CJA
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Inoue, S.
Right arrow Articles by Sakaki, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Inoue, S.
Right arrow Articles by Sakaki, T.
Canadian Journal of Anesthesia 50:86-91 (2003)
© Canadian Anesthesiologists' Society, 2003
Neuroanesthesia and Intensive Care

Noxious stimuli do not modify myogenic motor evoked potentials by electrical stimulation during anesthesia with propofol-based anesthesia

[Des stimuli douloureux ne modifient pas les potentiels évoqués myogènes moteurs obtenus par stimulation électrique pendant l’anesthésie à base de propofol]

Satoki Inoue, MD*, Masahiko Kawaguchi, MD*, Masahiro Takahashi, MD*, Meiko Kakimoto, MD*, Takanori Sakamoto, MD*, Katsuyasu Kitaguchi, MD*, Hitoshi Furuya, MD*, Tetsuya Morimoto, MD{dagger} and Toshisuke Sakaki, MD{dagger}

* From the Department of Anesthesiology and
{dagger} Neurosurgery Nara Medical University Japan

Address correspondence to: Dr. Satoki Inoue, Department of Anesthesiology, Neuroanesthesia Research, VA Medical Center, UCSD, 3350 La Jolla Village Drive, San Diego, California 92161, USA. Phone: 858-552-8585, ext. 7086; Fax: 858-534-0104; E-mail: sinoue{at}vapop.ucsd.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Purpose: To investigate whether motor evoked potentials (MEP) to transcranial electrical stimulation under constant blood propofol concentration are affected by the arousing effect of surgical noxious stimuli.

Methods: Twenty patients who underwent elective spinal surgery were studied. Patients were anesthetized with 50% nitrous oxide in oxygen, fentanyl, and propofol to maintain the bispectral index (BIS) score around 50. MEP in response to a multipulse transcranial electrical stimulation at stimulus sites of C3–C4 were recorded over the right abductor pollicis brevis muscle. Changes of peak-to-peak amplitude and onset latency of MEP, BIS score before and after surgical stimuli were evaluated. Propofol plasma concentration was measured at the same time points.

Results: Both MEP amplitude and latency did not change significantly after surgical stimuli although BIS increased significantly (48 ± 6 to 58 ± 5; P < 0.05). Plasma propofol concentration was maintained at the same level between the two measurement points (3.3 ± 0.7 to 3.3 ± 0.7 µg•mL-1). There was no relation between BIS change and changes of MEP amplitude and latency, and propofol plasma concentration.

Conclusion: MEP to the transcranial electrical stimulation under a constant and clinically appropriate blood propofol concentration are not affected by surgical noxious stimuli.


   Introduction
TOP
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
THE inhibition of myogenic motor evoked potentials (MEP) observed with most anesthetic agents limits the ability to titrate anesthetic levels and achieve an adequate depth of anesthesia during intraoperative MEP monitoring.1–10 Therefore, anesthetic concentrations are generally not modified when MEP monitoring is used. In addition, these anesthetics are usually used at relatively low doses, and patients undergoing intraoperative MEP monitoring often demonstrate symptoms of light anesthesia in response to noxious stimuli during surgery.1–10 Ideally, anesthesia for intraoperative MEP monitoring should not inhibit MEP monitoring and, simultaneously, should provide adequate anesthesia in response to surgical stimuli.

Multiple investigators have documented the usefulness of computer processed electroencephalography (EEG), such as the bispectral index (BIS), to quantify assessment of anesthetic depth.11–13 In general, anesthetic depth is affected by noxious stimuli. BIS appears to be sensitive to the changes in anesthetic depth produced by noxious stimuli, including surgery.11–13 Furthermore, it is conceivable that noxious stimuli might also increase evoked potential signals, including MEP. If the arousing effect of surgical noxious stimuli affects MEP even under constant anesthetic concentration, the modification of monitoring results might lead to a misestimation of motor function. Simultaneously, adjustment of the anesthetic regimen would be required to provide adequate anesthesia against noxious stimuli. The present study was conducted to investigate whether MEP to transcranial electrical stimulation under constant blood propofol concentration are affected by the arousing effect of surgical noxious stimuli using BIS as an assessment of anesthetic depth.


