Neuromuscular Blockade:
Summary of Recommendations
Neuromuscular Blocking Agents
Neuromuscular blocking agents are muscle relaxants that block transmission at
the neuromuscular junction and cause paralysis of affected skeletal muscles.
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Types of Neuromuscular Blocking Agents
Depolarizing
Non
-Depolarizing
➢
Succinylcholine
➢
Vecuronium
➢
Rocuronium
➢
Cisatracurinum
Neuromuscular Blockade Benefits/Risks
• Neuromuscular blocking drugs, both depolarizing and nondepolarizing are used
to facilitate airway management, improve surgical conditions, and, in some cases,
to ensure immobility during critical points in an operation.
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• The use of NMBs is associated with serious complications when their paralytic
effects have not disappeared or been reversed at the end of surgery. Inadequate
recovery from the effects of neuromuscular blocking drugs is associated with
adverse outcomes.
1
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1. Thilen, Stephan R., Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, et al. 2023. “2023 American Society of
Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force
on Neuromuscular Blockade.” Anesthesiology 138 (1): 13–41. doi: https://doi.org/10.1097/ALN.0000000000004379
Risk: Residual Weakness
• Consequences of Residual Neuromuscular Blockade
• Hypoxemia
• Impaired pulmonary function
• Postoperative Pneumonia
• Respiratory Failure
• Subjectively worse recovery
• Avoiding residual weakness can be accomplished by measuring the patent's train-of-four
ratio and ensuring a ratio >/= to 0.9 prior to extubation.
• ASA 2023 Practice Guidelines recommend quantitative neuromuscular monitoring over
qualitative assessment to avoid residual neuromuscular blockade.
• Strength of recommendation: Strong
• Strength of evidence: Moderate
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1. Thilen, Stephan R., Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, et al. 2023. “2023 American Society of
Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on
Neuromuscular Blockade.” Anesthesiology 138 (1): 13–41. doi: https://doi.org/10.1097/ALN.0000000000004379
Train-of-Four Monitoring
Train of Four (TOF) is used to measure the depth of neuromuscular blockade using
a peripheral nerve stimulator (PNS). The PNS delivers four equal pulses/stimuli to
a nerve at 2 Hz. The train of four count is the counting of muscle twitches in
response to each stimuli.
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1. Thilen, Stephan R., Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, et al. 2023. “2023 American Society of
Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on
Neuromuscular Blockade.” Anesthesiology 138 (1): 13–41. doi: https://doi.org/10.1097/ALN.0000000000004379
What is Post-Tetanic Count (PTC)?
• When TOF Count is 0/4, PTC is measured to assess depth of blockade.
• PTC applies high frequency tetanic stimulation of 50-Hz for 5 seconds, followed by
a 3 second pause and then a single twitch stimulation at 1 Hz.
• Quantitative monitors with PTC functionality result a number between 0 - 15.
• More twitches = closer to recovery of TOF Count: 1/4
• Conversion for Monitoring Sites:
• TOF Count: 1/4 at orbicularis oculi (face) = TOF 0/4 with 5-10 PTC count at AP (hand)
• If TOF=0/4 but diaphragm is signaling recovery based on ventilator response:
Patient is at shallow end of deep blockade. Measure PTC count. Readminister
rocuronium at PTC count between 5 and 10 to maintain deep level of blockade.
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ASA Guidelines
Recommends objective or quantitative monitoring
whenever neuromuscular blocking agents are used.
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Stephan R. Thilen, Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, Lars I. Eriksson, Myron Yaster, Mark D.
Grant, Madhulika Agarkar, Anne M. Marbella, Jaime F. Blanck, Karen B. Domino; 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and
Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade. Anesthesiology 2023;
138:13–41 doi: https://doi.org/10.1097/ALN.0000000000004379
Monitoring Sites
Common Sites
• Diaphragm: Recovers from blockade first but cannot monitor.
• Adductor pollicis (hand): Recovers from blockade last. Recommended
• If hand not accessible, orbicularis oculi (facial) or posterior tibial (ankle) nerve can be used.
*Strong evidence against using posterior tibial nerve in patients with peripheral neuropathy.
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When is NMB Reversal needed?
Patients with adequate spontaneous recovery of train-of-four ratio ≥ 0.9
can be identified with quantitative monitoring. These patients do not
require pharmacological antagonism.
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Defasciculating dose: Nondepolarizing agent given to reduce the duration and intensity of muscle twitches
when succinylcholine is used. Recommended dose is 10% of paralyzing dose.
Note: If defasciculating dose was administered, TOF is recommended with reversal advised for ratios <0.9.
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1. Stephan R. Thilen, Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, Lars I. Eriksson, Myron Yaster, Mark D. Grant,
Madhulika Agarkar, Anne M. Marbella, Jaime F. Blanck, Karen B. Domino; 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of
Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade. Anesthesiology 2023; 138:13–41 doi:
https://doi.org/10.1097/ALN.0000000000004379
Assess Level of Blockade
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If TOF Count <4/4, sugammadex is
recommended to reverse deep and
moderate blockade from rocuronium and
vecuronium.
FDA- approved dosing recommendations for
sugammadex:
• TOF ≥2/4: 2 mg/kg
• TOF <2/4: 4 mg/kg
• Emergency Reversal needed after
single dose of rocuronium: 16 mg/kg
*Sugammadex does not reverse neuromuscular blockade induced by cisatracurium or succinylcholine.
Assess Level of Blockade
If TOF Count = 4/4 with ratio 0.4-0.9 (minimal blockade), neostigmine is an acceptable alternative for
reversal.
• Neostigmine can reverse the effects of rocuronium, vecuronium, or cisatracurium.
• Neostigmine dose should not exceed 40 µg/kg.
