Suxamethonium

Suxamethonium is the only depolarising neuromuscular blocking drug in clinical use. It has the fastest onset and shortest duration of all muscle relaxants, which makes it the usual choice when the airway must be secured within about 60 seconds. It causes fasciculations, a rise in serum potassium, and rare but life-threatening reactions including malignant hyperthermia and hyperkalaemic cardiac arrest.

Class. Depolarising neuromuscular blocking drug.

Mechanism. Agonist at the nicotinic acetylcholine receptor of the motor end plate. It produces persistent depolarisation, so the muscle fibre cannot respond to further stimulation (phase I block). After large or repeated doses the block can change character to a non-depolarising (phase II) block.

Pharmacokinetics. Intravenous onset 30 to 60 seconds, clinical duration 5 to 10 minutes. Intramuscular onset 2 to 3 minutes, duration 10 to 30 minutes. Hydrolysed very rapidly by plasma cholinesterase (pseudocholinesterase) to succinylmonocholine, then slowly to succinic acid and choline. Very little reaches the neuromuscular junction, so reduced or atypical enzyme activity prolongs the block from minutes to hours. Small amounts are excreted unchanged in urine.

Indications are tracheal intubation, especially rapid sequence induction, emergency airway rescue (laryngospasm), and brief procedures needing profound relaxation. It is not used for maintenance.

Adults

• Intubation and rapid sequence induction: 1 to 1.5 mg/kg intravenously, using actual body weight. Doses under 1 mg/kg give poorer intubating conditions.
• Laryngospasm without intravenous access: 3 to 4 mg/kg intramuscularly (maximum 150 mg).
• Laryngospasm with intravenous access: 0.25 to 0.5 mg/kg intravenously.
• Repeat dose: 0.5 to 1 mg/kg. Give atropine 0.4 to 0.6 mg intravenously first, because a second dose causes bradycardia.
• Cumulative doses of more than 4 to 6 mg/kg increase the chance of phase II block. There is no fixed maximum, but avoid infusions in routine practice.

Children

• Neonates and infants: 2 mg/kg intravenously.
• Children over 1 year: 1 to 2 mg/kg intravenously.
• Intramuscular: 4 to 5 mg/kg (maximum 150 mg) when there is no intravenous access.
• Give atropine 10 to 20 micrograms/kg (minimum 100 micrograms) before the dose or before any repeat dose, because bradycardia is more frequent in children.

Contraindications. Personal or family history of malignant hyperthermia; hyperkalaemia; burns, crush injury or major trauma after the first 24 to 48 hours (risk persists for months); denervation and upper motor neurone lesions such as stroke, spinal cord injury and prolonged immobilisation; neuromuscular disease and muscular dystrophy; known severe cholinesterase deficiency; prolonged critical illness with myopathy; hypersensitivity.

Boxed-warning-level risks. Acute rhabdomyolysis with hyperkalaemic cardiac arrest, particularly in boys with undiagnosed muscular dystrophy; malignant hyperthermia; anaphylaxis (among the most frequent causes of anaesthetic anaphylaxis).

Adverse effects. Common: fasciculations, postoperative myalgia, rise in serum potassium of about 0.5 mmol/L, bradycardia (especially on repeat dosing), raised intragastric, intraocular and intracranial pressure, masseter spasm. Serious: hyperkalaemic arrest, malignant hyperthermia, anaphylaxis, prolonged apnoea from cholinesterase deficiency, phase II block, bradycardia progressing to asystole.

Interactions. Anticholinesterases (neostigmine, organophosphates, ecothiopate eye drops) prolong the block. Lithium, magnesium and ester local anaesthetics prolong it. Aminoglycosides and volatile agents add to it. Pretreatment with a small dose of a non-depolarising drug reduces fasciculations but raises the suxamethonium dose needed.

Common prescribing errors. Using it in burns, long immobilisation or neuromuscular disease; giving a repeat dose without atropine; using too low a dose (under 1 mg/kg) in rapid sequence induction; using degraded vials stored at room temperature for weeks; not checking for a family history of anaesthetic problems.

Special groups

• Pregnancy: plasma cholinesterase activity falls by about 25% so recovery is slightly slower; clinically important placental transfer is minimal at usual doses.
• Breastfeeding: compatible.
• Older adults: usual dose; slightly slower onset.
• Kidney impairment: acceptable if the serum potassium is normal; avoid with hyperkalaemia.
• Liver impairment: reduced cholinesterase synthesis prolongs the block; severe disease may give prolonged apnoea.
• Regional: the drug loses potency out of the refrigerator, and cold chain failure is common, so check storage and expiry. Cholinesterase testing is seldom available, so a family history of prolonged paralysis should be taken seriously. Where sugammadex is unavailable, rocuronium at 1 to 1.2 mg/kg is an alternative for rapid sequence induction.

Formulations. Injection 50 mg/mL and 100 mg/mL; prefilled syringes in some markets.

Administration. Inject rapidly intravenously followed by a flush. Store at 2 to 8 degrees Celsius; most labels allow storage at room temperature for up to 14 days (check the label). Never leave in a syringe with an alkaline drug such as thiopental.

Baseline. Personal and family anaesthetic history, neuromuscular disease, burns or immobilisation, serum potassium if risk factors are present, current medicines.

Monitoring. Continuous electrocardiogram, oxygen saturation, capnography. Train-of-four monitoring where available, to separate phase I from phase II block. In a patient who does not recover movement in the expected time, check for cholinesterase deficiency.

Therapeutic drug monitoring. Not used. A plasma cholinesterase activity and dibucaine number are sent after prolonged apnoea.

Dose reduction and stopping thresholds. Do not repeat without atropine. Do not use in the contraindicated states. After a reaction, document and refer the patient for testing.

Referral and escalation. Prolonged paralysis from cholinesterase deficiency needs continued ventilation with sedation until recovery, which can take 2 hours or longer, and sampling for cholinesterase activity. Hyperkalaemia with arrhythmia needs calcium chloride 10 mL of 10% intravenously, insulin 10 units with 25 g glucose, and salbutamol. Malignant hyperthermia needs dantrolene 2.5 mg/kg intravenously rapidly, repeated up to a total of 10 mg/kg, with cooling and intensive care. Anaphylaxis needs intramuscular adrenaline.