Question 12

College Answer

The question specifically asked for factors that influenced the speed of onset of neuromuscular block. This information is different to the factors that influence neuromuscular blockade in general which was what many candidates focussed on. It was expected candidates would  address the main factors known to influence the speed of onset of neuromuscular block: -potency of the agent used (inverse relationship to speed of onset); rate of delivery of the agent to the NMJ (blood flow / muscle group); and mechanism of the neuromuscular block (nondepolarising vs depolarising).

Discussion

• Factors that influence the rate of agent delivery to the muscles:
  • Route of administration (IV faster than IM)
  • Site of IV administration (CVC faster than PIVC)
  • Rate of administration (flushed bolus faster than infusion)
  • Cardiac output (faster in pregnancy, slower in cardiogenic shock)
  • Muscle position (those proximal to the heart affected faster)
• Factors that influence plasma-effect site equilibration
  • Potency of the agent (less potent agents have faster onset)
    (this is the most important determinant and is mainly due to the larger molar concentration of the effective dose of the low potency agents)
  • Factors which influence diffusion to the site (minor influence),
    of which the only one that matters is:
    • Protein binding (less bound drugs have faster onset)
• Factors that increase the required effective concentration (slowing the onset):
  • Factors that increase acetylcholine concentration
    • Acetylcholinesterase inhibitors
  • Factors that increase the number of receptors
    • Critical illness polyneuromyopathy
    • Burns
    • Tetanus
    • Spinal injury
    • Stroke
    • Antiepileptic agents
  • Factors that reduce the number of acetylcholine receptors, such as myasthenia gravis (for non-depolarising agents, this slows the onset)
  • Factors that hyperpolarise the motor endplate
    • Hyperkalemia (for nondepolarisng agents)
    • Hypercalcemia
    • Malignant hyperthermia
• Factors that decrease the required effective concentration (hastening the onset):
  • Factors that reduce the synthesis or storage of acetylcholine
    • Hemicholinium
    • Vesamicol
  • Factors that decrease acetylcholine release
    • Foetal/neonatal motor endplates
    • General anaesthetic agents (volatiles)
    • Regional local anaesthesia
    • Frusemide
    • Calcium channel blockers
    • Aminoglycosides
  • Factors that partially depolarise the motor endplate
    • Hypermagnesemia
    • Hypocalcemia
    • Hyperkalemia (for depolarising agents)
  • Pre-curarisation or "priming" with a low dose of non-depolarising agent
  • Factors that reduce the number of acetylcholine receptors, such as myasthenia gravis (for depolarising agents, this slows the onset)

Kim, Yong Byum, Tae-Yun Sung, and Hong Seuk Yang. "Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents." Korean journal of anesthesiology 70.5 (2017): 500-510.