Monitoring techniques; neuromuscular blockade and depth of anaesthesia

PHYSICS

Monitoring techniques; neuromuscular blockade and depth of anaesthesia

Learning objectives After reading this article, you should be able to: C discuss the different patterns of nerve stimulation for neuromuscular 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

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 anaesthesia. 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 consciousness 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.

2007 survey showed that less than 10% of UK anaesthetists routinely use nerve stimulators.3 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 induction 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 determined 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.

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 technologies 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) recommends 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 influence 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

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

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.

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Please cite this article in press as: Wycherley AS, Bembridge JL, Monitoring techniques; neuromuscular blockade and depth of anaesthesia, Anaesthesia and intensive care medicine (2017), http://dx.doi.org/10.1016/j.mpaic.2017.03.003

PHYSICS

Patterns of nerve stimulation Pattern of nerve stimulation Train-of-four (TOF)

Partial non-depolarizing blockade

Control/no block

0.2ms

Partial depolarizing blockade

500ms = 2Hz No fade

Fade

T1 T2

T3 T4

1.5s

Double burst stimulation (DBS)

0.2ms

20ms = 50Hz Fade

No fade

750ms

Tetanic stimulation

0.2ms 50Hz

PTC > 5

Tetanic fade

PTC = 5 No fade

5s

PTC > 5

3s 1s = 1Hz

Figure 1

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-depolarizing agents. The TOF ratio 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; however, 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.

nerve terminal and increases intracellular calcium levels, exaggerating the response to subsequent stimuli. Where TOF would fail to elicit a response, single twitches that follow tetanic stimulation may elicit a response. This is known as post-tetanic

Train-of-four count

Tetanic stimulation: where NMB is profound, high-frequency stimulation can be used to induce tetanic muscular contraction. Tetany mobilizes additional acetylcholine from the pre-synaptic

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Train-of-four count

Twitches present

Number of acetylcholine receptors blocked

0 1 2 3 4

None T1 T1, T2 T1, T2, T3 All

100% 90% 80% 75% <75%

Table 1

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PHYSICS

reduction in level of general anaesthesia, with potential for 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 alveolar 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.

potentiation (PTP). The post-tetanic count (PTC) is the number 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 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.

Level of consciousness monitoring Consciousness cannot be measured directly. The ‘isolated forearm 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).

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

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 distribution 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 dimensionless 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 consciousness. BIS is the only DoA monitor recommended by NICE for use in patients at risk of awareness and those receiving TIVA.8

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 incidence 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 anaesthetists.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

Objective methods of measuring response to nerve stimulation Technique

Measurement

Benefits

Limitations

Mechanomyography (MMG)

A muscle is placed in a static position under a fixed degree of tension. A strain gauge detects the change in muscle tension during muscular contraction Stimulating and recording electrodes are used to measure electrical action potentials generated during muscular contraction A piezoelectric ceramic wafer is placed on an isolated muscle and its acceleration is measured during muscular contraction

Considered by many as the ‘gold-standard’ method

Bulky and impractical for routine clinical use

Portable and easy to use

Prone to interference (movement, diathermy)

Convenient with results comparable to MMG

Cannot monitor tetany or double burst stimulation

Electromyography (EMG)

Acceleromyography (AMG)

Table 2

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PHYSICS

Level of consciousness monitoring systems Monitoring system

Manufacturer

Technology

Upper monitoring range

Lower monitoring range

Target range for anaesthesia

Bispectral index (BIS) Narco-Compact M

Covidien, (Mansfield, USA) GE Healthcare (Chalfont St. Giles, UK) MT MonitorTechnik (Bad Bramstedt, Germany) Medical Device Management (Braintree, UK)

Processed EEG Processed EEG

100 (awake) A (awake)

0 (no EEG activity) F (very deep hypnosis)

40e60 (SQI>85) E

Processed EEGand EMG Stimulus evoked potentials

91 (awake)

0 (no EEG activity)

40e60

100 (awake)

0 (no EEG activity)

30e45

M-Entropy aepEX

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

Table 3

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

The Narcotrend-Compact M monitor is another EEG-based level of consciousness monitor that is similar to BIS. It analyses 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).

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. Recommendations 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 antidepolarizing 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 anaesthesia 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 intraoperative 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.

Stimulus evoked potentials Somatosensory evoked potentials have many clinical applications. 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

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Please cite this article in press as: Wycherley AS, Bembridge JL, Monitoring techniques; neuromuscular blockade and depth of anaesthesia, Anaesthesia and intensive care medicine (2017), http://dx.doi.org/10.1016/j.mpaic.2017.03.003