What is the treatment for moderate pulmonary hypertension (PH) post-operatively?

From the Guidelines

The treatment of moderate pulmonary hypertension after surgery should prioritize a multifaceted approach focusing on optimizing oxygenation and reducing right ventricular afterload, with inhaled nitric oxide (iNO) at 10-40 ppm being a first-line option for immediate post-surgical management, as supported by the most recent evidence 1.

Key Considerations

• Ensuring adequate oxygenation with supplemental oxygen to maintain oxygen saturation above 92% is crucial, as hypoxemia can worsen pulmonary vasoconstriction.
• Pulmonary vasodilators, such as iNO, are the cornerstone of pharmacological therapy, offering selective pulmonary vasodilation without systemic effects.
• For patients requiring longer-term therapy, oral phosphodiesterase-5 inhibitors like sildenafil or tadalafil are effective options.
• Endothelin receptor antagonists, such as bosentan, may be added for persistent symptoms, and diuretics like furosemide can help manage fluid overload.
• Hemodynamic support with inotropes may be necessary if right ventricular dysfunction is present.

Management Strategies

• Inhaled epoprostenol (Flolan) at 10-50 ng/kg/min can be used as an alternative to iNO.
• Oral phosphodiesterase-5 inhibitors, such as sildenafil (starting at 20 mg three times daily) or tadalafil (40 mg once daily), are effective for longer-term therapy.
• Endothelin receptor antagonists like bosentan (62.5 mg twice daily, increasing to 125 mg twice daily after 4 weeks) may be added for persistent symptoms.
• Diuretics, such as furosemide (20-40 mg IV or oral daily), should be used to manage fluid overload, which can exacerbate pulmonary pressures.
• Hemodynamic support with inotropes like dobutamine (2-10 μg/kg/min) or milrinone (0.375-0.75 μg/kg/min) may be necessary if right ventricular dysfunction is present, as discussed in 1.

Perioperative Care

• A thorough preoperative evaluation and discussion of risks and benefits in advance of surgery is critical, as emphasized in 1 and 1.
• Optimizing PAH-specific therapy and volume status as much as possible prior to surgery is essential.
• A multi-disciplinary team approach, including surgeons and cardiac anesthesiologists, is necessary to formulate an approach to perioperative care, as highlighted in 1.

From the FDA Drug Label

Treprostinil injection is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%) The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, reduce the infusion rate to 0.625 ng/kg/min. The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks of treatment and then 2.5 ng/kg/min per week for the remaining duration of infusion, depending on clinical response.

Treatment of moderate pulmonary hypertension after surgery can be managed with treprostinil (INH), with an initial dose of 1.25 ng/kg/min and gradual increases based on clinical response 2.

• Key considerations:
  • Initiate at 1.25 ng/kg/min and adjust as needed
  • Increase infusion rate in increments of 1.25 ng/kg/min per week for the first four weeks
  • Monitor for systemic effects and adjust dose accordingly
  • Avoid abrupt cessation of infusion Epoprostenol (INH) is also an option, with an initial dose of 2 ng/kg/min and increases in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established 3.
• Key considerations:
  • Initiate at 2 ng/kg/min and adjust as needed
  • Increase infusion rate in increments of 2 ng/kg/min every 15 minutes or longer
  • Monitor for dose-limiting pharmacologic effects and adjust dose accordingly
  • Avoid abrupt cessation of infusion

From the Research

Treatment of Moderate Pulmonary Hypertension after Surgery

• The treatment of moderate pulmonary hypertension after surgery is a complex issue, and there is limited evidence to guide therapy 4.
• Basic principles of management include maintenance of systemic perfusion pressure, optimization of cardiac inotropy, use of lung-protective ventilator strategies, and attempting to reduce right-ventricular afterload using pulmonary vasodilators 4.
• Sildenafil and bosentan are two medications that have been used to treat pulmonary arterial hypertension, and some studies have investigated their use in combination 5, 6, 7.
• One study found that adding bosentan to sildenafil therapy did not improve outcomes in patients with pulmonary arterial hypertension 5.
• Another study found that sildenafil, when added to stable bosentan therapy, had no benefit over placebo for 12-week change from baseline in 6-min walk distance 6.
• However, a human ex vivo model study suggested that the combination of sildenafil and bosentan may be beneficial in reducing pulmonary vessel contraction 7.
• A systematic review and economic evaluation of various treatments for pulmonary arterial hypertension, including epoprostenol, iloprost, bosentan, sitaxentan, and sildenafil, found that bosentan, sitaxentan, and sildenafil may be cost-effective, while iloprost and epoprostenol may not be 8.

Medication Options

• Sildenafil: a phosphodiesterase-5 inhibitor that has been shown to improve exercise capacity and delay clinical worsening in patients with pulmonary arterial hypertension 5, 6.
• Bosentan: an endothelin receptor antagonist that has been shown to improve exercise capacity and delay clinical worsening in patients with pulmonary arterial hypertension 5, 6, 7.
• Epoprostenol: a prostacyclin analogue that has been shown to improve exercise capacity and survival in patients with pulmonary arterial hypertension, but is more expensive than other options 8.
• Iloprost: a prostacyclin analogue that has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, but is more expensive than other options 8.
• Sitaxentan: an endothelin receptor antagonist that has been shown to improve exercise capacity and delay clinical worsening in patients with pulmonary arterial hypertension, but is no longer available due to safety concerns 8.