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High-Dose Nitroglycerin for SCAPE – But How High?

January 10, 2024

Written by Millie Cossé

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High-dose nitroglycerin improves outcomes in patients with sympathetic crashing acute pulmonary edema (SCAPE) without significant side effects when compared to low-dose nitroglycerin.

What is your eSCAPE plan?
SCAPE is a vicious cycle: Increased sympathetic tone leads to increased vasoconstriction and afterload, worsening heart failure. Simultaneously, this vasoconstriction promotes the shift of fluids into the lungs. Both states worsen pulmonary edema, leading to a miserable patient and additional sympathetic activation, thereby worsening the cycle. So how do we break the cycle? The core pillars of SCAPE treatment are improved oxygenation with PEEP (via BiPAP or CPAP) and afterload reduction with nitroglycerin. However there remains some uncertainty regarding nitroglycerin dosing in this patient group.

This open-label randomized control trial of 54 patients at a tertiary care emergency department in India aimed to compare efficacy of high-dose and low-dose nitroglycerin in the treatment of patients with SCAPE. Authors defined high-dose as a 600-1000 mcg bolus followed by infusion of 100 mcg/min, and low-dose as infusion of 20-40 mcg/min without a bolus. The primary outcome was symptom resolution at 6 hours and 12 hours. At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the high- dose group, compared with 3 (11.5%) in the low-dose group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the high-dose group versus 19.5% in low-dose group.

How will this change my practice?
When treating SCAPE, I tend to start a nitro drip at 200 mcg/min with no bolus but with a plan to rapidly up-titrate (by ~100 mcg/min) every few minutes as needed and have seen remarkably quick improvement with this approach. EMCrit recommends a bolus of 1000-2000 mcg over ~2 minutes (e.g. 400-800 mcg/min for 2.5 mins) followed by an infusion at 100-300 mcg/min. While we don’t have any large prospective studies to suggest a true optimal dosing strategy, this paper adds to the available evidence which suggests that patients experiencing SCAPE need at least 100 mcg/min of nitroglycerin.

High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial. Emerg Med J. 2023 Nov 28:emermed-2023-213285. doi: 10.1136/emermed-2023-213285. Online ahead of print.