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 end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level 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.

Acute respiratory distress syndrome: the Berlin Definition.

Background There have been few detailed, in-person interviews and examinations to obtain follow-up data on 5-year outcomes among survivors of the acute respiratory distress syndrome (ARDS). Methods We evaluated 109 survivors of ARDS at 3, 6, and 12 months and at 2, 3, 4, and 5 years after discharge from the intensive care unit. At each visit, patients were interviewed and examined; underwent pulmonary-function tests, the 6-minute walk test, resting and exercise oximetry, chest imaging, and a quality-of-life evaluation; and reported their use of health care services. Results At 5 years, the median 6-minute walk distance was 436 m (76% of predicted distance) and the Physical Component Score on the Medical Outcomes Study 36-Item Short-Form Health Survey was 41 (mean norm score matched for age and sex, 50). With respect to this score, younger patients had a greater rate of recovery than older patients, but neither group returned to normal predicted levels of physical function at 5 years. Pulmonary function wa...

Functional disability 5 years after acute respiratory distress syndrome.

Background As more patients survive the acute respiratory distress syndrome, an understanding of the long-term outcomes of this condition is needed. Methods We evaluated 109 survivors of the acute respiratory distress syndrome 3, 6, and 12 months after discharge from the intensive care unit. At each visit, patients were interviewed and underwent a physical examination, pulmonary-function testing, a six-minute–walk test, and a quality-of-life evaluation. Results Patients who survived the acute respiratory distress syndrome were young (median age, 45 years) and severely ill (median Acute Physiology, Age, and Chronic Health Evaluation score, 23) and had a long stay in the intensive care unit (median, 25 days). Patients had lost 18 percent of their base-line body weight by the time they were discharged from the intensive care unit and stated that muscle weakness and fatigue were the reasons for their functional limitation. Lung volume and spirometric measurements were normal by 6 months, but carbon monoxide d...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa022450

One-Year Outcomes in Survivors of the Acute Respiratory Distress Syndrome

Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition. The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision. The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO2/FiO2 thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy. This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.

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The Berlin definition of ARDS: An expanded rationale, justification, and supplementary material

To measure the reliability of chest radiographic diagnosis of acute respiratory distress syndrome (ARDS) we conducted an observer agreement study in which two of eight intensivists and a radiologist, blinded to one another's interpretation, reviewed 778 radiographs from 99 critically ill patients. One intensivist and a radiologist participated in pilot training. Raters made a global rating of the presence of ARDS on the basis of diffuse bilateral infiltrates. We assessed interobserver agreement in a pairwise fashion. For rater pairings in which one rater had not participated in the consensus process we found moderate levels of raw (0.68 to 0.80), chance-corrected ( κ 0.38 to 0.55), and chance-independent ( Φ 0.53 to 0.75) agreement. The pair of raters who participated in consensus training achieved excellent to almost perfect raw (0.88 to 0.94), chance-corrected ( κ 0.72 to 0.88), and chance-independent ( Φ 0.74 to 0.89) agreement. We conclude that intensivists without formal consensus training can achiev...

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.1.9809003

Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome.

OBJECTIVES To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury. DESIGN Prospective blinded cohort analysis. SETTING Three university-affiliated medical-surgical intensive care units. PATIENTS A total of 28 survivors of acute lung injury, 1-2 yrs after diagnosis, from a multicenter prospective randomized controlled trial comparing pressure (peak inflation pressure < or =30 cm H2O) and volume (tidal volume < or =8 mL/kg) limited ventilation to a conventional (peak inflation pressure < or =50 cm H2O, tidal volume 10-15 mL/kg) ventilation strategy. MEASUREMENTS AND MAIN RESULTS Physicians blinded as to treatment group evaluated 20 of 28 survivors (treatment group, 7; control group, 13). Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups (treatment group, 373+/-171 m vs. control group, 375+/-129 m; p = .84). Pulmonary function testing showed reduced diffusing capacity (treatment group, 64+/-29% predicted vs. control group, 74+/-14% predicted; p = .68) and normal volumes, flows, and blood gases. Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Questionnaire were worse for patients in the treatment group compared with the control group (Emotional Function 3.8+/-1.4 vs. 5.1+/-0.08; p = .05, Mastery 4.7+/-1.7 vs. 6.2+/-0.8; p = .03). There were no between-group differences in the scores of the Spitzer Quality of Life Index (a generic Health Related Quality of Life instrument), although they were reduced (7.5+/-1.9) and comparable to patients with chronic disease. CONCLUSIONS We found that 1-2 yrs after the onset of their illness, survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases. We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury.

Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma.

To examine the agreement between two classifications of acute respiratory distress syndrome (ARDS) that are used interchangeably in clinical practice and clinical research, we classified 118 patients taking part in a randomized trial with respect to the presence of ARDS using the North American–European Consensus Committee (NAECC) and the Lung Injury Severity Score (LISS) criteria. The incidence of ARDS using NAECC criteria was 55.1% (95% confidence interval, 46.1% to 64.1%), and using the LISS criteria 61.9% (95% confidence interval, 53.1% to 70.6%). The p value on the difference between these proportions was 0.07. Raw agreement, chance-corrected agreement (kappa), and chance-independent agreement (phi) on the study occurrence of ARDS using the two classifications were, respectively, 0.73 (95% CI, 0.65 to 0.81), 0.46 (95% CI, 0.32 to 0.61), and 0.63 (95% CI, 0.41 to 0.79). No single component of either index contributed to disagreement to an appreciably greater extent than other components. Baseline char...

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.163.2.2006067

John R. Kachura

Papers

Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome.

Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma.

Agreement between Alternative Classifications of Acute Respiratory Distress Syndrome