When to use nitroglycerin (glyceryl trinitrate) in acute pulmonary edema?

From the Guidelines

Nitroglycerin should be used in pulmonary edema when it's associated with acute heart failure, especially with hypertension or acute coronary syndrome, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Key Considerations

• The typical starting dose is 0.4 mg sublingually, which can be repeated every 5 minutes for a total of 3 doses, or as an intravenous infusion starting at 5-10 mcg/min and titrating up by 5-10 mcg/min every 3-5 minutes based on response, with a maximum dose of 200 mcg/min.
• Continuous monitoring of blood pressure is essential, as nitroglycerin should not be given if systolic blood pressure is below 90 mmHg.
• Nitroglycerin works by dilating veins at lower doses, reducing preload and pulmonary congestion, and at higher doses, it dilates arteries, reducing afterload and improving cardiac output.

Important Precautions

• Patients should be positioned upright if possible to further reduce venous return, and supplemental oxygen should be administered concurrently.
• Nitroglycerin should be used cautiously in patients taking phosphodiesterase inhibitors like sildenafil due to the risk of severe hypotension, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

Clinical Context

• The use of nitroglycerin in pulmonary edema is supported by the 2013 ACCF/AHA guideline for the management of heart failure, which recommends its use as an adjuvant to diuretic therapy for relief of dyspnea in patients admitted with acutely decompensated heart failure 1.
• The ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008 also support the use of nitroglycerin in the early phase of acute heart failure, with a recommended initial dose of 10-20 mg/min and titration up to 5-10 mg/min every 3-5 minutes as needed 1.

From the FDA Drug Label

Although the usual starting adult dose range reported in clinical studies was 25 mcg/min or more, these studies used PVC administration sets. THE USE OF NON-ABSORBING TUBING WILL RESULT IN THE NEED FOR REDUCED DOSES. Some patients with normal or low left ventricular filling pressures or pulmonary capillary wedge pressure (e.g., angina patients without other complications) may be hypersensitive to the effects of nitroglycerin and may respond fully to doses as small as 5 mcg/min.

The use of nitroglycerin in pulmonary edema is not directly addressed in the provided drug label. However, it can be used in patients with low left ventricular filling pressures or pulmonary capillary wedge pressure.

• The initial dosage should be 5 mcg/min delivered through an infusion pump capable of exact and constant delivery of the drug.
• Titration must be adjusted to the clinical situation, with dose increments becoming more cautious as partial response is seen.
• Continuous monitoring of physiologic parameters (i.e., blood pressure and heart rate in all patients, other measurements such as pulmonary capillary wedge pressure, as appropriate) MUST be performed to achieve the correct dose 2.

From the Research

Indications for Nitroglycerin in Pulmonary Edema

• Nitroglycerin (NTG) is commonly used for the management of pulmonary edema in acute heart failure presentations 3.
• High-dose NTG may be an effective way to decrease times to achieve blood pressure targets in patients with acute pulmonary edema 3, 4.
• NTG can be used to treat hypertensive cardiogenic pulmonary edema, which presents with a sudden onset of severe dyspnea, tachycardia, and tachypnea 4, 5.

Dosage and Administration

• High-dose NTG (≥100 μg/min) may be more effective than low-dose NTG (<100 μg/min) in achieving blood pressure targets in patients with acute pulmonary edema 3.
• NTG can be titrated every 3 minutes, increasing by 15 mcg/min until a dose of 120 mcg/min is reached 4.
• High-dose NTG can be used in combination with other treatments, such as bilevel positive airway pressure (BiPAP) ventilation, to manage acute hypertensive cardiogenic pulmonary edema 5.

Clinical Outcomes

• High-dose NTG has been shown to improve clinical outcomes, including time to resolution of severe hypertension, in patients with acute pulmonary edema 3, 4.
• NTG can help to reduce the need for endotracheal intubation and admission to the intensive care unit (ICU) in patients with acute pulmonary edema 4, 5.
• The use of NTG in patients with acute pulmonary edema requires careful monitoring of blood pressure and other clinical parameters to minimize the risk of adverse effects 3, 6.