An observational study on the timing of intubation and outcome in COVID-19 ARDS patients who were treated with high flow nasal oxygen prior to invasive mechanical ventilation: A time series analysis (InOutHFNO trial).

Background and Aims: Prolonged high flow nasal oxygen (HFNO) application might delay intubation and increase mortality in acute hypoxemic respiratory failure (AHRF) patients. Intubation in coronavirus disease 2019 (COVID-19) AHRF (CAHRF) patients 24 to 48 hours after HFNO initiation has been associated with increased mortality in previous studies. This cut-off period is variable in previous studies. A time series analysis could reflect more robust data on outcome in relation to HFNO duration before intubation in CAHRF. Methods: A retrospective study was conducted at 30-bedded ICU of a tertiary care teaching hospital from July 2020 to August 2021. The study cohort comprised 116 patients who required HFNO and were subsequently intubated following HFNO failure. A time series analysis of patient outcomes on each day of HFNO application prior to invasive mechanical ventilation (IMV) was done. Results: ICU and hospital mortality was 67.2%. Beyond day 4 of HFNO application, there was a trend towards increased risk-adjusted ICU and hospital mortality for each day delay in intubation of CAHRF patients on HFNO [OR 2.718; 95% CI 0.957-7.721; P 0.061]. This trend was maintained till day 8 of HFNO application, after which there was 100% mortality. Taking day four as a cut-off in the timeline of HFNO application, we have observed an absolute mortality benefit of 15% with early intubation despite a higher APACHE-IV score than the late intubation group. Conclusion: IMV beyond the 4th day of HFNO initiation in CAHRF patients increases mortality.