What is the dosing protocol for an ISDN (Isosorbide Dinitrate) drip?

ISDN Drip Protocol Using 10 mg Ampule

Critical Recommendation

Nitroglycerin, not ISDN, is the only nitrate formulation available and recommended for intravenous use in the United States—intravenous ISDN drips are not standard practice in U.S. protocols. 1

Why ISDN IV is Not Standard Practice

• The American College of Cardiology explicitly states that nitroglycerin is the only nitrate formulation available for intravenous use in the United States 1
• The American College of Cardiology recommends using nitroglycerin instead of ISDN for intravenous nitrate therapy 1
• ISDN is primarily formulated for oral and sublingual routes, not continuous intravenous infusion 2, 3

If ISDN IV Must Be Used (Non-U.S. Settings)

Dosing Protocol from Research Evidence

Starting dose: 50 mcg/min, titrated upward based on hemodynamic response 4

Dose range: 50 to 533 mcg/min (mean effective dose approximately 326 mcg/min) 4

Titration strategy:

• The effective dose cannot be predicted from baseline hemodynamic values and must be individualized through careful titration 4
• Titrate to achieve ≥25% reduction in pulmonary artery wedge pressure if elevated 4
• Monitor for hypotension as the primary dose-limiting factor 4

Preparation from 10 mg Ampule

• Dilute 10 mg (10,000 mcg) ISDN in 100-250 mL of D5W or normal saline
• Use non-PVC tubing to prevent drug absorption 1
• Example: 10 mg in 100 mL = 100 mcg/mL concentration

Expected Hemodynamic Effects

• Reduction in pulmonary artery wedge pressure from approximately 32 mm Hg to 24 mm Hg 4
• Decrease in mean blood pressure (96 to 90 mm Hg) 4
• Reduction in systemic vascular resistance (1715 to 1548 dynes·s·cm⁻⁵) 4
• Increase in cardiac index from 2.37 to 2.54 L/min/m² 4
• Decrease in mean right atrial pressure (11 to 7 mm Hg) 4

Critical Monitoring Requirements

Blood pressure monitoring:

• Avoid systolic BP <90 mm Hg or >30 mm Hg below baseline 2
• In previously normotensive patients, do not titrate systolic BP below 110 mm Hg 2
• In hypertensive patients, do not reduce mean arterial pressure by >25% 2

Special caution in right ventricular infarction:

• Exercise extreme caution in patients with inferior wall MI due to frequent RV involvement 1, 5
• These patients depend on adequate RV preload and can experience profound hypotension 1, 5

Contraindications:

• Sildenafil use within 24 hours 2, 5
• Tadalafil use within 48 hours 2, 5
• Initial systolic BP <90 mm Hg 2
• Marked bradycardia or tachycardia 2

Tolerance Development

Critical timing:

• Tolerance to hemodynamic effects develops after 24 hours of continuous therapy 1, 5
• Significant coronary vasodilating effects persist after 2-day infusion but tolerance develops within 5 days 6
• Provide a nitrate-free interval of at least 10-14 hours daily to prevent tolerance 1, 5

Preferred Alternative: Nitroglycerin IV Protocol

Starting dose: 5-10 mcg/min 2, 1

Titration:

• Increase by 10 mcg/min every 3-5 minutes until symptom relief or BP response 2
• If no response at 20 mcg/min, use increments of 10-20 mcg/min 2
• Maximum dose typically 200 mcg/min 2

Advantages over ISDN:

• Very short half-life (several minutes) making it suitable for precise IV titration 1
• Standard formulation available in the U.S. 1
• More predictable pharmacokinetics for acute management 1

Common Pitfalls to Avoid

• Do not use ISDN IV if nitroglycerin is available—it is the preferred agent 1
• Do not attempt to predict effective ISDN dose from baseline hemodynamics—titration is mandatory 4
• Do not continue infusion beyond 24-48 hours without a nitrate-free interval—tolerance will develop 1, 6
• Do not use in patients who recently took phosphodiesterase inhibitors—risk of profound hypotension and death 2, 5
• Do not use standard oral ISDN dosing protocols for IV administration—these are completely different routes with different pharmacokinetics 2, 3