Management of Intentional Diphenhydramine Overdose
The management of intentional diphenhydramine overdose requires immediate assessment of ABCs (Airway, Breathing, Circulation), cardiac monitoring, and administration of sodium bicarbonate for cardiotoxicity, with consideration of early intubation for airway protection in severe cases. 1
Initial Assessment and Stabilization
Airway and Breathing:
- Assess for respiratory depression (diphenhydramine can cause central respiratory depression)
- Consider early endotracheal intubation for airway protection in severe cases with altered mental status 1
- Avoid succinylcholine as a neuromuscular blocker due to potential interactions 1
- Administer oxygen as needed 1
Circulation:
- Establish IV access immediately 1
- Position patient appropriately (Trendelenburg for hypotension, sitting up for respiratory distress) 1
- Obtain ECG to assess for QRS prolongation and terminal rightward axis deviation (in lead aVR) 1
- For QRS prolongation >100 ms, administer sodium bicarbonate (1-2 mEq/kg IV bolus) 1
- For refractory hypotension, administer IV fluids and vasopressors as needed
Cardiac Monitoring and Management
- ECG monitoring: Continuous cardiac monitoring is essential due to risk of QRS prolongation and arrhythmias 1
- Sodium bicarbonate administration: For life-threatening cardiotoxicity, administer sodium bicarbonate bolus IV (1000 mEq/L in adults) 1
- Target pH: Maintain serum pH 7.45-7.55 to overcome sodium channel blockade 1
- Consider VA-ECMO: For refractory cardiac arrest due to severe diphenhydramine toxicity 1
Neurological Management
- Seizure management: Administer benzodiazepines for seizures or agitation 2
- Monitor for status epilepticus: This is a potential complication requiring aggressive management 3
- Toxic psychosis: Patients may present with hallucinations and bizarre behavior requiring sedation and monitoring 4
Gastrointestinal Decontamination
- Do not induce emesis due to risk of rapid deterioration and seizures 2
- Activated charcoal: Consider only if patient presents within 1 hour of ingestion and has a protected airway 2
- Orogastric lavage: May be considered in massive ingestions with early presentation and protected airway 3
Monitoring and Supportive Care
- Vital signs monitoring: Every 30 minutes during initial treatment, then hourly for at least 4 hours 1
- Observation period: Close observation for 24 hours after severe reactions 1
- Laboratory monitoring: Electrolytes, renal function, hepatic function, and drug levels if available
- Potassium repletion: Aggressive potassium repletion may be necessary 3
Special Considerations
- Physostigmine: Should be reserved for administration in a hospital setting for severe anticholinergic symptoms without contraindications (not QRS prolongation) 2, 5
- Co-ingestions: Be alert for co-ingested substances, particularly alcohol, benzodiazepines, or other CNS depressants 6
- Psychiatric evaluation: All patients with intentional overdose require psychiatric assessment once medically stable 2
Disposition
ICU admission criteria:
- QRS prolongation >100 ms
- Hypotension requiring vasopressors
- Seizures or status epilepticus
- Significant altered mental status requiring airway protection
- Severe anticholinergic symptoms
Psychiatric consultation: Required for all intentional overdoses prior to discharge 2
Pitfalls and Caveats
- Underestimating toxicity: Diphenhydramine overdose can rapidly progress from mild drowsiness to severe toxicity with seizures and cardiac arrest
- Missing cardiotoxicity: Always obtain ECG and monitor for QRS prolongation
- Delayed symptoms: Anticholinergic effects may worsen over time, requiring extended observation
- Co-ingestions: Always consider the possibility of multiple substances, especially in intentional overdoses
- Social media challenges: Be aware of trends like the "Benadryl challenge" that may lead to intentional overdoses, especially in adolescents 3