What are the clinical manifestations and management of cholinergic toxicity?

Cholinergic Effects: Clinical Manifestations and Management

Clinical Manifestations of Cholinergic Toxicity

Cholinergic toxicity presents with a characteristic constellation of symptoms captured by the mnemonic "Red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, full as a flask"—though this actually describes anticholinergic toxicity; cholinergic toxicity presents with the opposite picture: excessive secretions, miosis, bradycardia, and fasciculations. 1

Muscarinic Effects (SLUDGE/DUMBELS Syndrome)

• Excessive secretions: Profuse salivation, lacrimation, bronchorrhea, and diaphoresis occur due to overstimulation of muscarinic receptors in secretory glands 2, 1
• Respiratory distress: Severe bronchial constriction, wheezing, prolonged expiration, stridor from laryngeal spasm, and moist rales develop from airway smooth muscle contraction and excessive secretions 2
• Cardiovascular effects: Initial brief hypertension and tachycardia (minutes) from nicotinic stimulation of sympathetic ganglia, followed by prolonged bradycardia, hypotension, and AV conduction disturbances from muscarinic receptor overstimulation 2, 1
• Gastrointestinal hypermotility: Abdominal cramping, diarrhea, nausea, and vomiting from increased smooth muscle activity 2
• Urinary urgency: Bladder contraction and urinary frequency from detrusor muscle stimulation 3
• Miosis: Pupillary constriction from activation of pupillary constrictor muscles 1

Nicotinic Effects

• Neuromuscular manifestations: Involuntary fasciculations, muscle weakness progressing to flaccid paralysis from overstimulation at the neuromuscular junction 1
• Initial sympathetic surge: Brief catecholamine release causing hypertension and tachycardia before muscarinic effects dominate 2

Central Nervous System Effects

• Neuropsychiatric symptoms: Agitation, seizures, restlessness, anxiety, confusion, and delirium from central acetylcholine excess 1
• Respiratory depression: Central respiratory drive impairment in severe cases 2

Cardiac Complications

• Malignant arrhythmias: Ischemic ST-T changes, prolonged QTc (poor prognostic sign), ventricular arrhythmias from coronary vasospasm or direct myocardial toxicity 2
• Conduction abnormalities: AV dissociation, heart block, and paradoxical bradycardia if intubation is delayed 2

Management of Cholinergic Toxicity

Immediate Airway Management

Secure the airway immediately with endotracheal intubation, preferably via the nasal route, as excessive secretions and perspiration can dislodge oral tubes. 2

• Aggressive secretion management: Regularly aspirate airways by sterile technique starting immediately after intubation 2
• Verify tube position repeatedly: Continuous verification is essential due to overwhelming oral and airway secretions 2
• Mechanical ventilation: Use pressure-controlled mandatory ventilation with 100% oxygen and PEEP to deliver adequate minute volume 2
• Monitor for barotrauma: Watch for sudden airway pressure elevation or blood pressure decrease, though this may be difficult in chaotic conditions 2

Pharmacological Antidotes

Atropine is the gold standard treatment for cholinergic toxicity, as it blocks muscarinic receptor overstimulation caused by acetylcholine accumulation. 1

• Atropine dosing: Administer to reverse muscarinic effects (bronchorrhea, bronchospasm, bradycardia), though it does not halt severe bronchoconstriction in all cases 2, 1
• Critical limitation: Atropine does not address nicotinic effects at the neuromuscular junction, which require oximes for reversal 1
• Adjunctive bronchodilators: When atropine fails to control severe bronchoconstriction, add β-agonists (aerosolized albuterol 2.5 mg in 3 mL saline) 2
• Additional respiratory support: Consider ipratropium bromide inhalation (0.5 mg) combined with intravenous methylprednisolone (125 mg three times daily) for noncardiogenic pulmonary edema 2

Cardiovascular Support

• Treat bradycardia and hypotension: Atropine reverses muscarinic-mediated cardiac depression 2
• Monitor for arrhythmias: Prolonged QTc indicates poor prognosis; manage malignant ventricular arrhythmias with standard protocols 2
• Address underlying causes: Correct acidosis and hypoxia, which worsen cardiac abnormalities 2

Critical Management Pitfalls

• Avoid physical restraints: In agitated patients, restraints exacerbate hyperthermia and worsen lactic acidosis 4
• Use benzodiazepines for agitation: First-line treatment for CNS symptoms, not antipsychotics which may worsen cholinergic effects 4
• Consider physostigmine cautiously: While physostigmine can produce dramatic reversal of anticholinergic toxicity within minutes, it is contraindicated in cholinergic toxicity as it would worsen acetylcholine excess 4

Specific Considerations

• Distinguish from anticholinergic toxicity: Cholinergic toxicity causes wet, sweaty skin and excessive secretions, whereas anticholinergic toxicity causes hot, dry skin and urinary retention 3
• Irinotecan-related cholinergic syndrome: Occurs within 24 hours of administration with diarrhea, emesis, diaphoresis, abdominal cramping, and less commonly hyperlacrimation and rhinorrhea 2
• Risk factors: Patients with chronic respiratory diseases, cardiovascular diseases, or those on β-blockers and ACE inhibitors face increased risk 2