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Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses

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Abstract

Purpose

Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.

Methods

We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.

Results

We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)—44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.

Conclusions

There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses.

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Abbreviations

APACHE:

Acute Physiology and Chronic Health Evaluation

APVR:

Airway pressure release ventilation

ARDS:

Acute respiratory distress syndrome

ARM:

Alveolar recruitment maneuvers

CI:

Confidence interval

HFOV:

High-frequency oscillatory ventilation

HR:

Hazard ratio

ICU:

Intensive care unit

IV:

Intravenous

M:

Mortality

MV:

Mechanical ventilation

NA:

Not available

OR:

Odds ratio

PAC:

Pulmonary artery catheter

PCV:

Pressure-controlled ventilation

PEEP:

Positive end-expiratory pressure

PGE1:

Prostaglandin E1

PLV:

Partial liquid ventilation

PO:

By mouth

PPV:

Positive pressure ventilation

RCT:

Randomized controlled trial

RR:

Relative risk

SIMV:

Synchronized intermittent ventilation

SOFA:

Sequential Organ Failure Assessment score

VCV:

Volume-controlled ventilation

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Acknowledgments

The authors will like to thank the Cleveland Clinic medical librarian Kim Brady for her invaluable help in the PubMed, Cochrane, and clinicaltrial.gov searches. A. R. T. is supported by CTSA KL2 [Grant # TR000440] from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The Meta-Research Innovation Research Center at Stanford (METRICS) is supported by a grant by the Laura and John Arnold Foundation.

Conflicts of interest

The authors have no significant conflicts of interest with any companies or organization whose products or services may be discussed in this article.

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Authors and Affiliations

  1. Department of Pulmonary, Allergy, and Critical Care Medicine, Respiratory Institute, Cleveland, OH, USA

    Adriano R. Tonelli, Joe Zein & Jacob Adams

  2. Department of Medicine and Meta-Research Innovation, Research Center at Stanford (METRICS), Stanford University, 1265 Welch Rd, MSOB X306, Stanford, CA, 94305, USA

    John P. A. Ioannidis

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  1. Adriano R. Tonelli
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  2. Joe Zein
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  4. John P. A. Ioannidis
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Correspondence to John P. A. Ioannidis.

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Tonelli, A.R., Zein, J., Adams, J. et al. Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses. Intensive Care Med 40, 769–787 (2014). https://doi.org/10.1007/s00134-014-3272-1

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