PHYSICS
Monitoring techniques;
neuromuscular blockade and
depth of anaesthesia
Alexander S Wycherley
Jane L Bembridge
Abstract
This article outlines the physical principles underlying peripheral nerve
stimulation and depth of anaesthesia monitoring in relation to anaes-
thesia. The patterns of nerve stimulation most commonly used in clinical
practice are described including train-of-four, double burst stimulation
and tetanic stimulation, as well as methods used to measure motor
response. The key technologies currently used to monitor level of con-
sciousness during anaesthesia are also described, namely methods
based on electroencephalography and stimulus evoked potentials,
including limitations of their use. Published clinical guidelines on the
use of both nerve stimulators and level of consciousness monitors are
also discussed.
Keywords Awareness; bispectral index; depth of anaesthesia;
monitoring; neuromuscular blockade; train-of-four
Royal College of Anaesthetists CPD matrix: 1A03, 2A04
A range of technologies exist to allow monitoring of the
peripheral and central nervous systems during anaesthesia.
Knowledge of the physical principles underlying these tech-
nologies is essential to ensure correct use and avoid
complications.
Neuromuscular monitoring
Neuromuscular monitoring is essential during all phases of
anaesthesia, especially during recovery from neuromuscular
blockade (NMB). The Difficult Airway Society (DAS) recom-
mends the routine use of peripheral nerve stimulators to confirm
reversal of NMB prior to extubation.1 A number of clinical
techniques may be used to assess reversal of NMB, including the
ability to protrude the tongue, lift the head for 5 seconds or
deliver a vital capacity breath. These methods are prone to in-
fluence from factors such as residual sedation and patient
compliance. Guidelines on the Recommended Standards of
Monitoring from the Association of Anaesthetists of Great Britain
and Ireland (AAGBI) state that whenever muscle relaxants are
used, a nerve stimulator must be available during induction,
maintenance and recovery from anaesthesia.2 Despite this, a
2007 survey showed that less than 10% of UK anaesthetists
routinely use nerve stimulators.3
Alexander S Wycherley BSc MBChB FRCA is a Senior Anaesthetics Registrar
at Leeds Teaching Hospitals, UK. Conflicts of interest: none declared.
Jane L Bembridge MBCh BFRCA is a Consultant Anaesthetist at Bradford
Royal Infirmary, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 15:6
Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en junio 09, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.
Learning objectives
After reading this article, you should be able to:
C discuss the different patterns of nerve stimulation for neuro-
muscular monitoring
C explain the operation of a range of depth of anaesthesia
monitors
C relate the use of neuromuscular and depth of anaesthesia
monitoring to current guidelines
Nerve stimulators
The use of a nerve stimulator to determine residual NMB was
first described by Christie and Churchill-Davidson in 1958.4 A
nerve stimulator is a battery powered hand-held device able to
generate and deliver an electrical DC current. Current is typically
delivered transcutaneously using standard silver/silver chloride
ECG electrodes. Skin should be cleaned prior to the application of
electrodes to reduce electrical impedance. The negative (black)
cathode is placed over a distal point of the nerve, and the positive
(red) anode is placed proximally.
The diaphragm is relatively resistant to NMB. During induc-
tion and maintenance of anaesthesia, it is preferable to monitor a
similarly resistant muscle to ensure adequate relaxation, such as
the orbicularis oculi above the eye (innervated by the facial
nerve). During recovery, monitoring of a more sensitive muscle,
such as the adductor pollicis of the thumb (ulnar nerve), is
preferable to confirm full return of muscle power. Other sites
used for monitoring include the common peroneal nerve at the
fibular head (causing ankle dorsiflexion) and the posterior tibial
nerve at the ankle (causing ankle plantar flexion). The maximal
stimulus is the current required to stimulate all nerve fibres in a
given nerve, and is typically 50 mA; however, this varies
inversely with impedance (typically 0e5 kU), which is deter-
mined by: electrical contact, tissue thickness, hair, moisture, and
temperature. Most nerve stimulators deliver a supramaximal
stimulus that is 125% maximal stimulus. A number of different
patterns of stimulation can be used.
Patterns of nerve stimulation
Single twitch: a single square wave is applied for 0.2 ms. This
can be delivered at repeated intervals, such as every second (1
Hz). Its use is limited by the need for a control twitch as a
reference before the administration of a neuromuscular blocking
agent.
Train-of-four: the train-of-four (TOF) pattern was developed by
Ali et al. in 1970 as a clinical tool for the assessment of NMB
(Figure 1).5 TOF is especially useful when assessing the effects of
non-depolarizing drugs due to the phenomenon of fade, which
occurs due to depletion of pre-synaptic stores of acetylcholine.
Increasing non-depolarizing block causes twitch height to reduce
in a sequential manner, with T4 (the 4th twitch) disappearing
first and T1 last. The number of twitches seen is known as the
TOF count (Table 1). During recovery, T1 reappears first and T4
last. At the reappearance of T3, reversal agents may be safely
given to antagonize non-depolarising agents. The TOF ratio
300 Ó 2014 Elsevier Ltd. All rights reserved.
 PHYSICS

