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NEUROSURGICAL ANESTHESIA

The Effects of the Neuromuscular Blockade Levels on Amplitudes of Posttetanic Motor-Evoked Potentials and Movement in Response to Transcranial Stimulation in Patients Receiving Propofol and Fentanyl Anesthesia

Yuri Yamamoto, MD^*, Masahiko Kawaguchi, MD^*, Hironobu Hayashi, MD^*, Toshinori Horiuchi, MD^*, Satoki Inoue, MD^*, Hiroyuki Nakase, MD, Toshisuke Sakaki, MD, and Hitoshi Furuya, MD^*

From the Departments of *Anesthesiology and Neurosurgery, Nara Medical University, Nara, Japan.

Address correspondence and reprint requests to Masahiko Kawaguchi, MD, Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Address e-mail to drjkawa{at}naramed-u.ac.jp.

	Abstract

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BACKGROUND: Patient movement in response to transcranial stimulation during monitoring of myogenic motor-evoked potentials (MEPs) may interfere with surgery. We recently reported a new technique to augment the amplitudes of myogenic MEPs, called "post-tetanic MEPs (p-MEPs)," in which tetanic stimulation of a peripheral nerve was applied prior to transcranial stimulation. We conducted the present study to determine an appropriate level of neuromuscular blockade during the monitoring of p-MEPs with a focus on patient movement.

METHODS: In 15 patients under propofol/fentanyl anesthesia, conventional MEPs (c-MEPs) and p-MEPs in response to transcranial electrical stimulation were recorded from the abductor hallucis muscle. For p-MEP recording, tetanic stimulation to the posterior tibial nerve at an intensity of 50 mA for 5 s was started 6 s prior to transcranial stimulation. The level of neuromuscular blockade was assessed by recording the amplitude of compound muscle action potentials (T1) from the abductor hallucis brevis muscle in response to supramaximal electrical stimulation of the median nerve at the wrist. After the baseline recordings of c-MEP and p-MEP at a T1 of 50% of control, 0.1 mg/kg of vecuronium was injected and the amplitudes of c-MEPs and p-MEPs were recorded. Patient movement was also assessed with the movement score ranging from 1 to 4 (1 = no movement, 4 = severe movement).

RESULTS: T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs before and 15–45 min after the administration of vecuronium were significantly higher than those of c-MEPs. When T1 and %T1 were less than and equal to 1 mV and 10%, respectively, the movement score was 1 or 2 in all patients, indicating that microscopic surgery was possible without the interruption of surgical procedures. When T1 was around 1 mV (0.8–1.2 mV), the success rates of recording of c-MEPs and p-MEPs were 73% (11 of 15) and 100% (15 of 15), respectively.

CONCLUSIONS: Under propofol/fentanyl anesthesia, p-MEP could be recorded at a T1 of 1 mV, in which patient movement in response to transcranial stimulation did not interfere with surgery. This technique may be used in patients without preoperative motor deficits, in which patient movement during surgical procedures is not preferable.

	Introduction

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Intraoperative monitoring of motor-evoked potentials (MEPs) to transcranial electrical stimulation of the motor cortex provides a method for monitoring the functional integrity of descending motor pathways during operations in which there is a risk for spinal cord injury. However, clinical and experimental use of these techniques has shown that the elicited responses are very sensitive to suppression by anesthetics and muscle relaxants.1–3 Because complete neuromuscular blockade abolishes the myogenic MEPs, partial neuromuscular blockade was conducted for anesthetic management during the monitoring of myogenic MEPs. Van Dongen et al.4 suggested that stable neuromuscular blockade aimed at 45%–55% of baseline can provide reliable and recordable muscle responses during intraoperative myogenic MEPs. However, this level of neuromuscular blockade elicits patient movement in response to transcranial stimulation. This may interfere with surgery, especially microscopic surgery. The development of MEPs methods in which no patient movement is induced in response to transcranial stimulation may therefore be an important clinical challenge.

We previously reported the new technique to augment the amplitudes of myogenic MEPs, called "posttetanic MEPs (p-MEPs)," in which tetanic stimulation of peripheral nerves at 25–50 mA for 3–5 s is performed 1–2 s before transcranial stimulation.5 Since tetanic stimulation of peripheral nerves after the administration of a nondepolarizing neuromuscular blocking drug enhances subsequent muscle responses to electrical stimulation, known as posttetanic enhancement, the amplitudes of myogenic MEPs can be significantly enlarged when target muscles are enhanced by tetanic stimulation in advance. Using this technique, MEPs could be reliably recorded even at a deeper level of neuromuscular blockade, in which percentage of twitch height (%T1) of control is 5%, compared with that in the previous studies (%T1 of 45%–55%). In the present study, we hypothesized that we might be able to perform MEPs monitoring without patient movement in response to transcranial stimulation, if p-MEPs were used under the deep level of neuromuscular blockade. The current study was therefore conducted to determine an appropriate level of neuromuscular blockade during monitoring p-MEPs with a focus on patient movement in response to transcranial stimulation. Amplitudes of p-MEPs and success rate of p-MEP recordings were compared with those of conventional MEPs (c-MEP) without tetanic stimulation.

