Risk Factors for 28-Day in-Hospital Mortality in Mechanically Ventilated Patients with COVID-19: An International Cohort Study (preprint)

ABSTRACT

Background: Risk factors associated with mortality in patients with coronavirus disease 2019 (COVID-19) on mechanical ventilation are still not fully elucidated. Thus, we aimed to identify patient-level factors, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation (28-day IMV mortality) in patients with COVID-19. Methods: Prospective observational cohort study in 148 intensive care units in the global COVID-19 Critical Care Consortium . Patients with clinically suspected or laboratory confirmed COVID-19 infection admitted to the intensive care unit (ICU) from February 2 nd through December 29th, 2020, requiring IMV. No study-specific interventions were performed. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of IMV and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day IMV mortality. Results: A total of 1713 patients were included in the survival analysis, 588 patients died in hospital within 28 days of commencing IMV (34.3%). Cox-regression analysis identified associations between the hazard of 28-day IMV mortality with age (HR 1.27 per 10-year increase in age, 95% CI 1.17 to 1.37, P<0.001), PEEP upon commencement of IMV (HR 0.78 per 5-cmH 2 O increase, 95% CI 0.66-0.93, P=0.005). Time-dependent parameters associated with 28-day IMV mortality were serum creatinine (HR 1.30 per doubling, 95% CI 1.19-1.42, P<0.001), lactate (HR 1.16 per doubling, 95% CI 1.06-1.27 P=0.001), PaCO 2 (HR 1.31 per doubling, 95% CI 1.05-1.64, P=0.015), pH (HR 0.82 per 0.1 increase, 95% CI 0.74-0.91, P<0.001), PaO 2 /FiO 2 (HR 0.56 per doubling, 95% CI 0.50-0.62, P<0.001) and mean arterial pressure (HR 0.92 per 10 mmHg increase, 95% CI 0.88-0.97, P=0.002). Conclusions: This international study establishes that in mechanically ventilated patients with COVID-19, older age and clinically relevant variables monitored at the bedside are risk factors for 28-day IMV mortality. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.