Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in patients requiring endotracheal tubes with mechanical ventilation [1]. The reported prevalence of VAP in trauma patients is about 4-fold higher than that in non-trauma patients [2]. Before 2013, the Centers for Disease Control and Prevention (CDC), the American Thoracic Society, and the Infectious Diseases Society of America collaborated to provide the surveillance definition of VAP [3-6]. However, over time, many concerns were raised about the effectiveness, reproducibility, and interpretation of VAP rates [7]. In 2013, the National Healthcare Safety Network (NHSN) replaced the previous definition of pneumonia with a classification of ventilator-associated events (VAEs). The concept of VAEs was defined to overcome many of the limitations of traditional VAP definitions, with the aim of establishing definitions that are objective, reproducible, automated, and a powerful predictor of poor outcomes [8]. VAEs are common complications in patients undergoing mechanical ventilation in the intensive care unit (ICU) [9,10]. These can lead to further complications that can extend the duration of mechanical ventilation, the length of stay (LOS) in the ICU, as well as costs, morbidity, and mortality [11,12]. Therefore, we analyzed the patients who received mechanical ventilator support at Jeju Regional Trauma Center.

From January 2020 to January 2021, 492 patients were admitted to Jeju Regional Trauma Center, of whom 210 patients received ventilator support. Among them, 84 patients had at least 4 calendar days of ventilator support. In accordant with 2013 CDC/NHSN VAE surveillance criteria, those who were under 18 years old (n=4), received extracorporeal membrane oxygenation therapy (n=6), and had incomplete data (n=1) were excluded from this study (n=11). Finally, the study population comprised 73 patients, of whom 48 had no VAEs (65.8%), 16 met the definition for VACs (21.9%), three met the criteria for IVACs (4.1%), and six met the criteria for PVAP (8.2%). The subjects categorized as belonging to the no-VAE group had no VAEs during mechanical ventilatory support. The subjects in the VAE group had at least one VAE criterion (including VACs, IVACs, and PVAP). There were no significant differences in demographics, comorbidities, injury characteristics, clinical data, and laboratory values between the two groups (Table 2). Additionally, there were no significant differences in ICU LOS (P=0.200), ventilator support days (P=0.164), the incidence of nosocomial complications, and in-hospital mortality (P=0.111) between the two groups (Tables 3, 4). However, the VAE subjects were more likely to have higher GCS scores (P=0.012) and chest AIS (P=0.024) (Tables 2, 5) and less likely to have normal kidney function as measured by the GFR (P=0.001) (Table 3) than the no-VAE subjects. The VAE subjects had a higher number of bronchoscopies (P=0.004) and were more likely to have acute respiratory distress syndrome (P=0.021) than the no-VAE subjects (Table 4). Continuous values were converted to categorical values for logistic regression analysis. The cutoff values were set as 65 years for age, 3 points for AIS, 15 points for ISS, 7 points for GCS, and 75 mL/min/1.73 m² for GFR. In the multivariate analysis, the risk for VAE occurrence was 4.7-fold higher in patients with chest AIS ≥3 (OR, 4.73; 95% CI, 1.46–17.9) and 4.1-fold higher in those with a GFR <75 mL/min/1.73 m² (OR, 4.15; 95% CI, 1.32–14.1). The in-hospital mortality risk was more than 4-fold higher in patients with a GFR <75 mL/min/1.73 m² (OR, 4.19; 95% CI, 1.30–14.3) (Table 6). In addition, VAEs occurred in 50.0% of patients with a chest AIS ≥3 within 15 days of mechanical ventilatory support (Fig. 1). The median VAE-free duration of patients with a chest AIS ≥3 was significantly shorter than that of patients with a chest AIS <3 (P=0.013).

To our best knowledge, this study is the first surveillance study of the incidence, risk factors, and outcomes with the newly defined concept of VAEs in trauma patients. The present study revealed that several factors were associated with VAE occurrence and in-hospital mortality in polytrauma patients.

