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Emergency and Acute Medicine – Iron Poisoning
Basics and pathophysiology
Iron poisoning is a potentially life-threatening toxicologic emergency, most commonly seen in pediatric accidental ingestions and adult intentional overdoses. Peak serum iron concentrations usually occur 2–4 hours after ingestion. Serum iron levels obtained more than 4–6 hours after ingestion may be misleading because iron rapidly redistributes into tissues; enteric-coated or sustained-release preparations require serial measurements. After absorption, free iron shifts intracellularly, causing direct cellular injury. The gastrointestinal tract sustains corrosive injury that can lead to hemorrhage, profound fluid loss, shock, and perforation. The liver receives the highest iron load via portal circulation, resulting in hemorrhagic periportal necrosis. Free iron disrupts mitochondrial oxidative phosphorylation, catalyzes lipid peroxidation and free radical formation, increases anaerobic metabolism, and produces metabolic acidosis. Cardiovascular depression, venodilation, cerebral edema, and acidemia result from these mechanisms.
Etiology and toxic doses
Toxicity depends on the amount of elemental iron ingested. Doses below 20 mg/kg are generally nontoxic, while ingestions greater than 40 mg/kg are associated with moderate to severe toxicity. Lethality is possible at doses exceeding 60 mg/kg. Elemental iron content varies by formulation: ferrous sulfate contains approximately 20% elemental iron (a 325-mg tablet contains 65 mg elemental iron), ferrous gluconate contains 12%, and ferrous fumarate contains 33%. Prenatal vitamins may contain 60–90 mg elemental iron per tablet, whereas children’s vitamins usually contain 5–18 mg per tablet. Historically, iron poisoning carried one of the highest pediatric mortality rates due to adult iron products; modern children’s chewable preparations are considerably safer.
Clinical presentation
Iron poisoning classically progresses through five stages, though patients may skip stages or present at any point. Stage 1 (0.5–6 hours) is characterized by gastrointestinal symptoms including abdominal pain, vomiting, diarrhea, hematemesis, and hematochezia. Stage 2 (6–24 hours) is a deceptive latent phase during which GI symptoms improve despite ongoing cellular injury; hypotension and acidosis may develop. Stage 3 (6–72 hours) involves shock and systemic toxicity with hypoperfusion, severe metabolic acidosis, coma, and coagulopathy. Stage 4 (2–3 days) is marked by hepatic failure with hypoglycemia, jaundice, coagulopathy, and markedly elevated transaminases. Stage 5 (2–4 weeks) presents with gastric outlet or small bowel obstruction due to scarring. Absence of symptoms within the first 6 hours makes a significant ingestion unlikely.
Diagnosis and essential workup
Acute iron poisoning is primarily a clinical diagnosis, and treatment decisions should not rely solely on laboratory values. Serum iron levels peak between 2 and 6 hours after ingestion, with 4 hours being the most common peak; delayed peaks occur with sustained-release formulations. Laboratory evaluation typically reveals an anion gap metabolic acidosis, early hyperglycemia followed by late hypoglycemia, leukocytosis, anemia if bleeding is significant, abnormal liver function tests, and coagulopathy in severe cases. Total iron-binding capacity is not useful and should not be obtained. Abdominal radiographs may reveal radiopaque tablets, although absence of pill fragments does not exclude severe poisoning. Imaging is also useful for detecting perforation.
Differential diagnosis
The differential diagnosis includes sepsis, acetaminophen toxicity, gastrointestinal bleeding from other causes, and toxic ingestions that cause anion gap metabolic acidosis such as salicylates, cyanide, methanol, ethylene glycol, heavy metals, mushrooms, and theophylline.
Emergency management
Initial management focuses on airway, breathing, and circulation. Patients with altered mental status or hemodynamic instability may require intubation. Establish venous access, initiate aggressive fluid resuscitation for hypotension, and place the patient on cardiac monitoring and pulse oximetry. Activated charcoal is ineffective for iron and should not be used. Gastric lavage has not shown outcome benefit. Sodium bicarbonate, phosphate preparations, and oral deferoxamine are not recommended. If tablets are visualized on abdominal radiograph or there is a history of significant ingestion, whole bowel irrigation with polyethylene glycol solution via nasogastric tube may be considered, with careful monitoring for gastrointestinal bleeding or perforation. Endoscopic or surgical removal may be required for massive ingestions with bezoar formation.
