• Clinical science

Skeletal muscle relaxants

Abstract

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

Depolarizing NMJ blockers (depolarizing muscle relaxants)
Time until onset of effect Duration of action Elimination Characteristics

Succinylcholine

  • ∼ 60 seconds
  • 5–10 min
  • 100%: enzymatic hydrolysis
  • Used for anesthesia induction (esp. rapid sequence induction)
  • Not used for maintenance of muscle relaxation
  • Dose adjustment in patients with low concentrations of plasma cholinesterase enzyme
  • Contraindications
Nondepolarizing NMJ blockers (nondepolarizing muscle relaxants)
Time until onset of effect Duration of action Elimination Characteristics
Short-acting

Mivacurium

  • 2–4 min
  • 15–25 min
  • Recovery time is longer in patients with low plasma cholinesterase levels.
Intermediate-acting

Rocuronium

  • 1–3 min
  • 60–90 min
  • 70% hepatic
  • 30% renal
  • Used for rapid-sequence induction of anesthesia when succinylcholine is contraindicated (second fastest acting muscle relaxant) The laryngeal adductors are slower to respond to rocuronium than the adductor pollicis. This should be taken into account before laryngeal intubation.
  • Dose adjustment required in patients with hepatic insufficiency
  • Does not cause histamine release (see “Side effects” below)
  • Specifically antagonized by sugammadex
Atracurium
  • 2–3 min
  • 45–60 min
  • 60%: enzymatic hydrolysis
  • 30%: Hoffmann elimination
  • Ideal for patients with renal and hepatic insufficiency
  • Causes histamine release
  • Laudanosine, a metabolite of atracurium, is a CNS stimulant.
Cisatracurium
  • 3–5 min
  • 45–60 min
  • Ideal for patients with renal and hepatic insufficiency
  • Does not cause histamine release
Vecuronium
  • 2–3 min
  • 60–90 min
  • 70% hepatic
  • 30% renal
  • Alternative to rocuronium and succinylcholin for rapid sequence induction
  • Recommended for patients with cardiovascular disease
  • Dose adjustment required in renal/hepatic insufficiency
  • Specifically antagonized by sugammadex
Long-acting Pancuronium
  • 3–5 min
  • 90–120 min
  • 70% renal
  • 30% hepatic
  • Used if skeletal muscle paralysis > 1 hour is required
  • Cardiovascular side effects are common
  • Dose adjustments required in renal/hepatic insufficiency

References:[1][2][3][4][5][6][7]

Effects

The neuromuscular junction (NMJ)

Depolarizing muscle relaxants

Nondepolarizing muscle relaxants

Paralysis affects the small muscles of the face first, progresses to the extremities and trunk, and affects the intercostal muscles and diaphragm last!
References:[4][8][9][10]

Side effects

Depolarizing NMJ blocker (succinylcholine)

Nondepolarizing NMJ blockers

References:[4][8][11][10][12][13][14][15][16]

We list the most important adverse effects. The selection is not exhaustive.

Indications

  • 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; prevents the patient from moving during surgery

References:[3]

Monitoring

  • 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: Four electric stimuli are administered along the ulnar nerve every 2 seconds; the number of twitches of the adductor pollicis muscle are counted. Other peripheral nerves (facial nerve, posterior tibial nerve, etc.) can be tested in a similar fashion.
    • Interpretation
      • 0 twitches indicates profound NMJ block; 1–2 twitches indicate a partial block.
      • 1 twitch per electric stimulus indicates no NMJ block.
    • In cases of inadequate reversal → postoperative residual neuromuscular weakness → upper airway obstruction (pharyngeal muscle weakness) and inadequate ventilation

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last updated 11/20/2018
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