This patient with bradycardia, diaphoresis, hypersalivation, miosis, and bronchorrhea with wheezing has signs of cholinergic toxicity.  Most cases of cholinergic toxicity are due to organophosphate pesticides.  However, the occurrence in multiple patients in a crowded city setting suggests intentional organophosphate exposure, possibly due to a chemical weapon (eg, sarin, soman).  These agents have been used in multiple military and terrorist attacks; the gas is colorless, tasteless, and often has a slight, fruity odor.

Organophosphates inhibit cholinesterase in the muscarinic and nicotinic cholinergic synapses, leading to decreased acetylcholine degradation and overstimulation of the corresponding receptors.  In addition to widespread increased visceral smooth muscle tone and glandular secretions due to muscarinic hyperactivity (mnemonic: DUMBELS—see table), nicotinic hyperactivity causes muscle weakness and paralysis that can lead to rapid respiratory depression and death.

Organophosphate poisoning can be confirmed with the measurement of red blood cell acetylcholinesterase activity.  Atropine, a competitive inhibitor of acetylcholine at the muscarinic receptors, can also be used for both diagnosis and treatment.  The absence of anticholinergic signs (eg, mydriasis, erythema, tachycardia) after a small dose of atropine (ie, 1 mg) supports the diagnosis of organophosphate poisoning.  Treatment usually requires much larger doses.  Further management includes pralidoxime, a cholinesterase-reactivating agent that treats both the muscarinic and nicotinic effects of organophosphates.

(Choice A)  An arterial blood gas with carboxyhemoglobin level is used to confirm carbon monoxide toxicity.  Patients with carbon monoxide poisoning typically have headache, nausea, confusion, and cherry red–appearing lips and skin.  Signs of cholinergic excess are unexpected.

(Choice B)  A basic metabolic panel and plasma osmolality test can support toxic alcohol ingestion (eg, methanol, ethylene glycol), which results in both anion and osmolal gaps.  In addition to altered mental status, methanol causes visual blurring and blindness, whereas ethylene glycol causes flank pain and hematuria.

(Choice C)  A Geiger-Müller counter can help diagnose radiation exposure.  Acute radiation syndrome typically causes tachycardia, nausea, vomiting, and diarrhea and progresses to include anemia and encephalopathy.

(Choice D)  Methemoglobin levels are elevated in patients with methemoglobinemia, which typically occurs with administration of dapsone and some topical anesthetics (eg, benzocaine).  Affected patients have cyanosis, dyspnea, and tachycardia.

Educational objective:
Organophosphates inhibit cholinesterase in both the muscarinic and nicotinic cholinergic synapses, leading to increased visceral smooth muscle tone and glandular secretions (mnemonic: DUMBELS) as well as muscle fasciculations, weakness, and paralysis.  Organophosphate poisoning can be confirmed with the measurement of red blood cell acetylcholinesterase activity.