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High-Dose Nitroglycerin for Sympathetic Crashing Acute Pulmonary Edema


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 ActionNitroglycerin, an organic nitrate, is a vasodilating agent that relieves tension on vascular smooth muscle and dilates peripheral veins and arteries (at higher doses)
DoseChest 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
AdministrationIV 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/PDOnset: 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 EffectHeadache Hypotension Syncope  Rebound hypertension Tolerance with prolonged use  ~24 hours
Warnings and Drug Interactions PDE inhibitors Aortic stenosis, preload-dependent cardiomyopathy, hypertrophic obstructive cardiomyopathy, hypotension at any time
Compatibility•    Incompatible with levofloxacin,  SMX-TMP, daptomycin, and phenytoin

jipruitt@augusta.edu                                                                                                                                                      For educational purposes only

  Overview of Evidence
Author, year Design/ sample sizeIntervention & ComparisonOutcome
Patrick, 2020Observational   n=48IV NTG 1 mg bolus by EMSHigh 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, 2018Case report   n=3Sublingual 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 failedHigh dose NTG associated with: Normalize respiratory statusNo intubation + no ICU admission
Paone, 2018Case report   n= 1IV NTG infusion    400 mcg/min titrated by 50 mcg/minHigh dose NTG bolus associated with:          Symptomatic resolution @ 6 minutes
Wilson, 2016Observational    n=395IV NTG bolus 500–2000 mcg Q3–5 min   vs   IV NTG infusion 20–35 mcg/min   vs   IV NTG bolus + infusionHigh dose NTG bolus associated with: Decreased ICU admissionShorter LOS No differences in adverse outcomes (intubation)
Levy, 2007Observational   n=29IV NTG Bolus 2 mg IV Q3 minHigh dose NTG bolus associated with:     Reduced intubation, need for bi-level positive pressure ventilation, and ICU admission
Sharon, 2000RCT   n= 40IV bolus isosorbide 4 mg Q4 min   vs   Isosorbide infusion starting @ 10 mcg/min + BiPAPHigh dose isosorbide bolus associated with:     Decrease intubations, MI, mortality, and improved PaO2
Cotter,  1998RCT   n= 104IV isosorbide dinitrate 3 mg Q5 min + furosemide 50 mg   vs   IV isosorbide infusion 16 mcg/min titrate Q15min + furosemide 80 mg Q15 minHigh dose isosorbide bolus associated with: Reduction in mechanical ventilation and MIImprovement in Pa02 and RR Less adverse effects  


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