Research Note

Journal of International Medical Research

41(3) 762–770
Electromyographic response ! The Author(s) 2013
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DOI: 10.1177/0300060513484435
under different levels of imr.sagepub.com

neuromuscular blockade
during middle-ear surgery
Won Joo Choe1, Jun Hyun Kim1, Si Young Park2
and Jin Kim2

Abstract
Objective: To investigate facial nerve monitoring in patients receiving the partial nondepolarizing
neuromuscular blocking agents (NMBAs), remifentanil and propofol.
Methods: Patients with normal facial function and advanced middle-ear disease were enrolled. For
total intravenous anaesthesia (TIVA), propofol and remifentanil were infused as induction/
maintenance anaesthesia. Stimulation thresholds and amplitudes were recorded at each train-of-
four (TOF) nerve stimulation level. Time differences between start of TOF and electromyographic
(EMG) amplitude decreases (Ti), and between complete recovery of TOF and EMG amplitudes
(Tr), were calculated.
Results: Fifteen patients were enrolled. Mean  SD Ti was 3.4  1.28 min; Tr was 18.7  4.41 min.
Amplitude of stimulation was apparent mostly at TOF level 1. In most cases, no or a weak response
(<100 mV) was observed at TOF 0. Mean  SD threshold of electrical stimulation was
0.31  0.10 mA at TOF 1. At TOF > 2, all cases showed EMG response on electrical stimulation.
Conclusions: Induction of TIVA using propofol and remifentanil provided reliable conditions for
delicate microsurgery. Minimal NMBA use, considered as producing TOF levels >1, was sufficient
for facial nerve monitoring in neuro-otological surgery.

Keywords
Facial nerve, monitoring, electromyography, total intravenous anaesthesia, propofol, remifentanil
train-of-four, neuro-otological surgery

