# Inhaled nitric oxide for acute respiratory distress syndrome in adults: a systematic review and meta-analysis

## TL;DR

This study reviews the use of inhaled nitric oxide in adults with ARDS and finds it may not improve survival or patient outcomes and could increase the need for kidney treatments.

## Contribution

The study provides a systematic review and meta-analysis of randomized trials on inhaled nitric oxide for ARDS, focusing on patient-centered outcomes.

## Key findings

- iNO may not improve mortality in adult ARDS patients.
- iNO slightly improves oxygenation but increases the need for renal replacement therapy.
- Evidence is very uncertain about the effect of iNO on ECMO use.

## Abstract

Although inhaled nitric oxide (iNO) is used as a rescue therapy in patients with acute respiratory distress syndrome (ARDS), its impact on patient-centered outcomes remains uncertain. To address this gap, we conducted a systematic review of randomized controlled trials (RCTs) to test the hypothesis that the addition of iNO to standard care improves survival in adult patients with ARDS.

We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for RCTs evaluating iNO in adult patients with ARDS through October 28, 2025. The primary outcome was mortality at the longest follow-up. Secondary outcomes included acute kidney injury (AKI), receipt of renal replacement therapy (RRT), duration of mechanical ventilation, length of intensive care unit stay, length of hospital stay, receipt of extracorporeal membrane oxygenation (ECMO), mean pulmonary artery pressure, partial pressure of arterial oxygen/fraction of inspiratory oxygen (PaO2/FiO2) ratio, elevated methemoglobin concentrations (> 5%), elevated nitrogen dioxide concentrations (> 3 ppm), extubation, and reintubation. We pooled data using a random-effects model, assessed the risk of bias with the Cochrane RoB 2 tool, and graded certainty with the GRADE approach.

We included 11 RCTs comprising 1302 patients. Only one study was of low risk of bias. iNO therapy may result in no difference in mortality at the longest follow-up (relative risk [RR], 1.07; 95% confidence interval [CI], 0.93–1.23; I2 = 0%; low certainty). iNO may improve PaO₂/FiO₂ ratio slightly (mean difference, 15.03 mmHg; 95% CI, 6.19–23.86; I2 = 0%; low certainty). The evidence is very uncertain about the effect on ECMO use (RR, 0.45; 95% CI, 0.10–2.17; I2 = 45%; very low certainty). iNO may increase the need for RRT (RR, 1.56; 95% CI, 1.17–2.08; I2 = 0%; low certainty). No clear differences were observed in other secondary outcomes. No study reported data on reintubation.

Although iNO may improve oxygenation slightly, it may not confer survival or other patient-centered benefits and may increase the need for RRT. High-quality randomized evidence is needed to guide the optimal patient selection for this therapeutic option.

PROSPERO (registration number: CRD42024573383).

The online version contains supplementary material available at 10.1186/s40560-025-00845-4.