The Effects of Stimulation Pattern and Sevoflurane
Concentration on Intraoperative Motor-Evoked Potentials
Peter C. Reinacher, MD, Hans-Joachim Priebe, MD, Winfried Blumrich, MD,
Josef Zentner, MD, and Kai M. Scheufler, MD
Department of Neurosurgery, University Hospital, Aachen, Germany; Department of Anesthesiology, Department of Neurosurgery,
University Hospital, Freiburg, Germany; Cranio Facial Center Hislanden, Hislanden Medical Center, Aaran, Switzerland
The usefulness of intraoperative monitoring of motor-
evoked potentials (MEPs) during inhaled anesthesia is
limited by the suppressive effects of volatile anesthetics
onMEP signals.We investigated the effects of different
stimulation patterns and end-tidal concentrations of
sevoflurane on intraoperative transcranial electrical
MEPs. In 12 patients undergoing craniotomy, stimula-
tion patterns (300–500V, 100–1000Hz, 1–5 stimuli) and
multiples (0.5, 0.75, and 1.0) of minimum alveolar con-
centration (MAC) of sevofluranewere varied randomly
while remifentanil was administered at a constant rate
of 0.2
g
kg
1
min
1.MEPswere recorded from the-
nar and hypothenar muscles and analyzed without
knowledge of the respective MAC. Three-way analysis
of variance revealed significantmain effects for increas-
ing stimulation intensity, frequency, and number of
stimuli on MEP amplitude (P  0.05). Maximum MEP
amplitudes and recording success rates were observed
during 4 stimuli delivered at 1000 Hz and 300 V. A sig-
nificant main effect of sevoflurane concentration (0.5
versus 0.75 and 1 MAC multiple) on MEP amplitude
was observed at the thenar recording site only (P 
0.05). In conclusion, MEP characteristics varied signifi-
cantly with changes in stimulation pattern and less so
with changes in sevoflurane concentration. The results
suggest that high frequency repetitive stimulation al-
lows intraoperative use of MEP monitoring during up
to 1MACmultiple of sevoflurane and constant infusion
of remifentanil up to 0.2
g
kg
1
min
1.
(Anesth Analg 2006;102:888–95)
U se of motor-evoked potentials (MEP) has been es-tablished in intraoperative neurophysiologicalmonitoring of the descending motor pathways be-
cause of the capability of detecting impending iatrogenic
lesions within the motor system at an early, potentially
reversible stage. However, myogenic MEPs are signifi-
cantly suppressed by general anesthesia, particularly by
volatile anesthetics (1–8). The ability to obtain reproduc-
ible responses during intraoperative MEP monitoring
has been considerably improved by the introduction of
repetitive high-frequency stimulation devices and spe-
cifically modified total IV anesthesia protocols (4,9–14).
Whereas the effects of total IV as well as inhaled
anesthesia (including isoflurane, halothane, enflurane
and desflurane) on intraoperative myogenic MEPs
during transcranial electrical stimulation have been
reported (1–3,5,7–9,15), the effect of sevoflurane has
only been studied during single stimulus and paired
stimuli (16). When sevoflurane was administered at
clinically relevant concentrations, transcranial stimu-
lation of the motor cortex with either single stimulus
or paired stimuli did not overcome the depressant
effects of sevoflurane on MEPs (16).
The present study was designed to further define
the effect of different stimulation patterns (induced by
changes in stimulus number, stimulation frequency,
and intensity) and different end-tidal concentrations
of sevoflurane on MEPs evoked by repetitive transcra-
nial electrical stimulation during intracranial neuro-
surgical procedures. We hypothesized that increasing
sevoflurane concentrations produce significant dose-
dependent suppressive effects on MEP amplitude,
which may be partially overcome by choosing appro-
priate stimulation patterns.
Methods
The study protocol complies with the declaration of
Helsinki. After approval by the local Ethics Commit-
tee and the patient’s informed written consent, the
Supported, in part, by a grant from the German Research Foun-
dation (Ze 267/3-2).
Accepted for publication September 27, 2005.
Address correspondence and reprint requests to Kai-Michael
Scheufler, MD, Abt. Cranio Facial Center Hirslanden, Hirslanden
Medical Center CH-500, Aaran, Switzerland. Address e-mail to
kai.scheufler@hirslanden.ch.
DOI: 10.1213/01.ane.0000195235.02162.5d
©2006 by the International Anesthesia Research Society
888 Anesth Analg 2006;102:888–95 0003-2999/06

motor pathways were monitored prospectively by
transcranial MEP in 12 patients (6 male, 6 female; ASA
physical status II–III: n  5/7; mean age: 48 yr [range,
25–61 yr]; mean weight: 72 kg [range, 61–94 kg]; mean
height: 171 cm [range, 164–187 cm]) during supraten-
torial intracranial procedures. Pre-existing impair-
ment of the muscle groups under investigation was
excluded by preoperative clinical and neurophysio-
logical assessment, including electromyography.
