Natural History and Management of Iron Overdose
Acute iron overdose is potentially life-threatening and requires prompt recognition and treatment based on clinical staging, with deferoxamine therapy indicated for severe cases showing signs of systemic toxicity.
Clinical Stages of Iron Toxicity
Iron overdose typically progresses through five clinical stages:
Stage 1 (0-6 hours): Gastrointestinal Phase
- Characterized by vomiting, diarrhea, abdominal pain, and hematemesis
- Potential for hypovolemic shock due to GI bleeding and fluid losses
- Metabolic acidosis may begin to develop
Stage 2 (6-24 hours): Apparent Recovery Phase
- Deceptive period of clinical improvement
- Critical time for continued monitoring despite apparent stability
- High risk for underestimating severity if patient is discharged during this phase
Stage 3 (12-48 hours): Systemic Toxicity Phase
- Recurrence of shock
- Metabolic acidosis worsens
- Development of hepatic failure
- Coagulopathy
- Potential for renal failure
- Cardiac dysrhythmias and cardiomyopathy (leading causes of sudden death) 1
Stage 4 (2-5 days): Hepatic Failure Phase
- Progressive liver dysfunction
- Coagulopathy worsens
- Hypoglycemia
- Encephalopathy
Stage 5 (2-6 weeks): Late Complications
- Gastric scarring and potential pyloric stenosis
- Persistent liver damage in severe cases
Diagnostic Approach
Laboratory Assessment
- Serum iron levels (peak at 4-6 hours post-ingestion)
- Total iron-binding capacity (TIBC)
- Calculate percent transferrin saturation (serum iron/TIBC × 100%)
- Complete blood count
- Comprehensive metabolic panel
- Coagulation studies
- Arterial blood gas (for acid-base status)
Imaging
- Abdominal radiograph to detect radio-opaque iron tablets
- May show tablets in stomach and small bowel in significant ingestions 2
Management Algorithm
1. Severity Assessment
- Mild toxicity: Minimal symptoms, serum iron <300 μg/dL, <20% of ingested tablets visible on X-ray
- Moderate toxicity: GI symptoms, serum iron 300-500 μg/dL
- Severe toxicity: Significant GI symptoms, shock, acidosis, serum iron >500 μg/dL
2. Gastrointestinal Decontamination
- Gastric lavage if presenting within 1-2 hours of ingestion
- Whole bowel irrigation with polyethylene glycol solution for significant ingestions or visible tablets on X-ray 2
- Caution: Activated charcoal does NOT bind iron effectively
3. Chelation Therapy with Deferoxamine
Indications for deferoxamine therapy:
- Serum iron level >500 μg/dL
- Significant clinical toxicity (shock, acidosis, altered mental status)
- Persistent vomiting and diarrhea
Dosing regimen: 3
Intramuscular route (preferred for patients not in shock):
- Initial dose: 1000 mg
- Followed by 500 mg every 4 hours for two doses
- Additional doses of 500 mg every 4-12 hours as needed
- Maximum: 6000 mg in 24 hours
Intravenous route (only for patients in cardiovascular collapse):
- Initial dose: 1000 mg at rate not exceeding 15 mg/kg/hr
- Followed by 500 mg over 4 hours for two doses
- Additional doses of 500 mg over 4-12 hours as needed
- Maximum: 6000 mg in 24 hours
- Switch to IM route as soon as clinically feasible
4. Supportive Care
- Aggressive fluid resuscitation for hypovolemic shock
- Correction of metabolic acidosis
- Management of coagulopathy
- Glucose administration for hypoglycemia
- Vasopressors if needed for persistent shock
Special Considerations
Pediatric Patients
- Acute iron ingestions >60 mg/kg are potentially serious 2
- Children <6 years represent a significant proportion of cases (28.4%) 4
- More vulnerable to rapid dehydration from GI losses
Adolescents and Young Adults
- Peak incidence in females 13-20 years (predominantly intentional ingestions) 4
- Higher risk for severe toxicity due to larger ingestions
Pitfalls to Avoid
- Discharging patients during the apparent recovery phase (Stage 2) - continued observation is essential
- Relying solely on reported dose - poor correlation between stated dose and serum iron levels 4
- Delaying chelation therapy in severely symptomatic patients while awaiting laboratory confirmation
- Administering vitamin C supplements during treatment - may accelerate iron mobilization and increase toxicity 1
- Missing delayed presentations - some patients may present days after ingestion with liver failure and metabolic derangements 5
Prognosis
With prompt recognition and appropriate management, mortality from acute iron overdose has decreased significantly. However, severe cases can still result in permanent organ damage, particularly to the liver, or death if treatment is delayed or inadequate.