Monitoring of Neuromuscular Blockade

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

Source: T. Fuchs-Buder,J.-U. Schreiber and C. Meistelman. Monitoring neuromuscular block: an update. Anaesthesia, 2009, 64 (Suppl. 1), pages 82–89.

 

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 Hz

Four stimuli

30-50 Hz for 5 sec

3 impulses at 50 Hz repeated after 750 msec

30 Hz for 5 sec, 3 sec later

ST 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

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

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 pollicis

Orbicularis oculi

Post tetanic count

Train of four  

Relaxant

Dependent

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

Relaxant

Dependent

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

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

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.

References:

  1. Balraj Appadu, Abhay Vaidya. Monitoring techniques: neuromuscular blockade and depth of anesthesia. Anaesthesia and Intensive care medicine. June 2008;9(6):247-250.
  2. Conor D McGrath, Jennifer M Hunter. Monitoring if neuromuscular block. Contin Educ ANaesth Crit Care Pain. Feb 2006;6(1):7-12. 
  3. T. Fuchs-Buder,J.-U. Schreiber and C. Meistelman. Monitoring neuromuscular block: an update. Anaesthesia, 2009, 64 (Suppl. 1), pages 82–89.
  4. Helbo-Hansen HS, Jensen B, Norreslet J, Kirkegaard-Nielsen H, de Haas IM. Response to single twitch or single burst stimulation of ulnar nerve as predictive guide for intubating conditions. Acta Anaesthesiol Scand 1995 May;39(4):498-502. 
  5. Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in humans. British Journal of Anaesthesia 1970;42:967-78. 
  6. Augustina D Saenz, David C Spencer. Peripheral nerve stimulator- Train of four monitoring. Medscape.
  7. Lee CM. Train-of-4 quantitation of competitive neuromuscular block. Anesthesia and Analgesia. 1975;54:649-653. 
  8. Samet A, Capron F, Alla F, Meistelman C, Fuchs-Buder T. Single acceleromyographic train-of-four, 100-Hertz tetanus or double-burst stimulation:which test performs better to detect residual paralysis? anesthesiology 2005;102:51-6. 
  9. Simon Hughes, Richard Griffiths. Anesthesia monitoring techniques. Anesthesia and intensive care. 2002. page 477-480. 
  10. Lagneau F, Benayoun L, Plaud B, Bonnet F, Favier J, Marty J. The interpretation of train-of-four monitoring in intensive care: what about the muscle site and the current intensity? Intensive Care Med. 2001 Jun;27(6):1058-63. 
  11. Y Satoh, A Masuda, H Toyooka, K Amaha. Effect of tetanic stimulation on subsequent train-of-four responses at various levels of vecuronium-induced neuromuscular block. Br J Anaesth. 1994;73(3):416-417. 
  12. El-Orbany MI, Joseph NJ, Salem MR. The relationship of posttetanic count and train-of-four responses during recovery from intense cisatracurium-induced neuromuscular blockade. Anesth Analg. 2003 Jul;97(1):80-4. 
  13. J Engbaek, D Ostergaard, J Viby-Mogensen. Double burst stimulation (DBS): A new pattern of nerve stimulation to identify residual neuromuscular block. Br J Anaesth. 1989;62(3):274-278.
  14. Murphy Glen S, Szokol Joseph W, Avram Michael J, Greenberg Steven B, Marymont Jesse H, Vender Jeffery S, Gray Jayla, Landry Elizabeth, Gupta Dhanesh K. Anesthesiology Nov 2011;115(5):946-954. 
  15. Mihai T Tarata. Mechanomyography versus electromyography in monitoring the muscular fatigue. Biomed Eng Online 2003;2:3.