FRCA Notes

Suxamethonium

  • Suxamethonium (succinylcholine) is a depolarising NMBA comprising of two acetylcholine molecules joined back-to-back via their acetyl groups:
    • Suxamethonium chemical formula
  • Other depolarising agents from the 'methonium' family, although not used in UK practice, include:
    • Decamethonium
    • Suxethonium
  • Rapid sequence induction i.e. where rapid, profound neuromuscular blockade is required
  • Facilitate intubation for short surgical procedures or those where only brief blockade is desired (e.g. surgical requirement for facial or recurrent laryngeal nerve monitoring)
  • To reduce muscle twitching associated with electro-convulsive therapy

Presentation

  • Presents as a clear, colourless solution of its chloride salt
  • Concentration of 50mg/ml
  • Stored at 4ºC (i.e. in the fridge)

Dosing

  • IV: 1 - 1.5mg/kg (not affected by age)
    • Onset of action within 30s and determined by the end of fasciculations
    • Duration 3-5mins

  • IM: 2 - 4mg/kg (typically reserved for paediatric patients)

  • Binds the nAChR causing membrane depolarisation
  • Its hydrolysing enzyme (plasma cholinesterase) isn't present at the NMJ therefore suxamethonium has a duration of action longer than native acetylcholine

  • Persistent depolarisation of the receptor initiates local current circuits:
    • enders voltage-gated sodium channels within 1-2mm of the receptor inactive
    • The area of electrical inexcitability prevents action potential transmission
    • This leads to muscle relaxation
  • This initial depolarising block is a Phase I block
  • Muscle function starts to recover in 5 mins and is complete 15mins post 1mg/kg dose

  • If further doses of suxamethonium are given, it may become a Phase II block [i.e. similar characteristics to non-depolarising block, although different mechanism]

Absorption

  • Minimal oral bioavailability

Distribution

  • Rapid distribution
  • 20% protein-bound
  • Only 20% of initial IV dose reaches NMJ
  • VD = 0.14L/kg

Metabolism

  • Rapidly hydrolysed by plasma cholinesterase (plasma and liver)

    • Suxamethonium → succinylmonocholine + choline → succinic acid + choline

  • Succinylmonocholine is weakly active

Excretion

  • <10% excreted unchanged in the urine due to rapid metabolism
  • Half-life 1-2mins

Cardiovascular

  • Arryhthmogenic, especially in paediatric patients
    • Stimulation of muscarinic AChR in the sinus node can cause:
      • Nodal or sinus bradycardia
      • Ventricular arrhythmias
    • Bradycardia is often more severe after a second dose

Neurological

  • IOP (normally 15mmHg) is raised by 10mmHg for minutes post-suxamethonium dose
  • The mechanism is unknown
    • ?Transient dilation of choroidal blood vessels
    • ?Contraction of tonic myofibrils
  • Co-administration of thiopentone will keep IOP static
  • This is significant in the presence of globe perforation

  • Repeated doses may cause a phase 2 block (this is not more common in neonates)

Gastrointestinal

  • Raises intragastric pressure by 10cmH2O
  • However there is a simultaneous increase in LOS tone and therefore no increased risk of reflux

Metabolic

  • Hyperkalaemia
    • There is a small rise in serum potassium as depolarisation causes K+ efflux into the extracellular fluid (0.2 - 0.4mmol/L)
    • Patients with neuromuscular disorders or (>10%) burns are susceptible to a sudden release of K+, which may be large enough to cause cardiac arrest
    • Extra-junctional AChR (foetal subtype) proliferate over the surface of the muscle
      • Paraplegic patients: period of particular risk is in the first 6 months although continues in those with progressive muscular disease
      • Neuromuscular disorders including dermatomyositis, dystrophia myotonica and others
      • Burns patients: safe for the first 24hrs after thermal injury and from 18 months afterwards
      • Renal failure patients are not at increased risk of sudden hyperkalaemia per se, though may already have high K+ levels and therefore be at increased risk

Musculoskeletal

  • Myalgia - commonest in young female patients mobilising rapidly post-operatively
    • Pre-medication with small doses of diazepam, gallamine (non-depolarising NMBA) and dantrolene have limited effect at reducing myalgia

Adverse reaction