CLINICAL INVESTIGATION
Comparison of the Effects of Propofol and Sevoflurane Combined With Remifentanil on Transcranial Electric Motor-evoked and Somatosensory-evoked Potential Monitoring During Brainstem Surgery Joaquı´n Herna´ndez-Palazo´n, MD, PhD,* Virginia Izura, MD, PhD,w Diego Fuentes-Garcı´a, MD, PhD,* Claudio Piqueras-Pe´rez, MD,z Paloma Dome´nech-Asensi, MD, PhD,* and Luis Falco´n-Aran˜a, MD, PhD*
Background: We compared the effect of propofol and sevoflurane combined with remifentanil under comparable bispectral index (BIS) levels on transcranial electric motor-evoked potentials (TceMEPs) and somatosensory-evoked potentials (SSEPs) during brainstem surgery. Materials and Methods: A total of 40 consecutive patients (20 per group) undergoing brainstem surgery were randomly assigned to 2 groups receiving either 0.5 MAC sevoflurane or propofol at an effect-site concentration of 2.5 mg/mL for maintenance of anesthesia. Remifentanil was administered to both groups at a rate of 0.25 to 0.35 mg/kg/min along with cisatracurium (0.03 to 0.04 mg/kg/h). TceMEP recordings were carried out in the abductor pollicis brevis, abductor hallucis, and tibialis anterior muscles, whereas cortical SSEPs were measured with posterior tibial nerve stimulation. Amplitudes and latencies of TceMEPs and SSEPs were recorded at 1, 2, 3, and 4 hours after the induction of anesthesia. Results: BIS values remained in the 45 to 60 range. Amplitudes of TceMEPs were significantly higher in the propofol group than those in the sevoflurane group (P < 0.05, at all study time points in abductor pollicis brevis and abductor hallucis muscles and only 4 h after anesthetic induction for tibialis anterior muscle), whereas latencies were shorter in the propofol group than those in the sevoflurane group (P < 0.05). No differences were observed in latency and amplitude while recording SSEPs between the 2 anesthetic techniques. None of the patients had TceMEPs and SSEPs amplitude or latency changes, exceeding our set limit. Conclusions: Both sevoflurane and propofol at low dosages combined with remifentanil under comparable BIS values and
Received for publication August 8, 2014; accepted December 1, 2014. From the Departments of *Anesthesia; wNeurophysiology; and zNeurosurgery, Hospital Clı´ nico “Virgen de la Arrixaca,” Murcia, Spain. The authors have no funding or conflicts of interest to disclose. Reprints: Diego Fuentes-Garcı´ a, MD, PhD, Ctra Madrid-Cartagena, s/n. 30120 El Palmar, Murcia, Spain (e-mail: smart10015@hotmail. com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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partial muscle relaxation can be used when monitoring of TceMEPs and SSEPs is required for brainstem surgery. Key Words: monitoring, transcranial electric motor-evoked potentials, somatosensory-evoked potentials, propofol, sevoflurane, surgery, brainstem (J Neurosurg Anesthesiol 2015;27:282–288)
I
ntraoperative neurophysiological monitoring has been established as one of the paths by which modern neurosurgery can improve surgical results while minimizing morbidity. This proceeding consists of the monitoring of functional integrity of the neural pathways and mapping of techniques for identification and preservation of the cranial nerves, their motor nuclei, and corticospinal or corticobulbar pathways during posterior-fossa and brainstem surgery.1 During these surgical procedures, small injuries can produce significant neurological deficits, and therefore global integrity of the brainstem must be monitored through the combination of diverse techniques of evoked potentials (multimodal intraoperative monitoring), such as brainstem auditory-evoked potentials (BAEPs), somatosensory-evoked potentials (SSEPs), transcranial electric motor-evoked potentials (TceMEPs), and free-run electromyography of the V, VI, VII, IX, X, XI, and XII cranial nerves. During monitoring of tumors in the lower brainstem and fourth ventricle, the multimodal intraoperative monitoring with TceMEPs, SSEPs, electromyography, and auditory brainstem responses assists in “mapping” to identify the least risky surgical approach, as the anatomic landmarks are inconstant.2 Similarly, this need for multimodal intraoperative monitoring also applies to surgery on the brain and brainstem where the motor and sensory pathways are anatomically separated and supplied by separate vascular sources. Anesthetic effects on BAEPs are not very profound, with small shifts in latency after changes in anesthetic drug level and without interferences in monitoring.3,4 Nevertheless, anesthetic effects on SSEPs and TceMEPs are more profound than changes in BAEPs, driving to an J Neurosurg Anesthesiol
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increase in latency and an amplitude decline in a dosedependent way, even though diverse authors found that intravenous anesthetic drugs induce a much lower decrease.5 Indeed, total intravenous anesthesia with propofol and opioids is commonly used for spinal surgery when SSEPs and TceMEPs are monitored. However, because in certain clinical settings there are greater hemodynamic changes with propofol, many anesthesiologists would prefer to use low dose of halogenated anesthetics (eg, 0.5 MAC).6,7 To the best of our knowledge, there are no direct comparative studies involving sevoflurane and propofol with remifentanil in the monitoring of both SSEPs and TceMEPs during the surgery of intraparenchymal and extraparenchymal brainstem lesions. The aim of this study was to compare the effect of propofol and sevoflurane on the amplitudes and latencies of TceMEPs and SSEPs, when these agents are used with remifentanil for the maintenance of anesthesia to achieve a comparable bispectral index (BIS) value during brainstem surgery.
MATERIALS AND METHODS Patients After approval by the IRB from Hospital Clı´ nico “Virgen de la Arrixaca,” 40 consecutive patients (18 to 68 years old) undergoing elective brainstem surgery were included in this study after obtaining informed consent. The intraparenchymal and extraparenchymal brainstem lesions were: vestibular neurinoma (23 patients), trigeminal neurinoma (4), meningioma of the foramen magnum (5), ependymoma of the fourth ventricle (1), brainstem epidermoid cyst (2), and petrous meningoma (5). Each patient was randomized to receive either sevoflurane or propofol during surgery (20 patients in each group). Patients with contraindications to cortical stimulation (seizures, pacemaker, cranial surgery, or implants) were excluded.8 Patients were assigned to the groups before surgery by using computer-generated random numbers. The investigators were unaware of drug allocation at the time of recruitment.
Anesthetic Protocol Patients received intravenous midazolam 1 to 2 mg in the operating room. Before anesthetic induction, invasive blood pressure was monitored through the radial artery, along with ECG, pulse oximetry, BIS (BIS Vista Monitor, Aspect Medical Systems, Natick, MA), and end-tidal CO2 (PETCO2). After tracheal intubation, a thermometer was placed in the nasopharynx and central venous pressure was monitored through a peripheral catheter. Body temperature was kept in the 361C to 371C range by thermal means. Neuromuscular function was monitored by isotonic myography with a peripheral nerve stimulator (TOF-Watch-SX, Organon Ireland Ltd, Dublin, Ireland) placed at the ulnar nerve. Patients included in our study received an infusion of remifentanil 0.5 mg/kg/min until tracheal intubation, followed by Copyright
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remifentanil at a rate of 0.25 to 0.35 mg/kg/min, and lowering infusion speed until 0.2 mg/kg/min during skin closure. Anesthetic induction consisted of propofol 1.5 to 2 mg/kg, whereas anesthesia maintenance is varied depending on the study group assignment, with either an end-tidal sevoflurane concentration of 0.5 MAC or TCI propofol (Marsh pharmacokinetic model) with an effectsite concentration of 2.5 mg/mL to keep BIS values in the 45 to 60 range. When the patient lost consciousness, a calibration of acceleromyograph was performed to establish baseline values for the T1 (first twitch of the trainof-4, TOF). Neuromuscular blockade for tracheal intubation was achieved with a bolus of cisatracurium 0.15 mg/kg followed by an infusion (0.03 to 0.04 mg/kg/h) to maintain T1 near 20% of control values to prevent an excessive motion during surgery. Mechanical ventilation was applied during anesthesia with O2/air (FiO2, 0.4) adjusting respiratory parameters to keep PaCO2 values between 30 and 35 mm Hg. Bupivacaine (0.5%) with epinephrine was used for skin anesthesia before start of surgery, along with lidocaine (1%) in skull pins application points. Hypertensive episodes (systolic arterial pressure [SAP] > 140 mm Hg longer than 1 min) were treated with additional bolus doses of remifentanil (1 mg/kg). Esmolol (1 mg/kg) was used when high SAP persisted after 4 consecutive remifentanil boluses and also during tracheal extubation. Conversely, during low SAP episodes (SAP < 90 mm Hg longer than 1 min), the remifentanil infusion was lowered to 0.2 mg/kg/min, adding ephedrine (5 mg) if low SAP persisted, despite reduction in remifentanil infusion. After the end of surgery, anesthetic drugs were stopped and the patient was sent to the PACU while the neurosurgeon assessed appearance of neurological dysfunction.
