Can intravenous (IV) iron replacement cause pulmonary issues during infusion?

Can IV Iron Cause Pulmonary Issues During Infusion?

Yes, IV iron can cause respiratory symptoms during infusion, including shortness of breath, transient cough, bronchospasm, and stridor, though these are uncommon and typically occur as part of a hypersensitivity reaction rather than isolated pulmonary disease. 1

Mechanism of Respiratory Reactions

The respiratory symptoms that occur during IV iron infusion are primarily due to complement activation-related pseudo-allergy (CARPA) rather than true IgE-mediated allergic reactions. 1, 2 This is a critical distinction because:

• CARPA reactions are caused by labile free iron released from the iron carbohydrate nanoparticle, which activates complement and triggers mast cell degranulation without requiring prior sensitization 1
• These reactions occur most frequently at the beginning of infusion and are usually self-limited 1
• True IgE-mediated anaphylaxis with severe respiratory compromise is extremely rare 2, 3

Classification of Respiratory Symptoms by Severity

Moderate Hypersensitivity Reactions

Respiratory symptoms in this category include: 1

• Transient cough
• Shortness of breath
• Often accompanied by tachycardia or hypotension (drop in systolic BP ≥30 mmHg from baseline or SBP ≤90 mmHg)

Severe/Life-Threatening Reactions

More concerning respiratory manifestations include: 1

• Stridor (indicating airway compromise)
• Bronchospasm (wheezing)
• Angioedema of tongue and/or airway
• Involvement of respiratory system as part of multi-organ anaphylaxis

Management Algorithm

During Infusion - If Respiratory Symptoms Develop:

Immediate Actions: 1, 4

1. STOP the infusion immediately
2. Switch IV line to normal saline at keep-vein-open (KVO) rate
3. Notify physician
4. Monitor vital signs continuously (BP, pulse, respiratory rate, O2 saturation, temperature)

For Moderate Respiratory Symptoms (transient cough, shortness of breath): 1, 4

• Monitor for ≥15 minutes while maintaining IV normal saline at KVO
• Consider IV hydrocortisone 100-500 mg
• Consider IV famotidine 20 mg
• If hypoxemic, administer oxygen by mask or nasal cannula
• If hypotensive, recline patient and administer NS bolus 1000-2000 mL

For Severe Respiratory Symptoms (stridor, bronchospasm, angioedema): 1, 4

• Immediately call emergency services or resuscitation team
• Administer EPINEPHRINE (1 mg/mL) 0.3 mg IM into anterolateral mid-third of thigh
• Consider β2 agonist nebulizer (Albuterol 0.083%)
• Administer oxygen
• Treat as anaphylaxis with full resuscitation protocols

Risk Factors for Respiratory Reactions

Patients at higher risk include those with: 1, 5

• History of severe asthma or eczema
• Mastocytosis
• Multiple drug allergies
• Prior reaction to IV iron
• Fast infusion rates (slower rates are associated with lower reaction rates)

Prevention Strategies

Key preventive measures include: 1, 4, 5

• Use slower infusion rates - this is the most evidence-based prevention strategy, as faster rates are associated with higher reaction risk
• Observe closely during the first 10 minutes, as immediate reactions occur during the first minute 1
• Ensure proper IV line placement to avoid extravasation 4
• Consider alternative iron formulations if reactions occur, as different formulations have varying stability and labile iron content 1

Important Caveats

• Avoid first-generation antihistamines (like diphenhydramine) and vasopressors, as they can potentially convert minor infusion reactions into hemodynamically significant adverse events 4
• The majority (>80%) of IV iron rechallenges after previous reactions are tolerable and safe, with no reports of major reactions during re-exposure in studied populations 6
• Premedication use remains controversial with conflicting evidence on benefit 6, 5
• True isolated pulmonary disease (such as pulmonary fibrosis or chronic lung injury) from IV iron is not documented; respiratory symptoms occur acutely as part of hypersensitivity reactions 1