   Materials and methods
TOP
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
After Institutional approval and informed consent, 20 patients (nine men and 11 women), classified as ASA physical status I or II and scheduled to undergo elective cervical or lumbar spinal surgery, were enrolled.

All patients were premedicated with roxatidine (H2 blocker) 75 mg orally two hours preoperatively. Anesthesia was induced with propofol 1.5–2.5 mg•kg-1, fentanyl 7–8 µg•kg-1 and vecuronium 0.1 mg•kg-1 and maintained with 50% nitrous oxide in oxygen, propofol 3–6 mg•kg-1•hr-1 and fentanyl 4–5 µg•kg-1•hr-1. After the trachea was intubated, the lungs were ventilated mechanically to maintain PaCO2 between 35–40 mmHg. Systolic blood pressure was maintained at 100–130 mmHg. When hypotension or hypertension was observed, a bolus of ephedrine or nicardipine was administered.

Muscle relaxation was monitored and controlled by the following. Compound muscle action potentials from the right abductor pollicis brevis muscle (APB) in response to supramaximal electrical stimulation (constant-current square wave pulses of 0.2 msec duration) of the median nerve at the wrist were recorded as a means of assessing the degree of neuromuscular blockade. This response is known in the neurophysiologic literature as the muscle (M) response.14 The control value was defined as that at admission to the operating room without the effect of vecuronium. The level of M-response was maintained at 40–50% of control with a continuous infusion of vecuronium. Other monitoring included the electrocardiogram, intraarterial pressure, oxygen saturation by pulse oxymetry, end-tidal CO2 concentration, and rectal temperature.

Transcranial stimulation was performed using a multipulse device (D-185; Digitimer, Welwyn, Garden City, UK). A train-of-five pulses with an interstimulus interval of 2 msec were used as in our previous study.7 The outputs were delivered to the scalp by a single pair of 14.5 mm silver disc electrodes, applied to C3 (anode) and C4 (cathode); (international 10–20 system). Five consecutive stimulations at C3 and C4 were made. The stimulus intensity was set at 700 V.

MEP were recorded from the right APB (the same site as for recording of M-response). Evoked myographic responses were amplified with a 0.3–3 kHz band pass filter and displayed on oscilloscopes (MEB-5508; Nihon Koden, Tokyo, Japan). Experimental MEP study was performed after the induction of anesthesia and before the start of surgery. Peak-to-peak amplitudes and onset latencies were monitored. The mean amplitude and latency were calculated from five consecutive responses to stimulation using a pair of C3–C4 disc electrodes.

The EEG signal was recorded using the Aspect A-1000 EEG monitor (Aspect Medical System, Natick, MA, USA). Silver-silver chloride EEG pads (Zipprep; Aspect Medical Systems) were attached to patient’s forehead according to a standard montage.15 The low - and high - frequency filters were set to 0.25 Hz and 30 Hz, respectively. By ten minutes before the start of surgery, the propofol infusion rate was adjusted to maintain stable BIS score around 50. The propofol infusion rate was not changed thereafter.

To investigate whether MEP to transcranial electrical stimulation under constant blood propofol concentration are affected by arousing effect of surgical noxious stimuli, MEP were collected two minutes before and after the start of surgery. In most cases, approximately 60 min had passed after induction of anesthesia when the first MEP collections were conducted. The start of surgery in this study was defined when the initial surgical incision was made. No interventions were made to standardize the degree of stimulation by surgeons because surgical sites were different among patients. At same time points, BIS score, mean arterial pressure (MAP), and heart rate (HR) were recorded and blood samples were collected to confirm that propofol plasma concentration remained constant. Five millilitres of blood were drawn into a heparinized syringe, collected into a glass tube, centrifuged for ten minutes at 3000 rpm, and 2.0 mL of plasma were stored at -20°C for propofol analysis. Plasma concentrations of propofol were determined by high-performance liquid chromatography.