Electrophysiological Monitoring The same trained neurophysiologist took all measurements, and also used the same device each time and did not know which anesthetic technique was being used. Staggered monitoring TceMEPs and SSEPs was performed with a Protektor 16 IOM System (Xltek, Natus Medical Incorporated). TceMEPs were recorded by measuring myogenic responses from the upper extremity abductor pollicis brevis (APB) muscles and the tibialis anterior (TA) and abductor hallucis (AH) muscles in the lower extremities with needle electrodes after a brief highvoltage (300 to 800 V) train of anodal electric stimuli (pulse width = 0.5 ms; N = 4 to 6; interpulse interval = 4 ms). The multipulse stimulus was delivered between 2 corkscrew needle electrodes placed over the motor cortex regions at C3 (anode) and C4 (cathode) (international 10 to 20 system). Stimulation output was increased from 50 mA in steps of 5 mA until a reproducible TceMEPs was elicited. The intensity was then increased and fixed at 10% above this threshold intensity. At least 2 stimulators were capable of delivering a maximum output of 200 mA current intensity to obtain TceMEPs with Protecktor 16 IOM System.
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SSEPs were elicited with 0.3 ms square-wave electric pulses presented sequentially to the posterior tibial nerve at a rate of 4.7 pulses/s. A stimulus of 20 mA was used in SSEP monitoring, and a range of 100 to 200 swepps are delivered depending on SEPP amplitude and definition. Filter setting used was hi-cut 3 kHz and low-cut 20 Hz. SSEPs were recorded also by corkscrew needle electrodes affixed to Cz and referenced to Fpz (international 10 to 20 system). During operation, the cortex potentials included PN37 compound wave for the lower limbs. During intervention, SSEPs and TceMEPs were monitored, and peak-to-peak amplitudes and onset latency were measured. A decrease of more than 50% in amplitude or an increase of more than 10% in latency was defined as abnormal SSEPs. Abnormal TceMEP changes were defined if a 50% decrease of amplitude or 2 ms delay of latency in TceMEPs was recorded as an alarm criterium.
Recording of Data and Indicators Mean arterial blood pressure (MAP), heart rate (HR), pulse oxygen saturation, BIS values, PETCO2, and temperature were measured before the induction of anesthesia and at 1, 2, 3, and 4 hours after induction. Latencies and amplitudes of TceMEPs and SSEPs were recorded at 1, 2, 3, and 4 hours after the induction of anesthesia. Evoked potentials in nonaffected extremity were registered in patients with previous neurological involvement. If patients did not have abnormal responses in both extremities, then the mean value of amplitudes and latencies on both sides were recorded.
Statistical Analysis According to the results obtained by Li et al9 and accepting an alpha risk of 0.05 and beta risk of 0.05 in a bilateral contrast, 11 subjects per group were required to identify a difference of 350 mV or higher, assuming a SD of 200 mV and a rate of loss of 10%. To get a better statistical power, we considered 20 patients per group. Data distributions were tested for normality with the Kolmogorov-Smirnov test. Data are presented as mean ± SD. Comparison of 2 means was applied with 1way analysis of variance (ANOVA), and of several means with repeated-measures ANOVA. Statistical analysis was performed by using SPSS statistical software, version 17.0 (SPSS Inc., Chicago, IL). P < 0.05 was considered as significant.
RESULTS Patient Characteristics A total of 40 patients were eligible for this study. Combined intraoperative monitoring of evoked potentials was successful in all patients and no complication resulted from this monitoring. No patient had neurological deficit in the postoperative period. There were no significant differences between groups relating to sex, age, height, weight, associated diseases, operation time, blood loss, urine output, or fluid infusion volume (Table 1).
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TABLE 1. Comparison of Patient Demographic and Clinical Characteristics Between Groups Propofol (n = 20) Sevoflurane (n = 20) Age (y) Male/female (n [%]) BMI (kg/m2) Associated diseases (n [%]) Hypertension Dyslipidemia Diabetes mellitus Smoking Surgery time (min) Estimated blood loss (mL) Infusion volume (mL) Urine output (mL)
38 ± 12 14 (70)/6 (30) 25.5 ± 3.6
45 ± 17 11 (55)/9 (45) 26.7 ± 3.7
2 (10) 1 (5) 1 (5) 5 (25) 364 ± 102 715 ± 592 4400 ± 1912 2154 ± 1336
2 (10) 2 (10) 2 (10) 6 (30) 414 ± 127 502 ± 608 4870 ± 1536 2533 ± 988
Values expressed as mean ± SD. No significant differences were found between groups. BMI indicates body mass index.
MAP, HR, PETCO2, BIS, and Body Temperature After the induction of anesthesia, HR and MAP were maintained in all patients at a level of ± 20% of that before the anesthetic induction. However, HR in the sevoflurane group was significantly lower than those in the propofol group after induction (P < 0.05). PETCO2, BIS, and body temperature were not significantly different between both groups for the different measurement points (Table 2).
Amplitudes and Latencies of TceMEPs TceMEPs were elicited safely and adequately during surgery in all patients, and the voltage threshold needed to enlist TceMEPs was similar in both groups. No significant differences between groups were found in the current intensity threshold needed to obtain MEPs (156 ± 23 mA, group propofol vs. 165 ± 18 mA, group sevoflurane; P = 0.249). TceMEPs were successfully obtained from all patients with APB, AH, and TA muscle recordings. Amplitudes of TceMEPs from the upper extremity APB were significantly higher in the propofol group than those in the sevoflurane group at 1 hour (P < 0.01), 2 hours (P < 0.05), 3 hours (P < 0.01), and 4 hours (P < 0.001) after the induction of anesthesia, whereas latencies were shorter in the propofol group than those in the sevoflurane group at 1, 2, and 3 hours (P < 0.05), and 4 hours (P < 0.01) after the induction of anesthesia (Table 3). The amplitudes of TceMEPs from the AH muscle were significantly higher in the propofol group than those in the sevoflurane group at all time points (P < 0.01) after the induction of anesthesia, whereas the latencies were significantly shorter in the propofol group than those in the sevoflurane group at 1 hour (P < 0.05) and 2 hours (P < 0.01) after the induction of anesthesia (Table 3). No significant differences between groups were observed with respect to amplitudes of TceMEPs of the TA muscle, except 4 hours after the induction of anesthesia, when amplitudes were higher in the propofol group. Copyright
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TceMEPs and SSEPs Monitoring for Brainstem Surgery
TABLE 2. Comparison of MAP, HR, T, PETCO2, and BIS at Different Time Points After Anesthesia Induction Between Groups MAP (mm Hg) HR (bpm) T (1C) PETCO2 (mm Hg) BIS
Groups
Baseline
1h
2h
3h
4h
Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane
95 ± 13 87 ± 9 76 ± 17 69 ± 12 36.4 ± 0.2 36.3 ± 0.3 — — 98 ± 1 97 ± 2
80 ± 15 74 ± 9 72 ± 12 64 ± 9* 36.6 ± 0.5 36.1 ± 0.6 30 ± 4 29 ± 3 52 ± 6 49 ± 3
81 ± 14 80 ± 7 73 ± 9 65 ± 11* 36.6 ± 0.5 36.3 ± 0.5 30 ± 3 29 ± 3 49 ± 3 51 ± 5
79 ± 9 80 ± 14 76 ± 10 68 ± 8* 36.7 ± 0.4 36.6 ± 0.4 29 ± 2 28 ± 2 50 ± 4 49 ± 4
82 ± 11 78 ± 12 73 ± 11 72 ± 13 36.7 ± 0.4 36.7 ± 0.4 30 ± 2 28 ± 3 49 ± 4 50 ± 4
Values as mean ± SD. *P < 0.005 comparing the propofol and sevoflurane groups. BIS indicates bispectral index; HR, heart rate; MAP, mean arterial blood pressure; PETCO2, end-tidal carbon dioxide partial pressure; T, temperature.