Date received: 2 February 2013; accepted: 16 February 2013

1
Department of Anaesthesiology and Pain Medicine, Inje
University College of Medicine, Ilsan Paik Hospital,
Gyeonggi-do, Republic of Korea
2
Department of Otorhinolaryngology, Inje University
College of Medicine, Ilsan Paik Hospital, Gyeonggi-do,
Republic of Korea
Corresponding author:
Dr Jin Kim, Department of Otorhinolaryngology, Inje
University College of Medicine, Ilsan Paik Hospital, 2240
Daehwa-dong, IlsanSeo-gu, Goyang-si, Gyeonggi-do,
Republic of Korea.
Email: jinsound@gmail.com
Choe et al.
Introduction
Given the unique location, size and delicate
content of the middle ear, great care must be
taken during the perioperative period in
patients undergoing middle-ear surgery.
Special considerations include the provision
of a bloodless surgical field, attention to the
patient’s head position, airway manage-
ment, facial nerve monitoring, recognition
of the effect of nitrous oxide on the middle
ear, and the prevention of postoperative
nausea and vomiting.1–4 Neuromuscular
blocking agents (NMBAs) commonly used
in anaesthesiology for muscle relaxation
frequently impede intraoperative electro-
myographic (EMG) monitoring of the
motor-evoked potentials of the facial
nerve.5 NMBAs act directly on the neuro-
muscular junction and block signal trans-
mission, which provides favourable surgical
conditions but may interfere with facial
nerve monitoring.6
Delicate microsurgical intervention
demands absolute immobility of the patient
in neurosurgery, and facial nerve injury is a
devastating potential complication.7
Intraoperative monitoring of the facial
nerve during neurosurgical procedures is
widely accepted, to aid in the preservation
of facial nerve function.811
The preservation of facial nerve function
can be achieved by using large doses of
narcotics and volatile anaesthetic agents,
without the administration of a muscle
relaxant.8,1113 This anaesthetic technique
is poorly tolerated by some patients with
severe haemodynamic instability, however,
necessitating the use of vasopressors to
support the circulatory system.6, Others
have recommended the use of partial
NMBAs, which protect patients from the
cardiovascular depression that results from
high-dose anaesthesia while keeping patients
immobilized.14,15 Surgeons using this tech-
nique should be aware that sudden (unex-
pected) patient movement may jeopardize
763
surgical success. Maintaining a balance
between haemodynamic stability and abso-
lute immobility, while preserving an optimal
condition for facial EMG monitoring, is
essential.
Propofol, which is a widely used intra-
venous (i.v.) anaesthetic agent, does not
enhance the neuromuscular blockade pro-
duced by NMBAs. Propofol causes the
widespread inhibition of the N-methyl-D-
aspartate (NMDA) subtype of the glutam-
ate receptor through the modulation of
sodium-channel gating, and contributes
to the central nervous system (CNS) effects
of the drug, with no effect on evoked EMG
or twitch tension.16,17 Although many dif-
ferent compounds can be used in various
combinations to provide total i.v. anaesthe-
sia (TIVA), the combination of remifentanil
and propofol produces excellent results.
Remifentanil provides analgesia and haemo-
dynamic stability while blunting responses
to noxious stimuli; propofol provides hyp-
nosis and amnesia, and is an antiemetic.18,19
Thus, remifentanil and propofol TIVA can
be used as an optimal anaesthetic technique,
especially for neuromuscular monitoring of
the peripheral nervous system, because
blockade levels can be controlled simply by
administering the appropriate dosage of a
nondepolarizing NMBA; the appropriate
dosage can be determined readily from
response to train-of-four (TOF) nerve
stimulation.20,21
In TOF nerve stimulation, four supra-
maximal stimuli (2 Hz) are given every 0.5 s
and each stimulus in the train causes the
muscle to contract; the degree to which the
response diminishes provides the basis for
evaluation. The degree of blockade by
nondepolarizing NMBAs can be determined
directly from the TOF response.22,23
The present study investigated the effect-
iveness of facial nerve monitoring in
patients who had received partial nondepo-
larizing NMBAs and a combination of
remifentanil and propofol to induce TIVA.
764
The appropriate level of NMBAs for facial
nerve monitoring in neurosurgery was also
determined.
Patients and methods
Study population
Consecutive patients with normal facial
function who had advanced middle-ear dis-
ease (characterized by a dehiscent fallopian
canal on the tympanic segment or a defective
fallopian canal due to advanced cholestea-
toma) were enrolled in this prospective
study. The study was conducted at Inje
University, Ilsan Paik Hospital, Gyeonggi-
do, Republic of Korea, between October
2011 and September 2012.
Prior to surgery, all patients were checked
by temporal bone computed tomography
scan, to investigate the fallopian canal and
integrity of the intratemporal facial nerve, in
addition to middle-ear disease. Patients were
scheduled for elective otological surgery
(intact canal wall or open mastoidectomy
with tympanoplasty) under general anesthe-
sia with TIVA. Those who had an intact
fallopian canal, without facial nerve expos-
ure or interference of facial nerve integrity,
were excluded from the study. There were no
other specific inclusion or exclusion criteria
for the study.
The study was approved by the
Committee for Medical Ethics of Inje
University Hospital. Written informed con-
sent was obtained from all patients prior to
enrolment.
General anaesthesia protocol
All patients received premedication of
