Timing of invasive mechanical ventilation and death in critically ill adults with COVID-19: A multicenter cohort study

Abstract

Purpose: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

Materials and methods: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox model.

Results: Among the 1879 patients included in this analysis (1199 male [63.8%]; median age, 63 [IQR, 53-72] years), 1526 (81.2%) initiated IMV early and 353 (18.8%) initiated IMV late. A total of 644 of the 1526 patients (42.2%) in the early IMV group died, and 180 of the 353 (51.0%) in the late IMV group died (adjusted HR 0.77 [95% CI, 0.65-0.93]).

Conclusions: In critically ill adults with respiratory failure from COVID-19, early compared to late initiation of IMV is associated with reduced mortality.

Fig 1. Study cohort and emulated trial flow.

Abbreviations: ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation.

Fig 2. Mortality in early versus late initiation of IMV groups.

Abbreviations: IMV, invasive mechanical ventilation.

Fig 3. Primary and subgroup analyses examining mortality in early versus late initiation of IMV groups.

The hazard ratios are adjusted for the following covariates: age; sex; race; body mass index; hypertension; diabetes mellitus; coronary artery disease; congestive heart failure; chronic lung disease; active malignancy; days from symptom onset to ICU admission; hospital size (number of pre-COVID-19 ICU beds); and severity-of-illness covariates assessed on the day of IMV initiation (the renal, liver, and coagulation components of the Sequential Organ Failure Assessment score [13], the PaO₂:FiO₂ ratio, shock, concurrent therapies received [corticosteroids; tocilizumab; prone positioning; neuromuscular blockade], and inflammation. Sensitivity analysis #1 kept discharged patients in the risk set until day 90. Sensitivity analysis #2 excluded patients who died in the first 7 days of ICU admission, with follow-up for each patient starting on day 8 after ICU admission. Sensitivity analysis #3 was further adjusted for date of ICU admission, hospital geographic region, and hospital type. The exploratory analysis included patients not intubated during ICU days 1–7 in the “late IMV” group. Abbreviations: BMI, body mass index; HR, hazard ratio; IMV, invasive mechanical ventilation. ^aInflamation was defined as at least one of the following on the day of IMV initiation or prior: C-reactive protein >100 mg/L, interleukin-6 >80 pg/ml, or ferritin >1,000 ng/mL. Non-inflamed was defined as at least one value below the thresholds above, and no values that were above the thresholds. These thresholds above were selected based on prior studies [–22].