Neostigmine (Prostigmin)

Anesthesia Implications

Classification: Acetylcholinesterase Inhibitor
Therapeutic Effects: Nondepolarizing neuromuscular blockade reversal
Time to Onset: less than 3 minutes
Time to Peak: 3-14 minutes
Duration: 40-60 minutes

Contraindications

Peritonitis
Mechanical obstruction of the intestines or urinary tract

Use with caution in patients with: Bradycardia, bronchial asthma, peptic ulcers, epilepsy, and arrhythmias

Primary Considerations

Uses – good for reversal of nondepolarizing neuromuscular blockers (eg. rocuronium, vecuronium, atracurium, cisatracurium)

Bradycardia – this is the primary concern when giving neostigmine. Neostigmine causes an increased quantity of acetylcholine at the synapse. This effectively competes with the neuromuscular blocker, but also causes an increase in muscarinic affects (such as bradycardia). To counter this affect, glycopyrrolate (0.01 mg/kg) is given with neostigmine (0.05 mg/kg).

OB – Must be given slowly in the parturient. If given rapidly, neostigmine can increase uterine tone and thereby cause preterm labor and/or fetal distress.

Reduced affects – aminoglycoside antibiotics, hypothermia, hypokalemia, and acidosis all weaken the reversal affects of neostigmin

Succinylcholine – should not be used to reverse succinylcholine. In fact, neostigmine will prolong its affects.

Cholinergic crisis – Excessive neostigmine can contribute to a cholinergic crisis. The symptoms are nausea, vomiting, brady/tachycardia, excessive salivation, sweating, bronchospasm, weakness, and paralysis.
Treatment: 10 mcg/kg IV every 3-10 minutes until muscarinic symptoms subside. Pralidoxime (15 mg/kg) IV over 2 minutes will reverse nicotinic symptoms. Supportive treatment (eg. ventilator support) as needed.

IV push dose

Neuromuscular Blockade Reversal: 0.05 mg/kg with glycopyrrolate (0.01 mg/kg). MAX: 5 mg.

Method of Action

Competes with acetylcholine in binding to acetylcholinesterase and thereby prevents hydrolysis of acetylcholine. Additional acetylcholine at the postsynaptic receptors leads to improved transmission of impulses across the neuromuscular junction. Additional acetylcholine also leads to muscarinic affects such as bradycardia and salivation – which is countered, or decreased by co-administration of glycopyrrolate or atropine.

Metabolism

Hepatic and plasma esterase