Neuromuscular monitoring

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347
Neuromuscular Monitoring : A Review
Babita Ghai, Jeetinder Kaur Makkar, Jyotsna Wig
ABSTRACT
Residual neuromuscular blockade in the postoperative period contributes to significant morbidity and
possibly mortality. The incidence of residual neuromuscular blockade has been shown to decrease with the
use of neuromuscular monitoring and short acting neuromuscular blocking drugs. Because of marked
variation in patient's sensitivity to neuromuscular blockade, the neuromuscular function of the patient
receiving intermediate or long action muscle relaxant should be monitored. This article reviews the basic
principles of peripheral nerve stimulation, pattern of nerve stimulation and methods used to evaluate evoked
neuromuscular responses.
KEYWORDS : Neuromuscular blocking agents, Train of four, Double burst stimulation
Drs. Babita Ghai, Assistant Professor, Jeetinder Kaur Makkar, Senior Resident, Jyotsna Wig, Professor and
Head, Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education &
Research, Chandigarh-160012, India.
Correspondence : Babita Ghai,
Neuromuscular blocking agents (NMBA) are being
used in clinical anesthesia for more than half a century
now. Under anesthesia and during recovery from
anesthesia, assessment of neuromuscular function can
be done either by clinical tests or by the response of
muscle to nerve stimulation. Clinical tests for assessment
of neuromuscular function are muscle tone, head lift,
eye opening, tongue protrusion, handgrip, tidal volume,
peak inspiratory pressure etc.
In perioperative period, a variety of factors can
influence response of a patient to NMBA. Because of
marked variation in patient sensitivity to NMBA,
problem of postoperative residual NM paralysis is
increasing. Therefore, the response of the muscle to
nerve stimulation should be assessed to titrate use of
NMBA to desired clinical effect in an anesthetized
patient. The use of peripheral nerve stimulation allows
the clinician to assess the intensity of neuromuscular
blockade (NMB). Profound muscle relaxation (to permit
tracheal intubation and ensure immobility), moderate
muscle relaxation (to facilitate surgical procedure) and
recovery of neuromuscular function can be evaluated
by monitoring evoked muscle response to nerve
stimulation. This article reviews an overview of anatomy
and physiology of neuromuscular transmission,
fundamental principles of neurostimulation, patterns of
nerve stimulation, equipment used for neuromuscular
monitoring and evaluation of recorded evoked responses.
Neuromuscular junction
The region of approximation between motor nerve
fiber and a muscle cell is the neuromuscular junction
(NMJ) (Figure-1).1 The membrane of the nerve terminal
and muscle fiber are separated by a narrow gap of 20-
50 nm called synaptic cleft. Adult NMJ is formed by
three cells that constitute the synapse- the Schwann
cell, the motor nerve and the muscle fiber (Figure-1).
The motor neuron from the ventral horn of the spinal
cord innervates the muscle. Each muscle fiber receives
only one synapse. The motor neuron loses its myelin
sheath to terminate on the muscle fiber and forms a
spray of terminal branches against the muscle surface
and is covered by Schwann cell. The terminal Schwann
cell extends to the muscle fiber enclosing NMJ and
separating it from extra cellular fluid.1 The nerve terminal
has vesicles clustered around the membrane thickening,
which are the active zone. The muscle surface (muscle
end plate) is corrugated with deep invaginations of the
J Anaesth Clin Pharmacol 2006; 22(4) : 347-356
348
junctional cleft- the primary and secondary clefts. The
shoulders of the folds are densely populated with
acetylcholine (Ach) receptors.2
Neuromuscular transmission : An overview
Ach is synthesized and stored in small vesicles in
axonal terminal of motor nerves. Each vesicle contains
approximately 5,000 to 10,000 molecules. Ach in the
nerve terminal is available in two fractions: a small,
immediately available, active pool stored in vesicles
and a larger reserve pool found both free in cytoplasm
and in vesicles.3 When a nerve is stimulated, action
potential is generated and reaches the nerve terminal,
the voltage gated ion channels open and calcium influx
occurs. This leads to fusion of 200-400 vesicles from
the active pool with the axonal membrane and release
Ach into the synaptic cleft.4 Released Ach gets attached
to the receptors on the muscle end plate and depolarizes
it by opening ion channels. This produces an end plate
potential and triggers adjacent muscle membrane into
initiating a contraction.2
Fundamental principles of neurostimulation :
Neuromuscular function is monitored by evaluating
the response of the muscle to supramaximal stimulation
of a peripheral motor nerve. Stimulation of a single
muscle fiber follows all-or-none principle. However,
when the whole muscle is stimulated, the response
depends upon the number of muscle fibers stimulated.
