What is the treatment for acute angioedema?

Treatment of Acute Angioedema

The treatment of acute angioedema depends critically on determining whether it is histamine-mediated (allergic) or bradykinin-mediated, as these require completely different therapeutic approaches—standard allergy treatments (epinephrine, antihistamines, corticosteroids) are effective only for histamine-mediated angioedema and are completely ineffective for bradykinin-mediated forms such as hereditary angioedema (HAE) or ACE inhibitor-induced angioedema. 1

Immediate Airway Assessment (All Types)

Assess for airway compromise immediately—this is the single most critical first step regardless of angioedema type. 2, 3

• Monitor patients with oropharyngeal or laryngeal involvement in a facility capable of performing intubation or tracheostomy, as laryngeal attacks carry historical mortality rates approaching 30% without proper management 1, 2, 4
• Consider elective intubation if signs of impending airway closure develop: voice changes, inability to swallow, or difficulty breathing 1, 3
• Avoid direct visualization of the airway unless absolutely necessary, as instrumentation trauma can worsen angioedema 1, 3, 4
• Have backup tracheostomy equipment immediately available 3

Histamine-Mediated Angioedema (Allergic)

For histamine-mediated angioedema with significant symptoms or any airway involvement, administer intramuscular epinephrine 0.3 mL (0.1%) immediately—this is the cornerstone of treatment. 2, 3

• Give IV diphenhydramine 50 mg and IV methylprednisolone 125 mg as adjunctive therapy 2, 3
• Add H2 blockers: ranitidine 50 mg IV or famotidine 20 mg IV 2, 3
• For chronic management, use high-dose second-generation H1 antihistamines (fourfold the standard dose), adding montelukast if antihistamines alone fail 1, 2

Clinical clue: Histamine-mediated angioedema typically presents with accompanying urticaria and pruritus. 1, 4

Bradykinin-Mediated Angioedema (HAE and ACE Inhibitor-Induced)

For hereditary angioedema attacks, administer plasma-derived C1 inhibitor concentrate (1000-2000 U IV), icatibant 30 mg subcutaneously, or ecallantide as first-line therapy—these are the only effective treatments. 1, 2, 3

FDA-Approved On-Demand Treatments for HAE

• Icatibant (bradykinin B2 receptor antagonist): 30 mg subcutaneously in the abdominal area; may repeat at 6-hour intervals if inadequate response or symptom recurrence; maximum 3 injections in 24 hours 5
• Plasma-derived C1 inhibitor concentrate: 1000-2000 U intravenously 1, 2
• Ecallantide (plasma kallikrein inhibitor): Available as alternative 1

Critical pitfall: Epinephrine, corticosteroids, and antihistamines have NO significant effect on bradykinin-mediated angioedema and waste critical time. 1, 2

ACE Inhibitor-Induced Angioedema

• Immediately discontinue the ACE inhibitor permanently 2, 3, 4
• Consider icatibant 30 mg subcutaneously as bradykinin pathway-targeted therapy 2, 3
• Never rechallenge with ACE inhibitors; consider alternative antihypertensives 4, 6

When Specific Therapies Unavailable

Fresh frozen plasma (10-15 mL/kg) may be used if specific targeted therapies are unavailable, but be prepared for paradoxical worsening of symptoms due to provision of additional contact system substrates. 1, 2

• Fresh frozen plasma contains C1INH but also provides plasma prekallikrein, factor XII, and high-molecular-weight kininogen, which can trigger additional bradykinin generation 1
• Viral transmission risk is an additional concern 1

Symptomatic Management

For abdominal attacks, provide aggressive IV hydration (to address third-space fluid sequestration), antiemetics for nausea/vomiting, and appropriate analgesia. 1, 2

• Avoid out-of-hospital use of potent narcotics (fentanyl patches, oxycodone) due to addiction risk in patients with frequent attacks 1
• Extremity attacks may be disabling but have no specific symptomatic therapy 1

Observation and Disposition

Observe patients with oropharyngeal or laryngeal involvement until symptoms significantly improve—never discharge without adequate observation period. 1, 3, 4

• Duration of observation should be individualized based on attack severity and location 1
• Attacks typically worsen progressively for 24 hours, then remit over 48-72 hours 1

Special Populations

Pediatric Patients

• Tranexamic acid is the preferred long-term prophylaxis in children where first-line C1-INH replacement is unavailable 2, 4
• Weight-based epinephrine dosing for histamine-mediated angioedema 4
• Attenuated androgens carry high side effect burden in children and should be avoided except in exceptional circumstances 2, 4

Pregnant Patients

C1-INH concentrate is the only recommended acute and prophylactic treatment for pregnant patients with HAE. 2, 3

Critical Pitfalls to Avoid

• Never delay epinephrine in histamine-mediated angioedema with airway involvement 3, 4
• Never use standard allergy treatments for confirmed or suspected bradykinin-mediated angioedema—they are completely ineffective 1, 2, 4
• Never discharge patients with oropharyngeal or laryngeal involvement prematurely 1, 3, 4
• Never prescribe ACE inhibitors to patients with any history of angioedema 4, 6

Long-Term Prophylaxis for HAE Patients

• Attenuated androgens (danazol 100 mg on alternate days) for patients with frequent attacks 1, 2
• Tranexamic acid (30-50 mg/kg/day) where first-line treatments unavailable 1, 2
• Regular monitoring with blood tests and hepatic ultrasounds for patients on attenuated androgens 2
• Short-term prophylaxis with C1-INH concentrate (1000-2000 U IV) before dental or surgical procedures 2, 4