TY - JOUR
T1 - Attributable mortality of acute respiratory distress syndrome
T2 - A systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation
AU - Torres, Lisa K.
AU - Hoffman, Katherine L.
AU - Oromendia, Clara
AU - Diaz, Ivan
AU - Harrington, John S.
AU - Schenck, Edward J.
AU - Price, David R.
AU - Gomez-Escobar, Luis
AU - Higuera, Angelica
AU - Vera, Mayra Pinilla
AU - Baron, Rebecca M.
AU - Fredenburgh, Laura E.
AU - Huh, Jin Won
AU - Choi, Augustine M.K.
AU - Siempos, Ilias I.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - ARDS
KW - clinical epidemiology
KW - critical care
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UR - http://www.scopus.com/inward/citedby.url?scp=85104409390&partnerID=8YFLogxK
U2 - 10.1136/thoraxjnl-2020-215950
DO - 10.1136/thoraxjnl-2020-215950
M3 - Article
C2 - 33863829
AN - SCOPUS:85104409390
SN - 0040-6376
VL - 76
SP - 1176
EP - 1185
JO - Thorax
JF - Thorax
IS - 12
ER -