If the nerve is stimulated with sufficient intensity, all
the muscle fibers supplied by the nerve contract and a
maximal response is triggered. After administration of
a neuromuscular blocking drug, the response of muscle
decreases in parallel to number of nerve fibers blocked.
The degree of reduction in response to continuous
stimulation reflects the extent of neuromuscular
blockade.5
Current
For the above principle to be effective, the stimulus
must be truly maximal throughout the period of
monitoring. The amount of current required to elicit a
detectable muscle response is the threshold current
(15mA).6 The current needed to induce depolarization
in all the fibers in a nerve bundle is the maximal current.
For clinical monitoring, a supramaximal current is usually
applied, which is 10%-20% greater than the maximal
current and 2-3 times higher than the threshold current.7
A 50-60m A current across surface electrode is required
to produce a supramaximal response which may be
painful in an awake patient. Though this is not a concern
during anesthesia, it may become uncomfortable during
recovery. Although several investigators have indicated
the use of submaximal current to assess NM function
postoperatively,8-10 the accuracy in monitoring is
unacceptable at low current.11 Therefore; supramaximal
current should always be used whenever possible.
Character of waveform and pulse duration
The impulse should be monophasic and rectangular
(i.e. it should be a square wave) so that constant current
is maintained over the entire impulse. A biphasic pulse
may cause burst of action potential in nerve (repetitive
firing), thus increasing the response to the stimulation.
The optimal pulse duration is of 0.2 to 0.3 ms. A pulse
exceeding 0.5ms may stimulate the muscle directly or
cause repetitive firing.5
Resistance
The force opposing the flow of energy to the
peripheral nerve is the resistance. Current is equal to
voltage divided by the resistance. Any increase in
resistance (cooling of skin) will require a proportionate
increase in voltage to maintain a constant current. MostFigure-1Neuromuscular junction
GHAI B; ET AL: NEUROMUSCULAR MONITORING
349
peripheral nerve stimulators deliver a constant current
over a range of changing resistance by varying the
internal voltage. Resistance between the surface
electrodes and the skin can be reduced by removing
hair, decornifying and degreasing the skin and cleaning
the area beneath the electrodes with alcohol.12
Patterns of nerve stimulation (Figure 2)
Five patterns of nerve stimulation are commonly
used in clinical practice
 Single twitch stimulation.
 Train-of-four stimulation.
 Tetanic stimulation.
 Post-tetanic count stimulation.
 Double burst stimulation.
