What is the management of myocardial infarction (MI) with regards to pain relief and vasodilation, particularly with nitrates (e.g. nitroglycerin) and other therapies?

From the Guidelines

Pain management in myocardial infarction (MI) primarily involves nitroglycerin and morphine, with nitroglycerin serving dual purposes of pain relief and vasodilation, and should be administered as 0.4 mg sublingually every 5 minutes for up to three doses, followed by intravenous nitroglycerin at 5-200 mcg/min if needed for ongoing pain or hypertension, as recommended by the most recent guidelines 1.

Key Considerations

• Nitroglycerin works by relaxing vascular smooth muscle, reducing preload and afterload, which decreases myocardial oxygen demand and improves coronary blood flow to ischemic areas.
• However, nitroglycerin is contraindicated in patients with hypotension (systolic BP <90 mmHg), right ventricular infarction, or recent phosphodiesterase-5 inhibitor use.
• Morphine sulfate (2-4 mg IV, repeated every 5-15 minutes) is indicated when nitroglycerin fails to relieve pain.
• Other important MI management includes aspirin (325 mg chewed immediately), antiplatelet therapy (P2Y12 inhibitors like clopidogrel 300-600 mg loading dose), anticoagulation (unfractionated heparin or low-molecular-weight heparin), and beta-blockers (metoprolol 5 mg IV every 5 minutes for 3 doses, followed by oral therapy) 1.

Additional Therapies

• Oxygen should be administered only for hypoxemia (O2 saturation <90%).
• The primary goal is rapid reperfusion through percutaneous coronary intervention or fibrinolytic therapy when PCI is unavailable within 120 minutes of first medical contact.
• Nitrates should not be administered to patients with NSTE-ACS who recently received a phosphodiesterase inhibitor, especially within 24 hours of sildenafil or vardenafil, or within 48 hours of tadalafil 1.

From the FDA Drug Label

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload) Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Management of Myocardial Infarction (MI) with Nitrates:

• Nitrates, such as nitroglycerin, are used for pain relief and vasodilation in the management of MI.
• The goal of nitrate therapy is to reduce myocardial oxygen demand by decreasing preload and afterload, and to improve coronary blood flow.
• Key Benefits:
  • Reduction of left ventricular end-diastolic pressure (preload)
  • Decrease in peripheral vascular resistance and arterial pressure (afterload)
  • Dilation of large epicardial coronary arteries
• Administration:
  • Sublingual nitroglycerin tablets can be used for acute anginal attacks, with a dose repeated approximately every 5 minutes until relief is obtained 2
  • Intravenous nitroglycerin can be used for more severe cases, with careful monitoring of blood pressure and hemodynamic parameters 3

From the Research

Management of Myocardial Infarction with Nitrates

• Nitrates, such as nitroglycerin, are used in the management of myocardial infarction (MI) for pain relief and vasodilation 4, 5, 6, 7, 8.
• The use of nitrates in acute MI has been shown to reduce morbidity and mortality, particularly in patients with left ventricular failure 4, 6, 7.
• Intravenous nitroglycerin is the preferred route of administration, with a dose of 5 micrograms/min initially, increasing by 5-10 micrograms/min every 5-10 minutes until mean arterial pressure is reduced 10-20% or pulmonary capillary wedge pressure is reduced to 15 mm Hg 4.
• Nitrates have been shown to relieve symptoms and improve left ventricular hemodynamics during acute myocardial ischemia, and to reduce indices of infarct evolution when administered early (less than 6 hours) 6.

Side Effects and Contraindications

• Common side effects of nitrate therapy include headache, hypotension, and dizziness 5.
• Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy 5.
• Nitrates should be used with caution in patients with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine, due to the risk of severe life-threatening hypotension or death 5.

Clinical Practice and Trials

• Current clinical practice utilizes intravenous nitroglycerin as initial therapy for patients receiving intravenous thrombolytic therapy and/or acute percutaneous transluminal coronary angioplasty within 4-6 hours of the onset of symptoms of acute MI 7.
• Meta-analyses and trials, such as GISSI-3 and ISIS-4, have shown mixed results regarding the benefit of nitrates in acute MI, with some suggesting a reduction in mortality and others showing no significant benefit 8.
• Further trials are required to assess the possibility of an early acute benefit of nitrate therapy in subgroups of infarcts 8.