What is the emergency room disposition for angioedema of the lip due to Angiotensin-Converting Enzyme (ACE) inhibitor use?

From the Guidelines

The primary step in managing lip angioedema due to ACE inhibitors in the emergency room is to immediately discontinue the ACE inhibitor and monitor the patient closely for airway compromise, as discontinuation is the cornerstone of therapy for these patients 1.

Key Considerations

• Discontinuation of the ACE inhibitor is crucial, although there might be a significant time lag between discontinuation of the drug and the propensity for angioedema 1.
• Patients need to be observed in a controlled environment in case they require intubation, highlighting the importance of close monitoring for airway compromise.
• Treatment with antihistamines, corticosteroids, or epinephrine has not been shown to be efficacious for ACE-I–associated angioedema, suggesting that traditional allergy treatments may not be effective in this context 1.

Management Approach

• For severe cases, icatibant or fresh frozen plasma may be considered as they target the bradykinin pathway responsible for ACE inhibitor-induced angioedema 1.
• Disposition depends on severity - patients with mild symptoms that improve can be discharged with close follow-up after observation, while those with significant or progressing swelling should be admitted for monitoring.
• Upon discharge, patients must be instructed never to take ACE inhibitors again and should receive alternative antihypertensive medications.

Important Notes

• The evidence from 1 provides the most recent and highest quality guidance on managing ACE inhibitor-associated angioedema, emphasizing the importance of discontinuing the offending agent and supportive care.
• Other studies, such as 2, may discuss angioedema in different contexts but do not directly inform the management of ACE inhibitor-induced angioedema in the emergency setting.

From the FDA Drug Label

Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue. The patient with lip angioedema due to ACE inhibitor should be treated with epinephrine (IM) as part of the emergency management of an allergic reaction. Key considerations for emergency room disposition include:

• Airway management: monitoring for signs of airway compromise
• Vital sign monitoring: close monitoring of blood pressure, heart rate, and oxygen saturation
• Further treatment: consideration of additional treatments, such as antihistamines or corticosteroids, as needed 3

From the Research

Emergency Room Disposition for Lip Angioedema due to ACE Inhibitor

• The primary focus for the treatment of ACE inhibitor-induced angioedema is airway management 4
• In the absence of high-quality evidence, no specific medication therapy is recommended for its treatment 4
• If the treating physician feels the patient's presentation is more typical of an acute allergic reaction or anaphylaxis, it may be appropriate to treat for those conditions 4
• Any patient with suspected ACE inhibitor-induced angioedema should immediately discontinue that medication 4

Pathophysiology and Risk Factors

• The pathophysiology of ACE inhibitor-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation 5
• Angioedema occurs more frequently in African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy 5

Treatment Modalities

• Treatment modalities include antihistamines, steroids, and epinephrine, as well as endotracheal intubation in cases of airway compromise 5
• The efficacy of treatment of ACE inhibitor-induced angioedema with bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor warrants further study 6
• One study examining off-label use of icatibant has demonstrated efficacy over control 6

Disposition and Follow-up

• Patients with a history of ACE inhibitor-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 5
• Angioedema may recur even after ACE inhibitor discontinuation, and increased awareness of delayed ACE inhibitor-induced angioedema following ACE inhibitor discontinuation is important for both providers and pharmacists to provide appropriate diagnosis and monitoring 7