What assessment findings are expected in a patient with a slightly elevated phenytoin level and a history of seizure disorders?

Assessment Findings in Phenytoin Toxicity at 22 mcg/mL

At a phenytoin level of 22 mcg/mL (slightly above the therapeutic range of 10-20 mcg/mL), you should expect to see nystagmus as the earliest and most common sign of toxicity. 1

Expected Clinical Findings at This Level

Primary Neurological Signs

• Nystagmus is the hallmark finding at levels just above 20 mcg/mL and represents the most sensitive indicator of early phenytoin toxicity 2, 3
• Ataxia may begin to appear as levels exceed 20 mcg/mL, though this typically becomes more prominent at higher concentrations 2
• Mild cognitive changes or somnolence can occur, though these are more variable at this borderline toxic level 2

Less Likely Findings at 22 mcg/mL

• Severe confusion, disorientation, or hallucinations typically require significantly higher levels (>30-40 mcg/mL) 4
• Paradoxical seizures are rare and generally occur only at very high toxic concentrations (>38-93 mcg/mL in reported cases), not at 22 mcg/mL 5, 6
• Coma or severe obtundation requires substantially higher levels 4

Critical Clinical Context

Protein Binding Considerations

• If this patient has hypoalbuminemia (albumin <25 g/L), the free phenytoin fraction will be elevated, potentially causing more severe toxicity than the total level suggests 4
• In hypoalbuminemic patients, total levels of 22 mcg/mL can correspond to toxic free phenytoin levels (>2 mg/L therapeutic range is 0.5-2 mg/L) 4
• Consider checking free phenytoin levels if the patient has renal failure, hepatic dysfunction, or malnutrition 4

Dose-Related Toxicity Spectrum

• The FDA label confirms that optimum control without clinical signs of toxicity occurs with levels between 10-20 mcg/mL 1
• At 22 mcg/mL, watch specifically for nystagmus, ataxia, tremor, and cognitive impairment as the primary dose-related adverse effects 7

Management Implications

Immediate Assessment

• Perform careful neurological examination focusing on eye movements (horizontal and vertical nystagmus), gait testing (ataxia), and mental status 2
• Check serum albumin to determine if free phenytoin measurement is warranted 4
• Assess for other factors that may increase toxicity risk: renal failure, hepatic disease, or interacting medications 1

Common Pitfall to Avoid

• Do not assume the patient is having breakthrough seizures and increase the phenytoin dose - paradoxical seizures from toxicity are possible, though rare at this level 5, 6
• If seizures occur with a level of 22 mcg/mL, consider other causes before attributing them to subtherapeutic dosing 6