Discussion
To our knowledge, ours is the largest study evaluating the predictors of developing ARDS and mortality in trauma patients, and one of a few studies evaluating trauma-induced ARDS across multiple institutions using post-2007 data.1 12–24 Furthermore, this is one of the few studies investigating ARDS in patients with an ISS ≤15. Using a large national trauma database, we identified and characterized patients who developed ARDS after a traumatic injury. Our key findings are as follows. First, the overall incidence of ARDS has decreased; however, mortality in patients with ARDS has actually increased in trauma patients. Second, ARDS is not a disease process of severely injured patients alone; in our study, nearly a third of the patients with ARDS had an ISS ≤15. Third, the strongest risk factors for the development of ARDS were direct thoracic injury and a history of cardiopulmonary or hematologic disease and alcoholism. Fourth, although TILC was an independent risk factor for the development of ARDS, on subgroup analysis, patients with or without TILC had relatively similar risk factors for the development of ARDS (table 3). Fifth and finally, mortality in patients with ARDS was due not to direct thoracic injury but rather to patient-level factors such as older age, male gender, more severe injury, and certain comorbidities (table 5).
In our study, we identified a 1% overall incidence of ARDS in US trauma centers. Some reports have indicated that the incidence has remained unchanged during the past decade. But according to the majority of the literature, the incidence of trauma-induced ARDS has decreased—a finding that aligns with our clinical experience and findings in this study.23 47–49 The decreased incidence is likely due to improved resuscitative and critical care strategies developed during the past two decades. Key areas of clinical improvement include widespread adoption of lung-protective strategies for mechanical ventilation and of restrictive fluid strategies for resuscitation. Our data strengthen the claim that trauma-induced ARDS incidence is decreasing over time in the USA.
ARDS is not a disease process of just the severely injured; we observed nearly one-third of patients who developed ARDS had an ISS ≤15. Given this finding, we included patients with an ISS ≤15 in our analysis, which also accounts for the low incidence of ARDS identified in this study. This finding is important, as previous studies on trauma-induced ARDS have excluded this population from analysis.22 25–32 Risk factors were significantly different for developing ARDS in patients with minor (vs. major) injury. Patients who developed ARDS with major injury were more likely to have direct thoracic injury, perhaps contributing to their elevated ISS via an increased AIS chest score. Surprisingly, patients who developed ARDS with minor injuries were more likely to be older (>46 years old) and have multiple comorbidities. There is much interest in better understanding the role patient comorbidities play in the development and management of patients with ARDS, as nearly all ARDS clinical trials and epidemiologic studies since 1998 have excluded patients with major comorbidities.50 In this study we identified that patients with a history of alcoholism, bleeding disorders, and cardiopulmonary comorbidities after minor trauma were more likely to develop trauma-induced ARDS than patients after major trauma (table 4). Future research is needed to investigate the effect of patient comorbidities on the development of trauma ARDS and how the presence of specific patient comorbidities influences current ARDS prevention strategies.
Central to this study’s objective, we have identified that the direct thoracic factors—flail chest, multiple rib fractures, and TILC—are significant contributors to the development of ARDS. Multiple studies have documented an inconsistent correlation between the volume of TILC and the development of ARDS.51 These suggest interactions with other factors occurring around the time of injury may be involved in the development of ARDS. In our subgroup analysis, stratified by TILC, we found that patients with or without TILC had relatively similar risk factors for the development of ARDS. The presence of significant injury burden, represented by an elevated ISS and low GCS motor component score, was identified as an important extrathoracic predictor of ARDS. It is likely that contribution from a robust systemic inflammatory response resulted in the deterioration of lung function, as observed with experimental data in animals and in human subjects with additional risk factors.52 53 Similarly, the possibility of additional insults to the lung such as aspiration-induced lung injury seen frequently as a complication of low GCS score from TBI accounts for the deterioration of lung function to a full-blown ARDS. Our laboratory has shown in small animals a combination of aspiration-induced lung injury when added to TILC produces a synergistic increase in lung injury and inflammation.54 Additionally, elderly age, male sex, illegal drug use, history of alcoholism, bleeding disorder, cardiac history, obesity, and respiratory disease were the most significant predictors for the development of ARDS in trauma patients. These findings supplement those of previous studies that also aimed to identify risk factors in trauma patients.1 13 17 29 33 35 Previous studies have suffered from many limitations. For example, the majority of multi-institutional studies performed used pre-2007 accrual periods, before the widespread implementation of critical care practices devised by ARDSNet (short for the multicenter ARDS Network initiated by the National Heart, Lung, and Blood Institute of the National Institutes of Health), with the majority of studies published using post-2007 patient data being single institution in nature.1 12–24 Additionally, previous studies included a relatively limited number of patients with ARDS, as compared with our study’s 28 597 patients.1 13 17 29 33 35
In our study, 22% of the patients with ARDS died while hospitalized. The precise incidence of mortality in patients with ARDS has generated much controversy.13 15 35 55 We found that mortality in patients with ARDS has increased over time in the USA, strengthening the claim that mortality is not declining. Although ARDS is considered an independent risk factor for mortality in trauma patients, the contribution of associated injuries and comorbidities to mortality is unclear.13 35 Predictors of mortality in our study patients included extrathoracic risk factors as a higher ISS and a lower GCS motor component score. Patient characteristics associated with higher mortality included increased age, male gender, and non-Medicaid insurance status. Comorbidities associated with higher mortality include a history of bleeding disorder, CHF, and diabetes mellitus. We found that patients with ARDS secondary to direct thoracic injury (including TILC, flail chest, and rib fractures) had improved survival, as compared with ARDS due to other mechanisms. This finding suggests that the nature of the inflammatory response to direct thoracic injury (vs. to extrathoracic risk factors) is distinctly different. It is well known that in basic research of direct and indirect risk factors, the mechanisms, nature of inflammatory attribute, type of cellular and cytokine response, and healing are entirely different.56 57 We propose using the stratification of direct thoracic and extrathoracic risk factors as a methodology in the future to evaluate risk factors in studies involving trauma-induced ARDS.
This study has several limitations, the major one being its retrospective study design. We were also limited by the elements within the database, which did not include such relevant information as the units of blood products, the volume of crystalloid solutions, or the patient’s cause of death. Additionally, the NTDB does not differentiate between ALI and ARDS; thus, this study may overestimate the clinical burden of ARDS as it includes patients with a PaO2:FiO2 ratio of 200 to 300 mm Hg in the definition of ARDS. Although in-hospital mortality was reported, no follow-up information was available regarding patient survival after hospital discharge.