Contemporary ACE-I Angioedema Outcomes, A Retrospective Cohort Analysis of Airway Interventions ROBERT SHAWN WILLS

Abstract  This presentation investigates the implementation of antihistamines and other medications used for allergic reactions in an acute care hospital setting, and how they change the airway intervention outcomes for patients presenting with Angiotensin Converting Enzyme-Inhibitor induced angioedema. This topic was chosen to highlight a knowledge deficit in the acute and rapid treatment of individuals presenting with ACE-I induced angioedema to the Emergency Department, which could prove beneficial to better outcomes for clients. There is currently no known diagnostic testing to confirm ACE-I induced angioedema, nor is there an FDA approved intervention for this complication (Chan, Soliman, 2015).

ACE-I Induced Angioedema Cascade Inhibition of angiotensin converting enzyme (e.g. Lisinopril) Inability to break down bradykinin Excess bradykinin leads to blood vessel dilation Increased endothelial permeability Plasma extravasation and severe swelling to the orofacial and perioral area (Rasmussen, Mey, Bygum, 2014).

Current Treatment Process  Patient may presents with any of the following:  Facial swelling / Tongue swelling / Difficulty breathing  Differentiated from anaphylaxis with absence of urticarial, and exclusive to oral/perioral area  Initial treatment:  Airway management  oxygen therapy, 100% NRB, endotracheal intubation  Typical medication orders  Antihistamines, steroids, adrenaline, B2- adrenergic agonists  Observation/Treatment Period:  Can become fatal if airway becomes obstructed  Resolution:  Symptoms typically resolve in 12 – 24 hours (Ismail, Leo, Grigoriadou, Laffan, Menon, 2015)

Status of Clinical Trials Associated with ACE-I induced Angioedema Ecallantide, a drug approved for use in resolving hereditary angioedema, has since been found to negligibly influence the recovery rate for subjects suffering from an acute attack of angioedema secondary to ACE-I (Thomas, Shah, 2011). Icatibant, also approved for use in treatment of hereditary angioedema, is a promising drug being studied internationally to reduce the symptoms and complications of ACE-I induced Angioedema(Bas, et.al., 2015). Investigational studies assessing the efficacy of new drug therapies to resolve the angioedema response caused by ACE-I:

ACE-I Prevalence and Use  A significant amount of American society is being treated with anti-hypertensives for diseases including:  Hypertension  Congestive heart failure  Coronary artery disease  Diabetic neuropathy  The relatively low cost and high reliability of ACE-Inhibitors makes them a common choice for treatment.  Increased prevalence of complications associated with this class of drug, such as angioedema (Rasmussen, Mey, Bygum, 2014).  In a randomized, double-blind trial of more than 12,000 subjects treated with an ACE-I, 0.68% of patients reported instances of angioedema (Rasmussen, Mey, Bygum, 2014).  Supplemental studies found people of African descent have up to 3 times higher risk for developing this adverse reaction to ACE-I use, as well as having a precipitation effect for those with hereditary angioedema, either idiopathic or acquired (Rasmussen, Mey, Bygum, 2014).

Retrospective Review In a retrospective chart review study that had taken place at Temple University Hospital during the calendar year of 2012, a total of 88 patients were found to have presented with reasonably confirmed ACE-I induced angioedema (Chan, Soliman, 2015). Of the 88 subjects identified, 28 subjects still required airway intervention despite treatment with conventional steroid and antihistamine medication administration (Chan, Soliman, 2015). Of the 28, 27 required endotracheal or nasotracheal intubation, while 1 of the group identified was found to have required an emergent cricothyroidotomy despite conventional treatment (Chan, Soliman, 2015).

Contemporary View  Numerous case studies have investigated the efficacy of antihistamine and steroid treatments on client’s presenting with acute facial angioedema  Negligible benefit to clients with acute angioedema attack symptoms and recovery time have been found (Ismail, et.al., 2015).  The most recently established first line therapy for clients diagnosed with ACE-I induced angioedema include bradykinin inhibitors or C-1 Inhibitor substitutes  Currently only found in donated fresh frozen plasma  Inhibition of C-1 and bradykinin facilitates the elimination of the inflammation markers that lead to the profuse facial swelling (Ismail, et.al., 2015).

Prospective View  Given the current evidence of poor efficacy of contemporary use of steroids and antihistamine use in client’s presenting with ACE-I induced angioedema, and large percentage of those affected do not respond effectively leaving a major need for further research and education.  Acute care settings need to adequately and safely treat angioedema attacks with continued education and awareness placed on this terrifying condition  Advances need to be made in order to better facilitate care of those seeking medical intervention, often that of resolving airway obstruction (Chan, Soliman, 2015).  There is also discussion for future investigation of antifibrinolytics and attenuated androgens on the acute angioedema attack (Ismail, et.al., 2015).

Reference Bas, M., Greve, J., Stelter, K., Havel, M., Strassen, U., Rotter, N., & Hoffmann, T. K. (2015). A randomized trial of icatibant in ACE-inhibitor-induced angioedema. New England Journal Of Medicine, 372(5), doi: /NEJMoa Chan, N. J., & Soliman, A. M. (2015). Angiotensin Converting Enzyme Inhibitor- Related Angioedema: Onset, Presentation, and Management. Annals Of Otology, Rhinology & Laryngology, 124(2), doi: / Ismail, S., Leo, C., Grigoriadou, S., Laffan, J., & Menon, M. (2015). Lesson of the month 2: The limitations of steroid therapy in bradykinin-mediated angioedema attacks. Clinical Medicine, 15(1), Lewis, L. M., Graffeo, C., Crosley, P., Klausner, H. A., Clark, C. L., Frank, A., &... Chyung, Y. (2015). Ecallantide for the acute treatment of Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Annals Of Emergency Medicine, 65(2), doi: /j.annemergmed Rasmussen, E. R., MEY, K., & BYGUM, A. (2014). Angiotensin-converting Enzyme Inhibitor-induced Angioedema -- A Dangerous New Epidemic. Acta Dermato- Venereologica, 94(3), doi: / Thomas, M. C., & Shah, S. (2011). New treatment options for acute edema attacks caused by hereditary angioedema. American Journal Of Health-System Pharmacy, 68(22), doi: /ajhp100718