Clinical Predictors of Hospital Mortality Differ Between Direct and Indirect ARDS

Abstract

Background: Direct (pulmonary) and indirect (extrapulmonary) ARDS are distinct syndromes with important pathophysiologic differences. The goal of this study was to determine whether clinical characteristics and predictors of mortality differ between direct or indirect ARDS.

Methods: This retrospective observational cohort study included 417 patients with ARDS. Each patient was classified as having direct (pneumonia or aspiration, n = 250) or indirect (nonpulmonary sepsis or pancreatitis, n = 167) ARDS.

Results: Patients with direct ARDS had higher lung injury scores (3.0 vs 2.8; P < .001), lower Simplified Acute Physiology Score II scores (51 vs 62; P < .001), lower Acute Physiology and Chronic Health Evaluation II scores (27 vs 30; P < .001), and fewer nonpulmonary organ failures (1 vs 2; P < .001) compared with patients with indirect ARDS. Hospital mortality was similar (28% vs 31%). In patients with direct ARDS, age (OR, 1.29 per 10 years; P = .01; test for interaction, P = .03), lung injury scores (OR, 2.29 per point; P = .001; test for interaction, P = .058), and number of nonpulmonary organ failures (OR, 1.67; P = .01) were independent risk factors for increased hospital mortality. Preexisting diabetes mellitus was an independent risk factor for reduced hospital mortality (OR, 0.47; P = .04; test for interaction, P = .02). In indirect ARDS, only the number of organ failures was an independent predictor of mortality (OR, 2.08; P < .001).

Conclusions: Despite lower severity of illness and fewer organ failures, patients with direct ARDS had mortality rates similar to patients with indirect ARDS. Factors previously associated with mortality during ARDS were only associated with mortality in direct ARDS. These findings suggest that direct and indirect ARDS have distinct features that may differentially affect risk prediction and clinical outcomes.

Keywords: ARDS; diabetes; direct lung injury; indirect lung injury; mortality.

Figure 1

Study population. Risk factors for ARDS were recorded and each patient classified into direct ARDS or indirect ARDS as described. “Other” risk factors included alveolar hemorrhage (4), eosinophilic pneumonia (2), sickle cell crisis (1), acute myeloid leukemia (1), graft vs host disease (1), blast crisis (1), tumor lysis syndrome (2), drug toxicity (2), fat emboli (1), bronchiolitis obliterans organizing pneumonia (1), fat embolus (1), alveolar proteinosis (1), Wegener’s granulomatosis (1), primary graft dysfunction (1), and no known risk factors (1).

Figure 2

Hospital mortality increased with age only with direct ARDS. Mortality in direct ARDS (blue line) rose with increasing age, whereas age had no association with mortality in indirect ARDS (red line). Data are adjusted for sex, weight, Simplified Acute Physiology Score II, lung injury score, number of organ failures, and diabetes mellitus.

Figure 3

Hospital mortality increased with lung injury score only with direct ARDS. Mortality in direct ARDS (blue line) increased with increasing lung injury score, whereas lung injury score had no association with mortality in indirect ARDS (red line). Data are adjusted for age, sex, weight, Simplified Acute Physiology Score II, number of organ failures, and diabetes mellitus.

Figure 4

Preexisting DM was associated with reduced mortality only in direct ARDS. Patients with preexisting DM had reduced mortality from direct ARDS compared with indirect ARDS, whereas there was no impact of ARDS subtype on mortality in the absence of DM. The adjusted OR for the effect of DM on hospital mortality in ARDS is 0.45 (95% CI, 0.22-0.96 [P = .04]; test for interaction, P = .02). P values shown were determined by using Pearson χ² test. DM = diabetes mellitus.