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

Treatment for Diphenhydramine (Benadryl) Overdose

For diphenhydramine overdose, immediately administer sodium bicarbonate 1-2 mEq/kg IV bolus for QRS prolongation or wide-complex dysrhythmias, and benzodiazepines for seizures or severe agitation, while providing aggressive supportive care with continuous cardiac monitoring. 1, 2

Initial Management

• Stop any ongoing diphenhydramine administration immediately and assess airway, breathing, and circulation 2
• Establish intravenous access and administer supplemental oxygen as needed 2
• Begin continuous cardiac monitoring with particular attention to QRS duration and rhythm 1, 2
• Administer IV fluids for volume resuscitation 2

Cardiovascular Toxicity Management

Diphenhydramine acts as a sodium channel blocker similar to tricyclic antidepressants, causing QRS prolongation and potentially life-threatening dysrhythmias 1, 2. This is the most critical aspect requiring immediate intervention.

Sodium Bicarbonate Administration

• For QRS prolongation (>100 msec) or wide-complex dysrhythmias, administer sodium bicarbonate 1-2 mEq/kg IV bolus immediately 1, 2
• The American Heart Association specifically recommends sodium bicarbonate for life-threatening cardiotoxicity from sodium channel blocker poisoning, which includes diphenhydramine 1
• Repeat sodium bicarbonate boluses as needed to maintain QRS narrowing 3
• Monitor for improvement in cardiac conduction within minutes of administration 4

Hypotension Management

• If hypotension persists despite fluid resuscitation, administer vasopressors such as dopamine or vasopressin 2
• Aggressive potassium repletion should be performed simultaneously with sodium bicarbonate administration 3

Neurological Toxicity Management

Seizures and Agitation

• Administer benzodiazepines (diazepam first-line or midazolam) for seizures or severe agitation 1, 2, 5
• Benzodiazepines may be given by EMS personnel if authorized by medical direction 5
• Be prepared for status epilepticus requiring intubation in massive overdoses 3

Altered Mental Status

• Patients with moderate to severe symptoms including agitation, hallucinations, abnormal muscle movements, loss of consciousness, or respiratory depression require emergency department referral 5
• Do NOT administer physostigmine in the prehospital setting—this should be reserved for hospital administration only 5

Gastrointestinal Decontamination

• Do NOT induce emesis due to risk of rapid deterioration with loss of consciousness or seizures 5
• Do NOT administer activated charcoal en route to the emergency department due to aspiration risk 5
• Orogastric lavage may be considered in the hospital setting for recent massive ingestions 3

Advanced Interventions for Refractory Cases

In cases of massive overdose (>7.5 g) where standard supportive measures fail:

• Consider charcoal hemoperfusion and hemodialysis for life-threatening toxicity unresponsive to sodium bicarbonate and pressors 4
• One case report documented rapid improvement in ECG findings within 40 minutes of charcoal hemoperfusion initiation in a 16 g overdose 4
• This contradicts older teaching that diphenhydramine is unsuitable for extracorporeal removal, but may be lifesaving in massive overdoses 4

Observation and Disposition Guidelines

Referral Criteria

• All patients with suicidal intent, intentional abuse, or suspected malicious intent require emergency department evaluation 5
• Children <6 years ingesting ≥7.5 mg/kg require emergency department referral 5
• Patients ≥6 years ingesting ≥7.5 mg/kg or ≥300 mg (whichever is less) require emergency department referral 5

Home Observation

• Asymptomatic patients with subtherapeutic ingestions can be observed at home with poison center follow-up at 4 hours post-ingestion 5
• If >4 hours have elapsed since ingestion and the patient remains asymptomatic, emergency department referral is not necessary 5

Critical Pitfalls to Avoid

• Never use neuromuscular blockers metabolized by cholinesterase (succinylcholine, mivacurium) in anticholinergic toxicity 1, 2
• Do not delay sodium bicarbonate administration while waiting for laboratory confirmation—treat based on ECG findings 1, 3
• Recognize that cardiovascular collapse can occur rapidly, even after initial stabilization 6
• Be aware of the "Benadryl challenge" social media trend leading to intentional massive overdoses in adolescents 3
• Diphenhydramine toxicity can be fatal—the largest documented fatal overdose was 7.5 g in a 14-year-old despite aggressive life support 6