302


Table 1. Description of Study Population Characteristic


No. of ventilated patients in ICU No. of ventilation episodes No. of ventilator days


Ventilator-associated pneumonia (VAP)


APACHE II score 0–10


11–20 21–30 >30


Age at ICU admission 0–40 y


41–60 y


61–80 y (reference) >80 y


Time in hospital before ICU admission 0–3 d (reference) 4–6 d


6–10 d >10 d


Time in ICU before mechanical ventilation 0 d (reference) 1 d 2 d


3–4 d >4 d


Diagnosis


Cardiovascular (reference) Respiratory


Gastrointestinal


Central nervous system Other diagnoses


Antibiotic treatment 48 h before and/or after ICU admission


Male Trauma


Year at ICU admission 2006 2007 2008 2009


2010þ


Episode First


Second Third


Note. ICU, intensive care unit.


19,522 (40.08) 7,740 (15.89) 7,936 (16.29) 10,740 (22.05) 2,767 (5.68)


14,424 (29.62)


31,724 (65.13) 5,053 (10.37)


6,447 (13.24) 7,915 (16.25) 10,088 (20.71) 11,547 (23.71) 12,708 (26.09)


45,486 (93.39) 2,911 (5.98) 308 (0.63)


100


Baseline, No. (%) 45,486 48,705


314,196 3,655 (7.45)


9,092 (18.67) 22,134 (45.45) 13,277 (27.26) 4,202 (8.63)


6,061 (12.44) 12,983 (26.66) 25,043 (51.42) 4,618 (9.48)


35,580 (73.05) 3,367 (6.91) 2,901 (5.96) 6,857 (14.08)


39,993 (82.11) 2,675 (5.49) 1,465 (3.01) 1,548 (3.18) 3,024 (6.21)


20 40 60 80


pre−ventilation 0


−20 −15 −10 −5 0 5 10 15 20 25 30 days from ventilation


Fig. 1. Graphical visualization of a random sample of 100 patients. Time origin is the start of mechanical ventilation. The corresponding time periods are marked as black (hospitalization before ICU admission) and gray lines (time in ICU before ventilation). The gray line after time 0 shows the duration of ventilation at risk for VAP. The dots show the occurrence of VAP. Extubation without VAP occurs if the gray line ends with- out a dot.


studies have found that the VAP hazard rate decreases over ventilation time.10 Finally, the length of stay in the hospital and intensive care unit (ICU) before intubation might impact the char- acteristic of VAP because patients who have been in the hospital for ≥2 days before intubation are more likely to be colonized with multidrug-resistant pathogens.2 In this study,we aimed to provide and apply an appropriate stat-


istical model to study the risks for VAP. Specifically, we accounted for duration of mechanical ventilation as at-risk time, competing events, preintubation length of hospital or ICU stay, multiple ventilation episodes, andother important andpotential confounding factors.Wefocused on the challenging task of interpreting the results from a competing-risks analyses.


Materials and methods Spanish ICU data


We used a multicenter database from the Spanish surveillance network HELICS-ENVIN (http://hws.vhebron.net/envin-helics/), embedded in the HELICS project (Hospitals in Europe Link for Infection Control through Surveillance).11 We included ICUs that contributed to the registry between January 2006 and June 2011, and we included only ventilated adult patients who stayed at least 2 days in an ICU, due to the definition of hospital-acquired infec- tions. Up to 3 ventilation episodes were considered. Ventilation episodes following a VAP were excluded for the following reasons: (1) because VAP was not specified as the reason for ventilation; (2) to avoid noncausal artefacts; and (3) to ensure a true incident VAP outcome. The study population contained 158 ICUs with 45,486 admissions, 48,705 ventilation episodes, and 314,196 ventilator days. This Deutsche Forschungsgemeinschaft (DFG) research project was approved by the Ethics committee of University Medical Center Freiburg, Germany.


Statistical methods


The time from 48 hours after first intubation until the occurrence of VAP (event of interest) or 48 hours after extubation (competing event) was studied using a competing-risks analysis, without administrative censoring. We estimated the actual hazard rates for VAP and 48 hours after extubation (hereafter termed extubation) in dependency of duration of ventilation as the at-risk time. The cumulative incidences of both events were estimated using the Aalen-Johansen method.12


post−ventilation


Martin Wolkewitz et al


Patients


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