Treatment of Diphenhydramine (Benadryl) Overdose
Immediately stop diphenhydramine 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
Initial Stabilization and Assessment
Stop all diphenhydramine immediately and assess airway, breathing, and circulation (ABCs). 1 Establish intravenous access and position the patient appropriately for monitoring. 1 Administer supplemental oxygen as needed to maintain adequate oxygenation. 1
Monitor for anticholinergic toxicity affecting multiple organ systems, particularly cardiac sodium channel blockade causing QRS prolongation. 1 Diphenhydramine acts as a sodium channel blocker and can cause cardiac toxicity similar to tricyclic antidepressants. 1 Continuous vital sign monitoring and cardiac monitoring are essential. 1
Cardiovascular Management
For QRS prolongation (>0.10 msec) or wide-complex dysrhythmias, administer sodium bicarbonate 1-2 mEq/kg IV bolus immediately. 1, 2 This overcomes the sodium channel blockade caused by diphenhydramine. 3 Repeated doses may be necessary for persistent wide-complex tachycardia. 3
For hypotension unresponsive to IV fluid resuscitation, administer vasopressors such as dopamine or vasopressin. 1 Aggressive potassium repletion should be performed simultaneously with sodium bicarbonate administration. 3
Neurological Management
For seizures or severe agitation, administer benzodiazepines as first-line therapy. 1, 2 Status epilepticus is a life-threatening complication that can occur rapidly after diphenhydramine overdose, sometimes within one hour of ingestion. 4 Intubation may be required for airway protection in patients with status epilepticus or severe altered mental status. 3
Physostigmine should be reserved for administration in a hospital setting only and should not be given in the prehospital environment. 2 While physostigmine has been used to stabilize cardiac rhythms in some cases, its use requires careful consideration and hospital-based monitoring. 4
Decontamination Considerations
Do not induce emesis following oral diphenhydramine exposure. 2 Because diphenhydramine can cause rapid loss of consciousness or seizures, activated charcoal should not be administered en route to an emergency department. 2
If the patient presents early and is alert without contraindications, orogastric lavage may be considered in the hospital setting for massive ingestions. 3 However, this decision should be made by emergency department physicians based on timing and clinical status.
Supportive Care
Administer IV fluids for volume resuscitation and maintain continuous vital sign monitoring. 1 Monitor cardiovascular and neurologic status meticulously, as most diphenhydramine overdoses require excellent supportive care. 3
Special Populations and Considerations
For patients on beta-blockers with refractory symptoms, administer glucagon. 1 Patients receiving beta-adrenergic blocking agents may require more intensive and prolonged treatment for anaphylactoid-type reactions or cardiovascular instability. 5
Avoid neuromuscular blockers metabolized by cholinesterase in patients with anticholinergic toxicity. 1 This is a critical pitfall to avoid, as these agents can worsen the clinical picture.
Referral and Disposition Criteria
All patients with suicidal intent, intentional abuse, or suspected malicious intent should be referred to an emergency department. 2
Refer patients to the emergency department if they exhibit:
- Any changes in behavior beyond mild drowsiness or mild stimulation 2
- Agitation, staring spells, inconsolable crying, hallucinations 2
- Abnormal muscle movements, loss of consciousness, seizures, or respiratory depression 2
- Ingestion of ≥7.5 mg/kg in children <6 years 2
- Ingestion of ≥7.5 mg/kg or 300 mg (whichever is less) in patients ≥6 years 2
Patients may be observed at home if:
- No symptoms are present and >4 hours have elapsed since ingestion 2
- Ingestion is less than toxic dose with no or mild symptoms only 2
- Follow-up call should be made at approximately 4 hours post-ingestion 2
Critical Pitfalls
Death can occur within two hours of massive diphenhydramine overdose, with rapid CNS stimulation including status epilepticus being the most dangerous complication. 4 From 2019-2020, antihistamines were found in 15% of all US drug overdose deaths, with diphenhydramine being the most common antihistamine involved. 6 There is currently no specific antidote for diphenhydramine overdose, making aggressive supportive care and management of complications paramount. 6