Trauma has been strikingly increasing with the development of road construction, traffic transport and a sharp increase in the number of vehicles. Among the deaths due to trauma, about one half of patients suffer from road traffic injury (RTI), most of these patients with post-traumatic acute respiratory distress syndrome (ARDS) have severe multiple injuries.1–3 Although multiple studies concentrated on risk factors, especially in mortality from post-traumatic ARDS,4–6 none included a patient population resricted to RTI. We hypothesized that not all of the traditional risk factors in previous prospective studies4,7 were independently associated with mortality of post-traumatic ARDS from severe traffic injury or, rather, we want to sieve distinctive factors from those risk factors. We also hypothesized there may exist significantly different risk factors in stratified patients; i.e., surviving beyond 96 hours, more severe RTI with higher injury score and long-term mechanical ventilation as well.
All patients were due to RTI as a single cause admitted to the emergency intensive care unit (EICU) between May 2002 and April 2007 in the Second Affiliated Hospital of Zhejiang University in China; a level 1 academic emergency trauma center.
Information on patients' demographic characteristics, treatment procedures and injury severity were collected at the time of EICU admission. The criteria used for ARDS met definition of the American-European Consensus Conference.8 The commonly accepted definition of multiple injuries was consistent with both several injury sites (from two or more than two anatomic sites) and injury in one anatomic site threatening life.9 Severity of injury was quantified by injury severity score10 and the simplified acute physiology score and chronic health evaluation score (APACHE II)11 in EICU admission. We included adult patients (age ≥18 years), those with an length of EICU stay longer than 48 hours and those accepting mechanical ventilation more than 24 hours. Patients who were readmitted to EICU by virtue of non-traffic injury or transferred to EICU from other hospitals after long-term treatment were excluded. Mortality was assessed at the 28th day after RTI.
The following 23 items were selected as potential risk factors: (1) gender; (2) age, ≥60 years or <60 years; (3) smoking; (4) alcohol abuse, insobriety for more than three times a week; (5) diabetes; (6) duration of trauma factor interval from trauma occurring to trauma factor discharged, ≥1 hour or <1 hour; (7) injury severity score, ≥16 or <16; (8) APACHE II score, ≥20 or <20; (9) pulmonary contusion, diagnosed by CT scan; (10) chest trauma; (11) traumatic shock, ≥0.5 hour or <0.5 hour; (12) multiple blood transfusions in 24 hours, ≥10 units or <10 units;12,13 (13) operation; (14) traumatic pancreatitis; (15) hepatic dysfunction; (16) renal dysfunction; (17) gastrointestinal hemorrhage; (18) aspiration of gastric contents; (19) sepsis; (20) glucocorticoid dose, urbason ≥160 mg/d or <160 mg/d;14,15 (21) duration of glucocorticoid using, ≥3 days or <3 days; (22) duration of mechanical ventilation, ≥7 days or <7 days; and (23) positive end-expiratory pressure (PEEP) parameter, ≥10 cmH2O or <10cmH2O.16,17
Patients were divided into a survivors group and a nonsurvivors group and were statistically compared by using the chi-square test for categorical variables and Student's t test for continuous variables. Variables presenting significant differences between groups in univariate comparison were entered in stepwise Logistic regression analysis. Significance of individual interaction among these terms was determined using likelihood test, however, none of the interaction terms was significant (P >0.05), there was no significant co-linearity between any of the independent variables. Goodness of fit in the regression model was evaluated by the Hosmer-Lemeshow test (P <0.05). Adjusted ORs with 95% CI were calculated. All of the statistical analyses were performed using a statistical software package (SPSS for Windows, version 11.0, SPSS Inc, Chicago, IL, USA). A two-side P value of <0.05 was considered statistically significant.
During the 5-year study period, 247 patients were consecutively admitted to our study. Demographic characteristics of the patient population are shown in Table 1. Compared with the survivors group, the nonsurvivors group had a higher APACHE II score.
