Management of Phenytoin Level 12 with Albumin 27 g/L
Critical Assessment: Calculate Free Phenytoin Level
Your patient likely has phenytoin toxicity despite a "therapeutic" total level of 12 mcg/mL, because the low albumin (27 g/L or 2.7 g/dL) dramatically increases the free (active) phenytoin fraction. 1, 2, 3
Immediate Action Required
- Measure free phenytoin level immediately - this is the only reliable way to assess true drug exposure in hypoalbuminemia 2, 3, 4
- Use the Sheiner-Tozer equation to estimate free phenytoin while awaiting lab results: Free phenytoin = Total phenytoin / [(0.2 × albumin) + 0.1] 1
- With albumin 2.7 g/dL and total phenytoin 12 mcg/mL, the estimated free phenytoin is approximately 18 mcg/mL (therapeutic range for free phenytoin is only 1-2 mcg/mL) 5, 1
Clinical Significance of This Discrepancy
- Total phenytoin levels are unreliable in hypoalbuminemia - the [total phenytoin]/[albumin] ratio correlation breaks down significantly when albumin is low 6
- Phenytoin is highly protein-bound (approximately 90%), so reduced albumin causes disproportionate increases in free (active) drug 7, 4
- Patients with hypoalbuminemia can develop severe phenytoin toxicity with "normal" total levels - case reports document coma, disorientation, myoclonia, and hallucinations at total levels of 18 mcg/mL when albumin was <25 g/L 2, 3
Assess for Phenytoin Toxicity Symptoms
Examine the patient immediately for signs of toxicity:
- Neurological manifestations: nystagmus, ataxia, cognitive changes, drowsiness, decreased level of consciousness, cerebellar signs 5, 2, 3
- Severe toxicity signs: disorientation, myoclonia, hallucinations, comatose state 3
- Hepatotoxicity: elevated liver enzymes (can occur with phenytoin toxicity) 1
Management Algorithm
If Free Phenytoin is Elevated (>2 mcg/mL) or Patient is Symptomatic:
- Hold phenytoin immediately until free levels normalize and symptoms resolve 1, 3
- Monitor neurological status closely 2, 3
- Check liver function tests 1
- Once toxicity resolves, restart at a significantly reduced dose (typically 30-50% reduction) 3
If Free Phenytoin is Therapeutic (1-2 mcg/mL) and Patient is Asymptomatic:
- Reduce phenytoin dose by approximately 30-40% to account for hypoalbuminemia 4
- Monitor free phenytoin levels (not total levels) going forward 2, 4
- Recheck free phenytoin in 5-7 days after dose adjustment 7
Address the Underlying Hypoalbuminemia
- Identify and treat the cause of albumin 27 g/L - this is moderate hypoalbuminemia requiring investigation 8
- Common causes include: inflammation (measure CRP), malnutrition, liver disease, nephrotic syndrome (check urine protein), protein-losing enteropathy 9
- Inflammatory states are the most common cause in hospitalized patients and directly suppress albumin synthesis even with adequate nutrition 8, 9
- Provide nutritional support with protein intake 1.2-1.3 g/kg/day if malnourished 8
Critical Pitfalls to Avoid
- Never rely on total phenytoin levels alone in hypoalbuminemia - this is the most common error leading to unrecognized toxicity 6, 2, 3, 4
- Do not assume hypoalbuminemia is purely nutritional - inflammation is usually the primary driver 8, 9
- Elderly and critically ill patients are at highest risk for this complication due to frequent hypoalbuminemia 1, 4
- Be aware that drug-drug interactions (NSAIDs, salicylates) can further displace phenytoin from albumin, worsening toxicity 4
Ongoing Monitoring Strategy
- Monitor free phenytoin levels exclusively in this patient - total levels will remain misleading until albumin normalizes 2, 4
- Recheck free phenytoin 5-7 days after any dose change (time to steady state) 7
- Monitor albumin levels regularly and reassess phenytoin dosing as albumin improves 8
- Target free phenytoin 1-2 mcg/mL for seizure control 5, 7