Patterns of nerve stimulation

Pattern of nerve Control/no block Partial non-depolarising Partial depolarising

stimulation blockade blockade

Train-of-four 0.2ms 500ms = 2Hz

(TOF)
T1 Fade No fade
T2
T3

T4

1.5s

Double burst 0.2ms 20ms = 50Hz

stimulation (DBS)
Fade No fade

750ms

Tetanic 0.2ms
stimulation 50Hz PTC > 5 Tetanic fade PTC = 5

No fade PTC > 5

5s 3s 1s = 1Hz

Figure 1

describes the difference in twitch height between T4 and T1.
Following the work of Ali et al., a TOF ratio of 0.7 was previously
accepted as demonstrating an adequate level of reversal; how-
ever, recent guidelines from DAS recommend a TOF ratio of 0.9
or above prior to extubation.1
TOF is less useful in determining a partial depolarizing block.
Depolarizing blocks do not exhibit fade, so each twitch is
reduced equally. If large or repeated doses of depolarizing agent
are given, a phase-II block may develop which exhibits many
characteristics of a non-depolarizing block.

Train-of-four count Tetanic stimulation: where NMB is profound, high-frequency

Train-of-four count Twitches present
0 None
1 T1
2 T1, T2
3 T1, T2, T3
4 All
Table 1
stimulation can be used to induce tetanic muscular contraction.
Number of acetylcholine
Tetany mobilizes additional acetylcholine from the pre-synaptic
receptors blocked
nerve terminal and increases intracellular calcium levels, exag-
100% gerating the response to subsequent stimuli. Where TOF would
90% fail to elicit a response, single twitches that follow tetanic stim-
80% ulation may elicit a response. This is known as post-tetanic
75% potentiation (PTP). The post-tetanic count (PTC) is the number
<75% of twitches seen after tetanic stimulation (Figure 1). The PTC is
inversely related to the time before reappearance of T1 of TOF,
and is specific to individual anaesthetic agents. A tetanic

ANAESTHESIA AND INTENSIVE CARE MEDICINE 15:6 301 Ó 2014 Elsevier Ltd. All rights reserved.

Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en junio 09, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.
 PHYSICS
contraction in a non-depolarizing block will exhibit tetanic fade
and PTP, whereas a depolarizing block will be uniformly reduced
with no PTP. Tetanic stimulation is not routinely used as the
intense stimulus may be extremely painful.
Double burst stimulation: smaller degrees of neuromuscular
block may be easier to detect using double burst stimulation
(DBS) (Figure 1). The ratio between the height of the first and
second twitch (DBS ratio) correlates well with the TOF ratio.
Measuring response
Although visual and tactile means are most commonly used to
interpret response to nerve stimulation, studies have shown that
even experienced users are unable to detect fade with a TOF ratio
above 0.4 using TOF and 0.6 using DBS.6 This is much lower
than the 0.9 recommended by DAS.1 A number of more objective
methods exist to more accurately measure response to nerve
stimulation (Table 2).
Depth of anaesthesia monitoring
Awareness remains a potentially devastating complication of
general anaesthesia, leading to long-term psychological trauma,
and accounting for 10% of anaesthesia-related claims to the NHS
Litigation Authority. Previous studies have indicated an inci-
dence of awareness under general anaesthesia of 1e2 per 1000
cases. More recently, the baseline survey from the 5th National
Audit Project of the Royal College of Anaesthetists found an
incidence of less than 1 in 15,000 as self-reported by UK anaes-
thetists.7 Guidance from NICE advocates the use of depth of
anaesthesia (DoA) monitors in patients at high risk of unintended
awareness,8 though their routine use is not a requirement of
minimum monitoring standards set by either the AAGBI or the
American Society of Anesthesiologists.2,9
Clinical methods
Clinical signs such as sweating, lacrimation, and changes in heart
rate, blood pressure and respiratory pattern may indicate a
reduction in level of general anaesthesia, with potential for
Objective methods of measuring response to nerve stimulation
Technique Measurement
Mechanomyography A muscle is placed in a static
(MMG) position under a fixed degree
of tension. A strain gauge
detects the change in muscle
tension during muscular
contraction
Electromyography Stimulating and recording
(EMG) electrodes are used to measure
electrical action potentials
generated during muscular
contraction
Acceleromyography A piezoelectric ceramic wafer
(AMG) is placed on an isolated muscle
and its acceleration is measured
during muscular contraction
Table 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 15:6
Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en junio 09, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.
awareness to occur. It is important to continually monitor these
clinical signs during any anaesthetic, but they are not specific to
level of consciousness. Measurement of end-tidal minimum alve-
olar concentration (MAC) is an essential monitoring standard for
patients receiving volatile anaesthetic agents;2 however, this does
not guarantee adequate DoA, as MAC can vary significantly with
factors such as age, comorbidity and type of surgery. For patients
receiving total intravenous anaesthesia (TIVA), no monitoring
system currently exists that can measure real-time plasma or effect
site concentrations of intravenous anaesthetic agents.
Level of consciousness monitoring
Consciousness cannot be measured directly. The ‘isolated fore-
arm technique’ measures responsiveness to commands in a limb
of an anaesthetized patient that is isolated from the effects of
NMB through application of a tourniquet. It is recognized by
some as the ‘gold-standard’ against which DoA monitors are
assessed, but the research technique is not suitable as a clinical
level of consciousness monitor. Specialist equipment has been
developed for wider clinical use. These devices all measure brain
electrical activity, either by analysis of spontaneous cortical
electrical activity (electroencephalogram, or EEG) or by stimulus
evoked electrical activity (Table 3).
EEG-based systems
The most widely studied DoA monitor is bispectral index (BIS).
BIS measures real-time EEG in the frontotemporal region of the
brain using a disposable four-electrode sensor placed on the
patient’s forehead. The phase relationships and frequency dis-
tribution of component EEG waves are processed and modified
using power spectral analysis to identify specific patterns of EEG
activity.10 EEG patterns that correlate with sedation and loss of
consciousness are identified using the BIS algorithm. A dimen-
sionless number is then generated ranging from 0 to 100 (the BIS
value). A signal quality index (SQI) is also displayed, indicating
the reliability of the BIS value (Table 3). BIS was developed by
studying anaesthetized healthy volunteers and identifying the
EEG patterns that correlate clinically with sedation and loss of
Benefits Limitations
Considered by many as Bulky and impractical for
the ‘gold-standard’ method routine clinical use
Portable and easy to use Prone to interference
(movement, diathermy)
Convenient with results Cannot monitor tetany or
comparable to MMG double burst stimulation
302 Ó 2014 Elsevier Ltd. All rights reserved.
 PHYSICS

Level of consciousness monitoring systems

Monitoring system Manufacturer Technology Upper monitoring Lower monitoring Target range for
range range anaesthesia

Bispectral index Covidien, Processed EEG 100 (awake) 0 (no EEG activity) 40e60 (SQI>85)
(BIS) (Mansfield, USA)
Narco-Compact M GE Healthcare Processed EEG A (awake) F (very deep hypnosis) E
(Chalfont St. Giles, UK)
M-Entropy MT MonitorTechnik Processed EEG 91 (awake) 0 (no EEG activity) 40e60
(Bad Bramstedt, Germany) and EMG
aepEX Medical Device Management Stimulus evoked 100 (awake) 0 (no EEG activity) 30e45
(Braintree, UK) potentials

EEG, electroencephalogram; EMG, electromyogram; SQI, signal quality index.

