What is the management of nystagmus in phenytoin (antiepileptic medication) toxicity?

Management of Nystagmus in Phenytoin Toxicity

The primary management of nystagmus in phenytoin toxicity is to temporarily withdraw phenytoin and provide supportive care until serum levels return to the therapeutic range. 1, 2

Clinical Manifestations and Diagnosis

• Nystagmus is one of the earliest dose-related adverse effects of phenytoin toxicity, typically appearing at serum concentrations of approximately 20 mcg/mL 1
• Other neurological manifestations occur at progressively higher concentrations:
  • Ataxia appears at approximately 30 mcg/mL 1
  • Dysarthria and lethargy typically manifest when serum concentrations exceed 40 mcg/mL 1
• Downbeat nystagmus specifically may occur with phenytoin toxicity and resolves when levels return to therapeutic range 3

Management Algorithm

Step 1: Confirm Phenytoin Toxicity

• Measure serum phenytoin levels immediately 1, 2
• Assess for other manifestations of toxicity (ataxia, dysarthria, lethargy, confusion) 2, 4
• Rule out other causes of nystagmus (stroke, structural lesions) as phenytoin toxicity is sometimes misdiagnosed as brainstem or cerebellar stroke (14% of cases) 4

Step 2: Immediate Management

• Temporarily withdraw phenytoin 2, 4
• Ensure adequate respiratory and circulatory support 1
• Prevent injuries due to ataxia and confusion 2
• Manage associated symptoms:
  • Treat nausea and vomiting if present 2
  • Monitor for hypotension (rare with oral phenytoin but more common with IV administration) 5

Step 3: Decontamination Considerations

• For recent oral ingestion, consider activated charcoal 2
• Note that multiple-dose activated charcoal remains controversial despite increased clearance rates in experimental studies 2

Step 4: Monitoring and Follow-up

• Continue monitoring serum phenytoin levels until they return to therapeutic range 1, 4
• Be aware that phenytoin has zero-order pharmacokinetics in overdose, resulting in a greatly increased half-life and prolonged duration of symptoms 2
• No invasive methods of enhanced elimination (plasmapheresis, hemodialysis, hemoperfusion) have shown clinical benefit 2

Special Considerations

• Nystagmus may persist at higher-than-normal therapeutic levels in some patients who require higher concentrations for seizure control 6
• Fosphenytoin (a phenytoin pro-drug) has similar dose-related adverse effects including nystagmus, but fewer cardiovascular complications compared to IV phenytoin 5
• Common causes of phenytoin toxicity include:
  • Excessive self-medication
  • Misunderstanding of prescription orders
  • Drug interactions affecting phenytoin metabolism 4

Prognosis

• The clinical course is typically uneventful with temporary withdrawal of phenytoin and supportive care 4
• Complete resolution of nystagmus follows the return of phenytoin levels to the therapeutic range 3
• Deaths are unlikely after phenytoin intoxication alone 2

Pitfalls and Caveats

• Do not restart phenytoin at the same dose after resolution of toxicity; reassess appropriate dosing 2, 4
• Avoid treating the "numbers" (serum concentrations) rather than the patient's clinical condition; some patients may tolerate higher levels with minimal toxicity 6
• Be aware that phenytoin toxicity is relatively under-diagnosed in emergency settings 4
• There is no specific antidote for phenytoin toxicity 1, 2