Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.
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2022-01
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Abstract
Importance
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.Objective
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.Interventions
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.Results
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
ClinicalTrials.gov identifier: NCT03081052.Type
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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 https://hdl.handle.net/10161/29715.
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Kamrouz Ghadimi
Dr. Kamrouz (Kam) Ghadimi is an experienced cardiovascular acute care specialist (cardiovascular anesthesiology and intensive care), established investigator, physician leader, and associate professor of Anesthesiology and Critical Care at Duke Health.
His clinical practice is rooted in the cardiothoracic surgical ICU and operating rooms. He has broad expertise in all topics involving perioperative cardiovascular medicine and intensive care, including the management of acutely ill patients after surgery or those receiving extracorporeal life support (ECLS/ECMO). His specific area of expertise focuses on the enhancement of blood circulation through the lungs and the reversal of bleeding with prevention of thrombosis after surgery and circulatory life support. He has published original research, invited reviews, and guidance documents in several high-impact multidisciplinary journals and networks, including JAMA, Circulation, BMJ, Journal of the American College of Cardiology, Journal of Heart and Lung Transplantation, and Journal of Thrombosis & Haemostasis. He has also published in anesthesiology specialty journals, including Anesthesia & Analgesia, Anesthesiology, Current Opinion in Anesthesiology, and the British Journal of Anaesthesia. Dr. Ghadimi has served on the Editorial Board for the Journal of Cardiothoracic and Vascular Anesthesia since 2018 and has served as a peer reviewer for more than 30 top-medical journals worldwide.
Over his career, he has developed a global multidisciplinary network of collaborators and colleagues in academic medicine, private practice, larger healthcare systems, and offices of the federal government. He has experience with grant funding from a variety of sponsors, including federal, industry, foundation, philanthropy, and institutional sources. He also holds positions on several other national and international committees aimed at improving cardiovascular health in patients undergoing surgery and post-surgical intensive care. He is a selected task force and writing committee member of the 2024 American College of Cardiology and American Heart Association Perioperative Cardiovascular Guidelines. He has devoted the majority of his career to the service of patients requiring cardiovascular perioperative and surgical intensive care.
In addition to a doctorate in Medicine, Dr. Ghadimi holds a Bachelor’s in Economics from Boston University and a Master’s in Clinical Research from Duke University School of Medicine and the National Institutes of Health. He is also an inventor with patents/patents pending, a medical consultant, a mentor, and an investor. He is a founding member and the original academic director of True Learn, an eLearning company focused on board exam preparation for multiple medical subspecialties. This resource is used by many physicians around the country. Beyond developing an educational platform that has reached several thousand physicians and physicians-in-training, Dr. Ghadimi has formally mentored 22 pre-doctorate and post-doctorate trainees, with several mentees continuing their faculty careers in academic practice. In addition, he serves as a resource for a multitude of other physicians, physicians-in-training, and allied healthcare professionals.
Currently, Dr. Ghadimi serves as Director of the Clinical Research Unit for the Department of Anesthesiology at Duke Health, leading a cohesive, high-performing management team that oversees 45 staff working with Anesthesiology faculty and faculty in other departments to operationalize more than 80 innovative research protocols annually (single- and multi-site studies) to advance the fields of perioperative medicine, intensive care, pain management, and brain and heart health. He is leading digital health and artificial intelligence implementation in research workflow to rapidly leverage capabilities for automation and efficiency with the evolving guidance of cybersecurity compliance. He has also led the expansion of the Human Biospecimen Repository within the Department of Anesthesiology, where participants from prospective studies have generously donated biofluids and tissue for the advancement of disease-specific biology and translational research. Dr. Ghadimi is currently involved in the One Duke Gen precision medicine initiative for Duke Health to catalyze high-impact translational discoveries through expansive data-driven partnerships.
John Michael Reynolds
Brandi Anne Bottiger
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 (https://anesthesiology.duke.edu/?page_id=818051). 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
Jerrold Henry Levy
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
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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