Attributable Mortality of Ventilator-associated Pneumonia. Replicating Findings, Revisiting Methods

Abstract

Rationale: Estimating the impact of ventilator-associated pneumonia (VAP) from routinely collected intensive care unit (ICU) data is methodologically challenging.Objectives: We aim to replicate earlier findings of limited VAP-attributable ICU mortality in an independent cohort. By refining statistical analyses, we gradually tackle different sources of bias.Methods: Records of 2,720 adult patients admitted to Ghent University Hospital ICUs (2013-2017) and receiving mechanical ventilation within 48 hours after admission were extracted from linked Intensive Care Information System and Computer-based Surveillance and Alerting of Nosocomial Infections, Antimicrobial Resistance, and Antibiotic Consumption in the ICU databases. The VAP-attributable fraction of ICU mortality was estimated using a competing risk analysis that is restricted to VAP-free patients (approach 1), accounts for VAP onset by treating it as either a competing (approach 2) or censoring event (approach 3), or additionally adjusts for time-dependent confounding via inverse probability weighting (approach 4).Results: A total of 210 patients (7.7%) acquired VAP. Based on benchmark approach 4, we estimated that (compared with current preventive measures) hypothetical eradication of VAP would lead to a relative ICU mortality reduction of 1.7% (95% confidence interval, -1.3 to 4.6) by Day 10 and of 3.6% (95% confidence interval, 0.7 to 6.5) by Day 60. Approaches 1-3 produced estimates ranging from -0.7% to 2.5% by Day 10 and from 5.2% to 5.5% by Day 60.Conclusions: In line with previous studies using appropriate methodology, we found limited VAP-attributable ICU mortality given current state-of-the-art VAP prevention measures. Our study illustrates that inappropriate accounting of the time dependency of exposure and confounding of its effects may misleadingly suggest protective effects of early-onset VAP and systematically overestimate attributable mortality.

Keywords: causality; confounding factors (epidemiology); hospital mortality; survival analysis; ventilator-associated pneumonia.

Figure 1.

Study flow diagram. APACHE = Acute Physiology and Chronic Health Evaluation; ICU = intensive care unit; VAP = ventilator-associated pneumonia.

Figure 2.

Results of the four different CR analysis approaches for estimating the time-dependent population-attributable fraction (PAF) of intensive care unit (ICU) mortality due to ventilator-associated pneumonia (VAP): a CR analysis restricted to VAP-free patients (approach 1; panel A), a CR analysis that treats VAP as a competing event (approach 2; panel B), a CR analysis that treats VAP as a censoring event (approach 3; panel C), and a CR analysis adjusted for time-dependent confounding (approach 4; panel D). Upper panels: observed cumulative incidence of ICU mortality (black curves) and estimated counterfactual VAP-free cumulative incidence of ICU mortality (gray curves). Lower panels: estimated PAF of ICU death due to VAP (solid lines) and 95% pointwise confidence intervals (shaded areas). CR = competing risk.