Single twitch stimulation:
Single supramaximal stimuli are applied at
frequency of 0.1 Hz (once every 10 seconds)to 1.0
Hz (once every second). 0.1Hz is generally used. If
the frequency is >0.15 Hz, the evoked response
gradually decreases and settles at lower levels.13 A
frequency of 1.0 Hz shortens the time for detection of
supramaximal stimulation, hence this frequency is
sometimes used during the induction of anesthesia for
evaluating baseline response. The twitch height will
remain normal until 75% of Ach receptors are blocked
and will completely disappear when 90% to 95% of
Ach receptors are occupied.14 There are few limitations
associated with this pattern of stimulation. A controlled
twitch height must be obtained before muscle relaxant
is administered and specialized recording equipment is
required to compare subsequent responses. The
response of stimulation is frequency dependent. At
0.1Hz, there is no impact on NM transmission. When
frequency is increased to 1.0 Hz, fade will be observed
and a faster onset of NMB can develop in the stimulated
muscle.13
Train-of-Four Stimulation (TOF)
This is the most widely used mode of nerve
stimulation. Four supramaximal stimuli of 2Hz (four
stimuli every 0.5 sec) are applied over 2 second interval
which are repeated every 10-12 second. The response
is observed as TOF count or TOF ratio.5
The TOF count is an assessment of number of
twitches (0-4) after TOF stimulation. It is commonly
used in operation room and intensive care unit because
it can be quantified without recording devices. In the
absence of NMB, all four responses of equal height
are present. Absent 4th response represents 75-80%
receptor blockade. When 85%, 85-90% and 90-98%
of Ach receptors are blocked, T3, T2, T1 responses
are abolished respectively.15 The fade in response to
TOF stimulation provides the basis for evaluation.
TOF ratio is measured by dividing the amplitude
of fourth to the amplitude of first response. Its accurate
determination requires specialized recording devices.
In the absence of NMB, TOF ratio is 1. In partial non-
depolarizing block, the ratio decreases and is inversely
proportional to the degree of block. In partial
depolarizing block, the amplitude of all the four responses
Figure-2
Patterns of stimulation
J Anaesth Clin Pharmacol 2006; 22(4) : 347-356
350
decreases but TOF remains 1.0. If fade appears in
depolarizing block, it indicates phase II block.5
TOF monitoring has many advantages. Unlike
single twitch pattern, it does not require the recording
of control value. During non-depolarizing block, the
degree of block can be read directly from TOF
responses even if control value is lacking.15,16 TOF
ratio is more sensitive in detecting subtle degree of
NMB than single twitch stimulation. TOF monitoring is
less painful than tetanic stimulation, therefore, it can be
used to detect residual block in awake patients. TOF
monitoring can be performed more frequently (once
every 10-12 seconds) without influencing the twitch
height. This is in contrast to tetanic stimulation which,
if repeated within less than 2 minutes, may
show exaggerated response because of posttetanic
potentiation.12
Tetanic stimulation
This pattern of stimulation consists of very rapid
delivery of electrical stimuli ranging from 30-100Hz.
The twitch responses fuse and a single sustained muscle
contraction is obtained. 50Hz (once every 20 seconds)
for 5 seconds is the most commonly used strength. In
normal NM transmission, sustained muscle contraction
is observed. In partial nondepolarizing (>70-75% block)
and phase II block, fade is observed. Fade is followed
by posttetanic potentiation, if single twitch stimulation
is administered which is 2 minutes of tetanic
stimulation.12
Mechanism of fade and post tetanic potentiation
High frequency stimulation of motor nerve
produces large release of immediately available stores
of Ach in the nerve terminal. As the stores become
depleted, the rate of Ach release decreases until
equilibrium between mobilization and synthesis is
achieved. Normal muscular contraction occurs with high
frequency nerve stimulation because far more Ach is
released than is required to produce a full muscular
response (a wide margin of safety). In the presence of
partial non-depolarizing block, the number of free Ach
receptors on the postsynaptic membrane is reduced.
This reduces the margin of safety of neuromuscular
transmission and leads to reduced force of muscle
contraction (fade).17 Fade can be observed with TOF,
tetanic or double burst stimulation modes. Muscle
relaxants can also produce fade by blocking presynaptic
cholinergic receptors which play a role in the
mobilization of Ach in motor neurons.18 High frequency
stimulation of motor nerve also facilitates the mobilization
of Ach from the reserve pools to the immediate stores
and increases the synthesis of Ach. This enhanced
synthesis and mobilization of Ach explains the
phenomenon of posttetanic potentiation.5
Tetanic stimulation has many disadvantages. It is
extremely painful and should not be used in awake
patients. In late phases of recovery, it may produce a
lasting antagonism of NMB, the muscle used can't
assess the recovery of NMB.19,20 It is not very useful
in every day clinical practice except for post-tetanic
count stimulation.
