Is GTN (glyceryl trinitrate) infusion better than Isoket (isosorbide dinitrate) for acute pulmonary edema?

GTN vs Isoket for Acute Pulmonary Edema

Both GTN (glyceryl trinitrate/nitroglycerin) and Isoket (isosorbide dinitrate) are equally effective for acute pulmonary edema, with no evidence demonstrating superiority of one over the other—choose based on local availability and familiarity, prioritizing high-dose infusion (≥100 mcg/min for GTN, 1-10 mg/h for ISDN) combined with low-dose diuretics rather than the specific nitrate formulation. 1

The Evidence Shows No Difference Between Nitrate Types

The European Society of Cardiology guidelines explicitly state that both glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) are acceptable options for acute heart failure with pulmonary edema, listing them interchangeably without preference. 1 The 2012 ESC guidelines recommend "an i.v. infusion of a nitrate" for patients with pulmonary congestion and systolic BP >110 mmHg, again making no distinction between formulations. 1

What matters is the dosing strategy, not which nitrate you choose:

• GTN dosing: Start at 20 mcg/min, increase to 200 mcg/min as tolerated 1
• ISDN dosing: 1-10 mg/h 1
• Both should be titrated to the highest hemodynamically tolerable dose 1, 2

High-Dose Nitrates Are Superior to Low-Dose

The critical distinction is not GTN versus ISDN, but rather high-dose versus low-dose nitrate therapy:

• High-dose nitrates combined with low-dose furosemide are superior to high-dose diuretic treatment alone for severe pulmonary edema 1, 2
• Patients receiving high-dose GTN (>100 mcg/min) achieve blood pressure targets 3.5 times faster than low-dose strategies 3
• In sympathetic crashing acute pulmonary edema (SCAPE), high-dose GTN achieved symptom resolution in 65.4% at 6 hours versus only 11.5% with low-dose 4
• High-dose ISDN (4 mg IV boluses every 4 minutes) reduced intubation rates to 20% compared to 80% with conventional therapy in one study 5

Practical Algorithm for Nitrate Use

Initial assessment:

• Confirm systolic BP >110 mmHg (contraindicated if <110 mmHg) 1
• Rule out severe aortic or mitral stenosis (relative contraindication) 1

Starting therapy:

• Begin with sublingual nitroglycerin 0.4-0.6 mg every 5-10 minutes while establishing IV access 6, 2
• Start IV nitrate infusion immediately: GTN at 20-30 mcg/min OR ISDN at 1 mg/h 1, 6
• Administer low-dose furosemide 40 mg IV bolus (not high-dose monotherapy) 2

Titration strategy:

• Increase GTN by 15-30 mcg/min every 3-5 minutes until target reached 3, 7
• Target: Systolic BP reduction of 10 mmHg mean arterial pressure OR systolic BP 90-100 mmHg 1
• Maximum doses used safely: GTN up to 200 mcg/min 1, with case reports of ultra-high doses (>500 mcg/min) 8

Monitoring:

• Check BP every 3-5 minutes during titration 1, 2
• Reduce dose if systolic BP falls below 90-100 mmHg 1
• Discontinue if BP drops further 1

Critical Pitfalls to Avoid

Do not use low-dose nitrates: The evidence consistently shows that suboptimal dosing has limited effectiveness and may fail to prevent intubation. 1, 2, 3, 4

Do not use high-dose diuretics as monotherapy: Furosemide transiently worsens hemodynamics for 1-2 hours (increases SVR, increases LV filling pressures, decreases stroke volume), and aggressive diuresis is associated with worsening renal function and increased mortality. 2

Beware of nitrate tolerance: Effectiveness is limited to 16-24 hours with continuous high-dose IV infusion. 1

Monitor for hypotension aggressively: The most common adverse effect limiting therapy is excessive BP reduction—this requires continuous monitoring during the acute phase. 1

Supporting Evidence for Either Nitrate

One study specifically examined high-dose ISDN (repeated 4 mg boluses) and found it superior to BiPAP ventilation, with only 20% requiring intubation versus 80% in the BiPAP group. 5 However, this study compared ISDN to a different intervention entirely, not to GTN.

The most recent high-quality evidence focuses on GTN dosing strategies rather than comparing nitrate types, with a 2024 randomized trial demonstrating clear superiority of high-dose GTN (>100 mcg/min) over conventional low-dose in SCAPE patients. 4

The bottom line: Use whichever nitrate is immediately available in your institution, but ensure you use high-dose infusion combined with judicious low-dose diuretics rather than aggressive diuresis alone. 1, 2, 4