Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.



Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication.


To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO.

Design, setting, and participants

This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation.


Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU).

Main outcomes and measures

The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome.


A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes.

Conclusions and relevance

Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO.

Trial registration identifier: NCT03081052.





Published Version (Please cite this version)


Publication Info

Ghadimi, Kamrouz, Jhaymie Cappiello, Mary Cooter-Wright, John C Haney, John M Reynolds, Brandi A Bottiger, Jacob A Klapper, Jerrold H Levy, et al. (2022). Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial. JAMA surgery, 157(1). p. e215856. 10.1001/jamasurg.2021.5856 Retrieved from

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Kamrouz Ghadimi

Associate Professor of Anesthesiology

Dr. Ghadimi is a cardiothoracic anesthesiologist, intensivist (ICU doctor), researcher, educator, and director of the clinical research unit in the Department of Anesthesiology at Duke Health. He has published over 100 peer-reviewed manuscripts, book chapters, online reviews, and editorials. His expertise involves the perioperative and intensive care management of patients undergoing cardiac and noncardiac surgery, with a special focus on the treatment of bleeding and inflammation related to shock and mechanical circulatory support and on the modification of pulmonary circulation to optimize end-organ blood flow.

Clinical Education
Dr. Ghadimi is a medical school graduate of Boston University School of Medicine, completed his internship in general surgery at the University of California Irvine Medical Center and Long Beach Veterans Affairs Medical Center and completed clinical anesthesiology residency at the Allegheny Health Network in Pittsburgh, Pennsylvania. He completed advanced clinical fellowship specialization in adult Critical Care Medicine (surgical focus) and Cardiothoracic Anesthesiology at the University of Pennsylvania Health System in Philadelphia, Pennsylvania. 

Dr. Ghadimi's expertise and instruction spans across the cardiothoracic operating rooms and cardiothoracic surgical ICU environments. His expertise includes perioperative hemostasis & thrombosis, critical care of the heart or lung transplant recipient, and critical care for the patient on mechanical circulatory support, which may include extracorporeal life support (ECMO) or ventricular assist devices/systems.

Research Education
Dr. Ghadimi is a clinical and translational researcher and holds a Master in Health Sciences (M.H.Sc.) from the Duke-NIH Clinical Research Training Program. 


John Michael Reynolds

Professor of Medicine

Brandi Anne Bottiger

Associate Professor of Anesthesiology

I have been a member of the Cardiothoracic Anesthesiology division and Department of anesthesiology for >10 years, caring for cardiac and thoracic surgical patients. I am the current cardiothoracic anesthesiology fellowship director of 14 fellows (  My academic interests are in education, CTA content development, and specific interests in outcomes improvement after lung transplantation. Additionally, I have greatly appreciated my leadership role and ability to engage with the Duke Transplant Center.


Jacob A Klapper

Associate Professor of Surgery

Jerrold Henry Levy

Professor of Anesthesiology

Jerrold Levy is Professor of Anesthesiology, Critical Care, and Surgery (Cardiothoracic) at Duke University Medical Center in Durham, NC. He obtained his medical degree from the University of Miami, where he was an intern in internal medicine, and undertook his residency in the Department of Anesthesiology of the Massachusetts General Hospital and Harvard Medical School in Boston, where he was also Chief Resident, and completed fellowships in both Respiratory ICU and Cardiac Anesthesiology.  He previously was Professor, Deputy Chair for Research, and Chief of Cardiothoracic Anesthesiology at Emory University School of Medicine. His clinical and research interests include anticoagulation and its reversal, therapeutic strategies to prevent and treat coagulopathy and acute inflammatory responses in critically ill patients, clinical applications of recombinant and purified protein concentrates to treat bleeding, and pharmacologic approaches to treat shock.  He is currently Chair of the Subcommittee on Perioperative and Critical Care Thrombosis and Hemostasis for the International Society of Thrombosis and Hemostasis, Executive Editor of Anesthesiology, and consultant to the FDA‘s Biologic Products Advisory Committee.  He is the author of over 450 publications on PubMED, with over 100,000 citations on Google Scholar and a h-index of 95. He is also fluent in French and conversational in Spanish and Japanese.


Matthew Hartwig

Professor of Surgery

Dr. Hartwig is a thoracic surgeon with a clinical focus in lung transplantation and robotic assisted minimally invasive thoracic surgery for the treatment of diseases of the chest.  He serves as the Surgical Director of the Duke Lung Transplant Program and the Esophageal Center at Duke.  Additionally, he directs the Surgical Office of Clinical Research, which manages the clinical research portfolio for the Department of Surgery.  He also leads a successful program of clinical, basic and translational research in thoracic surgery and lung transplantation. He currently directs the Duke Ex Vivo Organ Laboratory (DEVOL), is the Chief of Lung Transplant Research, and is a faculty member at the Duke Clinical Research Institute (DCRI).

Dr. Hartwig has over 150 peer reviewed publications, received numerous awards, chaired many sessions at national and international meetings, serves regularly on NIH study sections, and is on the editorial board of many prominent journals. He has also personally mentored over pre-and post-doctoral trainees, many of whom are now engaged in their own successful research careers.

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