Attributable Mortality of Ventilator-Associated Pneumonia A Reappraisal Using Causal Analysis

Rationale: Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. Objectives: We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. Methods: Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. Measurements and Main Results: Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. Conclusions: Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.