Iron Toxicity

• Can cause Vin-rose urine due to the treatment of iron toxicity with deferoxamine
• Iron overdose is one of the leading causes of death from toxicologic agents in children younger than 6 years.
• Iron is most often available in ferrous sulfate tablets containing 20% elemental iron.
• Other formulations include ferrous gluconate with 12% elemental iron and ferrous fumarate with 33% elemental iron.

Clinical
 

• ingestions <20 mg/kg are often asymptomatic and do not require treatment.
• Doses of 20-60 mg/kg cause moderate symptoms.
• Ingestions of >60 mg/kg produce severe toxicity and are often lethal without therapy.
• Serum iron levels should be measured at least 4 hours after the ingestion.
• Levels obtained more than 6 hours after ingestion may lead to an underestimation of the toxicity because of the binding and redistribution of ferritin.
• Mild-to-moderate toxicity generally manifests at levels of 350-500 mcg/dL.
• Hepatotoxicity is usually observed at levels >500 mcg/dL, and levels >800 mcg/dL are associated with severe toxicity.

Course

• The clinical course of patients with iron toxicity is often described in 4 phases, though patients rarely progress through all of these stages.
• Phase I occurs within the first 6 hours of ingestion and is due to the acute corrosive effects of iron. This phase is characterized by GI symptoms, such as nausea, vomiting, and diarrhea, with hematemesis and hematochezia in some patients. Blood loss accompanied by third-space effects leads to hypotension and shock, with their concomitant risk of mortality.
• In phase II, patients often appear to improve, and their vital signs normalize until approximately 12-48 hours after the ingestion.
• During phase III, patients often begin to have dramatic systemic effects, including lethargy, coma, hypotension, anion-gap metabolic acidosis, acute renal failure, and coagulopathy. Rarely, approximately 2-5 days after ingestion, patients may have acute hepatic failure, a delayed complication of phase III characterized by jaundice, encephalopathy, coagulopathy, elevated transaminase levels, and hypoglycemia.
• Finally, phase IV leads to long-term complications from the corrosive effects of iron on the intestinal mucosa. Scarring, stricture formation, and gastric outlet obstruction are observed 2-6 weeks after ingestion.

Treatment

• Although vomiting might be induced with syrup of ipecac if the ingestion is known to have occurred within 2 hours of presentation, this modality of decontamination, as well as gastric lavage and use of activated charcoal, is relatively ineffective.
  Whole-bowel irrigation, and potentially surgery for refractory cases, should be considered if iron tablets or a clump of iron is noted on plain radiographs.
• The specific antidote for most moderate-to-severe cases is deferoxamine, a chelator that binds the ferric ion and promotes the elimination of iron by forming ferrioxamine, a water-soluble compound that is excreted in the urine.
• Indications for its use are based on clinical and laboratory parameters and include shock, altered mental status, persistent GI symptoms, metabolic acidosis, iron pills visible on radiographs, serum iron level >500 mcg/dL, or estimated dose >60 mg elemental iron per kilogram of body weight.
• Chelation therapy should be started if a serum iron level is not available or if it is deemed unreliable and the patient has symptoms.

Vin rose urine

• Excretion of the deferoxamine-iron complex results in pink-red urine that is classically called vin-rose urine.
• The urine collected in the tubes demonstrates progression of the color change over 16 hours in the child in this case, who was treated with intravenous deferoxamine 15 mg/kg/h given over this period.
• despite having toxic serum levels of iron, 30% of patients do not demonstrate the classic vin-rose urine.
•  Before deferoxamine treatment is started, one must obtain a baseline urine sample for comparison. A change to pink-red is considered a positive sign.

Endpoint for cessation of therapy

• is clinically significant resolution of the patient's shock and/or acidosis (usually in 8-12 h and <24 h).
• is when the color of the patient's urine returns to normal.
• Prolonged treatment with deferoxamine has been associated with adult respiratory distress syndrome, but this usually occurs only if the agent is administrated for >24 hours.
• Therefore, consultation with a pharmacologist and a regional poison center (see American Association of Poison Control Centers) are advised to obtain dosing recommendations.
• Patients should be observed for the recurrence of toxicity 2-3 hours after deferoxamine therapy is stopped.

References
Clark K. Toxicity, iron. eMedicine Journal [serial online]. 2005. Available at: http://www.emedicine.com/ped/topic2835.htm.
Spanierman C. Toxicity, iron. eMedicine Journal [serial online]. 2005. Available at: http://www.emedicine.com/emerg/topic285.htm.