What is the most likely substance ingested by a patient presenting with anticholinergic toxidrome, including dry mucous membranes, dilated pupils, and altered mental status, with a history of depression, anxiety, and chronic back pain?

Anticholinergic Toxidrome: Diphenhydramine Overdose

The most likely substance this patient ingested is diphenhydramine, which classically presents with the anticholinergic toxidrome characterized by dry mucous membranes, flushed skin, dilated pupils, tachycardia, hyperthermia, altered mental status with agitated delirium, and visual hallucinations (picking at the air). 1

Clinical Reasoning

Why Diphenhydramine is the Answer

The patient's presentation matches the classic anticholinergic syndrome, often remembered as "Red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, full as a flask." 1 Specifically:

• Dry mucous membranes and hot, dry, erythematous skin are pathognomonic for anticholinergic poisoning 1
• Mydriasis (dilated pupils) is characteristic of anticholinergic toxicity 1
• Agitated delirium with visual hallucinations (picking/swiping at air) represents the "mad as a hatter" component 1
• Mild hyperthermia (38.1°C) with tachycardia (124 bpm) and hypertension (158/94) fit the anticholinergic profile 1
• Hypoactive or absent bowel sounds would be expected (though not mentioned in this case) 1

Diphenhydramine is specifically listed as a common cause of anticholinergic poisoning in the guideline evidence, along with antihistamines, tricyclic antidepressants, sleep aids, and cold preparations. 1 Given her history of depression, anxiety, and chronic pain, diphenhydramine is readily accessible as an over-the-counter sleep aid and is frequently used in intentional overdoses. 2

Why Not the Other Options

Phenelzine (MAOI) would cause serotonin syndrome with:

• Diaphoretic (sweaty) skin, not dry 1
• Sialorrhea (excessive salivation), not dry mucous membranes 1
• Hyperactive bowel sounds with possible diarrhea 1
• Increased muscle tone predominantly in lower extremities with hyperreflexia and clonus 1

Pseudoephedrine (sympathomimetic) would cause:

• Diaphoresis, not dry skin 1
• Agitation but typically without the profound visual hallucinations seen here
• Would not cause the characteristic dry mucous membranes or mydriasis in the same pattern

Tramadol can cause serotonin syndrome (similar to phenelzine) or seizures, but would present with:

• Diaphoresis and sialorrhea 1
• Neuromuscular hyperactivity with clonus 1
• Not the dry anticholinergic picture seen here

Management Approach

Immediate Stabilization

• Supportive care with continuous cardiorespiratory monitoring 1
• Benzodiazepines for agitation (first-line treatment) 1, 3
• Aggressive cooling measures for hyperthermia if temperature rises 1
• IV fluid resuscitation for hypotension if it develops 1

Specific Antidote Consideration

Physostigmine is the specific antidote for severe anticholinergic toxicity and can produce dramatic reversal within minutes. 4 However, its use should be reserved for:

• Life-threatening complications: severe agitated delirium unresponsive to benzodiazepines, resistant cardiotoxicity, or seizures 5, 3
• Dosing: 0.5-2 mg IV at slow controlled rate, may repeat if life-threatening signs persist 4
• Duration of action is short (45-60 minutes), so repeated dosing may be necessary 4

Important caveat: Physostigmine is contraindicated if there is evidence of tricyclic antidepressant toxicity (wide QRS complex) as it can worsen cardiac conduction abnormalities and precipitate asystole. 5 The patient's ECG should be carefully evaluated before administration.

Decontamination

• Gastric lavage may be considered if presentation is within 1-2 hours of massive ingestion and airway is protected 2, 5
• Activated charcoal if patient can safely swallow or has protected airway

Monitoring

• Serial ECGs to monitor for QRS widening (suggesting co-ingestion of tricyclic antidepressants) 5
• Core temperature monitoring 1
• Continuous cardiac monitoring for dysrhythmias 1
• Electrolyte monitoring, particularly potassium 2

Common Pitfalls

Do not confuse with serotonin syndrome: The key differentiating features are the dry skin and mucous membranes in anticholinergic toxicity versus diaphoresis and sialorrhea in serotonin syndrome. 1

Avoid physostigmine if tricyclic co-ingestion suspected: Check for QRS widening on ECG before administering physostigmine, as it can be lethal in tricyclic overdose. 5

Physical restraints are contraindicated: They may exacerbate hyperthermia through isometric muscle contractions and worsen lactic acidosis. 1

Diphenhydramine toxicity is increasingly common due to social media trends like the "Benadryl challenge" and its widespread over-the-counter availability. 2 Emergency providers should maintain high clinical suspicion in young patients presenting with altered mental status and anticholinergic signs.