The impact of timing of initiating invasive mechanical ventilation in COVID-19-related respiratory failure

Purpose: Optimal timing of initiating invasive mechanical ventilation (IMV) in coronavirus disease 2019 (COVID-19)-related respiratory failure is unclear. We hypothesized that a strategy of IMV as opposed to continuing high flow oxygen or non-invasive mechanical ventilation each day after reaching a high FiO2 threshold would be associated with worse in-hospital mortality.

Methods: Using data from Kaiser Permanente Northern/Southern California's 36 medical centers, we identified patients with COVID-19-related acute respiratory failure who reached ≥80% FiO2 on high flow nasal cannula or non-invasive ventilation. Exposure was IMV initiation each day after reaching high FiO2 threshold (T₀). We developed propensity scores with overlap weighting for receipt of IMV each day adjusting for confounders. We reported relative risk of inpatient death with 95% Confidence Interval.

Results: Of 28,035 hospitalizations representing 21,175 patient-days, 5758 patients were included (2793 received and 2965 did not receive IMV). Patients receiving IMV had higher unadjusted mortality (63.6% versus 18.2%, P < 0.0001). On each day after reaching T₀ through day >10, the adjusted relative risk was higher for those receiving IMV compared to those not receiving IMV (Relative Risk>1).

Conclusions: Initiation of IMV on each day after patients reach high FiO2 threshold was associated with higher inpatient mortality after adjusting for time-varying confounders. Remaining on high flow nasal cannula or non-invasive ventilation does not appear to be harmful compared to IMV. Prospective evaluation is needed.