Treatment and Management of Angioedema
Immediate Airway Assessment is the Absolute Priority
Assess for airway compromise immediately upon presentation, as this is the most critical first step in managing any patient with angioedema. 1, 2 Patients with oropharyngeal or laryngeal involvement must be monitored in a facility capable of performing intubation or tracheostomy. 1, 2
Signs Requiring Elective Intubation
- Change in voice or hoarseness 1, 3
- Loss of ability to swallow 1
- Difficulty breathing or dyspnea 1, 3
- Inspiratory stridor 4, 3
Avoid direct visualization of the airway unless absolutely necessary, as trauma from the procedure can worsen angioedema. 1 Ensure backup tracheostomy equipment is immediately available if intubation is unsuccessful. 1
Rapidly Differentiate Angioedema Type
The presence or absence of urticaria is the key clinical differentiator that determines treatment approach. 1 Treatment for histamine-mediated versus bradykinin-mediated angioedema is completely different, and using the wrong approach can be fatal. 1, 2, 5
Histamine-Mediated Angioedema Features
- Urticaria present in approximately 50% of cases 1, 6
- Pruritus present 1
- Rapid onset (minutes) 1
- Associated with known allergen exposure (foods, medications, insect stings) 6
Bradykinin-Mediated Angioedema Features
- Absence of urticaria and pruritus 1
- Slower onset (hours) 1
- Current or recent ACE inhibitor use 1, 7
- Recurrent abdominal pain attacks 1
- Family history of recurrent angioedema 1
Treatment Based on Angioedema Type
Histamine-Mediated Angioedema
For significant symptoms or any airway involvement, administer epinephrine (0.1%) 0.3 mL intramuscularly or 0.5 mL by nebulizer immediately. 8, 1, 2 This is the single most important intervention for histamine-mediated angioedema with airway compromise. 1
Additional first-line medications:
- IV diphenhydramine 50 mg 1, 2
- IV methylprednisolone 125 mg 1, 2
- H2 blockers: ranitidine 50 mg IV or famotidine 20 mg IV 1, 2
For chronic management without airway involvement:
- Second-generation H1 antihistamines at 2-4 times the standard FDA-approved dose 1, 2
- Add montelukast if antihistamines alone fail 2, 9
- Avoid first-generation antihistamines due to sedation and cognitive decline, particularly in elderly patients 1
Bradykinin-Mediated Angioedema (Hereditary or ACE Inhibitor-Induced)
Standard angioedema treatments (epinephrine, corticosteroids, antihistamines) are completely ineffective for bradykinin-mediated angioedema and should NOT be used. 1, 2, 9, 4, 5 This is the most common treatment error in emergency settings. 9
First-line treatment options:
Plasma-derived C1 inhibitor concentrate 1000-2000 U (or 20 IU/kg) intravenously is the preferred treatment, with median time to initial symptom relief of 0.25 hours and complete resolution at 8.4 hours. 1, 2, 9
Icatibant 30 mg subcutaneously in the abdominal area provides rapid symptom relief by directly blocking bradykinin B2 receptors. 1, 2, 10 This is FDA-approved for acute attacks of hereditary angioedema in adults 18 years and older. 10 If response is inadequate or symptoms recur, additional 30 mg injections may be administered at intervals of at least 6 hours, with a maximum of 3 injections in 24 hours. 10
Fresh frozen plasma 10-15 mL/kg may be considered if specific targeted therapies are unavailable, but use with caution as it can paradoxically worsen some attacks. 1, 2
ACE Inhibitor-Induced Angioedema Specific Management
Immediately discontinue the ACE inhibitor permanently. 1, 2 Symptoms can recur for weeks to months after discontinuation. 1
Do not substitute an ARB, as cross-reactivity can occur and safety is uncertain. 1
Consider icatibant 30 mg subcutaneously or tranexamic acid 1g every 6 hours for severe cases. 1, 4
Prophylaxis for Hereditary Angioedema Patients
Short-Term Prophylaxis (Before Dental/Surgical Procedures)
Administer plasma-derived C1 inhibitor 1000-2000 U intravenously before procedures as first-line prophylaxis. 1, 2 Without prophylaxis, risk of angioedema after dental extraction is 21.5% and after non-dental surgical procedures is 5.7%. 1
Alternative options when first-line unavailable:
- Attenuated androgens (danazol 2.5-10 mg/kg for 5-10 days before procedure, maximum 200 mg) 1, 2
- Tranexamic acid 2
- Fresh frozen plasma 1
Long-Term Prophylaxis (For Frequent Attacks)
Consider long-term prophylaxis when attack frequency, severity, or location significantly impacts quality of life despite on-demand therapy. 1
Options include:
- Androgens (danazol 100 mg on alternate days, titrated to lowest effective dose) 1, 2, 9
- Tranexamic acid 30-50 mg/kg/day 1, 2
- Plasma-derived C1-INH 1
Patients on attenuated androgens require regular monitoring with blood testing and periodic hepatic ultrasounds. 1
Special Populations
Pregnant Patients
C1-INH is the only recommended acute and prophylactic treatment for pregnant patients with hereditary angioedema. 1, 2 Attenuated androgens are contraindicated due to potential side effects. 1
Children
Tranexamic acid is the preferred drug for long-term prophylaxis in children where first-line agents are unavailable. 1, 2
Women with Hereditary Angioedema
Avoid estrogen-containing birth control pills and estrogen replacement therapy, as they increase attack frequency. 1 Recommend barrier methods, intrauterine devices, or progestins instead. 1
Critical Pitfalls to Avoid
Never delay epinephrine administration in histamine-mediated angioedema with airway compromise. 1 Patients at risk should carry an epinephrine autoinjector. 8
Never use antihistamines, corticosteroids, or epinephrine for bradykinin-mediated angioedema—they are completely ineffective. 1, 2, 9, 4, 5
Never discharge patients with oropharyngeal or laryngeal involvement without adequate observation. 1 Laryngeal attacks are potentially life-threatening with historical mortality rates of approximately 30% or higher. 2, 9
Never substitute an ARB for an ACE inhibitor in patients who developed ACE inhibitor-induced angioedema. 1
ACE inhibitors can cause angioedema even after long-term use—do not dismiss the diagnosis based on duration of therapy. 7 ACE inhibitors account for 39% of angioedema cases presenting to emergency departments. 3