	METHODS

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After institutional approval at Nara Medical University, Nara, Japan, written informed consent was obtained from each patient. Fifteen patients (female 4, male 11; mean age 59 yr) without preoperative motor dysfunction undergoing elective spinal surgery were enrolled in the studies. Diseases in these patients included cervical spondylosis (n = 4), cervical hernia (n = 3), lumbar spinal stenosis (n = 4), and others (n = 4). Anesthesia was standardized in all patients. Anesthesia was induced with propofol, 1–2 µg/kg fentanyl, and 0.1 mg/kg vecuronium and was maintained with 40% oxygen, propofol (2.3–3.0 µg/mL of target-controlled infusion), and fentanyl (total doses of 0.3–0.5 mg). After the trachea was intubated, the lungs were ventilated mechanically to maintain the level of partial pressure of arterial carbon dioxide between 35 and 40 mm Hg. The rectal temperature was maintained between 35.5 and 37.0°C. Physiologic monitoring included electrocardiography, intraarterial pressure, oxygen saturation measurement by pulse oximetry, end-tidal carbon dioxide concentration, and rectal temperature.

Monitoring of Neuromuscular Blockade
The level of neuromuscular blockade was assessed by recording the amplitude of compound muscle action potentials, defined as T1, from the abductor hallucis brevis muscle (APB) in response to supramaximal electrical stimulation of the median nerve at the wrist. To elicit the muscle response, a square wave pulse of 0.2 ms in duration was administered through a pair of adhesive gel Ag/AgCl electrodes. The level of neuromuscular blockade was described as T1 (mV) and percentage of T1 (%T1, %) of control value without neuromuscular blockade.

c-MEP and p-MEP Measurements
For recording c-MEPs, transcranial electrical stimulation was performed by using a multipulse stimulator (D-185; Digitimer, Welwyn Garden City, United Kingdom). Stimulation was performed by train-of-five pulses with an interstimulus interval of 2 ms. The outputs were delivered to the scalp by a single pair of 14.5-mm silver disk electrodes applied to C3 (cathode) and C4 (anode) (International 10–20 System). The stimulus intensity of transcranial stimulation was determined at the beginning of MEPs monitoring and was set just supramaximal to each stimulus. The compound muscle action potentials were recorded from the skin over the abductor hallucis muscle (AH). A ground electrode was placed on the left or right arm proximal to the elbow. Evoked myographic responses were amplified with a 0.3- to 3-kHz band-pass filter and were displayed on oscilloscopes (Neuropack, Nihon Koden, Tokyo, Japan). For recording p-MEPs, the same stimulation and recording setups as mentioned above were used except for the application of tetanic stimulation before transcranial stimulation. Tetanic stimulation to the posterior tibial nerve at the ankle with an intensity of 50 mA for 5 s was started 6 s before transcranial electrical stimulation (interstimulus interval of 1 s). The compound muscle action potentials were recorded from the skin over the AH at the side ipsilateral to tetanic stimulation. These MEPs recordings were performed before any surgical interventions that might have resulted in impaired spinal cord functioning.

Study Protocol
When %T1 was recovered to 50% of baseline after induction of anesthesia, 0.1 mg/kg of vecuronium was injected and T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the degree of patient movement was recorded every 5 min. p-MEPs were recorded 15 s after recording of c-MEPs. The data of our preliminary studies indicated that there were no residual effects (augmentation and fatigue) 5 min after p-MEPs. For the assessments of T1 and MEPs amplitudes, peak-to-peak amplitudes of compound muscle action potentials were used. Patient movement was evaluated by a single blinded neurosurgeon (H.N.) using the movement score (1 = no movement, 2 = mild movement—microscopic surgery is possible, 3 = moderate movement—microscopic surgery is impossible, but macrosurgery is possible, 4 = severe movement—any surgery is impossible). The recording was completed when %T1 was recovered to 50% again.

Statistical Analysis
Data of T1, %T1, and MEPs amplitude were expressed as mean ± sd. Movement scores were shown as median with interquartile range in box plots. Differences in amplitudes between c-MEP and p-MEP were analyzed using the Wilcoxon's signed rank test. P values <0.05 were considered significant.