Statistical analysis
Because MEP amplitude-related data did not appear to be distributed normally, they are presented as median, and tenth, 25th, median, 75th, and 90th percentiles. MEP latency-related data are expressed as mean ± SD. A paired t test to compare physiologic variables, BIS score, propofol concentration, and latency of MEP between the two time points, Wilcoxon signed-ranks test was used to compare amplitudes of MEP. The relationships between BIS and MEP amplitude and latency, and propofol concentration before and after the start of surgery were evaluated by Pearson’s correlation. Because these values varied with individual patients, especially MEP amplitude and BIS score, the relationships were also analyzed using percent change of these values. Any change of MEP amplitude of more than 50% was defined as a significant modification according to Zhou et al.16 because within- patient variability of MEP, which may lead to a misinterpretation of the MEP, is generally observed.17,18 Results were considered significant at P < 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Preoperative motor function was normal in all patients. Their age was 57 ± 19 yr, height 159 ± 9 cm, and weight 55 ± 10 kg (mean ± SD). Disease in the patients included lumbar disc hernia (n = 9), cervical disc hernia (n = 5), ossification of the posterior spinal ligament (n = 3), compression fracture of the lumbar vertebral body (n = 2), and spinal cord tumour (n = 1).

MEP were recorded successfully in all but one patient. MEP peak-to-peak amplitude did not change significantly after the start of surgery (Figure 1Go) although BIS score did increase significantly (48 ± 6 to 58 ± 5; P < 0.05). MEP latency did not change (20.9 ± 1.8 to 20.9 ± 1.9 sec). Plasma propofol concentration was constant (3.3 ± 0.7 to 3.3 ± 0.7 µg•mL-1). Absolute and percent changes in BIS were not related to changes in MEP latency or amplitude or propofol concentration (Figures 2 and 3GoGo). MAP and HR did not change significantly (78 ± 9 to 81 ± 11 mmHg and 63 ± 10 to 67 ± 14 beats•min-1, respectively). No patient showed a significant positive change of MEP amplitude.



View larger version (13K):
[in this window]
[in a new window]
  		FIGURE 1 Amplitude of motor evoked potentials (MEP) from the right abductor pollicis brevis muscle to transcranial electrical stimulation at stimulus sites of C3–C4 before and after the start of surgery.

Horizontal bars represent the tenth, 25th, median, 75th, and 90th percentiles. One participant was excluded from the analysis because MEP were not elicited (n = 19). Before: two minutes before the start of surgery; after: two minutes after the start of surgery.

 


View larger version (14K):
[in this window]
[in a new window]
  		FIGURE 2 Relationships between changes in bispectral index score (BIS) and that of motor evoked potentials (MEP) amplitude and latency, and propofol plasma concentration before and after the start of surgery (n = 19).

 


View larger version (14K):
[in this window]
[in a new window]
  		FIGURE 3 Relationships between percent change of bispectral index score (BIS) and that of motor evoked potentials (MEP) amplitude and latency, and propofol plasma concentration before and after the start of surgery (n = 19).

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
These results show that noxious stimuli strong enough to change BIS values do not affect MEP to five-pulse transcranial electrical stimulation with a constant plasma propofol concentration. Therefore, we can conclude that MEP can be obtained consistently regardless of anesthetic depth (as evaluated by BIS) if the anesthetic regimen is not changed.

Although a number of authors have reported the effects of anesthetics on MEP induced by motor cortex stimulation, the effect of noxious surgical stimuli on intraoperative MEP monitoring remains unclear. The most plausible explanation for our results is that the effect of an anesthetic on the spinal cord is independent of its supraspinal effects.19–24 It is likely that synaptic transmission is the primary site at which anesthetics suppress MEP, specifically at the level of the spinal interneuronal or motoneuronal systems.4 These spinal systems and their evoked potentials do not appear to be affected by the change in anesthetic depth at the supraspinal level. Otherwise, MEP amplification by surgical stimuli might be masked by five-pulse transcranial electrical stimulation, which is an effective way of achieving discharge in a large set of spinal motoneurons. In other words, the amplification by surgical stimuli is only allowed to go so far; however, our study design did not allow the physiology of this response to be determined.