However, the latencies were significantly shorter in the propofol group than those in the sevoflurane group at 1, 3 (P < 0.05), and 4 hours (P < 0.01) after induction (Table 3). In repeated-measures ANOVA, we analyzed the measurements registered at all time points to assess whether the drug effect continued during the course of anesthesia. With this test, there were no significant differences in amplitudes and latencies recorded from APB, AH, and AT muscles at all time points in both propofol and sevoflurane groups (Table 3). None of the patients had TceMEPs amplitude or latency changes exceeding our set limits so as to require immediate attention during the surgical procedure. There were no complaints of headache, seizures, or skin burns TABLE 3. Summary of TceMEPs Results in APB, TA, and TA Muscles 1h
2h
3h
4h
Abductor pollicis brevis muscle Amplitudes (mV) Propofol 1427 ± 479 1388 ± 557 1392 ± 390 1325 ± 236 Sevoflurane 610 ± 141w 593 ± 366* 603 ± 251w 486 ± 168z Latencies (ms) Propofol 28 ± 3 27 ± 4 26 ± 3 25 ± 3 Sevoflurane 31 ± 3* 28 ± 2* 29 ± 3* 29 ± 3 w Abductor hallucis muscle Amplitudes (mV) Propofol 823 ± 245 899 ± 341 946 ± 315 948 ± 307 Sevoflurane 360 ± 147w 418 ± 207w 412 ± 215w 359 ± 157w Latencies (ms) Propofol 43 ± 5 42 ± 5 42 ± 5 41 ± 5 Sevoflurane 47 ± 5* 45 ± 4* 44 ± 4 45 ± 5 Tibialis anterior muscle Amplitudes (mV) Propofol 585 ± 198 606 ± 225 627 ± 235 666 ± 233 Sevoflurane 356 ± 155 434 ± 205 411 ± 161 364 ± 151* Latencies (ms) Propofol 31 ± 4 30 ± 4 29 ± 3 28 ± 3 Sevoflurane 34 ± 5* 32 ± 4 32 ± 5* 33 ± 5w Values as mean ± SD. *P < 0.05. wP < 0.01. zP < 0.001 between groups. APB indicates abductor pollicis brevis; TA, tibialis anterior; TceMEPs, transcranial electrical motor-evoked potentials.
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postoperatively, and all patients had a normal neurological examination.
Amplitudes and Latencies of SSEPs The SSEP measurements are detailed in Table 4. A stimulus of 20 mA was used in SSEP monitoring. The SSEPs latency and amplitude were not significantly different at any time points between the 2 groups. In addition, in repeated-measures ANOVA, there were no significant differences in amplitudes and latencies during the course of study in the propofol and sevoflurane groups (Table 4).
DISCUSSION The combination of TceMEP and SSEP monitoring during surgery for intraparenchymal and extraparenchymal brainstem lesions has become a safe, reliable, and sensitive method to detect and reduce injury to the brainstem, allowing an early intervention to avoid permanent impairment.10 The sensory and motor pathways may be independently assessed during surgery, as the number of false negatives is significantly reduced and there is probably a positive influence on the final postoperative outcome.2,9 Brainstem surgery bears a risk of damage to the corticospinal tract, and TceMEPs are used intraoperatively to monitor corticospinal tract function to detect damage at a reversible stage and thus avoid permanent neurological deficits. Therefore, the effects of anesthetic drugs on TceMEPs are an important consideration in intraoperative neurological monitoring during surgery for intraparenchymal and extraparenchymal brainstem lesions. Propofol and sevoflurane have been used successfully for the maintenance of anesthesia in neurosurgical procedures, because its pharmacokinetics provides similar advantages related to a fast recovery from anesthesia, even after a prolonged period. With respect to sevoflurane it is because of a low Ostwald coefficient for blood-gas,11 and in case of propofol is explained by a fast metabolic clearance rate.12 Thereby, remifentanil was successfully used in patients with mild increase in intracranial pressure during intracranial surgery, adding as an advantage the ability to use high doses during maintenance of anesthesia, and thus to reduce
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TABLE 4. Changes of SSEPs 1h Amplitudes PN37 (mV) Propofol 1.58 ± 0.52 Sevoflurane 1.47 ± 0.45 Latencies PN37 (ms) Propofol 37.6 ± 5.4 Sevoflurane 40.0 ± 6.2
2h
3h
4h
1.45 ± 0.28 1.43 ± 0.41
1.45 ± 0.33 1.44 ± 0.42
1.55 ± 0.38 1.31 ± 0.37
38.5 ± 6.9 39.6 ± 5.7
37.5 ± 6.3 39.4 ± 6.1
37.1 ± 4.6 39.2 ± 5.7
Values as mean ± SD. Comparison of latencies and amplitudes showed no differences between groups or within groups. SSEPs indicates somatosensory-evoked potentials.
volatile anesthetics or propofol to a minimal dose,13 enhancing registration of evoked potentials. In the present study, our findings demonstrated that TceMEP recordings were larger in amplitude with the use of a propofol infusion at a target of 2.5 mg/mL for anesthesia maintenance compared with recordings with sevoflurane at an end-tidal concentration of 0.5 MAC, both combined with a remifentanil infusion under comparable BIS values. Propofol was associated with a significantly greater amplitude compared with sevoflurane during the study period in myogenic responses from the upper extremity (APB muscles) and lower limb (AH and TA muscles). Propofol was also associated with shorter records in waveform latency compared with sevoflurane, and these differences also remained stable for all study periods. Although presurgical values were not recorded, the difference in amplitudes of TceMEPs between the propofol and sevoflurane groups was higher than 50%, and in latencies it was greater than 10%.9 However, none of the patients included in this study had TceMEPs amplitude or latency changes, exceeding our set limits so as to require immediate attention during the surgical procedure. Although factors such as body temperature, hypotension, and hypercapnia may also affect TceMEPs, in our study the MAP, PETCO2, and temperature were similar in both groups and within normal. Although, in a recent study conducted by Lieberman et al14 in pigs, it was observed that hypotension from hemorrhage, instead of vasodilation, is associated with a decrease in TceMEP amplitude, and restoration of TceMEPs with epinephrine, but not phenylephrine, indicates that cardiac output and oxygen delivery affect TceMEPs more than MAP; therefore, monitoring of cardiac output may be beneficial when using TceMEP monitoring. Results similar to our study were found by Chong et al15 who showed during spinal surgery that inhalational anesthetic agents such as sevoflurane and desflurane suppress TceMEP amplitudes in a dose-dependent manner. The use of 0.3 MAC of desflurane, but not sevoflurane, provided good MEP recordings acceptable for clinical interpretation for both the upper and lower limbs. According to other authors,6,15,16 our findings show that TceMEPs recordings from the upper limbs were larger in amplitude compared with recordings from the lower limbs for both sevoflurane and propofol, indicating that the lower limbs seem to be more sensitive to the anesthetic-induced depression. It remains
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unclear as to what mechanism is responsible for the discrepancy in TceMEP responses between the upper and lower limbs. It may be the results of differences in the corticospinal drive mechanism between the upper and lower limbs, for example, D-wave refractory periods.6 In addition, despite the long duration of brainstem surgery, the “anesthetic fade” was not clearly observed, possibly because this phenomenon is more evident in patients with neurological impairment by spinal cord pathology and then in those with preserved neurological function as in our study.17 In addition, it was observed that the use of inhalational anesthesia during adult spinal surgery is associated with significantly higher rates of false-positive changes compared with TIVA during TceMEP monitoring independently from preoperative motor status18; however, in this study, the specific types and dosages of anesthetic agents were not strictly controlled and no attempt was made to match patients according to anesthesia depth (eg, BIS). Although the potential confounding effects of inhalational anesthesia on TceMEP monitoring should be considered, in our study we did not record any persistent loss of amplitude of TceMEPs in one or more muscles, and it was not associated with any postoperative neurological deficit. In contrast, it was stated that suppression of TceMEPs by volatile anesthetics could be at least partially overcome by increasing the frequency of stimulation, thus allowing for summation and increasing waveform amplitude. Shida et al16 evaluated the effect of stimulation frequency on MEPs during either a propofolbased or sevoflurane-based maintenance anesthetic techniques, both with remifentanil. Magnetic MEPs were obtained from the AH and TA muscles in patients during spinal surgery. Coinciding to our study, sevoflurane anesthesia resulted in a decrease higher than 50% in amplitude of waveforms and a small but significant increase in latency, although this suppression was overcome by an increase in stimulation frequency. In addition, these authors verified that anesthesia with propofol caused no significant changes in amplitude or latency. These results confirm data from Reinacher et al19 who demonstrated in patients undergoing craniotomy that high-frequency repetitive stimulation allows the intraoperative use of TceMEP monitoring during up to 1 MAC of sevoflurane and a constant infusion of remifentanil up to 0.2 mg/kg/min. Similar to our study, Yang et al20 demonstrated that lowdose anesthesia by either a TIVA protocol with propofolbased or sevoflurane-based mixture anesthesia protocol with partial neuromuscular blockade can help the intraoperative spinal cord monitoring to successfully elicit TceMEPs and perform a reliable monitoring for patients below 12 years old. SSEPs provide an established modality for monitoring of the function of the somatosensory pathways during surgery on the spinal cord, brain, and brainstem to detect iatrogenic neurological injury, being a very good indicator of brainstem integrity. However, SSEPs are sensitive to anesthetics agents, and some studies found that the effects of anesthetics interfered with SSEPs Copyright
