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Introduction: Sympathetic crashing acute pulmonary edema (SCAPE) presents as a rapid onset of respiratory distress due to elevated sympathetic tone and afterload, requiring prompt management. Prior studies support use of high-dose nitroglycerin (HDN) and non-invasive positive pressure ventilation, but limited sample sizes have restricted generalizability. The goal of this study is to determine if HDN infusions impacted the duration of time spent in the emergency department (ED). Methods: A single-center, retrospective chart review of adult patients between August 2022 to August 2024, was performed. Patients were included if they received a nitroglycerin infusion and presented with systolic blood pressure ≥ 160 mmHg and respiratory distress. Patients receiving ≥ 100 mcg/min of nitroglycerin within 1 hour were classified as HDN and those receiving < 100 mcg/min were categorized as low-dose nitroglycerin (LDN). The primary outcome was ED length of stay (LOS). Secondary outcomes included hospital LOS, ICU admission, intubation, hypotension, in-hospital mortality, and total nitroglycerin dose administered in the ED. A sample size of 100 patients was required for 80% power with an alpha set at 0.05 Results: A total of 105 patients met inclusion criteria, with 43 (41%) in the HDN group and 62 (59%) in the LDN group. Baseline characteristics were similar between groups besides initial systolic blood pressure, which was lower in the LDN group (p=0.008). There was no significant difference in ED LOS with a median 2.57 hours [IQR 2.03-3.06] in the HDN group vs 2.57 hours [IQR 1.88-3.30] in the LDN group. Although not statistically significant, intubation rates were lower in the HDN group compared to the LDN group (16.9% vs. 9.5%, respectively). Total nitroglycerin received was significantly higher in the HDN group (8.7 mg vs 2.1 mg; p < 0.001). There was no difference between both cohorts in ICU admission, hypotension rates, and mortality. Conclusions: Although the primary outcome did not reach statistical significance, intubation rates were lower in the high-dose group without an associated increase in adverse safety events. These findings suggest that HDN infusions may be a safe therapeutic option for SCAPE. Overall, this study adds to the existing literature and highlights the need for more high-quality research.