Acute Angioedema

Updated: Aug 28, 2018
Author: Thomas E Green, DO, MPH, CPE, MMM, FACEP, FACOEP; Chief Editor: Erik D Schraga, MD 

Overview of Angioedema Treatment

The goals of emergency treatment of angioedema are to prevent spontaneous eruption, to maintain a patent airway if eruption does occur, and to stop progression of disease.[1] Laryngeal edema may occur rapidly. In these cases, a definitive airway such as an endotracheal tube should be established. If the airway cannot be effectively secured with an endotracheal tube, a surgical airway is indicated, usually in the form of an emergency cricothyrotomy.[2] Life-threatening airway obstruction (if swelling occurs in the throat) and anaphylactic reactions are possible complications.[3]

Treatment of angioedema includes histamine blockers (H1 and H2), steroids, and, in those with severe symptoms, epinephrine (intramuscular or subcutaneous).[4, 5] However, hereditary angioedema (HAE) is generally refractory to treatment with these drugs. Anabolic steroids (eg, danazol), a C1 esterase inhibitor, or a kallikrein inhibitor (ecallantide) may be used for the acute phase of an attack of HAE.

For more information on angioedema, see Acquired Angioedema, Hereditary Angioedema, and Pediatric Angioedema.

Patient education

A helpful resource for patients and their family members is the Hereditary AngioEdema Association.

For patient education information, see the Allergy Center and Skin, Hair, and Nails Center, as well as Hives and Angioedema.


Prehospital Care

Laryngeal edema from angioedema can progress rapidly and cause an immediate life-threatening emergency. In these cases, a definitive airway such as an endotracheal tube should be established.

Anaphylaxis is another possible complication. Treatment with epinephrine (EpiPen), histamine blockers, and steroids should also be initiated by emergency medical services (EMS) personnel, especially in cases of angioedema due to hypersensitivities.[4]


Emergency Department Care

The initial goal of therapy is airway management. The most skilled person available must handle airway interventions because of the often massive degree of oral obstruction that is involved. A definitive airway must be established if edema is extensive or progressing.

Most patients with mild acute angioedema may be treated in the same way as those with an allergic reaction. Severe symptoms require steroids, H1 and H2 blockers, and subcutaneous epinephrine in addition to antihistamines.[4]

First-line antihistamine treatment

For antihistamine treatment, diphenhydramine, cetirizine, loratadine, or fexofenadine are the first-line drugs. However, hydroxyzine (10–100 mg daily at bedtime) can be tried when other H1 antihistamines are inadequate.[4]

H2 blockers

Because 15% of H2 receptors are in the skin, use of H2 blockers is warranted to treat angioedema. The most commonly used agents are ranitidine or cimetidine. The H2 antagonists are highly selective and do not affect the H1 receptors; therefore, they must be used in conjunction with other therapies.[6]


Doxepin (Adapin, Sinequan) is an excellent alternative to antihistamines because it has both H1 and H2 activity. Doxepin, a tricyclic antidepressant, blocks both types of histamine receptors and is a much more potent inhibitor of H1 receptors than either diphenhydramine or hydroxyzine; however, sedation is an even greater problem and may limit the usefulness of this drug.

Additional treatments

Intravenous epinephrine (1:10,000) should be used in patients who demonstrate upper airway obstruction, acute respiratory failure, or shock.[4] Aerosolized epinephrine may also be used to help with obstructed airway.

The beta2-adrenergic agonist terbutaline (Brethaire, Brethine) has been shown to be more effective at controlling urticaria than placebo.[6] However, efficacy is low for urticaria and angioedema; therefore, it is seldom used for treatment of angioedema.[6]

Patients with hypotension due to sequestration of fluid in the extravascular space may require large amounts of intravenous fluids to maintain hemodynamic stability.[7]

Abdominal pain from angioedema of the GI tract mucosa can be as intense as pain from an acute abdomen. The pain is treated with opiates.

