What is the management of angioedema in a patient?

Management of Angioedema

Immediate Airway Assessment and Stabilization

All patients with oropharyngeal or laryngeal angioedema must be monitored in a facility capable of performing emergency intubation or tracheostomy, as airway compromise is the primary life-threatening concern. 1, 2, 3

• Early intubation or tracheotomy should be considered at the first signs of upper airway involvement, including voice changes, difficulty swallowing, or breathing difficulty 1
• Patients with upper airway angioedema require continuous observation even after initial stabilization 4
• Endotracheal intubation is generally preferred over tracheostomy for temporary airway management, though tracheostomy may be necessary for definitive control 4

Determine the Type of Angioedema

Histamine-Mediated vs Bradykinin-Mediated

The presence or absence of urticaria and pruritus is the key clinical differentiator—histamine-mediated angioedema typically presents with both, while bradykinin-mediated does not. 5, 6

• Histamine-mediated angioedema has rapid onset (minutes), often with urticaria, pruritus, and responds to epinephrine, antihistamines, and corticosteroids 5, 6
• Bradykinin-mediated angioedema has slower onset (hours), no urticaria, often presents with abdominal symptoms, and does NOT respond to standard anaphylaxis treatment 5, 6
• Medication history is critical: ACE inhibitors cause angioedema in <1% of patients (more common in Black patients and women), while ARBs have 2-17% cross-reactivity 1, 2, 3

Treatment Based on Mechanism

For Histamine-Mediated Angioedema

Initial treatment should follow standard anaphylaxis protocols with epinephrine, antihistamines, and systemic corticosteroids. 5, 6

• Epinephrine is first-line therapy 5, 7
• H1-antihistamines (diphenhydramine) should be administered 7
• Intravenous methylprednisolone for inflammatory control 7

For Bradykinin-Mediated Angioedema (HAE or ACE Inhibitor-Induced)

Standard anaphylaxis treatments (epinephrine, antihistamines, corticosteroids) are NOT effective and should not be relied upon for bradykinin-mediated angioedema. 1, 2, 5

First-Line Targeted Therapies (in order of preference):

1. Plasma-derived C1-INH concentrate (Berinert): 20 U/kg IV, most effective when given within 6 hours of attack onset 1, 8
2. Icatibant (bradykinin B2 receptor antagonist): subcutaneous injection, approved for acute HAE attacks 1, 2, 5
3. Ecallantide (plasma kallikrein inhibitor): approved for acute HAE attacks, cannot be self-administered 1

Alternative Therapy When First-Line Agents Unavailable:

Fresh frozen plasma (FFP) 10-15 ml/kg can be used if targeted therapies are unavailable, though response is slower and carries risk of transfusion reactions and viral transmission. 1, 2, 5

• FFP contains approximately 1 unit/ml of C1-INH 1
• Median time to symptom resolution is 4 hours (range 2-12 hours) 1
• 5% of patients experience transfusion reactions, including rare severe anaphylaxis 1
• FFP can occasionally worsen symptoms acutely 1, 5

Specific Management for ACE Inhibitor-Induced Angioedema

Immediately discontinue the ACE inhibitor permanently—all ACE inhibitors are contraindicated for life after confirmed ACE inhibitor-induced angioedema. 1, 2, 3, 5

• ARBs may be considered as alternative therapy, but use extreme caution as 2-17% of patients develop angioedema with ARBs after ACE inhibitor angioedema 2, 3
• Beta-blockers like atenolol are safe to continue as they do not interact with the bradykinin pathway 2
• Targeted therapies (icatibant, FFP) may be considered for acute management, though evidence is variable and they are not currently formally recommended 5, 6

Supportive Care for Abdominal Attacks

Aggressive intravenous hydration is essential for abdominal attacks due to third-space fluid sequestration that can cause significant hypotension. 1

• Narcotic analgesics may be necessary for severe pain control 1
• Antiemetics for nausea and vomiting 1
• Avoid out-of-hospital use of potent narcotics (fentanyl patches, oxycodone) due to addiction risk 1

Long-Term Prophylaxis Considerations

All HAE patients should have access to on-demand treatment for self-administration at home, as early treatment (within 2-6 hours of onset) significantly improves outcomes. 1

• Self-administration reduces time to treatment from 3.4 hours to 1.4 hours and halves time to complete resolution 1
• Any attack with potential to interfere with activities of daily living or become moderate-to-severe should be treated early 1
• Long-term prophylaxis options include plasma-derived C1-INH, berotralstat (oral), or lanadelumab (subcutaneous) 9

Common Pitfalls to Avoid

• Do not rely on antihistamines, corticosteroids, or epinephrine alone for bradykinin-mediated angioedema 1, 2, 5
• Do not use attenuated androgens or antifibrinolytic agents for acute attacks—they are ineffective 1
• Do not delay airway management while waiting for pharmacologic treatment to work 1
• Do not restart ACE inhibitors after confirmed ACE inhibitor-induced angioedema 1, 3, 5