Iron overdose has been one of the leading causes of poisoning deaths in children younger than 6 years. Iron is used in pediatric and prenatal vitamin and mineral supplements and for treatment of anemia. Iron tablets are particularly tempting to young children because they look like candy. Iron overdose in adults is typically a suicide attempt.[1]
Iron overload may develop chronically as well, especially in patients requiring multiple transfusions of red blood cells. This condition develops in patients with sickle cell disease, thalassemia, and hematologic malignancies such as myelodysplastic syndromes.[2, 3, 4]
For full discussion of iron toxicity in children, see Pediatric Iron Toxicity.
Iron toxicity can be classified as corrosive or cellular. Ingested iron can have an extremely corrosive effect on the gastrointestinal (GI) mucosa, which can manifest as nausea, vomiting, abdominal pain, hematemesis, and diarrhea; patients may become hypovolemic because of significant fluid and blood loss.
Cellular toxicity occurs with the absorption of excessive quantities of ingested iron. Severe overdose causes impaired oxidative phosphorylation and mitochondrial dysfunction, which can result in cellular death. The liver is one of the organs most affected by cellular iron toxicity, but other organs such as the heart, kidneys, lungs, and the hematologic systems also may be impaired. With chronic iron overload, the deposit of iron into the heart may cause death due to myocardial siderosis.
With both corrosive and cellular toxicity, the end result is significant metabolic acidosis, due to several factors. Hypoperfusion due to significant volume loss, vasodilatation, and negative inotropic effect of iron will result in lactic acidosis. Inhibition of oxidative phosphorylation will promote anaerobic metabolism.
Individuals demonstrate signs of GI toxicity after ingestion of more than 20 mg/kg. Moderate intoxication occurs when ingestion of elemental iron exceeds 40 mg/kg. Ingestions exceeding 60 mg/kg can cause severe toxicity and may be lethal.[5]
Suggested iron doses are based on calculation of the amount of elemental iron. Different iron preparations (salts) contain different amounts of elemental iron, as follows:
The 2023 Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System reported 5780 single exposures to iron or iron salts, with 20 major outcomes and 1 death. In addition, the AAPCC reported 7511 single exposures to multiple vitamins containing iron, with no major outcomes or deaths. Overall, 79% of vitamin exposure cases were in children younger than 6 years.[6]
Safekeeping of all medications, not just iron pills, from young children is important. Common medicines and vitamins may be lethal. Also see Vitamin Toxicity. The most effective measure to prevent iron ingestion is to store iron tablets in areas that are inaccessable to children.
For patient education information, see Iron Poisoning.
Gastrointestinal (GI) manifestations such as vomiting and diarrhea (especially when hemorrhagic) are an important feature of acute iron toxicity. Pediatric patients who are alert and not vomiting most likely did not ingest a toxic dose of iron; in adults, however, abdominal pain and vomiting may be absent. More than four episodes of vomiting suggests significant iron toxicity. Hemorrhagic gastroenteritis, even in the absence of a history of iron ingestion, should raise suspicion for iron toxicity. The absence of GI symptoms would strongly suggest a non-toxic ingestion.
Iron poisoning is often classified into five distinct stages, as follows:
Understanding the course of poisoning is important. In particular, the second stage may lure the physician into a false sense of security and result in premature and inappropriate discharge of a patient.
Features of stage 1 iron toxicity are as follows:
Features of stage 2 iron toxicity are as follows:
Features of stage 3 iron toxicity are as follows:
Features of stage 4 iron toxicity are as follows:
Stage 5 iron toxicity is characterized by scarring of the healing GI tract; the stomach and/or intestines may be affected, resulting in gastric outlet or intestinal obstruction. This phase usually occurs weeks after a severe poisoning.
Complications of iron toxicity include the following:
The workup for iron toxicity includes the following studies:
For serum iron measurement, samples should be drawn at least 4 hours postingestion, to allow levels to reach steady state; however, levels drawn more than 6 hours after ingestion may underestimate toxicity because of ferritin binding and redistribution of iron. With extended-release products, consider a level at 8 hours. The significance of results is as follows:
Glucose levels exceeding 150 mg/dL are common with severe iron toxicity. Monitoring glucose levels is important because hepatic dysfunction may cause hypoglycemia.
