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

Abstract

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 A cohort design with retrospective chart review study was conducted at two Canadian hospitals. Patients with aortic stenosis (moderate or severe) and without aortic stenosis were included if they presented with acute cardiogenic pulmonary edema, received intravenous or sublingual nitroglycerin, and had an echocardiography report available. The primary outcome 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 (N=65) and an equal number of matched episodes with moderate aortic stenosis (N=65) and no aortic stenosis (N=65). Nitroglycerin was administered intravenously only in 70% of cases, intravenously and sublingually in 25%, and sublingually only in the remaining 5%. After adjustment for sex, initial systolic blood pressure, furosemide dose, and use of noninvasive ventilation, moderate and severe aortic stenosis were not associated with clinically relevant hypotension after receipt of nitroglycerin (adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.40 to 2.37 for moderate aortic stenosis; adjusted OR 0.99, 95% CI 0.41 to 2.41 for severe aortic stenosis). The incidence of clinically relevant hypotension 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.