Immediate Management of Phenytoin Poisoning
For acute phenytoin overdose, provide supportive care only—there is no antidote, and aggressive interventions like hemodialysis or multiple-dose activated charcoal do not improve outcomes. 1, 2
Initial Assessment and Stabilization
- Assess and secure the airway immediately, particularly if the patient shows altered mental status or signs of CNS depression 1, 2
- Check vital signs continuously, focusing on respiratory rate, blood pressure, and cardiac rhythm 1, 3
- Establish IV access and obtain bedside glucose testing to rule out hypoglycemia as a contributor to altered mental status 4
- Perform continuous cardiac monitoring with serial ECGs, though serious cardiac complications (arrhythmias, hypotension) are rare with oral ingestion 3
Critical distinction: Cardiac toxicity is primarily associated with IV phenytoin administration at rapid rates (>50 mg/min), not oral overdoses 3, 5
Supportive Care Measures
- Manage nausea and vomiting with antiemetics as needed, since these are among the most common presenting symptoms 1, 6
- Implement fall precautions immediately—ataxia and unsteady gait significantly increase injury risk and are the primary morbidity concern 2, 6
- Provide IV fluids for hydration, especially if vomiting is prominent 1
- Monitor respiratory function closely; intubation may be required if the patient becomes comatose, though this is uncommon 1, 2
What NOT to Do
- Do not attempt hemodialysis, hemoperfusion, or plasmapheresis—there is no evidence these invasive methods improve outcomes 2
- Do not administer multiple-dose activated charcoal—while experimental studies show increased clearance, this has never translated to clinical benefit 2
- Single-dose activated charcoal may be considered only if the patient presents within 1-2 hours of ingestion and can protect their airway 2
- Do not give flumazenil if benzodiazepine co-ingestion is suspected, as it can precipitate seizures 7, 8
Laboratory and Diagnostic Workup
- Obtain serum phenytoin level to confirm diagnosis and guide duration of observation 1, 6
- Perform comprehensive metabolic panel including albumin (hypoalbuminemia increases free phenytoin fraction and toxicity risk) 3
- Check for co-ingestants with urine drug screen, serum acetaminophen, and salicylate levels 4
- Serial ECGs are reasonable but rarely show significant abnormalities in oral overdose 3
Expected Clinical Course and Monitoring
Toxicity manifestations follow a predictable pattern based on serum levels: nystagmus appears at 20 mcg/mL, ataxia at 30 mcg/mL, and dysarthria/lethargy above 40 mcg/mL 1
- Temporary withdrawal of phenytoin is the cornerstone of management 6
- Expect prolonged hospitalization due to zero-order (saturation) pharmacokinetics—the half-life dramatically increases in overdose, extending symptom duration 2, 6
- Monitor for progression to confusion, lethargy, or coma in severe cases (levels >40-50 mcg/mL) 1, 6
- Seizures can paradoxically occur in severe phenytoin toxicity, though this is uncommon 1, 2
Observation Period and Disposition
- Observe until ataxia resolves and the patient can ambulate safely without fall risk 2, 6
- Minimum observation of 6-8 hours for asymptomatic patients, but most will require 24-48 hours or longer given prolonged elimination 2, 6
- All patients have uneventful clinical courses with supportive care alone—mortality from phenytoin ingestion alone is extremely rare 2, 6, 9
- Psychiatric evaluation is mandatory before discharge for intentional overdoses 4
Common Pitfalls to Avoid
- Do not misdiagnose as stroke—brainstem or cerebellar stroke is the most common misdiagnosis (14% of cases) due to ataxia, nystagmus, and dysarthria 6
- Do not restart phenytoin until levels are clearly declining and symptoms have substantially improved 6
- Do not discharge patients who still have significant ataxia—the fall risk is the primary source of morbidity 2, 6
- Consider co-ingestants, especially alcohol and other CNS depressants, which can complicate the clinical picture 1