Practice Essentials
Iron poisoning is a common toxicologic emergency in young children. Contributing factors include the availability of a wide range of iron products and their candylike appearance. Many prenatal vitamins contain significant quantities of iron, and 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 50 mg/kg.
Iron exerts both local and systemic effects and is corrosive to the gastrointestinal mucosa and can directly 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 as well as helping to guide treatment. In the 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 First Aid for Poisoning in Children, Child Safety Proofing, and Iron Poisoning Treatment.
Pathophysiology
The absorption of iron is normally very tightly controlled by the gastrointestinal (GI) system. However, in overdose, local damage to the GI mucosa allows unregulated absorption, which leads to potentially toxic serum levels.
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 demonstrate all of the phases, depending in part on the amount of iron ingested.
Phase 1
Phase 1, initial toxicity, predominantly manifests as GI effects. This phase begins during the first 6 hours after ingestion and is associated with vomiting, diarrhea, and abdominal pain. Both hematemesis and hemetachezia may develop, 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 hypovolemia 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
Phase 2 is known as the latent phase and typically occurs 4-12 hours postingestion. It is usually associated with an improvement in GI 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, the vital signs worsen (eg, progressive tachycardia, developing hypotension) and laboratory analysis demonstrates progressive metabolic acidosis and, potentially, the beginning of other end-organ dysfunction (ie, elevation of transaminase levels).
Phase 3
Phase 3 typically begins within 12-24 hours post-ingestion, although it may occur within a few hours after 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:
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Conversion of free plasma iron to ferric hydroxide is accompanied by a rise in hydrogen ion concentration.
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Free radical damage to mitochondrial membranes prevents normal cellular respiration and electron transport, with the subsequent development of lactic acidosis.
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Hypovolemia and hypoperfusion contribute to acidosis.
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Cardiogenic shock contributes to hypoperfusion.
A coagulopathy is observed and may be due to two different mechanisms. First, 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
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
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.
The oxidative potential of iron was first proposed by Fenton in 1894. The importance of reduced oxygen species in biological reactions became apparent with the discovery of superoxide dismutase by McCord and Fridovich in 1969. The potential role of metal ion catalysis was reported the following year. Subsequently, a plethora of evidence has accumulated linking chronic excess body iron to cardiovascular disease, carcinogenesis, aging, stroke, Alzheimer disease, and Parkinson disease. The organ damage that occurs in the hereditary iron overloading disorders is well documented and can be averted and improved by decreasing the excess iron. Acute iron overload likewise produces tissue and organ damage due to the presence of free ionic iron.
Etiology
As with any ingestion, the risk of ingestion increases as the availability of the medication increases. One study found an association between iron poisoning in young children and recent birth of a sibling. [3] Childproof containers for multivitamins and prenatal vitamins may be of some assistance in decreasing exposure. The introduction of unit-dose packaging was followed by a decrease in the incidence of nonintentional ingestion of iron by young children and a decrease in mortality from iron poisoning. [4]
Epidemiology
Frequency
United States
In 2018, the American Association of Poison Control Centers (AAPCC) reported 4459 single exposures to iron and iron salts: 2173 were in children aged 5 years and younger, 156 in children 6 to 12 years old, and 540 in patients 13 to 19 years old. In addition, the AAPCC reported thousands of exposures to multivitamins with iron in children. [5]
Age
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.
Prognosis
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 50 mg/kg. Ingestion of more than 250 mg/kg of elemental iron is potentially lethal.
Complications of iron toxicity include the following:
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Infectious - Yersinia enterocolitica septicemia
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Pulmonary - Acute respiratory distress syndrome (ARDS)
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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.
Patient Education
Educate parents about the need for childproofing the home and keeping medications out of reach of children. For patient education information, see First Aid for Poisoning in Children, Child Safety Proofing, and Iron Poisoning Treatment.
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The oxidative potential of iron was first proposed by Fenton in 1894. The importance of reduced oxygen species in biological reactions became apparent with the discovery of superoxide dismutase by McCord and Fridovich in 1969. The potential role of metal ion catalysis was reported the following year. Subsequently, a plethora of evidence has accumulated linking chronic excess body iron to cardiovascular disease, carcinogenesis, aging, stroke, Alzheimer disease, and Parkinson disease. The organ damage that occurs in the hereditary iron overloading disorders is well documented and can be averted and improved by decreasing the excess iron. Acute iron overload likewise produces tissue and organ damage due to the presence of free ionic iron.
