Tox Talks

Originally Published: Modern Resident, Dec/Jan 2010

Submitted by: Saadiyah Bilal, Publications Committee, Co-Chair

Iron toxicity remains a common toxidrome in the emergency department and is the leading cause of pediatric overdose death under age 6. Its antidote, defuroxamine, was recently designated by the Antidote Summit Authorship Group (Ann Emerg Med, Sept. 2009) as a medicine recommended for availability within 60 minutes of every emergency department in the country.



A slew of media attention over pediatric overdoses in the early 1990s initially prompted a 1997 FDA mandate for single-pill packaging of all pills containing over 30mg of elemental iron. However, a 2003 challenge by the Nutritional Health Alliance (NHA), an association including manufacturers and distributers of dietary supplements, led the FDA to reverse their ruling. Iron supplements no longer require special packaging, nor carry overdose warnings.

Iron pills thus offer a readily-available method of intentional and unintentional overdose. Toxicity begins as 10-12mg/kg of elemental iron (not mg/kg of vitamin). Prenatal vitamins contain about 65mg elemental iron, while pediatric vitamins contain 15-20mg elemental iron.

Iron is a strong redox reagent. Acute toxicity progresses in five phases, with mild overdose typically occurring in the first phase. Phase one (0.5-2h) includes direct corrosive toxicity of the GI mucosa with abdominal pain, hematemesis and hematochezia. Phase two (6-24h) latency shows silent metabolic acidosis. Phase three (12-24h) is shock, secondary to severe necrosis, fluid loss and metabolic acidosis. This is when patients die. Phase four (2-3d) is hepatotoxicity. Phase five (2-8wk) is obstruction due to GI scarring.

Management is supportive, with abdominal X-ray (to look for pill fragments), serum iron levels and an ABG. Defuroxamine is indicated for serum iron >500µg/dL and/or symptoms of shock.
More key points:

• Activated charcoal does NOT WORK for metals.
• Liquid and chewable iron often DO NOT show up on X-ray. This does NOT exclude ingestion.
• Iron creates a gap acidosis (MUDPILES).
• Measure serum iron at 4-6 hours s/p ingestion (time of peak absorption).
• Use iron chelation by defuroxamine for shock or serum iron >500µg/dL.
• Defuroxamine is SAFE IN PREGNANCY. Neither it, nor iron, transfers to the fetus.

References:

1. Dart R, Borron S et al. "Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care." Ann of Em. Vol 54, No 3. Sept 2009.
2. Peronne, J. "Chap. 40: Iron" Goldfrank's Toxicologic Emergencies, 8th ed. 2006.