Antagonist-assisted neuromuscular-blockade reversal

• "Cholinesterase Inhibitors; Neuromuscular Reversal and Anticholinergic Pharmacology"

  Attribution: Nguyen D Cholinesterase Inhibitors; Neuromuscular Reversal and Anticholinergic Pharmacology" https://www.youtube.com/watch?v=eDdwS82A3ww University of Kentucky Department of Anesthesia

• Edrophonium (Tensilon), neostigmine (Prostigmin), or pyridostigmine (Mestinon):  effective by increasing acetylcholine availability of neuromuscular junction (secondary to acetylcholinesterase inhibition).

• Physostigmine (Antilirium): not used because dosage requirement is excessive.

• Anticholinesterase agents are usually administered during spontaneous neuromuscular-blockade recovery.

  •   Recovery rate is the sum of:

    • (1) Spontaneous recovery from the blocking drug and 

    • (2) The activity of the pharmacologic antagonist (anticholinesterase drugs).

  •  Therefore: pharmacologic antagonism is more effective for short-or intermediate-acting neuromuscular-blocking drugs (undergoing plasma hydrolysis or Hoffmann elimination) compared to long-acting nondepolarizing neuromuscular-blocking agents

• Special Considerations: use of muscarinic antagonists with anticholinesterases in reversal of neuromuscular blockade.

  • Reversal of nondepolarizing neuromuscular-blockade: necessitates only nicotinic cholinergic effects of anticholinesterases agents.

  • Minimizing muscarinic receptor-mediated effects of anticholinesterase drugs is beneficial an accomplished by a concurrent administration of atropine or glycopyrrolate (antimuscarinics).

  • The antimuscarinic agent should have a more rapid onset than the anticholinesterase drugs, reducing drug-induced bradycardia.

    •  If edrophonium (Tensilon)(0.5 mg/kg) is used; atropine 7 µg/kg is appropriate.

    •  A higher dose atropine (10-15 µg/kg) has been recommended, particularly if nonopioid-based maintenance anesthetic has been used.

    •  If neostigmine is used (slower onset of action compared edrophonium (Tensilon)), then atropine or glycopyrrolate (Robinul) may be administered as the antimuscarinic agent;

      • Concurrent administration of these drugs results in an initial tachycardia because of atropine's more rapid onset.

• Factors influencing the speed and extent of neuromuscular blockade reversal by anticholinesterase agents:

  • Intensity neuromuscular-blockade when reversal is initiated (train-of-four visible twitches)

  • Which nondepolarizing neuromuscular-blocking drug is being reversed

    • Edrophonium (Tensilon): less effective than neostigmine in reversing deep neuromuscular blockade (twitch height < 10% of control) produced by continuous atracurium (Tracrium), vecuronium (Norcuron), or pancuronium (Pavulon) infusions.

    • Edrophonium (Tensilon), probably better than neostigmine (Prostigmin)for reversing atracurium (Tracrium)blockade

    • Neostigmine (Prostigmin), probably better than edrophonium (Tensilon) for reversing vecuronium (Norcuron) blockade

  • Prevention/inhibition of anticholinesterase-mediated antagonism of neuromuscular-blockade.

    • Possible factors:

      • Certain antibiotics.

      • Hypothermia.

      • Respiratory acidosis (PaCO₂ >50 mm Hg.

      • Hypokalemia/metabolic acidosis.

  • Reversal of phase II block (following prolonged/repeated succinylcholine (Anectine)): may be reversed with edrophonium (Tensilon) or neostigmine (Prostigmin) in patients with normal plasma cholinesterase.

    •  In patients with atypical plasma cholinesterase, phase II block reversal may not be reliable, requiring mechanical ventilation until blockade subsides.