What is the treatment approach for a patient with suspected iron toxicity, considering factors such as age, weight, and medical history?

Treatment of Iron Toxicity

Immediate Assessment and Risk Stratification

For acute iron poisoning, patients who have ingested ≥40 mg/kg of elemental iron or who exhibit severe symptoms (persistent vomiting/diarrhea, altered consciousness, hematemesis, bloody diarrhea) require immediate referral to an acute care facility for chelation therapy with deferoxamine. 1

Key Clinical Decision Points

Serum iron concentration measured 4-6 hours post-ingestion is the most critical laboratory test for determining toxicity and need for treatment. 2, 3

• Iron concentrations ≥350 μg/dL with symptoms, or ≥500 μg/dL without symptoms, are considered toxic and require deferoxamine treatment 3
• Patients with only minor GI symptoms and iron concentration ≤300 μg/dL at 2-4 hours post-ingestion are unlikely to develop further toxicity (negative predictive value 100%) 3
• Serum iron levels should be obtained at least 4 hours after exposure to allow adequate absorption time 3

Symptom-Based Triage

Patients with mild symptoms (nausea, vomiting, diarrhea without systemic toxicity) and ingestion <40 mg/kg can be observed at home with appropriate follow-up. 1

• Severe or persistent symptoms warrant immediate hospital referral regardless of estimated dose 1
• Asymptomatic patients beyond 6 hours post-ingestion are unlikely to develop symptoms and do not require prolonged observation 1

Acute Iron Intoxication Treatment Protocol

Deferoxamine Administration

Deferoxamine is the definitive antidote for iron toxicity and should be initiated promptly in patients meeting treatment criteria. 4

For Patients in Cardiovascular Collapse:

• Intravenous route ONLY for patients in shock 4
• Initial dose: 1000 mg IV at rate NOT exceeding 15 mg/kg/hr 4
• Subsequent doses: 500 mg over 4 hours for two doses 4
• Additional doses of 500 mg may be given over 4-12 hours based on clinical response 4
• Maximum daily dose: 6000 mg in 24 hours 4
• Switch to intramuscular administration as soon as cardiovascular stability permits 4

For Hemodynamically Stable Patients:

• Intramuscular route is preferred for all patients NOT in shock 4
• Initial dose: 1000 mg IM 4
• Follow with 500 mg IM every 4 hours for two doses 4
• Subsequent doses of 500 mg every 4-12 hours depending on clinical response 4
• Maximum daily dose: 6000 mg in 24 hours 4

Critical Infusion Rate Warning

The IV infusion rate must not exceed 15 mg/kg/hr for the first 1000 mg; subsequent dosing must be slower, not exceeding 125 mg/hr. 4 Rapid infusion can cause hypotension and cardiovascular collapse.

Adjunctive Supportive Measures

Deferoxamine is an adjunct to standard supportive care, not a replacement. 4

• Maintain clear airway and adequate ventilation 4
• Control shock with IV fluids, blood products, oxygen, and vasopressors as needed 4
• Correct metabolic acidosis aggressively 5, 6
• Replace blood components if gastrointestinal hemorrhage occurs 5
• Monitor and correct coagulation disorders 5

Advanced Interventions for Severe Cases

In life-threatening toxicity with massive overdose, hemodialysis may assist in decreasing serum iron concentration when combined with deferoxamine. 6 One case report demonstrated reduction of serum iron from 2150 to 160 mcg/dL at 24 hours with combined DFO and hemodialysis. 6

• Surgical removal of iron tablets may be indicated in rare circumstances when large numbers of tablets are visible in the GI tract 5
• Exchange transfusion should be reserved for unusual poisonings where conservative therapy fails 5

Chronic Iron Overload Treatment

Hereditary Hemochromatosis

Therapeutic phlebotomy is the first-line treatment for hereditary hemochromatosis and should be initiated once diagnosis is confirmed. 7, 8

Phlebotomy Protocol:

