Abstract
BackgroundAlthough diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark. Patients with DAD may have higher mortality than those without DAD. Therefore, we aimed to identify the factors associated with DAD in patients with ARDS.MethodsWe analyzed autopsy samples of 356 patients who had ARDS at the time of death. DAD was assessed by two pathologists, and ARDS criteria were evaluated by two intensivists. Criteria for severe ARDS included the degree of hypoxemia and the ancillary variables of the current Berlin definition assessed within 48 h before death: radiographic severity, high positive end-expiratory pressure (PEEP) level, and physiological variables (i.e., altered respiratory system compliance and large anatomic dead space).ResultsAfter multivariable analysis, high PEEP levels, physiological variables, and opacities involving only three quadrants on chest radiographs were not associated with DAD. The four markers independently associated with DAD were (1) duration of evolution (OR 3.29 [1.95–5.55] for patients with ARDS ≥ 3 days, p < 0.001), (2) degree of hypoxemia (OR 3.92 [1.48–10.3] for moderate ARDS and 6.18 [2.34–16.3] for severe ARDS, p < 0.01 for both), (3) increased dynamic driving pressure (OR 1.06 [1.04–1.09], p = 0.007), and (4) radiographic severity (OR 2.91 [1.47–5.75] for patients with diffuse opacities involving the four quadrants, p = 0.002). DAD was found in two-thirds of patients with a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 100 mmHg and opacities involving the four quadrants.ConclusionsIn addition to severe hypoxemia, diffuse opacities involving the four quadrants were a strong marker of DAD.
Highlights
Diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark
Patients with diffuse alveolar damage (DAD) were more hypoxemic and more hypercapnic. They had more increased dynamic driving pressure, and all ancillary variables proposed for severe ARDS in the Berlin definition were associated with DAD (Table 1)
Patients with DAD had more altered compliance of the respiratory system, larger anatomical dead space as indicated by higher expired volume per minute corrected by Partial pressure of arterial carbon dioxide (PaCO2), higher positive end-expiratory pressure (PEEP) levels, and more diffuse opacities on chest radiographs
Summary
Diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark. Diffuse alveolar damage (DAD), including the presence of hyaline membranes, interstitial edema, cell necrosis and proliferation, or fibrosis, is considered the typical histological pattern of ARDS [2, 3]. This histological hallmark of DAD is not observed in all patients fulfilling the criteria for ARDS. Patients without DAD exhibited other histological patterns, such as diffuse interstitial pneumonia, pulmonary infarction or hemorrhage, lymphangitis, cancer infiltration, bacterial pneumonia without DAD, or no lung histological abnormalities at all
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