What are the considerations for using vasopressors (vasoactive medications that constrict blood vessels) in patients with pulmonary hypertension (high blood pressure in the lungs)?

From the Guidelines

Vasopressors should be used cautiously in patients with pulmonary hypertension, with careful consideration of their effects on pulmonary vascular resistance and right ventricular function, and norepinephrine is generally preferred as a first-line agent at doses of 0.01-3 mcg/kg/min. When administering vasopressors, continuous hemodynamic monitoring is essential, ideally with a pulmonary artery catheter to directly measure pulmonary pressures 1. The goal should be to maintain adequate systemic blood pressure (mean arterial pressure 65-75 mmHg) to ensure coronary perfusion while minimizing increases in pulmonary vascular resistance. Combining vasopressors with pulmonary vasodilators like inhaled nitric oxide, prostacyclins, or phosphodiesterase inhibitors may help counterbalance the potential adverse effects on pulmonary circulation 1.

Some key considerations for vasopressor use in pulmonary hypertension include:

• Avoiding phenylephrine due to its potential to increase pulmonary vascular resistance and worsen right ventricular afterload
• Using epinephrine and dopamine with extreme caution due to their potential to increase pulmonary pressures
• Maintaining systemic vascular resistance greater than pulmonary vascular resistance to prevent right ventricular ischemia
• Considering the use of inotropes with neutral or beneficial effects on pulmonary vascular resistance, such as dobutamine or milrinone

It's also important to address the underlying cause of shock simultaneously, as vasopressors are supportive rather than definitive therapy 1. Additionally, the use of advanced vasoactive agents approved only for the management of pulmonary arterial hypertension should not be routinely offered to patients with pulmonary hypertension resulting from left heart disease or hypoxemic lung diseases 1.

In terms of specific therapies, options may include:

• Endothelin receptor antagonists, such as ambrisentan or bosentan
• Phosphodiesterase inhibitors, such as sildenafil or tadalafil
• Prostacyclin analogues, such as epoprostenol or iloprost
• Soluble guanylate cyclase stimulators, such as riociguat
• Prostacyclin receptor agonists, such as selexipag 1.

Ultimately, the choice of therapy should be individualized based on the patient's specific condition and response to treatment, and guided by the most recent and highest quality evidence available 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. The use of vasopressors in patients with pulmonary hypertension is not directly addressed in the provided drug label for sildenafil.

• The label discusses the mechanism of action of sildenafil as a PDE-5 inhibitor, leading to vasodilation of the pulmonary vascular bed.
• It does not provide information on the use of vasopressors, which are vasoactive medications that constrict blood vessels, in patients with pulmonary hypertension. Therefore, the use of vasopressors in this context is not supported by the provided drug label 2.

From the Research

Considerations for Vasopressor Use in Pulmonary Hypertension

• The use of vasopressors in patients with pulmonary hypertension (PH) requires careful consideration, as these medications can increase pulmonary artery pressure and worsen right ventricular failure 3, 4, 5.
• Vasopressors should be used cautiously to maintain systemic blood pressure, while avoiding excessive increases in pulmonary artery pressure 4, 5.
• The choice of vasopressor and inotrope should be individualized based on patient response and take into consideration their effects on vascular resistance and cardiac output 5, 6.

Alternative Therapies

• Pulmonary vasodilators, such as prostacyclins, inhaled nitric oxide, and phosphodiesterase type 5 inhibitors, may be used to reduce pulmonary artery pressure and improve right ventricular function 3, 4.
• Inotropes, such as dobutamine and milrinone, may be used to improve right ventricular contractility 3, 4.
• Ventricular assist devices and extracorporeal life support may be considered in patients with severe right ventricular failure 4.

Limitations and Hazards of Vasodilator Therapy

• Vasodilator therapy may not be effective in reducing pulmonary vascular resistance and may lead to systemic hypotension, exacerbation of pulmonary hypertension, and worsening of right ventricular failure 7.
• Beneficial hemodynamic responses to vasodilator therapy are seen in only 15% to 25% of patients with primary pulmonary hypertension 7.