TY - JOUR
T1 - Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials
AU - Schenck, Edward J.
AU - Oromendia, Clara
AU - Torres, Lisa K.
AU - Berlin, David A.
AU - Choi, Augustine M.K.
AU - Siempos, Ilias I.
N1 - Funding Information:
FUNDING/SUPPORT: This work was supported by the National Institutes of Health [Grants KL2TR000458-10 to E. J. S., R01 HL055330 to A. M. K. C., and P01 HL108801 to A. M. K. C.].
Publisher Copyright:
© 2018 American College of Chest Physicians
PY - 2019/3
Y1 - 2019/3
N2 - Background: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it. Methods: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a PaO 2 to FIO 2 ratio (PaO 2 :FIO 2 ) > 300 on the first study day following enrollment. Results: The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P <.0001) than ARDS > 1 day. PaO 2 :FIO 2 at screening, change in PaO 2 :FIO 2 from screening to enrollment, use of vasopressor agents, FIO 2 at enrollment, and serum bilirubin levels were useful predictive variables. Conclusions: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials.
AB - Background: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it. Methods: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a PaO 2 to FIO 2 ratio (PaO 2 :FIO 2 ) > 300 on the first study day following enrollment. Results: The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P <.0001) than ARDS > 1 day. PaO 2 :FIO 2 at screening, change in PaO 2 :FIO 2 from screening to enrollment, use of vasopressor agents, FIO 2 at enrollment, and serum bilirubin levels were useful predictive variables. Conclusions: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials.
KW - ICUs
KW - acute lung injury
KW - acute respiratory failure
KW - epidemiology
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U2 - 10.1016/j.chest.2018.09.031
DO - 10.1016/j.chest.2018.09.031
M3 - Article
C2 - 30359616
AN - SCOPUS:85057380873
SN - 0012-3692
VL - 155
SP - 474
EP - 482
JO - CHEST
JF - CHEST
IS - 3
ER -