0.05 mg/kg midazolam and 0.2 mg glycopyr-
rolate intramuscularly (i.m.) at 1 h and just
before the induction of anaesthesia, respect-
ively. Standard evaluations using electrocar-
diography, pulse oximetry and noninvasive
blood pressure monitoring were carried out.
For TIVA, propofol and remifentanil were
Journal of International Medical Research 41(3)
administered concurrently by i.v. infusion
using a target-controlled infusion system
(OrchestraÕ Base Primea, Fresenius Vial
S.A.S., Brezins, France), for induction and
maintenance of anaesthesia. Effect-site con-
centrations of propofol and remifentanil
were kept within the ranges of 2–5 mg/ml
and 2–5 ng/ml, respectively. After loss
of consciousness and TOF calibration,
0.6 mg/kg rocuronium bromide i.v. was
administered as a muscle relaxant. Depth
of anaesthesia was monitored using a bis-
pectral index score monitor (A-200; Aspect
Medical Systems, Newton, MA, USA) and
maintained within the range of 40–60.
Controlled ventilation was performed with
40% oxygen in air to maintain end-tidal
CO2 at 35–40 mm Hg during surgery. Body
temperature was maintained at 36–37 C
using a forced-air warming system through-
out surgery.
Facial monitoring
Intraoperative four-channel facial nerve
EMG monitoring was performed with a
NIM-Response 3.0 system (Medtronic
Xomed, Jacksonville, FL, USA) in all
patients. Two bipolar-paired subdermal
needle electrodes were placed in the orbicu-
laris oris and orbicularis oculi. The differ-
ence between electrode impedances
remained <1 k during the recordings for
all channels. The facial nerve was electrically
stimulated by a monopolar probe with a
0.5-mm tip. Square current waves of 100-ms
duration at a frequencyof 4 Hz were applied
as stimulation.
Two parameters were measured: (1) max-
imal amplitude of the responses (in mV) on
one of the two channels after supramaximal
stimulation at 2 mA (indicative of intensity);
(2) stimulation threshold (in mA), deter-
mined by increasing the stimulation inten-
sity in increments of 0.05 mA between 0.1
and 0.6 mA until a response >100 mV on at
least one channel was obtained.
Choe et al.
TOF nerve stimulation
Train-of-four (TOF) nerve stimulation was
used to evaluate the degree of neuromuscu-
lar function. TOF nerve stimulation was
defined by four supramaximal stimuli (2 Hz)
given every 0.5 s, causing the muscle to
contract. The degree to which the response
diminished provides the basis for evaluation.
After induction of general anaesthesia,
neuromuscular function was monitored at
the adductor pollicis of the thumb, using the
TOF-Watch (Organon Ireland, Dublin,
Republic of Ireland). The device was
stabilized by using 1-min repetitive TOF
stimulation, followed by 50-Hz tetanic
stimulation for 5 s and 3–4 min of repetitive
TOF stimulation. The supramaximal thresh-
old was determined using the CAL 2 mode
and the acceleration transducer was cali-
brated in the standard fashion, described in
the manufacturer’s instruction booklet.
After calibration of the TOF-Watch, each
participant received 0.6 mg/kg rocuronium
bromide i.v. and the trachea was intubated
when the level was 0, after full recovery of
TOF level at facial nerve exposure.
Additional bolus doses of 0.15 mg/kg rocur-
onium bromide i.v. were administered until
the TOF level decreased to 0. As the effects
of NMBAs disappeared, the TOF level and
EMG amplitude were concurrently rec-
orded. All neuromuscular response data
were recorded on an interfaced laptop.
Study procedure
After complete recovery of peripheral
neuromuscular function following NMBA
administration during induction, the base-
line facial nerve response evoked by elec-
trical stimulation was recorded. Then,
repeated doses of rocuronium bromide
were given to attain TOF level 0, and
administration of rocuronium bromide
ceased until the targeted TOF level at 0, 1,
2, 3 and 4 s was reached. Stimulation
765
thresholds and amplitudes of facial EMG
responses were recorded at each TOF level.
Preliminary experiments revealed a differ-
ence in response timing between the adduc-
tor pollicis and facial muscles. At the first
additional injection of rocuronium bromide,
the time difference between the start of TOF
decrease and that of the EMG amplitude
decrease was calculated (Ti). After recovery
from NMBAs, the time difference between
complete recovery of TOF and that of EMG
amplitude was calculated (Tr).
Statistical analyses
Statistical analyses were performed using
the SPSSÕ software package, version 16.0
(SPSS Inc., Chicago, IL, USA) for
WindowsÕ . Differences between groups
were tested for statistical significance using
an independent -samples t-test and Fisher’s
exact test. A P-value of < 0.05 was con-
sidered to be statistically significant.
Results
Fifteen patients – eight women and seven
men, mean age 59.1 years (range, 34–80
years) – were enrolled in the study. Thirteen
patients underwent primary surgery and two
patients underwent surgical revision. None
of the patients had temporary or permanent
facial nerve paralysis before or after surgery.
In all cases, the facial nerve could be
identified and clearly visualized during sur-
gery, and the baseline amplitude was
obtained after the TOF level of 4.
The mean  SD Ti was 3.4  1.3 min and
the mean  SD Tr was 18.7  4.4 min
(Figure 1). The amplitude of stimulation
on the exposed segment of the facial nerve
was apparent mostly at a TOF level of 1. In
most cases, no response or a weak (<100 mV)
response was observed at a TOF level of 0
(Figure 2A). The mean  SD threshold of
electrical stimulation was 0.31  0.10 mA at
a TOF level of 1. At TOF levels >2, all cases
766 Journal of International Medical Research 41(3)

