Postoperative inhaled nitric oxide after lung transplantation: A multicenter randomized clinical trial and exploratory analysis of treatment heterogeneity.

BACKGROUND

The efficacy of prophylactic inhaled nitric oxide (iNO) in preventing primary graft dysfunction (PGD) after lung transplantation remains uncertain. We hypothesized that postoperative iNO would reduce the incidence of severe PGD.

METHODS

In this multicenter, single-blind, randomized clinical trial conducted in China, adult lung transplant recipients were randomized (1:1) to receive iNO (10 ppm for 40 h followed by a protocolized taper to complete a planned 48-h course) or standard care. The primary outcome was PGD grade 2/3 at 48 h post-reperfusion.

RESULTS

Of 86 randomized patients, 81 were evaluable (iNO, n = 40; Control, n = 41). The incidence of PGD grade 2/3 at 48 h did not differ significantly between groups (35.0% vs. 53.7%; risk ratio [RR], 0.65; 95% CI, 0.39-1.09; P = 0.09). No significant differences were found in secondary outcomes. In exploratory subgroup analyses, lower risk was observed among recipients with high intraoperative estimated blood loss (EBL ≥800 mL, P for interaction <0.001) and prolonged cold ischemia time (CIT ≥443 min, P for interaction = 0.04).

CONCLUSIONS

Routine prophylaxis with iNO did not significantly reduce severe PGD in an unselected lung transplant cohort. But it may confer benefit in high-risk phenotypes characterized by ischemia-reperfusion stress. Future use should shift from universal to targeted prophylaxis.