Depolarising NMBs
Succinylcholine binds to the nicotinic ACh receptor causing depolarisation. It cannot be hydrolysed by acetylcholinesterase in the NMJ, and so remains bound to the receptor. This:
- Produces a sustained depolarisation which keeps voltage-gated sodium channels in their inactive state
- Prevents the post-junctional membrane from responding to further ACh release
| Property | Succinylcholine |
|---|---|
| Class | Depolarising muscle relaxant. |
| Uses | Facilitate tracheal intubation. |
| Presentation | Colourless solution of pH 3, at 50mg.ml-1. Structurally, it is two ACh groups joined at the acetyl groups. |
| Route of Administration | IV, IM. |
| Dosing | 1-2mg.kg-1 IV, 3-4mg.kg-1 IM up to 150mg. |
| Onset and Duration | IV onset in 30s to 1 minute, lasting 2-3 minutes, with offset typically within 10 minutes. Offset occurs due to dissociation of drug out of NMJ into plasma, as a concentration gradient is established by drug breakdown in plasma. Prolonged duration in patients with pseudocholinesterase deficiency. IM onset in 2-3 minutes. |
| Distribution | 30% protein bound. Nil distribution due to rapid metabolism - VD 0.25L.kg-1. Crosses placenta in very small amounts. |
| Metabolism | Rapid hydrolysis by plasma cholinesterases such that only 20% of administered dose reaches the NMJ. |
| Elimination | Minimal renal elimination due to rapid metabolism. |
| Resp | Apnoea, and suxamethonium apnoea. May cause masseter spasm. ↑ Salivation due to muscarinic effects. |
| CVS | Arrhythmia due to SA node stimulation, as well as secondary to hyperkalaemia. Bradycardia (due to muscarinic effects with second/large doses, or in children). |
| CNS | ↑ ICP (due to contraction), ↑ IOP (by 10mmHg - this is significant) such that it is contraindicated in globe perforation. |
| Metabolic | Malignant Hyperthermia. |
| MSK | Myalgias post depolarisation, particularly in young females. Prolonged blockade with pseudocholinesterase deficiency. |
| Renal and Electrolyte | Hyperkalaemia (K+ ↑ by ~0.5mmol.L-1) due to depolarisation causing K+ efflux, ↑ in burns (>10%), paraplegia (first 6 months) and neuromuscular disorders including muscular dystrophy and myopathies (including critical illness myopathy). |
| GIT | Intragastric pressure ↑ by 10cmH2O, matched by ↑ in LoS pressure. |
| Immunological | Anaphylaxis - highest risk of all NMBs at ~11/100,000 |
Adverse Effects
The adverse effects of suxamethonium can be remembered as three major, three minor, and three pressures:
- Major
- Anaphylaxis
- Suxamethonium Apnoea
- Malignant hyperthermia
- Minor
- Hyperkalaemia
- Myalgias
- Bradycardia
- Pressure
Phase I and Phase II Blockade
Initial blockade is termed Phase I, which is a partial depolarising block. Sustained use of suxamethonium may causes a Phase II block which:
- Appears similar to a non-depolarising block
- May be due to:
- Presynaptic inhibition of ACh synthesis and release
- Desensitisation of the post-junctional receptor
Key differences include:
| Property | Phase I Block | Phase II Block |
|---|---|---|
| Block Amplitude | Reduced | Reduced |
| Train-of-four ratio | >0.7 | < 0.7 |
| Post-tetanic potentiation | No | Yes |
| Effect of anticholinesterases | Block augmented | Block inhibited |
Malignant Hyperthermia
- Rare autosomal dominant genetic condition
- Triggered by suxamethonium and volatile anaesthetic agents
- Mutation of the ryanodine receptor causes excessive amounts of calcium to leave the sarcoplasmic reticulum, causing continual muscle contraction
- Results in greatly increased carbon dioxide, lactate, and heat production
- Cell lysis with myoglobulinaemia and hyperkalaemia results
Suxamethonium Apnoea
- A deficiency of butylcholinesterase causes suxamethonium to not be metabolised
- May be congenital (genetic) or acquired (hepatic failure)
- Can be treated with fresh frozen plasma
References
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Suxamethonium Chloride Injection BP PRODUCT INFORMATION
- Appiah-Ankam J, Hunter JM. Pharmacology of neuromuscular blocking drugs. Continuing Education in Anaesthesia Critical Care & Pain, Volume 4, Issue 1, 1 February 2004, Pages 2–7.
- Cook T, Harper N. Anaesthesia, Surgery, and Life-Threatening Allergic Reactions: Report and findings of the Royal College of Anaesthetists' 6th National Audit Project: Perioperative Anaphylaxis. Royal College of Anaesthetists'. 2018.