Inhaled nitric oxide after lung transplantation: a systematic review and meta-analysis of prospective studies

Lung transplantation (LT) improves survival and quality of life for patients with end-stage lung disease, but ischemia-reperfusion injury (IRI) poses significant challenges. IRI leads to prolonged ICU stays and increased mortality, primarily due to primary graft dysfunction (PGD), especially grade 3 PGD. Inhaled nitric oxide (iNO), a known vasodilator and antioxidant, has been explored for the management of IRI and for mitigating PGD3 severity. Some studies recommend its preventive use; however, insufficient evidence has delayed regulatory approval. A systematic review and meta-analysis was conducted across four databases (PubMed, Scopus, Cochrane Library, and Web of Science) from inception through September 2024. Prospective studies evaluating adult lung transplant recipients who received inhaled nitric oxide (iNO) compared to a placebo or control group were included. The primary outcome was the risk of grade 3 primary graft dysfunction (PGD3). Secondary outcomes included intensive care unit length of stay (ICU-LOS), duration of mechanical ventilation (MV), and 30-day mortality. Pooled estimates for the primary analysis were calculated using a random-effects model. Out of 2,503 studies screened, six met the eligibility criteria, encompassing 420 patients. iNO was administered 12 to 48 hours post-transplant at doses of 10 to 20 ppm. There was a trend toward a lower risk of PGD3 in patients who received iNO; however, this trend failed to reach statistical significance (RR = 0.73, 95% CI = 0.45–1.19, I² = 30%). In addition, no significant differences in ICU LOS (MD = −0.21 days, 95%CI = −3.78 to 3.36, I² = 65%), mechanical ventilation duration (MD = −0.20 days, 95% CI = −0.69 to 0.28, I² = 9%), or 30-day mortality (RR =0.94, 95% CI = 0.35–2.55, I² = 0%) were observed in the random-effects analysis. Inhaled nitric oxide is well tolerated, and there is a non-significant trend toward reducing the risk of PGD3 and shortening mechanical ventilation duration. Larger, high-quality RCTs are needed to confirm these therapeutic benefits and establish definitive clinical usage guidelines.