Intensive Care Medicine

, Volume 40, Issue 6, pp 769–787

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

  • Adriano R. Tonelli
  • Joe Zein
  • Jacob Adams
  • John P. A. Ioannidis
Systematic Review

DOI: 10.1007/s00134-014-3272-1

Cite this article as:
Tonelli, A.R., Zein, J., Adams, J. et al. Intensive Care Med (2014) 40: 769. doi:10.1007/s00134-014-3272-1

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.

Keywords

Acute respiratory distress syndromeTreatmentSurvivalMortality

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

Supplementary material

134_2014_3272_MOESM1_ESM.doc (879 kb)
Supplementary material 1 (DOC 879 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2014

Authors and Affiliations

  • Adriano R. Tonelli
    • 1
  • Joe Zein
    • 1
  • Jacob Adams
    • 1
  • John P. A. Ioannidis
    • 2
  1. 1.Department of Pulmonary, Allergy, and Critical Care MedicineRespiratory InstituteClevelandUSA
  2. 2.Department of Medicine and Meta-Research InnovationResearch Center at Stanford (METRICS), Stanford UniversityStanfordUSA