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recording.21 A 50% drop in cortical SSEP amplitude, whether associated with an increase in latency or not, is the universally accepted warning criteria.22 Some studies have shown that sevoflurane causes less depression than other volatile agents, allowing a safe and reliable monitoring.7 In addition, in some studies, propofol attenuated SSEPs when it was administered in boluses for induction and maintenance, causing large variation in concentration; however, when used as a target-controlled infusion technique, propofol did not alter SSEPs.7 Boisseau et al7 showed that sevoflurane, like other volatile anesthetics, caused a dose-related increase in latency and decrease in amplitude during spinal surgery, whereas propofol used in continuous infusion to maintain a stable concentration had a minimal effect on SSEP recording. Our study shows that, within BIS value between 45 and 60, both sevoflurane and propofol caused similar changes in SSEPs, with no differences in SSEPs registered between propofol and sevoflurane. None of the patients included in the study exceeded our set limits so as to require immediate attention during the surgical procedure. In this study, we applied 2 kinds of anesthetic techniques with a low concentration. Dosage of anesthesia was lower than the previously reported concentrations, and the results proved that the use of low-dose anesthesia, especially with propofol, could help to improve the successful rate of intraoperative-evoked potential recording. One of the questions regarding lowdose anesthesia is the depth of anesthesia. In this study, supplement of anesthesia with remifentanil can help to inhibit awareness under low-dose propofol or sevoflurane. We monitored intraoperative hypnotic state by the BIS to obtain a satisfactory anesthesia in our patients. In addition, regardless of the anesthetic technique used, it is of utmost importance to maintain a stable concentration of inhalational or intravenous anesthesia, as sudden changes in dose may induce evoked potential changes, driving to an impossible interpretation. Another question regarding low-dose anesthetic protocol is the body movement that may have serious consequences during intracranial surgery. Although complete neuromuscular block is contraindicated when TceMEPs are recorded from the muscles, partial block is sometimes used to either assist with surgical exposure, minimizing the risk of patient movement, or improve the signalto-noise ratio of monitored waveforms. However, with a partial neuromuscular blockade, some patients may not have adequate responses for intraoperative neurophysiological monitoring, and therefore it may be of particular problem in patients with neurological diseases or low-amplitude responses.23 Furthermore, sevoflurane at 0.5 to 1.0 CAM may enhance neuromuscular blockade and consequently reduce the amplitude of TceMEPs.24 Similarly, although the impact of a partial neuromuscular blockade on free-run EMG monitoring is not known, it might impact EMG monitoring, so that monitoring of neuromuscular function is important if used partial muscle relaxation during neurophysiological monitoring. Copyright
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TceMEPs and SSEPs Monitoring for Brainstem Surgery
In our patients, we used a continuous infusion of cisatracurium to a T1 reduced to 20% of baseline, considered acceptable by various authors for TceMEP monitoring in patients with normal neurological function.23 In contrast, some authors recommend the use of IV lidocaine (1.5 mg/kg/h) as an adjunct to general anesthesia with intraoperative neurophysiological monitoring because of its ability to reduce anesthetic requirements and decrease the incidence of patient movement during surgery without neuromuscular blockade.25 One limitation of this study is the lack of assessment of TceMEP responses before induction, because of the involved pain. Nevertheless, differences in results obtained between the propofol and sevoflurane groups suggest a higher decrease in TceMEPs in patients anesthetized with sevoflurane. Another limitation of this study is that BIS may actually not have given an equivalent anesthetic effect, given that the drugs have different mechanisms of action and different effects on the BIS; thus, it cannot be considered independent of the anesthetic technique.
CONCLUSIONS Both sevoflurane and propofol at low dosages combined with remifentanil under comparable BIS values and partial muscle relaxation can be used when TceMEP and SSEP monitoring is required for brainstem surgery. REFERENCES 1. Sala F, Manganotti P, Tramontano V, et al. Monitoring of motor pathways during brain stem surgery: what we have achieved and what we still miss? Neurophysiol Clin. 2007;37:399–406. 2. Sloan TB, Janik D, Jameson L. Multimodality monitoring of the central system using motor-evoked potentials. Curr Opin Anaesthesiol. 2008;21:560–564. 3. Manninen PH, Lam AM, Nicholas JF. The effects of isofluranenitrous oxide anesthesia on brainstem auditory evoked potentials in humans. Anesth Analg. 1985;64:43–47. 4. Drummond JC, Todd MM, Sang H. The effect of high dose sodium tiopental on brain stem auditory and median nerve somatosensory evoked response in humans. Anesthesiology. 1985;63:249–254. 5. Nathan N, Tabaraud F, Lacroix F, et al. Influence of propofol concentrations on multipulse transcranial motor evoked potentials. Br J Anaesth. 2003;91:493–497. 6. Sloan TB, Toleikis JR, Toleikis SC, et al. Intraoperative neurophysiological monitoring during spine surgery with total intravenous anesthesia or balanced anesthesia with 3% desflurane. Clin Monit Comput. 2014. doi: 10.1007/s10877-014-9571-9. [Epub ahead of print]. 7. Boisseau N, Madany M, Staccini P, et al. Comparison of the effects of sevoflurane and propofol on cortical somatosensory evoked potentials. Br J Anaesth. 2002;88:785–789. 8. Lo YL, Dan YF, Tan YE, et al. Intraoperative motor-evoked potential monitoring in scoliosis surgery: comparison of desflurane/ nitrous oxide with propofol total intravenous anesthetic regimens. J Neurosurg Anesthesiol. 2006;18:211–214. 9. Li F, Gorji R, Allott G, et al. The usefulness of intraoperative neurophysiological monitoring in cervical spine surgery: a retrospective analysis of 200 consecutive patients. J Neurosurg Anesthesiol. 2012;24:185–190. 10. Weinzierl MR, Reinacher P, Gilsbach JM, et al. Combined motor and somatosensory evoked potentials for intraoperative monitoring: intra- and postoperative data in a series of 69 operations. Neurosurg Rev. 2007;30:109–116. 11. Robinson BJ, Uhrich TD, Ebert TJ. A review of recovery from sevoflurane anaesthesia: comparisons with isoflurane and
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12. 13.
14. 15. 16.
17. 18.
propofol including meta-analysis. Acta Anaesthesiol Scand. 1999; 43:185–190. Favetta P, Degoute CS, Perdrix JP, et al. Propofol metabolites in man following propofol induction and maintenance. Br J Anaesth. 2002;88:653–658. Warner DS, Hindman BJ, Todd MM, et al. Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy. Anesth Analg. 1996; 83:348–353. Lieberman JA, Feiner J, Lyon R, et al. Effect of hemorrhage and hypotension on transcranial motor-evoked potentials in swine. Anesthesiology. 2013;119:1109–1119. Chong CT, Manninen P, Sivanaser V, et al. Direct comparison of the effect of desflurane and sevoflurane on intraoperative motor evoked potentials monitoring. J Neurosurg Anesthesiol. 2014;26:306–312. Shida Y, Shida C, Hiratsuka N, et al. 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. 2012;24:113–120. Lyon R, Feiner J, Lieberman JA. Progressive suppression of motor evoked potentials during general anesthesia. The phenomenon of “Anesthetic Fade.” J Neurosurg Anesthesiol. 2005;17:13–19. Tamkus AA, Rice KS, Kim HL. Differential rates of false-positive findings in transcranial electric motor evoked potential monitoring
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19. 20. 21. 22. 23. 24.
25.
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when using inhalational anesthesia versus total intravenous anesthesia during spine surgeries. Spine J. 2014;14:1440–1446. Reinacher PC, Priebe HJ, Blumrich W, et al. The effects of stimulation pattern and sevoflurane concentration on intraoperative motor-evoked potentials. Anesth Analg. 2006;102:888–895. Yang J, Huang Z, Shu H, et al. Improving successful rate of transcranial electrical motor-evoked potentials monitoring during spinal surgery in young children. Eur Spine J. 2012;21:980–984. Sloan TB. Anesthetics effects on electrophysiologic recording. J Clin Neurophysiol. 1998;15:217–226. American Electroencephalographic Society. Guideline eleven: guidelines for intraoperative monitoring of sensory evoked potentials. J Clin Neurophysiol. 1994;11:77–87. Sloan TB. Muscle relaxant use during intraoperative neurophysiologic monitoring. J Clin Monit Comput. 2013;27:35–46. Sekimoto K, Nishikawa K, Ishizeki J, et al. 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;18:106–111. Sloan TB, Mongan P, Lyda C, et al. Lidocaine infusion adjunct to total intravenous anesthesia reduces the total dose of propofol during intraoperative neurophysiological monitoring. J Clin Monit Comput. 2014;28:139–147.
