Impact of total propofol dose during spinal surgery: anesthetic fade on transcranial motor evoked potentials

Restricted access


Intraoperative neuromonitoring may be valuable for predicting postoperative neurological complications, and transcranial motor evoked potentials (TcMEPs) are the most reliable monitoring modality with high sensitivity. One of the most frequent problems of TcMEP monitoring is the high rate of false-positive alerts, also called “anesthetic fade.” The purpose of this study was to clarify the risk factors for false-positive TcMEP alerts and to find ways to reduce false-positive rates.


The authors analyzed 703 patients who underwent TcMEP monitoring under total intravenous anesthesia during spinal surgery within a 7-year interval. They defined an alert point as final TcMEP amplitudes ≤ 30% of the baseline. Variations in body temperature (maximum − minimum body temperature during surgery) were measured. Patients with false-positive alerts were classified into 2 groups: a global group with alerts observed in 2 or more muscles of the upper and lower extremities, and a focal group with alerts observed in 1 muscle.


False-positive alerts occurred in 100 cases (14%), comprising 60 cases with global and 40 cases with focal alerts. Compared with the 545 true-negative cases, in the false-positive cases the patients had received a significantly higher total propofol dose (1915 mg vs 1380 mg; p < 0.001). In the false-positive cases with global alerts, the patients had also received a higher mean propofol dose than those with focal alerts (4.5 mg/kg/hr vs 4.2 mg/kg/hr; p = 0.087). The cutoff value of the total propofol dose for predicting false-positive alerts, with the best sensitivity and specificity, was 1550 mg. Multivariate logistic analysis revealed that a total propofol dose > 1550 mg (OR 4.583; 95% CI 2.785–7.539; p < 0.001), variation in body temperature (1°C difference; OR 1.691; 95% CI 1.060–2.465; p < 0.01), and estimated blood loss (500-ml difference; OR 1.309; 95% CI 1.155–1.484; p < 0.001) were independently associated with false-positive alerts.


Intraoperative total propofol dose > 1550 mg, larger variation in body temperature, and greater blood loss are independently associated with false-positive alerts during spinal surgery. The authors believe that these factors may contribute to the false-positive global alerts that characterize anesthetic fade. As it is necessary to consider multiple confounding factors to distinguish false-positive alerts from true-positive alerts, including variation in body temperature or ischemic condition, the authors argue the importance of a team approach that includes surgeons, anesthesiologists, and medical engineers.

ABBREVIATIONS ASA = American Society of Anesthesiologists; AUC = area under the ROC curve; BIS = bispectral index; BMI = body mass index; EBL = estimated blood loss; IONM = intraoperative neuromonitoring; ROC = receiver operating characteristic; SBP = systolic blood pressure; TcMEP = transcranial motor evoked potential.

Article Information

Correspondence Hiroki Ushirozako: Hamamatsu University School of Medicine, Shizuoka, Japan.

INCLUDE WHEN CITING Published online February 8, 2019; DOI: 10.3171/2018.10.SPINE18322.

Disclosures Drs. Oe and Togawa belong to a donation-funded laboratory called the “Division of Geriatric Musculoskeletal Health.” Donations to this laboratory have come from Medtronic Sofamor Danek, Inc.; Japan Medical Dynamic Marketing, Inc.; and the Meitoku Medical Institution Jyuzen Memorial Hospital. Dr. Togawa reports an employee relationship with the Journal of Bone and Joint Surgery.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    A: Control and final TcMEP waveforms in the typical case with global alerts, showing that TcMEP amplitudes decreased to ≤ 30% of the baseline in the right abductor digiti minimi (ADM), bilateral quadriceps femoris (Quad), right hamstring (Ham), bilateral tibialis anterior (TA), and bilateral gastrocnemius (Gc) in the upper and lower extremities. B: Control and final TcMEP waveforms in the typical case with focal alerts, showing that TcMEP amplitudes decreased to ≤ 30% of the baseline in the right quadriceps in the lower extremities.

  • View in gallery

    Result of the TcMEP monitoring. FN = false negative; FP = false positive; TN = true negative; TP = true positive; RS = rescue cases.

  • View in gallery

    Total propofol dose for predicting false-positive TcMEP alerts using ROC curve analysis. The value of 1550 mg represents the cutoff point of the total propofol dose with the best sensitivity and specificity.



Antkowiak B: Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor. Anesthesiology 91:5005111999


Devlin VJAnderson PASchwartz DMVaughan R: Intraoperative neurophysiologic monitoring: focus on cervical myelopathy and related issues. Spine J 6 (6 Suppl):212S224S2006


Eggspuehler ASutter MAGrob DJeszenszky DDvorak J: Multimodal intraoperative monitoring during surgery of spinal deformities in 217 patients. Eur Spine J 16 (Suppl 2):S188S1962007


Fehlings MGBrodke DSNorvell DCDettori JR: The evidence for intraoperative neurophysiological monitoring in spine surgery: does it make a difference? Spine (Phila Pa 1976) 35 (9 Suppl):S37S462010


Inoue SKawaguchi MTakashi SKakimoto MSakamoto TKitaguchi K: Intraoperative monitoring of myogenic motor-evoked potentials from the external anal sphincter muscle to transcranial electrical stimulation. Spine (Phila Pa 1976) 27:E454E4592002


Jellinek DJewkes DSymon L: Noninvasive intraoperative monitoring of motor evoked potentials under propofol anesthesia: effects of spinal surgery on the amplitude and latency of motor evoked potentials. Neurosurgery 29:5515571991


Kakinohana MFuchigami TNakamura SKawabata TSugahara K: Propofol reduces spinal motor neuron excitability in humans. Anesth Analg 94:158615882002


