What is the management approach for a diphenhydramine (Benadryl) overdose?

Management of Diphenhydramine (Benadryl) Overdose

Diphenhydramine overdose requires immediate recognition of anticholinergic toxicity and prompt intervention with supportive care, with sodium bicarbonate administration for cardiac toxicity and benzodiazepines for neurological symptoms.

Clinical Presentation and Symptoms

• Diphenhydramine overdose presents with anticholinergic toxicity affecting multiple organ systems 1, 2
• Neurological symptoms include:
  • Altered mental status, ranging from drowsiness to agitation 2
  • Hallucinations, confusion, and delirium 3
  • Seizures and status epilepticus in severe cases 4
  • Movement disorders and tremors 2
• Cardiovascular manifestations include:
  • QRS prolongation due to sodium channel blockade 1
  • Tachycardia, which may progress to wide-complex dysrhythmias 4
  • Hypotension in severe cases 4
• Other symptoms may include:
  • Mydriasis (pupillary dilation) 2
  • Dry mouth and skin 5
  • Hyperthermia 2
  • Urinary retention 6

Initial Assessment and Management

• Stop any ongoing diphenhydramine administration immediately 1
• Assess ABCs (Airway, Breathing, Circulation) and level of consciousness 1
• Maintain intravenous access 1
• Position the patient appropriately:
  • Trendelenburg position if hypotensive 1
  • Sitting up if respiratory distress is present 1
  • Recovery position if unconscious 1
• Administer supplemental oxygen as needed 1

Specific Interventions

Cardiovascular Management

• For QRS prolongation (>0.10 msec) or wide-complex dysrhythmias:
  • Administer sodium bicarbonate 1-2 mEq/kg IV bolus 1, 4
  • May repeat sodium bicarbonate as needed for persistent QRS widening 4
• For hypotension unresponsive to fluids:
  • Administer vasopressors such as dopamine (400 mg in 500 mL of 5% dextrose) at 2-20 μg/kg/min 1
  • Consider vasopressin (25 U/250 mL, 0.01-0.04 U/min) for refractory hypotension 1
• For bradycardia (uncommon in diphenhydramine overdose):
  • Administer atropine 600 μg IV 1

Neurological Management

• For seizures or severe agitation:
  • Administer benzodiazepines (e.g., diazepam or midazolam) 1, 2
  • Consider intubation for status epilepticus or airway protection 4
• For severe anticholinergic delirium unresponsive to benzodiazepines:
  • Physostigmine may be considered in a hospital setting (not in pre-hospital care) 2

Gastrointestinal Decontamination

• Do not induce emesis due to risk of rapid onset of seizures or altered mental status 2
• Consider activated charcoal only if:
  • Patient presents within 1 hour of ingestion
  • Airway is protected or patient is alert
  • No contraindications exist 2
• Gastric lavage may be considered for massive ingestions with recent presentation 4

Supportive Care

• Administer IV fluids for volume resuscitation:
  • Normal saline 1-2 L at a rate of 5-10 mL/kg in the first 5 minutes 1
  • Continue with crystalloids in boluses of 20 mL/kg followed by slow infusion 1
• Monitor vital signs continuously, including cardiac monitoring 1
• Consider antihistamines for mild symptoms:
  • H1 antagonists (diphenhydramine 25-50 mg) may be paradoxically helpful in mild cases 1
  • H2 antagonists (ranitidine 50 mg IV) may be given in combination 1

Special Considerations

• For patients on beta-blockers with refractory symptoms:
  • Administer glucagon 1-5 mg IV over 5 minutes, followed by infusion (5-15 μg/min) 1
• For pediatric patients:
  • Children <6 years who ingest ≥7.5 mg/kg should be referred to an emergency department 2
  • Adjust medication doses based on weight 2
• Close observation for at least 24 hours after severe reactions 1

Common Pitfalls and Caveats

• Diphenhydramine is classified as a sodium channel blocker and can cause cardiac toxicity similar to tricyclic antidepressants 1
• Do not use neuromuscular blockers metabolized by cholinesterase (e.g., succinylcholine) in patients with anticholinergic toxicity 1
• Be aware that diphenhydramine is present in many over-the-counter preparations, which may lead to unintentional overdose 3
• Social media trends like the "Benadryl challenge" have increased intentional overdoses, especially among adolescents 4
• Symptoms may be delayed, so observation for at least 6 hours post-ingestion is recommended even in asymptomatic patients 2