Monitoring of Neuromuscular Blockade

Nerve stimulation

• The extent of neuromuscular blockade and recovery can be assessed clinically and with a nerve stimulator. ⁽¹⁾
• Stimulating a peripheral motor nerve with an electric impulse results in a muscular response following the all or none phenomenon
• The force and intensity of the response depends on the number of activated muscle fibers
• With sufficient stimulating intensity, all fibers of the innervated muscle should contract and a response at the maximum level should result. At this level, an additional increase of stimulating intensity will not lead to any increase of the muscle contraction
• For clinical application, it is widely recommended that an electric stimulus 15-20% above the level of maximum muscular response is used, i.e. supramaximal stimulus. This is to ensure that factors such as variability in skin impedance, donot have a significant influence on the muscular response and therefore, on the quality of measurement

Ideal Nerve Stimulator:⁽²⁾

• It should be battery operated and should deliver a constant current, up to a maximum of 80mA. 
• Skin resistane is affected by factors like skin temperature, adequacy of electrode application, disease state like diabetes or chronic renal failure. 
• The pulse stimulus should last no longer than 0.3 ms and be monophasic, square wave type. 
• The nerve stimulator should be capable of delivering a variety of patterns of stimulation including: Single twitch (at 1 Hz); TOF twitch stimulation (usually 2 Hz with at least a 10 s interval between trains); tetanic stimulation at 50 Hz for up to 5 s; and double burst stimulation. 
• Good electrical contact with the skin can be established using ECG electrodes of the silver/silver chloride variety. 
• The ideal stimulator would also enable monitoring of the evoked responses. 

Stimulating electrodes

• Skin should be cleaned using an alcohol solution and then rubbed.
• The electrodes should be placed correctly at the site to ensure that the current stimulates the target nerve appropriately
• It is recommended that the negative electrode should be placed at the distal site
• Skin temperature should be maintained > 32 deg C to avoid hypothermia related increases in skin impedance
• Site of nerve stimulation

Choosing a site for neuromuscular monitoring depends on several factors:

• The site should allow easy access
• Direct stimulation of the muscle should be avoided
• Selecting a nerve muscle unit that allows quantitative monitoring is recommended

The most common nerve muscle unit used for neuromuscular monitoring is the ulnar nerve- adductor pollicis muscle. When using quantitative accelerographic monitoring, the probe can be placed on the tip of the thumb. For optimal results in quantitative monitoring, the other four fingers should be fixed. 

Some surgical procedures do not allow easy access to the patients’ arms, e.g. during otorhinolaryngological surgery or if the patient is placed in a prone position. In the latter case, the use of tibialis posterior and flexor hallucis brevis nerve–muscle unit might be a suitable alternative. The electrodes have to be placed next to the medial malleolus. For accelerographic quantitative measurement, the probe of the device can be fixed at the tip on the plantar side of the big toe.

Another option is to use the stimulation of the facial nerve for neuromuscular monitoring by the recording of the contraction of orbicularis oculi or corrugator supercilii muscles. The electrical current intensity required at the facial nerve seems to be less than that required at other sites of stimulation. The accelerographic probe tip should be placed either just above the medial part of the corrugator supercilii muscle or at the lateral part below the eyebrow when using the orbicularis oculi muscle.

Stimulation patterns: clinically used stimulation pattern are: ⁽³⁾

• Single twitch stimulation
• The train of four (TOF) stimulation
• Tetanic stimulation
• Post tetanic count stimulation
• The double burst stimulation
• Single twitch stimulation

A single twitch consist of the application of a supramaximal stimulus to the nerve with a frequency between 0.1 Hz and 1.0 Hz. Without using suitable monitoring equipment, eg mechanomyograph or an electromyography, the technique does not provide reliable information either about the neuromuscular recovery or the onset of a neuromuscular block.

Neither absence of response to STS stimulation nor absence of response to SBS stimulation of the ulnar nerve at either 0.1 Hz or 0.05 Hz frequency does guarantee acceptable intubating conditions during nset of neuromuscular block induced by vecuronium 0.08 mg/kg when thiopentone is used as the sole anesthetic. ⁽⁴⁾

Train of four

Developed by Ali HH, Utting JE, Gray C, it allows a more reliable tactile assessment of a neuromuscular block. ⁽⁵⁾

Indications of peripheral nerve stimulation or TOF Monitoring: ⁽⁶⁾

• Initial endotracheal intubation 
• Facilitating mechanical ventilation in patients with severe lung injury 
• Reducing intracranial pressure
• Shivering including therapeutic hypothermia
• Status epilepticus 
• Treatment of muscle spasms related to drug overdose or tetanus 
• Preservation of delicate reconstructive surgery 
• Facilitation of diagnostic or therapeutic procedures

Contraindications of peripheral nerve stimulation: ⁽⁶⁾

• Inability to obtain a secure airway 
• Patient not on analgesia or sedation 
• Unstable bone fracture

The stimulation pattern consists of four twitches at 2 Hz. A stimulation free interval of atleast 10 10 second should be allowed between successive TOF stimulations to avoid fade during the measurement. TOF count describes the number of identifiable count describes the number of identifiable responses following a TOF stimulation pattern.

