• Historically most common in pediatrics and pregnant women.
  • Incidence has decreased significantly in the past decade.
• Prediction of toxic effects based on the amount of elemental iron ingested. Multiple preparations available containing variable amounts of elemental iron:
  • Ionic compounds:
    • Ferrous gluconate – 11% elemental iron
    • Ferrous sulfate – 20% elemental iron
    • Ferrous fumarate – 33% elemental iron
    • Ferrous succinate – 35% elemental iron
  • Non-ionic compounds have high elemental iron content but do not cause significant toxicity as their formulation makes them less caustic to the gastrointestinal (GI) tract, resulting in less iron absorption:
    • Iron polysaccharide – 46% elemental iron
    • Carbonyl iron – 100% elemental iron

• Iron is essential for multiple physiological functions:
  • In a normal GI tract, the proportion of iron absorbed decreases with increasing dose as gut transporters become saturated.
  • In physiologic conditions, iron is largely bound to transferrin or ferritin. A small proportion is free and unbound in serum.
• In an overdose, excess iron ions cause caustic injury to the GI tract resulting in increased iron absorption.
• Excess unbound iron ions cause multi-organ injury by:
  • Impaired ATP synthesis though uncoupling of oxidative phosphorylation.
  • Generation of free radical species that damage cell membranes through lipid peroxidation. Injury is pronounced in tissues with high iron concentrations (liver, intestine, heart).
  • Multifactorial metabolic acidosis from excess unbuffered protons, impaired cellular respiration and hypoperfusion.
• In severe exposures, patients can develop a mixed shock picture: hypovolemic, cardiogenic and distributive shock are all possible.

• Ingestions of 20-40 mg/kg elemental iron can cause GI irritation without significant systemic effects.
• Toxicity can be seen with ingestions > 40 mg/kg elemental iron.

Multiple phases of iron toxicity. Patients do not always follow this pattern, not all patients with severe toxicity will have a latent phase or develop hepatic failure.

• 0.5 to 6 hours – GI Symptoms: nausea, vomiting, diarrhea, abdominal pain, GI bleeding from corrosive effect of iron. An absence of any GI symptoms indicates a very low likelihood of significant systemic toxicity.
•  6 to 24 hours – Latent Phase: symptoms improve but don’t resolve.
• 6 to 48 hours: shock, metabolic acidosis, coma, coagulopathy, seizures.
• 2 to 4 days: hepatic failure.
• >2 weeks – convalescent phase: obstruction due to scarring from caustic effects.

• Initial work-up: electrolytes, creatinine, glucose, serum iron level, venous blood gas (VBG) and liver function tests.
• Abdominal X-ray – most iron pills are radio-opaque. Absence of radio-opaque pills on X-ray does not rule out a significant iron ingestion.
• Always check for co-ingestants in deliberate self-harm ingestions – ethanol level, acetaminophen level, ASA level, serum osmolality and urea/blood urea nitrogen (to calculate osmolar gap).
• Serum iron level interpretation:
  • Expect initial peak 2-6h after ingestion. Repeat every 2-4 hours until levels decline.
  • 50-90 umol/L – likely have GI symptoms.
  • 90-180 umol/L – possible severe toxicity.
  • >180 umol/L – possibly fatal.

• Resuscitation
  • Fluid resuscitation – patients are often volume deplete due to GI losses. Hypotension unresponsive to fluids may require vasopressors.
  • Protect airway and assist ventilation as needed.
• Decontamination
  • Iron does not bind activated charcoal.
  • If radio-opaque pills are seen on X-ray, consider whole bowel irrigation.
  • Discuss with BC poison centre.
• Targeted therapy
  • Deferoxamine is an iron chelator indicated for severe exposures.
  • Initiation should be discussed with a toxicologist.
  • Indications include:
    • Signs of severe toxicity beyond isolated GI irritation – shock, CNS symptoms, metabolic acidosis
    • Serum iron level > 90 umol/L regardless of symptoms
• Salvage therapy
  • Hemodialysis does not effectively remove iron
  • Liver transplantation may be considered
• Asymptomatic patients require monitoring for 6 hours after ingestion.

• Interpreting the latent phase as clinical resolution – symptomatic patients should be observed until complete resolution of symptoms, have declining serial serum iron levels, and be reviewed with BC local poison centre before medical clearance.
• Serum iron levels may fall in the presence of worsening signs and symptoms due to distribution of iron into tissue. Do not be falsely reassured by a declining serum iron level in isolation – the entire clinical picture (symptoms, physical exam, labs) should be considered when interpreting a serum iron level.

BC Drug and Poison Information Centre: 604-682-5050, or 1-800-567-8911.

1. British Columbia Drug and Poison Information Centre guidelines on iron overdose.

   
   

2. Bryant S.M., Leiken J.B. (2018) Iron. In: Brent J., Burkhart K., Dargan P., Hatten B., Megarbane B., Palmer R. (eds) Critical Care Toxicology. 

   
   

3. Perrone J. (2015) Iron. In: Hoffman R., Howland M., Lewin N., Nelson L., Goldfrank L. & Flomenbaum N. (eds) Goldfrank’s Toxicologic Emergencies. 10e. McGraw Hill.

   
   

4. Bateman, D. N., Eagling, V., Sandilands, E. A., Jackson, G., Crawford, C., Hawkins, L., Cheung, T., Cooper, G., Bradberry, S. M., Thompson, J. P., Thomas, S. H. L., & Eddleston, M. (2018). Iron overdose epidemiology, clinical features and iron concentration-effect relationships: the UK experience 2008–2017. Clinical Toxicology, 56(11), 1–9.