Acute Respiratory Distress Syndrome

VALID AND RELIABLE DEFINItions are essential to conduct epidemiological studies successful ly and to facilitate enrollment of a consistent patient phenotype into clinical trials. Clinicians also need such definitions to implement the results of clinical trials, discuss prognosis with families, and plan resource allocation. Following the initial description of acute respiratory distress syndrome (ARDS) by Ashbaugh et al in 1967, multiple definitions were proposed and used until the 1994 publication of the American-European Consensus Conference (AECC) definition. The AECC defined ARDS as the acute onset of hypoxemia (arterial partial pressure of oxygen to fraction of inspired oxygen [PaO2/FIO2] 200 mm Hg) with bilateral infiltrates on frontal chest radiograph, with no evidence of left atrial hypertension. A new overarching entity— acute lung injury (ALI)—was also described, using similar criteria but with less severe hypoxemia (PaO2/FIO2 300 mm Hg). The AECC definition was widely adopted by clinical researchers and clinicians and has advanced the knowledge of ARDS by allowing the acquisition of clinical and epidemiological data, which in turn have led to improvements in the ability to care for patients with ARDS. However, after 18 years of applied research, a number of issues regarding various criteria of the AECC definition have emerged, including a lack of explicit criteria for defining acute, sensitivity of PaO2/FIO2 to different ventilator settings, poor reliability of the chest radiograph criterion, and difficulties distinguishing hydrostatic edema (TABLE 1). *Authors/Writing Committee and the Members of the ARDS Definition Task Force are listed at the end of this article. Corresponding Author: Gordon D. Rubenfeld, MD, MSc, Program in Trauma, Emergency, and Critical Care, Sunnybrook Health Sciences Center, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada (gordon [email protected]). The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree 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) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance ( 40 mL/cm H2O), positive endexpiratory pressure ( 10 cm H2O), and corrected expired volume per minute ( 10 L/min). The draft Berlin Definition was empirically evaluated using patientlevel meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.