High-Dose Nitroglycerin for SCAPE

Sympathetic crashing acute pulmonary edema (SCAPE) is a subset of hypertensive heart failure which develops

rapidly due to an abrupt increase in catecholamine release, subsequently leading to increased pulmonary capillary

permeability and flooding of alveolar space. Preload and afterload reduction is key and is managed with non-invasive

ventilation (NIV) and pharmacologic agents such as nitroglycerin. However, nitroglycerin has dose-dependent

afterload reduction that requires doses >50-150 mcg/min.

Nitroglycerin (NTG)

Mechanism of

Action

Nitroglycerin, an organic nitrate, is a vasodilating agent that relieves 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

o Titrate to symptom improvement and tolerated blood pressure

Administration

IV infusion: 50-400 mcg/min until symptom resolution

IV bolus: 400-2000 mcg in syringe over 2-5 min (check hospital policy)

400 mcg Sublingual tablet: 2-4 tablets (equivalent to 160-320 mcg/min of IV nitroglycerin)

Ointment: slow onset 30-60 min

PK/PD

Onset: IV 1-5 min; sublingual 1-3 min

Peak: IV/sublingual 3-15 min

Duration: IV 5-10 min, sublingual 10-60 min

Elimination: 22% renal

Adverse Effect

Headache

Hypotension

Syncope

Rebound hypertension

Tolerance with prolonged use ~24 hours

Warnings and

Drug

Author,

year

Design/

sample size

Intervention & Comparison

Outcome

Patrick,

2020

Observational

n=48

IV NTG 1 mg bolus by EMS

High dose NTG associated with:

Decreased SBP by 31 mmHg from baseline

Decreased HR by 10 beats per minute

Increased 02 saturation from 86% to 98%

1/48 (2%) had symptomatic hypotension

Hsieh,

2018

Case report

n=3

Sublingual NTG 0.6 mg/tab x 3 doses

IV NTG bolus 1 mg every 2 min*

IV NTG infusion 40 mcg/min*

*If prior therapy failed

High dose NTG associated with:

• Normalize respiratory status

No intubation + no ICU admission

Paone,

2018

Case report

n= 1

IV NTG infusion

400 mcg/min titrated by 50 mcg/min

High dose NTG bolus associated with:

Symptomatic resolution @ 6 minutes

Wilson,

Hsieh Y. Turk J Emerg Med. 2018; 18(1): 34-36.

Wilson SS. Am J Emerg Med. 2017;35(1):126-31.

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• López-Rivera F. Am J Case Rep. 2019 Jan 21;20:83-90.
• Clemency BM, Prehosp Disaster Med. 2013 Oct;28(5):477-81.
• Patrick C. Prehosp Emerg Care. 2020 Jan 27:1-7.

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Hsieh Y. Turk J Emerg Med. 2018; 18(1): 34-36.

Wilson SS. Am J Emerg Med. 2017;35(1):126-31.

• Levy P. Ann Emerg Med. 2007;50:144-52.
• Sharon A . J Am Coll Cardiol. 2000;36(3):832-7.
• Cotter G. Lancet. 1998;351(9100):389-93.
• Paone S. Am J Emerg Med. 2018;36(8):1526.e5-1526.e7.
• López-Rivera F. Am J Case Rep. 2019 Jan 21;20:83-90.
• Clemency BM, Prehosp Disaster Med. 2013 Oct;28(5):477-81.
• Patrick C. Prehosp Emerg Care. 2020 Jan 27:1-7.