2025 Southeastern Residency Conference

Title: C1 Esterase Inhibitor for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema in Intubated Patients at a Community Teaching Health System


Authors: Christopher Reagin; Phillip Mohorn; Leslie Roebuck


Objective: Evaluate the use, clinical efficacy, and cost of C1 esterase inhibitors in patients intubated for ACEi-induced angioedema by assessing the duration of mechanical intubation


Self Assessment Question: What was the impact of C1 esterase inhibitor (C1EI) administration on the duration of mechanical ventilation in patients intubated for ACE inhibitor-induced angioedema?


Background: ACE inhibitor induced (ACEi-induced) angioedema is a rare but potentially life-threatening condition that can cause airway obstruction and require intubation. Its underlying mechanism involves bradykinin accumulation, leading to increased vascular permeability and tissue swelling. The management of ACEi-induced angioedema primarily focuses on supportive care, including airway management, cessation of the offending agent, and symptomatic relief. However, no FDA-approved treatments exist. C1 esterase inhibitor (C1EI) has been explored as a potential therapy, but its role remains unclear based on available literature. A retrospective analysis at our institution previously examined the efficacy of C1EIs in preventing mechanical ventilation in patients with ACEi-induced angioedema. Notably, some patients received the medication after they had already been intubated, which raised questions about the optimal timing of administration and its effect on outcomes, such as the duration of mechanical ventilation. This study aimed to assess C1EI’s effectiveness in intubated patients, focusing on duration of mechanical ventilation to clarify its clinical utility.


Methods: This was a retrospective, observational, cohort study conducted at a community teaching health system from January 2017 to August 2024. Patients intubated for ACEi-induced angioedema were identified through electronic health records and stratified into C1EI-treated and non-C1EI-treated groups. Both groups received standard of care (epinephrine 0.2 to 0.5 mg intramuscularly or 0.05 to 0.1 mg intravenously, corticosteroids at ≥ 50 to 100 mg hydrocortisone equivalent, a histamine-1 receptor antagonist, and a histamine-2 receptor antagonist). The primary outcome was duration of mechanical ventilation. Secondary outcomes included ICU length of stay (LOS), hospital LOS, in-hospital mortality, and angioedema-related medication costs. Continuous variables were analyzed using the Mann-Whitney U test, while categorical data were compared using Chi-square or Fisher’s exact test, with statistical significance set at p<0.05.


Results: A total of 22 patients met inclusion criteria (C1EI: 15, non-C1EI: 7). Median duration of mechanical ventilation was similar between groups (C1EI: 1.3 days [IQR: 1.1–1.6] vs. non-C1EI: 1.7 days [IQR: 1.3–2.3], p=0.078). No significant differences were observed in ICU LOS (C1EI: 2.3 days [IQR: 1.4–2.8] vs. non-C1EI: 3.0 days [IQR: 2.1–5.1], p=0.162), hospital LOS (C1EI: 4.1 days [IQR: 2.1–4.7] vs. non-C1EI: 3.5 days [IQR: 3.2–9.1], p=0.581), or in-hospital mortality (0% in both groups). However, median medication cost was significantly higher in the C1EI group ($12,743.8 [IQR: $9,117.5–$13,381.6] vs. $32 [IQR: $11.5–$68.5], p<0.001).


Conclusion: In this retrospective cohort study, the administration of C1EI did not significantly reduce the duration of mechanical ventilation or other clinical outcomes in patients intubated for ACEi-induced angioedema. However, its use was associated with substantially higher medication costs. Larger, prospective or propensity-matched studies are needed to clarify the role of C1EI in this patient population.