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Bedside Snapshot
- 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
Brand & Generic Names
- Generic Name: Neostigmine methylsulfate
- Brand Names: Bloxiverz, Prostigmin, generics
Medication Class
Reversible acetylcholinesterase inhibitor; parasympathomimetic
Pharmacology
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
Dosing & Administration
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):
| Indication / Scenario | Dose | Route / Timing | Notes |
|---|---|---|---|
| Reversal of non-depolarizing NMB (typical) | 0.02-0.07 mg/kg | IV over ≥1-2 min | Max ~5 mg; dose guided by depth of block and TOF monitoring |
| Common flat dosing example | 2.5-5 mg | IV once | Often combined with glycopyrrolate (e.g., 0.2 mg per 1 mg neostigmine) |
| Acute colonic pseudo-obstruction (Ogilvie's) | 2 mg | IV slow push over 3-5 min | Continuous ECG monitoring; atropine ready; may repeat once after several hours if incomplete response |
| Total maximum dose for Ogilvie's | 4 mg | IV (e.g., 2 mg × 2 doses) | Lack of response → reconsider diagnosis, rule out mechanical obstruction/perforation |
| Renal impairment | Lower end of dosing range | IV | Prolonged effect possible; adjust cautiously |
| Timing for NMB reversal | Give when TOF ratio ≥0.2-0.3 | — | Too early in deep block → incomplete reversal and more side effects |
Antimuscarinic Required: Always combine with glycopyrrolate or atropine for NMB reversal to prevent bradycardia and other muscarinic effects.
Contraindications
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
Adverse Effects
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)
Monitoring
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
Indications / Clinical Uses (ED/ICU/Anesthesia Focus)
- 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
Clinical Pearls
Ceiling Effect: For NMB reversal, neostigmine has a ceiling effect—beyond a certain point, more drug adds muscarinic toxicity without better reversal; ensure adequate spontaneous recovery before dosing.
Ogilvie's Success: Success rates with neostigmine are high when diagnosis is correct and mechanical obstruction excluded; if it fails, consider endoscopic decompression early.
Draw Atropine First: Always draw up atropine before giving neostigmine for Ogilvie's; severe bradycardia and even asystole are well-described.
Sugammadex vs Neostigmine: Sugammadex has replaced neostigmine in many ORs for rocuronium reversal, but neostigmine remains essential where sugammadex is unavailable, restricted, or cost-prohibitive.
References
- 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.