What is the nitroglycerin protocol for managing angina or suspected myocardial infarction?

Nitroglycerin Protocol for Angina and Acute Coronary Syndromes

For suspected acute coronary syndrome, administer one 0.3-0.6 mg sublingual nitroglycerin tablet at symptom onset; if pain is unimproved or worsening after 5 minutes, call 9-1-1 immediately before taking additional doses—do not wait for three doses before seeking emergency care. 1

Prehospital and Initial Management

First Dose Decision Tree

Contraindications—Do NOT give nitroglycerin if: 1, 2

• Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline
• Marked bradycardia or tachycardia
• Suspected right ventricular infarction (especially with inferior MI—obtain right-sided ECG first)
• Recent phosphodiesterase inhibitor use (sildenafil within 24 hours, tadalafil/vardenafil within 48 hours)

Exception: In hospitalized patients with systolic BP <90 mmHg but ongoing ischemic pain, a single sublingual dose may be attempted only after IV access is established. 1, 2

Dosing Protocol for Suspected ACS

Sublingual nitroglycerin (tablet or spray): 3

• Initial dose: 0.3-0.6 mg sublingual (or 0.4 mg spray)
• Timing: At first sign of chest discomfort
• Patient position: Sitting (reduces orthostatic hypotension risk) 3

Critical 5-minute decision point: 1

• If pain unimproved or worsening after 5 minutes → Call 9-1-1 immediately, then may give second dose
• If pain significantly improved (chronic stable angina only) → May repeat every 5 minutes for maximum 3 doses total
• If pain persists after 3 doses over 15 minutes → Emergency medical attention required

Common pitfall: The outdated "three doses before calling" approach delays critical care in ACS. The modern protocol prioritizes early EMS activation after just one ineffective dose. 1

Intravenous Nitroglycerin Protocol

Indications for IV Nitroglycerin

• Ongoing refractory ischemic symptoms despite sublingual dosing 1
• Acute hypertension with myocardial ischemia 1
• Acute left ventricular failure/pulmonary edema with adequate blood pressure 4

IV Initiation and Titration

Starting dose: 10 mcg/min via continuous infusion through non-absorbing tubing 1

Titration algorithm: 1

1. Increase by 10 mcg/min every 3-5 minutes initially
2. If no response at 20 mcg/min, use increments of 10-20 mcg/min
3. Once partial BP response observed, reduce increment size and lengthen intervals
4. Ceiling dose: 200 mcg/min commonly used (though doses up to 300-400 mcg/min do not increase methemoglobin) 1

Titration endpoints: 1, 5

• Symptom relief (primary goal—do not continue increasing if symptoms resolve)
• Blood pressure response: Reduce MAP by 10% in normotensive patients or up to 30% in hypertensive patients
• Never allow systolic BP to fall below 90 mmHg 5
• In previously normotensive: maintain SBP ≥110 mmHg
• In hypertensive: do not reduce >25% below baseline MAP

Special Considerations for Inferior MI

Critical assessment before nitroglycerin in inferior MI: 2, 5

• Obtain right-sided ECG to evaluate for RV infarction
• Patients with RV involvement are critically dependent on preload—nitroglycerin can cause profound hypotension
• In acute inferior MI with RV involvement: nitroglycerin is contraindicated 2
• In old inferior MI: hemodynamic vulnerability is substantially reduced unless residual RV dysfunction or ongoing ischemia present 5

If hypotension develops during infusion: 5

1. Immediately discontinue nitroglycerin
2. Elevate legs to increase venous return
3. Administer rapid IV fluid bolus

Transition and Maintenance Therapy

Converting from IV to Oral/Topical

Timing: After 12-24 hours free of ischemic symptoms, attempt dose reduction and conversion 1

Avoid abrupt cessation: Gradual dose reduction prevents rebound ischemia (ECG changes documented with abrupt discontinuation) 1

Non-parenteral alternatives: 1

• Transdermal: 0.2-0.8 mg/hour every 12 hours (allows nitrate-free interval)
• Isosorbide dinitrate: 5-80 mg 2-3 times daily
• Isosorbide mononitrate: 20 mg twice daily or 60-240 mg extended-release once daily

Tolerance Prevention

Tolerance develops after 24 hours of continuous therapy—prevention strategies: 1

• Incorporate 10-12 hour nitrate-free interval (typically overnight)
• Use lower doses with intermittent dosing
• If continued IV therapy >24 hours required, may need periodic dose increases
• Do not continue IV nitroglycerin in patients free of ischemic signs/symptoms

Caveat: Some patients experience increased anginal frequency during nitrate-free intervals; balance tolerance prevention against symptom control. 1

Prophylactic Use

Timing: 5-10 minutes before activities expected to precipitate angina 3, 6

Evidence: Prophylactic sublingual nitroglycerin increases angina-free walking time, delays ST-segment depression, and improves exercise tolerance. 6

Combination with Vasopressors (Advanced)

In acute LV failure with hypotension requiring vasopressor support: 7

• Norepinephrine 0.2 mcg/kg/min (central line), titrate to maintain SBP >90 mmHg
• Nitroglycerin can be added at lower starting dose (5 mcg/min) to reduce elevated filling pressures
• Requires intensive monitoring with arterial line
• Target: maintain SBP >90 mmHg while reducing pulmonary wedge pressure by 10-30%

This combination is Class IIb, Level C evidence—expert consensus rather than trial data. 7

Practical Considerations

Side effects: 1, 3

• Headache (common, may indicate drug activity)
• Hypotension (most serious complication)
• Paradoxical bradycardia with hypotension
• May aggravate hypoxemia via ventilation-perfusion mismatch

Patient education: 3

• Do not chew, crush, or swallow sublingual tablets
• Burning/tingling sensation is common but not a reliable potency indicator
• Store in original glass container, tightly capped
• Sit when taking to prevent falls from lightheadedness

Drug interactions: 3

• Alcohol: additive hypotension
• Aspirin: enhanced vasodilatory effects
• Tricyclic antidepressants/anticholinergics: may impair sublingual dissolution (consider spray formulation)