On the CBC, a white blood cell (WBC) count of more than 15,000/mm3 is associated with severe iron poisoning. A CBC is also helpful because anemia from blood loss may develop.
LFTs are indicated because hepatic dysfunction is common in severe iron poisoning. The liver is the first organ outside of the GI tract to receive a large iron load, which enters through the portal blood supply.
Electrolyte measurements and kidney function tests assist in calculation of the anion gap (see the Anion Gap calculator) and detection of electrolyte abnormalities and the presence of prerenal azotemia. Iron toxicity is one of the causes of acidosis with an increased anion gap, as noted in the mnemonic MUDPILES:
Iron tablets remain radiopaque for a few hours postingestion, and may be visible on a kidneys, ureters, bladder (KUB) film. However, the absence of radiopacities does not rule out a significant or even potentially lethal ingestion.
Magnetic resonance imaging (MRI) has become widely accepted as the primary method for noninvasively quantifying liver iron concentration.[8] Annual measurements of liver iron concentration by MRI has been recommended for all patients receiving long-term chronic transfusion therapy, along with MRI measurement of cardiac iron in patients at high risk of cardiac iron deposition.[8, 9]
MRI measurement of liver iron has also been suggested as a surrogate marker for total body iron in dialysis patients, who routinely receive parenteral iron in conjunction with erythropoiesis-stimulating agents for treatment of anemia. However, while these findings challenge the current reliance on transferrin saturation and serum ferritin levels as markers of iron load, the clinical relevance of MRI for this patient population remains to be determined.[10]
In patients with acute iron overdose, intravenous access should be established immediately. Patients who are hypovolemic should receive fluid boluses of 20 mL/kg of normal saline or lactated Ringer solution. Provide oxygen to patients in shock.
Assume that symptomatic patients are hypovolemic. Administer vigorous volume therapy with isotonic crystalloids (eg, normal saline, lactated Ringer solution) in 20 mL/kg boluses to attain and maintain hemodynamic stability. Give supplemental oxygen.
Gastric lavage with a large-bore orogastric tube may remove iron from the stomach. Ideally, lavage should be performed 1-2 hours postingestion, although later use may be appropriate if evidence of iron products in the stomach is observed on a radiograph. However, iron has a gelatinous texture and may be difficult to remove.
Consultation with a toxicologist is recommended. Obtain a gastroenterology consultation for patients who have large iron bezoars. Transfer patients if intensive care or deferoxamine is not available locally.
The goals of pharmacotherapy are to reduce iron levels, prevent complications, and reduce morbidity. Deferoxamine (Desferal) is used for chelation of iron in both acute and chronic toxicity.
The oral chelating agent deferasirox (Exjade) is approved by the US Food and Drug Administration (FDA) for the treatment of chronic iron overload due to blood transfusions in patients 2 year of age and older; it is also approved for treatment of chronic iron overload resulting from non–transfusion-dependent thalassemia.
Clinical Context: Drug of choice for iron intoxication. Freely soluble in water. Approximately 8 mg of iron is bound by 100 mg of deferoxamine. Excreted in urine and bile and gives urine a red discoloration. Readily chelates iron from ferritin and hemosiderin but not transferrin. Most effective when administered continuously by infusion. May be administered by IM injection or slow IV infusion. Does not effectively chelate other trace metals of nutritional importance. Provided in vials containing 500 mg of lyophilized sterile drug. Add 2 mL of sterile water to each vial for injection, bringing the concentration to 250 mg/mL. For IV use, may be diluted in 0.9% sterile saline, 5% dextrose solution, or Ringer solution. IV administration route is preferred, with the usual dose 15 mg/kg/hour. Histamine may be released, resulting in hypotension that is treatable by fluid resuscitation. The duration of therapy usually is 24 hours, and should be guided by a medical toxicologist.
Clinical Context: Indicated for treatment of chronic iron overload caused by blood transfusion.
Clinical Context: Laxative with strong electrolytic and osmotic effects that has cathartic actions in the GI tract.