What is the treatment for a diphenhydramine (Benadryl) overdose?

Management of Diphenhydramine (Benadryl) Overdose

For diphenhydramine overdose, immediately stop any ongoing administration, secure the airway, establish IV access, administer sodium bicarbonate 1-2 mEq/kg IV bolus for QRS widening, and give benzodiazepines for seizures or severe agitation. 1

Immediate Assessment and Stabilization

• Stop diphenhydramine administration immediately and assess airway, breathing, and circulation 1
• Establish intravenous access and position the patient appropriately (recumbent with legs elevated if hypotensive) 2, 1
• Administer supplemental oxygen as needed 1
• Monitor vital signs continuously, including continuous cardiac monitoring for QRS widening 1, 3

Cardiovascular Management

Diphenhydramine acts as a sodium channel blocker and can cause cardiac toxicity similar to tricyclic antidepressants, manifesting as QRS prolongation and wide-complex dysrhythmias. 1

• For QRS prolongation >0.10 msec or wide-complex dysrhythmias, administer sodium bicarbonate 1-2 mEq/kg IV bolus immediately 1, 3
• For hypotension unresponsive to IV fluid resuscitation, administer vasopressors such as dopamine or vasopressin 1
• For patients on beta-blockers with refractory hypotension, administer glucagon (child: 20-30 μg/kg; adult: 1-5 mg), which may be repeated or followed by infusion of 5-15 μg/min 2, 1

Neurological Management

Anticholinergic toxicity from diphenhydramine commonly presents with agitation, hallucinations, seizures, and altered mental status. 3, 4

• For seizures or severe agitation, administer benzodiazepines 1, 3
• Avoid physostigmine in the out-of-hospital setting; it should be reserved for hospital administration only 3
• Avoid neuromuscular blockers metabolized by cholinesterase in patients with anticholinergic toxicity 1

Decontamination Considerations

• Do not induce emesis due to the risk of rapid deterioration with loss of consciousness or seizures 3
• Do not administer activated charcoal en route to the emergency department because of the potential for sudden loss of consciousness or seizures 3
• For dermal exposures, perform skin decontamination with water or soap and water unless moderate to severe symptoms are already present, in which case transportation should not be delayed 3

Triage and Referral Criteria

Specific dose thresholds determine the need for emergency department evaluation:

• Children <6 years: Refer to ED if ingestion ≥7.5 mg/kg 3
• Patients ≥6 years: Refer to ED if ingestion ≥7.5 mg/kg OR ≥300 mg (whichever is less) 3
• All patients with suicidal intent, intentional abuse, or suspected malicious intent require immediate ED referral 3
• Any patient with symptoms beyond mild drowsiness or mild stimulation (including agitation, hallucinations, abnormal muscle movements, loss of consciousness, seizures, or respiratory depression) requires ED referral 3

Observation Periods

• For oral diphenhydramine exposures: If asymptomatic after 4 hours, ED referral is not necessary 3
• For dermal exposures: If asymptomatic 8 hours after thorough skin decontamination, ED referral is not necessary 3
• Patients with subtherapeutic ingestions and no or mild symptoms can be observed at home with poison center follow-up at approximately 4 hours post-ingestion 3

Supportive Care

• Administer IV fluids for volume resuscitation 1
• For mild anticholinergic symptoms, consider H1 or H2 antihistamines, though these will have limited immediate effect 2, 1
• Maintain continuous monitoring until symptoms resolve 1

Critical Pitfalls to Avoid

The most serious complications include cardiac conduction abnormalities (QRS widening), seizures, and cardiovascular collapse. 5, 6, 7

• Diphenhydramine can cause life-threatening toxicity even at therapeutic doses when given intravenously, particularly in infants and young children 7
• Massive overdoses (>7.5 g) have resulted in death despite aggressive supportive measures 6
• In refractory cases with persistent hypotension and QRS prolongation despite sodium bicarbonate, charcoal hemoperfusion may be considered as rescue therapy 5
• The FDA drug label warns to "get medical help or contact a Poison Control Center right away" in case of accidental overdose 8