ARDS Berlin definition
Time: within 1 week of known clinical onset or new or worsening respiratory symptoms.
Thoracic imaging changes: X-ray or CT scan showing dense shadowing of both lungs and not fully explained by pleural effusion, lobe/pulmonary collapse or nodules.
Causes of pulmonary edema: respiratory failure that cannot be fully explained by heart failure or fluid overload. If risk factors are not present, an objective evaluation (e.g., echocardiography) is required to rule out hydrostatic edema.
Oxygenation status.
Mild: PaO2/FIO2 = 201-300 mmHg and positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≤ 5 cm H2O
Moderate: PaO2/FIO2=101~200 mmHg, and PEEP≥5 cm H2O
Severe: PaO2/FIO2≤100 mmHg and PEEP≥10 cm H2O
If the altitude is higher than 1,000 m, the correction factor should be calculated as PaO2/FIO2×(atmospheric pressure/760).
The new definition of acute respiratory distress syndrome (ARDS) presented at the international meeting of the American Thoracic Society classified according to mild, moderate and severe hypoxia, suggesting that the more severe the hypoxia, the higher the morbidity and mortality rate and the longer the survivors receive mechanical ventilation. The risk of death for patients with mild, moderate and severe ARDS was 27%, 32% and 45%, respectively, and the median time for survivors to receive mechanical ventilation was 5, 7 and 9 days, respectively. The study was published online May 21 in JAMA.
Niall D. Ferguson, MD, chair of the Department of Critical Care Medicine at the University of Toronto, Canada, and Gordon D. Rubenfeld, MD, professor of medicine and head of the Trauma/Acute Care Program at Sunnybrook Health Sciences Centre, University of Toronto, reported that the new definition was developed based on the consensus opinion of an international expert panel and was validated using a meta-analysis of 2 large-scale data sets from 7 centers totaling 4,457 patients. The new definition was empirically validated by a meta-analysis of 2 large data sets from 7 centers with a total of 4,457 patients. The European Society for Acute and Critical Care Medicine formed an expert panel in Berlin, Germany, in 2011 to develop a new definition of ARDS, hoping to build on the definition proposed by the 1994 American-European Consensus Conference (AECC). Since the AECC definition was widely adopted, several questions regarding reliability and validity have arisen. The American Thoracic Society and the Society of Critical Care Medicine also expressed support for this consensus initiative in 2011.
In accordance with the new Berlin definition, patients with mild ARDS have mild hypoxia, defined as an arterial partial pressure of oxygen/fraction of inspired oxygen ratio between 201 and 300 mmHg (PaO2/FIO2= 201-300 mmHg); those with moderate hypoxia (PaO2/FIO2=101-200 mmHg) are considered to have moderate ARDS, and those with severe hypoxia (PaO2/ FIO2≤100 mmHg) were patients with severe ARDS.
The investigators reported that the Berlin definition also initially incorporated four ancillary parameters for severe ARDS, but a meta-analysis conducted later showed that these parameters did not improve the predictive value of the definition for morbidity and mortality, and they were removed. The parameters that were removed were: imaging severity, respiratory compliance, positive end-expiratory pressure, and corrected expiratory volume per minute.
Dr. Rubenfeld emphasized that these parameters are still important for clinicians to assess and understand ARDS and were not included in the definition of severe ARDS because adding them would have complicated the definition and would not have improved its predictive value. He also cautioned, “The Berlin definition and the AECC definition are not a prognostic model per se; we simply used the endpoint of morbidity and mortality to refine the Berlin definition.”
The logistic regression model analysis showed that the Berlin definition had higher predictive validity for morbidity and mortality than the AECC definition based on the area under the ROC curve (AUROC) calculation. The Berlin definition had an AUROC of 0.577 compared with 0.536 for the AECC definition, a statistically significant difference.
The investigators reported meta-analysis data from four multicenter clinical studies and three single-center physiologic studies. 22% of patients met the Berlin definition of mild ARDS, 50% met moderate ARDS, and 28% met severe ARDS. days, and 1 day, respectively. Of patients classified as having mild ARDS at baseline according to the Berlin definition, 29% progressed to moderate ARDS within 7 days and 4% progressed to severe ARDS. 13% of patients classified as having moderate ARDS at baseline progressed to severe ARDS within 7 days.
The investigators noted that this combination of consensus discussion and empirical evaluation may serve as a model to facilitate the development of more accurate evidence-based definitions of critical illness in the future. In the past, the definition of ARDS relied solely on expert consensus, Dr. Rubenfeld said, adding that it was because of the empirical evaluation that several of the initially proposed ancillary parameters were removed, otherwise we would have been presented with a complex definition of ARDS that was not really necessary.
The study was co-funded by the European Society of Critical Care Medicine, the National Institutes of Health, and the Canadian Institutes of Health Research (CIHR), and was kindly funded by CareFusion, with Dr. Ferguson receiving the CIHR Newcomer to Research Award. . Some of the other authors declare financial interests with Maquet Medical, Hemodec, Faron, AstraZeneca, U.S. Biotest, Sirius Genetics, Sanofi-Aventis, Immunetrics, Abbott, Eli Lilly, Ikaria, GlaxoSmithKline, Tarix, Apeiron, and/or Novalung have a financial interest.
New Definition Aids Academic Research and Improves Clinicians’ Understanding of ARDS
Commenting on the new definition, Dr. Marc Moss, professor of medicine/chair of the Department of Critical Care Medicine at the University of Colorado, said, “The definition of ARDS at past AECC consensus conferences has clearly been problematic. There was some uncertainty about the criteria for oxygenation, the differentiation of acute lung injury from ARDS, and the criteria for the timing of acute lung injury. And there is some variability in the interpretation of thoracic radiograph scoring results, and the older definition may also have excluded suspected pulmonary edema in patients who had a pulmonary artery catheter in place.” He said, “These investigators have tried to address some of these issues. The approach they took was very novel and both unique and reasonable. For other syndromes that define a disease by meeting certain criteria, I think this approach could be used to develop definitions as well.”
Dr. Moss noted, “The new definition will improve the generalizability of relevant studies and make it easier to conduct clinical trials in acute lung injury, especially in terms of discovering the only potentially useful therapies for patients with the most severe ARDS.” “In terms of clinical practice, I’m not sure at this point that this will make a big difference, but it should improve the uniformity of the ARDS definition. In addition, by publishing a new version of the ARDS definition in a high-impact journal, this may help increase clinicians’ awareness of patients with ARDS. With increased awareness, clinicians will be able to treat them more quickly and appropriately, such as with low tidal volume ventilation or restrictive fluid management strategies as long as the patient is hemodynamically stable.