Oxygenation Trajectories After Inhaled Nitric Oxide in Nonintubated and Mechanically Ventilated Patients With COVID-19

Abstract

Background

Inhaled nitric oxide (iNO) is an inhaled vasodilator used in hypoxemic respiratory failure; however, the evidence supporting its benefits is lacking. This study evaluated the physiologic impact of iNO on oxygenation trajectories using slope-based analysis in a predominantly nonintubated population with COVID-19, a group underrepresented in existing iNO research.

Research Questions

Is iNO associated with improvement in hypoxemia in patients with respiratory failure resulting from COVID-19? Does this improvement vary by respiratory support method (intubated vs nonintubated) and are changes in hypoxemia associated with outcomes such as mortality and progression to intubation?

Study Design and Methods

Retrospective chart review of 142 patients with COVID-19 admitted to the ICUs of Stanford Hospital and its affiliated community hospital, Stanford Health Care—Tri-Valley, who received iNO between March 2020 and July 2022. The primary end point was the change in slope of the oxygen saturation as measured by pulse oximetry (Spo₂) to Fio₂ ratio after iNO administration. Mixed-effects modeling was applied to evaluate the change in Spo₂ to Fio₂ slope before and after iNO administration. Hyperresponsiveness and hyporesponsiveness were defined based on highest and lowest quartile change in slope. Baseline clinical factors and secondary outcome were compared.

Results

Mixed-effects modeling showed that iNO was associated with a statistically significant improvement in Spo₂ to Fio₂ ratio across all patients, including the 122 patients (90%) receiving a high-flow nasal cannula when iNO was initiated. Before iNO administration, Spo₂ to Fio₂ ratio was declining with an Spo₂ to Fio₂ slope of –4.3/h (95% CI, –5.6 to –3.0/h). After iNO administration, slope increased to 6.4/h (95% CI, 4.7-8.0/h). The hyperresponsive and hyporesponsive groups did not differ significantly in baseline characteristics, including respiratory method preceding iNO administration, or outcomes, including 30-day mortality (13.3% vs 23.3%; P = .50) and progression to intubation by day 30 (32.4% vs 20.0%; P = .18).

Interpretation

iNO was associated with improvement in Spo₂ to Fio₂ ratio in patients admitted with hypoxemic respiratory failure resulting from COVID-19, particularly among nonintubated patients. Magnitude of improvement was not associated with 30-day mortality or need for intubation.