INDEX

    Iron Overdose

    Toxicology

    Last Updated Jul 03, 2020
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    Context

    • 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

    Pathophysiology

    • 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.

    Toxic Dose

    • 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.

    Signs and Symptoms

    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.

    Diagnostic Process

    • 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.

    Recommended Treatment

    • 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.

    Clinical Pitfalls

    • 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.

    Consult

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

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