Kim DHZaremski JKwon BJenis LWoodard EBode R: Risk factors for false positive transcranial motor evoked potential monitoring alerts during surgical treatment of cervical myelopathy. Spine (Phila Pa 1976) 32:304130462007


Kobayashi KImagama SIto ZAndo KHida TIto K: Transcranial motor evoked potential waveform changes in corrective fusion for adolescent idiopathic scoliosis. J Neurosurg Pediatr 19:1081152017


Kobayashi SMatsuyama YShinomiya KKawabata SAndo MKanchiku T: A new alarm point of transcranial electrical stimulation motor evoked potentials for intraoperative spinal cord monitoring: a prospective multicenter study from the Spinal Cord Monitoring Working Group of the Japanese Society for Spine Surgery and Related Research. J Neurosurg Spine 20:1021072014


Langeloo DDLelivelt ALouis Journée HSlappendel Rde Kleuver M: Transcranial electrical motor-evoked potential monitoring during surgery for spinal deformity: a study of 145 patients. Spine (Phila Pa 1976) 28:104310502003


Lieberman JALyon RFeiner JHu SSBerven SH: The efficacy of motor evoked potentials in fixed sagittal imbalance deformity correction surgery. Spine (Phila Pa 1976) 33:E414E4242008


Lyon RFeiner JLieberman JA: Progressive suppression of motor evoked potentials during general anesthesia: the phenomenon of “anesthetic fade.” J Neurosurg Anesthesiol 17:13192005


Macdonald DB: Intraoperative motor evoked potential monitoring: overview and update. J Clin Monit Comput 20:3473772006


Macdonald DB: Safety of intraoperative transcranial electrical stimulation motor evoked potential monitoring. J Clin Neurophysiol 19:4164292002


Macdonald DBSkinner SShils JYingling C: Intraoperative motor evoked potential monitoring—a position statement by the American Society of Neurophysiological Monitoring. Clin Neurophysiol 124:229123162013


Nagle KJEmerson RGAdams DCHeyer EJRoye DPSchwab FJ: Intraoperative monitoring of motor evoked potentials: a review of 116 cases. Neurology 47:99910041996


Nathan NTabaraud FLacroix FMouliès DViviand XLansade A: Influence of propofol concentrations on multipulse transcranial motor evoked potentials. Br J Anaesth 91:4934972003


Pankowski RRoclawski MDziegiel KCeynowa MMikulicz MMazurek T: Transient monoplegia as a result of unilateral femoral artery ischemia detected by multimodal intraoperative neuromonitoring in posterior scoliosis surgery: a case report. Medicine (Baltimore) 95:e27482016


Pechstein UNadstawek JZentner JSchramm J: Isoflurane plus nitrous oxide versus propofol for recording of motor evoked potentials after high frequency repetitive electrical stimulation. Electroencephalogr Clin Neurophysiol 108:1751811998


Pelosi LLamb JGrevitt MMehdian SMWebb JKBlumhardt LD: Combined monitoring of motor and somatosensory evoked potentials in orthopaedic spinal surgery. Clin Neurophysiol 113:108210912002


Rappaport MRuiz Portillo SOrtiz DFountain SSKula TA Jr: Effects of stimulus intensity and duration on posterior tibial nerve somatosensory-evoked potential patterns obtained under anesthesia. Spine (Phila Pa 1976) 19:152515291994


Richards CD: Actions of general anaesthetics on synaptic transmission in the CNS. Br J Anaesth 55:2012071983


Scheufler KMZentner J: Total intravenous anesthesia for intraoperative monitoring of the motor pathways: an integral view combining clinical and experimental data. J Neurosurg 96:5715792002


Shida YShida CHiratsuka NKaji KOgata J: High-frequency stimulation restored motor-evoked potentials to the baseline level in the upper extremities but not in the lower extremities under sevoflurane anesthesia in spine surgery. J Neurosurg Anesthesiol 24:1131202012


Sloan TB: Anesthetic effects on electrophysiologic recordings. J Clin Neurophysiol 15:2172261998


Sloan TBHeyer EJ: Anesthesia for intraoperative neurophysiologic monitoring of the spinal cord. J Clin Neurophysiol 19:4304432002


Sutter MAEggspuehler AGrob DPorchet FJeszenszky DDvorak J: Multimodal intraoperative monitoring (MIOM) during 409 lumbosacral surgical procedures in 409 patients. Eur Spine J 16 (Suppl 2):S221S2282007


Tamkus AARice KSKim HL: Differential rates of false-positive findings in transcranial electric motor evoked potential monitoring when using inhalational anesthesia versus total intravenous anesthesia during spine surgeries. Spine J 14:144014462014


Thirumala PDCrammond DJLoke YKCheng HLHuang JBalzer JR: Diagnostic accuracy of motor evoked potentials to detect neurological deficit during idiopathic scoliosis correction: a systematic review. J Neurosurg Spine 26:3743832017


Yoshida GAndo MImagama SKawabata SYamada KKanchiku T: Alert timing and corresponding intervention with intraoperative spinal cord monitoring for high risk spinal surgery. Spine (Phila Pa 1976) [epub ahead of print] 2018


Ziewacz JEBerven SHMummaneni VPTu THAkinbo OCLyon R: The design, development, and implementation of a checklist for intraoperative neuromonitoring changes. Neurosurg Focus 33(5):E112012




All Time Past Year Past 30 Days
Abstract Views 61 61 61
Full Text Views 34 34 34
PDF Downloads 21 21 21
EPUB Downloads 0 0 0


Google Scholar