What are the signs of cholinergic excess?

Signs of Cholinergic Excess

Cholinergic excess produces a characteristic constellation of muscarinic, nicotinic, and central nervous system manifestations that can be rapidly fatal if not recognized and treated immediately. 1, 2

Muscarinic Effects (SLUDGE/DUMBELS Syndrome)

The muscarinic receptor overstimulation from acetylcholine accumulation produces the most prominent and clinically recognizable features:

Secretory Manifestations

• Profuse secretions including excessive salivation, lacrimation, bronchorrhea, and diaphoresis result from overstimulation of muscarinic receptors in exocrine glands 1, 2
• These secretions can be so overwhelming that they cause airway obstruction and require continuous sterile suction 2

Respiratory System

• Severe respiratory distress develops from bronchial constriction, wheezing, prolonged expiration, stridor, and moist rales due to airway smooth-muscle contraction combined with excess secretions 2
• Central respiratory depression may occur in severe cases as acetylcholine excess impairs the respiratory drive 2

Gastrointestinal System

• Gastrointestinal hypermotility manifests as abdominal cramping, diarrhea, nausea, and vomiting secondary to increased smooth muscle activity 1, 2
• Hyperactive bowel sounds are characteristic 1

Cardiovascular System

• Bradycardia and hypotension dominate the cardiovascular picture after an initial brief period of tachycardia and hypertension 1, 2
• AV-node conduction disturbances including heart block and AV dissociation can occur 2
• Malignant arrhythmias such as prolonged QTc and ventricular tachyarrhythmias may arise from coronary vasospasm or direct myocardial toxicity 2

Nicotinic Effects

• Brief catecholamine surge produces transient hypertension and tachycardia before muscarinic effects dominate, reflecting early nicotinic stimulation of the sympathetic system 2
• Involuntary skeletal muscle contractions followed by complete depolarization-like block result from constant activation of nicotinic receptors 1
• Muscle fasciculations, weakness, and ultimately flaccid paralysis develop as nicotinic receptors become overstimulated 1

Central Nervous System Manifestations

• Anxiety, disorientation, and general convulsions occur from acetylcholine accumulation in the CNS 1
• Coma can ensue within seconds after exposure to severe cholinergic agents, evolving rapidly to respiratory arrest 1

Clinical Pitfalls and Recognition

The biphasic cardiovascular response is a critical diagnostic feature: an initial brief hypertension and tachycardia from nicotinic sympathetic ganglia activation is followed by prolonged bradycardia and hypotension from muscarinic overload 1, 2. Clinicians who only observe the initial tachycardia may miss the diagnosis before the patient deteriorates into profound bradycardia and cardiovascular collapse.

Hemodynamic collapse accompanied by bradycardia is a muscarinic action that precedes death 1. The overwhelming secretions can cause tube migration even after intubation, requiring continuous verification of tube position 2.

Specific Clinical Contexts

• Irinotecan-related cholinergic syndrome typically appears within 24 hours of drug administration, presenting with diarrhea, vomiting, diaphoresis, abdominal cramping, and occasionally excessive lacrimation or rhinorrhea 2
• Rivastigmine overdose can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions, with additional symptoms including diarrhea, abdominal pain, dizziness, tremor, headache, somnolence, confusional state, hyperhidrosis, hypertension, hallucinations, and malaise 3