Muscle relaxants
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Neuromuscular blocking drugs
Neuromuscular blocking drugs used in anaesthesia are also known as muscle relaxants. By specific blockade of the neuromuscular junction they enable light anaesthesia to be used with adequate relaxation of the muscles of the abdomen and diaphragm. They also relax the vocal cords and allow the passage of a tracheal tube. Their action differs from the muscle relaxants used in musculoskeletal disorders that act on the spinal cord or brain. Neuromuscular blocking drugs are highly polar water soluble drugs that do not cross the blood-brain barrier.Patients who have received a neuromuscular blocking drug should always have their respiration assisted or controlled until the drug has been inactivated or antagonised. They should also receive sufficient concomitant inhalational or intravenous anaesthetic or sedative drugs to prevent awareness.
Non-depolarising neuromuscular blocking drugs
Mechanism of action
Non-depolarising neuromuscular blocking drugs (also known as competitive muscle relaxants) compete with acetylcholine for cholinergic receptor sites at the neuromuscular junction.The action of non-depolarising neuromuscular blocking drugs can be reversed with anticholinesterases such as neostigmine.
Classification
Non-depolarising neuromuscular blocking drugs can be divided into the aminosteroid and benzylisoquinolinium groups (see below).| Aminosteroid group | Benzylisoquinolinium group |
|---|---|
| Pancuronium bromide Rocuronium bromide Vecuronium bromide | Atracurium besilateCisatracuriumMivacurium |
Characteristics
Non-depolarising neuromuscular blocking drugs have a slower onset of action than suxamethonium chloride. These drugs can be classified by their duration of action as short-acting (15–30 minutes), intermediate-acting (30–40 minutes), and long-acting (60–120 minutes), although duration of action is dose-dependent. Drugs with a shorter or intermediate duration of action, such as atracurium besilate and vecuronium bromide, are more widely used than those with a longer duration of action, such as pancuronium bromide.
Non-depolarising neuromuscular blocking drugs have no sedative or analgesic effects and are not considered to trigger malignant hyperthermia.
For patients receiving intensive care and who require tracheal intubation and mechanical ventilation, a non-depolarising neuromuscular blocking drug is chosen according to its onset of effect, duration of action, and side-effects. Rocuronium bromide, with a rapid onset of effect, may facilitate intubation. Atracurium besilate or cisatracurium may be suitable for long-term neuromuscular blockade since their duration of action is not dependent on elimination by the liver or the kidneys.
Atracurium
Atracurium besilate, a mixture of 10 isomers, is a benzylisoquinolinium neuromuscular blocking drug with an intermediate duration of action. It undergoes non-enzymatic metabolism which is independent of liver and kidney function, thus allowing its use in patients with hepatic or renal impairment. Cardiovascular effects (flushing and hypotension) are associated with significant histamine release. Histamine release can be minimised by administering slowly or in divided doses over at least 1 minute.The RCEM expect candidates to have specific knowledge of atracurium
Depolarising neuromuscular blocking drugs
Suxamethonium chloride (Succinylcholine) is the only depolarising neuromuscular blocking drug in clinical use.
Mechanism of action
Suxamethonium acts by mimicking acetylcholine at the neuromuscular junction but hydrolysis is much slower than for acetylcholine. This is because acetylcholine is hydrolysed by acetylcholinesterase (which is extremely rapid) where as suxamethonium is hydrolysed by plasma cholinesterases which is much slower. Depolarisation is therefore prolonged resulting in neuromuscular blockade.Suxamethonium has the most rapid onset of action of any of the neuromuscular blocking drugs and is ideal if fast onset and brief duration of action are required, e.g. with tracheal intubation. At standard doses profound block is usually achieved within 60 seconds. Neuromuscular block starts to recover within 3 min and is complete within 12–15 min.
Unlike the non-depolarising neuromuscular blocking drugs, its action cannot be reversed and recovery is spontaneous.
Anticholinesterases such as neostigmine potentiate the neuromuscular block of suxamethonium
Administration
Suxamethonium chloride should be given after anaesthetic induction because paralysis is usually preceded by painful muscle fasciculations. While tachycardia occurs with single use, bradycardia may occur with repeated doses in adults and with the first dose in children. Premedication with atropine reduces bradycardia as well as the excessive salivation associated with suxamethonium chloride use.Prolonged paralysis may occur in dual block, which occurs with high or repeated doses of suxamethonium chloride and is caused by the development of a non-depolarising block following the initial depolarising block. Individuals with myasthenia gravis are resistant to suxamethonium chloride but can develop dual block resulting in delayed recovery. Prolonged paralysis may also occur in those with low or atypical plasma cholinesterase. Assisted ventilation should be continued until muscle function is restored.
Common side effects
- Arrhythmias (bradycardia may occur with repeated doses)
- Flushing
- Involuntary muscle contractions
- Myoglobinuria
- Myopathy
- Post procedural muscle pain
- Rash
Malignant hyperthermia
Suxamethonium is a recognised trigger of malignant hyperthermia. This is a rare but serious condition. In genetically susceptible individuals suxamethonium may induce the release of stored calcium ions within muscle cells. The resulting increase in intracellular calcium causes large scale muscle contraction which generates excessive heat and results in metabolic acidosis. Untreated mortality approaches 75% whilst with appropriate treatment mortality drops to around 5%
Treatment is with dantrolene and rapid cooling along with other supportive measures
Suxamethonium is a recognised trigger of malignant hyperthermia. This is a rare but serious condition. In genetically susceptible individuals suxamethonium may induce the release of stored calcium ions within muscle cells. The resulting increase in intracellular calcium causes large scale muscle contraction which generates excessive heat and results in metabolic acidosis. Untreated mortality approaches 75% whilst with appropriate treatment mortality drops to around 5%
Treatment is with dantrolene and rapid cooling along with other supportive measures
Contra-indications
- Hyperkalaemia
- High risk of developing hyperkalaemia e.g. prolonged immobilisation, severe burns, major trauma, skeletal muscle myopathies
- Low plasma-cholinesterase activity (including severe liver disease)
- Neurological disease involving acute wasting of major muscle
- Personal or family history of congenital myotonic disease
- Personal or family history of malignant hyperthermia