In absence of neuromuscular blockade all four responses are of equal amplitude. Loss of the fourth response represents a 75-80% neuromuscular blockade. The disaapearance of of responses three, two and one can be associated with a block of about 85%, 90% and 98-100% respectively. ⁽⁷⁾

TOF ratio is obtained by dividing the amplitude (height) of the fourth response by amplitude of the first response of TOF sequence and taken as a measure of neuromuscular recovery following non depolarizing neuromuscular blockade.

For exact estimation of TOF ratio a mechanomyographic, acceleromyographic or electromyographic device that record the responses is necessary. Tactile estimation is accurate in detecting fade during TOF stimulation only if TOF ratio is < 0.4. ⁽⁸⁾ An objectively measured TOF ratio of 0.7 represents adequate diaphragmatic recovery. However, to ensure sufficient return of pharyngeal muscle function, a TOF ratio of > 0.9 is necessary.

The accepted values for TOF count are: ⁽⁹⁾

• 1 twitch for tracheal intubation 
• 1-2 twitches for during established anesthesia
• 3-4 twitches before reversal of neuromuscular blockade is attempted

The current intensity should be tested before the onset of blockade for good TOF interpretation. The orbicularis oculi is less sensitive to cistracurium than adductor pollicis and plantar flexor both at onset and after a prolonged infusion. The recovery from relaxation is faster on orbicularis oculi and plantar flexor than on adductor pollicis. ⁽¹⁰⁾

Tetanic stimulation

Tetanic stimulation is a high frequency (50-200 Hz) stimulation pattern that is usually applied for 5 seconds. The muscular response is perceived as a single, forceful and sustained contraction when no block is present. In case of incomplete neuromuscular recovery following non depolarizing neuromuscular blockade, a fade effect can be observed on stimulation.

The tetanus induced effect on subsequent TOF is more apparent and lasts longer at greater degrees than at lesser degrees of neuromuscular block. ⁽¹¹⁾

Post tetanic count

Post tetanic count allows the tactile or visual evaluation of a deep non depolarizing neuromuscular block that does not respond  to a TOF stimulation. During PTC stimulation, a 50 HZ tetanic stimulation is applied for 5 seconds followed by 1 Hz supramaximal single stimuli after a gap of 3 second. The PTC results in the number of single stimulus responses following the tetanic stimulation and should ideally be 0 if a very deep neuromuscular block is desired. If, however, five to seven responses are detectable, return of the TOF response is imminent.

Monitoring posttetanic count during intense neuromuscular blockade allows the clinician to estimate the intensity of the blockade and estimate recovery time. There is a correlation between PTC and TOF recovery from intense cisatracurium-induced neuromuscular blockade allowing better monitoring of intense degree of blockade during both iv(propofol) and isoflurane anesthesia. ⁽¹²⁾

Double burst stimulation

The technique allows greater tactile evaluation of minor neuromuscular blockade than tactile evaluation of the TOF ratio. Two burst of stimuli at 50 Hz with an interval of 750 ms are applied during. A burst consists of two or three impulses. The burst are combined as a series of 3 and 3 impulses or 3 and 2 impulses. In clinical practice, DBS 3,2 is usually used. A fading of the second impulse series compared to the first correlates with an incomplete neuromuscular recovery with a comparable TOF ratio < 0.6. Therefore, the method is more sensitive for tactile evaluation of a residual blockade in comparison with a tactile evaluation of the fade using TOF stimulation.

Double burst stimulation (DBS) is more sensitive than the TOF in manual detection of residual block. ⁽¹³⁾

Recommendations for use of different stimulation patterns for the assessment of neuromuscular blockade in various clinical situations

Stimulation pattern	Onset of block	Deep block (TOF = 0)	Moderate block (TOF >0)	Recovery
Train of four (TOF)	Adequate	Not adequate	Adequate	Intermediate (tactile estimation)Adequate (quantitative estimation)
Double burst stimulation	Intermediate	Not adequate	Not adequate	Intermediate
Post tetanic count	Not adequate	Adequate	Not adequate	Not adequate
Tetanus (50/ 100 Hz)	Not adequate	Not adequate	Not adequate	Intermediate

