36 Prevention of Invasive Airway Management in Drug-Induced Angioedema Using Icatibant

Abstract

Angioedema occurs in 0.1 to 1.0% of patients taking Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARB). Standard supportive care with drug discontinuation, epinephrine, antihistamines, and corticosteroids is recommended. Some cases progress to life threatening oral edema requiring invasive airway management (IAM), such as endotracheal intubation, cricothyrotomy, or tracheotomy. Icatibant, a selective bradykinin B2 receptor antagonist, has been used off-label in ACEI/ARB-associated angioedema to prevent tracheotomy. Icatibant has an average wholesale price of $9,606 per dose, limiting administration to patients experiencing airway compromise. The primary outcome of this study was to evaluate whether icatibant can abort IAM in life-threatening ACEI/ARB-associated oral angioedema. The secondary purpose was to evaluate patient outcome and cost. A retrospective review was performed of ten months of pre- and post-implementation of a criteria-based protocol using a 30 mg subcutaneous dose of icatibant for life-threatening ACEI/ARB- associated oral angioedema with attending emergency physician-documented imminent IAM. This included all patients who presented to the Ohio State University Wexner Medical Center University Hospital emergency department (ED), a tertiary care academic center, or University Hospital East ED, an inner city teaching hospital, with angioedema and secondarily ACEI/ARB-associated angioedema based on an admission or discharge ICD-9 diagnosis code of 995.1, and ACEI or ARB home medication use within 24 hours. Pre-implementation review was from January 1, 2011 to October 31, 2011 and post-implementation review was from May 1, 2013 to February 28, 2014. Outcome data included number of patients with IAM, patient length of stay (LOS), and total hospital cost. Total ED visits during each review period were approximately 96,000. In the pre-implementation period, 93 patients with a diagnosis of angioedema were identified, of whom 42 were associated with ACEI and two with ARB use (47% of angioedema patients and 0.04% of all ED visits). Eighteen drug-associated patients were admitted with six (6 of 44, 13.6%) receiving either endotracheal intubation (4 cases), cricothyrotomy (1 case), or tracheotomy (1 case). LOS ranged from 2 to 16 days and averaged 7.7 days, with an associated hospital cost of $17,878 + $24,482. In the post-implementation period, there were 143 cases of angioedema, of which 63 were associated with ACEI and three with ARB use (46% of angioedema patients and 0.07% of all ED patients). Thirty-two drug-associated patients were admitted and one (non-icatibant) standard supportive care patient received IAM with a LOS of 6 days and hospital cost of $15,137. Icatibant was used in seven of the drug-associated patients (10.6%), none of whom subsequently required IAM. Length of stay for icatibant patients averaged 0.5 days with a total hospital cost of $5,951 + $1,575. None of the icatibant patients had any reported side effects or adverse reactions. Visible angioedema decrease occurred within one hour in all cases. The use of icatibant in ACEI/ARB-associated angioedema patients with imminent invasive airway management was associated with a reduction in invasive airway management, length of stay, and total hospital cost, compared to standard supportive care.