Combat Trauma-Related Acute Respiratory Distress Syndrome: A Scoping Review

Abstract

OBJECTIVE:

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known complications of injuries in combat casualties, but there has been no review characterizing them. This scoping review aims to map the combat trauma-related ALI/ARDS literature and characterize these conditions in the military population.

DATA SOURCES:

Pubmed was searched from 1969 to April 2022.

STUDY SELECTION:

Studies were included if they examined ALI/ARDS or related entities (blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces).

DATA EXTRACTION:

Study years, design, location, number of patients, target outcomes as related to ALI/ARDS or related entities, and results were collected.

DATA SYNTHESIS:

The initial search yielded 442 studies, with 22 ultimately included. Literature on ALI/ARDS comes mostly from retrospective data and case studies, with limited prospective studies. The incidence and prevalence of ALI/ARDS range from 3% to 33%, and mortality 12.8% to 33%. BLI, a known antecedent to ALI/ARDS, has an incidence and mortality ranging from 1.4% to 40% and 11% to 56%, respectively. Risk factors for ALI/ARDS include pulmonary injury, inhalation injury, blunt trauma, pneumonia, higher military injury severity score, higher injury severity score, higher fresh frozen plasma volumes, higher plasma and platelet volumes, the use of warm fresh whole blood, female sex, low blood pressure, and tachycardia. Literature has demonstrated the effectiveness in transportation of these patients and the utility of extracorporeal life support.

CONCLUSIONS:

ALI/ARDS incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%. ALI/ARDS has been associated with injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Studies are limited to mostly retrospective data, and more data are needed to better characterize these conditions.

KEY POINTS

• Question: What do we know about combat- trauma related ALI/ARDS in the military, and what are the gaps in research on these conditions?

• Findings: This scoping review demonstrates that the ALI/ARDS incidences and mortality in modern combat range from 3-33% and 12.8-33%, respectively. Risk factors include injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Of the 22 studies found, most were retrospective.

• Meaning: More studies are needed to better characterize these conditions, and a systematic review is not yet warranted.

The disease processes of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have been described in a variety of presentations for over 100 years (1). Although the term ARDS was first coined in 1967 (2), the most widely accepted definition of ALI and ARDS came in 2012, when the terms were combined (3). The Berlin definition defines ARDS as the acute onset of hypoxemia, defined as a ratio of Pao₂ to Fio₂ less than or equal to 300 mm Hg with bilateral airspace disease on chest imaging not primarily due to hydrostatic edema (3, 4). The Berlin definition incorporates three categories of ARDS—mild, moderate, and severe—based on the degree of hypoxemia, doing away with the term ALI in favor of mild ARDS, which is the essence of its previous definition (though ALI can still be seen in medical literature) (4).

Trauma is a well-defined etiology of ARDS, and there have been a number of studies summarizing its literature and characterizing it in the civilian trauma population (5–11). However, data specific to combat trauma-related ARDS are lacking. Rough descriptions of its manifestations, including the use of the terms “wet lung,” “shock lung,” and “DaNang lung,” have been noted in military medical literature since World War I, though without codified diagnostic criteria (12, 13). The studies that do exist with definitive diagnoses and data have been completed in a variety of patient populations, in different contexts, each with different inclusion/exclusion criteria, with no one source synthesizing the results. What is definitively known is that it represents a significant burden to the military population, with reported incidences and mortalities as high as 33% (14, 15). The injury etiologies of combat trauma-related ARDS, the combat environment and younger population it occurs in, the combat-theater resources present to treat it, and the significant burden on the military population makes combat trauma-related ARDS a unique etiology with serious consequences that requires a specific understanding for its proper treatment.

To better understand ARDS within the combat trauma population, we conducted a scoping review of its literature. We seek to characterize the epidemiology of ARDS, namely its incidence/prevalence, risk factors, morbidity and mortality, and treatment. We also seek to characterize the depth and breadth of the research completed to identify gaps in knowledge and guide future research efforts. We believe a scoping review will provide the focus needed to map the literature, answer our research questions, and determine the need for a systematic review.

MATERIALS AND METHODS

Authors followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist from the Enhancing the Quality and Transparency of Health Research (EQUATOR) guidelines (SDC PRISMA-ScR Checklist, http://links.lww.com/CCX/B58) and searched Pubmed on April 04, 2022, from 1969 to April 2022 using keyword searches of “combat trauma ARDS,” “combat trauma acute lung injury,” “combat trauma blast lung injury,” “combat trauma transfusion related acute lung injury,” “combat thoracic trauma,” “combat trauma acute respiratory failure,” “combat trauma pulmonary contusion,” “US military ARDS.” Studies were included if they had data on patients with a diagnosis of ARDS or related entities (ALI, blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces). Studies that described similar presentations as ARDS or related entities but did not use aforementioned diagnoses were not included. Studies using animal models, simulations, molecular pathophysiological research, or narrative descriptions with no patient data were excluded. Studies that studied lung pathologies such as hemothorax, pneumothorax, and penetrating thoracic injury, among others, that did not explicitly include data on the diagnoses of interest were excluded. The Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram in Figure 1 provides further information on the search methodology. Variables collected include incidence, prevalence, morbidity metrics, mortality, risk factors/independent predictors, as well as information on treatment and transportation practices. We also collected study characteristics to include methods, dates, location, inclusion/exclusion criteria, descriptive patient data, and narrative information from case studies. Data were collected from all sources of evidence into a single table, but only data relevant to the discussion of ARDS or related entities were included in this article.