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Comparison of the Effects of Propofol and Sevoflurane Combined With Remifentanil on Transcranial Electric Motor-evoked and Somatosensory-evoked Potential Monitoring During Brainstem Surgery Joaquı´n Herna´ndez-Palazo´n, MD, PhD,* Virginia Izura, MD, PhD,w Diego Fuentes-Garcı´a, MD, PhD,* Claudio Piqueras-Pe´rez, MD,z Paloma Dome´nech-Asensi, MD, PhD,* and Luis Falco´n-Aran˜a, MD, PhD*
Background: We compared the effect of propofol and sevoflurane combined with remifentanil under comparable bispectral index (BIS) levels on transcranial electric motor-evoked potentials (TceMEPs) and somatosensory-evoked potentials (SSEPs) during brainstem surgery. Materials and Methods: A total of 40 consecutive patients (20 per group) undergoing brainstem surgery were randomly assigned to 2 groups receiving either 0.5 MAC sevoflurane or propofol at an effect-site concentration of 2.5 mg/mL for maintenance of anesthesia. Remifentanil was administered to both groups at a rate of 0.25 to 0.35 mg/kg/min along with cisatracurium (0.03 to 0.04 mg/kg/h). TceMEP recordings were carried out in the abductor pollicis brevis, abductor hallucis, and tibialis anterior muscles, whereas cortical SSEPs were measured with posterior tibial nerve stimulation. Amplitudes and latencies of TceMEPs and SSEPs were recorded at 1, 2, 3, and 4 hours after the induction of anesthesia. Results: BIS values remained in the 45 to 60 range. Amplitudes of TceMEPs were significantly higher in the propofol group than those in the sevoflurane group (P < 0.05, at all study time points in abductor pollicis brevis and abductor hallucis muscles and only 4 h after anesthetic induction for tibialis anterior muscle), whereas latencies were shorter in the propofol group than those in the sevoflurane group (P < 0.05). No differences were observed in latency and amplitude while recording SSEPs between the 2 anesthetic techniques. None of the patients had TceMEPs and SSEPs amplitude or latency changes, exceeding our set limit. Conclusions: Both sevoflurane and propofol at low dosages combined with remifentanil under comparable BIS values and
Received for publication August 8, 2014; accepted December 1, 2014. From the Departments of *Anesthesia; wNeurophysiology; and zNeurosurgery, Hospital Clı´ nico “Virgen de la Arrixaca,” Murcia, Spain. The authors have no funding or conflicts of interest to disclose. Reprints: Diego Fuentes-Garcı´ a, MD, PhD, Ctra Madrid-Cartagena, s/n. 30120 El Palmar, Murcia, Spain (e-mail: smart10015@hotmail. com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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partial muscle relaxation can be used when monitoring of TceMEPs and SSEPs is required for brainstem surgery. Key Words: monitoring, transcranial electric motor-evoked potentials, somatosensory-evoked potentials, propofol, sevoflurane, surgery, brainstem (J Neurosurg Anesthesiol 2015;27:282–288)
I
ntraoperative neurophysiological monitoring has been established as one of the paths by which modern neurosurgery can improve surgical results while minimizing morbidity. This proceeding consists of the monitoring of functional integrity of the neural pathways and mapping of techniques for identification and preservation of the cranial nerves, their motor nuclei, and corticospinal or corticobulbar pathways during posterior-fossa and brainstem surgery.1 During these surgical procedures, small injuries can produce significant neurological deficits, and therefore global integrity of the brainstem must be monitored through the combination of diverse techniques of evoked potentials (multimodal intraoperative monitoring), such as brainstem auditory-evoked potentials (BAEPs), somatosensory-evoked potentials (SSEPs), transcranial electric motor-evoked potentials (TceMEPs), and free-run electromyography of the V, VI, VII, IX, X, XI, and XII cranial nerves. During monitoring of tumors in the lower brainstem and fourth ventricle, the multimodal intraoperative monitoring with TceMEPs, SSEPs, electromyography, and auditory brainstem responses assists in “mapping” to identify the least risky surgical approach, as the anatomic landmarks are inconstant.2 Similarly, this need for multimodal intraoperative monitoring also applies to surgery on the brain and brainstem where the motor and sensory pathways are anatomically separated and supplied by separate vascular sources. Anesthetic effects on BAEPs are not very profound, with small shifts in latency after changes in anesthetic drug level and without interferences in monitoring.3,4 Nevertheless, anesthetic effects on SSEPs and TceMEPs are more profound than changes in BAEPs, driving to an J Neurosurg Anesthesiol
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increase in latency and an amplitude decline in a dosedependent way, even though diverse authors found that intravenous anesthetic drugs induce a much lower decrease.5 Indeed, total intravenous anesthesia with propofol and opioids is commonly used for spinal surgery when SSEPs and TceMEPs are monitored. However, because in certain clinical settings there are greater hemodynamic changes with propofol, many anesthesiologists would prefer to use low dose of halogenated anesthetics (eg, 0.5 MAC).6,7 To the best of our knowledge, there are no direct comparative studies involving sevoflurane and propofol with remifentanil in the monitoring of both SSEPs and TceMEPs during the surgery of intraparenchymal and extraparenchymal brainstem lesions. The aim of this study was to compare the effect of propofol and sevoflurane on the amplitudes and latencies of TceMEPs and SSEPs, when these agents are used with remifentanil for the maintenance of anesthesia to achieve a comparable bispectral index (BIS) value during brainstem surgery.
MATERIALS AND METHODS Patients After approval by the IRB from Hospital Clı´ nico “Virgen de la Arrixaca,” 40 consecutive patients (18 to 68 years old) undergoing elective brainstem surgery were included in this study after obtaining informed consent. The intraparenchymal and extraparenchymal brainstem lesions were: vestibular neurinoma (23 patients), trigeminal neurinoma (4), meningioma of the foramen magnum (5), ependymoma of the fourth ventricle (1), brainstem epidermoid cyst (2), and petrous meningoma (5). Each patient was randomized to receive either sevoflurane or propofol during surgery (20 patients in each group). Patients with contraindications to cortical stimulation (seizures, pacemaker, cranial surgery, or implants) were excluded.8 Patients were assigned to the groups before surgery by using computer-generated random numbers. The investigators were unaware of drug allocation at the time of recruitment.
Anesthetic Protocol Patients received intravenous midazolam 1 to 2 mg in the operating room. Before anesthetic induction, invasive blood pressure was monitored through the radial artery, along with ECG, pulse oximetry, BIS (BIS Vista Monitor, Aspect Medical Systems, Natick, MA), and end-tidal CO2 (PETCO2). After tracheal intubation, a thermometer was placed in the nasopharynx and central venous pressure was monitored through a peripheral catheter. Body temperature was kept in the 361C to 371C range by thermal means. Neuromuscular function was monitored by isotonic myography with a peripheral nerve stimulator (TOF-Watch-SX, Organon Ireland Ltd, Dublin, Ireland) placed at the ulnar nerve. Patients included in our study received an infusion of remifentanil 0.5 mg/kg/min until tracheal intubation, followed by Copyright
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TceMEPs and SSEPs Monitoring for Brainstem Surgery
remifentanil at a rate of 0.25 to 0.35 mg/kg/min, and lowering infusion speed until 0.2 mg/kg/min during skin closure. Anesthetic induction consisted of propofol 1.5 to 2 mg/kg, whereas anesthesia maintenance is varied depending on the study group assignment, with either an end-tidal sevoflurane concentration of 0.5 MAC or TCI propofol (Marsh pharmacokinetic model) with an effectsite concentration of 2.5 mg/mL to keep BIS values in the 45 to 60 range. When the patient lost consciousness, a calibration of acceleromyograph was performed to establish baseline values for the T1 (first twitch of the trainof-4, TOF). Neuromuscular blockade for tracheal intubation was achieved with a bolus of cisatracurium 0.15 mg/kg followed by an infusion (0.03 to 0.04 mg/kg/h) to maintain T1 near 20% of control values to prevent an excessive motion during surgery. Mechanical ventilation was applied during anesthesia with O2/air (FiO2, 0.4) adjusting respiratory parameters to keep PaCO2 values between 30 and 35 mm Hg. Bupivacaine (0.5%) with epinephrine was used for skin anesthesia before start of surgery, along with lidocaine (1%) in skull pins application points. Hypertensive episodes (systolic arterial pressure [SAP] > 140 mm Hg longer than 1 min) were treated with additional bolus doses of remifentanil (1 mg/kg). Esmolol (1 mg/kg) was used when high SAP persisted after 4 consecutive remifentanil boluses and also during tracheal extubation. Conversely, during low SAP episodes (SAP < 90 mm Hg longer than 1 min), the remifentanil infusion was lowered to 0.2 mg/kg/min, adding ephedrine (5 mg) if low SAP persisted, despite reduction in remifentanil infusion. After the end of surgery, anesthetic drugs were stopped and the patient was sent to the PACU while the neurosurgeon assessed appearance of neurological dysfunction.