Patients with mild, limited urticaria may be reassured that symptoms are self-limited, typically disappear within hours to days, and do not need to be treated if itching is not incapacitating. Chronic angioedema responds well to steroids and H2 blockers.

Causative factors for angioedema should always be sought. However, many patients have the idiopathic form of the disease.[8]


Hereditary Angioedema

Hereditary angioedema (HAE) is generally refractory to treatment with catecholamines, antihistamines, and steroids. Anabolic steroids, such as danazol, may be used for the acute phase of an attack of HAE. C1 inhibitor concentrate (Berinert) may also be infused IV as short-term acute treatment of larngeal, abdominal, or facial HAE.[9, 10] Most patients respond 10 minutes after infusion.[11] Another brand of C1 inhibitor (Cinryze) is also used for prophylaxis in recurrent cases.

In December 2009, ecallantide (Kalbitor) was approved by the US Food and Drug Administration (FDA) for treating acute HAE attacks. During attacks, unregulated plasma kallikrein activity results in excessive bradykinin generation, resulting in swelling, inflammation, and pain. Ecallantide is a potent, selective, reversible inhibitor of plasma kallikrein, thereby reducing the conversion of kininogen to bradykinin.[12, 13]

An analysis of clinical trials assessed the efficacy of ecallantide in the treatment of moderate-to-severe attacks of HAE based on time to treatment. Results showed rapid and sustained improvement of symptoms when ecallantide was administered within 6 hours of symptom onset.[14]

Icatibant (Firazyr), a selective bradykinin B2 receptor antagonist, was approved by the US Food and Drug Administration for treatment of acute attacks HAE in adults in August 2011. Approval was based on 3 double-blind, randomized, controlled clinical trials known as For Angioedema Subcutaneous Treatment (FAST) 1, 2, and 3.[15, 16]

FAST 3 was a placebo-controlled study of 98 adult patients with a median age of 36 years. The primary endpoint was assessed using a 3-item composite visual analog score (VAS), composed of averaged assessments of skin swelling, skin pain, and abdominal pain. The median time to 50% reduction in symptoms for patients with cutaneous or abdominal attacks treated with icatibant (n=43) compared with placebo (n=45) was 2 hours (95% confidence interval [CI], 1.5, 3.0) versus 19.8 hours (95% CI, 6.1, 26.3), respectively (P< .001). The median times to almost complete symptom relief were 8 versus 36 hours for icatibant and placebo, respectively. Additional rescue medications were used by 3 patients (7%) treated with icatibant and 18 patients (40%) treated with placebo.[16]

Patients are given epsilon-aminocaproic acid or tranexamic acids, which are antifibrinolytics for short-term prophylaxis. The mechanism of action in not well understood; however, infusions have been shown to decrease symptoms.[12]

Transfusions of fresh frozen plasma (FFP) have been shown to decrease recurring angioedema. Two units are typically infused before dental procedures or situations that may precipitate attacks.[12] FFP is not recommended for treatment of acute attacks.



An immunologist may be of benefit when dealing with difficult cases in patients with an unknown history of angioedema. An immunologist may be able to recommend treatment modalities for patients with hereditary angioedema after the airway has been secured.

Allergy and immunology follow-up for allergy/tryptase testing and/or genetic testing for hereditary angioedema may be indicated.


Further Outpatient Care

Premature discharge from the ED should be avoided. Patients presenting with minor symptoms of angioedema without progression after 4-6 hours of observation may be safely discharged home on a short course of steroids and antihistamines. Patients should be provided with an epinephrine auto-injector (EpiPen) at time of discharge. For patients with documented Helicobacter pylori infection and a history of chronic urticaria, an appropriate antibiotic combination for eradication may stop the urticarial eruptions.

To prevent future episodes, patients need to avoid precipitating factors such as drugs, food, stress, cold, or heat. Allergy testing may be indicated.

Referral for institution of prophylaxis may be appropriate in patients with hereditary angioedema. Candidates for prophylaxis include patients with frequent attacks (ie, more than 4 times per year [1 attack every 3 months]) or those with a history of laryngeal edema.[12]


Questions & Answers