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 (T(0)). 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 T(0) 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.