Evaluation of Initial Dose of Nitroglycerin for Acute Heart Failure Exacerbation Authors: Amaury Santiago Malave, Christopher Lloyd, Lena Tran Background Nitroglycerin, a vasodilator, administered as an intravenous (IV) bolus at doses between 400 to 800 mcg and infusions of 100-200 mcg/min have shown to rapidly decrease preload, afterload, and improve myocardial oxygen supply in patients with pulmonary edema and acute decompensated heart failure. Literature suggests these higher IV doses of nitroglycerin have led to reduced intensive care unit (ICU) admissions and intubations; however, there is currently limited guidance for an initial nitroglycerin bolus dose or infusion rate, leading to frequent underdosing. The objective of this study is to evaluate the use of nitroglycerin for acute heart failure exacerbations and to assess the significance of nitroglycerin doses on ICU admission and need for mechanical ventilation.
Methods This study was reviewed by the local investigational review board and deemed a quality improvement project. A retrospective data analysis was conducted on adult patients presenting to AdventHealth Central Florida hospitals between August 6, 2023 and August 29, 2025 with acute heart failure exacerbation requiring intravenous nitroglycerin and non-invasive positive airway pressure (NIPAP). Patients were stratified according to nitroglycerin initiation strategy: 1) higher-intensity nitroglycerin (HIN) which included receiving an IV nitroglycerin bolus and/or initiation of continuous infusion at ≥ 100 mcg/min. 2) lower-intensity nitroglycerin (LIN) which consisted of starting a continuous infusion at < 100 mcg/min with no bolus. Data was collected from the electronic health record and included baseline demographics, nitroglycerin bolus dose (if administered), initial infusion rate, and maximum infusion rate. Safety data included baseline and repeated measurements of systolic blood pressure, heart rate, respiratory rate, and oxygen saturation. The primary outcome was ICU admission. Secondary outcomes included hospital length of stay, endotracheal intubation, incidence of hypotension, infusion duration, time to NIPAP discontinuation, and change in vital signs two hours after infusion initiation. Continuous variables were analyzed using means with standard deviations and medians with interquartile ranges, as appropriate, and compared using Student’s t-test or the Mann-Whitney U test.
Results A total of 181 patients met inclusion criteria, with 99 managed using HIN and 82 managed using a LIN. ICU admission occurred in 59.6% of patients in the higher-intensity group compared to 68.2% in the lower-intensity group, though this difference did not reach statistical significance (p = 0.226). Rates of endotracheal intubation (2.02% vs 4.88%, p = 0.285) and hypotension (4.04% vs 3.66%, p = 0.894) were similar between groups. Hospital length of stay and time to NIPAP discontinuation were not significantly different. The HIN group received significantly greater initial and maximum infusion rates (p < 0.001 for both comparisons). Median infusion duration was significantly shorter in the higher-intensity group (3 vs 4 hours, p=0.033). Changes in systolic blood pressure, respiratory rate, heart rate, and oxygen saturation were comparable between groups.
Conclusion In this retrospective analysis of patients with acute heart failure exacerbations requiring NIPAP, a higher-intensity nitroglycerin initiation strategy was associated with lower ICU admission and intubation rates compared to a lower-intensity approach, although these differences did not reach statistical significance. Of note, this higher-intensity strategy was not associated with increased hypotension or adverse effects and resulted in a shorter median infusion duration. While the study was not powered to detect small differences in clinical outcomes, the observed trends suggest that more aggressive upfront nitroglycerin dosing may be both feasible and well tolerated in appropriately selected patients. These findings support the need for prospective, adequately powered studies to further evaluate dose thresholds for nitroglycerin strategies that can meaningfully reduce ICU admission and respiratory deterioration in acute heart failure exacerbations.