• Doses higher than 50µg/kg associated with paradoxical effect.
• When neostigmine has reached peak effect, and the TOF count is 4/4 but ratio is <0.9:
1. Allow for continued spontaneous recovery, if situation allows
2. Administer sugammadex if rocuronium or vecuronium were used
3. If a low dose of neostigmine was initially used, administer additional neostigmine (not to exceed a
total of 50 μg/kg)
1
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1. Stephan R. Thilen, Wade A. Weigel, Michael M. Todd, Richard P. Dutton, Cynthia A. Lien, Stuart A. Grant, Joseph W. Szokol, Lars I. Eriksson, Myron Yaster, Mark D. Grant, Madhulika Agarkar, Anne M. Marbella, Jaime F. Blanck, Karen B. Domino;
2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade. Anesthesiology 2023;
138:13–41 doi: https://doi.org/10.1097/ALN.0000000000004379
Qualitative Monitoring
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Qualitative Monitoring (Subjective)
Qualitative monitoring can be assessed in the following ways:
1. Clinical assessment - Asking patient to respond to directions. This method is
not reliable for assessing recovery from neuromuscular blockade.
2. Peripheral nerve stimulator: Train-of-four Count
• Provider counts twitches.
• Difficult to decipher difference in twitch strength between first and fourth twitch.
• Sustained Tetany: Muscle twitches appear to have the same intensity between first and fourth
twitch. It can seem that there is no fade however, fade cannot be reliably detected until the TOF
ratio is > 0.4
• PNS are inadequate at low levels of blockade
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Donati F. Residual paralysis: a real problem or did we invent a new disease? Can J Anaesth. 2013
Jul;60(7):714-29. doi: 10.1007/s12630-013-9932-8. Epub 2013 Apr 27. PMID: 23625545.
Clinical Assessment:
• Tidal volume
• Grip strength
• Ask patient to raise head
*Not reliable clinical indicators.
TOF Fade: In a partially paralyzed muscle, the
response to the second burst using TOF is reduced.
Qualitative Monitoring (Subjective)
Quantitative Monitoring
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Train-of-Four (TOF) Count
• TOF Count: Measures the magnitude of muscle twitch along a nerve (adductor
pollicis used most common) displayed as a percentage. This is measured four times,
spaced out over half a second each.
• T1 = Twitch 1
• T2 = Twitch 2
• T3 = Twitch 3
• T4 = Twitch 4
• Prior to giving the non-depolarizing medication, we expect to see the ratio between T1 & T4 =
100% (equal twitch strength).
• One minute after administering the medication, magnitude of muscle twitch decreases.
For example:
• T1 = 100%
• T2 = 70%
• T3 = 50%
• T4 = 30%
Ratio = 0.3
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Train-of-Four Ratio Explained
• TOF Ratio = T4/T1
• Using our example, we would use the magnitude of the fourth twitch divided by magnitude
of the first twitch.
• T1 = 100%
• T2 = 70%
• T3 = 50%
• T4 = 30%
• T4/T1 = 30%/100% = Ratio of 0.3
• After another minute, rocuronium is administered and you assess your patient again. Here are the
counts:
• T1 = 75%, T2=50%, T3=30%, T4=15%.
• Leaving us with a TOF Count: 4/4 with Ratio = 0.2 (15%/75%)
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Calibration and Normalization- Quantitative Monitoring
Calibration
• Adds a few extra steps in beginning
of case
• Can be omitted if delays are a patient
safety concern
• Median time to calibrate was 34
seconds
1
• Allows for accurate baseline
measurement
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Normalization
• Using baseline value, calculate the
recovery percentage needed for each
patient.
• Baseline value % X 0.9
• Can raise threshold of recovery to
adjust to patient’s baseline
*Baseline values can be larger than 100%
1. Renew JR, Hex K, Johnson P, Lovett P, Pence R. Ease of Application of Various Neuromuscular Devices for Routine
Monitoring.Anesth Analg. 2021;132(5):1421-1428. doi:10.1213/ANE.0000000000005213
Mechanomyography
• Measures isometric contractile force after
neurostimulation.
• Detects changes in active skeletal muscle.
• Regulated to research use
• Historic gold standard: All new monitors are
validated against mechanomyography prior to
release.
• Not common for daily practice.
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Acceleromyography (AMG)
• Most frequently studied
• Transducer fixed to thumb: 3D transducers can
measure acceleration of thumb movements following
neurostimulation.
• Can use EKG leads to reduce cost
• Bluetooth connectivity
• Reverse Fade Phenomenon: Baseline measurements
can exceed 100% in sleeping patient prior to paralytic.
**Important to place the monitors on pre-induction to
get baseline value for normalization.**
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Electromyography (EMG)
• Measures electricity rather than motion - can be used when
AMG fails or arms are tucked.
• Used for Neuro/Spine cases
• Consistent response
• Susceptible to interference from electrical equipment (cautery)
• Lower temperatures (< 34C) can amplify measure response
• Higher cost due to single use electrodes.
• Portable: Operating Rooms:
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Summary of Recommendations
• Quantitative NMB monitoring is recommended for all patients receiving neuromuscular
blockade.
• Muscles respond differently to NMB – adductor pollicis is recommended site for TOF
monitoring.
• Fade is not reliably detected with the naked eye until train-of-four ratio is >0.4.
• Calibration of the NMB monitor allows the provider to obtain baseline data before
induction
• Acceleromyography is most commonly used form of quantitative monitoring.
• Use EMG when arms need to be tucked.
• Reversal with sugammadex is recommended for deep & moderate levels of
neuromuscular blockade from rocuronium or vecuronium.
• Reversal with neostigmine is acceptable for patients with minimal blockade from
vecuronium or rocuronium or for patients receiving cisatracurium.
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