What is the appropriate management for a patient who deliberately ingested approximately 75 phenytoin tablets?

Management of Deliberate Phenytoin Overdose (75 Tablets)

Provide supportive care with close monitoring as the primary management strategy, since there is no antidote for phenytoin overdose and death is unlikely from oral ingestion alone. 1, 2

Immediate Assessment and Stabilization

Airway and Vital Signs

• Assess respiratory and circulatory function immediately, as death from phenytoin overdose occurs due to respiratory and circulatory depression 1
• Prepare for potential intubation if the patient develops depressed consciousness or coma, though this typically occurs only in severe cases 2
• Monitor cardiac function, though cardiac complications (arrhythmias, hypotension) are rare with oral ingestion and more commonly seen with IV administration 2

Expected Toxicity Profile

• Initial symptoms include nystagmus (appears at plasma levels 20 mcg/mL), ataxia (30 mcg/mL), and dysarthria 1
• More severe manifestations include tremor, hyperreflexia, lethargy, slurred speech, nausea, and vomiting 1
• The patient may progress to coma and hypotension in severe cases 1
• Important caveat: Marked individual variation exists—some patients tolerate levels as high as 50 mcg/mL without toxicity, while others show toxicity at lower levels 1

Gastrointestinal Decontamination

Activated Charcoal Consideration

• Administer activated charcoal if the patient presents early after ingestion 2
• Do not use multiple-dose activated charcoal—while experimental studies show increased clearance rates, this has not translated into clinical benefit 2
• There is no evidence that any method of gastrointestinal decontamination improves outcomes 2

Supportive Care Measures

Symptom Management

• Manage nausea and vomiting aggressively 2
• Prevent injuries from confusion and ataxia through environmental safety measures and close observation 2
• Provide sedation if severe agitation develops, though this is not a typical phenytoin toxicity manifestation 2

Monitoring Requirements

• Check phenytoin levels immediately and serially, as the American Academy of Neurology recommends monitoring when signs of toxicity develop (ataxia, nystagmus, tremor, somnolence, confusion) 3
• Monitor for hypokalemia if any alkalinization therapy is considered, though this is not standard for phenytoin overdose 4
• Observe for prolonged duration of symptoms due to zero-order pharmacokinetics causing greatly increased half-life in overdose 2

Enhanced Elimination Considerations

Standard Approach

• There is no evidence that invasive methods of enhanced elimination (plasmapheresis, hemodialysis, hemoperfusion) provide clinical benefit 2
• Phenytoin is highly protein-bound, limiting effectiveness of standard dialysis 1

Exceptional Circumstances

• Consider hemodialysis only if the patient remains comatose with persistently toxic levels for many days (>12 days) without clinical improvement 5
• If hemodialysis is pursued, a high cut-off dialyzer (allowing removal of molecules up to 45 kDa) can achieve phenytoin clearance of ~80 mL/min and reduce half-life from >1000 hours to ~18 hours during treatment 5
• Combination of activated charcoal hemoperfusion with high-flux hemodialysis reduced half-life to 7-13 hours in one case of severe IV overdose with levels of 117 mg/L 6
• Critical caveat: These invasive measures should be reserved only for life-threatening cases with prolonged coma and persistently toxic levels, as they are not standard of care 2, 5, 6

Expected Clinical Course

Pharmacokinetic Considerations

• Expect prolonged hospitalization due to zero-order (saturable) pharmacokinetics causing dramatically extended half-life in overdose 2
• The lethal dose in adults is estimated at 2-5 grams, and doses as high as 25 times the therapeutic dose (resulting in levels >100 mcg/mL) have been survived with complete recovery 1
• Native phenytoin clearance may be inadequate to relevantly lower concentrations in severe overdose 6

Prognosis

• Deaths are unlikely after phenytoin ingestion alone 2
• Consider the possibility of co-ingestion with other CNS depressants including alcohol in acute overdose 1
• Complete recovery is expected with appropriate supportive care, though symptoms may persist for days to weeks 1, 2

Key Pitfalls to Avoid

• Do not use phenytoin itself to treat seizures if they occur from toxicity—phenytoin can paradoxically cause seizures at toxic levels 7
• Do not pursue aggressive enhanced elimination measures routinely—reserve these only for exceptional cases with prolonged coma and no clinical improvement 2, 5
• Do not discharge prematurely—the prolonged half-life in overdose can result in delayed peak toxicity and extended symptom duration 2