished.
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general agreement that anesthesia with either inhalational agent is suitable for SEP monitoring if used in moderate concentrations. In accordance, our results show compatibility of inhalational anesthetics with the intraoperative recording of neural activity along the descending pathways, whereas muscular activity is abolished at concentrations beyond 0.5 MAC. The small number of animals used for this study prohibits the statistical analysis of our data. However, it was the aim of this study to provide comprehensive data indicating the possibilities and limits of intraoperative MEP monitoring during anesthesia with these inhalational agents in humans. One may speculate about the neuropharmacological mechanisms of the essential suppression of EMG responses. Larsen (10) observed a slight reduction of EMG amplitudes obtained in response to peripheral nerve stimulation with halothane that was attributed to a dampening effect on central pathways. In accordance, EMG amplitudes in our animals were reduced only to 92% of the baselines by 1.5 MAC halothane after stimulation of the cervical and lumbar nerve roots. Moreover, spinal evoked responses were stable several minutes after cardiac arrest. This clearly indicates a deep action site of the electrical impulse, activating axons rather than dendrites of nerve cells and thus providing D waves (3) . Therefore, the suppression of EMG responses after central stimulation as observed in our experiments cannot be explained by an effect of the anesthetics at the cortical or neuromuscular level. We hypothesize that the descending impulse may be affected at the level of the spinal interneuronal or motoneuronal system. Further neurophysiological analysis should be able to explain in more detail the mechanism that is involved in the alleged interaction of inhalational agents with the descending motor system. In conclusion, the intraoperative monitoring of descending pathways by means of MEP during anesthesia with the inhalational agents halothane, enflurane, and isoflurane is feasible only when neural activity is evaluated. Similar to monitoring with SEP, the evaluation of descending neural activity is compatible at even 1.5 MAC of any of the three anesthetics. With regard to amplitudes of the potentials, proximal recording sites along the spinal cord are preferable to recording from the cauda equina. However, it is not advisable to record muscular activity when concentrations of more than 0.25 MAC are applied. Received, June 12, 1991. Accepted, February 14, 1992. Reprint requests: J. Zentner, M.D., Department of Neurosurgery, Sigmund-Freud-Str. 25, D-5300 Bonn 1, Germany. REFERENCES: (1-22) 1. 2.
Barker AT, Jalinous R, Freeston IL: Noninvasive magnetic stimulation of the human cortex. Lancet 1:1106-1107, 1985. Boyd SG, Rothwell JC, Cowan JMA, Webb PJ, Morley T: A method of monitoring
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anesthesia. Therefore, this study was designed to provide more data on the influence of these anesthetics on both muscular and neural activity. It was the aim of our work to compare these agents on an equianesthetic basis, while physiological parameters such as blood pressure, temperature, and blood gases were kept constant throughout the procedure. This was achieved by continuous and discontinuous monitoring of these parameters during ventilation with an oxygen/air/anesthetic mixture with increasing anesthetic concentrations (0.25 to 1.5 MAC). Baseline values were obtained under analgosedation with droperidol/fentanyl, which have been shown to have only a minor effect on MEP (22). Our results clearly indicate a major suppressive effect of halothane, enflurane, and isoflurane on the EMG responses elicited by the electrical stimulation of the motor cortex. This effect was similar for all agents tested in this study. With 0.25 MAC of any of the agents, EMG amplitudes were reduced to an average of 41% of the baseline values. At the same time, latencies increased by 0.3 milliseconds. With 0.5 MAC, EMG responses were obtained in only 3 of 10 animals with amplitudes of an average of 6% of the baselines and an increase in latencies by an average of 0.5 milliseconds. EMG responses were absent in all animals at concentrations of 1.0 and 1.5 MAC. In accordance with our findings, Haghighi et al. (7) observed a dose-dependent decrease in amplitudes and an increase in latencies of muscle responses in rats during isoflurane anesthesia. On the other hand, spinal evoked responses were obtained at all concentrations of halothane, enflurane, and isoflurane. With all of the anesthetics, we found amplitudes of spinal responses to be slightly reduced, depending on their