CK Monitoring in Diphenhydramine Overdose Without Seizures
Yes, obtain a creatine kinase (CK) level in diphenhydramine overdose even without seizures, as rhabdomyolysis can occur from the overdose itself independent of seizure activity.
Rationale for CK Monitoring
Diphenhydramine overdose can directly cause rhabdomyolysis without seizures occurring. A documented case demonstrated intentional diphenhydramine ingestion resulting in CK levels exceeding 2 million IU/L, which responded to aggressive IV hydration 1. This establishes that the anticholinergic toxicity and direct muscle effects of diphenhydramine can cause severe muscle breakdown independent of seizure-related muscle injury.
Risk Factors in Anticholinergic Overdose
The anticholinergic syndrome from diphenhydramine overdose includes several mechanisms that can lead to rhabdomyolysis 2:
- Agitated delirium with increased motor activity can cause skeletal muscle injury even without frank seizures 2
- Hyperthermia (though typically mild elevation <38.8°C in pure anticholinergic poisoning) contributes to muscle breakdown 2
- Muscle rigidity may occur, though typically less severe than in serotonin syndrome or neuroleptic malignant syndrome 2
Clinical Algorithm for CK Assessment
Obtain baseline CK in all diphenhydramine overdose patients at presentation, regardless of seizure history 1, 3:
- Draw CK at presentation and repeat at 6-hour intervals if initial level is elevated 3
- Monitor for clinical signs of muscle injury: muscle pain, weakness, dark urine 4
- Assess renal function (creatinine, eGFR) concurrently, as elevated CK increases acute kidney injury risk 1, 4
- Check electrolytes and myoglobin if CK is significantly elevated (>5000 U/L) 4
Treatment Implications
If CK elevation is detected 1, 4:
- Initiate aggressive IV fluid resuscitation immediately - this is the primary intervention that rapidly lowers CK levels 1
- Consider urine alkalization and diuretic agents when CK is significantly elevated 4
- Serial CK monitoring until downtrending, especially if eGFR <90 mL/min/1.73m² 4
Common Pitfall to Avoid
Do not assume that absence of seizures eliminates rhabdomyolysis risk in diphenhydramine overdose. While seizures are a well-recognized cause of CK elevation 2, 4, the direct toxic effects of diphenhydramine on muscle tissue, combined with increased motor activity from agitated delirium, create independent risk for severe rhabdomyolysis 1. The case report of CK >2 million IU/L demonstrates this can be life-threatening even without documented seizure activity 1.
Additional Monitoring Considerations
Beyond CK, anticholinergic overdose requires assessment for 2:
- Cardiac monitoring (tachycardia, potential for dysrhythmias)
- Temperature monitoring (hyperthermia risk)
- Mental status assessment (agitated delirium vs. paradoxical sedation)
- Urinary retention evaluation