Is chest imaging relevant in diagnosing acute respiratory distress syndrome in polytrauma patients? A population-based cohort study

Acute respiratory distress syndrome (ARDS) is clinically characterized by severe dyspnea, cyanosis refractory to oxygen therapy, loss of lung compliance, and diffuse alveolar infiltrates on chest radiograph [1]. This is caused by an increased permeability of the alveolar–capillary barrier resulting in lung edema with protein-rich fluid causing an impairment of arterial oxygenation. Lung edema, endothelial and epithelial injuries are accompanied by an influx of neutrophils into the interstitium and broncho-alveolar space. Activation and recruitment of neutrophils play an important role in progression of ARDS [2].

Over the years, the definition of ARDS has often been modified with Berlin criteria being the most recent [3, 4]. To facilitate prognosis, ARDS was divided into three categories based on the degree of hypoxemia using the partial pressure of arterial oxygen and fraction of inspired oxygen (PaO₂/FiO₂). Additionally, radiological findings were standardized and bilateral diffuse pulmonary infiltrates on chest X-ray or CT scan (without evidence of heart failure) have to be present [4‐6]. Like previous definitions, the Berlin ARDS criteria also have been criticized, and several authors have questioned its usefulness [7‐9].

Historically, ARDS has been a significant cause of trauma-related morbidity and mortality, with reported mortality rates up to 40% [10, 11]. Many treatment strategies have been created; however, most of them had limited success [12]. Nowadays, the treatment is still limited and mainly consists of supportive mechanical ventilation with low tidal volume and inspiratory pressure ventilation. With improvement of trauma, critical-care mortality caused by ARDS has decreased in the last years [5, 13‐18]. However, it still uses significant intensive care unit (ICU) resources.

In contrast to several studies reporting continuously high ARDS-related deaths [5, 13‐17, 19], we recently showed low incidence of ARDS and low mortality rates [18]. However, we did observe many polytrauma patients who developed some degree of acute hypoxic respiratory failure (AHRF) without the bilateral diffuse pulmonary infiltrates that characterize ARDS. We felt that these AHRF patients were similar to ARDS patients except for the bilateral diffuse pulmonary infiltrates. Therefore, we conducted a prospective study in polytrauma patients in which we compared outcome parameters of ARDS patients with similar degree of hypoxic respiratory failure, but without the classical radiological findings (AHRF patients). We hypothesized that there was no difference in outcome between both groups. Further, we hypothesized that chest imaging was only relevant to detect abnormalities that need additional treatment other than supportive mechanical ventilation with low tidal volume and inspiratory pressure ventilation.

During the 5-year study period, 267 consecutive polytrauma patients who were admitted to ICU and survived 48 h were included. Hundred and thirty-four patients (50%) were intubated pre-hospitally, 72 in ED (27%), 52 in operating room (OR, 20%), 3 in ICU (1%), and 6 were not intubated at all (2%). Hundred and thirty-six (51%) of them were directly admitted to ICU and 131 patients (49%) were transported to the OR for surgery straight from ED and were admitted to ICU postoperatively. Seventy-five percent of the population were male with a median age of 45 (26–59) years. They sustained predominantly blunt injuries (97%) and had a median ISS of 29 (22–35). Even though isolated TBI patients were excluded median AIS head was 3 (1–4). Twenty-four percent of the patients underwent an urgent laparotomy and 83 patients (31%) sustained a pelvic fracture (Table 1). One hundred patients (37%) developed a pulmonary complication (pneumonia, pulmonary embolism or thorax empyema). Patients stayed on the ventilator for 7 (3–12) days. They spent 8 (4–14) days in ICU and 22 (13–33) days in hospital. Eighty-three patients developed MODS (31%, additional data on MODS development, severity, and duration are added as supplemental figures (supplemental Figs. 1 and 2), and 35 patients (13%) died (Table 1). Death in 28 patients was caused by brain injury (80%), 3 patients with high cervical spine injury failed to wean from the ventilator (9%), 1 patient died of MODS (3%), 1 patient died of sepsis (3%), 1 patient due to cardiac arrest (3%), and 1 polytrauma patient died of ARDS (3%) with additional fresh-water submersion. Fifteen patients (6%) developed ARDS (7 patients developed grade 2 ARDS and 8 patients developed grade 3 ARDS). Seventy-five (28%) patients did not develop any signs of acute hypoxic respiratory failure (AHRF). The remaining 192 patients all developed some degree of AHRF; 52 Patients developed grade 1 AHRF, 97 patients developed grade 2 AHRF, and 28 patients developed grade 3 AHRF (Fig. 1). Patients who developed grade 1 AHRF were excluded from further analysis.

In this population of severely injured patients, 72% of patients developed some degree of AHRF. These AHRF patients were older, more often male, had higher ISS, needed more crystalloids and blood products than patients who did not develop AHRF. Further, they developed more often pulmonary complications, stayed longer on the ventilator, longer in ICU and in hospital, and died more often. Most patients died of brain injury even though we excluded patients with isolated TBI. The percentage of brain/spinal cord injury-related deaths was higher than most reports about the cause of death in polytrauma [22, 23]. We have shown this in previous studies [18, 24], and this could be partly explained by the fact that our level-1 trauma center is the only referral center for brain and spinal cord injuries in the state [20].

