Can Deferoxamine Cause ARDS?
Yes, deferoxamine can cause acute respiratory distress syndrome (ARDS), particularly when administered as prolonged continuous intravenous infusions exceeding 24 hours or at excessively high doses. 1
FDA-Recognized Risk
The FDA drug label explicitly states that "acute respiratory distress syndrome has been reported following treatment with excessively high intravenous doses of deferoxamine mesylate in patients with acute iron intoxication and in patients with thalassemia." 1 This represents the highest level of evidence establishing this causal relationship.
Clinical Context and Risk Factors
The risk of deferoxamine-induced ARDS appears strongly linked to:
- Duration of continuous IV infusion: ARDS develops most commonly when deferoxamine is infused continuously for longer than 24 hours 2
- High infusion rates: Rates of 15 mg/kg/hour administered for 65-92 hours have resulted in fatal ARDS 2
- Total treatment duration: In one series, no patients treated for less than 24 hours developed pulmonary complications, but 4 of 14 patients treated longer than 24 hours developed ARDS 2
Mechanism and Clinical Presentation
The pathophysiology likely involves free radical generation through prooxidant activity of the iron-deferoxamine complex, particularly at the alveolar surface. 3
Clinical features include:
- Onset typically 32-72 hours after starting continuous infusion 2
- Tachypnea and hypoxemia 4
- Diffuse interstitial pattern on chest radiograph 4
- Restrictive pulmonary dysfunction on testing 4
- Can progress to life-threatening respiratory failure 4
Critical Distinction: Acute Iron Poisoning vs. Chronic Iron Overload
This pulmonary toxicity risk creates a clinical paradox, as the American Heart Association guidelines recommend continuous 24-hour intravenous deferoxamine at 50 mg/kg/day for cardiac decompensation in thalassemia patients, with treatment potentially continuing for months. 5 However, this recommendation applies to chronic iron overload with cardiac failure, where the benefit-risk calculation differs from acute iron poisoning.
For acute iron poisoning specifically, the evidence strongly suggests limiting continuous IV deferoxamine to no more than 24 hours to minimize ARDS risk. 2, 6
Practical Recommendations to Minimize Risk
- Limit duration: Do not administer continuous IV deferoxamine for longer than 24 hours in acute iron poisoning 2
- Target initial chelation: Use adequate doses to chelate readily available serum iron during the first 24 hours without unnecessarily prolonging treatment 7
- Monitor respiratory status carefully: Watch for tachypnea, hypoxemia, and chest radiograph changes, particularly after 32+ hours of infusion 2, 4
- Consider route: For chronic iron overload requiring prolonged therapy, subcutaneous administration may be safer than continuous IV, though this still requires careful pulmonary monitoring 5
Additional Monitoring Considerations
Beyond ARDS risk, deferoxamine requires monitoring for other toxicities including hypotension with rapid IV bolus, visual and auditory disturbances, and increased infection risk (particularly Yersinia and Klebsiella). 8, 1