Figure 1.

PRISMA flow diagram outlining search methodology. ALI = acute lung injury, ARDS = acute respiratory distress syndrome, BLI = blast lung injury, TRALI = transfusion related acute lung injury.

RESULTS

See SDC Table 1 (http://links.lww.com/CCX/B58).

Table 1 details the studies included and data abstracted from our search as well as summaries of the information found. The initial search yielded 442 records, of which the titles and abstracts were screened for relevance. After excluding 356 records, 86 were sought for retrieval, 40 duplications were removed, and 46 full-text documents were assessed for eligibility, with 22 studies ultimately included. Figure 1 provides further details. A majority of studies included (17/22) were retrospective reviews, with one prospective observational study and four case reports or series also included. The studies only researched populations in the U.S. Central Command (CENTCOM) area of operations, namely Iraq and Afghanistan, and were conducted anywhere from 2009 to 2018, with only eight of 22 studies being released prior to the 2012 Berlin definition. The data in these studies were drawn primarily (11 of 22 studies) from the U.S. or U.K. Joint Trauma Theater Registry (JTTR), formerly known as “the Department of Defense Trauma Registry (DoDTR),” with a majority of the large retrospective reviews or prospective studies studying populations from 2001 to 2011. The other studies focused primarily on the care of these patients or were descriptive narratives of case presentations.

Incidence and Prevalence

Many studies focus on the population of combat trauma patients requiring transfusion. In this population, incidences range from 6.4% to 33% (14, 16–18). In nontransfusion-associated studies, ARDS was found in 3% of Critical Care Transport Team (CCATT) patients (19), 0.9% of all patients in the DoDTR from 2001 to 2008 (20), and 22.7% of French evacuees from war zones from 2003 to 2018 (21). Three studies focused on patients at high risk for ARDS. In patients admitted to a burn ICU, prevalence of 11 (22) and 33% (15) have been reported, and in patients with thoracic trauma, 1.4% were found to have ARDS with an additional 1.4% found to have BLI (23). BLI was studied in seven of the 22 studies, with incidences and prevalences reported ranging from 1.4% to 40% (23–29).

Risk Factors

The literature reviewed shows that there are a number of modifiable and nonmodifiable risk factors for combat trauma-related ARDS. The modifiable risk factors include higher fresh frozen plasma (FFP) volume (14), higher plasma and platelet volume (17), warm fresh whole blood (WFWB) (16), low blood pressure (20), and tachycardia (20), and in burn patients, FFP and pneumonia are risk factors for moderate/severe ARDS (22). The nonmodifiable include pulmonary injury (14), blunt trauma (16), higher military injury severity score (MISS) (20), and female sex (20), and in burn patients, inhalation injury (II) and higher injury severity score (ISS) are risk factors for moderate/severe ARDS (22). Factors that have not been found to be associated with ARDS include platelet/RBC ratio (17), crystalloid/packed RBC (PRBC) ratio (17), explosion injury (20), and, in burn patients, resuscitation volume (22). There is contrasting literature on whether a mounted mechanism of injury (27) or a dismounted mechanism of injury (26) is more associated with BLI.

Morbidity and Mortality

There are limited data on the mortality and morbidity of combat trauma-related ARDS. Reported mortality values range from 12.8% to 48% (15, 17, 20, 22). Multiple studies also showed that ALI/ARDS is associated with increased mortality (20, 22, 23). Increased critical care utilization resources demonstrating increased ventilator days (median, 6 vs 1 d) and ICU length of stay (median, 8 vs 2 d), as well as hospital length of stay (median, 11 vs 7 d) in ARDS versus non-ARDS have also been shown (20). BLI mortality ranges from 8.1% to 56% (24–28).

Treatment and Transportation

The studies on treatment and transportation of combat trauma-related ARDS patients are more limited, with three retrospective reviews, two of which study populations of 40 or less, and five case studies or series. In an evaluation of the impact of the Acute Respiratory Distress Syndrome Clinical Network (ARDSNet) protocol compliance in CCATT, 62% were noncompliant per tidal-volume and ARDSNet table recommendations, and higher compliance was associated with improved outcomes including decreased ALI/ARDS, ventilator days, ICU days, and 30-day mortality (30). The studies also detail the successful use of the CCATT (30, 31), Acute Lung Rescue Team (ALRT) (32), and the use of extracorporeal life support (ECLS) (33–36) in the transportation and treatment of patients with severe respiratory failure.

