Iron is found in many over-the-counter (OTC) multivitamins. Iron toxicity from intentional or accidental ingestion is a common poisoning. The acute ingestion of iron is especially hazardous to children. Life-threatening toxicity is associated with pediatric ingestion of potent adult preparations, such as prenatal vitamins. Serious iron ingestion in adults is usually associated with suicide attempts.
Ingestion of less than 20 mg/kg of elemental iron is non-toxic. Ingestion of 20 mg/kg to 60 mg/kg results in moderate symptoms. Ingestion of more than 60 mg/kg can result in severe toxicity and lead to severe morbidity and mortality. The amount of elemental iron ingested is different depending on the formulations of iron salts. The most common iron formulations are 325 mg ferrous sulfate tablets, which contains 20% (or 65 mg) of elemental iron per tablet; 300 mg ferrous gluconate tablets, which contain 12% (or 36 mg) of elemental iron per tablet; and 100 mg ferrous fumarate tablets, which contain 33% (or 33 mg) of elemental iron per tablet. Prenatal vitamins may contain 60 to 90 mg of elemental iron per tablet. Children's vitamins vary from 5 to 19 mg of elemental iron per tablet.
In 2015, the Annual Report of the American Association of Poison Control Centers (AAPCC) National Poison Data System reported 4072 single exposures to iron or iron salts. Out of these, 3211 cases were unintentional ingestion. Furthermore, 2036 of reported cases occurred in children 5 years old or younger, and 1161 cases were treated in a healthcare facility. There was one death.
Iron toxicity is classified as corrosive or cellular. Ingested iron can cause direct caustic injury to the gastrointestinal mucosa, resulting in nausea, vomiting, abdominal pain, and diarrhea. Significant fluid and blood loss can lead to hypovolemia. Hemorrhagic necrosis of gastrointestinal mucosa can lead to hematemesis, perforation, and peritonitis. At the cellular level, iron impairs cellular metabolism in the heart, liver, and central nervous system. Free iron enters cells and concentrates in the mitochondria. This disrupts oxidative phosphorylation, catalyzes lipid peroxidation, forms free radicals, and ultimately leads to cell death.
Serum iron level peaks at 2 to 4 hours post-ingestion, but serum concentrations of enteric-coated or sustained release formulations are erratic and warrant serial levels. Approximately 10% of ingested iron is absorbed from the intestine and is subsequently bound to transferrin. Normal serum iron levels range from 50 to 150 micrograms/dL, and total iron-binding capacity (TIBC) ranges from 300 to 400 micrograms/dL. When iron levels rise after a significant ingestion, transferrin becomes saturated. Excess iron will circulate in the blood as free iron, which is directly toxic to target organs.
The clinical course of iron toxicity is divided into five stages. The progression from stage to stage may be very rapid, and not every patient goes through every stage. During the first stage (0.5 to 6 hours), the patient mainly exhibits gastrointestinal (GI) symptoms including abdominal pain, vomiting, diarrhea, hematemesis, and hematochezia. The second stage (6 to 24 hours) represents an apparent recovery phase, as the patient’s GI symptoms may resolve despite toxic amounts of iron absorption. The third stage (6 to 72 hours) is characterized by the recurrence of GI symptoms, shock, and metabolic acidosis. Iron-induced coagulopathy, hepatic dysfunction, cardiomyopathy, and renal failure are also observed in this stage. The fourth stage (12 to 96 hours) is characterized by elevation of aminotransferase levels and possible progression to hepatic failure. The fifth stage (2 to 8 weeks) represents the consequences of the healing of the injured GI mucosa including pyloric or proximal bowel scarring and obstruction. A patient may present in or skip any of the five stages. Determination of the iron toxicity stage should be based on symptoms and clinical manifestations and not on time of ingestion.
The diagnosis of iron toxicity is based on the history and clinical presentation. Serum iron levels are used to determine a patient’s potential for toxicity. A serum iron level measured at its peak, 4 to 6 hours after ingestion, is the most useful laboratory test. Sustained-release or enteric-coated preparation may have erratic absorption, and therefore a second level 6 to 8 hours post-ingestion should be checked. Peak serum iron levels below 350 micrograms/dL are associated with minimal toxicity. Levels between 350 to 500 micrograms/dL are associated with moderate toxicity. Levels above 500 micrograms/dL are associated with severe systemic toxicity. Iron is rapidly cleared from the serum and deposited in the liver. Therefore, the iron level drawn after ingestion may be deceptively low if measured after its peak.
Other laboratory tests include electrolytes, kidney function, serum glucose, coagulation studies, complete blood count, and liver function. Plain radiographs may reveal iron in the GI tract, but many iron preparations are not radiopaque. Normal radiographs do not exclude iron ingestion.
Patients who remain asymptomatic 4 to 6 hours after ingestion or those who have not ingested a potentially toxic amount do not require any treatment for iron toxicity.
Patients who have GI symptoms that resolve after a short period of time and have normal vital signs require supportive care and an observation period, as it may represent the second stage of iron toxicity.
Patients who are symptomatic or demonstrate signs of hemodynamic instability require aggressive management and admission to an intensive care unit. The following is used for the treatment of iron toxicity:
Patients with GI symptoms or evidence of dehydration should be admitted. Patients receiving deferoxamine treatment should be admitted as well. Intensive care unit admission is indicated for patients presenting with coma, shock, metabolic acidosis, or iron levels over 1000 mg/dL. Psychiatric referral is indicated for patients with an intentional overdose. Patients can be safely discharged if they are asymptomatic after a 6 to 12-hour observation period and have a negative radiograph, or if they have mild GI symptoms that resolve without metabolic acidosis and serum iron level under 350 mg/dL after a 6 to 12 hour observation period.
Other diseases or conditions that can present similarly to iron toxicity include sepsis; acetaminophen toxicity; other toxic ingestions that cause anion gap metabolic acidosis including salicylate, cyanide, methanol, and ethylene glycol toxicity; mushroom ingestion; heavy metal toxicity; theophylline toxicity; and GI bleed from other causes.
The managment of patients with iron toxicity is usually done with a multidisciplinary team that includes the emergency department physician, posion control specialist, internist, intensivist, nurse practitioner and a hematologist. The key is to reverse the hypotension and hypovolemia. The us of the chelating agent, deferoxamine may be used in severe cases of metabolic acidosis. Patients with hemodynamic instability should be admitted to the ICU. Prior to discharge, a mental health nurse should see the patient if there is suspicion of an intentional overdose. Finally, it is important to educate patients on safe storage of the iron pills away from the reach of children. .
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