	RESULTS

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Changes in T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score after the administration of vecuronium are shown in Figure 1. T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs before and 15–45 min after the administration of vecuronium were significantly higher than those of c-MEPs (Fig. 1). Figure 2 shows the associations among T1 or %T1, the amplitudes of MEPs and the movement score. When T1 and %T1 were less than and equal to 1 mV and 10%, respectively, movement score was 1 or 2 in all patients and microscopic surgery was possible without the interruption of surgical procedures. The median (mean) amplitudes of c-MEPs and p-MEPs were 65 µV (172 µV) and 327 µV (477 µV), respectively, when T1 was around 1 mV (0.8–1.2 mV). At around 1 mV of T1, amplitudes of p-MEPs were significantly higher than those of c-MEPs. The success rates of recording of c-MEPs and p-MEPs when T1 was around 1 mV (0.8–1.2 mV) were 73% (11 of 15) and 100% (15 of 15), respectively.

View larger version (20K): [in this window] [in a new window]   Figure 1. Changes in T1 (a), %T1 (b), the amplitudes of conventional (closed circle) and posttetanic (open circle) motor evoked potentials (c-MEPs and p-MEPs, respectively) (c), and the movement score (d) after the injection of 0.1 mg/kg vecuronium. T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs were significantly higher than those of c-MEPs at all time points except for 5, 10 min after injection. Patient movement was evaluated by a single blinded neurosurgeon using the movement score (1 = no movement, 2 = mild movement—microscopic surgery is possible, 3 = moderate movement—microscopic surgery is impossible, but macrosurgery is possible, 4 = severe movement—any surgery is impossible). In a, b, and c, data were expressed as mean ± sd. Box plots (bars; median, box; 25–75 percentile, closed circle; 10–90 percentile) were shown in d. *P < 0.05 versus c-MEPs.

View larger version (19K): [in this window] [in a new window]   Figure 2. The associations among T1, %T1, the amplitudes of motor-evoked potentials (MEPs) and the movement score were shown. Open circle and gray circle indicate movement score 1–2 and 3–4, respectively. Note that when T1 and %T1 were less than and equal to 1 mV and 10%, respectively, the movement scores were 1 or 2 in all patients, indicating that microscopic surgery was possible without the interruption of surgical procedures.

	DISCUSSION

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
The results of the present study show that the level of neuromuscular blockade can affect the amplitudes of c-MEPs and p-MEPs and the degree of patient movement in response to transcranial stimulation and the amplitudes of p-MEPs were significantly augmented compared with those of c-MEPs. In patients without preoperative motor dysfunction under propofol/ fentanyl anesthesia, p-MEPs could be recorded at a T1 of 1 mV or %T1 of 10%, in which patient movement in response to transcranial stimulation did not interfere with surgery.

Because complete neuromuscular blockade abolishes myogenic MEPs, the concept of partial neuromuscular blockade was advocated for anesthetic management during the monitoring of MEPs, but the ideal level of neuromuscular blockade for MEPs monitoring is still controversial. Kalkman et al.6 recommended the neuromuscular level of one or two responses to train-of-four stimulation because MEPs were recordable to a satisfactory extent at this level. van Dongen et al.4 suggested that a stable neuromuscular blockade aimed at 45%–55% of baseline can provide reliable and recordable muscle responses during intraoperative myogenic MEPs. Sekimoto et al.7 used the level of 40%–50% of one twitch of train-of-four for monitoring of MEPs during propofol/ fentanyl/nitrous oxide anesthesia.

However, these levels of neuromuscular blockade may elicit patient movement in response to transcranial stimulation. In fact, operative procedures have to be paused when transcranial stimulation is performed. MEPs recording cannot be performed during surgery where movement impairs the safety and ability of the surgeon to operate. This process may reduce the quality of MEPs monitoring as well as operative procedures. Based on the results in the present study, the median movement score was 3 with 45%–55% of %T1, indicating that microscopic surgery was impossible at this level of neuromuscular blockade. To attenuate patient movement in response to transcranial stimulation, we had to control the neuromuscular blocking level to approximately 1 mV of T1 or 10% of %T1. With this level of neuromuscular blockade, success rates of c-MEPs and p-MEPs were 73% and 100%, respectively, and median amplitudes of c-MEPs and p-MEPs were 65 and 327 µV, respectively. It means that monitoring of c-MEPs with this level of neuromuscular blockade is not reliable, but p-MEPs can be recorded to a satisfactory extent. Therefore, p-MEPs may enable MEP monitoring to be free from movements of patients in response to transcranial stimulation.