Among survivors beyond the first 24 hours in EICU admission, the unadjusted ORs were associated with duration of trauma factor, APACHE II score, pulmonary contusion, aspiration of gastric contents, sepsis and duration of mechanical ventilation (Table 2). Based on our previous clinical experience and results of this study, most of severe RTI patients developed ARDS within 96 hours after injury. The model was consequently refitted to exclude patients who died within 96 hours of EICU admission in order to enhance the comparability. There was incremental mortality associated with those risk factors, especially appearing in APACHE II score, duration of trauma factor and aspiration of gastric contents (Table 3). When we eliminate the patients who acquired an APACHE II score <20, leaving more severe RTI patients (APACHE II score ≥20) available for analysis, prediction of distinguished higher ORs in risk factors were not observed and only an appreciably small augmentation of adjusted ORs were manifested in duration of trauma factor, sepsis and duration of mechanical ventilation. On the contrary, the adjusted OR in aspiration of gastric contents declined (Table 4). In order to confirm the assumption that long-term mechanical ventilation possibly promote other risk factors to induce higher mortality in RTI patients, a patient population requiring duration of mechanical ventilation ≥7 days were brought into further analysis and significance of adjusted OR only in trauma factor and sepsis appeared in Table 5.
In this retrospective cohort study, we evaluated the effect of 23 high-risk items impacting mortality within a severe RTI population with post-traumatic ARDS. The results suggest that for those patients admitted to EICU, increase of the overall mortality is associated with several risk factors out of the 23 items, especially including duration of trauma factor, aspiration of gastric contents and sepsis. Pulmonary contusion resulting in disputing lung parenchyma with rupture of small airways, alveoli and capillaries may be the most common cause of development of ARDS in previous studies,1,18 however, it is not the main impacting factor in mortality of post-traumatic ARDS in our study. Significance was not observed in adjusted ORs: surviving beyond 96 hours EICU admission, APACHE II score ≥20 and duration of mechanical ventilation ≥7 days. It is possible that pulmonary contusion only indicates acutely short-term worsening of oxygenation due to direct crush injury, blood spilling intrabronchially into the normal tissue causing airway obstruction, bronchospasm and airway collapse as well. Its contribution to mortality gradually attenuates in long-term outcomes (surviving beyond 96 hours EICU admission and duration of mechanical ventilation ≥7 days) on account of adequate mechanical support to maintain severe RTI patients' respiratory needs and improving oxygenation simultaneously.
Although the APACHE II score in several studies is taken as the main assessment index of mortality in the trauma population, and there is a definite relationship between the severity of injury and the likelihood of subsequent ARDS,7,19 the same conclusion in mortality were made in surviving beyond 96 hours (OR 2.534; 95%CI 1.367–4.557) but not in duration of mechanical ventilation beyond 7 days (OR 2.069; 95%CI 0.738–5.714; P=0.099). Therefore, similar to pulmonary contusion, the impact of the APACHE II score calculated at the time of EICU admission in post-traumatic mortality probably exists in prophase after severe RTI. Multiple therapeutic measures, for instance, immediate damage-control operations to mitigate secondary injury, defensive ventilation strategy to prevent ventilator-associated lung injury, correctly treating infections, were enforced to relieve severe multiple traumatic damage.
In our past experience the duration of trauma factors determined by the degree of injury and outcomes in EICU admission with longer duration generally manifested higher mortality. In our trial aiming at the severe RTI population, the long-term consequence of duration of trauma factor was denoted in both surviving beyond 96 hours EICU admission (OR 3.911; 95%CI 1.685–8.764) and duration of mechanical ventilation ≥7 days (OR 2.317; 95%CI 1.853–6.736), mortality markedly rose 3–4 folds. The results have been proposed that it is vital to discard trauma factors as early as possible.
