Skeletal muscle relaxants are drugs that block the neuromuscular junction (NMJ) by binding to acetylcholine (ACh) receptors located on it. This process leads to paralysis of all skeletal muscles, starting with the small muscles of the face and paralyzing the diaphragm last. Succinylcholine, the only depolarizing NMJ-blocking drug, binds to ACh receptors and causes a prolonged depolarization of the motor end plate, resulting in flaccid paralysis. Nondepolarizing NMJ-blocking drugs bind to the ACh receptors and prevent depolarization of the motor end plate (depolarization block). These drugs are subdivided into short-acting, intermediate-acting, and long-acting agents. Based on the duration of action, NMJ-blocking drugs are useful adjuncts to anesthetic agents and are, therefore, used for laryngeal intubation, artificial ventilation, or intraoperative skeletal muscle relaxation. All NMJ-blocking drugs cause respiratory arrest (apnea) by paralyzing the diaphragm and intercostal muscles, requiring patients to be artificially ventilated. Succinylcholine is a known trigger of malignant hyperthermia and can also cause hyperkalemia, postoperative muscle pain, and cardiac arrhythmias. Nondepolarizing drugs that cause histamine release (atracurium) or have sympathomimetic properties (pancuronium) can cause bronchospasms and tachycardia. Patients who have received NMJ-blocking drugs must be monitored either clinically (e.g., ability to lift head/legs or open eyes) or with a peripheral nerve stimulator to assess the degree of skeletal muscle paralysis. Antagonists to nondepolarizing drugs (neostigmine, pyridostigmine, sugammadex) are used to reverse the NMJ block. Inadequate reversal can cause respiratory complications. Succinylcholine does not have a specific antagonist.
|Overview of NMJ blockers|
|Depolarizing NMJ blockers (depolarizing muscle relaxants)|
|Mechanism of action||Onset||Duration||Elimination||Indications||Adverse effects||Additional considerations|
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|Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)|
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|Vecuronium || || || |
|Atracurium|| || || || || |
|Cisatracurium || || || |
|Long-acting||Pancuronium|| || || || || || |
|Tubocurarine|| || || || || |
- Binds to ACh receptors → depolarization of cell membrane at motor end plate → skeletal muscle fasciculations
- Acetylcholinesterase cannot break down succinylcholine → persistent depolarization of the motor end plate → unresponsiveness of the motor end plate to subsequent nerve impulses (depolarized block) → flaccid paralysis of the skeletal muscles
- Within 5–10 minutes, plasma cholinesterases metabolize succinylcholine (a short-acting muscle relaxant).
- Succinylcholine has no antagonist.
- Phase I blockade
Phase II blockade
- Despite continued depolarization by succinylcholine, the postsynaptic membrane repolarizes and becomes desensitized,; (i.e., resistant to depolarization by acetylcholine) leading to prolonged muscle relaxation.
- Cholinesterase inhibitors may reverse the effects of phase II blockade.
- Train-of-four stimulation shows a fade-off in the amplitude of the muscle twitch.
- Compete with ACh to bind with the (nicotinic) ACh receptors at the motor end plate (competitive antagonists) → prevents depolarization of the motor end plate (nondepolarization block)
- Neostigmine, pyridostigmine, and edrophonium are usually coadministered with anticholinergics, such as atropine or glycopyrrolate, to counter muscarinic effects like bradycardia, nausea, and bronchospasm.
- Sugammadex: a selective relaxant binding agent and rapid-acting antidote for rocuronium and vecuronium
- Assessment of anesthetic depth and possible continued postsurgical effect requires neuromuscular monitoring.
- Train-of-four stimulation shows a fade-off in the amplitude of the muscle twitch
Paralysis affects the small muscles of the face first, progresses to the extremities and trunk, and affects the intercostal muscles and diaphragm last.
- Mechanism: depolarization of large muscle groups → efflux of potassium ions into the extracellular space
- Succinylcholine is contraindicated in case of hyperkalemia or in conditions associated with a high-risk of hyperkalemia, including:
- Postoperative muscle pain due to muscle fasciculations (see “Effects” above)
- Prolonged muscle paralysis, respiratory depression and/or apnea in patients with a congenital deficiency of plasma cholinesterase
- Cardiac arrhythmias
- Raised intragastric pressure → emesis
- Adverse effects due to histamine release (atracurium, mivacurium): rash, bronchospasm, hypotension
- Tachycardia (pancuronium)
- Respiratory depression or apnea
- Critical illness myopathy
We list the most important adverse effects. The selection is not exhaustive.
Skeletal muscle relaxants are used as adjuncts to anesthetic agents:
- Laryngeal intubation and rapid sequence induction of anesthesia : drugs with fast onset of action (e.g., succinylcholine, rocuronium)
- Artificial ventilation (during anesthesia or in intubated ICU patients)
- Abdominal muscle relaxation during laparotomy
- Patients who have been given NMJ blockers should be monitored.
- Clinical assessment: ability of the patient to spontaneously open the eyes, lift the head/legs, or the presence of spontaneous ventilation help determine the degree of paralysis
Neuromuscular monitoring: objectively determines degree of muscle paralysis with the help of a peripheral nerve stimulator
- Method: train-of-four response
- 0 twitches indicates profound NMJ block
- 1–2 twitches indicate a partial block.
- 1 twitch per electric stimulus indicates no NMJ block.
- Inadequate reversal (postoperative residual neuromuscular weakness) can lead to upper airway obstruction (pharyngeal muscle weakness) and inadequate ventilation