Pediatric Iron Toxicity
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Iron poisoning is a common toxicologic emergency in young children. Contributing factors include the availability of iron tablets and their candylike appearance. Ferrous sulfate tablets (20% elemental iron) are routinely administered to postpartum women, many of whom have toddlers in the family.
The potential severity of iron poisoning depends on the amount of elemental iron ingested. Calculation of the amount of elemental iron ingested involves the number of tablets ingested and the percentage of elemental iron in the salt that the tablets contain. [1] (See Presentation/History.)
Children may show signs of toxicity with ingestions of 10-20 mg/kg of elemental iron. Serious toxicity is likely with ingestions of more than 60 mg/kg. Iron exerts both local and systemic effects and is corrosive to the gastrointestinal mucosa and can affect the heart, lungs, and liver. Excess free iron is a mitochondrial toxin that leads to derangements in energy metabolism.
Although iron poisoning is a clinical diagnosis, serum iron levels are useful in predicting the clinical course of the patient. In treatment of iron poisoning, consider both bowel decontamination with whole bowel irrigation and chelation using intravenous deferoxamine.
In addition, chronic iron overload may develop in pediatric cancer patients who receive multiple transfusions. At one center, iron overload was diagnosed in 37% of pediatric patients who received 10 or more transfusions. Chelation therapy may be beneficial in these cases. [2]
To prevent iron poisoning, educate parents about the need for childproofing the home and keeping medications out of reach of children. For patient education information, see the First Aid and Injuries Center, as well as Iron Poisoning in Children and Poison Proofing Your Home.
The absorption of iron is normally very tightly controlled by the GI system. However, in overdose, local damage to the GI mucosa allows unregulated absorption, which leads to potentially toxic serum levels.
Much of the pathophysiology of iron poisoning is a result of metabolic acidosis and its effect on multiple organ systems. Toxicity manifests as local and systemic effects. Typically, iron poisoning is described in 5 sequential phases. No consensus has been reached regarding the number of phases and the times assigned to those phases. Patients may not always demonstrate all of the phases.
Phase 1, initial toxicity, predominantly manifests as GI effects. This phase begins during the first 6 hours postingestion and is associated with hemorrhagic vomiting, diarrhea, and abdominal pain. This is predominantly due to direct local corrosive effects of iron on the gastric and intestinal mucosa. Early hypovolemia may result from GI bleeding, diarrhea, and third spacing due to inflammation. This can contribute to tissue hypoperfusion and metabolic acidosis.
Convulsions, shock, and coma may complicate this phase if the circulatory blood volume is sufficiently compromised. In these cases, the patient progresses directly to phase 3, possibly within several hours.
Phase 2 is known as the latent phase and typically occurs 4-12 hours postingestion. It is usually associated with an improvement in symptoms, especially when supportive care is provided during phase 1. During this time, iron is absorbed by various tissues, and systemic acidosis increases. Clinically, the patient may appear to improve, especially to nonmedical personnel, because the vomiting that occurs in phase 1 subsides. However, laboratory analysis demonstrates progressive metabolic acidosis and, potentially, the beginning of other end-organ dysfunction (ie, elevation of transaminase levels).
Phase 3 typically begins within 12-24 hours postingestion, although it may occur within a few hours following a massive ingestion. Following absorption, ferrous iron is converted to ferric iron, and an unbuffered hydrogen ion is liberated. Iron is concentrated intracellularly in mitochondria and disrupts oxidative phosphorylation, resulting in free radical formation and lipid peroxidation. This exacerbates metabolic acidosis and contributes to cell death and tissue injury at the organ level.
Phase 3 consists of marked systemic toxicity caused by this mitochondrial damage and hepatocellular injury. GI fluid losses lead to hypovolemic shock and acidosis. Cardiovascular symptoms include decreased heart rate, decreased myocardial activity, decreased cardiac output, and increased pulmonary vascular resistance. The decrease in cardiac output may be related to a decrease in myocardial contractility exacerbated by the acidosis and hypovolemia. Free radicals from the iron absorption may induce damage and play a role in the impaired cardiac function.
The systemic iron poisoning in phase 3 is associated with a positive anion gap metabolic acidosis. The following explanations for the acidosis have been proposed:
Conversion of free plasma iron to ferric hydroxide is accompanied by a rise in hydrogen ion concentration.
Free radical damage to mitochondrial membranes prevents normal cellular respiration and electron transport, with the subsequent development of lactic acidosis.
Hypovolemia and hypoperfusion contribute to acidosis.
Cardiogenic shock contributes to hypoperfusion.
A coagulopathy is observed and may be due to 2 different mechanisms. Free iron may exhibit a direct inhibitory effect on the formation of thrombin and thrombin’s effect on fibrinogen in vitro. This may result in a coagulopathy. Later, reduced levels of clotting factors may be secondary to hepatic failure.
Phase 4 may occur 2-3 days postingestion. Iron is absorbed by Kupffer cells and hepatocytes, exceeding the storage capacity of ferritin and causing oxidative damage. Pathologic changes include cloudy swelling, periportal hepatic necrosis, and elevated transaminase levels. This may result in hepatic failure.
Phase 5 occurs 2-6 weeks postingestion and is characterized by late scarring of the GI tract, which causes pyloric obstruction or hepatic cirrhosis. See the image below.
As with any ingestion, the risk of ingestion increases as the availability of the medication increases. Childproof containers for multivitamins and prenatal vitamins may be of some assistance in decreasing exposure. In addition, some consideration has been given to changing the appearance of prenatal vitamins to make them look less like candy.