Post-tetanic count (PTC) stimulation
PTC can be used to evaluate intense NMB when
no response to single twitch or TOF can be measured.
PTC involves application of 50Hz tetanic stimulation
for 5 seconds followed 3 seconds later by1 Hz single
supramaximal stimulus. This modality is used when
profound muscle relaxation is required (to ensure smooth
tracheal intubation) and complete immobility of the
patients is essential (during surgery on an open globe
or in cases of elevated intracranial pressure). During
these times, the PTC should be 0.21 PTC is also used
to estimate the time to recover from intense NMB.
When PTC of 1 is recorded in patients who had received
pancuronium, approximately 30-40 minutes will elapse
Figure-3
Ulnar nerve stimulation
GHAI B; ET AL: NEUROMUSCULAR MONITORING
351
before T1 in TOF is observed.22 During vecuronium or
atracurium NMB, PTC of 1 will predict return of T1
within 7-8 minutes.23,24
Double burst stimulation (DBS)
DBS allows manual (tactile) detection of subtle
degree of NMB without the use of recording devices. It
involves application of two short bursts of 50Hz which
are separated 750 ms,. It consists of a series of 3 and 2
impulses (DBS 3, 2) or 3 and 3 impulses (DBS 3, 3).
Good correlation between the ratio of second burst to
first burst (D2/D1) and TOF ratio has been reported.25
Fade is more easily detected manually with DBS than
with TOF. Fade can only be detected reliably on manual
evaluation of TOF response, when TOF ratio is <0.4.26,27
However, manual assessment of DBS response allows
detection of fade up to TOF ratio of 0.6.26
Equipment used for NM monitoring
 The nerve stimulator,
 The stimulating electrodes, and
 The recording equipment.
The nerve stimulator
It delivers the stimulus to the electrodes. Although
many nerve stimulators are commercially available, not
all meet the basic requirement for clinical use. The real
nerve stimulator should have the following properties.
 It should deliver monophasic and rectangular
waveform pulse of constant current.
 It should deliver a current up to 60-70 mA but not
>80mA.
 It should be battery operated and should have a
battery check.
 It should have either built in warning system or
current level display that alerts the user when the
current selected is not delivered to the nerve (in
case of increased skin resistance)
 It should have polarity indicators for electrodes.
 It should deliver different modes of stimulation.
The Stimulation Electrodes
Electrical impulses are transmitted from the
stimulator to the nerve by means of surface or needle
electrodes. Surface electrodes arecommonly used in
clinical anaesthesia. These are pregelled silver/sliver
chloride electrodes having approximately 7-8 mm
diameter of the conducting area.5
If tissue resistance prevents the stimulating current
from reaching the nerve (i.e. in the morbidly obese
patients), needle electrodes can be used. A Current =
10mA will usually produce supramaximal stimulation
when subcutaneous needle electrodes are used.28
Although specially coated needle electrodes are
commercially available, ordinary steel injection needles
can be used.
Sites of nerve stimulation
In clinical anesthesia, the ulnar nerve at the wrist
Figure-4
Electrode placement for stimulation of ulnar nerve and
for recording of compound action potential from three
sites of hand (Electromyography). A) Abductor digiti
minimi muscle in the hypothenar eminence B) Adductor
pollicis muscle in the thenar eminence C) First dorsal
interosseus muscle
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is the most popular site for nerve stimulation, and the
response at the adductor pollicis is observed or recorded.
During many surgical procedures, the patient's arm may
not be accessible due to positioning. In these situations,
facial nerve is often used for stimulation and the
contraction of the muscles around the eye is evaluated.
Median nerve, posterior tibial nerve and common
peroneal nerves are sometimes used.