concentration. With 0.25 MAC, amplitudes were an average of 95% of the baselines and decreased to 91% with 0.5 MAC and to 81% with 1.0 MAC. However, with 1.5 MAC of any of the agents, potentials were also obtained although amplitudes were reduced to an average of 77% with an increase in latencies by an average of 0.3 milliseconds. Complete temporary paralyzation of the animals as achieved by the administration of 15 mg of succinylcholine did not show any changes in epidurally recorded potentials. However, muscle potentials recorded simultaneously from the paraspinal muscles adjacent to the epidural recording sites were abolished after the succinylcholine block. Thus, it is clearly shown that spinal responses represent neural activity. The effect of inhalational anesthetics on spinal evoked motor responses is similar to that described for cortical and spinal evoked somatosensory potentials. It is well known that amplitudes and latencies of SEP are influenced in a dose-related fashion. Salzmann et al. (18) studied SEP monitoring in 116 patients undergoing surgery for spinal fusion and found that halothane (0.5%) slightly increased latencies and variably decreased the amplitudes of the potentials. This corresponds with Koht's study (9) of 395 spinal cord patients. Isoflurane and enflurane cause a similar dose-dependent increase in latencies and a decrease in SEP amplitudes (13,15,19). There is
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spinal potentials to trancranial motor cortex stimulation: intraoperative recording, in Rossini PM, Marsden CD (eds): Non-invasive Stimulation of Brain and Spinal Cord. New York, Alan R Liss, 1988, pp 297-304. Salzmann SK, Beckman AL, Marks HG, Naidu R, Bunnell WP, MacEwen GD: Effects of halothane on intraoperative scalp-recorded somatosensory evoked potentials to posterior tibial nerve stimulation in man. Electroencephalogr Clin Neurophysiol 65:3645, 1988. Sebel PS, Ingram DA, Flynn PJ, Rutherford CF, Rogers H: Evoked potentials during isoflurane anaesthesia. Br J Anaesth 58:580585, 1986. Simpson RK, Baskin DS: Corticomotor evoked potentials in acute and chronic blunt spinal cord injury in the rat: Correlation with neurological outcome and histological damage. Neurosurgery 20:131-137, 1987. Tsubokawa T, Yamamoto T, Hirayama T, Maejima S, Katayama Y: Clinical application of corticospinal evoked potentials as a monitor of pyramidal function. Nihon Univ J Med 28:27-37, 1986a. Zentner J, Kiss I, Ebner A: Influence of anesthestics--nitrous oxide in particular--on electromyographic response evoked by transcranial electrical stimulation of the cortex. Neurosurgery 24:253-256, 1989.
COMMENTS Dr. Zentner and associates report the effects of halothane, enflurane, and isoflurane on the transmission of the motor evoked potential. Bipolar epidural motor cortex stimulation was performed on 10 rabbits, and responses were recorded epidurally over the upper and lower thoracic spine and the proximal limb muscles. Their results, in agreement with the findings of our laboratory, show that these agents significantly suppress the motor evoked potentials as recorded from the muscle. In addition, the authors found that the signal as recorded over the spine is more resistant to suppression and suggest that this site can be used for monitoring. However, because the spinal motor evoked potential is known to be more resistant to interventions, it remains to be seen whether spinal recording will be sensitive enough to serve as a reliable monitor of motor function. John Oro Columbia, Missouri The work is an important step in defining the characteristics of motor evoked potentials. The effect of volatile anesthetics on the motor pathways at the level of the anterior horn is clearly demonstrated. In addition to providing additional information about the physiology of the action of these anesthetic
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functions in corticospinal pathways during scoliosis surgery with a note on motor conduction velocities. J Neurol Neurosurg Psychiatry 49:251-257, 1986. Day BL, Thompson PD, Dick JP, Nakashima K, Marsden CD: Different sites of action of electrical and magnetic stimulation of the human brain. Neurosci Lett 75:101-106, 1987. Fehlings MG, Tator CH, Linden RD, Piper IR: Motor evoked potentials recorded from normal and spinal cord-injured rats. Neurosurgery 20:125-130, 1987. Ginsburg HH, Shetter AG, Raudzens PA: Postoperative paraplegia with preserved intraoperative somatosensory evoked potentials. J Neurosurg 63:296-300, 1985. Grundy B: Intraoperative monitoring of sensory-evoked potentials. Anesthesiology 58:72-87, 1983. Haghighi SS, Green D, Oro JJ, Drake RK, Kracke GR: Depressive effect of isoflurane anesthesia on motor