Electrophysiological Monitoring The same trained neurophysiologist took all measurements, and also used the same device each time and did not know which anesthetic technique was being used. Staggered monitoring TceMEPs and SSEPs was performed with a Protektor 16 IOM System (Xltek, Natus Medical Incorporated). TceMEPs were recorded by measuring myogenic responses from the upper extremity abductor pollicis brevis (APB) muscles and the tibialis anterior (TA) and abductor hallucis (AH) muscles in the lower extremities with needle electrodes after a brief highvoltage (300 to 800 V) train of anodal electric stimuli (pulse width = 0.5 ms; N = 4 to 6; interpulse interval = 4 ms). The multipulse stimulus was delivered between 2 corkscrew needle electrodes placed over the motor cortex regions at C3 (anode) and C4 (cathode) (international 10 to 20 system). Stimulation output was increased from 50 mA in steps of 5 mA until a reproducible TceMEPs was elicited. The intensity was then increased and fixed at 10% above this threshold intensity. At least 2 stimulators were capable of delivering a maximum output of 200 mA current intensity to obtain TceMEPs with Protecktor 16 IOM System.
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SSEPs were elicited with 0.3 ms square-wave electric pulses presented sequentially to the posterior tibial nerve at a rate of 4.7 pulses/s. A stimulus of 20 mA was used in SSEP monitoring, and a range of 100 to 200 swepps are delivered depending on SEPP amplitude and definition. Filter setting used was hi-cut 3 kHz and low-cut 20 Hz. SSEPs were recorded also by corkscrew needle electrodes affixed to Cz and referenced to Fpz (international 10 to 20 system). During operation, the cortex potentials included PN37 compound wave for the lower limbs. During intervention, SSEPs and TceMEPs were monitored, and peak-to-peak amplitudes and onset latency were measured. A decrease of more than 50% in amplitude or an increase of more than 10% in latency was defined as abnormal SSEPs. Abnormal TceMEP changes were defined if a 50% decrease of amplitude or 2 ms delay of latency in TceMEPs was recorded as an alarm criterium.
Recording of Data and Indicators Mean arterial blood pressure (MAP), heart rate (HR), pulse oxygen saturation, BIS values, PETCO2, and temperature were measured before the induction of anesthesia and at 1, 2, 3, and 4 hours after induction. Latencies and amplitudes of TceMEPs and SSEPs were recorded at 1, 2, 3, and 4 hours after the induction of anesthesia. Evoked potentials in nonaffected extremity were registered in patients with previous neurological involvement. If patients did not have abnormal responses in both extremities, then the mean value of amplitudes and latencies on both sides were recorded.
Statistical Analysis According to the results obtained by Li et al9 and accepting an alpha risk of 0.05 and beta risk of 0.05 in a bilateral contrast, 11 subjects per group were required to identify a difference of 350 mV or higher, assuming a SD of 200 mV and a rate of loss of 10%. To get a better statistical power, we considered 20 patients per group. Data distributions were tested for normality with the Kolmogorov-Smirnov test. Data are presented as mean ± SD. Comparison of 2 means was applied with 1way analysis of variance (ANOVA), and of several means with repeated-measures ANOVA. Statistical analysis was performed by using SPSS statistical software, version 17.0 (SPSS Inc., Chicago, IL). P < 0.05 was considered as significant.
RESULTS Patient Characteristics A total of 40 patients were eligible for this study. Combined intraoperative monitoring of evoked potentials was successful in all patients and no complication resulted from this monitoring. No patient had neurological deficit in the postoperative period. There were no significant differences between groups relating to sex, age, height, weight, associated diseases, operation time, blood loss, urine output, or fluid infusion volume (Table 1).
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TABLE 1. Comparison of Patient Demographic and Clinical Characteristics Between Groups Propofol (n = 20) Sevoflurane (n = 20) Age (y) Male/female (n [%]) BMI (kg/m2) Associated diseases (n [%]) Hypertension Dyslipidemia Diabetes mellitus Smoking Surgery time (min) Estimated blood loss (mL) Infusion volume (mL) Urine output (mL)
38 ± 12 14 (70)/6 (30) 25.5 ± 3.6
45 ± 17 11 (55)/9 (45) 26.7 ± 3.7
2 (10) 1 (5) 1 (5) 5 (25) 364 ± 102 715 ± 592 4400 ± 1912 2154 ± 1336
2 (10) 2 (10) 2 (10) 6 (30) 414 ± 127 502 ± 608 4870 ± 1536 2533 ± 988
Values expressed as mean ± SD. No significant differences were found between groups. BMI indicates body mass index.
MAP, HR, PETCO2, BIS, and Body Temperature After the induction of anesthesia, HR and MAP were maintained in all patients at a level of ± 20% of that before the anesthetic induction. However, HR in the sevoflurane group was significantly lower than those in the propofol group after induction (P < 0.05). PETCO2, BIS, and body temperature were not significantly different between both groups for the different measurement points (Table 2).
Amplitudes and Latencies of TceMEPs TceMEPs were elicited safely and adequately during surgery in all patients, and the voltage threshold needed to enlist TceMEPs was similar in both groups. No significant differences between groups were found in the current intensity threshold needed to obtain MEPs (156 ± 23 mA, group propofol vs. 165 ± 18 mA, group sevoflurane; P = 0.249). TceMEPs were successfully obtained from all patients with APB, AH, and TA muscle recordings. Amplitudes of TceMEPs from the upper extremity APB were significantly higher in the propofol group than those in the sevoflurane group at 1 hour (P < 0.01), 2 hours (P < 0.05), 3 hours (P < 0.01), and 4 hours (P < 0.001) after the induction of anesthesia, whereas latencies were shorter in the propofol group than those in the sevoflurane group at 1, 2, and 3 hours (P < 0.05), and 4 hours (P < 0.01) after the induction of anesthesia (Table 3). The amplitudes of TceMEPs from the AH muscle were significantly higher in the propofol group than those in the sevoflurane group at all time points (P < 0.01) after the induction of anesthesia, whereas the latencies were significantly shorter in the propofol group than those in the sevoflurane group at 1 hour (P < 0.05) and 2 hours (P < 0.01) after the induction of anesthesia (Table 3). No significant differences between groups were observed with respect to amplitudes of TceMEPs of the TA muscle, except 4 hours after the induction of anesthesia, when amplitudes were higher in the propofol group. Copyright
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TceMEPs and SSEPs Monitoring for Brainstem Surgery
TABLE 2. Comparison of MAP, HR, T, PETCO2, and BIS at Different Time Points After Anesthesia Induction Between Groups MAP (mm Hg) HR (bpm) T (1C) PETCO2 (mm Hg) BIS
Groups
Baseline
1h
2h
3h
4h
Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane Propofol Sevoflurane
95 ± 13 87 ± 9 76 ± 17 69 ± 12 36.4 ± 0.2 36.3 ± 0.3 — — 98 ± 1 97 ± 2
80 ± 15 74 ± 9 72 ± 12 64 ± 9* 36.6 ± 0.5 36.1 ± 0.6 30 ± 4 29 ± 3 52 ± 6 49 ± 3
81 ± 14 80 ± 7 73 ± 9 65 ± 11* 36.6 ± 0.5 36.3 ± 0.5 30 ± 3 29 ± 3 49 ± 3 51 ± 5
79 ± 9 80 ± 14 76 ± 10 68 ± 8* 36.7 ± 0.4 36.6 ± 0.4 29 ± 2 28 ± 2 50 ± 4 49 ± 4
82 ± 11 78 ± 12 73 ± 11 72 ± 13 36.7 ± 0.4 36.7 ± 0.4 30 ± 2 28 ± 3 49 ± 4 50 ± 4
Values as mean ± SD. *P < 0.005 comparing the propofol and sevoflurane groups. BIS indicates bispectral index; HR, heart rate; MAP, mean arterial blood pressure; PETCO2, end-tidal carbon dioxide partial pressure; T, temperature.
