Diphenhydramine Poisoning & Lipid Emulsion Therapy

1. Diphenhydramine Poisoning

① Diphenhydramine

• Used for nausea, vomiting, allergic rhinitis, allergy treatment, and as a sleep aid.
• A first-generation H1 antihistamine available over the counter.

② Mechanism of Action

• Competes with histamine for H1 receptor binding sites in airway, vasculature, gastrointestinal tract, and CNS.
• Occupies H1 receptors in the frontal cortex, temporal cortex, hippocampus, and pons in the CNS, leading to sedation.
• Overdose can cause severe neurological and respiratory symptoms.
• Effects on Muscarinic Receptors
  • May cause anticholinergic effects such as blurred vision, dry mouth, urinary retention, erectile dysfunction, tachycardia, nausea, and constipation.

③ Toxic Effects

• Cardiovascular Effects
  • ECG changes including QRS complex widening and tachycardia due to potassium channel blockade.
  • Prolonged QT interval, flattened T waves, and increased risk of life-threatening arrhythmias such as Torsades de Pointes.
• Serum Peak Levels
  • Reached approximately 2-3 hours after oral ingestion.
• Half-Life
  • Children: ~5 hours (range: 4–7 hours).
  • Adults: ~9 hours (range: 7–12 hours).
  • Elderly: ~13.5 hours (range: 9–18 hours).
• Lipid Solubility
• Toxic Dose
  • Dose-dependent toxicity.
  • Retrospective studies indicate moderate symptoms (agitation, confusion, hallucinations, ECG abnormalities) at 0.3 g.
  • Severe symptoms (delirium, seizures, coma, death) at doses exceeding 1 g.

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2. Evaluation & Treatment of Diphenhydramine Poisoning

① Rapid Assessment of Toxicity & Overdose Severity

• Perform ABCDE approach (Airway, Breathing, Circulation, Disability, Exposure).
• ECG to assess for arrhythmias (e.g., Torsades de Pointes).
• If seizures occur, check serum creatinine, urine output, and creatine phosphokinase to rule out rhabdomyolysis.

② Treatment

• Activated Charcoal
  • Delayed absorption due to anticholinergic effects may make activated charcoal useful.
  • Avoid if airway protection is not ensured.
• No Specific Antidote
• Supportive Treatment
  • Seizures: Benzodiazepines (e.g., Lorazepam).
  • Ventricular Arrhythmias: Sodium bicarbonate.
• Intravenous Lipid Emulsion Therapy

③ When to Seek Emergency Care

• Children: If dose is <7.5 mg/kg, home observation is sufficient unless behavioral changes occur.
• If dose is ≥7.5 mg/kg, referral to a medical facility is required.

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3. Lipid Emulsion Therapy in Diphenhydramine Poisoning

① Mechanism of Lipid Emulsion Therapy

• Acts as a “lipid sink” for lipophilic diphenhydramine molecules.
• Removes diphenhydramine from sodium channels, reversing sodium channel blockade.

② Dosing <20% intravenous lipid emulsion>

• Patients >70 kg: 100 mL IV bolus, followed by 200–250 mL over 15–20 min.
• Patients <70 kg: 1.5 mL/kg IV bolus, then 0.25 mL/kg/min IV infusion.

③ Adverse Effects

• Immediate: Allergic reactions, dyspnea, hyperlipidemia, hypercoagulability.
• Delayed: Transient liver enzyme elevation, hepatosplenomegaly, thrombocytopenia.

References: UpToDate, Rosen’s Emergency Medicine, NIH.