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

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%; Pā€‰=ā€‰.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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1001/jamasurg.2021.5856

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.

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.

Scholars@Duke

Ghadimi

Kamrouz Ghadimi

Associate Professor of Anesthesiology

Overview
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. 

Expertise
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. 

Reynolds

John Michael Reynolds

Professor of Medicine

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