However, the latencies were significantly shorter in the propofol group than those in the sevoflurane group at 1, 3 (P < 0.05), and 4 hours (P < 0.01) after induction (Table 3). In repeated-measures ANOVA, we analyzed the measurements registered at all time points to assess whether the drug effect continued during the course of anesthesia. With this test, there were no significant differences in amplitudes and latencies recorded from APB, AH, and AT muscles at all time points in both propofol and sevoflurane groups (Table 3). None of the patients had TceMEPs amplitude or latency changes exceeding our set limits so as to require immediate attention during the surgical procedure. There were no complaints of headache, seizures, or skin burns TABLE 3. Summary of TceMEPs Results in APB, TA, and TA Muscles 1h
2h
3h
4h
Abductor pollicis brevis muscle Amplitudes (mV) Propofol 1427 ± 479 1388 ± 557 1392 ± 390 1325 ± 236 Sevoflurane 610 ± 141w 593 ± 366* 603 ± 251w 486 ± 168z Latencies (ms) Propofol 28 ± 3 27 ± 4 26 ± 3 25 ± 3 Sevoflurane 31 ± 3* 28 ± 2* 29 ± 3* 29 ± 3 w Abductor hallucis muscle Amplitudes (mV) Propofol 823 ± 245 899 ± 341 946 ± 315 948 ± 307 Sevoflurane 360 ± 147w 418 ± 207w 412 ± 215w 359 ± 157w Latencies (ms) Propofol 43 ± 5 42 ± 5 42 ± 5 41 ± 5 Sevoflurane 47 ± 5* 45 ± 4* 44 ± 4 45 ± 5 Tibialis anterior muscle Amplitudes (mV) Propofol 585 ± 198 606 ± 225 627 ± 235 666 ± 233 Sevoflurane 356 ± 155 434 ± 205 411 ± 161 364 ± 151* Latencies (ms) Propofol 31 ± 4 30 ± 4 29 ± 3 28 ± 3 Sevoflurane 34 ± 5* 32 ± 4 32 ± 5* 33 ± 5w Values as mean ± SD. *P < 0.05. wP < 0.01. zP < 0.001 between groups. APB indicates abductor pollicis brevis; TA, tibialis anterior; TceMEPs, transcranial electrical motor-evoked potentials.
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postoperatively, and all patients had a normal neurological examination.
Amplitudes and Latencies of SSEPs The SSEP measurements are detailed in Table 4. A stimulus of 20 mA was used in SSEP monitoring. The SSEPs latency and amplitude were not significantly different at any time points between the 2 groups. In addition, in repeated-measures ANOVA, there were no significant differences in amplitudes and latencies during the course of study in the propofol and sevoflurane groups (Table 4).
DISCUSSION The combination of TceMEP and SSEP monitoring during surgery for intraparenchymal and extraparenchymal brainstem lesions has become a safe, reliable, and sensitive method to detect and reduce injury to the brainstem, allowing an early intervention to avoid permanent impairment.10 The sensory and motor pathways may be independently assessed during surgery, as the number of false negatives is significantly reduced and there is probably a positive influence on the final postoperative outcome.2,9 Brainstem surgery bears a risk of damage to the corticospinal tract, and TceMEPs are used intraoperatively to monitor corticospinal tract function to detect damage at a reversible stage and thus avoid permanent neurological deficits. Therefore, the effects of anesthetic drugs on TceMEPs are an important consideration in intraoperative neurological monitoring during surgery for intraparenchymal and extraparenchymal brainstem lesions. Propofol and sevoflurane have been used successfully for the maintenance of anesthesia in neurosurgical procedures, because its pharmacokinetics provides similar advantages related to a fast recovery from anesthesia, even after a prolonged period. With respect to sevoflurane it is because of a low Ostwald coefficient for blood-gas,11 and in case of propofol is explained by a fast metabolic clearance rate.12 Thereby, remifentanil was successfully used in patients with mild increase in intracranial pressure during intracranial surgery, adding as an advantage the ability to use high doses during maintenance of anesthesia, and thus to reduce
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TABLE 4. Changes of SSEPs 1h Amplitudes PN37 (mV) Propofol 1.58 ± 0.52 Sevoflurane 1.47 ± 0.45 Latencies PN37 (ms) Propofol 37.6 ± 5.4 Sevoflurane 40.0 ± 6.2
2h
3h
4h
1.45 ± 0.28 1.43 ± 0.41
1.45 ± 0.33 1.44 ± 0.42
1.55 ± 0.38 1.31 ± 0.37
38.5 ± 6.9 39.6 ± 5.7
37.5 ± 6.3 39.4 ± 6.1
37.1 ± 4.6 39.2 ± 5.7
Values as mean ± SD. Comparison of latencies and amplitudes showed no differences between groups or within groups. SSEPs indicates somatosensory-evoked potentials.
volatile anesthetics or propofol to a minimal dose,13 enhancing registration of evoked potentials. In the present study, our findings demonstrated that TceMEP recordings were larger in amplitude with the use of a propofol infusion at a target of 2.5 mg/mL for anesthesia maintenance compared with recordings with sevoflurane at an end-tidal concentration of 0.5 MAC, both combined with a remifentanil infusion under comparable BIS values. Propofol was associated with a significantly greater amplitude compared with sevoflurane during the study period in myogenic responses from the upper extremity (APB muscles) and lower limb (AH and TA muscles). Propofol was also associated with shorter records in waveform latency compared with sevoflurane, and these differences also remained stable for all study periods. Although presurgical values were not recorded, the difference in amplitudes of TceMEPs between the propofol and sevoflurane groups was higher than 50%, and in latencies it was greater than 10%.9 However, none of the patients included in this study had TceMEPs amplitude or latency changes, exceeding our set limits so as to require immediate attention during the surgical procedure. Although factors such as body temperature, hypotension, and hypercapnia may also affect TceMEPs, in our study the MAP, PETCO2, and temperature were similar in both groups and within normal. Although, in a recent study conducted by Lieberman et al14 in pigs, it was observed that hypotension from hemorrhage, instead of vasodilation, is associated with a decrease in TceMEP amplitude, and restoration of TceMEPs with epinephrine, but not phenylephrine, indicates that cardiac output and oxygen delivery affect TceMEPs more than MAP; therefore, monitoring of cardiac output may be beneficial when using TceMEP monitoring. Results similar to our study were found by Chong et al15 who showed during spinal surgery that inhalational anesthetic agents such as sevoflurane and desflurane suppress TceMEP amplitudes in a dose-dependent manner. The use of 0.3 MAC of desflurane, but not sevoflurane, provided good MEP recordings acceptable for clinical interpretation for both the upper and lower limbs. According to other authors,6,15,16 our findings show that TceMEPs recordings from the upper limbs were larger in amplitude compared with recordings from the lower limbs for both sevoflurane and propofol, indicating that the lower limbs seem to be more sensitive to the anesthetic-induced depression. It remains
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unclear as to what mechanism is responsible for the discrepancy in TceMEP responses between the upper and lower limbs. It may be the results of differences in the corticospinal drive mechanism between the upper and lower limbs, for example, D-wave refractory periods.6 In addition, despite the long duration of brainstem surgery, the “anesthetic fade” was not clearly observed, possibly because this phenomenon is more evident in patients with neurological impairment by spinal cord pathology and then in those with preserved neurological function as in our study.17 In addition, it was observed that the use of inhalational anesthesia during adult spinal surgery is associated with significantly higher rates of false-positive changes compared with TIVA during TceMEP monitoring independently from preoperative motor status18; however, in this study, the specific types and dosages of anesthetic agents were not strictly controlled and no attempt was made to match patients according to anesthesia depth (eg, BIS). Although the potential confounding effects of inhalational anesthesia on TceMEP monitoring should be considered, in our study we did not record any persistent loss of amplitude of TceMEPs in one or more muscles, and it was not associated with any postoperative neurological deficit. In contrast, it was stated that suppression of TceMEPs by volatile anesthetics could be at least partially overcome by increasing the frequency of stimulation, thus allowing for summation and increasing waveform amplitude. Shida et al16 evaluated the effect of stimulation frequency on MEPs during either a propofolbased or sevoflurane-based maintenance anesthetic techniques, both with remifentanil. Magnetic MEPs were obtained from the AH and TA muscles in patients during spinal surgery. Coinciding to our study, sevoflurane anesthesia resulted in a decrease higher than 50% in amplitude of waveforms and a small but significant increase in latency, although this suppression was overcome by an increase in stimulation frequency. In addition, these authors verified that anesthesia with propofol caused no significant changes in amplitude or latency. These results confirm data from Reinacher et al19 who demonstrated in patients undergoing craniotomy that high-frequency repetitive stimulation allows the intraoperative use of TceMEP monitoring during up to 1 MAC of sevoflurane and a constant infusion of remifentanil up to 0.2 mg/kg/min. Similar to our study, Yang et al20 demonstrated that lowdose anesthesia by either a TIVA protocol with propofolbased or sevoflurane-based mixture anesthesia protocol with partial neuromuscular blockade can help the intraoperative spinal cord monitoring to successfully elicit TceMEPs and perform a reliable monitoring for patients below 12 years old. SSEPs provide an established modality for monitoring of the function of the somatosensory pathways during surgery on the spinal cord, brain, and brainstem to detect iatrogenic neurological injury, being a very good indicator of brainstem integrity. However, SSEPs are sensitive to anesthetics agents, and some studies found that the effects of anesthetics interfered with SSEPs Copyright
