Iron Toxicity

Etiology and Pathophysiology

Iron poisoning is a potentially fatal pediatric emergency, with severity directly related to the amount of elemental iron ingested.
Adult iron preparations and prenatal vitamins are the most toxic sources, whereas children's vitamins, multivitamin preparations, and nonionic forms (carbonyl iron, iron polysaccharide) rarely contain enough elemental iron to cause significant toxicity.

The risk assessment and severity of iron toxicity are determined strictly by the amount of elemental iron ingested, rather than the total weight of the iron salt tablet.
The therapeutic dose for treating iron deficiency anemia is typically 3 to 6 mg/kg/day.
Acute ingestions exceeding these therapeutic limits are categorized based on the milligram per kilogram (mg/kg) of elemental iron ingested, which correlates with expected clinical manifestations.

Dose of Elemental Iron Ingested	Expected Toxicity and Clinical Features
<20 mg/kg	Asymptomatic / Non-toxic: Individuals typically do not exhibit any symptoms and require no specific treatment.
20−60 mg/kg	Mild to Moderate Toxicity: Results primarily in local gastrointestinal (GI) symptoms such as abdominal pain, vomiting, and diarrhea.
60−120 mg/kg	Severe Toxicity: High potential for systemic toxicity, including metabolic acidosis, shock, coagulopathy, and hepatorenal failure.
>120 mg/kg	Potentially Lethal: Associated with life-threatening systemic collapse, severe morbidity, and high mortality.

Iron has a direct corrosive effect on the gastrointestinal mucosa, leading to hematemesis, melena, ulceration, and potential perforation.
The presence of free iron causes massive volume losses, increased capillary membrane permeability, and vasodilation, which collectively precipitate early hypotension.
Iron accumulates in target tissues, notably the Kupffer cells of the liver and myocardial cells, causing hepatotoxicity, coagulopathy, and cardiac dysfunction.
Profound metabolic acidosis occurs due to a combination of hypovolemia, hypotension, and iron's direct interference with oxidative phosphorylation and the Krebs cycle.

Iron Salt / Preparation	Percentage of Elemental Iron	Calculation Rule
Ferrous Fumarate	33%	Divide total salt dose by 3
Ferrous Sulfate (dried)	≈30%	Divide total salt dose by 3.3
Ferrous Sulfate (heptahydrate)	20%	Divide total salt dose by 5
Ferrous Gluconate	12%	Divide total salt dose by 9
Ferric Chloride	≈28.5%	Divide total salt dose by 3.5
Ferrous Chloride	25%	Divide total salt dose by 4

The clinical progression of acute iron toxicity is classically described in five overlapping stages.
Patients who remain completely asymptomatic without gastrointestinal symptoms within $6$ hours of ingestion are highly unlikely to develop serious toxicity.

Phase	Time After Ingestion	Characteristic Clinical Features
1. Gastrointestinal	$6$ hours	Vomiting, diarrhea, hematemesis, hematochezia.
2. Latent	$6 - 24$ hours	Resolution of gastrointestinal symptoms, tachycardia, acidosis, depressed mental status.
3. Systemic	$12 - 24$ hours	Return of gastrointestinal symptoms, severe acidosis (HAGMA), leukocytosis, coagulopathy, renal failure, lethargy or coma, and cardiovascular collapse.
4. Hepatic	$2 - 5$ days	Fulminant liver failure, coagulopathy.
5. Obstructive	$3 - 6$ weeks	Pyloric or bowel scarring leading to obstruction.

Serum iron levels should be drawn $4 - 6$ hours post-ingestion in symptomatic patients or those with a history of a massive exposure.
A serum iron concentration $< 350$ $μ$ g/dL at $4 - 8$ hours suggests a low risk for significant toxicity.
A serum iron concentration of $350 - 500$ $μ$ g/dL indicates moderate toxicity.
A serum iron concentration $> 500$ $μ$ g/dL signifies that significant, life-threatening toxicity is likely.
Routine laboratory evaluation must include an arterial or venous blood gas, lactate, complete blood count, serum glucose, liver transaminases, and coagulation parameters.
Iron poisoning classically presents with an elevated anion gap metabolic acidosis (part of the MUDPILES mnemonic).
An abdominal radiograph (KUB) should be obtained as it may reveal radiopaque iron tablets (part of the CHIPPED mnemonic), although the absence of radiopacities does not rule out iron ingestion.

Activated charcoal does not bind to elemental iron and is entirely ineffective for gastrointestinal decontamination in this setting.
Whole-bowel irrigation (WBI) is the definitive decontamination strategy of choice for iron ingestion, serving to mechanically flush unabsorbed iron pills from the gastrointestinal tract.
Hemofiltration may be considered as an adjunctive method to remove iron from the systemic circulation.

Deferoxamine is the specific chelating antidote utilized for moderate to severe iron intoxication.
The deferoxamine-iron complex is excreted in the urine, classically imparting a reddish ("vin rosé") discoloration, though the intensity of this color should not be used to guide or terminate therapy.
Therapy is maintained until clinical symptoms resolve and the metabolic acidosis is fully corrected.

Antidote Parameter	Guidelines for Deferoxamine Administration
Indications	Serum iron concentration $> 500$ $μ$ g/dL OR the presence of moderate to severe symptoms (e.g., metabolic acidosis, lethargy) regardless of the serum iron level.
Dosage	Continuous intravenous infusion initiated at $15$ mg/kg/hr (maximum dose: $6$ g/24 hr).
Adverse Effects	Hypotension (which can be mitigated by titrating the dose up slowly).
Complications of Prolonged Use	Infusions lasting $> 24$ hours are associated with acute respiratory distress syndrome (ARDS) and Yersinia sepsis.