There are several limitations to the study protocol that must be discussed. The effects of different propofol concentrations or BIS scores on our results could be important. In light of ethical concerns, we wanted to avoid higher BIS scores using lower propofol doses. It has been reported that a BIS of 40–55 is usually required during general anesthesia. We targeted a BIS of approximately 50 for this study, which required a plasma propofol concentration of over 3 µg•mL-1.11–13 This is recognized as a clinically appropriate concentration and probably higher than those used in other MEP studies.25 Using a clinically appropriate propofol-based anesthetic, may, possibly, have limited our ability to test our study hypothesis. However, the surgical stimuli appeared to be sufficient to change anesthetic depth even under clinically appropriate propofol-based anesthesia.

The question may also be raised as to whether the anesthetic depth truly changed after the noxious stimuli. The significance of an increase in mean BIS from 48–58 is unclear. The absence of an increase in MAP or HR despite an increase in BIS raises questions about the clinical significance of the BIS increase. Yet, we believe the increase in BIS indicated a change in anesthetic depth, as BIS scores have been reported to be clinically reliable in this assessment.11–13 Furthermore, BIS increases in response to noxious stimuli prior to or in the absence of hemodynamic or motor reactivity as evidence of inadequate anesthesia in some patients.26

Our results support the use of MEP monitoring; however, the response to alterations in anesthetic depth following noxious stimuli remains unclear, creating a dilemma between the need to provide adequate anesthesia and the desire to consistently obtain MEP recordings. It is true that the use of agents that depress MEP or modifications to their concentration in response to noxious stimuli should be avoided. As our results showed, it is also true that anesthetic depth is changed by noxious stimuli during MEP monitoring. Over this decade, methods of intraoperative MEP monitoring have developed greatly, but we should strive to improve the quality of anesthesia during intraoperative MEP monitoring.

In conclusion, we have demonstrated that MEP to transcranial electrical stimulation under a constant and clinically appropriate propofol blood concentration are not affected by surgical noxious stimuli.


   Acknowledgments
 
The authors thank Dr. Daniel P. Davis (Assistant Professor of the Department of Emergency Medicine, University of California, San Diego, USA) for his editorial assistance.


   Footnotes
 
Financial support: this work was supported by Grant-in Aid for Scientific Research C2-10671439, Ministry of Education, Tokyo, Japan.

Revision received October 17, 2002. Accepted for publication June 11, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 Kalkman CJ, Drummond JC, Ribberink AA, Patel PM, Sano T, Bickford RG. Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans. Anesthesiology 1992; 76: 502–9.[Medline]

2 Kalkman CJ, Drummond JC, Ribberink AA. Low concentrations of isoflurane abolish motor evoked responses to transcranial electrical stimulation during nitrous oxide/opioid anesthesia in humans. Anesth Analg 1991; 73: 410–5.[Abstract/Free Full Text]

3 Kawaguchi M, Inoue S, Kakimoto M, et al. The effect of sevoflurane on myogenic motor-evoked potentials induced by single and paired transcranial electrical stimulation of the motor cortex during nitrous oxide/ketamine/fentanyl anesthesia. J Neurosurg Anesthesiol 1998; 10: 131–6.[Medline]

4 Zentner J, Albrecht T, Heuser D. Influence of halothane, enflurane, and isoflurane on motor evoked potentials. Neurosurgery 1992; 31: 298–305.[Medline]

5 van Dongen EP, ter Beek HT, Aarts LP, et al. The effect of two low-dose propofol infusions on the relationship between six-pulse transcranial electrical stimulation and the evoked lower extremity muscle response. Acta Anaesthesiol Scand 2000; 44: 799–803.[Medline]

6 van Dongen EP, ter Beek HT, Schepens MA, et al. The influence of nitrous oxide to supplement fentanyl/low-dose propofol anesthesia on transcranial myogenic motor-evoked potentials during thoracic aortic surgery. J Cardiothorac Vasc Anesth 1999; 13: 30–4.

