Neostigmine (Bloxiverz)

• Acetylcholinesterase Inhibitor: Increases acetylcholine at nicotinic (neuromuscular junction) and muscarinic (heart, gut, bronchi) receptors
• Two Main Critical-Care Uses:
  • Reversal of non-depolarizing neuromuscular blockers (NMBs) like rocuronium/vecuronium at end of anesthesia when sugammadex unavailable
  • Treatment of acute colonic pseudo-obstruction (Ogilvie's syndrome) when conservative therapy fails
• Always Paired with Antimuscarinic: NMB reversal always combined with glycopyrrolate or atropine due to muscarinic effects (bradycardia, secretions, bronchospasm)
• Dosing: 0.02-0.07 mg/kg IV (max ~5 mg) for NMB reversal; 2 mg IV slow push over 3-5 minutes for Ogilvie's with continuous ECG monitoring and atropine at bedside
• Critical Safety: For Ogilvie's, must exclude mechanical obstruction/perforation before administration; severe bradycardia and asystole are well-described

• Generic Name: Neostigmine methylsulfate
• Brand Names: Bloxiverz, Prostigmin, generics

Reversible acetylcholinesterase inhibitor; parasympathomimetic

Mechanism of Action:

• Reversibly inhibits acetylcholinesterase, the enzyme that hydrolyzes acetylcholine (ACh) in synaptic clefts
• At neuromuscular junction: Increased ACh competes with non-depolarizing NMBs (rocuronium, vecuronium) for nicotinic receptors, restoring neuromuscular transmission and skeletal muscle strength
• At muscarinic receptors: In heart, GI tract, and airways, increased ACh causes parasympathetic effects—bradycardia, bronchoconstriction, increased secretions, increased GI motility
• In acute colonic pseudo-obstruction: Enhancing ACh in enteric nervous system and smooth muscle increases colonic motility and may relieve functional obstruction

Pharmacokinetics (IV):

• Onset: Clinical effect begins within 5-10 minutes after IV administration for NMB reversal, depending on depth of neuromuscular blockade
• Peak effect: Approximately 7-10 minutes after dosing
• Duration: ~45-90 minutes for neuromuscular reversal; GI motility effects may last several hours
• Distribution: Quaternary ammonium compound, highly polar; does NOT cross blood-brain barrier meaningfully
• Metabolism/elimination: Partly hepatic; ~50% excreted unchanged in urine; elimination half-life ~50-90 minutes, prolonged in significant renal impairment

Available Forms:

• Injection: Commonly 1 mg/mL (e.g., 10 mg/10 mL) vials for IV/IM administration
• Oral tablets: 15 mg tablets for chronic MG therapy (much less commonly used than pyridostigmine)
• For both NMB reversal and Ogilvie's syndrome, IV route is standard and preferred

Neostigmine Dosing (Adult):

Contraindications:

• Suspected or confirmed mechanical intestinal obstruction or peritonitis (for GI indication)
• Urinary tract obstruction (risk of worsening urinary retention)
• Known hypersensitivity to neostigmine or formulation components

Major Precautions:

• Bradycardia, AV block: Must have atropine or glycopyrrolate available; bradyarrhythmias are major risk with IV dosing
• Asthma or severe COPD: Risk of bronchospasm and increased bronchial secretions
• Recent MI, severe CAD, decompensated heart failure: Bradycardia and hypotension can reduce coronary perfusion
• In Ogilvie's: Must exclude perforation or mechanical obstruction with imaging before giving neostigmine; otherwise may precipitate perforation

Common (Cholinergic):

• Bradycardia, hypotension
• Increased salivation and bronchial secretions
• Nausea, vomiting, abdominal cramping, diarrhea
• Sweating, miosis

Serious:

• Symptomatic bradycardia, asystole, AV block
• Bronchospasm and respiratory distress
• Severe cholinergic crisis with muscle weakness (overdose or in MG patients)

During and After Administration:

• Continuous ECG and blood pressure monitoring, especially for Ogilvie's dosing
• For NMB reversal: Train-of-four (TOF) monitoring if available plus clinical assessment (hand grip, head lift, tidal volume, airway protection)
• Respiratory status: work of breathing, wheezing/bronchospasm, secretions
• In Ogilvie's: Abdominal distension, tenderness, and bowel function to gauge response and detect early perforation

• Reversal of residual non-depolarizing neuromuscular blockade: Rocuronium, vecuronium at end of general anesthesia or procedural paralysis
• Acute colonic pseudo-obstruction (Ogilvie's syndrome): When conservative measures (NPO, NG/rectal decompression, mobilization, electrolyte correction) have failed
• Myasthenia gravis: Historically and in some regions as adjunct; pyridostigmine preferred for chronic oral therapy

• 1. Lexicomp. (2024). Neostigmine: Drug information. Wolters Kluwer.
• 2. Ponec, R. J., Saunders, M. D., & Kimmey, M. B. (1999). Neostigmine for the treatment of acute colonic pseudo-obstruction. New England Journal of Medicine, 341(3), 137–141.