Iron

Pathophysiology

The primary mechanism for iron-induced tissue damage is free radical production and lipid peroxidation 

• Local toxicity: mucosal damage to GI mucosa leading to pain, vomiting, diarrhea, GI bleeds

• Systemic toxicity: damage to the cardiovascular system and liver leading to shock, liver failure, and multiorgan dysfunction.

Toxic Dose:

• <20 mg/kg of elemental iron are often asymptomatic

• >60 mg/kg of elemental iron can be associated with serious toxicity

Common examples: Adult ferrous sulfate tablets and prenatal vitamins

Presentation

• GI phase (30 min - 6 hours ): Abdominal pain, vomiting, diarrhea, hematemesis, and/or melena

  If no GI symptoms develop within six hours of a presumed iron ingestion, it is unlikely that iron toxicity will occur. Ingestion of enteric-coated iron tablets is an exception to the "six-hour rule.”

• Latent phase (6 - 24 hours): Period of apparent recovery

  Important to not mistake these patients for those with resolved or asymptomatic ingestions as they can continue to clinically deteriorate. Monitor for signs of developing shock and acidosis.

• Shock and metabolic acidosis phase (6 - 72 hours): Shock can be hypovolemic (fluid/blood loss), distributive (iron can increase capillary leak and vasodilation), or cardiogenic

  Monitor for multisystem organ failure:

  - GI hemorrhage leading to bowel perforation

  - Acute lung injury and ARDS

  - Coagulopathy may worsen bleeding and hypovolemia

  - Renal and neurologic dysfunction (lethargy, coma)

• Hepatoxicity phase (12 - 96 hours): Hepatic necrosis

• Bowel obstruction phase (2 - 8 weeks after ingestion): Results from GI scarring, typically in gastric outlet

  Consider in patients returning to the ED after iron ingestion with new vomiting.

Diagnosis

Consult Poison Control: 1800-222-1222

• Serum iron concentration (SIC) 4-6 hours after ingestion. Sustained release or enteric-coated preparations may have delayed absorption so repeat SIC at 6-8 hours

• CMP to assess electrolytes, liver, and renal function

• Consider blood gas, lactate, PT/PTT, T&S if concerned about acidosis or coagulopathy

• Screen for co-ingestions

• EKG

• Abdominal radiograph:  The presence of radiopaque pills in the stomach confirms the ingestion of iron and can help dictate if gastric decontamination is indicated. Be mindful of false negatives as not all formulations of iron will be radiopaque.

Management

1. IV fluid bolus and maintenance fluids

2. Gastric decontamination

1. Charcoal is NOT indicated in iron ingestions as it binds iron poorly

2. Whole bowel irrigation is indicated for patients with a large number of pills visualized on abdominal radiography

3. Deferoxamine: A chelating agent that binds ferric iron that is then renally excreted

   1. Indications:

      • SIC >500 mcg/dL

      • Elevated anion gap metabolic acidosis

      • Severe symptoms

      • Abdominal radiograph reveals a significant number of pills

   2. Adverse effects:

      • Hypotension during initial administration due to histamine release. Avoid by providing vigorous fluid resuscitation.

      • ARDS can develop in those who receive continuous infusions for >32 hours.

4. Monitoring

   1. Ingestions <60 mg/kg or those with a 4-6 hour iron level <500 mcg/dL may be observed for 6 hours and discharged if stable

   2. Ingestions <40 mg/kd do not require further evaluation or treatment unless significantly symptomatic or suicidal

References