Neuromuscular blockade

Neuromuscular blockade involves the use of neuromuscular blocking agents (NMBAs) (i.e. paralytics) to facilitate endotracheal intubation and/or surgical procedures.

Drugs used

Non-depolarizing agents bind to and INHIBIT acetylcholine receptors at the end plate of the neuromuscular junction. Common examples below include:

Steroidal non-depolarizing agents (hepatic and/or renal excreted):

• Rocuronium
• Vecuronium

Benzylisoquinolinium non-depolarizing agents (broken down by Hoffman Elimination):

• Cisatrocurium (the cis-enantiomer of atrocurium)

Depolarizing agents on the other hand bind and ACTIVATE acetylcholine receptors causing sustained depolarization of the neuromuscular junction (i.e. muscle contraction) followed by paralysis. The prototypical example being:

• Succinylcholine

Depolarizing agents have different implications for neuromuscular blockade monitoring as discussed below.

Monitoring

Train of Four

Equipment (Quantitative Monitoring)

In order to assess the level of paralysis during an anesthesia event, train of four monitoring (either quantitative or qualitative) is typically used throughout the duration of the procedure (e.g. during routine assessments) and prior to extubation. Quantitative train of four monitoring is the most accurate assessment of neuromuscular blockade and is preferred as it mitigates the risk of residual paralysis and subsequent post-op pulmonary complications. Equipment that can be used includes:

• Electromyography (EMG)
• Acceleromyography (AMG)
• Kinemyography (KMG)

These monitors calculate a train of four ratio (TOFR) which the provider uses to determine the depth of paralysis. This ratio is the magnitude of the 4th twitch divided by the magnitude of the 1st twitch. A higher ratio indicates lighter paralysis. Prior to extubation, for example, providers look for a TOFR of at least >0.9 indicating almost complete recovery of muscle strength/function.

All of the above involve the stimulation of peripheral nerves, the differences being what is actually measured. EMG measures evoked muscle responses (a.k.a. action potentials). AMG measures the acceleration of thumb contraction using Newton's Second Law of Motion (Force = Mass x Acceleration). KMG uses mechanosensors that generate measurable electrical signals. All are valid for use in quantitative train of four monitoring. AMG and KMG require unrestricted motion of the hand or muscle interrogated while EMG does not. AMG and KMG are also subject to the phenomenon of "reverse fade." EMG on the other hand can be affected by electrical interference in the operating room (cautery) but nonetheless is usually the monitoring device of choice.

Qualitative Monitoring

In lieu of EMG, providers may also use a nerve stimulator and palpate for muscle contraction in order to assess depth of paralysis. This is less accurate and generally overestimates recovery from paralysis. The risk of this is residual paralysis which contributes to higher rates of post-op pulmonary complications.

Methods of assessment

Train of Four Count (TOFC)

Electrical stimulus is applied to a peripheral nerve and the number of twitches counted corresponds to the amount/percent of acetylcholine receptors blocked:

1 twitch = >95%

2 twitches = 85-90%

3 twitches = 80-85%

4 twitches = 70-75%

When administering reversal drugs, TOFC is used to determine readiness or dosing of medication.

• If using Neostigmine/Glycopyrrolate: generally given when TOFC is 4

• If using Sugammadex: 4 mg/kg for 1-2 twitches, 2 mg/kg for 3-4 twitches, 16 mg/kg for immediate reversal

Post Tetanic Count (PTC)

With PTC, a large 50 Hz stimulus is applied for 5 seconds followed by subsequent 1 Hz stimuli over 20 seconds. PTC is used when the TOFC is zero. PTC can indicate time to recovery (e.g. a PTC of 1 indicates recovery from paralysis in approximately 30 minutes).

Sites of Use (for helpful graphics, can refer to UpToDate)

Ulnar Nerve

Generally the preferred site of monitoring. It is easily accessible. There is a lower chance of direct muscle stimulation which is not an assessment of nerve function/neuromuscular blockade. If surgical positioning interferes with intraoperative monitoring, can consider measuring closer to the end of the case if able to access the limb at that time. Facial Nerve Facial Nerve

Facial Nerve

May be necessary depending on surgical positioning, however is prone to more inaccuracies due to direct muscle stimulation. The palpated muscles may either be the orbicularis occuli (which generally correlates with diaphragm and larynx recovery) as well as the geniohyoid muscle (upper airway recovery). Posterior Tibial Nerve Posterior Tibial Nerve

Posterior Tibial Nerve

Generally used with AMG.

Fade

Fade is the progressive decrease in amplitude in response to nerve stimulation as a result of increased levels of paralysis. This is important as twitches are counted until the provider appreciates a significant drop in amplitude. It is difficult to assess twitches/fade when the TOFR is >0.4 (which is still a significant paralysis).

Of note, fade is generally not observed when depolarizing agents such as succinylcholine are used (instead, there is a uniform decrease in amplitude). Fade may still be observed with depolarizing agents if patients are in phase II of paralysis where there is desensitization of the neuromuscular junction after prolonged acetylcholine channel opening.

Reversal Methods (with dosing)

Traditional Agents

Glycopyrrolate (given first to prevent bradycardia): 0.1-0.2 mg/kg IV

Neostigmine: 0.03-0.07 mg/kg IV (max 5 mg)

Newer Agents

Sugammadex: 4 mg/kg for 1-2 twitches, 2 mg/kg for 3-4 twitches, 16 mg/kg for immediate reversal

Considerations for Sugammadex include the risk of arrhythmias, hypersensitivity reactions (increased with larger doses). Although there is concern with the use of Sugammadex in patients with kidney dysfunction (as it is renally cleared), recent studies have shown its safe use in patients with end stage renal disease (ESRD).