High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema

High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema (SCAPE)

Pharmacy Friday Pearl – Pharmacy & Acute Care University

SCAPE is a form of hypertensive heart failure triggered by a surge in catecholamines.
The result is pulmonary capillary leakage and alveolar flooding.
Management includes non-invasive ventilation and pharmacologic agents such as nitroglycerin.
Dose-dependent afterload reduction with nitroglycerin requires doses >50–150 mcg/min.

Parameter	Details
Mechanism of Action	Organic nitrate vasodilator that reduces tension on vascular smooth muscle and dilates peripheral veins and arteries (at higher doses).
Dose	• Chest pain: 5–400 mcg/min (starting at 5 mcg/min) • Pulmonary edema/afterload reduction: 50–400 mcg/min • Titrate to symptom improvement and tolerated blood pressure
Administration	• IV infusion: 50–400 mcg/min until symptom resolution • IV bolus: 400–2000 mcg over 2–5 min (check hospital policy) • Sublingual: 400 mcg tab, 2–4 tablets (≈160–320 mcg/min IV) • Ointment: slow onset 30–60 min
PK/PD	• Onset: IV 1–5 min; SL 1–3 min • Peak: 3–15 min • Duration: IV 5–10 min; SL 10–60 min • Elimination: 22% renal
Adverse Effects	Headache, hypotension, syncope, rebound hypertension, tolerance with prolonged use (~24 hrs)
Warnings/Interactions	• PDE inhibitors • Aortic stenosis, preload-dependent cardiomyopathy, hypertrophic obstructive cardiomyopathy, hypotension at any time
Compatibility	Incompatible with levofloxacin, SMX-TMP, daptomycin, and phenytoin

Clinical pearl: Higher doses of IV or bolus nitroglycerin may reduce ICU admissions and intubation risk in SCAPE.

Author/Year	Design (n)	Intervention & Comparison	Key Findings
Patrick, 2020	Observational (n=48)	IV NTG 1 mg bolus by EMS	↓SBP by 31 mmHg, ↓HR by 10 bpm, ↑O2 from 86% to 98%; 2% symptomatic hypotension
Hsieh, 2018	Case Report (n=3)	SL NTG 0.6 mg x 3, IV NTG bolus 1 mg Q2 min, then infusion 40 mcg/min	Normalized respiratory status, avoided intubation & ICU admission
Paone, 2018	Case Report (n=1)	IV NTG 400 mcg/min titrated	Symptom resolution at 6 minutes
Wilson, 2016	Observational (n=395)	IV NTG bolus (500–2000 mcg) Q3–5 min vs infusion vs both	↓ICU admissions, shorter LOS, no increase in intubations
Levy, 2007	Observational (n=29)	IV NTG bolus 2 mg IV Q3 min	↓Intubation, ↓BiPAP/ICU admission
Sharon, 2000	RCT (n=40)	IV isosorbide bolus 4 mg Q4 min vs infusion + BiPAP	↓Intubation, MI, mortality; ↑PaO₂
Cotter, 1998	RCT (n=104)	IV isosorbide bolus 3 mg Q5 min + furosemide vs infusion titration	↓MV & MI, ↑PaO₂, fewer adverse effects

High-dose nitroglycerin (bolus and/or infusion) is effective in rapidly reducing preload and afterload in SCAPE.
Doses of ≥400 mcg/min (or equivalent bolus) are supported by case reports and observational studies.
High-dose IV or sublingual NTG has been associated with improved respiratory status, fewer ICU admissions, and reduced need for intubation.
Symptomatic hypotension is rare but monitoring is necessary, especially with bolus regimens.
Bolus dosing strategies may outperform continuous infusions in acute SCAPE decompensation.

Nitroglycerin. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved March 5, 2020, from http://www.micromedexsolutions.com/
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