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Meta-Analysis
. 2021 Dec;76(12):1176-1185.
doi: 10.1136/thoraxjnl-2020-215950. Epub 2021 Apr 16.

Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation

Lisa K Torres  1 , Katherine L Hoffman  2 , Clara Oromendia  2 , Ivan Diaz  2 , John S Harrington  1 , Edward J Schenck  1 , David R Price  1 , Luis Gomez-Escobar  1 , Angelica Higuera  3 , Mayra Pinilla Vera  3 , Rebecca M Baron  3 , Laura E Fredenburgh  3 , Jin-Won Huh  4 , Augustine M K Choi  1 , Ilias I Siempos  5   6
Affiliations
Meta-Analysis

Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation

Lisa K Torres et al. Thorax. 2021 Dec.

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.

Keywords: ARDS; clinical epidemiology; critical care.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Flow diagram of studies included in the systematic review and meta-analysis.
Abbreviation: ARDS: acute respiratory distress syndrome.
Figure 2.
Figure 2.
Forest plot of in-hospital all-cause mortality among septic, trauma, and other patients
Figure 3.
Figure 3.. Forest plot of mortality incidence of ARDS among patients included in the three ICU cohorts of the original analysis.
Abbreviations: ARDS: acute respiratory distress syndrome, ICU: intensive care unit. Confounders for which adjustment was made included age, comorbidities, modified sequential organ failure assessment (i.e., after excluding its respiratory component) score, and cohort. The adjusted estimate for increased mortality of any ARDS was 15% [95% confidence intervals (CI) 3%–26%], mild ARDS was 1% (95% CI −27%–29%), moderate ARDS was 16% (95% CI 2%–31%), and severe ARDS was 23% (95% CI 3%–44%). ARDS was categorized as mild, moderate and severe according to the Berlin definition.
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References

    1. Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016;315(8):788–800. doi: 10.1001/jama.2016.0291 - DOI - PubMed
    1. National Heart L, and Blood Institute website. Lung Diseases [Available from: https://www.nhlbi.nih.gov/science/lung-diseases accessed September 7, 2018.
    1. Injury PEToAL. PETAL Network [Available from: http://petalnet.org/ accessed September 7, 2018.
    1. Ferring M, Vincent J. Is outcome from ARDS related to the severity of respiratory failure? European Respiratory Journal 1997;10(6):1297–300. - PubMed
    1. Bekaert M, Timsit JF, Vansteelandt S, et al. Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 2011;184(10):1133–9. doi: 10.1164/rccm.201105-0867OC [published Online First: 2011/08/20] - DOI - PubMed

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