Neuromuscular Blockade — Block Onset

Drug Factors

• Dose: Higher dose (eg. multiples of ED95) = faster onset.
• Plasma clearance: Postulated that drugs with faster clearance (eg. sux) have faster onset.
• Potency:
  • Inverse log relationship between potency and speed of onset (non-depolarisers).
  • Low potency = bigger dose needed (more molecules), so higher conc gradient between plasma and site of action = more rapid onset.
• Depolarisers vs non-depolarisers.

Patient Factors

• Rate of injection: faster rate = faster onset.
• Site of injection: Central vein (more rapid distribution)> peripheral vein > IM
• Cardiac output and muscle blood ­flow: Higher CO and muscle ­flow = faster delivery to site of action.
• Priming: small dose of non-depolariser as a premed can partially block NMJ, followed by intubating dose. This decreases time from intubating dose to intubation conditions.
• Disease states: eg. myasthenia gravis (fewer ACh receptors, so needs more sux, but about 10% dose of non-depolariser).

Other factors

• Muscle group: Fastest affected = small, rapidly moving muscle groups (eye, digits), with trunk/abdo muscles last affected.
• Recovery is in reverse order: diaphragm/intercostals recover first.
• Onset more rapid in muscle groups relevant to intubation: laryngeal, masseters. Slower in monitored muscles (eg.adductor pollicus).
• Probably due to muscle blood fl­ow.
• Smaller volume of distribution due to blood loss can augment potency ie: speed of onset(Stoelting)

Drugs:

eg. ephedrine can increase speed of rocuronium onset. Inhalationals/aminoglycosides.

JC 2019

Answer by JC