All patients were premedicated with 7.5 mg mida-
zolam per os approximately 1 h before induction of
anesthesia. No other centrally acting drugs were ad-
ministered. On arrival in the operating room, catheters
were inserted in peripheral veins and the radial artery
on the arm opposite of the MEP recording site for
administration of fluids and drugs (including IV an-
esthetics), continuous recording of mean arterial blood
pressure (MAP) and regular blood sampling for blood
gas analysis (ABL®; Radiometer, Copenhagen, Den-
mark), respectively. Peripheral oxygen saturation
(Spo2) and depth of anesthesia were monitored con-
tinuously via pulse oximetry (Siemens, Erlangen, Ger-
many) and electroencephalograph EEG bispectral in-
dex (17) (BIS Monitor; Aspect Medical Systems,
Newton, MA), respectively.
Anesthesia was induced by continuous IV infusion
of remifentanil (0.2–0.5
g
kg
1
min
1) and propo-
fol (1–1.5 mg/kg). Cisatracurium (0.1 mg/kg) was
administered to facilitate endotracheal intubation. To
assure systemic arterial oxygen partial pressures
(Pao2) 100 mm Hg at all times, fractional inspired
oxygen concentration (Fio2) was administered at a
minimum of 0.5 in air and adjusted to maintain Spo2
at 99% throughout the investigation. To assure sys-
temic arterial CO2 partial pressures (Paco2) of 35-42
mm Hg, ventilation was adjusted to maintain end-
tidal Paco2 between 28 and 35 mm Hg throughout the
investigation. A warming/cooling blanket was used
to maintain rectal temperature between 35°C and
37°C.
Hypotension (MAP60 mm Hg in normotensive or
70 mm Hg in hypertensive patients, respectively)
and bradycardia (heart rate 45 bpm) were treated
with IV administration of Akrinor® (1–2 mL IV of a 2:8
Cafedrin-HCl/Theodrenalin-HCl normal saline mix-
ture) and 5–10 mg etilefrin (Effortil®; Boehringer In-
gelheim, Basel, Switzerland), respectively. All vital
signs were recorded continuously (SC 9000®; Sie-
mens). Fluid administration was guided by central
venous pressure and urine output. All anesthetics
were administered by two of the investigators (W. B.,
H.-J. P.).
In each patient, the end-tidal concentration of
sevoflurane was varied randomly (sealed envelope
technique) corresponding to 0.5, 0.75 and 1.0 multi-
ples of minimum alveolar concentration (MAC) of
sevoflurane. The reported age-adjusted sevoflurane
MAC values vary considerably. For the age brackets
18–25 yr, 26–40 yr, and 40 yr we defined 1 MAC
as 2.6%, 2.2%, and 1.8%, respectively (18,19). After
each change in sevoflurane concentration, the end-
tidal concentration of sevoflurane had to have re-
mained unchanged at the selected concentration,
and the continuously monitored MAP and heart rate
values had to have remained within a 5% range for
15 min before MEPs were recorded. Throughout the
investigation, remifentanil was administered un-
changed at 0.2
g
kg
1
min
1.
MEPs were recorded by standard neurophysiologi-
cal equipment (Spirit® evoked potential system; Nico-
let Biomedical, Madison, WI). Compound muscle ac-
tion potentials were derived from subdermal needle
electrodes placed in the abductor pollicis brevis (the-
nar) and abductor digiti minimi (hypothenar) muscles
using a belly-tendon montage. Before commencing
with MEP recordings, complete recovery from neuro-
muscular blockade was verified by train-of-four and
double-burst stimulation. Electrode impedances be-
low 5 k were accepted (mean electrode impedances
1 k). The high and low pass filters were set at 30 Hz
and 3 kHz, respectively. The notch filter was deacti-
vated. The stimulating device (Digitimer™ D185;
Digitimer Ltd., Welwyn Garden City, Hertfordshire,
UK) was connected to the Spirit™ evoked potential
system and served as an external triggering device. It
was capable of delivering trains of constant-voltage
rectangular electrical stimuli of 200
s duration at
frequencies ranging from 100–1000 Hz and stimulat-
ing intensities of 1–1000 V. Stimuli were delivered
transcranially via subdermal needle electrodes placed
at Cz (cathode) and contralaterally to the craniotomy
site C3 or C4 (anode) according to the international
10/20 system. The stimulation was performed con-
tralaterally to the craniotomy side to allow intraoper-
ative MEP recording of unaffected motor pathways.
After craniotomy and dural opening, the study proto-
col was started.
Each recording cycle assessed MEPs in response to
a) variation in stimulation current (100, 150, 200, 250,
300 V) at constant stimulation frequency (500 Hz) and
constant number of stimuli (n  4), b) variation in
stimulation frequency (100, 200, 500, 1000 Hz) at con-
stant stimulation intensity (300 V) and constant num-
ber of stimuli (n  4), or c) variation in number of
stimuli (n  1–5) at constant stimulation intensity (300
V) and constant stimulation frequency (500 Hz). Thus,
12 different stimulation patterns were investigated at
each of the 3 sevoflurane concentrations (Table 1).
Two consecutive MEP recordings (separated by 30 s)
were performed after each change in stimulation pat-
tern (i.e., 12  2 measurements per MAC). To exclude
conditioning effects of repetitive stimulation on MEP
characteristics, the stimulation pattern was varied
randomly.
ANESTH ANALG NEUROSURGICAL ANESTHESIA REINACHER ET AL. 889
2006;102:888–95 STIMULATION PATTERN, SEVOFLURANE CONCENTRATION, AND MEP