The VAE group was more likely to have higher GCS scores, which were used to define the severity of traumatic brain injuries (TBIs) in several studies. Patients with TBIs often suffer from profound suppression of cellular immunity and impaired consciousness [14], and they usually require endotracheal intubation and mechanical ventilatory care, both of which increased the incidence of VAP. Therefore, severe TBI patients were more vulnerable to VAP [15]. However, chest injury and the combination of chest injury and TBI were found to be independent predictors for the development of pneumonia in polytrauma patients [15]. This suggests that TBI itself was not associated with the development of pneumonia. Our results showed that patients in the VAE group had relatively higher GCS scores, although the GCS scores were not related to in-hospital mortality.

Second, blunt chest trauma may cause intra-thoracic organ injuries, which may lead to serious complication and mortality in polytrauma patients [16]. The risk of respiratory failure and subsequent pneumonia development depends on the severity of the chest injury [17]. Hofman et al. [18] reported that although chest trauma was not an independent risk factor for mortality, it was an independent risk factor for pneumonia. Their results showed that a chest AIS ≥3 in poly-traumatized patients was associated with an increased risk of pneumonia (OR, 4.193; P=0.004) in multivariate regression analysis. The present study showed similar results, in that the patient with a chest AIS ≥3 were likely to have a higher risk of VAE.

Lastly, several recent studies showed that reduced renal function was associated with an increased risk of pneumonia [19]. An explanation for this is that decreased renal function may increase the risk of infection due to immune impairment, which is supported by reports of abnormalities in neutrophil and lymphocyte function [20]. The observed association between kidney function and infection may be due to an increased susceptibility to infection and/or a greater severity of infection in older patients with chronic kidney disease [21]. Our study also showed similar results, as decreased renal function was associated with VAE occurrence and in-hospital mortality. VAEs themselves did not affect the risk of in-hospital mortality. However, patients with a low GFR showed a statistically significant increase in mortality. In other words, posttraumatic acute kidney injury (AKI) can be a direct risk factor for mortality in trauma patients. Harrois et al. [22] performed a systematic review and meta-analysis of AKIs in trauma patients that included 24 studies with 25,182 patients. In their analysis, they observed that posttraumatic AKI was associated with a 3.4-fold increased risk of mortality (95% CI, 2.1–5.7) and they observed that the risk factors for posttraumatic AKI were specific race, old age, hypertension, and diabetes mellitus. In our study, we performed a subgroup analysis based on GFR that showed statistically significant differences in patients’ age (P=0.0153) and hypertension (P=0.0388) between the two groups (Table 7).

This study had several limitations. First, the study period was short, and the sample size was small. Although we were able to derive several risk factors associated with VAE occurrence and in-hospital mortality, it is necessary to estimate more significant risk factors using a largescale study in the future. Second, although the number of bronchoscopies was significantly higher (P=0.004) in the VAE group, we were not able to establish a significant effect of bronchoscopy on VAE occurrence and in-hospital mortality. However, there is some evidence that diagnostic bronchoscopy may improve VAP-related outcomes [23,24]. Bronchoscopic sputum aspiration has also shown promising results and significant benefits in various indicators, including shorter mechanical ventilation, reduced hospital LOS, and improved weaning success rates [25]. Considering these points, it will also be necessary to study whether bronchoscopy may affect the occurrence and mortality rate of VAE in trauma patients. Third, in this study, the effect of tracheostomy was not considered in patients with a mechanical ventilator. However, tracheostomy may have several advantages, such as improved airway suctioning, less direct laryngeal injury, decreased airway resistance for promoting weaning from mechanical ventilation, and decreased risk for nosocomial pneumonia [26]. Thus, research on the association between tracheostomy and VAE occurrence is needed in the future.

In conclusion, based on our study results, traumatized patients with chest AIS ≥3 or GFR <75 mL/min/1.73 m² on admission should be intensively monitored to detect patients at risk for VAEs and modify their care plans to reduce the risk of VAEs during mechanical ventilator support. VAEs should be closely monitored to identify infections in the target subjects early and to achieve desirable results. We should also actively consider modalities that can minimize the duration of mechanical ventilators (less than 15 days) in patients with a chest AIS ≥3 to reduce VAE occurrence.