The Modifying Effects of Stimulation Pattern and Propofol
Plasma Concentration on Motor-Evoked Potentials
Kai M. Scheufler, MD*, Peter C. Reinacher, MD†, Winfried Blumrich, MD‡, Josef Zentner, MD*,
and Hans-Joachim Priebe, MD†
*Department of Neurosurgery, University Hospital, Freiburg, Germany; †Department of Neurosurgery, University
Hospital, Aachen, Germany; and ‡Department of Anesthesiology, University Hospital, Freiburg, Germany
The quality of intraoperative motor-evoked potentials
(MEPs) largely depends on the stimulation pattern and
anesthetic technique. Further improvement in intraop-
erativeMEP recording requires exact knowledge of the
modifying effects of each of these factors. Accordingly,
we designed this study to characterize the modifying
effect of different stimulation patterns during different
propofol target plasma concentrations (PTPCs) on in-
traoperatively recorded transcranial electricalMEPs. In
12 patients undergoing craniotomy, stimulation pat-
terns (300–500V; 100–1000Hz; 1–5 stimuli)werevaried
randomly at different PTPCs (2, 4, and 6
g/mL).
Remifentanil was administered unchanged at 0.2

g·kg

1
· min

1
.MEPswere recorded from the thenar
and hypothenar muscles. Analysis of MEPs was
blinded to the PTPC. Three-way analysis of variance
revealed significant main effects of increasing stimula-
tion intensity, frequency, and number of stimuli on
MEP amplitude (P 0.05). MaximumMEP amplitudes
and recording success rates were observed with three
or more stimuli delivered at 1000 Hz and 150 V. A
significantmain effect of PTPC (2 vs 4 and 6
g/mL) on
MEP amplitude was observed at the thenar recording
site only (P 0.05). An amplitude ratio calculated from
correspondingMEPs evoked by double and quadruple
stimulation proved to be insensitive to changes in
PTPC. In conclusion, MEP characteristics varied signif-
icantly in response to changes in stimulation pattern
and less to changes in PTPC.
(Anesth Analg 2005;100:440–7)
I
ntraoperative assessment of motor-evoked poten-
tials (MEPs) has gained increasing popularity in
routine clinical practice. Although the clinical value
of intraoperative MEP monitoring in detecting im-
pending iatrogenic lesions in the motor system at an
early, reversible stage is well documented, its intraop-
erative usefulness has been improved by the introduc-
tion of total IV anesthesia protocols (1,2) and repetitive
high-frequency stimulation devices (3,4). Despite such
technical advances, meaningful interpretation of intra-
operative MEP changes relies on suitable recording
conditions that minimize alterations in neuronal im-
pulse generation and conduction and that generate
reproducible signals. This, in turn, requires detailed
knowledge of the effect of anesthetic technique and
stimulation pattern on MEP characteristics.
Previous investigations have examined the effect of
various anesthetic techniques and stimulation pat-
terns on the quality of intraoperative MEP recording
(1,2,5–9). This study was designed to further define
the effect of different stimulation patterns (induced by
changes in stimulus number, frequency, and intensity)
and various propofol target plasma concentrations
(PTPCs) on MEPs evoked by repetitive transcranial
electrical stimulation during intracranial neurosurgi-
cal procedures. We hypothesized that variations in
both stimulation pattern and PTPC would modify
MEPs. By analyzing the effect of different stimulation
patterns on MEP characteristics under surgical anes-
thesia, this study aimed to further improve the clinical
utility of intraoperative MEP monitoring.
Methods
The study protocol complies with the Declaration of
Helsinki. After approval by the institutional Medical
Ethics Review Board and after we obtained written,
informed consent, 12 patients (4 men and 8 women;
ASA physical status classification: I, n 2; II, n 5; III,
n 5; age: mean, 49 yr; range, 22–67 yr; weight: mean,
Supported by Grant Ze 267/3-2 from the German Research
Foundation.
Accepted for publication July 20, 2004.
Address correspondence and reprint requests to Kai M. Scheufler,
MD, Abt. Allgemeine Neurochirurgie, Universita¨tsklinikum
Freiburg, Breisacher Str. 64, D-79106 Freiburg, Germany. Address
e-mail to scheufle@nz11.ukl.uni-freiburg.de.
DOI: 10.1213/01.ANE.0000141678.04200.86
2005 by the International Anesthesia Research Society
440 Anesth Analg 2005;100:440–7 0003-2999/05

73 kg; range, 50–105 kg) admitted for supratentorial
intracranial procedures were studied prospectively.
Impairment of the muscle groups targeted for intra-
operative investigation was excluded by preoperative
clinical and neurophysiological assessment, including
electromyography.
To minimize the possibility of intraoperative aware-
ness at small PTPCs (see below), all patients were
premedicated with 7.5 mg of midazolam by mouth 1 h
before the induction of anesthesia. No other centrally
acting drugs were administered. On arrival in the
operating room, catheters were inserted in peripheral
veins and the radial artery on the arm opposite to the
MEP recording site for the administration of fluids
and IV anesthetics, continuous recording of mean ar-
terial blood pressure (MAP), and regular blood sam-
pling for blood gas analysis (ABL
®
; Radiometer,
Copenhagen, Denmark), respectively. Peripheral oxy-
gen saturation (Spo
2
) and depth of anesthesia were
monitored continuously via pulse oximetry (Siemens,
Erlangen, Germany) and electroencephalographic
bispectral index (BIS) (10) (BIS-Monitor; Aspect Med-
ical Systems, Newton, MA), respectively.
Anesthesia was induced by continuous IV infusion
of remifentanil (0.2–0.5
g·kg

