Clinical impact of ventilator-associated pneumonia in patients with the acute respiratory distress syndrome: a retrospective cohort study

Abstract

Background: The clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS).

Methods: Patients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO₂/FiO₂ ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes.

Results: Among the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO₂/FiO₂ ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, - 19 [- 20; - 13.5] days) and vasopressor-free days (- 5 [- 9; - 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04-4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11-5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32-4.49, P = 0.80).

Conclusions: VAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.

Keywords: Acute respiratory distress syndrome; COVID-19; Hospital-acquired infection; Intensive care unit; Mechanical ventilation; Outcome; Ventilator-associated pneumonia.

Fig. 1

Cumulative likelihood of survival over time in patients with and without VAP. VAP ventilator-associated pneumonia, HR hazard ratio (indicated with 95% confidence interval). Day 0 indicates the date of intubation. Panel A, all patients with acute respiratory distress syndrome (ARDS); Panel B, patients with non-coronavirus disease 2019 (COVID-19)-related ARDS; Panel C, patients with COVID-19-related ARDS

Fig. 2

Trends in PaO₂/FiO₂ ratio, extra-respiratory SOFA score values and total SOFA score values in patients with VAP. VAP ventilator-associated pneumonia, ARDS acute respiratory distress syndrome, COVID-19 coronavirus disease 2019, SOFA sepsis-related organ failure assessment. Panels A, C and E, all patients with ARDS; panels B, D and F, patients with COVID-19-related ARDS versus patients with ARDS from other causes

Fig. 3

Cumulative likelihood of MV weaning in patients with and without VAP. MV mechanical ventilation, VAP ventilator-associated pneumonia, sHR cause-specific hazard ratio (indicated with 95% confidence interval). day 0 indicates the date of intubation. Note that the curve of the no-VAP subgroup ends at day 36 of MV, since all patients without VAP had been extubated or had died at this time. For the VAP subgroup, the curve ends at day 89 of MV for the same reasons