Chelation therapy
Deferoxamine (DFO) is the treatment of choice for significant iron poisoning and should be administered as early as possible, ideally within 24 hours. It chelates free iron, forming a complex excreted in urine, which may turn a characteristic “vin rose” color. Intravenous infusion is preferred and should be titrated carefully due to the risk of hypotension; infusion rates may be increased to 15 mg/kg/hour and adjusted as tolerated. Treatment decisions should be based on clinical status as well as laboratory data, especially in late presenters, because serum iron levels may be deceptively low after redistribution. Prolonged DFO therapy beyond 24–48 hours increases the risk of acute respiratory distress syndrome and should be used cautiously. Resolution of acidosis and systemic toxicity is the best endpoint for therapy. Regional poison control consultation is strongly recommended for moderate to severe cases.
Disposition and follow-up
Patients with gastrointestinal symptoms, dehydration, altered mental status, hypotension, metabolic acidosis, shock, serum iron levels above 500 mg/dL, rising iron levels, or those requiring deferoxamine therapy should be admitted. ICU admission is indicated for coma, severe acidosis, shock, or extremely elevated iron levels. Patients who remain asymptomatic after 6 hours of observation, have normal radiographs, minimal symptoms, and serum iron levels below 350 mg/dL may be discharged with careful instructions. Follow-up is important for patients at risk of delayed gastric outlet obstruction. Psychiatric evaluation is required for intentional ingestions.
Pearls and pitfalls
Resolution of early gastrointestinal symptoms does not exclude ongoing or worsening toxicity. Deferoxamine may be indicated even in late presentations with relatively low serum iron levels if there is evidence of intracellular poisoning such as metabolic acidosis. Clinical status, not laboratory values alone, should guide management decisions.
Basics and pathophysiology
Iron poisoning is a potentially life-threatening toxicologic emergency, most commonly seen in pediatric accidental ingestions and adult intentional overdoses. Peak serum iron concentrations usually occur 2–4 hours after ingestion. Serum iron levels obtained more than 4–6 hours after ingestion may be misleading because iron rapidly redistributes into tissues; enteric-coated or sustained-release preparations require serial measurements. After absorption, free iron shifts intracellularly, causing direct cellular injury. The gastrointestinal tract sustains corrosive injury that can lead to hemorrhage, profound fluid loss, shock, and perforation. The liver receives the highest iron load via portal circulation, resulting in hemorrhagic periportal necrosis. Free iron disrupts mitochondrial oxidative phosphorylation, catalyzes lipid peroxidation and free radical formation, increases anaerobic metabolism, and produces metabolic acidosis. Cardiovascular depression, venodilation, cerebral edema, and acidemia result from these mechanisms.
Etiology and toxic doses
Toxicity depends on the amount of elemental iron ingested. Doses below 20 mg/kg are generally nontoxic, while ingestions greater than 40 mg/kg are associated with moderate to severe toxicity. Lethality is possible at doses exceeding 60 mg/kg. Elemental iron content varies by formulation: ferrous sulfate contains approximately 20% elemental iron (a 325-mg tablet contains 65 mg elemental iron), ferrous gluconate contains 12%, and ferrous fumarate contains 33%. Prenatal vitamins may contain 60–90 mg elemental iron per tablet, whereas children’s vitamins usually contain 5–18 mg per tablet. Historically, iron poisoning carried one of the highest pediatric mortality rates due to adult iron products; modern children’s chewable preparations are considerably safer.
