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Abstract
Background Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS.
Objective To estimate the attributable mortality, if any, of ARDS.
Design First, we performed a systematic review and meta-analysis of observational studies reporting mortality of critically ill patients with and without ARDS matched for underlying risk factor. Next, we conducted a survival analysis of prospectively collected patient-level data from subjects enrolled in three intensive care unit (ICU) cohorts to estimate the attributable mortality of critically ill septic patients with and without ARDS using a novel causal inference method.
Results In the meta-analysis, 44 studies (47 cohorts) involving 56 081 critically ill patients were included. Mortality was higher in patients with versus without ARDS (risk ratio 2.48, 95% CI 1.86 to 3.30; p<0.001) with a numerically stronger association between ARDS and mortality in trauma than sepsis. In the survival analysis of three ICU cohorts enrolling 1203 critically ill patients, 658 septic patients were included. After controlling for confounders, ARDS was found to increase the mortality rate by 15% (95% CI 3% to 26%; p=0.015). Significant increases in mortality were seen for severe (23%, 95% CI 3% to 44%; p=0.028) and moderate (16%, 95% CI 2% to 31%; p=0.031), but not for mild ARDS.
Conclusions ARDS has a direct causal link with mortality. Our findings provide information about the extent to which continued funding of ARDS prevention trials has potential to impart survival benefit.
PROSPERO Registration Number CRD42017078313
- ARDS
- critical care
- clinical epidemiology
Data availability statement
Data are available upon reasonable request. Deidentified subject data are available upon reasonable request from researchers whose proposed use of data has been approved. Inquiries for reuse of data may be made by emailing lkt9003@med.cornell.edu.
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Data availability statement
Data are available upon reasonable request. Deidentified subject data are available upon reasonable request from researchers whose proposed use of data has been approved. Inquiries for reuse of data may be made by emailing lkt9003@med.cornell.edu.
Footnotes
Contributors IIS conceived the study. LKT, KH and IIS had full access to all data in the study. LKT, KH, ID and IIS contributed to the study concept and design. LKT performed the literature search. LKT, KH, CO, ID, JSH, EJS, DRP, LG-E, AH, MPV, RMB, LEF, J-WH and IIS collected, analysed and interpreted the data. LKT and KH wrote the draft manuscript. LKT, KH, JSH, AMKC and IIS revised the manuscript for important intellectual content. IIS had final responsibility for the decision to submit for publication.
Funding This work was supported by the National Institutes of Health (NIH) grants R01 HL055330 and P01 HL108801 (to AMKC). LKT was supported in part by NIH T32 HL134629 (to FJ Martinez), Weill Cornell CTSC UL1-TR-002384 and KL2-TR-002385 and the Stony Wold-Herbert Fund Fellowship. JSH was supported by the Stony Wold-Herbert Fund Fellowship. IIS was supported by grants from the Hellenic Thoracic Society (2019) and the Hellenic Foundation for Research and Innovation (80-1/15.10.2020).
Competing interests AMKC is a cofounder and stock holder of and serves on the Scientific Advisory Board for Proterris, which develops therapeutic uses for carbon monoxide. He also has a use patent on carbon monoxide. He served as a consultant for an advisory board meeting of Teva Pharmaceutical Industries, July 2018. RMB serves on the Advisory Board for Merck. LEF reports clinical trials support from Asahi Kasei Pharma America. None declared: LKT, KH, CO, ID, JSH, EJS, DRP, LG-E, AH, MPV, JWH and IIS.
Provenance and peer review Not commissioned; externally peer reviewed.
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