What are the phases of iron toxicity in a patient in the Intensive Care Unit (ICU)?

Phases of Iron Toxicity in the ICU

Iron toxicity progresses through five distinct clinical phases, with the most critical being the initial gastrointestinal phase (0-6 hours) and the potentially fatal hepatotoxic phase (2-5 days), requiring immediate recognition and aggressive chelation therapy with deferoxamine for severe cases.

Phase I: Gastrointestinal Phase (0-6 hours post-ingestion)

This initial phase is characterized by direct corrosive injury to the gastrointestinal mucosa 1:

• Nausea, vomiting, and diarrhea are the hallmark symptoms, occurring frequently even with mild ingestions 2
• Hematemesis and bloody diarrhea indicate severe toxicity requiring immediate referral 2
• Necrotizing gastroenteritis may develop in severe cases, potentially requiring blood transfusion 1
• Patients ingesting ≥40 mg/kg elemental iron with persistent or severe GI symptoms require immediate hospital evaluation 2

Critical pitfall: Mild GI symptoms alone should not delay assessment of severity—focus on dose ingested and presence of hematemesis or altered mental status 2.

Phase II: Latent Phase (6-24 hours post-ingestion)

This deceptively quiescent period represents temporary clinical improvement 1:

• Patients may appear to stabilize as GI symptoms resolve
• Asymptomatic patients beyond 6 hours post-ingestion are unlikely to develop subsequent toxicity and may not require prolonged observation 2
• However, this phase precedes potential cardiovascular collapse and should not be mistaken for recovery in patients with significant ingestions 1

Critical pitfall: Do not discharge patients with known large ingestions (>40 mg/kg) based solely on symptom resolution during this phase 2.

Phase III: Shock and Metabolic Acidosis Phase (12-48 hours post-ingestion)

This phase represents systemic iron toxicity with multi-organ involvement 1:

• Cardiovascular collapse and shock develop from direct myocardial toxicity and vasodilation 1
• Metabolic acidosis results from mitochondrial dysfunction and lactic acid accumulation 1
• Hyperglycemia and leukocytosis are common laboratory findings indicating severe toxicity 1
• Altered mental status progressing to coma may occur, as seen with serum iron levels >14,000 μg/dL 1
• Serum iron >500 μg/dL or exceeding total iron-binding capacity indicates severe toxicity requiring aggressive chelation 1

Management priority: Initiate continuous IV deferoxamine infusion immediately for severe cases, continuing for 48 hours or until serum iron normalizes 1. Phlebotomy is not indicated for acute iron poisoning 3.

Phase IV: Hepatotoxic Phase (2-5 days post-ingestion)

This phase carries the highest mortality risk 4:

• Acute liver failure with aminotransferases >4,000 U/L, elevated bilirubin, and coagulopathy (PT >50 seconds) 4
• Hepatotoxicity can occur even with serum iron levels as low as 340 μg/dL, far below the traditionally cited threshold of >1,700 μg/dL 4
• Mortality is high when hepatic injury develops 4
• Treatment includes deferoxamine plus empiric N-acetylcysteine once liver injury is apparent 4

Critical pitfall: Do not rely solely on peak serum iron levels to exclude hepatotoxicity risk—monitor liver function tests closely for 5 days post-ingestion 4.

Phase V: Late Sequelae Phase (2-8 weeks post-ingestion)

• Gastric outlet obstruction from scarring and stricture formation may develop 1
• Pyloric stenosis requiring surgical intervention can occur 1

ICU-Specific Considerations for Iron Load Toxicity

Chronic Iron Overload in Critically Ill Patients

While acute iron poisoning follows the phases above, ICU patients may also present with chronic iron toxicity 5, 6:

• Excess iron availability (high transferrin saturation, low transferrin levels) predicts mortality in ICU patients 5
• Transferrin saturation >55% and serum iron >10.5 μmol/mL are associated with poor short- and long-term survival 5
• Iron acts as a catalyst for free radical reactions (Fenton reaction), causing oxidative stress and multi-organ damage 6
• Ferroptosis (iron-dependent cell death) contributes to cardiac, kidney, liver, and other organ failures 6

Diagnostic Approach in ICU

• Serum iron levels should be measured immediately in suspected acute ingestion 1
• Abdominal radiographs can identify iron tablets in the GI tract 1
• Transferrin saturation and ferritin help assess chronic iron load in critically ill patients 5
• Liver function tests must be monitored for 5 days to detect hepatotoxicity 4

Treatment Algorithm for Acute Iron Toxicity in ICU

1. Immediate stabilization: Address shock with IV fluids and vasopressors; correct metabolic acidosis 1
2. GI decontamination: Gastric lavage with deferoxamine-bicarbonate solution for recent ingestions 1; whole-bowel irrigation with polyethylene glycol for visible tablets on imaging 1
3. Chelation therapy: Continuous IV deferoxamine for serum iron >500 μg/dL, severe symptoms, or metabolic acidosis 1
4. Supportive care: Packed red blood cells for GI bleeding; N-acetylcysteine if hepatotoxicity develops 1, 4
5. Avoid: Ipecac, activated charcoal, cathartics, and oral complexing agents are ineffective 2

Critical pitfall: In ICU patients with sepsis or active infection, use IV iron with extreme caution as animal studies suggest harm in the presence of severe infection 7. Iron chelation therapy may be beneficial in critically ill patients with evidence of excess iron availability 5.