Risk factors associated with intubation and readmissions in patients with angioedema: A single-center experience al. / Ann Allergy Asthma Immunol 127 (2021) xxx–xxx"?>

https://doi.org/10.1016/j.anai.2021.07.023Get rights and content

Abstract

Background

Given the heterogeneity of etiologies, pathophysiology, and presentation of angioedema, variations in clinical outcomes, such as intubation and hospital readmissions, need further clarification.

Objective

To determine the factors associated with intubation and hospital readmissions in patients with angioedema.

Methods

Retrospective study of patients evaluated with a diagnosis of angioedema in a 6-year period. Demographic and clinical data, such as medication use, family history, comorbidities, and symptoms, were recorded. Multivariable logistic regression was used to analyze factors associated with intubation, whereas Cox regression was used to analyze readmissions.

Results

Of 636 patients, the most common cause of angioedema was that induced by angiotensin-converting enzyme inhibitor (ACEI) at 58%. The overall mortality was 0.5%. After adjusting for sex, race, comorbidities, and type of angioedema, smoking (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = .02), calcium channel blocker therapy (OR, 1.91; 95% CI, 1.18-3.10; P = .009), histaminergic symptoms (OR, 3.21; 95% CI, 1.93-5.33; P < .001), and age (OR, 1.02; 95% CI, 1.00-1.04; P = .02) were independently associated with increased odds of intubation. Involvement of either the pharynx, larynx, or tongue was associated with higher odds of intubation (OR, 20.96; 95% CI, 10.63-41.33; P < .001). A total of 10% of the patients had a readmission for angioedema within 90 days, and 75% occurred within 30 days. After multivariable Cox regression analysis, only chronic obstructive pulmonary disease and asthma (OR, 2.13; 95% CI, 1.12-4.07; P = .02) and ACEI-related angioedema (OR, 2.93; 95% CI, 1.33-6.47; P = .008) were significantly associated with readmissions.

Conclusion

Smoking, calcium channel blocker use, histaminergic symptoms, age, and upper airway involvement were markedly associated with intubation. The presence of chronic obstructive pulmonary disease, asthma and ACEI-related angioedema were independently associated with increased odds of readmission.

Introduction

Angioedema is characterized by soft tissue swelling in nongravitational areas of the body, usually in the face, neck, upper airway, and gastrointestinal tract, resulting from fluid extravasation into the interstitial space.1 It is a common presentation to emergency departments (EDs) throughout the country.2 Different types of angioedema have been described according to the pathophysiological mechanism involved, including bradykinin-mediated, histaminergic, and idiopathic.1 The proper recognition of the pathophysiological mechanism driving the angioedema is important for individualizing the therapeutic approach.

Bradykinin-mediated angioedema most often presents as an adverse effect of typically prescribed medications, such as angiotensin-converting enzyme inhibitors (ACEIs). Less often, it is associated with several mutations that cause the loss of function of C1 esterase inhibitor or the gain of function of factor XII or plasminogen proteins.3, 4, 5 Bradykinin-mediated angioedema usually does not course with histaminergic symptoms, and the duration is more prolonged.6

Histaminergic angioedema is the most often described mechanism of angioedema, and it can be related to allergic or anaphylactic reactions to food and medications.7 This type of angioedema is usually accompanied by systemic manifestations, such as rash, pruritus, bronchospasm, and hypotension, and frequently is self-limited.7

If the mechanism of angioedema remains unclear despite exhaustive data gathering, physical examination, and workup, it is classified as idiopathic angioedema.

