Cholinergic Toxidrome

A cholinergic toxidrome occurs when acetylcholine accumulates because acetylcholinesterase cannot break it down. Excess acetylcholine stimulates muscarinic receptors in glands, smooth muscle, heart, and airways; nicotinic receptors at autonomic ganglia and the neuromuscular junction; and central nervous system synapses. The result is not one uniform pattern but three overlapping families of findings. Typical causes include organophosphate or carbamate pesticides, nerve agents, and excessive cholinesterase-inhibitor therapy such as pyridostigmine. Organophosphates phosphorylate acetylcholinesterase. With time, the inhibited enzyme may undergo “aging,” an irreversible chemical change that prevents reactivation. Carbamates carbamylate the enzyme more transiently and generally allow spontaneous recovery over hours. Severity depends on the combination of airway secretions, bronchospasm, neuromuscular weakness, and central respiratory depression. A patient can deteriorate even when one familiar sign, such as bradycardia or miosis, is absent.