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2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Neurosurg Anesthesiol
Volume 27, Number 4, October 2015
recording.21 A 50% drop in cortical SSEP amplitude, whether associated with an increase in latency or not, is the universally accepted warning criteria.22 Some studies have shown that sevoflurane causes less depression than other volatile agents, allowing a safe and reliable monitoring.7 In addition, in some studies, propofol attenuated SSEPs when it was administered in boluses for induction and maintenance, causing large variation in concentration; however, when used as a target-controlled infusion technique, propofol did not alter SSEPs.7 Boisseau et al7 showed that sevoflurane, like other volatile anesthetics, caused a dose-related increase in latency and decrease in amplitude during spinal surgery, whereas propofol used in continuous infusion to maintain a stable concentration had a minimal effect on SSEP recording. Our study shows that, within BIS value between 45 and 60, both sevoflurane and propofol caused similar changes in SSEPs, with no differences in SSEPs registered between propofol and sevoflurane. None of the patients included in the study exceeded our set limits so as to require immediate attention during the surgical procedure. In this study, we applied 2 kinds of anesthetic techniques with a low concentration. Dosage of anesthesia was lower than the previously reported concentrations, and the results proved that the use of low-dose anesthesia, especially with propofol, could help to improve the successful rate of intraoperative-evoked potential recording. One of the questions regarding lowdose anesthesia is the depth of anesthesia. In this study, supplement of anesthesia with remifentanil can help to inhibit awareness under low-dose propofol or sevoflurane. We monitored intraoperative hypnotic state by the BIS to obtain a satisfactory anesthesia in our patients. In addition, regardless of the anesthetic technique used, it is of utmost importance to maintain a stable concentration of inhalational or intravenous anesthesia, as sudden changes in dose may induce evoked potential changes, driving to an impossible interpretation. Another question regarding low-dose anesthetic protocol is the body movement that may have serious consequences during intracranial surgery. Although complete neuromuscular block is contraindicated when TceMEPs are recorded from the muscles, partial block is sometimes used to either assist with surgical exposure, minimizing the risk of patient movement, or improve the signalto-noise ratio of monitored waveforms. However, with a partial neuromuscular blockade, some patients may not have adequate responses for intraoperative neurophysiological monitoring, and therefore it may be of particular problem in patients with neurological diseases or low-amplitude responses.23 Furthermore, sevoflurane at 0.5 to 1.0 CAM may enhance neuromuscular blockade and consequently reduce the amplitude of TceMEPs.24 Similarly, although the impact of a partial neuromuscular blockade on free-run EMG monitoring is not known, it might impact EMG monitoring, so that monitoring of neuromuscular function is important if used partial muscle relaxation during neurophysiological monitoring. Copyright
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TceMEPs and SSEPs Monitoring for Brainstem Surgery
In our patients, we used a continuous infusion of cisatracurium to a T1 reduced to 20% of baseline, considered acceptable by various authors for TceMEP monitoring in patients with normal neurological function.23 In contrast, some authors recommend the use of IV lidocaine (1.5 mg/kg/h) as an adjunct to general anesthesia with intraoperative neurophysiological monitoring because of its ability to reduce anesthetic requirements and decrease the incidence of patient movement during surgery without neuromuscular blockade.25 One limitation of this study is the lack of assessment of TceMEP responses before induction, because of the involved pain. Nevertheless, differences in results obtained between the propofol and sevoflurane groups suggest a higher decrease in TceMEPs in patients anesthetized with sevoflurane. Another limitation of this study is that BIS may actually not have given an equivalent anesthetic effect, given that the drugs have different mechanisms of action and different effects on the BIS; thus, it cannot be considered independent of the anesthetic technique.
CONCLUSIONS Both sevoflurane and propofol at low dosages combined with remifentanil under comparable BIS values and partial muscle relaxation can be used when TceMEP and SSEP monitoring is required for brainstem surgery. REFERENCES 1. Sala F, Manganotti P, Tramontano V, et al. Monitoring of motor pathways during brain stem surgery: what we have achieved and what we still miss? Neurophysiol Clin. 2007;37:399–406. 2. Sloan TB, Janik D, Jameson L. Multimodality monitoring of the central system using motor-evoked potentials. Curr Opin Anaesthesiol. 2008;21:560–564. 3. Manninen PH, Lam AM, Nicholas JF. The effects of isofluranenitrous oxide anesthesia on brainstem auditory evoked potentials in humans. Anesth Analg. 1985;64:43–47. 4. Drummond JC, Todd MM, Sang H. The effect of high dose sodium tiopental on brain stem auditory and median nerve somatosensory evoked response in humans. Anesthesiology. 1985;63:249–254. 5. Nathan N, Tabaraud F, Lacroix F, et al. Influence of propofol concentrations on multipulse transcranial motor evoked potentials. Br J Anaesth. 2003;91:493–497. 6. Sloan TB, Toleikis JR, Toleikis SC, et al. Intraoperative neurophysiological monitoring during spine surgery with total intravenous anesthesia or balanced anesthesia with 3% desflurane. Clin Monit Comput. 2014. doi: 10.1007/s10877-014-9571-9. [Epub ahead of print]. 7. Boisseau N, Madany M, Staccini P, et al. Comparison of the effects of sevoflurane and propofol on cortical somatosensory evoked potentials. Br J Anaesth. 2002;88:785–789. 8. Lo YL, Dan YF, Tan YE, et al. Intraoperative motor-evoked potential monitoring in scoliosis surgery: comparison of desflurane/ nitrous oxide with propofol total intravenous anesthetic regimens. J Neurosurg Anesthesiol. 2006;18:211–214. 9. Li F, Gorji R, Allott G, et al. The usefulness of intraoperative neurophysiological monitoring in cervical spine surgery: a retrospective analysis of 200 consecutive patients. J Neurosurg Anesthesiol. 2012;24:185–190. 10. Weinzierl MR, Reinacher P, Gilsbach JM, et al. Combined motor and somatosensory evoked potentials for intraoperative monitoring: intra- and postoperative data in a series of 69 operations. Neurosurg Rev. 2007;30:109–116. 11. Robinson BJ, Uhrich TD, Ebert TJ. A review of recovery from sevoflurane anaesthesia: comparisons with isoflurane and
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Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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when using inhalational anesthesia versus total intravenous anesthesia during spine surgeries. Spine J. 2014;14:1440–1446. Reinacher PC, Priebe HJ, Blumrich W, et al. The effects of stimulation pattern and sevoflurane concentration on intraoperative motor-evoked potentials. Anesth Analg. 2006;102:888–895. Yang J, Huang Z, Shu H, et al. Improving successful rate of transcranial electrical motor-evoked potentials monitoring during spinal surgery in young children. Eur Spine J. 2012;21:980–984. Sloan TB. Anesthetics effects on electrophysiologic recording. J Clin Neurophysiol. 1998;15:217–226. American Electroencephalographic Society. Guideline eleven: guidelines for intraoperative monitoring of sensory evoked potentials. J Clin Neurophysiol. 1994;11:77–87. Sloan TB. Muscle relaxant use during intraoperative neurophysiologic monitoring. J Clin Monit Comput. 2013;27:35–46. Sekimoto K, Nishikawa K, Ishizeki J, et al. 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;18:106–111. Sloan TB, Mongan P, Lyda C, et al. Lidocaine infusion adjunct to total intravenous anesthesia reduces the total dose of propofol during intraoperative neurophysiological monitoring. J Clin Monit Comput. 2014;28:139–147.
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Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
