Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID‑19: treatment modalities, clinical response, and outcomes

Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID‑19: treatment modalities, clinical response, and outcomes

Armand Mekontso Dessap1,2,3* , Laurent Papazian4, Manuella Schaller5, Saad Nseir6, Bruno Megarbane7,
Luc Haudebourg8, Jean‑François Timsit9, Jean‑Louis Teboul10, Khaldoun Kuteifan11, Marc Gainnier12,
Michel Slama13, Patrick Houeto5, Laurent Lecourt5, Alain Mercat14 and Antoine Vieillard‑Baron15,16

Abstract

 Background Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory
distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective
of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of
C-ARDS patients.

Methods Multicentre, retrospective cohort study conducted in France.

Results From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight
and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66
(57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation
strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had
mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a
median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented
45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO
response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h
and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation
criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly
lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment
(adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03).

Conclusions Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This
improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement
in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective
studies.
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