Optimal nerve stimulation occurs when the
negative electrode is placed directly over the nerve.
The positive electrode is placed proximal to the negative
electrode to avoid depolarizing a different nerve. For
ulnar nerve stimulation, the electrodes are best applied
on the volar side of wrist. The distal electrode should
be placed 1 cm proximal to the point at which the
proximal flexion crease of the wrist crosses the radial
side of the tendon of flexor carpi ulnaris muscle
(Figure-3). The proximal electrode should preferably
be placed 2-3 cm proximal to the distal electrode or at
the ulnar groove of the elbow.5
While interpreting the motor response to the
peripheral nerve stimulation, it is important to remember
that different muscles have different onset times, offset
times and sensitivities to muscle relaxants. The results
obtained from one muscle cannot be extrapolated
automatically to other muscles. The diaphragm is the
most resistant of all the muscles to NMBA.12 In general,
diaphragm requires 1.4-2.0 times as much muscle
relaxant as the adductor pollicis muscle for the same
degree of block.29 However, the onset and offset times
are relatively rapid as a result of high regional blood
flow. The muscles of larynx and face are less resistant.5
Good intubating conditions can be predicted with more
confidence if the orbicularis oculi30 or corrugator
supercilii31 surrounding the eye are monitored, because
these muscles reflect the extent of NMB of the
laryngeal muscles better than adductor pollicis. The
abdominal muscles, the peripheral muscles of the limb,
the masseter and the upper airway muscles are more
sensitive.5 No clinically significant difference in
sensitivity exists between the arm (adductor pollicis)
and the leg (flexor hallucis brevis) muscles.32 However,
peripheral muscles of the limb takes the longest time to
recover. Because the adductor pollicis is one of the
last muscles to recover from NMB, the recovery of
the muscle indicates recovery that diaphragm and other
muscles are definitely recovered. It is essential to
monitor adductor pollicis to ensure full recovery of NM
function.
The precise source of these differences is
unknown. Possible cause may be the difference in the
margin of safety of the NM junction of different muscle
groups, fiber composition, innervation ratio, blood flow
and muscle temperature.5
Assessment of responses to nerve stimulation
(Recording devices)
Visual and tactile assessment
It is the most common method used to monitor
evoked responses. Unfortunately significant residual
muscle weakness might not be detected when this
method is used. Use of DBS pattern of stimulation
could improve detection of residual paresis in the
perioperative period.12
Electromyography (EMG)
EMG was the first method used for recording
NMB. It was introduced by Davidson and Chirstie in
1959.33 It records the electric activity (compound action
potential) of the stimulated muscle. Electrical activity
in muscle precedes the mechanical contraction. The
two active electrodes are placed over the body and the
tendinous insertion of the muscle to be monitored and a
Figure-5
Device for the recording of the mechanomyography of
adductor pollicis, featuring a forearm and a hand restrain,
and the strain gauge attached to the thumb which is in
partial abduction. The stimulating electrode has not been
applied for the purpose of clarity.
GHAI B; ET AL: NEUROMUSCULAR MONITORING
353
third neutral electrode is placed at a remote site. After
ulnar nerve stimulation, EMG responses are typically
measured from thenar eminence, the hypothenar
eminence or the first dorsal interosseous muscle of the
hand (Figure-4). EMG unit calculates the amplitude of
the signal, which represents either the sum of the
individual compound muscle action potentials or area
under the EMG curve.34 Good correlation between
EMG and mechanomyography (MMG) has been
reported35, but the two can not be interchangeably
used. Advantages of EMG are that it is less bulky and
easy to set up and it can be recorded from muscles
that are not accessible to mechanical recording. It can
also be used to investigate spontaneous muscle activity
such as breathing. However, it is an expensive device
and the quality of EMG can be adversely affected by
an electrical interference, improper electrode placement,
direct muscle stimulation and hypothermia. It does not
return to baseline value. It is mainly used for research
purposes.
