What are the treatment options for pulmonary hypertension in the Intensive Care Unit (ICU)?

From the Guidelines

Treatment of pulmonary hypertension in the ICU should prioritize a multifaceted approach focusing on optimizing oxygenation, managing acute right ventricular failure, and carefully selecting inotropes, vasopressors, and pulmonary vasodilators, with consideration of the most recent evidence from 2024 indicating the importance of specific management strategies for pulmonary hypertensive crises 1. The management strategy should include optimizing oxygenation through supplemental oxygen to maintain saturation above 92%, as hypoxemia can worsen pulmonary vasoconstriction. For acute right ventricular failure, intravenous inotropic support with dobutamine (2-20 mcg/kg/min) or milrinone (0.25-0.75 mcg/kg/min) should be initiated to improve cardiac output, as suggested by the 2014 Circulation Research study 1. Vasopressors like norepinephrine (0.01-3 mcg/kg/min) may be needed to maintain systemic blood pressure, with careful consideration to maintain systemic vascular resistance (SVR) greater than pulmonary vascular resistance (PVR) to avoid right ventricular ischemia. Pulmonary vasodilators are crucial, with inhaled nitric oxide (10-40 ppm) providing selective pulmonary vasodilation without systemic effects, as noted in the 2014 Circulation Research study 1. Alternatively, inhaled epoprostenol (50 ng/kg/min nebulized) can be used, and for patients with Group 1 PH, intravenous prostacyclins like epoprostenol (starting at 2 ng/kg/min and titrating upward) may be necessary. Volume status must be carefully managed, typically maintaining euvolemia or slight hypovolemia, as fluid overload can worsen right ventricular function. Mechanical ventilation strategies should include low tidal volumes (6 ml/kg) and moderate PEEP (5-10 cmH2O) to avoid increasing pulmonary vascular resistance, as recommended in the 2014 Circulation Research study 1. In refractory cases, extracorporeal membrane oxygenation (ECMO) may serve as a bridge to recovery or transplantation. It is also important to note that 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, as stated in the 2014 American Thoracic Society/American College of Chest Physicians policy statement 1. The underlying pathophysiology involves increased pulmonary vascular resistance leading to right ventricular strain and potential failure, which guides this multifaceted treatment approach. Key considerations in the ICU setting include:

• Optimizing oxygenation and managing acute right ventricular failure
• Careful selection of inotropes, vasopressors, and pulmonary vasodilators
• Maintenance of SVR greater than PVR to avoid right ventricular ischemia
• Use of pulmonary vasodilators such as inhaled nitric oxide or epoprostenol
• Careful management of volume status and mechanical ventilation strategies.

From the FDA Drug Label

Epoprostenol for injection is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases Infusion of epoprostenol for injection should be initiated at 2 ng/kg/min and increased 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.

The treatment option for pulmonary hypertension in the Intensive Care Unit (ICU) is epoprostenol (IV), which is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity. The dosage should be initiated at 2 ng/kg/min and increased 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 2, 2, 2.

From the Research

Treatment Options for Pulmonary Hypertension in the ICU

• The management of patients with pulmonary hypertension in the ICU can be challenging, particularly when they become hemodynamically unstable 3.
• Treatment options for pulmonary hypertension in the ICU include:
  • Vasopressors such as dobutamine, dopamine, phenylephrine, isoproterenol, and vasopressin 3.
  • Pulmonary vasodilators such as inhaled nitric oxide, intravenous prostacyclin, and sildenafil 3, 4.
  • Other therapeutic options such as endothelin-receptor antagonists (e.g. bosentan) and phosphodiesterase inhibitors (e.g. sildenafil) 4.
• Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure 3.
• The treatment plan should focus on identifying and treating the cause for decompensation, optimizing right ventricular preload, reducing right ventricular afterload, correcting hypotension, and augmenting right ventricular inotropy 5.

Management Considerations

• Patients with pulmonary arterial hypertension may require ICU care as a direct consequence of decompensated right heart failure or due to other maladies such as acute respiratory failure, septic shock, and gastrointestinal bleeding 5.
• The approach to ICU care of patients with pulmonary arterial hypertension requires special consideration with regard to intubation and mechanical ventilation, and management of volume status and hemodynamics 5.
• Early consultation with a pulmonary hypertension specialist and transfer to a tertiary care center with invasive monitoring and mechanical support capabilities is advised 6, 5.

Pharmacological Interventions

• The use of vasopressors and pulmonary vasodilators in patients with pulmonary hypertension in the ICU has been supported by the literature, with dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin being commonly used 3.
• Endothelin-receptor antagonists and phosphodiesterase inhibitors may also be useful in the treatment of pulmonary hypertension in patients with chronic renal failure 4.