What morning labs should be done for a diphenhydramine (Benadryl) overdose?

Morning Laboratory Evaluation for Diphenhydramine (Benadryl) Overdose

Order a comprehensive metabolic panel, complete blood count, creatine kinase, urinalysis, and ECG as your core morning labs following diphenhydramine overdose. 1

Essential Laboratory Studies

Metabolic and Electrolyte Assessment

• Complete metabolic panel (CMP) to evaluate electrolyte imbalances, renal function (BUN/creatinine), liver function (AST/ALT), and glucose levels 1
• Electrolyte abnormalities are critical to identify as they can exacerbate cardiac conduction abnormalities already present from diphenhydramine's anticholinergic and sodium channel blocking effects 2, 3
• Hypokalemia and hypochloremia may develop, particularly if the patient required sodium bicarbonate therapy overnight 4

Hematologic Evaluation

• Complete blood count (CBC) should be obtained, though diphenhydramine itself does not cause hematologic toxicity and does not require white blood cell monitoring 5
• The CBC helps identify complications from prolonged immobilization, aspiration, or other co-ingestions 1

Cardiac and Muscle Injury Markers

• Creatine kinase (CK) to assess for rhabdomyolysis, which can occur from prolonged seizures or agitation associated with anticholinergic toxicity 2
• Troponin if there were cardiac conduction abnormalities or hemodynamic instability overnight, as diphenhydramine overdose can cause cardiac toxicity 2, 6

Urinalysis

• Urinalysis to evaluate for myoglobinuria (from rhabdomyolysis) and to assess renal function 1
• Also helps identify urinary retention, a common anticholinergic effect of diphenhydramine 5, 7

Critical Monitoring Parameters

Electrocardiographic Assessment

• 12-lead ECG is essential as diphenhydramine overdose causes QTc prolongation (mean 453 ± 43 ms in overdose patients versus 416 ± 35 ms in controls) 3
• Monitor for cardiac conduction abnormalities and hemodynamic compromise, which can develop even after initial stabilization 2
• While torsades de pointes is rare with diphenhydramine (unlike second-generation antihistamines), significant QTc prolongation still occurs 3

Additional Considerations for Specific Clinical Scenarios

If seizures occurred overnight:

• Add lactate level to assess for metabolic acidosis 1
• Consider arterial blood gas if there are concerns about respiratory compromise or persistent acidosis 1

If co-ingestion is suspected:

• Toxicology screening may be warranted, though standard drug panels do not detect diphenhydramine 4
• Consider acetaminophen and salicylate levels as these are common co-ingestions in intentional overdoses 1

If the patient required sodium bicarbonate therapy:

• Monitor for hypernatremia, alkalemia, hypokalemia, and hypochloremia 4
• Serial electrolytes may be needed throughout the day 4

Common Pitfalls to Avoid

• Do not assume stability based on initial presentation - patients with toxic medication ingestions can have rapid decline in mental or hemodynamic status even when appearing to compensate 1
• Do not overlook renal function - diphenhydramine's anticholinergic effects can cause urinary retention, and rhabdomyolysis from seizures can lead to acute kidney injury 5, 1
• Do not forget to reassess cardiac status - the duration of diphenhydramine's effects is 4-6 hours, so morning labs should include repeat ECG even if the initial one was normal 5, 7