Iron poisoning

Iron poisoning typically occurs from ingestion of excess iron that results in acute toxicity.[1] Mild symptoms which occur within hours include vomiting, diarrhea, abdominal pain, and drowsiness.[2] In more severe cases, symptoms can include tachypnea, low blood pressure, seizures, or coma.[2] If left untreated, iron poisoning can lead to multi-organ failure resulting in permanent organ damage or death.[3]

Iron poisoning
Other namesiron toxicity, iron overdose

Iron is available over the counter as a single entity supplement in an iron salt form or in combination with vitamin supplements and is commonly used in the treatment of anemias.[3][2] Overdoses on iron can be categorized as unintentional ingestion which is predominantly associated with children or intentional ingestion involving suicide attempts in adults.[1] Unintentional ingestion of iron containing drug products are a major cause of mortality in children under the age of 6 years old in the United States.[1] As a response, in 1997 the US Food and Drug Administration (FDA) implemented a regulation requiring warning labels and unit dose packaging for products containing more than 30mg of elemental iron per dose.[4]

The diagnosis of iron poisoning is based on clinical presentation including laboratory tests for serum iron concentrations and metabolic acidosis along with physical examination.[4] Treatment for iron poisoning involves providing fluid replacement, gastrointestinal decontamination, administering deferoxamine intravenously, liver transplants, and monitoring the patient's condition.[4] The degree of intervention required depends on whether the patient is at risk for serious toxicity.[4]

Signs and symptoms

Clinical presentation of serious toxicity from iron poisoning in the absence of treatment progresses in 5 stages: the gastrointestinal (GI) phase, latent phase, shock and metabolic acidosis phase, hepatotoxicity stage, and bowel obstruction due to scarring.[2] The first indication of iron poisoning occurs within the first 6 hours upon ingestion involving gastrointestinal (GI) symptoms including abdominal pain accompanied by nausea and vomiting or bloody vomiting. After the first stage, the latent phase occurs where symptoms resolve and there is an apparent improvement in the patient's condition.[2] Following this stage, more severe symptoms may develop 6 to 72 hours post-ingestion including low blood pressure, fever, bleeding, jaundice, seizures, hypovolemic shock from fluid and blood loss.[4] During this stage, metabolic acidosis may also develop damaging internal organs such as the brain and liver.[4] In the fourth stage taking place 2 to 5 days after ingestion, mortality from liver failure, shock, blood loss and blood-clotting abnormalities can occur.[2] Patient's who survive iron poisoning progress to the fifth stage 2 to 8 weeks following ingestion and experience scarring of the GI mucosal lining resulting in bowel obstruction.[1]

In mild to moderate cases, patient's may be asymptomatic or only experience mild symptoms in the first stage without progressing to the later stages.[4]

Cause

In nature, iron is usually found in its oxidized form, iron (III) oxide, which is insoluble. Ferrous iron, iron (II), is soluble and its toxicity varies, largely with the integrity of the gastrointestinal lining. Iron supplements are typically used to treat anemia. Modalities include: diet, parasite control,[5] vitamin A, riboflavin (B2),[6] vitamin C (for absorption), folate(B9), vitamin B12 and multivitamin-multimineral supplements,[7] with or without iron; potentially avoiding the use of iron only supplements.[8]

Toxic dose

The amount of iron ingested may give a clue to potential toxicity. The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Toxic effects begin to occur at doses above 10–20 mg/kg of elemental iron. Ingestions of more than 50 mg/kg of elemental iron are associated with severe toxicity.[9]

  • A 325-mg tablet of ferrous sulfate heptahydrate has 65 mg (20%) of elemental iron
  • A 325-mg tablet of ferrous gluconate has 39 mg (12%) of elemental iron
  • A 325-mg tablet of ferrous fumarate has 107.25 mg (33%) of elemental iron
  • 200 mg ferrous sulfate, dried, has 65 mg (33%) of elemental iron

In terms of blood values, iron levels above 350–500 μg/dL are considered toxic, and levels over 1000 μg/dL indicate severe iron poisoning.[10]