The management of angioedema relies on the location, presence of airway compromise, and etiology. Although the reaction is most often benign and self-limited, angioedema can cause life-threatening upper airway obstruction. Hence, maintaining the upper airway patent until angioedema resolves is of utmost importance, which may require endotracheal intubation in severe cases.8 Most subjects with histaminergic-induced angioedema respond to histamine blockers, corticosteroids and epinephrine.7 Nevertheless, subjects with bradykinin-induced angioedema do not respond to antiallergic therapies. Hereditary angioedema is treated with approved therapies, such as C1-esterase inhibitor concentrate, icatibant, or ecallantide, in the acute setting.9, 10, 11 Meanwhile, these therapies have resulted in conflicting results in patients with ACEI-induced angioedema, in whom the optimal management remains unclear.12

ACEI-induced angioedema is a continued risk burden for patients with hypertension on these medications. ACEIs are typically prescribed for management of hypertension, cardiovascular disease, and renal disease. Notably, ethnic differences in the kallikrein and bradykinin systems have been described in African Americans compared with Whites, leading to an increased risk in this population.13

Therefore, we described the characteristics and outcomes of patients who presented to our institution with the diagnosis of angioedema within the last 6 years, focusing on the differences between ACEI-induced and non–ACEI-induced angioedema. In addition, the identification of subsets of patients at risk to develop severe or recurrent episodes of angioedema is needed to risk stratify patients at the time of admission or discharge for improving the medical management and outcomes. Hence, we proceeded to investigate the risk factors associated with intubation and hospital readmission within 90 days from discharge date.

Section snippets

Methods

This is a single-center retrospective study of patients evaluated in the ED or admitted in our institution with the diagnosis of angioedema between January 2015 and December 2020. We identified the index cases using the International Classification of Diseases (International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, Tenth Revision, Clinical Modification) code sets.

The diagnosis of angioedema was made on the basis of clinical

Demographic and Clinical Data

A total of 700 patients were reviewed spanning the time period from January 2015 to December 2020. There were 64 patients who were excluded owing to lack of diagnosis of angioedema or demographic and clinical variables. A final sample of 636 patients was included for the final analysis.

The mean age was 55.64 ± 16.90 years, and most of the patients were of female sex (57%) and African American (91%). The most common potential cause or trigger of angioedema was related to ACEI at 58%. A

Discussion

We have described the cases of angioedema that were evaluated at our institution within a 6-year period, from January 2015 to December 2020. The most common potential cause or trigger of angioedema was related to ACEI therapy (58%), whereas the remaining cases were classified as idiopathic, related to other drugs, such as CCBs and NSAIDs, and food allergies (Fig 1). Some studies have described the prevalence of ACEI-induced angioedema as 28% to 30% of all cases of angioedema.14,15 The

Supplementary Data

Supplementary data related to this article can be found at https://doi.org/10.1016/j.anai.2021.07.023.

References (40)

  • R Sinert et al.

    Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema

    J Allergy Clin Immunol Pract

    (2017)
  • LM Lewis et al.

    Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial

    Ann Emerg Med

    (2015)
  • C Beauchêne et al.

    [Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors]

    Rev Med Interne

    (2018)
  • JM Martinez Manzano et al.

    The use of intravenous tranexamic acid for patients with angiotensin-converting enzyme inhibitor-induced angioedema: a case series

    Ann Allergy Asthma Immunol

    (2021)
  • K Joseph et al.

    Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma

    Ann Allergy Asthma Immunol

    (2008)
  • A Tamimi et al.

    The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications

    Respir Med

    (2012)
  • M Kelly et al.

    National estimates of emergency department visits for angioedema and allergic reactions in the United States

    Allergy Asthma Proc

    (2013)
  • BL. Zuraw

    Clinical practice. Hereditary angioedema

    N Engl J Med

    (2008)
  • J Nussberger et al.

    Bradykinin-mediated angioedema

    N Engl J Med

    (2002)
  • JJ Moellman et al.

    A consensus parameter for the evaluation and management of angioedema in the emergency department

    Acad Emerg Med

    (2014)
  • Cited by (1)

    • Isolated angioedema: A review of classification and update on management

      2022, Annals of Allergy, Asthma and Immunology
      Citation Excerpt :

      It is important to recognize that other medications such as gliptins, which are dipeptidyl peptidase 4 inhibitors, are also associated with increased risk of AE.62,63 Other identified risk factors for more serious outcomes such as intubations include smoking, calcium channel blocker use, and age.64 The recommended treatment of ACEI is discontinuation of the medication.

    Disclosures: The authors have no conflicts of interest to report.

    Funding: The authors have no funding sources to report.

    View full text