Summary of pattern of neuromuscular stimulation

Feature	ST	TOF	Tetanus	DBS	PTC
Current strength	Supra-maximal	Supra or sub maximal	Supra or submaximal	Supra or submaximal	Supra or submaximal
Frequency/ Description	0.1 to 1 Hz	2 HzFour stimuli	30-50 Hz for 5 sec	3 impulses at 50 Hz repeated after 750 msec	30 Hz for 5 sec, 3 sec laterST at 1 Hz
Prerelaxant control	Needed	Not needed	Not needed	Not needed	Not needed
Pain on stimulation	–	– / +	++	+	++
Sensitivity of manual detection (visual/tactile)	Not sensitive	Not sensitive at TOF ratio of 0.4-0.7	Sensitive	Highly sensitive	Sensitive
Alteration of subsequent responses	Not altered	Not altered	Altered (post titanic facilitation)	Not altered	Altered
Interval between successive stimuli	5 sec	12 sec	6 min	12-15 sec	6 min
Receptor occupancy detection	75-90%	70-90%	70-90%	70-90%	> 90% also
Sensitivity for detection of subtle block	Not sensitive	Sensitive	Sensitive	Sensitive	Not applicable
Monitoring of profound block	Not useful	Not useful	Not useful	Not useful	Useful

ST- Single twitch, TOF- Train of four, PTC- post titanic count, DBS- double burst stimulation

Source: D Padmaja, Srinivas Mantha. Monitoring of neuromuscular junction. Indian J Anaesth. 2002;46(4):279-288. 

Relative sensitivities of muscle groups to nondepolarizing muscle relaxants

Muscle	Sensitivity
Vocal cord	Most sensitive
Diaphragm
Orbicularis oculi
Abdominal rectus
Adductor pollicis
Masseter
Pharyngeal
Extraocular	Least sensitive

Summary of application of neuromuscular junction monitoring

Clinical objective	Site	Twitch modality	Target response
Fast onset/ tracheal intubation	Orbicularis oculi	Single twitch or train of four	0 twitches
Profound blockade	Adductor pollicisOrbicularis oculi	Post tetanic countTrain of four	RelaxantDependent
Adequacy of relaxation (abdominal surgery)	Adductor pollicis	Train of four count	One or two twitches present
Predicting reversible block (when no TOF response present)	Adductor pollicis	Post tetanic count	RelaxantDependent
Detecting reversible block	Adductor pollicis	Train of four count	At least two twitches present
Detecting adequate neuromuscular function	Adductor pollicis	Double burst stimulus	No fade present

Equipments used for monitoring of neuromuscular blockade: two groups

1. Nerve stimulators allow a quantitative monitoring of the blockade
2. Nerve stimulators that donot allow quantitative monitoring

The use of nerve stimulators without an option of quantitative measurement does not allow for the reliable detection of minor levels of neuromuscular blocks ie. A TOF ratio between 0.7 and 1.0.

The most widely used methods are

• Acceleromyography
• Electromyography
• Mechanomyography

Acceleromyography

It is one of the most popular quantitative monitoring techniques in daily clinical use because it is comparatively cheap, practical and easy to use. After placement of stimulating electrodes on the target nerve a piezo electric element is placed over the muscle innervated by that nerve. Acceleromyography measures the isotonic acceleration of the stimulated muscle. The basis of the method is Newton’s second law (force = mass × acceleration). If the mass is constant, the force of muscle contraction can be calculated if acceleration is measured. The movement of the end organ eg the thumb, generates a voltage in the piezo electric element that correlates with the acceleration of the muscle.

The fixation of fingers and forearm is recommended when using the thumb as the end organ, the use of devices that produce a small elastic preload at the thumb may decrease the variability of measurements.

Accelromyography monitoring reduces the incidence of residual blockade and associated unpleasant symptoms of muscle weakness in the PACU and improves the overall quality of recovery. ⁽¹⁴⁾

Mechanomyography

Mechanomyography measures the isometric contraction of a muscle following nerve stimulation. A force transducer converts the force of contraction of the muscle into an electric signal. Ulnar nerve stimulation and measurement of the force of contraction of the adductor pollicis muscle are the most frequently used sites for this technique. A pre load of 200-300g must be applied for stabilization of the signal. In addition, the limb needs to be immobilized.

Mechanomyography can be used for indication of the degree of muscle activation and for monitoring the muscle fatigue development in the isometric contraction. ⁽¹⁵⁾

Electromyography

Electromyography is the oldest technique used for the estimation of neuromuscular blockade. Based on the fact that the force of muscular contraction is proportional to the compound action potential of the muscle, the device records the electric activity of the stimulated muscle, ie the compound action potential, following the stimulation of the corresponding nerve. The device records the amplitude of the signal as a sum of compound action potential. The recorded results show a good correlation with mechanomyography but cannot be used interchangeably.

Electromyography can be used only for the limbs but also at other sites of interest, eg diaphragm or the larynx. Careful skin preparation and maintaining constant skin temperature may improve the quality of signal. The equipment is not at bulky as for mechanomyography recordings. Electromyography has been primarily used for research studies.

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