Diagnosis

A detailed history of the ingestion, especially the number of pills taken, can be vital. Diagnosis of iron poisoning can be made in the absence of a specific history by clinical judgment, abdominal imaging, and lab assessment. Radioopaque tablets in the stomach on imaging may support a diagnosis of accidental or intentional ingestion of iron tablets. Excessive iron is toxic to the gastrointestinal mucosal, causing abdominal pain, vomiting, diarrhea, and bleeding (hematemesis/melena). Vomitus and/or stool may appear black or green from disintegrating iron tablets. Anion gap metabolic acidosis may be present and results from hydrogen ion production during iron absorption and increased lactic acid production due to hypoperfusion/shock. Serum iron levels can be tested and are useful regarding the administration of iron-binding ligands such as deferoxamine. Clinic presentation in the absence of treatment follows in stages and is dose dependent (how much iron was taken):[11][12]

Stage Time Post Ingestion Signs Symptoms
1 1–6 hours Vomiting, diarrhea, GI bleeding, circulatory shock from hemorrhage and vasodilation Abdominal pain
2 6–12 hours Possible resolution of some signs based on treatment and dosage of poisoning Resolution of symptoms (considered a dangerous period if severe poisoning but if mild then may indicate a true turning point)
3 12–36 hours Metabolic acidosis, circulatory collapse, hepatic failure

Renal failure

D.I.C.

Neurologic decline

4 2–6 weeks Signs of fibrosis at the pyloric region and elsewhere in the intestine with concomitant stenosis (narrowing)

Treatment

The first-line treatment of acute iron poisoning is aggressive volume resuscitation. Excessive iron is treated with deferoxamine, a chelating agent that binds free iron, forming a complex that can be renally excreted.

Later stage treatment consists of cleaning the iron from the blood, using a chelating agent such as deferoxamine. If this fails then dialysis is the next step.

See also

References

  1. Yuen, Ho-Wang; Becker, Wenxia (2020), "Iron Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29083637, retrieved 2020-12-30
  2. "Iron Poisoning - Injuries and Poisoning". MSD Manual Consumer Version. Retrieved 2020-12-30.
  3. Manoguerra, Anthony S.; Erdman, Andrew R.; Booze, Lisa L.; Christianson, Gwenn; Wax, Paul M.; Scharman, Elizabeth J.; Woolf, Alan D.; Chyka, Peter A.; Keyes, Daniel C.; Olson, Kent R.; Caravati, E. Martin (2005-01-01). "Iron Ingestion: an Evidence-Based Consensus Guideline for Out-of-Hospital Management". Clinical Toxicology. 43 (6): 553–570. doi:10.1081/CLT-200068842. ISSN 1556-3650.
  4. "UpToDate". www.uptodate.com. Retrieved 2020-12-31.
  5. Stoltzfus RJ, Dreyfuss ML (2000). "Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia" (PDF). International Nutritional Anemia Consultative Group, International Life Sciences Institute Press. Archived from the original (PDF) on 2008-09-10. Retrieved 2008-02-10.
  6. Allen LH (April 2002). "Iron Supplements: Scientific Issues Concerning Efficacy and Implications for Research and Programs". J. Nutr. 132 (4): 813S–9S. doi:10.1093/jn/132.4.813S. PMID 11925487.
  7. "What Is Anemia?". National Heart, Lung, and Blood Institute, U.S. Dept. of Health and Human Services. 18 May 2012.
  8. "Hemochromatosis and Anemia Diet". Iron Overload Diseases Association. Archived from the original on 2011-07-26. Retrieved 2008-02-10.
  9. "Iron Poisoning". Webmd.com. Retrieved 2012-04-09.
  10. "Iron Tests". The Free Dictionary by Falex. citing: Gale Encyclopedia of Medicine. Copyright 2008
  11. Pediatrics. Brown, Lloyd J., Miller, Lee T. (Lee Todd). Philadelphia: Lippincott Williams & Wilkins. 2005. ISBN 9780781721295. OCLC 54913574.CS1 maint: others (link)
  12. "Approach to the child with occult toxic exposure". www.uptodate.com. Retrieved 2018-01-04.
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