In contrast to high incidence of AHRF, the incidence of ARDS was low (6%). When comparing AHRF patients with ARDS patients, only PaCO₂ in ICU was different, with ARDS patients having a higher PaCO₂. All other parameters including resuscitation and outcome were comparable. In other words, the only other difference between ARDS and AHRF patients was bilateral infiltrates on chest X-ray since this is part of the definition of ARDS. One could only speculate why ARDS patients had higher first-measured PaCO₂ in ICU; is it because the influx of neutrophils into the lung has already started and ARDS is already in progress? Or do these patients develop ARDS, because they did not receive optimal low tidal volume and inspiratory pressure ventilation from the start?

Another interesting finding was that 11% of patients who developed grade 2 or 3 AHRF did not have any abnormalities on their chest X-ray at the time of hypoxia. Further, AHRF developed early (3 days) after injury. Since early AHRF may be related to fluid overload rather than complications such as pneumonia, a possible explanation could be that early pulmonary edema was already causing hypoxia, but was insufficient to be seen on X-ray.

We feel that it would be more useful to use criteria of hypoxemia without the bilateral infiltrates on chest imaging. The fact that a patient is identified as having ARDS rather than AHRF in general does not influence ventilator settings since lung-protective ventilation nowadays is the standard of care anyway. In this study, comparison between patients with and without AHRF showed that AHRF alone has the discriminative power to separate sick from the not-so-sick patients. Another argument for dismissing imaging out of the definition is the fact that many trauma patients sustain pulmonary contusions. Early after injury, it is very difficult to differentiate between bilateral infiltrates caused by ARDS or by bilateral pulmonary contusion. Vice versa, there is also the potential danger of labeling a patient as having ARDS based upon bilateral infiltrates which originate from a different source (such as pulmonary contusions). Obviously, chest imaging itself is still very valuable to diagnose entities such as pneumothorax and hemothorax that need additional treatment to lung-protective ventilation. We, therefore, do not suggest to reduce the use or abandonment of chest imaging in the trauma patients.

Further, a recent study showed that inter-observer reliability of diagnosing ARDS was only moderate (kappa 0.50). The disagreement between clinicians was explained by differences in how chest imaging studies were interpreted [9]. Further, Chung et al. have demonstrated that CT findings cannot differentiate between pathology-proven diffuse alveolar damage as can be seen in ARDS and histopathological features of pneumonia [25].

Like others [4, 5, 19, 26], we have also shown that ventilator days, days in ICU and in hospital increased with increasing grade of hypoxemia. The question is whether grading of hypoxemia according to the Berlin criteria is really relevant. It might be helpful for predicting prognosis, but not for diagnosis of ARDS since treatment strategies are limited and not reserved for a specific grade of hypoxemia. This has also been previously addressed by others [6]. Also, both autopsy study [27] and biopsy study [28] demonstrated that the Berlin criteria did not correlate with the presence of diffuse alveolar damage in more than 50% of patients categorized as moderate or severe ARDS.

These arguments raise the question whether the definition of ARDS is specific enough. Although the definition of ARDS, which is based on consensus criteria, is useful for screening, it is less suitable as a diagnostic test. ARDS is a heterogeneous syndrome and it is unlikely that it will be amenable to a single intervention. If consensus definitions of a heterogeneous syndrome are not specific enough, patient selection for interventional trials could be incorrect resulting in false-negative results. This issue has also been addressed by Laffey and Kavanagh in their comments on many negative trials in critical care [29].

AHRF patients received more crystalloids < 8 h and < 24 h after admission than no-AHRF patients; however, it was noted that crystalloid infusion was high in all the included patients. During the first 24 h after admission most patients were in ICU where intensivists decided on resuscitation, since there is a closed-format ICU in our hospital. During the beginning of the studies, there was an ongoing debate between trauma surgeons and intensivists on resuscitation in trauma patients. However, in recent years, there has been an increased awareness of the detrimental effects of excessive amount of crystalloids in severely injured patients. Nowadays, hemostatic resuscitation is aimed for in all polytrauma patients.

One of the limitations of this study is that it was conducted in polytrauma patients only. ARDS is a syndrome that occurs in a wide spectrum of patients of whom the majority are not trauma patients. In some patient groups, other than trauma, the finding of bilateral pulmonary infiltrates is relevant for diagnostic and prognostic purposes. We acknowledge that our data only address a small subset of patients suffering from ARDS.

Further, this study was performed at a single institution in which the clinical treatment and research were conducted by the same clinicians. Patients with isolated head injuries were excluded, because of possible different physiologic response to trauma, although we did include polytrauma patients who had associated head injuries. We chose to include these patients, since many of our severely injured patients have associated brain injury and they are also prone to ARDS. Another limitation is that we neither prospectively collected data on tidal volume and plateau pressures nor did we collect data on comorbidities that could have contributed to hypoxia such as COPD or pre-existing heart failure.

In conclusion, in this polytrauma population, many patients developed AHRF and only a few ARDS. Chest imaging did not seem to influence treatment strategies and outcome, since patients with similar hypoxemia but without bilateral diffuse pulmonary infiltrates had similar outcome as ARDS patients. Large-scale multicenter validation of ARDS criteria is warranted to investigate whether diffuse bilateral pulmonary infiltrates on chest imaging could be omitted as a mandatory part of the definition of ARDS in polytrauma patients.