Antagonist-assisted neuromuscular-blockade reversal

• 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.