1
·min

1
) and of
propofol administered to achieve PTPCs of 4
g/mL
(Alaris TCI/TIVA 9000, incorporating the Diprifu-
sor™ module; Zeneca Pharmaceuticals, Cheshire,
UK). Cisatracurium (0.1 mg/kg) was administered to
facilitate endotracheal intubation. Oxygenation, venti-
lation, body temperature, and systemic perfusion
pressure were continuously monitored and kept con-
stant. To ensure systemic arterial oxygen partial pres-
sures (Pao
2
)of100 mm Hg at all times, fractional
inspired oxygen concentration was administered at a
minimum of 0.5 in air and was adjusted to maintain
Spo
2
at 99% throughout the investigation. To ensure
a systemic arterial CO
2
partial pressure (Paco
2
)of
30–40 mm Hg, minute ventilation was adjusted to
maintain end-tidal partial pressure of CO
2
(Petco
2
)
between 25 and 35 mm Hg throughout the investiga-
tion. A warming/cooling blanket was used to main-
tain rectal temperature between 35°C and 37°C. Hy-
potension (MAP 60 mm Hg in normotensive or
70 mm Hg in hypertensive patients) was treated by IV
administration of 1–2 mL of Akrinor
®
(Cafedrin-HCl/
Theodrenalin-HCl) diluted 2:8 with normal saline so-
lution. All vital variables were recorded continuously
(SC 9000
®
; Siemens). Fluid administration was guided
by central venous pressure and urine output. All an-
esthetics were administered by two of the investiga-
tors (WB and H-JP). In each patient, PTPCs were var-
ied randomly among 2, 4, and 6
g/mL (sealed-
envelope technique). Throughout the investigation,
remifentanil was administered unchanged at 0.2

g·kg

1
·min

1
. After equilibration of each of the
PTPCs, the continuously monitored MAP and heart
rate values had to have remained within a 5% range
for at least 10 min before MEPs were recorded.
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 hypodermic needle
electrodes placed in the abductor pollicis brevis (the-
nar) and abductor digiti minimi (hypothenar) muscles
by using a belly-tendon montage. Electrode imped-
ances 5k were accepted (mean electrode imped-
ance, 1k). The high- and low-pass filters were set
at 30 Hz and 3 kHz, respectively. The notch filter was
deactivated. The stimulating device (Digitimer™
D185; Digitimer Ltd., Welwyn Garden City, Hertford-
shire, UK) was connected to the Spirit™ evoked po-
tential system and served as an external triggering
device. It was capable of delivering trains of constant-
voltage rectangular electrical stimuli with a duration
of 200
s at frequencies ranging from 100 to 1000 Hz
and stimulating intensities of 1–1000 V. Stimuli were
delivered transcranially via hypodermic needle elec-
trodes placed ipsilaterally to the craniotomy site at Cz
(cathode) and C3 or C4 (anode) according to the in-
ternational 10/20 system. After craniotomy and dural
opening, the study protocol was started.
Each recording cycle assessed MEPs in response to
(a) variation in stimulation current (100, 150, 200, 250,
or 300 V) at a constant stimulation frequency (500 Hz)
and a constant number of stimuli (n  4), (b) variation
in stimulation frequency (100, 200, 500, or 1000 Hz) at
a constant stimulation intensity (300 V) and a constant
number of stimuli (n  4), or (c) variation in the
number of stimuli (n  1–5) at a constant stimulation
intensity (300 V) and a constant stimulation frequency
(500 Hz). Thus, different stimulation patterns were
investigated at each of the 3 PTPCs. Two consecutive
MEP recordings (separated by 30 s) were performed
after each change in stimulation pattern (i.e., 12  2
measurements per PTPC). To exclude conditioning
effects of repetitive stimulation on MEP characteris-
tics, the stimulation pattern was varied randomly.
Amplitudes were measured from peak to baseline.
Latencies were defined as the interval between the
onset of the stimulation artifact and the onset of the
MEP. MEP amplitudes and latencies were indepen-
dently reviewed by two investigators blinded to the
PTPCs (PCR and KMS). Data evaluated by two inves-
tigators were averaged before further processing.
The sample size required to obtain statistical signif-
icance was calculated on the basis of MEP amplitude
changes during previous studies (2) and the standard
threshold for significant MEP amplitude changes (50%
of baseline values). Because assessment of all possible
combinations between the various stimulation vari-
ables (voltage, frequency, and number of stimuli) and
PTPCs was not feasible, our study protocol comprised
a reduced factorial design. The individual effects of
ANESTH ANALG TECHNOLOGY, COMPUTING, AND SIMULATION SCHEUFLER ET AL. 441
2005;100:440–7 STIMULATION PATTERN, PROPOFOL, AND MOTOR-EVOKED POTENTIALS