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

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Introduction

  • 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.

Pharmacology of Nitroglycerin (NTG)

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.

Overview of Key Evidence

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

Clinical Conclusions

  • 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.

Full Reference List

  1. Nitroglycerin. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved March 5, 2020, from http://www.micromedexsolutions.com/
  2. Kramer K. Am Heart J. 2000;140:451–5.
  3. Agrawal N. Crit Care Med. 2016;20:39–43.
  4. Mebazaa A. Eur J Heart Fail. 2015;17:544–58.
  5. Viau DM. Heart. 2015;101:1861–7.
  6. McMurray JJ. Eur J Heart Fail. 2012;14:803–69.
  7. López-Rivera F. Am J Case Rep. 2019 Jan 21;20:83–90.
  8. Clemency BM. Prehosp Disaster Med. 2013 Oct;28(5):477–81.
  9. Yancy CW. J Am Coll Cardiol. 2013;62:e147–239.
  10. Hsieh Y. Turk J Emerg Med. 2018;18(1):34–36.
  11. Wilson SS. Am J Emerg Med. 2017;35(1):126–31.
  12. Levy P. Ann Emerg Med. 2007;50:144–52.
  13. Sharon A. J Am Coll Cardiol. 2000;36(3):832–7.
  14. Cotter G. Lancet. 1998;351(9100):389–93.
  15. Paone S. Am J Emerg Med. 2018;36(8):1526.e5–1526.e7.
  16. Patrick C. Prehosp Emerg Care. 2020 Jan 27:1–7.

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