The worlds of Pediatrics and Toxicology often intersect, unfortunately. From very early on in my career I learned the significance of Poison Control access [1(800)222-1222]. We have discussed some important toxic exposures previously (ex, Laundry Pods, Lead Toxicity, Special Foreign Bodies, Carbon Monoxide, Huffing Hydrocarbons, Liquid Nicotine, Loperamide Overdose, and even Baclofen Pumps), but somehow I have let an important one slip past for several years. I thank Dr. Simone Lawson for reminding me that there are plenty of dangerous substances still out there that can endanger our patients. So let us take a minute to consume a morsel on Iron Toxicity:

[Much Appreciation to Dr. Michael Beuhler from Carolinas Medical Center for his recent Iron Toxicity review during CMC EM Conference!]

Iron Toxicity: Basics

• Iron exists in different sates.
  • Ferrous (+2 state)
    • Used in heme (ie, hemoglobins, myoglobin, cytochrome).
  • Ferric (+3 state)
    • Transportation and Storage form of iron.

• Transferrin binds iron.
  • Total Iron Binding Capacity (TIBC) is usually in excess of the iron that is present.
  • Unbound iron is bad!

• Iron containing preparations can make possible toxicity confusing! [Chang, 2011]
  • There are many different formulations (ferrous sulfate vs ferrous fumarate vs ferrous gluconate vs iron carbonyl).
  • Different preparations have various amounts of elemental iron in them.
  • Iron toxicity is based on the dose of elemental iron in a preparation, not the total dose of the medication.
  • Examples:
    • Children’s Multivitamins have up 20 mg of elemental iron.
    • Adult Multivitamins have up to 50 mg of elemental iron.
    • Prenatal Vitamins have up to 100 mg elemental iron!
      • Children (especially toddlers who like to put things in their mouths) who have a newly born sibling are at high risk for iron poisoning.
      • Mother likely still has prenatal vitamins around.
  • Iron Carbonyl (Fe 0) [ex, the iron found in hand warmers) actually has very low toxicity.

Iron Toxicity: Presentation

• Toxic exposure level: [Chang, 2011]
  • Symptoms can occur after as little as 20 mg/kg of elemental iron.
  • 40 mg/kg is the level at which Poison Control Centers recommend medical evaluation / possible hospitalization.
  • 60 mg/kg can lead to severe toxicity.

• 5 Stages of Toxicity described
• STAGE 1 (first 6 hours after ingestion) [Chang, 2011]
  • GI Insults
  • Lots of vomiting!
    • May even be black or green.
    • Overt hematemesis can also be seen from GI corrosive injury.
  • Abdominal Pain
  • Diarrhea
  • Bowel Wall necrosis
  • Children who do not display phase 1 symptoms for 6 hours are unlikely to have any further sequelae. [Chang, 2011]

• STAGE 2 (6 – 24 hours after ingestion) [Chang, 2011]
  • “Latent phase”… but ongoing acidosis and injury.
  • GI Symptoms resolve/improve.
  • Large ingestions may skip this stage.

• STAGE 3 (12 – 48 hours after ingestion) [Chang, 2011]
  • Continued Acidosis
  • Hepatic Dysfunction
    • Coagulopathy
    • Hypoglycemia, hyperammonemia
  • Hypotension and SHOCK
    • Cardiotoxic – negative inotropic properties.
    • Vasodilatory effects
    • Hypovolemia (from GI losses)
  • GI symptoms return
    • GI bleeding
    • Bowel perforation
  • CNS – may see seizures
  • Coagulopathy – free iron inhibits the entire coagulation cascade (in addition to the liver insult)
  • Acute Lung Injury – ARDS

• STAGE 4 (2 – 3 days later) [Chang, 2011]
  • Hepatic Failure
    • Liver receives the majority of the absorbed iron.
    • Iron-induced hepatotoxicity has a worse course than acetaminophen related insult.
  • Usually only seen with serum iron levels > 1000 microgram/dL.

• STAGE 5 (2 – 8 weeks later) [Chang, 2011]
  • Subacute inflammatory process.
  • GI strictures and obstruction.
  • GI fistulas can develop too.

• May not always be very distinct.
• Any stage can have mortality associated with it.

Iron Toxicity: Management

• Determine the dose of elemental iron ingested.
  • This can be challenging based on the formulation and specific preparation.
  • Contact your friendly Toxicologist or Poison Control to assist with this as it matters!

• Patient may go home without work-up if:
  • This was accidental (don’t overlook the possibility of suicidal ideation?), and
  • Ingestion was < 20 mg/kg of elemental iron, or
  • Ingestion was of Carbonyl form, or
  • Ingestion was of pediatric iron formulation, or
  • Patient has been symptom free for 6 hours after ingestion (respect vomiting… don’t just throw ondansetron at it), and
  • No concern for co-ingestion, and
  • Confidence in care-givers.

• Studies that are useful:
  • Serum Iron Level measured at 4-6 hours after ingestion. [Chang, 2011]
    • Levels of greater than 300 micrograms/dL (above the TIBC range) are considered concerning.
    • Peak levels for toxicity occur at 4-6 hours after ingestion.
  • Consider Acetaminophen Level (especially for intentional ingestions)!
  • Electrolytes (mostly for renal function and glucose)
  • Liver Function Tests (especially for clinically ill patients)
  • Coagulation Studies
  • Abdominal X-Ray may reveal pills (lack of pills does not rule-out ingestion)

• Therapies [Chang, 2011]
  • Fluid Resuscitation!
  • Whole Bowel Irrigation
    • For large ingestions
    • Polyethylene glycol 500 ml/hr for 9 months – 6 years
    • Polyethylene glycol 1000 ml/hr for 6 months – 12 years
    • Polyethylene glycol 2000 ml/hr for > 13 years
  • Chelation
    • Deferoxamine chelates Iron and Aluminum
    • Able to bind free iron and intracytoplasmic and mitochondrial free iron
    • No definitive trigger to administer. Based on entire clinical picture.
    • IV is preferred to IM.
    • 15 mg/kg/hr IV (although higher rates have been used).
    • SIDE EFFECTS:
      • Hypotension, Tachycardia/Bradycardia
      • Renal Failure, Acute Respiratory Distress
      • Increased risk for Yersinia enterocolitica sepsis

Moral of the Morsel

• Heavy Metals Matter! Iron in prenatal vitamins can lead to severe consequences!
• Elemental Iron, not Milligrams of Medicine. This can be challenging to figure out, so call for help to ensure accuracy.
• Respect Vomiting! It is not an ondansetron deficiency when you are concerned for iron toxicity.

References