Why give Flolan (epoprostenol) to a patient with worsening breathing and a history of pulmonary arterial hypertension (PAH) or other cardiopulmonary conditions?

Why Give Flolan (Epoprostenol) to a Patient with Worsening Breathing

Flolan (epoprostenol) should be given to patients with pulmonary arterial hypertension (PAH) who are experiencing worsening dyspnea because it represents the most effective therapy for severe disease (WHO Functional Class III-IV), directly addressing the underlying pulmonary vasoconstriction and vascular remodeling that causes progressive right heart failure and respiratory symptoms. 1, 2

Understanding the Clinical Context

When a PAH patient presents with worsening breathing, this typically signals:

• Disease progression despite current therapy, indicating need for treatment escalation 1
• Advancing functional class (moving toward or within WHO FC III-IV), where parenteral prostanoids show the strongest evidence 1
• Hemodynamic deterioration with increasing pulmonary vascular resistance and right ventricular strain 2

Why Epoprostenol Works for Worsening Dyspnea

Epoprostenol provides two critical mechanisms that directly address worsening breathing:

• Direct pulmonary vasodilation that reduces right and left ventricular afterload, immediately decreasing the work of breathing and improving gas exchange 2
• Rapid hemodynamic improvement with increases in cardiac output and stroke volume, which enhances oxygen delivery to tissues 2
• Short half-life (6 minutes) allows for rapid titration to clinical effect, making it ideal for unstable or deteriorating patients 2

Evidence-Based Indications for Epoprostenol

For WHO Functional Class IV Patients (Severe Dyspnea at Rest)

The American College of Chest Physicians recommends continuous IV epoprostenol as first-line monotherapy for treatment-naive WHO FC IV patients to improve functional class, 6-minute walk distance, and cardiopulmonary hemodynamics 1

• This is considered the therapy of choice for FC IV patients based on extensive clinical experience and survival benefit 1
• Rapid onset of action and titratability make it preferable over oral agents in severely ill patients 1

For WHO Functional Class III Patients with Rapid Progression

For FC III patients exhibiting rapid disease progression or markers of poor prognosis, the American College of Chest Physicians suggests initiating parenteral prostanoid therapy rather than oral agents 1

• Epoprostenol improves WHO functional class, 6-minute walk distance, and cardiopulmonary hemodynamics 1
• The greater complexity and risk are justified by superior efficacy in high-risk patients 1

For Patients Failing Oral Therapy

When patients on one or two classes of oral PAH medications develop clinical worsening, the American College of Chest Physicians advises adding IV epoprostenol 1

• This applies to patients on stable doses of endothelin receptor antagonists (ERAs) or PDE5 inhibitors who remain symptomatic 1
• Addition of epoprostenol improves WHO functional class, exercise capacity, and hemodynamics 1

Clinical Outcomes That Justify Use

Epoprostenol demonstrated survival benefit in NYHA Functional Class III-IV patients with idiopathic or heritable PAH in controlled trials 2

• Hemodynamic improvements include decreased pulmonary vascular resistance (mean -4 Wood units), increased cardiac index (+0.3 L/min/m²), and increased stroke volume (+6 mL/beat) 2
• Exercise capacity improved with statistically significant increases in 6-minute walk distance 2
• Symptomatic relief of dyspnea and fatigue measured by validated instruments 2
• Effects persist with long-term administration (at least 36 months in open studies) 2

Critical Implementation Considerations

Initiation Protocol

Start epoprostenol at 2 ng/kg/min and increase in 2 ng/kg/min increments every 15 minutes until tolerance limit is reached 2

• In clinical trials, mean dose reached 4.1 ng/kg/min by day 7 and 11.2 ng/kg/min by week 12 2
• Severely ill or unstable WHO FC IV patients should be hospitalized for initiation to ensure stabilization and proper patient/family education 1

Dose Adjustment for Worsening Symptoms

Base dose increases on persistence, recurrence, or worsening of pulmonary hypertension symptoms 2

• Adjust by 1-2 ng/kg/min increments at intervals of at least 15 minutes (clinically, every 24-48 hours) 2
• Monitor blood pressure and heart rate for several hours after each dose change 2

Common Pitfalls to Avoid

Never abruptly discontinue epoprostenol or make sudden large dose reductions except in life-threatening situations, as this can precipitate rebound pulmonary hypertension 2

• Ensure backup infusion pump and IV sets are always available to prevent interruptions in drug delivery 2
• Administer only through central venous catheter for chronic therapy (peripheral access acceptable only during initiation) 2
• Do not mix with other medications or solutions - epoprostenol must be reconstituted only with sterile water or normal saline 2

Infrastructure Requirements

Epoprostenol requires proper infrastructure and specialty center care 1

• Centers without proper infrastructure should refer patients to experienced pulmonary hypertension centers 1
• Family support is paramount for safe administration of this complex therapy 1
• 24-hour support for complicated patients must be available 1

When to Consider Lung Transplantation

Listing for lung transplantation should be considered concurrently for WHO FC IV PAH patients starting epoprostenol 1

• This recognizes that even optimal medical therapy may not be sufficient for the most severe cases 1