The results of the present study showed that the levels of neuromuscular blockade were similar between 1 mV of T1 and 10% of %T1 for the monitoring of MEPs. To calculate %T1, control T1 had to be recorded before the administration of neuromuscular blockade. However, it may be troublesome to record T1 before or during induction of anesthesia. Without the need to record a control T1, duration for anesthesia and monitoring preparation may be shortened. Therefore, we believe that T1 may be advantageous as the marker of the level of neuromuscular blockade during MEPs monitoring, compared with %T1.

There are several limitations in this study. First, the participants in this study had no preoperative motor deficit. It is therefore unclear whether the level of 1 mV of T1 is applicable to patients with preoperative motor deficits. In such patients, higher T1 may be required to record p-MEPs. Second, propofol/fentanyl anesthesia was used in this study, because these anesthetics have less suppressive effects on MEPs. However, recent evidence indicated that MEPs monitoring might be feasible under sevoflurane anesthesia.8 If sevoflurane were used during the study period, the degree of patient movement might be different from that under propofol/fentanyl anesthesia. Third, in the present study, the level of neuromuscular blockade was assessed using the amplitude of compound muscle action potentials from the APB and not from the AH, because this is the standard technique during the monitoring of MEPs in our institute. Moreover, our previous data showed no significant differences between the levels of neuromuscular blockade assessed from the APB and AH. We therefore believe that there is little influence from the monitoring sites for neuromuscular blockade. Finally, patient movement was evaluated using the movement score. This was accomplished qualitatively by a single blinded surgeon. However, more sophisticated methodologies to assess patient movement may be required. Further studies may be required.

In summary, we investigated the effects of neuromuscular blockade levels on the amplitudes of c-MEPs and p-MEPs and the degree of patient movement under propofol/fentanyl anesthesia. The results indicated that, in patients without preoperative motor dysfunction under propofol/fentanyl anesthesia, p-MEPs could be recorded at a T1 of 1 mV or %T1 of 10% with no or mild patient movement in response to transcranial stimulation. If patient movement in response to transcranial stimulation would be avoided, a surgical procedure can continue without an interruption for MEPs monitoring. These strategies may be considered as one of alternatives to improve the quality both of surgery and monitoring.

	Footnotes

 
Accepted for publication November 1, 2007.

	REFERENCES

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1. Kawaguchi M, Furuya H. Intraoperative spinal cord monitoring of motor function with myogenic motor-evoked potentials: a consideration in anesthesia. J Anesth 2004;18:18–28[Medline]
2. Sloan TB, Heyer EJ. Anesthesia for intraoperative neurophysiologic monitoring of the spinal cord. J Clin Neurophysiol 2002; 19:430–43[Web of Science][Medline]
3. Lotto ML, Banoub M, Schubert A. Effects of anesthetic agents and physiologic changes on intraoperative motor evoked potentials. J Neurosurg Anesthesiol 2004;16:32–42[Web of Science][Medline]
4. van Dongen EP, ter Beek HT, Schepens MA, Morshuis WJ, Langemeijer HJ, de Boer A, Boezeman EH. Within-patient variability of myogenic motor-evoked potentials to multipulse transcranial electrical stimulation during two levels of partial neuromuscular blockade in aortic surgery. Anesth Analg 1999;88:22–7[Abstract/Free Full Text]
5. Kakimoto M, Kawaguchi M, Yamamoto Y, Inoue S, Horiuchi T, Nakase H, Sakaki T, Furuya H. Tetanic stimulation of the peripheral nerve before transcranial electrical stimulation can enlarge amplitudes of myogenic motor evoked potentials during general anesthesia with neuromuscular blockade: Anesthesiology 2005;102:733–8[Web of Science][Medline]
6. Kalkman CJ, Drummond JC, Kennelly NA, Patel PM, Partridge BL. Intraoperative monitoring of tibialis anterior muscle motor evoked responses to transcranial electrical stimulation during partial neuromuscular blockade. Anesth Analg 1992;75:584–9[Abstract/Free Full Text]
7. Sekimoto K, Nishikawa K, Ishizeki J, Kubo K, Saito S, Goto F. The effects of volatile anesthetics on intraoperative monitoring of myogenic motor-evoked potentials to transcranial electrical stimulation and on partial neuromuscular blockade during propofol/fentanyl/nitrous oxide anesthesia in humans. J Neurosurg Anesthesiol 2006;18:106–11[Web of Science][Medline]
8. Reinacher PC, Priebe HJ, Blumrich W, Zentner J, Scheufler KM. The effects of stimulation pattern and sevoflurane concentration on intraoperative motor-evoked potentials. Anesth Analg 2006; 102:888–95[Abstract/Free Full Text]

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