Iron is used for the treatment of anemia and as a prenatal or daily mineral supplement. It is a common (and potentially fatal) ingestion due to its wide availability as an over-the-counter medication. Currently, there are many iron preparations that contain various amounts of iron salts. Most children's preparations contain 10-18 mg of iron per dose, and most adult preparations contain 60-90 mg of iron per dose. The following description of iron toxicity relates to ferrous (Fe²⁺) iron salts (eg, sulfate, gluconate, fumarate). Elemental iron products (eg, carbonyl iron and iron polysaccharide, which contain iron in its zero oxidation state [Fe⁰]) have not been reported to produce significant toxicity.

1. Iron salts have a direct corrosive effect on mucosal tissue and may cause hemorrhagic necrosis and perforation. Fluid loss from the GI tract can result in severe hypovolemia.
2. Excess absorbed iron causes cellular dysfunction and death, resulting in lactic acidosis and organ failure. Iron-induced reactive oxygen species cause oxidative and free radical injury and disrupt cellular process such as mitochondrial oxidative phosphorylation.

The acute lethal dose in animal studies is 150-200 mg/kg of iron. To calculate the iron content of various ferrous salts, divide the dose form by 3 (ferrous fumarate), 5 (ferrous sulfate), or 8 (ferrous gluconate). The resulting values are often called “elemental iron equivalents” although the iron is not in its elemental form (Fe⁰). The lowest reported lethal dose was in a 21-month-old child who ingested between 325 and 650 mg of elemental iron equivalents in the form of ferrous sulfate (5-10 adult tablets). Symptoms are unlikely if less than 20 mg/kg of elemental iron equivalents has been ingested. Doses of 20-30 mg/kg may produce self-limited vomiting, abdominal pain, and diarrhea. Ingestion of more than 40 mg/kg is considered potentially serious, and more than 60 mg/kg is potentially lethal. There are no reported cases of serious or fatal poisoning from the ingestion of children's chewable vitamins with iron, likely due to the lower iron content per tablet than typical iron supplements.

Iron poisoning is usually described in five stages. However, individual stages may overlap or be entirely absent.

1. First stage. Shortly after ingestion, the corrosive effects of iron cause abdominal pain, vomiting, and often bloody diarrhea. Massive fluid or blood loss into the GI tract may cause serious hemodynamic instability. Absence of GI symptoms within the first 6 hours of ingestion essentially excludes serious iron toxicity.
2. Second stage. Patients passing the first stage may experience a latent period of apparent improvement over 6-24 hours. However, ongoing cellular toxicity persists, and patients continue to demonstrate tachycardia, lethargy, and metabolic acidosis.
3. Third stage. This may occur within the first few hours of massive ingestion or 12-24 hours after a moderate ingestion. Systemic toxicity including coma, shock, seizures, metabolic acidosis, and coagulopathy are among the common findings. Yersinia enterocolitica sepsis may also occur (see below).
4. Fourth stage. This stage is characterized by hepatic failure that occurs 1-3 days post-ingestion. Coagulopathy worsens and may complicate bleeding and hypovolemia.
5. Fifth stage. In survivors, scarring from the initial corrosive injury may result in pyloric stricture or other intestinal obstruction within 2-8 weeks after ingestion.

Is based on a history of exposure and the presence of vomiting, diarrhea, hypotension, and other clinical signs.

1. Specific levels.
   1. Serum iron levels greater than 300-500 mcg/dL are common in patients with GI symptoms. Serum levels between 500 and 1,000 mcg/dL are associated with systemic toxicity. Iron levels greater than 1,000 mcg/dL represent significant poisoning and are associated with high morbidity and mortality. Obtain a serum iron level 4-6 hours after ingestion and repeat levels every 4-6 hours to rule out delayed absorption (e.g., from a sustained-release tablet or a tablet bezoar).
   2. The conventional method of measuring total iron-binding capacity (TIBC) is unreliable in iron overdose and should not be used to estimate free iron levels.
   3. Serum or plasma ferritin level is a more reliable marker for chronic iron toxicity and should not be used in acute settings.
2. Other useful laboratory studies include CBC, venous or arterial blood gases (to assess pH), electrolytes, glucose, BUN, creatinine, hepatic aminotransferases (AST and ALT), lactic acid, coagulation studies, and abdominal radiography.

Patients who have self-limited mild GI symptoms or who remain asymptomatic for 6 hours after ingestion are unlikely to develop serious intoxication and likely do not require treatment. In contrast, those with serious ingestion must be managed promptly and aggressively.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat shock caused by hemorrhagic gastroenteritis aggressively with IV crystalloid fluids or blood products. Patients are often markedly hypovolemic due to GI losses and third spacing of fluids into the intestinal wall and interstitial space. Vasopressors may be needed if patients are unresponsive to crystalloid fluids and/or blood products.
   3. Treat coma, seizures, and metabolic acidosis (p 36) if they occur.
2. Specific drugs and antidotes. For seriously poisoned patients (eg, shock, severe acidosis, or serum iron >500 mcg/dL), administer deferoxamine. Monitor the urine for the characteristic orange or pink-red (“vin rose”) color of the chelated deferoxamine-iron complex, although this may not always be seen.
   1. Dosing and route. The IV route is preferred. Give 15 mg/kg/h; faster rates (up to 45 mg/kg/h) reportedly have been well tolerated in single cases, but rapid boluses usually cause hypotension. The manufacturer's recommended maximum daily dose is 6 g; however, larger amounts have been given safely in massive iron overdoses. IM deferoxamine is not recommended in acute poisoning due to unreliable absorption.
   2. Treatment endpoint. A definitive endpoint for the cessation of deferoxamine is not well established. Discontinue therapy with clinical improvement, resolution of metabolic acidosis, and when the urine color returns to normal.
   3. Adverse effects. Rapid initial infusions are associated with hypotension. Prolonged deferoxamine therapy (>32-72 hours) is associated with adult respiratory distress syndrome (ARDS) and sepsis due to Yersinia enterocolitica.
3. Decontamination.
   1. Induced emesis is not recommended.
   2. Activated charcoal does not adsorb iron and is not recommended unless other drugs are co-ingested.
   3. Consider gastric lavage early after ingestion or if a large number of tablets are visible in the stomach on abdominal radiograph. Deferoxamine lavage is not effective and may enhance iron absorption.
   4. Whole-bowel irrigation is potentially effective and should be considered, especially if a large number of pills are visible on abdominal radiograph.
   5. Large ingestions may result in tablet concretions or bezoars. Repeated or prolonged whole-bowel irrigation may be considered. Endoscopy or surgical gastrotomy is rarely required but has been used.
4. Enhanced elimination
   1. Hemodialysis and hemoperfusion are not effective at removing iron but may be necessary to remove deferoxamine-iron complex in patients with renal failure.
   2. Exchange transfusion is occasionally used for massive pediatric ingestion, but may not be tolerated in patients with hemodynamic instability.
5. Other chelators.
   • 3. Deferiprone and deferasirox are oral chelators used for the treatment of chronic iron overload. Although there are no studies addressing their use in acute iron poisoning, they might be considered in patients where deferoxamine therapy is contraindicated or inadequate.
     1. Deferiprone: Combining deferiprone (75 mg/kg/day divided every 8 hours) with deferoxamine appeared to improve outcome in studies with chronic iron overload. Adverse effects include neutropenia (5%) and agranulocytosis (<1%).
     2. Deferasirox: Studies on chronic iron overloaded thalassemic patients showed deferasirox (30 mg/kg/day) was effective. Gastrointestinal symptoms are the most common adverse effects, but acute renal insufficiency has been reported.