Treatment of Angioedema

Immediate Airway Assessment is the Absolute Priority

Assess for airway compromise immediately—this is the most critical first step in managing any patient with angioedema, as laryngeal involvement can be life-threatening. 1, 2

Monitor closely for signs of impending airway closure: change in voice, loss of ability to swallow, or difficulty breathing 1, 2
Consider elective intubation before complete airway obstruction occurs if any of these warning signs are present 1, 2
All patients with oropharyngeal or laryngeal involvement must be observed in a medical facility capable of performing emergency intubation or tracheostomy 1, 2
Avoid direct visualization of the airway unless absolutely necessary, as trauma from the procedure can worsen the angioedema 3, 1
Ensure immediate availability of backup tracheostomy equipment in case intubation is unsuccessful 3, 1

Rapidly Determine the Type of Angioedema

Treatment differs dramatically based on whether angioedema is histamine-mediated or bradykinin-mediated—this distinction is critical because standard allergy treatments are completely ineffective for bradykinin-mediated disease. 1, 2

Clinical Clues to Differentiate:

Histamine-Mediated (Allergic):

Concomitant urticaria (hives) present in approximately 50% of cases 1, 4
Pruritus (itching) is typically present 1
Acute onset after exposure to allergen (food, medication, insect sting) 4, 5
Responds to antihistamines and epinephrine 5

Bradykinin-Mediated:

Absence of urticaria and pruritus 1
History of ACE inhibitor use (most common cause) 1, 6
Family history of recurrent angioedema suggests hereditary angioedema (HAE) 1
Recurrent abdominal pain attacks or unexplained swelling episodes 1
Does NOT respond to antihistamines, corticosteroids, or epinephrine 1, 2, 7

Treatment Based on Angioedema Type

For Histamine-Mediated (Allergic) Angioedema:

Administer epinephrine immediately for significant symptoms or any airway involvement—do not delay. 1, 2

Epinephrine 0.3 mL of 0.1% solution (1:1000) subcutaneously OR 0.5 mL by nebulizer 1, 2
IV diphenhydramine 50 mg 1, 2
IV methylprednisolone 125 mg 1, 2
Add H2 blocker: ranitidine 50 mg IV OR famotidine 20 mg IV 1, 2

For chronic histaminergic angioedema without acute airway involvement:

High-dose second-generation H1 antihistamines (fourfold the standard dose) 2
Add montelukast if antihistamines alone fail 2

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

Standard allergy treatments (epinephrine, antihistamines, corticosteroids) are NOT effective—do not waste time with these interventions. 1, 2, 7

First-Line Treatments for HAE:

Plasma-derived C1 inhibitor concentrate 1000-2000 U (or 20 IU/kg) intravenously 1, 2, 7

Icatibant 30 mg subcutaneously in the abdominal area 1, 2, 7, 8

FDA-approved for acute HAE attacks in adults ≥18 years 8
If response is inadequate or symptoms recur, additional 30 mg injections may be given at intervals of at least 6 hours 8
Do not administer more than 3 injections in 24 hours 8
Patients may self-administer upon recognition of an HAE attack 8

Alternative if specific therapies unavailable:

Fresh frozen plasma (FFP) 10-15 mL/kg may be considered, though this is not ideal 1, 2, 7

For ACE Inhibitor-Induced Angioedema:

Immediately and permanently discontinue the ACE inhibitor—this is non-negotiable. 1, 2, 7

Consider icatibant 30 mg subcutaneously for severe or progressive symptoms 1, 2, 7
FFP may be used if icatibant or C1 inhibitor are unavailable 7
Never restart the ACE inhibitor—patients who react to one ACE inhibitor will typically react to all others (class effect) 7
Switching to an ARB carries a modest recurrence risk (2-17%), though most patients tolerate ARBs without recurrence 7

Supportive Care for All Types

Provide symptomatic management while definitive treatment takes effect:

Analgesics for pain control (especially for abdominal attacks) 1, 2
Antiemetics for nausea and vomiting 1, 2
Aggressive IV hydration due to third-space fluid sequestration during abdominal attacks 1, 2
Continuous monitoring of vital signs and neurological status 1
Avoid narcotic addiction risk in HAE patients with frequent attacks 1

Prophylaxis for HAE Patients

Short-Term Prophylaxis (Before Dental/Surgical Procedures):

Plasma-derived C1 inhibitor 1000-2000 U intravenously is first-line 2, 7

Alternative options when first-line unavailable:

Attenuated androgens (danazol 2.5-10 mg/kg for 5-10 days before procedure, maximum 200 mg) 3, 2, 7
Fresh frozen plasma 3, 2
Tranexamic acid 2

Long-Term Prophylaxis (For Frequent Attacks):

Androgens (danazol 100 mg on alternate days, titrated to lowest effective dose) 3, 2, 7
Tranexamic acid 30-50 mg/kg/day 2, 7
Regular monitoring required: blood testing and periodic hepatic ultrasounds for patients on attenuated androgens 2

Note: Anabolic androgens and antifibrinolytic drugs do NOT provide reliably effective treatment for acute attacks—they require several days to become effective and should not be used for acute management. 3

Special Populations

Children:

Tranexamic acid is the preferred drug for long-term prophylaxis where first-line agents are unavailable 1, 2
Fresh frozen plasma for acute treatment when first-line agents unavailable 2
Attenuated androgens may exceptionally be considered but side effect burden is likely high 2

Pregnant Patients:

C1-INH is the only recommended acute and prophylactic treatment for pregnant patients with HAE 1, 2

Elderly Patients:

Elderly patients demonstrate increased systemic exposure to icatibant, though differences in efficacy and safety between elderly and younger patients have not been identified 8

Critical Pitfalls to Avoid

Delaying epinephrine in histamine-mediated angioedema with airway involvement 1, 2
Using antihistamines, corticosteroids, or epinephrine for bradykinin-mediated angioedema—these are completely ineffective 1, 2, 7
Discharging patients with oropharyngeal or laryngeal involvement without adequate observation 1, 2
Failing to recognize that laryngeal attacks carry historical mortality rates of approximately 30% or higher if untreated 2
Restarting ACE inhibitors after ACE inhibitor-induced angioedema 7
Obtaining medication history too late—ask about ACE inhibitors immediately 1

Key Takeaway for Emergency Management

The treatment algorithm is straightforward: (1) Secure the airway first, (2) Determine if urticaria/pruritus is present, (3) If present → treat as histamine-mediated with epinephrine/antihistamines/steroids, (4) If absent → treat as bradykinin-mediated with C1 inhibitor or icatibant, NOT with standard allergy treatments. 1, 2, 7

What is the treatment for angioedema?

Help us tailor your experience