7 Kawaguchi M, Sakamoto T, Inoue S, et al. Low dose propofol as a supplement to ketamine-based anesthesia during intraoperative monitoring of motor-evoked potentials. Spine 2000; 25: 974–9.[Medline]

8 Ubags LH, Kalkman CJ, Been HD, Porsius M, Drummond JC. The use of ketamine or etomidate to supplement sufentanil/N2O anesthesia does not disrupt monitoring of myogenic transcranial motor evoked responses. J Neurosurg Anesthesiol 1997; 9: 228–33.[Medline]

9 Thees C, Scheufler KM, Nadstawek J, et al. Influence of fentanyl, alfentanil, and sufentanil on motor evoked potentials. J Neurosurg Anesthesiol 1999; 11: 112–8.[Medline]

10 Zentner J, Thees C, Pechstein U, Scheufler KM, Wurker J, Nadstawek J. Influence of nitrous oxide on motor-evoked potentials. Spine 1997; 22: 1002–6.[Medline]

11 Vernon JM, Lang E, Sebel PS, Manberg P. Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia. Anesth Analg 1995; 80: 780–5.[Abstract]

12 Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg 1997; 84: 891–9.[Abstract]

13 Struys MM, De Smet T, Versichelen LF, Van de Velde S, Van den Broecke R, Mortier EP. Comparison of closed-loop controlled administration of propofol using bispectral index as the controlled variable versus "standard practice" controlled administration. Anesthesiology 2001; 95: 6–17.[Medline]

14 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]

15 Rampil IJ, Holzer JA, Quest DO, Rosenbaum SH, Correll JW. Prognostic value of computerized EEG analysis during carotid endarterectomy. Anesth Analg 1983; 62: 186–92.[Abstract/Free Full Text]

16 Zhou HH, Kelly PJ. Transcranial electrical motor evoked potential monitoring for brain tumor resection. Neurosurgery 2001; 48: 1075–81.[Medline]

17 van Dongen EP, ter Beek HT, Schepens MA, et al. Within patient variability of lower extremity muscle responses to transcranial electrical stimulation with pulse trains in aortic surgery. Clin Neurophysiol 1999; 110: 1144–8.[Medline]

18 Woodforth IJ, Hicks RG, Crawford MR, Stephen JP, Burke DJ. Variability of motor-evoked potentials recorded during nitrous oxide anesthesia from the tibialis anterior muscle after transcranial electrical stimulation. Anesth Analg 1996; 82: 744–9.[Abstract]

19 Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 1993; 79: 1244–9.[Medline]

20 Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993; 78: 707–12.[Medline]

21 Antognini JF, Carstens E, Tabo E, Buzin V. Effect of differential delivery of isoflurane to head and torso on lumbar dorsal horn activity. Anesthesiology 1998; 88: 1055–61.[Medline]

22 Antognini JF, Wang XW, Piercy M, Carstens E. Propofol directly depresses lumbar dorsal horn neuronal responses to noxious stimulation in goats. Can J Anesth 2000; 47: 273–9.[Abstract/Free Full Text]

23 Zhou HH, Jin TT, Qin B, Turndorf H. Suppression of spinal cord motoneuron excitability correlates with surgical immobility during isoflurane anesthesia. Anesthesiology 1998; 88: 955–61.[Medline]

24 Antognini JF, Carstens E, Buzin V. Isoflurane depresses motoneuron excitability by a direct spinal action: an F-wave study. Anesth Analg 1999; 88: 681–5.[Abstract/Free Full Text]

25 Casati A, Fanelli G, Casaletti E, et al. Clinical assessment of target-controlled infusion of propofol during monitored anesthesia care. Can J Anesth 1999; 46: 235–9.[Abstract/Free Full Text]

26 Luginbuhl M, Schnider TW. Detection of awareness with the bispectral index: two case reports. Anesthesiology 2002; 96: 241–3.[Medline]




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
N. Nathan, F. Tabaraud, F. Lacroix, D. Moulies, X. Viviand, A. Lansade, G. Terrier, and P. Feiss
Influence of propofol concentrations on multipulse transcranial motor evoked potentials
Br. J. Anaesth., October 1, 2003; 91(4): 493 - 497.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Inoue, S.
Right arrow Articles by Sakaki, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Inoue, S.
Right arrow Articles by Sakaki, T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS