What is the role of nitroglycerin (NTG) in the management of acute myocardial infarction (MI)?

Role of Nitroglycerin in Acute Myocardial Infarction

Nitroglycerin should be administered to patients with acute MI presenting with ischemic chest pain, provided systolic blood pressure is ≥90 mm Hg and there is no evidence of right ventricular infarction, marked bradycardia, or tachycardia. 1, 2

Mechanism of Benefit

Nitroglycerin provides therapeutic benefit in acute MI through three primary mechanisms 1:

• Dilation of epicardial conductance arteries, improving coronary blood flow
• Increased collateral blood flow to ischemic myocardium 3
• Decreased left ventricular preload, reducing myocardial oxygen demand 1

Initial Administration Protocol

Sublingual Nitroglycerin

• Administer sublingual nitroglycerin immediately to patients with ischemic pain unless systolic BP <90 mm Hg 1, 2
• Even with systolic BP <90 mm Hg, a single sublingual dose may be attempted if ongoing ischemic pain is present and IV access is established 1, 2
• Monitor vital signs closely for several minutes after initial dose 1

Intravenous Nitroglycerin

• IV nitroglycerin is preferred over sublingual or transdermal formulations for precise minute-to-minute control 1
• Avoid long-acting oral nitrate preparations in early acute MI management 1
• IV nitroglycerin is FDA-indicated for control of congestive heart failure in the setting of acute MI 4

Absolute Contraindications

Do not administer nitroglycerin if any of the following are present 2, 5:

• Systolic blood pressure <90 mm Hg or ≥30 mm Hg below baseline
• Right ventricular infarction (perform right-sided ECG in all inferior STEMIs before giving nitrates) 2
• Marked bradycardia or tachycardia (especially tachycardia >100 bpm without heart failure) 1, 5
• Relative hypotension in the presence of bradycardia or tachycardia 1

Critical Warning for Right Ventricular Infarction

Patients with RV infarction are critically dependent on adequate right ventricular preload to maintain cardiac output and can experience catastrophic hypotension with nitrate administration 1, 5. Nitroglycerin should be used with extreme caution or avoided entirely in suspected RV infarction 1, 2.

Titration and Monitoring

Hemodynamic Goals

When administering IV nitroglycerin 6:

• Decrease mean arterial pressure by 10% in normotensive patients
• Decrease mean arterial pressure by 30% in hypertensive patients
• Never allow systolic BP to fall below 90 mm Hg 6
• Control of clinical symptoms (pain, heart failure) is a key endpoint 6

Monitoring Requirements

• Frequent measurement of cuff blood pressure and heart rate is sufficient for titration 1
• Invasive hemodynamic monitoring may be preferable if high doses are required, blood pressure instability occurs, or there is doubt about left ventricular filling pressure adequacy 1

Management of Complications

Hypotension

If hypotension develops during nitroglycerin infusion 6:

• Immediately discontinue nitroglycerin
• Elevate legs to increase venous return
• Administer rapid IV fluid bolus

Other Adverse Effects

• Headache is frequent but manageable 1
• Worsening hypoxemia may occur through increased ventilation-perfusion mismatch 1
• Inadvertent systemic hypotension with worsening myocardial ischemia is the most serious complication 1, 2

Special Populations

Inferior Wall MI

Exercise particular caution in inferior wall MI patients 1:

• Carefully titrate nitroglycerin as these patients may have concomitant RV involvement
• Always obtain right-sided ECG to exclude RV infarction before administration 2
• Patients with inferior MI and RV involvement can experience profound hypotension during nitrate administration 6

Patients with Elevated Filling Pressures

Patients with elevated pulmonary capillary wedge pressure (>15 mm Hg) benefit most consistently from nitroglycerin alone, as the preload reduction is particularly beneficial 7. In contrast, patients with normal filling pressures may require blood pressure support with phenylephrine to prevent reflex tachycardia and hypotension 7.

Evidence for Infarct Size Reduction

While the FDA label notes that benefits in acute MI have not been definitively established 8, research evidence suggests potential benefit:

• Reduction in infarct size has been demonstrated in patients with inferior infarction (36% reduction) but not anterior infarction 9
• Decreased ST-segment elevation and improved hemodynamics have been consistently shown 10, 11
• 24-48 hour infusions have been associated with reduced short-term mortality and myocardial preservation 3

Current Clinical Practice Recommendations

Intravenous nitroglycerin should be used as initial adjunctive therapy 3:

• In patients receiving thrombolytic therapy or acute PCI within 4-6 hours of symptom onset
• For patients treated 6-12 hours after symptom onset, continue for 24-48 hours
• For congestive heart failure or arterial hypertension complicating acute MI
• For post-infarction unstable angina

Alternative Analgesics When Nitrates Are Contraindicated

When nitroglycerin is contraindicated 2, 5:

• Morphine sulfate (2-4 mg IV) for pain relief
• Beta-blockers as first-line treatment for reducing heart rate and myocardial oxygen demand in patients with tachycardia
• Urgent reperfusion therapy (angioplasty or fibrinolysis) provides the most effective relief by addressing underlying ischemia

High-Dose Considerations

Doses >200 mcg/min are associated with increased hypotension risk; consider alternative vasodilators such as calcium channel blockers at this threshold 6.