Table 3

consciousness. BIS is the only DoA monitor recommended by
NICE for use in patients at risk of awareness and those receiving
TIVA.8
The Narcotrend-Compact M monitor is another EEG-based
level of consciousness monitor that is similar to BIS. It ana-
lyses raw EEG data using power spectral analysis and automated
pattern recognition algorithms (Table 3).
M-Entropy combines EEG and electromyography (EMG) to
measure the irregularity of spontaneous brain and facial muscle
activity. During anaesthesia, EEG signals become more regular,
reducing the amount of disorder, measured as the EEG state
entropy (SE). Stimulus evoked contraction of the frontalis and
facial muscles also become more regular, measured as the EMG
response entropy (RE). With deepening anaesthesia, SE and RE
values fall together, but a significant rise in RE compared to SE
may indicate an inadequate analgesic component of anaesthesia
(Table 3).
Stimulus evoked potentials
Somatosensory evoked potentials have many clinical applica-
tions. When specific sensory modalities are stimulated, the
electrical activity of corresponding regions of the brain can be
measured. All anaesthetic agents increase the latency and reduce
the amplitude of early cortical responses in a dose-related
manner. The aepEX system uses auditory-evoked potentials
(AEP) to measure DoA. A disposable three-electrode sensor is
placed on the forehead and regular loud clicks are transmitted via
earphones at a nominal frequency of 7 Hz. AEPs are evoked and
by averaging a large number of EEG waveforms, the software can
compensate for a low signal-to-noise ratio to produce an index
value related to DoA (Table 3).
Limitations of depth of anaesthesia monitoring
All DoA monitors rely on steady-state conditions in normal
brain tissue and may be affected by any factor that leads to
reduced cortical metabolism such as ischaemia, hypoxia or
hypothermia. Interference may also be caused by other external
factors such as diathermy, movement artefact and pacemakers.
There is often a significant time lag between measurement and
display of the index value. Some systems, including BIS, are
insensitive to agents such as ketamine, nitrous oxide and
opiates, all of which are known to reduce MAC and level of
consciousness. Like all monitoring devices, DoA monitors
should be used as an adjunct to e rather than a replacement for
e continuous clinical assessment, and their use should be
tailored to the patient and situation. Users require appropriate
training and experience before adopting them into their routine
clinical practice. A
REFERENCES
1 Mitchell V, Dravid R, Patel A, et al. Difficult Airway Society Guidelines
for the management of tracheal extubation. Anaesthesia 2012; 11:
318e40.
2 The Association of Anaesthetists of Great Britain and Ireland. Rec-
ommendations for standards of monitoring during anaesthesia and
recovery. 4th edn. 2007. Also available at: http://www.aagbi.org/
publications/guidelines/docs/standardsofmonitoring07.pdf (accessed
13 September 2013).
3 Grayling M, Sweeney BP. Recovery from neuromuscular blockade: a
survey of practice. Anaesthesia 2007; 62: 806e9.
4 Christie TH, Churchill-Davidson HC. The St. Thomas’s Hospital
nerve stimulator in the diagnosis of prolonged apnoea. Lancet
1958; 1: 776.
5 Ali HH, Utting JE, Gray C. Quantitative assessment of residual anti-
depolarizing block (part II). Br J Anaesth 1971; 43: 478.
6 Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual
curarization using double burst stimulation: a comparison with train-
of-four. Anesthesiology 1989; 70: 578e81.
7 Pandit JJ, Cook TM, Jonker WR, O’Sullivan E. A national survey of
anaesthetists (NAP5) baseline to estimate an annual incidence of
accidental awareness during general anaesthesia in the UK. Br J
Anaesth 2013; 110: 501e9.
8 National Institute for Health and Care Excellence. Depth of anaes-
thesia monitors e bispectral index, E-Entropy and Narcotrend-
Compact M. 2012. Available online at: http://www.nice.org.uk/dg6
(accessed 13 September 2013).
9 American Society of Anesthesiologists. Practice advisory for intra-
operative awareness and brain function monitoring. Task Force
Report. Anesthesiology 2006; 104: 847e64.
10 Sigl JC, Chamoun NG. An introduction to bispectral analysis for the
electroencephalogram. J Clin Monit 1994; 10: 392e404.

ANAESTHESIA AND INTENSIVE CARE MEDICINE 15:6 303 Ó 2014 Elsevier Ltd. All rights reserved.

Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en junio 09, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.