Intraoperative Treatment of Pulmonary Hypertension: IV Milrinone vs Inhaled Flolan
Direct Recommendation
For intraoperative treatment of pulmonary hypertension, inhaled epoprostenol (Flolan) is the preferred agent over IV milrinone based on guideline recommendations and superior evidence for pulmonary-selective vasodilation without systemic hypotension. 1, 2
Guideline-Based Approach
Primary Recommendation for Acute Intraoperative Management
The European Society of Cardiology recommends inhaled nitric oxide or IV epoprostenol for severe right heart failure not responsive to supportive therapy in the perioperative setting, with guidance from a physician experienced in pulmonary arterial hypertension treatment. 1 While this guideline mentions both inhaled NO and IV epoprostenol, the inhaled route is specifically emphasized for its pulmonary selectivity.
Rationale for Inhaled Epoprostenol Superiority
Inhaled epoprostenol provides pulmonary-selective vasodilation, decreasing pulmonary vascular resistance and improving cardiac output without affecting systemic vascular resistance - a critical advantage during surgery when maintaining systemic blood pressure is essential. 2, 3
The American Thoracic Society specifically recommends inhaled nitric oxide for acute management because it decreases PVR, improves cardiac output, has a short half-life, and does not affect SVR. 2 Inhaled epoprostenol shares these same advantageous properties.
Evidence Supporting Inhaled Epoprostenol
Hemodynamic Effects in Cardiac Surgery
In a randomized, double-blind, placebo-controlled trial of 20 patients with pulmonary hypertension undergoing cardiac surgery, inhaled epoprostenol (60 mcg) significantly reduced systolic pulmonary artery pressure from 48.4 ± 18 mm Hg to 38.9 ± 11.9 mm Hg (P = 0.002) and reduced indexed right ventricular stroke work from 10.7 ± 4.57 g·m·m⁻² to 7.8 ± 3.94 g·m·m⁻² (P = 0.003). 3
Critically, there was no significant effect on systemic arterial pressures, left ventricular function, arterial oxygenation, platelet aggregation, or surgical blood loss. 3 The effect was completely reversed after 25 minutes, providing excellent titrability. 3
Combined Therapy Evidence
A retrospective cohort study of 128 cardiac surgical patients demonstrated that combined inhaled epoprostenol and inhaled milrinone (iE&iM) before cardiopulmonary bypass resulted in a positive pulmonary vasodilator response in 77.3% of patients. 4 This combination was associated with easier separation from CPB (69.7% vs 58.6% in nonresponders, P = 0.0181) and lower use of intravenous inotropes after CPB (8.1% vs 27.6%, P = 0.0052). 4
Higher baseline systolic pulmonary artery pressure predicted positive response to treatment (OR 1.63 per 5 mm Hg increase, P = 0.0006). 4
Why Not IV Milrinone Alone?
Systemic Hypotension Risk
The American College of Cardiology recommends selecting inotropes that have neutral or beneficial effects on pulmonary vascular resistance, including dobutamine, milrinone, and epinephrine. 2 However, dobutamine is often preferred over milrinone due to its shorter half-life when there is risk of hypotension. 2
This is a critical distinction: IV milrinone causes systemic vasodilation and can precipitate hypotension - a potentially catastrophic complication in the intraoperative setting where maintaining systemic vascular resistance greater than pulmonary vascular resistance is essential. 2
Lack of Pulmonary Selectivity
Unlike inhaled epoprostenol, IV milrinone lacks pulmonary selectivity and will decrease both systemic and pulmonary vascular resistance, potentially worsening the SVR:PVR ratio that is crucial for right ventricular perfusion. 2
Practical Implementation Algorithm
Step 1: Pre-CPB Administration
- Administer inhaled epoprostenol 60 mcg via ultrasonic mesh nebulizer after induction of anesthesia and before surgical incision. 3, 4
- Consider adding inhaled milrinone for synergistic effect in high-risk patients. 4
Step 2: Hemodynamic Monitoring
- Monitor MAP:MPAP ratio continuously; a 20% increase indicates positive response. 4
- Expect peak effect within 10 minutes and complete reversal by 25 minutes. 3, 5
Step 3: Repeat Dosing as Needed
- Redose inhaled epoprostenol every 20-25 minutes during the procedure if pulmonary hypertension persists. 3
- The short half-life allows for excellent titrability without accumulation. 3
Step 4: Transition Strategy
- Upon weaning from inhaled therapy, start or restart a phosphodiesterase inhibitor as replacement therapy to prevent rebound pulmonary hypertension. 2
Critical Pitfalls to Avoid
Do Not Use IV Milrinone as First-Line
Avoid using IV milrinone as monotherapy for intraoperative pulmonary hypertension because systemic hypotension may worsen right ventricular perfusion and precipitate cardiovascular collapse. 2 If inotropic support is needed, dobutamine is preferred due to its shorter half-life. 2
Maintain SVR > PVR
The American College of Chest Physicians advises against allowing PVR to exceed SVR, which can result in right ventricular ischemia. 2 Inhaled epoprostenol selectively reduces PVR without affecting SVR, maintaining this critical ratio. 3
Avoid Abrupt Discontinuation
Abrupt interruption of prostacyclin therapy should be avoided as this may lead to rebound pulmonary hypertension with symptomatic deterioration and even death. 1 Plan for overlap with oral or alternative therapy before discontinuing inhaled epoprostenol.
Monitor for Rebound
When transitioning off inhaled therapy, ensure phosphodiesterase inhibitor coverage is established to prevent rebound pulmonary hypertension. 2
Special Populations
Patients with Baseline SPAP > 55 mm Hg
Higher baseline systolic pulmonary artery pressure is an independent predictor of positive response to inhaled epoprostenol and milrinone combination (17.2% of responders vs 3.4% of nonresponders had SPAP > 55 mm Hg, P = 0.0037). 4
Patients with EuroSCORE II > 6.5%
EuroSCORE II > 6.5% predicts nonresponse to inhaled pulmonary vasodilator therapy (OR 5.19, P = 0.002), and these patients may require additional IV inotropic support. 4
Long-Term Considerations
For patients requiring ongoing therapy beyond the immediate perioperative period, the American College of Chest Physicians suggests continuous IV epoprostenol to improve WHO functional class and exercise capacity in WHO FC IV patients. 1 However, this represents chronic management rather than acute intraoperative treatment.