Neuromuscular blockers

Vivian Imbriotis | Dec. 4, 2025

Nondepolarizing NMBs mechanism:

  1. Competitively antagonize the nicotinic receptor
  2. Once >95% of sites are occupied, this prevents ACh binding \(\to\) prevents depolarization


Depolarizing NMBs (suxamethonium is the only one in use) mechanism:

  1. Continiously agonising the nicotinic receptor, keeping the channel open
  2. This maintains a depolarized endplate
  3. This initially results in a normal depolarization as the fast sodium channels move into the open state
  4. These sodium channels then become inactivated as the H gate closes
  5. For the fast sodium channels ringing the endplate, the lack of repolarization prevents opening of the H gate
  6. Further depolarization is not conducted
  7. This is called "accommodation block"


Rocuronium

Aminosteroid NDNMB

Dose: 0.9mg/kg

Onset in 60 seconds

Lasts ~30 minutes but highly variable

Intermediate incidence of anaphylaxis

Hepatically metabolized and excreted in bile

Precipitates with thiopentone


Vecuronium

Aminosteroid NDNMB

Dose: 0.1mg/kg

Onset in 3 minutes

Lasts ~30 minutes, less variable than roc

Low incidence of anaphylaxis

Hepatically metabolized and excreted in bile


Sugammadex

Binds to aminosteroid NMBs (i.e. roc and vec)

The complex is then excreted renally

Reversal of paralysis within 3 minutes

Half-life 2 hours

Dose 2mg/kg

Cisatracurium

Benzylisoquinoline (cis-enantiomer of atracurium)

4 minute onset

45 minute duration

0.15mg/kg dose

Organ-independent metabolism (Hoffman elimination)

Lowest incidence of anaphylaxis

Reliable pharmacokinetics \(\to\) NMB of choice for infusions

Near-immediate onset (one arm-heart-muscle circulation time)

~5 minute duration

1mg/kg IV

4mg/kg IM

Degraded by plasma pseudocholinesterase


Mechanism of action

  1. Continiously agonising the nicotinic receptor, keeping the channel open
  2. This maintains a depolarized endplate
  3. This initially results in a normal depolarization as the fast sodium channels move into the open state
  4. These sodium channels then become inactivated as the H gate closes
  5. For the fast sodium channels ringing the endplate, the lack of repolarization prevents opening of the H gate
  6. Further depolarization is not conducted
  7. This is called "accommodation block"
  8. With repeated doses, the muscles will fail to depolarize even with electrical stimulus (phase II block), mechanism unknown


"Scoline apnoea" (serum cholinesterase deficiency)

Congenital or acquired

Results in prolonged paralysis, up to hours

Acquired causes

  1. Liver disease (the liver makes the stuff), malnutrition, malignancy (no substrate)
  2. Pseudocholinesterase inhibitors (neostigmine, organophosphates, MOAIs)
  3. Cocaine (competes with sux for pseudocholinesterase)


Nicotinic receptor proliferation

Sux can result in hyperkalaemic arrest due to exaggerated potassium efflux from supranormal whole body depolarization

Spinal cord injury, extended immobility (and therefore critical illness), stroke, muscular dystrophy, burns all due to negative feedback (muscles starved for ACh upregulate their nicotinic receptors)


Anaphylaxis

Highest rate of any NBM


Malignant hyperthermia

Most common trigger

Unregulated calcium influx from the sarcoplasmic reticuluum via an abnormal ryanodine receptor

Massive ATP hydrolysis by myosin ATPase

Increased metabolic rate

Increased VCO2 and internal temperature

Lactate production and acidosis

Rhabdomyolysis and then renal failure