Inhaled Pulmonary Vasodilators in Cardiac Surgery

Quick Takes

  • For patients undergoing LVAD and heart transplantation, use of inhaled epoprostenol compared to inhaled nitric oxide had an equivalent effect on rates of postoperative right ventricular failure.
  • No differences in duration of mechanical ventilation, hospital and ICU length of stay, acute kidney injury, or mortality were seen.

Study Questions:

Among patients with advanced heart failure (HF) undergoing orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation, how does postoperative use of inhaled epoprostenol (iEPO) compare to inhaled nitric oxide (iNO) in reducing the rates of right ventricular failure (RVF) after major cardiac surgery?


This is a single-center, parallel-designed, double-blind, randomized clinical trial of two inhaled pulmonary-selective vasodilator (iPVD) therapies (iEPO vs. iNO) among patients with advanced HF undergoing major cardiac surgery with OHT or LVAD implant. Patients were stratified by assigned surgery and important preoperative risk factors. Patients received continuous iEPO or iNO just prior to separation from cardiopulmonary bypass and therapy was continued in the intensive care unit (ICU) until discontinuation criteria were met. The primary composite outcome included need for mechanical circulatory support for RVF after OHT and moderate to severe right heart failure after LVAD based on INTERMACS criteria. Secondary outcomes included duration of mechanical ventilation, hospital and ICU length of stay, acute kidney injury, and mortality (30 days, 90 days, 1 year).


There were 231 patients included in this study, enrolled from May 2017 to September 2020, with 120 receiving iEPO and 111 receiving iNO after surgery. Baseline characteristics (demographic data, history, hemodynamics, laboratory values, procedural characteristics, donor characteristics for OHT) were generally similar between the two groups. The primary outcome occurred for 30 patients (25.0%) in the iEPO group and 25 patients (22.5%) in the iNO group (absolute risk difference, 2.5%; 90% confidence interval, –6.6% to 11.6%; p = 0.012 in support of equivalence). Results for the primary outcome were similar with a per-protocol and an adjusted intention-to-treat analysis. Similar outcomes were seen in the OHT and LVAD subgroups. There were no significant between-group differences for the secondary outcomes.


Among patients with advanced HF undergoing major cardiac surgery with OHT or LVAD implantation, use of iEPO compared to iNO resulted in similar rates of postoperative RVF.


The use of an iPVD like iEPO and iNO after OHT and LVAD implantation is common because RVF occurs frequently postoperatively and is associated with morbidity and mortality in the population. Existing evidence for use of these agents is limited by study heterogeneity, small sample sizes, protocol differences, and limited long-term follow-up. The current study adds significantly to the literature and directly compares two commonly used agents. The results provide evidence of equivalence between the therapies, and with the appeal of potential cost-savings with iEPO use, this may become a more attractive option. It is interesting to note that there was a nonstatistically significant signal toward higher mortality with iEPO use at longer follow-up. However, it is unclear if can be attributed to a therapy used only during the index hospitalization; more follow-up studies are needed to clarify this observation. It will also be important going forward to consider what patients are most likely to benefit from iPVD after major cardiac surgery to better target our interventions.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Lipid Metabolism, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support

Keywords: Acute Kidney Injury, Cardiac Surgical Procedures, Cardiovascular Critical Care, Epoprostenol, Heart-Assist Devices, Heart Failure, Heart Transplantation, Hemodynamics, Intensive Care Units, Length of Stay, Nitric Oxide, Respiration, Artificial, Vasodilator Agents, Ventilation

< Back to Listings