One study found an association between iron poisoning in young children and recent birth of a sibling. [3]
United States
In 2017, the American Association of Poison Control Centers (AAPCC) reported 4400 single exposures to iron and iron salts: 2181 were in children under the age of 6 years, 142 in children 6 to 12 years old, and 516 in patients 13 to 19 years old; there were eight major outcomes and two deaths. In addition, the AAPCC reported 9640 single exposures to multiple vitamins with iron, 7926 of them in children younger than 6 years, with one major outcome and no deaths. [4]
Most exposures involve children younger than 6 years who have ingested pediatric multivitamin preparations. Many of the serious acute ingestions follow the pattern of ingestions in general and occur in children younger than 3 years.
Most exposures result in minimal toxicity. However, concentrated iron supplement overdoses can result in serious sequelae and death.
If a patient does not develop symptoms of iron toxicity within 6 hours of ingestion, iron toxicity is unlikely to develop. Expect clinical toxicity following an ingestion of 20 mg/kg of elemental iron. Expect systemic toxicity with an ingestion of 60 mg/kg. Ingestion of more than 250 mg/kg of elemental iron is potentially lethal.
Complications of iron toxicity include the following:
Infectious –Yersinia enterocolitica septicemia
Pulmonary – Acute respiratory distress syndrome (ARDS)
Gastrointestinal – Fulminant hepatic failure, hepatic cirrhosis, pyloric or duodenal stenosis
Susceptibility to Yersinia enterocolitica infection or sepsis is heightened in these patients because Yersinia requires iron as a growth factor. Deferoxamine acts to solubilize iron and aid in intracellular entry for Yersinia. Suspect Yersinia infection in patients who develop abdominal pain, fever, and diarrhea following resolution of iron toxicity.
Educate parents about the need for childproofing the home and keeping medications out of reach of children. For patient education information, see the First Aid and Injuries Center, as well as Iron Poisoning in Children and Poison Proofing Your Home.
Chang TP, Rangan C. Iron poisoning: a literature-based review of epidemiology, diagnosis, and management. Pediatr Emerg Care. 2011 Oct. 27(10):978-85. [Medline].
Sait S, Zaghloul N, Patel A, Shah T, Iacobas I, Calderwood S. Transfusion related iron overload in pediatric oncology patients treated at a tertiary care centre and treatment with chelation therapy. Pediatr Blood Cancer. 2014 Dec. 61(12):2319-20. [Medline].
Juurlink DN, Tenenbein M, Koren G, Redelmeier DA. Iron poisoning in young children: association with the birth of a sibling. CMAJ. 2003 Jun 10. 168(12):1539-42. [Medline].
Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler KM, Banner W. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th Annual Report. Clin Toxicol (Phila). 2018 Dec 21. 51(10):1-203. [Medline]. [Full Text].
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[Guideline] Höjer J, Troutman WG, Hoppu K, Erdman A, Benson BE, Mégarbane B, et al. Position paper update: ipecac syrup for gastrointestinal decontamination. Clin Toxicol (Phila). 2013 Mar. 51 (3):134-9. [Medline]. [Full Text].
Thanacoody R, Caravati EM, Troutman B, Höjer J, Benson B, Hoppu K, et al. Position paper update: Whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol (Phila). 2015 Jan. 53(1):5-12. [Medline].
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Gumber MR, Kute VB, Shah PR, Vanikar AV, Patel HV, Balwani MR, et al. Successful treatment of severe iron intoxication with gastrointestinal decontamination, deferoxamine, and hemodialysis. Ren Fail. 2013. 35 (5):729-31. [Medline].
Bryant SM, Leikin JB. Iron. Critical Care Toxicology. 2005. 687-693.
Eldridge DL, Holstege CP. Utilizing the laboratory in the poisoned patient. Clin Lab Med. 2006 Mar. 26(1):13-30, vii. [Medline].
Fine JS. Iron poisoning. Curr Probl Pediatr. 2000 Mar. 30(3):71-90. [Medline].
Madiwale T, Liebelt E. Iron: not a benign therapeutic drug. Curr Opin Pediatr. 2006 Apr. 18(2):174-9. [Medline].
[Guideline] Manoguerra AS, Erdman AR, Booze LL, et al. Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2005. 43(6):553-70. [Medline].
Jennifer S Boyle, MD, PharmD Consulting Staff, Emergency Medicine/Medical Toxicology, Salem Veterans Affairs Medical Center
Jennifer S Boyle, MD, PharmD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians
Disclosure: Nothing to disclose.
David T Lawrence, DO Assistant Professor, Department of Emergency Medicine, Division of Medical Toxicology, University of Virginia School of Medicine
David T Lawrence, DO is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology
Disclosure: Nothing to disclose.
Christopher P Holstege, MD Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Chief, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Center
Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, Medical Society of Virginia, Society of Toxicology, Wilderness Medical Society, European Association of Poisons Centres and Clinical Toxicologists, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Kathryn Clark Emery, MD Associate Professor, Department of Pediatrics, University of Colorado Health Sciences Center; Consulting Staff, Department of Emergency Medicine, Children’s Hospital of Denver
Kathryn Clark Emery, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children’s Medical Center
Disclosure: Received salary from Merck for employment.
Stephen L Thornton, MD Associate Clinical Professor, Department of Emergency Medicine (Medical Toxicology), University of Kansas Hospital; Medical Director, University of Kansas Hospital Poison Control Center; Staff Medical Toxicologist, Children’s Mercy Hospital
Stephen L Thornton, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology
Disclosure: Nothing to disclose.
Halim Hennes, MD, MS Division Director, Pediatric Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director of Emergency Services, Children’s Medical Center
Halim Hennes, MD, MS is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children’s Hospital of Wisconsin
Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society
Disclosure: Nothing to disclose.
Pediatric Iron Toxicity
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