Neostigmine

Quick Answer

Neostigmine is a reversible acetylcholinesterase inhibitor used to reverse non-depolarizing neuromuscular blockade (NMB) by increasing acetylcholine (ACh) concentration at the neuromuscular junction, overcoming competitive block. Structure: Quaternary ammonium carbamate (charged at physiological pH, does not cross blood-brain barrier, peripheral action only). Mechanism: Forms covalent bond with acetylcholinesterase enzyme at esteratic site, carbamoylating the enzyme (slower hydrolysis than acetylation by ACh), enzyme inactivated for 2-4 hours; increases ACh at all cholinergic synapses (nicotinic at NMJ for reversal, muscarinic at heart, glands, smooth muscle for side effects). Dosing: 0.05-0.07 mg/kg IV (maximum 5 mg) given with anticholinergic (glycopyrrolate 0.01 mg/kg or atropine 0.015 mg/kg); timing—wait until TOF count ≥4 or at least 10% twitch height (reversal less effective with profound block). Onset: 1-2 minutes (faster than edrophonium but slower than sugammadex), peak effect 5-10 minutes, duration 2-4 hours (matches glycopyrrolate duration). Side effects: Muscarinic effects (bradycardia, AV block, hypotension, increased secretions—bronchial and salivary, bronchospasm, increased GI motility—nausea/vomiting, abdominal cramps, diarrhoea); prevent by concurrent anticholinergic (glycopyrrolate preferred—less CNS penetration, longer duration, less tachycardia than atropine). Monitoring: TOF monitoring essential—confirm adequate reversal (TOF ratio >0.9, fade absent, head lift 5 seconds, tongue protrusion, grip strength) before extubation; inadequate reversal causes postoperative residual curarization (PORC—weakness, hypoxia, aspiration risk, reintubation). Contraindications: Mechanical bowel obstruction, urinary tract obstruction, peritonitis (increased GI motility dangerous); caution in asthma (increased secretions, bronchospasm). Comparison to sugammadex: Neostigmine slow onset (10-15 min to full reversal), requires some spontaneous recovery first (cannot reverse profound block), muscarinic side effects (requires anticholinergic), cheaper; sugammadex rapid (3-5 min), can reverse any depth of rocuronium/vecuronium block, no muscarinic effects, expensive. Clinical pearls: Must give with anticholinergic to prevent severe bradycardia; ineffective against depolarizing block (suxamethonium—wait for spontaneous recovery); inadequate for deep block (wait until 4 twitches visible); adequate reversal confirmed by TOF ratio >0.9 (clinical tests less sensitive). [1-10]