Mechanomyography (MMG)
MMG measures the isometric contraction of
adductor pollicis muscle response to ulnar nerve
stimulation. A force transducer is used for this purpose.
When ulnar nerve is stimulated, the thumb (the adductor
pollicis muscle) acts on a force displacement transducer
(Figure-5). The force of contraction is then converted
into an electrical signal, which is amplified, displayed
and recorded.5 As it measures isometric contraction,
preload of 200-300 gm must be attached to the thumb.
For accurate measurements, the hand must be
immobilized and the force transducer must be aligned
with the direction of movement of the thumb. It is an
economical device and is used for research purposes.
Acceleromyography
Acceleromyography measures the isotonic
acceleration of the stimulated muscle. It is based on
Newton's second law which states force equals mass
into acceleration. If mass is constant, muscle contraction
can be calculated if acceleration is measured. It uses a
small piezoelectric transducer, which is attached to the
stimulated muscle (Figure-6). The movement of muscle
generates voltage in the piezoelectric crystal, which is
proportionate to the acceleration of that muscle. The
signals are analysed in a specially designed analyzer
and results displayed.36 It was introduced primarily for
clinical use. The devices are small, portable and easy
to use. Because isotonic contraction is measured, no
preload is required. It can be used at the sites where
MMG cannot be used such as orbicularis oculi muscle.
Good correlation has been reported with MMG.37, 38
Evaluation of Recorded evoked responses
Intense NM blockade
Intense NMB is required for smooth tracheal
intubation and in few surgeries when patient immobility
is essential. During intense NMB, no response to TOF
or single twitch is observed. PTC may determine the
degree of intense blocked as mentioned previously.
Moderate or surgical blockade
During any surgical procedure, the smallest dose
of NMBAthat will provide optimal surgical condition
should be used. Surgical blocked begins when first
response to TOF reappears. Maintaining a TOF count
of 1 or 2 is appropriate.39 However, patient's movement
is still possible at this level. Fade on TOF, DBS and
posttetanic potentiation is present during partial non-
depolarizing block or phase II block. During pure
depolarizing block (phase I) no fade or posttetanic
potentiation is observed with TOF stimulation. All
responses are to TOF stimulation are decreased with
Figure-6
TOF watch-based on measurement of acceleromyography.
Note transducer fastened to thumb and position of
stimulating electrodes.
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pure depolarizing block and TOF ratio remains 1
(Figure-7).
Recovery
The return of the 4th response in TOF heralds'
recovery plan and antagonisms should be tried at this
point. Most NDM non depolarising muscle relaxant
can be fully reversed with in 10 minutes if T4 is present.5
Good correlation exists between TOF ratio and clinical
observation, but the relationship between TOF ratio
and signs and symptoms of residual blocked varies
greatly amongst patients.40
 When TOF ratio is 0.4 or less, the following are
observed
 Patient is unable to lift head or arm
 Tidal volume may be normal
 Vital capacity and inspiratory force will be reduced
 When TOF ratio is 0.6, the following are observed
 Patient is able to lift head for 3 seconds
 Open eyes widely
 Stick out tongue
 Vital capacity and inspiratory forces are still
reduced
 When TOF ratio is 0.7 -0.75, the following are
observed
 Patient can normally cough sufficiently
 Can lift head for at least for 5 seconds
 Grip strength may be as low as about 60% of
control
 When TOF ratio is 0.8 or more, the following are
observed
 Vital capacity and inspiratory forces are normal
 Patient may still have diplopia or facial weakness.
Adequate recovery of NM function requires return
of TOF ratio to 0.9, which cannot be guaranteed without
the use of mechanomyography, electromyography or
acceleromyography.41,42,43
To conclude, close neuromuscular monitoring
should be applied to all patients receiving muscle
relaxants because of marked variation in patient's
sensitivity to neuromuscular blockade. Monitoring
neuromuscular function during anaesthesia reduces the
incidence of morbidity and mortality associated with
residual paralyses.
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