The reported mortality of ARDS ranges from 31% to 74%; depending on the specific patient mix with most deaths occurring as a consequence of sepsis and multiple organ failure.20,21 Findings of our study also denoted that sepsis still is the main risk factor of mortality (APACHE II score ≥20 and duration of mechanical ventilation ≥7 days), particularly regarding the severe RTI population, and the result was consistent with previous conclusions in unclassified trauma patients as well. Mortality due to sepsis far exceeds all causes of EICU deaths and equals the number of deaths due to acute myocardial infarction.22
By the American College of Chest Physicians and Society of Critical Care Medicine defined systemic inflammatory response syndrome criteria,23 it seems that all enrolled RTI patients in EICU have systemic inflammatory response syndrome by virtue of their severe trauma conditions. Sepsis was present when systemic inflammatory response syndrome was accompanied by a known or suspected infection,24 secondary organ dysfunction or hypotension and hypoperfusion ensued. Infection could actually be considered a manifestation of multiorgan dysfunction syndrome as well as the cause of it.25 Insight into the inflammatory response, endothelial injury and coagulation cascade correlated to sepsis suggest promising new treatment regimens that markedly decline mortality and morbidity.26
Aspiration of gastric contents in EICU is constantly correlated to severe ventilation associated pneumonia, and also attributable to an increase in mortality in previous literature.27–31 The same conclusion was demonstrated in severe RTI patients surviving beyond 24 hours (OR 1.873; 95%CI 1.050–3.764) and 96 hours (OR 2.426; 95%CI 1.305–4.517). Nevertheless, similar results did not occur in more severe RTI patients with APACHE II scores ≥20 (OR 1.863; 95%CI, 0.939–3.307; P=0.097). In contrast, uniform analysis was manipulated in those patients with mechanical ventilation beyond 7 days speculated to acquire more severe complications, the absence of aspiration leading to an augmentation in the rate of mortality appeared. There may be several reasons to explain the difference. Aspiration of gastric contents resulting in severe complications in EICU is acknowledged, therefore, more attention was paid to this condition and it necessitated immediate actions of accepted suction treatment and routine semi-reclining position and enforcing infection prevention therapy were manipulated for critically ill patients incurring aspiration. Meanwhile, severe RTI patients (APACHE II score ≥20) with ventilation beyond 7 days had a higher risk rate (OR 2.629; 95%CI 1.380–5.963). Inadequate usage of glucocorticoid and mechanical ventilation leads to ventilation associated complications such as sepsis and barotrauma with increased mortality ensuing.
This study does have several potential limitations. Over a 5-year period, we collected large amounts of information related to severe RTI patients with post-traumatic ARDS that may not be generalized to other clinical settings and may be biased by time-related changes in medical strategy, including newly lung-protective ventilation therapy and new perceptions in curing sepsis. Although we used the commonly accepted diagnostic criteria for ARDS, these definitions may be less stringent, and there is a risk of misclassification.8,20 Overly exclusive standards may lead to a bias by excluding patients with pretraumatic pathophysiological dysfunction. Finally, because no specific or primary causes of death were collected in our series, we can not analyze deaths primarily due to ARDS versus other causes.
In summary, we have retrospectively demonstrated the impact of several risk factors in mortality of post-traumatic ARDS in severe RTI patients. In contrast to traditional trauma definition in single anatomic site or generally unclassified trauma populations, we conclusively see different outcomes regarding RTI population in real emergency circumstance. Impact of APACHE II score and pulmonary contusion contributing to prediction of mortality may exist in prophase after traffic injury. Consistent with previous studies, sepsis is still a vital risk factor associated with systemic inflammatory response syndrome, infection, and secondary multiple organ dysfunction. Duration of trauma factor impacts long-term mortality and should keep our attention. Therefore, promptly eliminating trauma factors becomes the critical therapeutic measure. Aspiration of gastric contents in EICU leading to incremental mortality due to severe ventilation associated pneumonia should not be ignored. Long-standing mechanical ventilation in severe RTI patients should be constrained on account of the occurrence of severe refractory complications.
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