Iron Toxicity

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

Gumber MR1, Kute VB, Shah PR, Vanikar AV, Patel HV, Balwani MR, Ghuge PP, Trivedi HL. Successful treatment of severe iron intoxication with gastrointestinal decontamination, deferoxamine, and hemodialysis. Ren Fail. 2013;35(5):729-31. PMID: 23635030. [PubMed] [Read by QxMD]
Chang TP1, Rangan C. Iron poisoning: a literature-based review of epidemiology, diagnosis, and management. Pediatr Emerg Care. 2011 Oct;27(10):978-85. PMID: 21975503. [PubMed] [Read by QxMD]
Aldridge MD1. Acute iron poisoning: what every pediatric intensive care unit nurse should know. Dimens Crit Care Nurs. 2007 Mar-Apr;26(2):43-8; quiz 49-50. PMID: 17312404. [PubMed] [Read by QxMD]
Morris CC1. Pediatric iron poisonings in the United States. South Med J. 2000 Apr;93(4):352-8. PMID: 10798501. [PubMed] [Read by QxMD]
Anderson BD1, Turchen SG, Manoguerra AS, Clark RF. Retrospective analysis of ingestions of iron containing products in the united states: are there differences between chewable vitamins and adult preparations? J Emerg Med. 2000 Oct;19(3):255-8. PMID: 11033271. [PubMed] [Read by QxMD]

Sean M. Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renowned educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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