DISCUSSION

In this scoping review, we obtained information regarding incidence, prevalence, morbidity metrics, mortality, risk factors/independent predictors, as well as information on treatment and transportation practices from 22 studies. We also collected study characteristics to include methods, dates, location, inclusion/exclusion criteria, descriptive patient data, and narrative information from case studies to allow us to assess the characteristics and scope of the current literature. Below we will discuss the information found in the context of the combat trauma-related ARDS literature in its entirety.

Incidence and Prevalence

The studies with reported incidences or prevalences on combat trauma patients who develop ARDS demonstrated similar demographic profiles (14–22). There are several potential explanations for the differences in reported values. Most studies used retrospective data or diagnostic code listings, making it less likely that they captured an accurate representation of the true incidence. However, Edens et al (14), with the second highest reported incidence, was the only prospective trial that used a predefined definition of ALI, increasing the likelihood that they detected its presence in otherwise complex trauma patients. Starkey et al (18) also found a higher incidence, but they used charted physiologic parameters and imaging to diagnose ARDS, perhaps resulting in a higher sensitivity than the other retrospective studies, which relied on chart diagnosis alone. Waters et al (15) reported the highest prevalence of ARDS at 33%. However, this study was completed in burn patients, and injury severity is a known risk factor for ARDS (5). The aforementioned studies had relatively smaller patient populations when compared with the large retrospective reviews. Large volume blood transfusion is an established risk factor for ALI/ARDS (37, 38), and the different volume cutoffs in each study’s inclusion criteria, or the lack of consideration of blood transfusion in the inclusion criteria, could also explain some of the variations. The optimization of medical care for combat trauma patients that occurred over these conflicts also may affect the reported incidences.

A number of studies have sought to characterize BLI. BLI occurs due to transient, high intrathoracic pressure from compression of the chest wall that disturbs the air/alveoli/capillary interface (39), with severe cases progressing to ARDS (40). During Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), this pattern of injury became increasingly more prevalent due to the use of improvised explosive devices (39). Aboudara et al (26) highlight the link between BLI and ARDS, with 17% of patients meeting criteria for moderate/severe ARDS, and the rest mild (26). The incidence and prevalence of reported BLI varied between studies, with larger studies having comparatively lower incidences and prevalence (23–25, 28). The smaller studies (26, 27) were also conducted on only patients injured in Afghanistan, as opposed to the other studies, which considered Iraq and Afghanistan. This difference in combat environments might also contribute to differences in incidences. Singleton et al (27) and Scott et al (28) were the only studies to use CT imaging to diagnose BLI, with prevalence of 40% and 8.1%, respectively, versus the other studies that used primarily retrospective data through chart diagnosis. Scott et al (28) had a much larger sample size than Singleton et al (27), and therefore likely provides more representative data.

Risk Factors

The studies of ALI/ARDS have identified a variety of modifiable and nonmodifiable risk factors for its development in combat trauma patients. Although there is less controversy over the nonmodifiable risk factors, the modifiable risk factors require further scrutiny. Edens et al (14) found that the volume of FFP administered was an independent predictor of ALI and a potential causative risk factor as detailed in civilian literature (41). However, FFP has beneficial effects on mortality through its treatment of underlying coagulopathies, and this should be considered when weighing the risks of FFP administration. Further, the practice patterns for blood product administration in combat causalities at the time of this study were still evolving (42), as can be seen in the variations of blood product ratios given to patients in this study (14). Chan et al (16) found that WFWB, another modifiable risk factor, was independently associated with ALI. However, patients who received WFWB were found to have increased injury and crystalloid use compared with those who did not, and in the naïve WFWB group, these were found to be independent predictors of ALI (16). Though the authors state they adjusted for confounders, it is possible that they could not entirely capture the extent of their influence. Additionally, 66% of the patients in their study who developed ALI never received WFWB, further suggesting a causal connection may be difficult to determine (16).

Park et al (17) found that increasing plasma and platelet volumes transfused were independent risk factors for ARDS. They also found that the platelet/RBC ratio and crystalloid/PRBC ratio had no impact on ARDS, despite what other civilian literature had suggested at the time (17). They noted that crystalloid infusion volume was an independent risk factor, but the CI they report was nonsignificant (17), limiting the strength of the conclusion. Civilian literature, however, has demonstrated a potential causative association between crystalloid infusion volume (43, 44) and platelet volumes (45) in the development of ARDS.