Figure 1. Changes in train-of-four (TOF) and electromyographic (EMG) responses over time in patients
(n ¼ 15), receiving partial nondepolarizing neuromuscular blocking agents (NMBAs) and remifentanil plus
propofol, to induce total intravenous anaesthesia (TIVA). Data on time differences between TOF level and
EMG response were obtained for each patient, defined as: Ti, on-time difference between start of TOF
decrease and start of EMG amplitude decrease; Tr, after recovery from NMBAs, time difference between
complete recovery of TOF and of EMG amplitude. Mean  SD Ti was 3.4  1.3 min; mean  SD Tr was
18.7  4.4 min; EsmeronÕ is a trade name of rocuronium bromide.

showed an EMG response on electrical knowledge of its anatomy, the goals of

stimulation (average threshold,
0.26  0.10 mA). No significant difference
in thresholds was observed between TOF
levels of 2 and 3, or between levels of 3 and 4.
The facial nerve stimulation threshold was
significantly higher at TOF level 1 than at
TOF level 2 (P < 0.05). The mean  ampli-
tudes of EMG response were 149.1 
75.6 mV at TOF level 1, 307.2  149.5 mV at
level 2, 403.8  134.3 mV at level 3 and
449.6  110.7 mV at level 4 (Figure 2B ).
Discussion
The NMBAs can render the facial muscula-
ture unresponsive to electrical and mechan-
ical stimulation in neurosurgery. For this
reason, anaesthetists are asked to avoid the
use of NMBAs when maintaining anaesthe-
sia during surgery.6 Although the best
means of protecting the facial nerve in
otological surgery is to possess a complete
intraoperative facial nerve monitoring
include early identification of the facial
nerve by electrical stimulation, warning the
surgeon of any unexpected facial nerve
manipulation and reducing mechanical
trauma to the facial nerve during the
operation.24
Unresponsiveness to intraoperative elec-
trical stimulation can be an issue for sur-
geons undertaking delicate microsurgical
interventions because no response at a high
current suggests substantial facial nerve
damage. Thus, maintaining a balance
between haemodynamic stability and abso-
lute immobility, while preserving optimal
conditions for facial EMG monitoring, is
essential. The present study investigated the
effectiveness of facial nerve monitoring in
patients who had received partial nondepo-
larizing NMBAs and a combination of
remifentanil and propofol to induce TIVA.
In addition, the appropriate levels of
Choe et al. 767

