What lab test should an Adult-Gerontology Acute Care Nurse Practitioner (AGACNP) order when monitoring serum phenytoin levels in a patient admitted for seizures?

Serum Albumin Must Be Ordered Alongside Phenytoin Levels

The AGACNP must order serum albumin (Option A) when monitoring phenytoin levels, as phenytoin is highly protein-bound and albumin levels are essential for interpreting total phenytoin concentrations and determining if free phenytoin measurement is needed.

Rationale for Albumin Monitoring

Protein Binding and Clinical Interpretation

• Phenytoin is extensively bound to serum albumin, and the free (unbound) fraction is the pharmacologically active component that correlates with both therapeutic efficacy and toxicity 1
• The FDA label explicitly states that "phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments," and drug interactions and clinical conditions affecting protein binding make serum level determinations "especially helpful" 2
• In patients with hypoalbuminemia, hepatic disease, or renal impairment—all common in critically ill seizure patients—the free fraction of phenytoin increases significantly, meaning total phenytoin levels become misleading 2, 1

Evidence for Albumin's Critical Role

• Research demonstrates a significant negative correlation between serum albumin levels and free fraction of phenytoin (r = -0.68, p < 0.001), with free fractions exceeding 18% in patients with hypoalbuminemia 1
• In 14.2% of patients studied, free phenytoin concentrations were better related to clinical effect than total levels, particularly in those with significant reductions in serum protein binding 1
• The relationship between phenytoin toxicity and free serum concentrations is particularly strong—in patients with toxicity, total phenytoin was elevated in only 42.9% of cases, while free phenytoin was elevated in 85.7% (p < 0.05) 1

Clinical Decision Algorithm

When total phenytoin levels are obtained:

• Always order serum albumin concurrently to interpret whether the total level accurately reflects the active drug concentration 1, 3
• If albumin is normal (≥3.5 g/dL), total phenytoin levels generally correlate well with clinical response 1
• If albumin is low (<3.5 g/dL), consider that the patient may have therapeutic or toxic free phenytoin levels despite "normal" total levels 1, 4
• In hypoalbuminemic patients with albumin <2.5 g/dL, strongly consider ordering free phenytoin levels directly, as calculation methods become unreliable 3, 4

Why Other Options Are Incorrect

Serum Sodium (Option B)

• Sodium monitoring is not routinely required for phenytoin level interpretation 2
• While hyponatremia can lower seizure threshold, it does not affect phenytoin pharmacokinetics or the interpretation of drug levels

Urine Sodium (Option C)

• Urine sodium has no role in phenytoin monitoring or interpretation 2

Serum Calcium (Option D)

• While chronic phenytoin therapy can affect bone metabolism and lead to hypocalcemia through vitamin D metabolism, this is a long-term concern, not an acute monitoring parameter needed for level interpretation 2
• Calcium does not affect phenytoin protein binding or the interpretation of serum levels

Critical Clinical Pitfalls

• Never assume a "normal" total phenytoin level (10-20 mcg/mL) is therapeutic in hypoalbuminemic patients—they may actually be toxic with free levels exceeding 8 mcg/mL 1
• Patients with hepatic or renal impairment require more frequent monitoring due to altered protein binding 5, 2
• The Sheiner-Tozer equation for calculating free phenytoin from total levels is unreliable in critically ill patients with hypoalbuminemia, showing poor accuracy in 33-36% of cases 4
• In neurointensive care patients with mean albumin of 2.63 g/dL, calculated free phenytoin showed only weak-moderate correlation with measured levels (r = 0.43-0.45) 4