evoked potentials. Neurosurgery 26:993-997, 1990. Katayama Y, Tsubokawa T, Yamamoto T, Maejima S: Spinal cord potentials to direct stimulation of the exposed motor cortex in humans: Comparison with data from trancranial motor cortex stimulation, in Rossini PM, Marsden CD (eds): Non-invasive Stimulation of Brain and Spinal Cord. New York, Alan R Liss, 1988, pp 305-311. Koht A: Anesthesia and evoked potentials: an overview. Int J Clin Monit Comput 5:167173, 1988. Larsen R: Anaesthesie. Baltimore, Urban and Schwarzenberg, 1985, p 135. Lesser RP, Raudzens PA, Lueders H, Nuwer MR, Goldie WD, Morris HH, Dinner DS, Klemm G, Hahn JF, Shetter AG, Ginsburg HH, Gurd AR: Postoperative neurological deficits may occur despite unchanged intraoperative somatosensory evoked potentials. Ann Neurol 19:22-25, 1986. Levy WJ: Clinical experience with motor and cerebellar evoked potential monitoring. Neurosurgery 20:169-182, 1987. McPherson RW, Mahla M, Johnson R, Traystman RJ: Effects of enflurane, isoflurane and nitrous oxide on somatosensory evoked potentials during fentanyl anesthesia. Anesthesiology 62:626-633, 1985. Merton PA, Morton HB: Stimulation of the motor cortex in the intact human subject. Nature 285:227, 1980. Nogueira MC, Brunko E, Vandesteen A, De Rood M, Zegers de Beyl D: Differential effects of isoflurane on SEP recorded over parietal and frontal scalp. Neurology 39:12101215, 1989. Patil AA, Nagaray MP, Mehta R: Cortically evoked motor action potentials in spinal cord injury research. Neurosurgery 16:473- 476, 1985. Pelosi L, Caruso G, Balbi P: Characteristics of
agents, this work also explains many of the difficulties that have been reported of using motor evoked potentials to monitor neural function during surgery. Reliable monitoring of motor evoked potentials will likely require either anesthesia without volatile agents or recording of the spinal cord potentials.
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Jasper R. Daube Rochester, Minnesota
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Figure 2. Influence of halothane (0.25 to 1.5 MAC) on MEP amplitudes as found in eight animals. Mean values and mean square errors are shown.
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Figure 1. Influence of halothane on MEP recorded from the fore leg (FL), hind leg (HL), lower thoracic spinal cord (LTSC), and cauda equina (CE) in a single animal. Potentials with 0.25 to 1.5 MAC halothane as well as those after complete paralyzation with 15 mg of succinylcholine are shown. Two to three recordings are superimposed.
Figure 4. Influence of enflurane on MEP recorded from the fore leg (FL), hind leg (HL), upper thoracic spinal cord (UTSC), and lower thoracic spinal cord (LTSC) in a single animal. Potentials with 0.25 to 1.5 MAC enflurane as well as those after complete paralyzation with 15 mg of succinylcholine are shown. Two to three recordings are superimposed.
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Figure 3. Influence of halothane (0.25 to 1.5 MAC) on MEP latencies as found in eight animals. Mean values and mean square errors are shown.
Figure 6. Influence of enflurane (0.25 to 1.5 MAC) on MEP latencies as found in six animals. Mean values and mean square errors are shown.
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Figure 5. Influence of enflurane (0.25 to 1.5 MAC) on MEP amplitudes as found in six animals. Mean values and mean square errors are shown.
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Figure 7. Influence of isoflurane on MEP recorded from the fore leg (FL), hind leg (HL), upper thoracic spinal cord (UTSC), and cauda equina (CE) in a single animal. Potentials with 0.25 to 1.5 MAC isoflurane as well as those after complete paralyzation with 15 mg succinylcholine are shown. Two to three recordings are superimposed.
Figure 9. Influence of isoflurane (0.25 to 1.5 MAC) on MEP latencies as found in seven animals. Mean values and mean square latencies are shown.
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Figure 8. Influence of isoflurane (0.25 to 1.5 MAC) on MEP amplitudes as found in seven animals. Mean values and mean square errors are shown.
Figure 11. Influence of cardiac arrest, achieved by the intravenous administration of 50 mg of potassium chloride, on MEP recorded from the upper thoracic spinal cord (UTSC) and cauda equina (CE) in a single animal. Potential findings 2 to 8 minutes after depression of blood pressure to the zero level are shown.
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Figure 10. Influence of 1.5 MAC halothane on EMG responses recorded from the fore leg (FL) and hind leg (HL) in response to stimulation of the cervical and lumbar nerve roots, respectively. Two recordings are superimposed.