• Remove 500 mL blood weekly or biweekly 7
• Check hematocrit/hemoglobin prior to each phlebotomy 7
• Allow hematocrit/hemoglobin to fall by no more than 20% of prior level 7
• Check serum ferritin every 10-12 phlebotomies 7
• Stop frequent phlebotomy when serum ferritin reaches 50-100 μg/L 7
• Continue maintenance phlebotomy at intervals to keep ferritin between 50-100 μg/L 7

Treatment should be initiated before development of cirrhosis or diabetes to normalize survival. 9 Phlebotomy is not indicated for primary hemochromatosis in patients already having iron deficiency, as this should be avoided. 7

Transfusion-Dependent Iron Overload

Iron chelation therapy is indicated for secondary iron overload due to chronic transfusions. 7, 8, 4

Chelation Options:

Deferoxamine (subcutaneous):

• Daily dose: 1000-2000 mg (20-40 mg/kg/day) over 8-24 hours via portable pump 4
• Duration of infusion must be individualized 4
• In children, average doses should not exceed 40 mg/kg/day until growth ceases 4
• In adults, average doses should not exceed 60 mg/kg/day 4

Deferasirox (oral):

• Starting dose: 14 mg/kg/day for transfusional iron overload 8
• Continue as long as transfusions are needed and iron overload remains clinically relevant 8

Deferiprone:

• Demonstrates superior cardiac iron clearance compared to deferoxamine (2.2% per month vs. 1.1-2.2%) 7
• Recommended dose: 92 mg/kg/day 7
• Particularly effective for cardiac siderosis 7

Combination therapy with subcutaneous deferoxamine plus oral deferiprone (both drugs taken together daily) has been used extensively for long-term management of patients with impaired left ventricular function. 7

Cardiac Iron Overload Management

Patients with cardiac T2 <6 ms have a 47% risk of developing heart failure within 1 year and should be treated similarly to those with overt heart failure.* 7

• Cardiac T2* between 6-10 ms warrants intensified chelation therapy 7
• Cardiac T2* between 10-20 ms can be managed with dose modifications or alternative chelators 7
• Cardiac iron clears slowly with half-life of approximately 13.5 months during continuous IV deferoxamine 7
• Treatment must continue for several years with regular T2* and cardiac function monitoring 7

Critical Pitfalls to Avoid

Do NOT use ipecac syrup, activated charcoal, cathartics, or oral complexing agents (bicarbonate, phosphate solutions) in iron poisoning management. 1 These interventions are ineffective and may delay definitive treatment.

Avoid supplemental vitamin C in iron-loaded patients, particularly those undergoing phlebotomy. 7 Vitamin C accelerates iron mobilization to levels that may saturate transferrin, increasing pro-oxidant activity and risk of sudden death in patients with cardiac involvement.

Do not administer deferoxamine concurrently with blood transfusion. 4 This can lead to errors in interpreting side effects such as rash, anaphylaxis, and hypotension.

Avoid excessive diuresis in elderly patients with heart failure and preserved ejection fraction during iron removal. 7

Monitoring Requirements

For acute iron toxicity:

• Serial serum iron concentrations 3
• Complete blood count and coagulation studies 5
• Arterial blood gas for metabolic acidosis 6
• Liver function tests 5

For chronic iron overload:

• Serum ferritin every 10-12 phlebotomies (do not check earlier than 8-10 weeks after IV iron infusion as ferritin is falsely elevated) 7
• Liver MRI (T2*) to quantify hepatic iron concentration 8
• Cardiac MRI (T2*) if signs of heart disease or markedly elevated ferritin 8
• Echocardiogram if cardiac symptoms present 8

Special Populations

Pregnant women: Use the same 40 mg/kg threshold for referral, but calculate dose using pre-pregnancy weight 1

Children with chewable vitamins plus iron: Observe at home; diarrhea from sorbitol should not prompt referral unless severe dehydration occurs 1

Patients with carbonyl iron or polysaccharide-iron complex ingestions: Observe at home with follow-up 1

Patients under age 3 with minimal iron overload: Deferoxamine should not be given unless significant iron mobilization (≥1 mg/day) can be demonstrated 4