Figure 2. Train-of-four (TOF) and electromyographic (EMG) responses in patients receiving partial
nondepolarizing neuromuscular blocking agents (NMBAs), and remifentanil plus propofol, to induce total
intravenous anaesthesia (TIVA). (A) Amplitude levels of stimulation on the exposed segment of the facial
nerve were apparent mostly at TOF level 1; in most cases, no response or a weak (< 100 mV) response was
observed at TOF 0; mean  SD threshold of electrical stimulation was 0.31  0.10 mA at TOF 1; at TOF > 2,
all cases showed an EMG response to electrical stimulation (mean  SD threshold, 0.26  0.10 mA).
(B) Mean  SD amplitudes of EMG response were 149.1  75.6 mV at TOF 1, 307.2  149.5 mV at TOF 2,
403.8  134.3 mV at TOF 3, and 449.6  110.7 mV at TOF 4. Each dot represents data from each patient.
768
NMBAs for facial nerve monitoring in
neurosurgery were determined. The facial
nerve was sequentially stimulated at various
TOF levels to determine an adequate and
suitable anaesthetic technique for facial
nerve monitoring. In all cases, NMBAs did
not affect the facial musculature when the
surgeon reached the facial nerve. The stimu-
lation threshold of the facial nerve at TOF
level 1 differed significantly from that at
other TOF levels. Above TOF level 2,
NMBA administration with TIVA provided
sufficient immobility, while preserving
the optimal conditions for facial EMG
monitoring.
Some authors have reported a difference
in sensitivity between facial and ulnar nerve
responses to NMBAs.25–28 The present
study showed the facial musculature to be
less sensitive than the hypothenar muscle to
the neuromuscular effect of NMBAs. This
allowed the evaluation of the time difference
in NMBA effectiveness, between the
responses of facial and ulnar nerves.
In this anaesthetic technique using
NMBAs and TIVA, the mean TOF levels
showed no increased risk of iatrogenic facial
nerve injury. Except for a short period at
level 0, which lasted for 10–15 min after
additional NMBA injection for mainten-
ance, the facial nerve was not endangered by
NMBAs during surgery. Propofol is widely
used as an i.v. agent for the induction of
general anaesthesia in patients >3 years of
age. Its use is characterized by rapid onset
and short duration of action which, together
with its stress control and amnesic proper-
ties, make it an ideal hypnotic agent for use
during surgical procedures.29,30 In contrast
to inhalational anaesthetics, which potenti-
ate the neuromuscular blocking effects of
NMBAs, propofol mainly contributes to the
CNS effects of the drug on spinal cord
neurons; it does not enhance neuromuscular
blockade induced by NMDAs that have no
effect on the evoked EMG.16,17 We consider
propofol to be a good anaesthetic because it
Journal of International Medical Research 41(3)
provides good surgical conditions for facial
nerve monitoring and favourable postopera-
tive conditions for middle-ear surgery, due
to its antiemetic effects. In addition, propo-
fol produces a favourable sense of wellbeing
in the patient.31–33 Remifentanil is a syn-
thetic opioid, with potent and selective
m-opioid receptor agonist activity, that is
rapidly metabolized in the blood and tissue,
with an elimination half-life of 9 min.34
Remifentanil was used in the present study
as it has been used successfully in without-
muscle relaxants anaesthesia, and maintains
a stable haemodynamic state during
surgery.35 In TIVA, using propofol and
remifentanil, the level of neuromuscular
blockade can be controlled simply with
NMBAs. Adjustment of NMBAs should,
however, be made by administering larger
maintenance doses at more frequent inter-
vals, or by using higher infusion rates for
otological surgery.
Intraoperative anaesthetic management
of patients undergoing neurotological sur-
gery is made more difficult by the need to
maintain a balance between haemodynamic
stability and absolute immobility, while
providing optimal conditions for facial
EMG monitoring. With TIVA using pro-
pofol and remifentanil, the controlled infu-
sion of NMBAs titrated to TOF level 1
and EMG responses in the hypothenar
muscle did not impair the capacity of
facial nerve monitoring to detect facial
nerve injury. Given the variability in
NMBA effects on different muscles, the
time difference between TOF levels of the
ulnar and facial nerves should be con-
sidered when assessing facial EMG. The
present study suggests that the induction of
TIVA using propofol and remifentanil
provides reliable surgical conditions for
delicate microsurgery, and that minimal
NMBA use – which is considered to be
that which produces TOF levels >1 in the
adductor pollicis – is sufficient for facial
nerve monitoring in neurotological surgery.
Choe et al.
Declaration of conflicting interest
The authors declare that there are no conflicts of
interest.
Funding
This work was supported by a 2012 grant from
the research foundation of Inje University,
Republic of Korea.
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