For nonmodifiable risk factors, Park et al (20) found that female sex was an independent predictor of ARDS in mechanically ventilated patients. However, their study only had 116 female patients out of a population of 4,679, and only eight developed ARDS, so caution is warranted in interpreting this finding (20). They also found that explosion injury did not independently increase the risk of ARDS, despite pulmonary contusion being a known risk factor for ARDS (20). The other nonmodifiable risk factors including pulmonary injury (14), blunt trauma (16), and II (14) could be causative as indicated by civilian literature (11, 46), whereas higher MISS (20) and higher ISS (5) may be more indicative of severe injury, though more studies are needed to investigate causation.

Similar risk factors as the ones identified by the literature here can be found in the civilian trauma literature, including the increased risk associated with ISS (5), FFP transfusion (37), and platelet transfusion (37, 44, 45). Further investigation of the protective effect of FFP versus the risk of ALI/ARDS, the true association between WFWB and crystalloid with ALI/ARDS, the differences in transfusion ratios effects on ALI/ARDS, and the effect of explosion injury on ALI/ARDS are needed to further characterize these findings in combat casualty patients. Additionally, there is disagreement in the literature on whether a mounted mechanism of injury (26) or a dismounted mechanism of injury (27) is more associated with BLI. There is no civilian literature to offer further clarity. As a known precipitant of ARDS (40) and as an injury with significant mortality, further studies of BLI are necessary to better characterize this etiology.

Morbidity and Mortality

There are limited data on mortality and morbidity, with reported mortality values ranging from 12.8% to 33% (15, 17, 20, 22) for ALI/ARDS and 11% to 56% (24–27) for BLI. The wide range of values is likely due to similar reasons as the aforementioned differences in incidences. More studies are needed to better characterize these values.

Treatment and Transportation

Clinical Practice Guidelines for combat trauma-related ARDS are similar to practice strategies in the civilian trauma population and are mostly derived from civilian literature (47). A proportion of the military-based literature centers on the transportation of these patients out of theater, with an additional focus on ECLS. CCATT, the primary method for transporting ARDS patients, has proven efficacious in the transportation of these patients (30, 31). In 2005, the ALRT was formed to respond when patients had respiratory failure too severe for CCATT evacuation, as defined by preset criteria (to include severe ARDS) (48). This team’s success was grounded in the use of, among other things, inhaled prostacyclin, prone positioning, pumpless CO₂ removal devices, and high-frequency ventilation (49), and has even used ECLS in the treatment and transportation of these patients (32).

ECLS has been shown to successfully treat severe respiratory failure with survival rates of 55–75% in the civilian population, with some of the highest success in trauma patients (50).

There have been multiple studies and case reports on ECLS’ utility in combat trauma patients with severe respiratory failure (33–35, 48), including in austere military environments (42). The Department of Defense has currently consolidated its ECLS evacuation capabilities to the 59th Medical Wing ECLS Transport Team (“ECMO team”) from the San Antonio Military Medical Center, Texas, in response to the decrease overseas operation tempo (48).

Limitations

This scoping review had several limitations. Studies were screened specifically for ALI/ARDS or related entities, but this does not take into account studies that described patients with the same pathophysiology as ALI/ARDS without using any of the aforementioned terms. Specifically, ALI/ARDS became firmly established in the literature with the American-European Consensus Conference (AECC) on ARDS in 1994, and studies prior to this may have been less likely to use this specific terminology. Further, this review was limited to U.S. and allied populations, and thus, the search was effectively limited to OIF and OEF, the only major conflicts since the AECC. Additionally, injuries such as hemothorax, pneumothorax, penetrating thoracic trauma, and other lung pathology seen in combat trauma patients were excluded from this study’s search to limit its focus. The authors recognize that many of these injuries can be antecedents to, or be present concomitantly with, ALI/ARDS, and further investigation may be needed to characterize their association. The studies available on combat trauma-related ALI/ARDS rely almost entirely on retrospective data or case studies, so caution is needed in interpreting the results presented here. Further, many articles reviewed used the JTTR, focusing on combat casualties in the CENTCOM area of operations (namely, Iraq and Afghanistan). This exposes this review to any biases inherit in the construction and use of the registry, and it makes the generalization of these findings to all combat trauma-related ARDS outside of CENTOM difficult.

CONCLUSIONS

ALI/ARDS remains an area of important research and innovations to better treat combat casualty patients. Incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%, depending on the patient population. Risk factors for ALI/ARDS include pulmonary injury, II, blunt trauma, pneumonia, higher MISS, higher ISS, higher FFP volumes, higher plasma and platelet volumes, the use of WFWB, female sex, low blood pressure, and tachycardia. However, more studies are necessary to better establish the risk factors, treatment, and transportation guidelines to optimize care within the military combat population before future large-scale combat operations occur. With only a limited amount of retrospective or case study data available on combat trauma-related ALI/ARDS, a systematic review is not yet warranted.