Clinical presentation
Iron poisoning classically progresses through five stages, though patients may skip stages or present at any point. Stage 1 (0.5–6 hours) is characterized by gastrointestinal symptoms including abdominal pain, vomiting, diarrhea, hematemesis, and hematochezia. Stage 2 (6–24 hours) is a deceptive latent phase during which GI symptoms improve despite ongoing cellular injury; hypotension and acidosis may develop. Stage 3 (6–72 hours) involves shock and systemic toxicity with hypoperfusion, severe metabolic acidosis, coma, and coagulopathy. Stage 4 (2–3 days) is marked by hepatic failure with hypoglycemia, jaundice, coagulopathy, and markedly elevated transaminases. Stage 5 (2–4 weeks) presents with gastric outlet or small bowel obstruction due to scarring. Absence of symptoms within the first 6 hours makes a significant ingestion unlikely.
Diagnosis and essential workup
Acute iron poisoning is primarily a clinical diagnosis, and treatment decisions should not rely solely on laboratory values. Serum iron levels peak between 2 and 6 hours after ingestion, with 4 hours being the most common peak; delayed peaks occur with sustained-release formulations. Laboratory evaluation typically reveals an anion gap metabolic acidosis, early hyperglycemia followed by late hypoglycemia, leukocytosis, anemia if bleeding is significant, abnormal liver function tests, and coagulopathy in severe cases. Total iron-binding capacity is not useful and should not be obtained. Abdominal radiographs may reveal radiopaque tablets, although absence of pill fragments does not exclude severe poisoning. Imaging is also useful for detecting perforation.
Differential diagnosis
The differential diagnosis includes sepsis, acetaminophen toxicity, gastrointestinal bleeding from other causes, and toxic ingestions that cause anion gap metabolic acidosis such as salicylates, cyanide, methanol, ethylene glycol, heavy metals, mushrooms, and theophylline.
Emergency management
Initial management focuses on airway, breathing, and circulation. Patients with altered mental status or hemodynamic instability may require intubation. Establish venous access, initiate aggressive fluid resuscitation for hypotension, and place the patient on cardiac monitoring and pulse oximetry. Activated charcoal is ineffective for iron and should not be used. Gastric lavage has not shown outcome benefit. Sodium bicarbonate, phosphate preparations, and oral deferoxamine are not recommended. If tablets are visualized on abdominal radiograph or there is a history of significant ingestion, whole bowel irrigation with polyethylene glycol solution via nasogastric tube may be considered, with careful monitoring for gastrointestinal bleeding or perforation. Endoscopic or surgical removal may be required for massive ingestions with bezoar formation.
Chelation therapy
Deferoxamine (DFO) is the treatment of choice for significant iron poisoning and should be administered as early as possible, ideally within 24 hours. It chelates free iron, forming a complex excreted in urine, which may turn a characteristic “vin rose” color. Intravenous infusion is preferred and should be titrated carefully due to the risk of hypotension; infusion rates may be increased to 15 mg/kg/hour and adjusted as tolerated. Treatment decisions should be based on clinical status as well as laboratory data, especially in late presenters, because serum iron levels may be deceptively low after redistribution. Prolonged DFO therapy beyond 24–48 hours increases the risk of acute respiratory distress syndrome and should be used cautiously. Resolution of acidosis and systemic toxicity is the best endpoint for therapy. Regional poison control consultation is strongly recommended for moderate to severe cases.
Disposition and follow-up
Patients with gastrointestinal symptoms, dehydration, altered mental status, hypotension, metabolic acidosis, shock, serum iron levels above 500 mg/dL, rising iron levels, or those requiring deferoxamine therapy should be admitted. ICU admission is indicated for coma, severe acidosis, shock, or extremely elevated iron levels. Patients who remain asymptomatic after 6 hours of observation, have normal radiographs, minimal symptoms, and serum iron levels below 350 mg/dL may be discharged with careful instructions. Follow-up is important for patients at risk of delayed gastric outlet obstruction. Psychiatric evaluation is required for intentional ingestions.
Pearls and pitfalls
Resolution of early gastrointestinal symptoms does not exclude ongoing or worsening toxicity. Deferoxamine may be indicated even in late presentations with relatively low serum iron levels if there is evidence of intracellular poisoning such as metabolic acidosis. Clinical status, not laboratory values alone, should guide management decisions.
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