A reappraisal of association between ventilator-associated events and mortality among critically ill patients using marginal structural model: multicenter observational study

Purpose

Ventilator-associated events (VAEs), developed by the US Centers for Disease Control and Prevention (CDC), are considered a new medical quality indicator associated with poor outcomes. However, previous studies failed to adjust for changes in patient severity, leaving open the possibility that VAEs are just a surrogate for severity. This study aimed to reevaluate the association between VAEs and mortality, adjusting for changes in severity over time.

Methods

This multicenter observational study was conducted in 18 ICUs in Japan between May 2020 and December 2022. Patients aged ≥ 12 years who received mechanical ventilation for ≥ 3 consecutive days were eligible. VAE was diagnosed according to the CDC definition. The primary outcome was 30-day in-hospital mortality, whose association with VAE was estimated by the inverse probability weighted proportional hazards model, with temporal changes in patient severity treated as time-dependent confounders.

Results

Among 1,094 subjects, 106 VAEs (9.7%) were identified, giving an incidence rate of 10.0 per 1,000 ventilation days. VAEs were significantly associated with increased 30-day hospital and ICU mortality (HR 2.00; 95% CI 1.23–3.26 and HR 1.92; 95% CI 1.03–3.57), and longer hospital and ICU length of stay (HR 0.72 95% CI 0.54–0.97 and HR 0.47; 95% CI 0.23–0.96). The population attributable risk fraction of VAE-related mortality was 8.8% for in-hospital deaths and 8.2% for ICU deaths.

Conclusions

VAEs were associated with an increased risk of mortality after adjustment for severity, as a time-dependent confounder.