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February 20, 2018

Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment

Author Affiliations
  • 1Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
  • 2Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
  • 3Department of Medicine, University Health Network and Sinai Health System, Toronto, Canada
  • 4Department of Medicine, University of Toronto, Toronto, Canada
  • 5Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons/New York—Presbyterian Hospital, New York
  • 6Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Canada
JAMA. 2018;319(7):698-710. doi:10.1001/jama.2017.21907
Key Points

Question  What advances in diagnosis and treatment of acute respiratory distress syndrome (ARDS) have been introduced in the last 5 years?

Findings  The diagnosis of ARDS is based on fulfilling the Berlin definition criteria for timing of the syndrome’s onset, origin of edema, chest radiograph findings, and hypoxemia. Few pharmacologic treatments are available and management remains supportive largely based on physiological approaches to lung-protective mechanical ventilation.

Meaning  The Berlin definition of ARDS addressed limitations from prior definitions but poor reliability of some criteria may contribute to underrecognition. Clinical guidelines can assist clinicians in the evidence-based use of 6 interventions related to mechanical ventilation and extracorporeal membrane oxygenation.


Importance  Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure that affects approximately 200 000 patients each year in the United States, resulting in nearly 75 000 deaths annually. Globally, ARDS accounts for 10% of intensive care unit admissions, representing more than 3 million patients with ARDS annually.

Objective  To review advances in diagnosis and treatment of ARDS over the last 5 years.

Evidence Review  We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 2012 to 2017 focusing on randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidelines. Articles were identified for full text review with manual review of bibliographies generating additional references.

Findings  After screening 1662 citations, 31 articles detailing major advances in the diagnosis or treatment of ARDS were selected. The Berlin definition proposed 3 categories of ARDS based on the severity of hypoxemia: mild (200 mm Hg<Pao2/Fio2≤300 mm Hg), moderate (100 mm Hg<Pao2/Fio2≤200 mm Hg), and severe (Pao2/Fio2 ≤100 mm Hg), along with explicit criteria related to timing of the syndrome’s onset, origin of edema, and the chest radiograph findings. The Berlin definition has significantly greater predictive validity for mortality than the prior American-European Consensus Conference definition. Clinician interpretation of the origin of edema and chest radiograph criteria may be less reliable in making a diagnosis of ARDS. The cornerstone of management remains mechanical ventilation, with a goal to minimize ventilator-induced lung injury (VILI). Aspirin was not effective in preventing ARDS in patients at high-risk for the syndrome. Adjunctive interventions to further minimize VILI, such as prone positioning in patients with a Pao2/Fio2 ratio less than 150 mm Hg, were associated with a significant mortality benefit whereas others (eg, extracorporeal carbon dioxide removal) remain experimental. Pharmacologic therapies such as β2 agonists, statins, and keratinocyte growth factor, which targeted pathophysiologic alterations in ARDS, were not beneficial and demonstrated possible harm. Recent guidelines on mechanical ventilation in ARDS provide evidence-based recommendations related to 6 interventions, including low tidal volume and inspiratory pressure ventilation, prone positioning, high-frequency oscillatory ventilation, higher vs lower positive end-expiratory pressure, lung recruitment maneuvers, and extracorporeal membrane oxygenation.

Conclusions and Relevance  The Berlin definition of acute respiratory distress syndrome addressed limitations of the American-European Consensus Conference definition, but poor reliability of some criteria may contribute to underrecognition by clinicians. No pharmacologic treatments aimed at the underlying pathology have been shown to be effective, and management remains supportive with lung-protective mechanical ventilation. Guidelines on mechanical ventilation in patients with acute respiratory distress syndrome can assist clinicians in delivering evidence-based interventions that may lead to improved outcomes.

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