Complications Associated With Nitrate Use in Patients Presenting With Acute Pulmonary Edema and Concomitant Moderate or Severe Aortic Stenosis

Study objective: We evaluate the incidence of complications associated with the use of nitrates in patients presenting with acute pulmonary edema and concomitant moderate or severe aortic stenosis compared with patients without aortic stenosis. Nitrates are contraindicated in severe aortic stenosis because of the theoretical yet unproven risk of precipitating profound hypotension. Methods: AcohortdesignwithretrospectivechartreviewstudywasconductedattwoCanadianhospitals.Patientswithaortic stenosis (moderate or severe) and without aortic stenosis were included if they presented with acute cardiogenic pulmonary edema,receivedintravenousorsublingualnitroglycerin,andhadanechocardiographyreportavailable.Theprimaryoutcome was clinically relevant hypotension, defined as hypotension leading to any of the following predefined events: nitroglycerin discontinuation, intravenous fluid bolus, vasopressor use, or cardiac arrest. The secondary outcome was sustained hypotension, defined as a systolic blood pressure less than 90 mm Hg and lasting greater than or equal to 30 minutes. Results: The cohort consisted of 195 episodes of acute pulmonary edema, representing 65 episodes with severe aortic stenosis (N¼65) and an equal number of matched episodes with moderate aortic stenosis (N¼65) and no aortic stenosis (N¼65). Nitroglycerin was administered intravenously only in 70% of cases, intravenously and sublingually in 25%, and sublinguallyonly in theremaining5%. Afteradjustmentfor sex, initialsystolicbloodpressure, furosemidedose,and useof noninvasiveventilation,moderateandsevereaorticstenosiswerenotassociatedwithclinicallyrelevanthypotensionafter receipt of nitroglycerin (adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.40 to 2.37 for moderate aortic stenosis;adjustedOR0.99,95%CI0.41to2.41forsevereaorticstenosis).Theincidenceofclinicallyrelevanthypotension was 26.2% for moderate and severe aortic stenosis and 23.1% in the no aortic stenosis reference group. The secondary outcome of sustained hypotension occurred in 29.2% of patients with severe aortic stenosis,16.9% with moderate aortic stenosis, and 13.8% in the no aortic stenosis group (adjusted OR for severe aortic stenosis 2.34; 95% CI 0.91 to 6.01). Conclusion: In this retrospective study, neither moderate nor severe aortic stenosis was associated with a greater risk of clinically relevant hypotension requiring intervention when nitroglycerin was used for acute pulmonary edema. Future studies should investigate safety and efficacy of nitroglycerin for patients with aortic stenosis because this study was limited by a small sample size and design limitations. Cautious use of nitroglycerin in patients with moderate or severe aortic stenosis and presenting with acute pulmonary edema may be a safer strategy than traditionally thought. [Ann Emerg Med. 2015;66:355-362.] Please see page 356 for the Editor’s Capsule Summary of this article.