O. John Ma
Iron toxicity from intentional or accidental ingestion is a common poisoning.
Significantly fewer poison center calls and deaths caused by ingestion of iron supplements were reported after the US Food and Drug Administration issued a regulation for unit-dose packaging.
Iron is a direct gastrointestinal (GI) irritant and causes vomiting, diarrhea, abdominal pain, mucosal ulceration, and GI bleeding after a significant ingestion.
Vomiting and diarrhea from iron toxicity can lead to hypovolemia, which in turn may produce hypotension, tissue hypoperfusion, and metabolic acidosis.
Toxic effects have been reported following oral doses as low as 10 to 20 milligrams/kg of elemental iron. Moderate toxicity occurs at doses of 20 to 60 milligrams/kg of elemental iron, and severe toxicity can be expected following doses greater than 60 milligrams/kg.
Based on clinical findings, iron poisoning can be divided into five stages. Patients can die in any stage of iron poisoning.
The first stage develops within the first few hours after the ingestion. The direct irritative effects of iron on the GI tract produce abdominal pain, vomiting, and diarrhea. Hematemesis is not unusual. Vomiting is the clinical sign most consistently associated with acute iron toxicity. The absence of these symptoms within 6 hours of ingestion essentially excludes a diagnosis of significant iron toxicity.
During the second stage, which can continue up to 24 hours following ingestion, the patient’s GI symptoms may temporarily resolve, thereby giving a false sense of security despite toxic amounts of absorbed iron. Although potentially asymptomatic, patients appear ill, and may have abnormal vital signs and evidence of poor tissue perfusion because of ongoing volume loss and worsening metabolic acidosis.
The third stage can either appear very early or develop hours after the second stage: shock and lactic acidosis develop. Iron-induced coagulopathy may worsen bleeding and hypovolemia. Hepatic dysfunction, cardiomyopathy, and renal failure also may occur.
The fourth stage develops 2 to 5 days after ingestion and manifests as elevation of aminotransferase levels that may progress to hepatic failure.
The fifth stage, which occurs 4 to 6 weeks after ingestion, involves gastric outlet obstruction secondary to corrosive effects of iron on the pyloric mucosa.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis of iron poisoning is based on the clinical picture and history provided by the patient, significant others, or EMS providers.
Order a basic metabolic panel, coagulation studies, complete blood count, hepatic enzymes, and a serum iron level.
It is crucial to note that a single serum iron level does not reflect what iron levels have been previously, what direction they are going, or the degree of iron toxicity in tissues. A single low serum level does not exclude the diagnosis of serious iron toxicity since peak levels following ingestion of different iron preparations are variable in timing.
Serum iron levels have limited use in directing management since toxicity is intracellular.
In general, serum iron levels between 300 and 500 micrograms/dL correlate with mild systemic toxicity and iron levels between 500 and 1000 micrograms/dL correlate with moderate systemic toxicity. Levels greater than 1000 micrograms/dL are associated with severe toxicity and increased morbidity.
The total iron-binding capacity (TIBC) does not aid in the assessment of iron-poisoned patients because it becomes falsely elevated in the presence of elevated serum iron levels or deferoxamine.
A plain radiograph may reveal iron in the GI tract; however, many iron preparations are not routinely detected, so negative radiographs do not exclude iron ingestion.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Patients who have remained asymptomatic for 6 hours after ingestion of iron and who have a normal physical examination do not require medical treatment for iron toxicity.
Patients whose symptoms resolve after a short period of time and have normal vital signs usually have mild toxicity and require only supportive care. This subset of patients still requires an observation period.
Patients who are symptomatic or demonstrate signs of hemodynamic instability after iron ingestion should be managed aggressively in the ED.
Place the patient on supplemental oxygen and a cardiac monitor, and secure intravenous (IV) access.
Administer aggressive IV crystalloids to help correct hypovolemia and hypoperfusion.
Perform gastric lavage in patients who present within 60 minutes of ingestion. Activated charcoal is not recommended.
Whole-bowel irrigation with a polyethylene glycol solution is efficacious. Administer 250 to 500 mL/h in children or 2 L/h in adults via nasogastric tube, which may clear the GI tract of iron pills before absorption occurs.
Administer antiemetics such as ondansetron (4 milligrams IV in adults; 0.1 milligram/kg IV to a maximum dose of 4 milligrams in children) or promethazine (25 milligrams IV in adults; 0.25 milligram/kg IV in pediatric patients).
Correct coagulopathy with vitamin K1 (5-10 milligrams SC) and fresh frozen plasma (10-25 mL/kg in adults; 10 mL/kg in pediatric patients). Order blood for type and screen or crossmatch, as necessary.
Deferoxamine is a chelating agent that removes iron from tissues and plasma. Deferoxamine is safe to administer to children and pregnant women. Deferoxamine therapy is indicated in patients with systemic toxicity, metabolic acidosis, worsening symptoms, or a serum iron level predictive of moderate or severe toxicity.
Intravenous infusion is the preferred route of deferoxamine administration because IM absorption is unpredictable in the hypovolemic patient. The recommended initial dose is 1000 milligrams IV. Since hypotension is the rate-limiting factor for IV infusion, it is recommended to begin with a slow IV infusion at 5 milligrams/kg/h. The rate can be increased to 15 milligrams/kg/h, as tolerated, within the first hour of treatment.
The recommended total amount of deferoxamine is 360 milligrams/kg or 6 grams during the first 24 hours.
Initiate deferoxamine therapy without waiting for the serum iron level in any clinically ill patient with a known iron ingestion.
Evaluate the efficacy of deferoxamine treatment through serial urine samples. As ferrioxamine is excreted, urine changes to a classic vin rose appearance. Clinical recovery is the most important factor guiding termination of deferoxamine therapy.
Patients who remain asymptomatic after 6 hours of observation have a normal physical examination, and a reliable history of an insignificant ingestion can be considered for discharge.
Patients initially symptomatic who become asymptomatic should be admitted for further evaluation since this may represent the second stage of iron toxicity.
Admit all patients who receive deferoxamine therapy to an intensive care setting.
Assess all patients for suicide risk. Consider child abuse or neglect in pediatric cases.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 192, “Iron,” by Stephanie H. Hernandez and Lewis S. Nelson.