Heterogeneous phenotypes of acute respiratory distress syndrome after major trauma

Abstract

Rationale: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma.

Objectives: To identify and characterize distinct phenotypes of ARDS after trauma, based on timing of syndrome onset.

Methods: Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort.

Measurements and main results: Three patterns of ARDS were identified; class I (52%) early onset on Day 1 or 2, class II (40%) onset on Days 3 and 4, and class III (8%) later onset on Days 4 and 5. Early-onset ARDS was associated with higher Abbreviated Injury Scale scores for the thorax (P < 0.001), lower lowest systolic blood pressure before intensive care unit admission (P = 0.003), and a greater red blood cell transfusion requirement during resuscitation (P = 0.030). In the external validation cohort, early-onset ARDS was also associated with a higher Abbreviated Injury Scale score for the thorax (P = 0.001) and a lower lowest systolic blood pressure before intensive care unit enrollment (P = 0.006). In addition, the early-onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2.

Conclusions: Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early-onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar-capillary barrier injury pattern in this phenotype.

Keywords: acute respiratory distress syndrome; critical illness; hemorrhagic shock; phenotype; trauma.

Figure 1.

Derivation and validation trauma cohorts. In the derivation cohort, subjects with acute respiratory disease syndrome (ARDS) were classified by latent class analysis into three classes. These classes were then collapsed into the simplified early- and late-onset ARDS based on a 48-hour cutoff. The 48-hour cutoff was used to categorize ARDS cases in the validation cohort into early- and late-onset ARDS.

Figure 2.

Latent class modeling estimated daily probabilities of acute respiratory distress syndrome (ARDS) for the identified (A) latent class I, (B) latent class II, and (C) latent class III. The graphs represent the estimated probability of being categorized as definite ARDS, equivocal, or definite non-ARDS on each study day for 5 days. The y axis indicates the conditional probabilities determined by the latent class model on a given day. The x axis represents the study day, with Day 1 being the day of presentation. The probability of definite ARDS among subjects in each latent class is given by solid diamonds connected by a solid black line. The probability of being categorized as equivocal or definite non-ARDS is given by the squares connected by a dashed line and gray triangles connected by a gray line, respectively.