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. 2018 Aug;44(8):1230-1239.
doi: 10.1007/s00134-018-5286-6. Epub 2018 Jul 3.

Subtypes of pediatric acute respiratory distress syndrome have different predictors of mortality

Nadir Yehya  1 , Garrett Keim  2 , Neal J Thomas  3
Affiliations

Subtypes of pediatric acute respiratory distress syndrome have different predictors of mortality

Nadir Yehya et al. Intensive Care Med. 2018 Aug.

Abstract

Purpose: Acute respiratory distress syndrome (ARDS) is heterogeneous in etiology, which may affect outcomes. Stratification into biologically-defined subtypes may reduce heterogeneity. However, it is unknown whether pediatric ARDS has clinically relevant subtypes. We aimed to determine whether clinical characteristics and predictors of mortality differed between direct and indirect ARDS, and separately between infectious and non-infectious ARDS.

Methods: This was a single center, prospective cohort study of 544 children with ARDS (Berlin) between July 2011 and June 2017, stratified into direct versus indirect ARDS, and separately into infectious versus non-infectious ARDS. Multiple logistic regression was used to test for predictors of mortality in the entire cohort, and separately within subtypes. Effect modification by subtype was assessed using interaction tests.

Results: Direct ARDS had lower severity of illness (p < 0.001) but worse oxygenation (p < 0.001), relative to indirect. Predictors of mortality were similar for direct and indirect ARDS. When comparing infectious and non-infectious ARDS, infectious ARDS had lower severity of illness (p < 0.001), worse oxygenation (p = 0.014), and lower mortality (p = 0.013). In multivariable analysis, immunocompromised status demonstrated effect modification between infectious and non-infectious ARDS (p = 0.005 for interaction), with no association with mortality in non-infectious ARDS.

Conclusions: In children, direct and indirect ARDS have distinct clinical characteristics, but similar outcomes and similar predictors of mortality. In contrast, infectious and non-infectious ARDS demonstrate heterogeneity of clinical characteristics, mortality, and predictors of mortality, with traditional predictors of ARDS mortality only applicable to infectious ARDS.

Keywords: ARDS; Children; Direct ARDS; Infectious ARDS; PARDS.

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Conflict of interest statement

CONFLICTS OF INTEREST

Dr. Yehya’s institution receives funding from the NIH (K12-HL-136688). Dr. Thomas reports personal fees from Therabron and Carefusion, all outside of the submitted work.

Figures

Figure 1:
Figure 1:
Kaplan-Meier survival curves for the outcomes of survival, ECMO-free survival, or probability of extubation given the competing risk of death, stratified by Berlin severity categories, at ARDS onset and at 24 hours. All curves are censored at 28 days. At ARDS onset, there is overlap of mild (blue) and moderate (blue) categories, whiles severe (black) demonstrates worse survival, ECMO-free survival, and lower probability of extubation. By 24 hours, there is improved separation of the categories for all outcomes, with residual overlap between resolved (green) and mild (red) ARDS.
Figure 2:
Figure 2:
Kaplan-Meier survival curves for immunocompetent (blue) and immunocompromised (red) subjects stratified by ARDS subtype. All curves are censored at 28 days.
Figure 3:
Figure 3:
Decision tree for mortality constructed from variables retained in final model using classification and regression tree (CART) methodology. The tree contains mortality at each decision point and the decision rules. The final model resulted in a tree with five terminal nodes: one low-risk (green), one intermediate risk (blue), and 3 high-risk (red).
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