Infection Control & Hospital Epidemiology Pneumonia (VAP) 0.020 0.20 Extubation without VAP
303
0.010
0.10
0.000 0 5 10 15 20 25 30
duration of mechanical ventilation (days)
Fig. 2. Hazard rates for ventilator-associated pneumonia (VAP) and extubation without VAP. Pneumonia (VAP) 0.30 0.20 0.10 0.00 010 5 15 20
duration of mechanical ventilation (days)
25 30
0.0 0.2 0.4 0.6 0.8 1.0
0 1015202530
duration of mechanical ventilation (days)
Fig. 3. Cumulative risk (incidence) of ventilator-associated pneumonia (VAP) and extubation without VAP, accounting for competing events (black) versus treated as censored (gray).
For each event (ie, VAP occurrence or extubation), a separate
cause-specific hazard analysis was performed via Cox proportional hazards models to explore etiological associations. For VAP as the event of interest, an adapted Cox regression analysis (the Fine and Gray model13) was performed to calculate subdistribution hazard ratios (sHRs) and to study the summary effects on the cumulative incidence of VAP. All regression models were stratified by ICU. For multiple ventilation episodes, the time in ICU before ventila- tion was updated. Because the update led to a correlation between the episode variable and time in the ICU before ventilation, only 3 main variables of interest were included: ie, time in ICU before mechanical ventilation, time in hospital before ICU admission, and multiple episodes. However, the following variables were further included to adjust for confounding:APACHEII score mea- sured at ICU admission, age, gender, trauma, diagnosis (eg, respi- ratory, gastrointestinal, central nervous system, cardiovascular, and other diagnoses), antibiotic treatment 48 hours before and/ or after ICU admission, and calendar year of admission. In all regression models, we used robust variance estimation to account for data clustering regarding multiple ventilation episodes.
Results
Among all 48,705 ventilation episodes in the ICU, 3,655 patients (7.45%) developed a VAP during their stay (Table 1). Figure 1
illustrates the time-dependent data structure of 100 randomly sampled patients.Time origin is the start of mechanical ventilation. The corresponding time periods, marked as black lines for hospi- talization before ICU admission and as gray lines for time in ICU before ventilation were entered into the Cox regression models as covariates. The gray line after time 0 shows the duration of venti- lation at risk for VAP; this time is modeled as an outcome variable in the Cox regression models.
Hazard rates
Figure 2 shows the duration-dependent hazard rates of VAP and extubation, which are interpreted as the instantaneous daily risk of experiencing the corresponding event VAP or extubation without VAP. Interestingly, the hazard rate ofVAPis low but increasing for earlier duration days, and after 5 duration days the hazard rate is decreasing. In contrast, the extubation rate only decreases, which means that most ventilated patients received short-term ventila- tion (2–4 days) without acquiring VAP.
Cumulative risks
The cumulative risk forVAP(Fig. 3, left, black line) depends on both hazard rates. The duration-dependent proportion of ventilated patients have acquired a VAP by duration day t. Analogously, the
Extubation without VAP
0.00 0 5 10 15 20 25 30
duration of mechanical ventilation (days)
Cumulative risk
Hazard rate
Cumulative risk
Hazard rate
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