Inhaled pulmonary vasodilator therapies confer similar outcomes in adult lung transplant

Compared with inhaled nitric oxide, inhaled epoprostenol was associated with similar risk for primary graft dysfunction and other postoperative outcomes in patients undergoing lung transplant.

“The cost of inhaled nitric oxide exceeds millions of dollars annually for large health care systems nationwide, and inhaled nitric oxide is approximately 7-fold more expensive than inhaled epoprostenol. Accordingly, inhaled epoprostenol has emerged as a cost-saving inhaled nitric oxide alternative at several institutions. Although similar antioxidative and vasodilatory properties of inhaled epoprostenol have been reported in lung transplant, the evidence supporting its use is not based on robust comparisons with inhaled nitric oxide that assessed clinically meaningful outcomes,” Kamrouz Ghadimi, MD, MHSc, anesthesiologist and critical care specialist at Duke University School of Medicine, and colleagues wrote in JAMA Surgery. “Furthermore, available data interpretation is complicated by retrospective observational studies, differing epoprostenol formulations and aerosol-generating devices and lack of standardized criteria for discontinuing treatment with either agent.”

INSPIRE-FLO was a randomized, masked, parallel-designed, equivalence clinical trial that enrolled 201 adults who underwent single or bilateral lung transplant from May 2017 to March 2020. Patients were categorized into five strata based on prognostic clinical features and were randomly assigned to receive inhaled nitric oxide (n = 98; median age, 64 years; 60.2% men) or inhaled epoprostenol (n = 103; median age, 64 years; 68% men) during lung transplant.

The primary outcome was development of severe primary graft dysfunction at 24, 48 or 72 hours after lung transplant. Secondary outcomes included mechanical ventilation duration, lengths of stay in hospital or ICU, acute kidney injury incidence and severity, postoperative tracheostomy placement, and mortality rates in-hospital, at 30 days and at 90 days.

In the unadjusted analysis, development of primary graft dysfunction occurred in 39.8% of patients assigned inhaled nitric oxide compared with 44.7% of patients assigned inhaled epoprostenol (risk difference = 4.9 percentage points; 95% CI, –6.4 to 16.2; P = .02).

In the post hoc analysis, at 48 or 72 hours, primary graft dysfunction occurred in 26.5% of patients assigned inhaled nitric oxide compared with 28.2% of patients assigned inhaled epoprostenol. At 72 hours, primary graft dysfunction occurred in 16.3% of patients assigned inhaled nitric oxide compared with 21.3% of patients assigned inhaled epoprostenol.

Researchers observed no significant differences in any secondary outcomes.

“Although the results of this investigation have changed practice at our institution, future directions may include implementation of a larger multicenter trial to substantiate these findings,” the researchers wrote.