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.