Working groups

Potential topics for an expansion of the Berlin Definition were proposed during an initial organizational meeting, after which an anonymous survey was distributed to committee members for their vote on which topics should addressed. The entire committee agreed to establish working groups to address three major areas for potential revision of the Berlin Definition:

Risk factors, timing, and extra-pulmonary organ involvement

Co-chairs: M. Gong and T.R. Martin

Members: A. Bersten, J.E. Gotts, K.D. Liu, M.A. Matthay, R. Mularski, N. Ramakrishnan, E. Rubin

Questions

1. How long before the onset of hypoxemia can symptoms be present?

2. Should sub-categories be created for patients with extra-pulmonary organ failure?

3. Should the primary risk factor be a part of each patient’s diagnosis?

Key evidence considered

• Liu KD, Glidden DV, Eisner MD, et al. Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury. Crit Care Med, 35(12):2755-61 (2007).

• Cooke CR, Kahn JM, Caldwell E, et al. Predictors of hospital mortality in a population-based cohort of patients with acute lung injury. Crit Care Med, 36(5):1412-20 (2008).

• Sheu CC, Gong MN, Zhai R, et al. The influence of infection sites on development and mortality of ARDS. Intensive Care Med, 36(6):963-70 (2010).

• Calfee CS, Janz DR, Bernard GR, et al. Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies. Chest, 147(6):1539-1548 (2015).

• Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos, II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest, 155(3):474-482 (2019).

• Ruan SY, Huang CT, Chien YC, et al. Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study. BMC Pulm Med, 21(1):183 (2021).

Chest imaging

Co-chairs: G.R. Bernard and E.D. Riviello

Members: Y. Arabi, A. Combes, B. Daniel, N. Ferguson, F.R. Machado, A. Mercat, M. Moss, A. Pesenti, A. Slutsky, L.B. Ware, K.D. Wick

Questions

1. Should the diagnostic criteria require a certain amount of respiratory support/be based upon provider interventions such as endotracheal intubation, PEEP, or CPAP?

2. Should the current severity categories of mild, moderate, and severe be modified?

3. Should diagnosis by SpO₂/FiO₂ be formally adopted as an alternative diagnostic criterion, and if so, which cutoffs should be used?

4. Should other measures of respiratory failure such as dead space, ventilatory ratio, or mean airway pressure in ventilated patients be included as severity modifiers?

Key evidence considered

• Rice TW, Wheeler AP, Bernard GR, et al. Comparison of the SpO₂/FIO₂ ratio and the PaO₂/FIO₂ ratio in patients with acute lung injury or ARDS. Chest, 132(2):410-7 (2007).

• Pandharipande PP, Shintani AK, Hagerman HE, et al. Derivation and validation of SpO₂/FIO₂ ratio to impute for PaO₂/FIO₂ ratio in the respiratory component of the Sequential Organ Failure Assessment score. Crit Care Med, 37(4):1317-21 (2009).

• Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med, 372(23):2185-96 (2015).

• Chen W, Janz DR, Shaver CM, Bernard GR, Bastarache JA, Ware LB. Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/FIO₂ Ratio Compared With PaO₂/FIO₂ Ratio. Chest, 148(6):1477-1483 (2015).

• Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of PaO₂/FIO₂ From SpO₂/FIO₂ Among Patients With Acute Respiratory Distress Syndrome. Chest, 150(2):307-13 (2016).

• Riviello ED, Kiviri W, Twagirumugabe T, et al. Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition. Am J Respir Crit Care Med, 193(1):52-9 (2016).

• Riviello ED, Buregeya E, Twagirumugabe T. Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition. Curr Opin Crit Care, 23(1):18-23 (2017).

• Vercesi V, Pisani L, van Tongeren PSI, et al. External confirmation and exploration of the Kigali modification for diagnosing moderate or severe ARDS. Intensive Care Med, 44(4):523-524 (2018).

• NHLBI Petal Clinical Trials Network, Moss M, Huang DT, et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med, 380(21):1997-2008 (2019).

• Calligaro GL, Lalla U, Audley G, et al. The utility of high flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine, 28:100570 (2020).

• Ranieri VM, Tonetti T, Navalesi P, et al. High Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in COVID-19 Patients. Am J Respir Crit Care Med, 205(4):431-439 (2021).

• Gershengorn HB, Hu Y, Chen JT, et al. The Impact of High-Flow Nasal Cannula Use on Patient Mortality and the Availability of Mechanical Ventilators in COVID-19. Ann Am Thorac Soc, 18(4):623-631 (2021).

• Wong AI, Charpignon M, Kim H, et al. Analysis of Discrepancies Between Pulse Oximetry and Arterial Oxygen Saturation Measurements by Race and Ethnicity and Association With Organ Dysfunction and Mortality. JAMA Netw Open, 4(11):e2131674 (2021).

• Fawzy A, Wu TD, Wang K, et al. Racial and Ethnic Discrepancy in Pulse Oximetry and Delayed Identification of Treatment Eligibility Among Patients With COVID-19. JAMA Intern Med, 182(7):730-738 (2022).

Oxygenation

Co-chairs: L.J. Brochard and J.G. Laffey

Members: A.C. Arroliga, C.S. Calfee, M.S. Herridge, D.F. McAuley, H. Qiu, M. Ranieri, B.T. Thompson, T. Twagirumuge

Questions

1. Should ARDS diagnosis require bilateral infiltrates? If not, should a certain number of quadrants be involved?

2. What imaging modalities are acceptable for diagnosis?

3. Should there be any requirement for serial imaging or infiltrates that persist for a certain amount of time?

4. Should the infiltrates be further characterized as they are now (not primarily attributable to nodules e.g., certain density?)

Key evidence considered

• Rubenfeld GD, Caldwell E, Granton J, Hudson LD, Matthay MA. Interobserver variability in applying a radiographic definition for ARDS. Chest, 116(5):1347-53 (1999).

• Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA, 315(8):788800 (2016).

• Peng JM, Qian CY, Yu XY, et al. Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study. Crit Care, 21(1):12 (2017).

• Goddard SL, Rubenfeld GD, Manoharan V, et al. The Randomized Educational Acute Respiratory Distress Syndrome Diagnosis Study: A Trial to Improve the Radiographic Diagnosis of Acute Respiratory Distress Syndrome. Crit Care Med, 46(5):743-748 (2018).

• Wooten WM, Shaffer LET, Hamilton LA. Bedside Ultrasound Versus Chest Radiography for Detection of Pulmonary Edema: A Prospective Cohort Study. J Ultrasound Med, 38(4):967-973 (2019).

• Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos, II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest, 155(3):474-482 (2019).

• Kotok D, Yang L, Evankovich JW, et al. The evolution of radiographic edema in ARDS and its association with clinical outcomes: A prospective cohort study in adult patients. J Crit Care, 56:222-228 (2020).

• Tierney DM, Huelster JS, Overgaard JD, et al. Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure. Crit Care Med, 48(2):151-157 (2020).

• Sachdev A, Khatri A, Saxena KK, Gupta D, Gupta N, Menon GR. Chest sonography versus chest radiograph in children admitted to paediatric intensive care - A prospective study. Trop Doct, 51(3):296-301 (2021).

• Maddali MV, Churpek M, Pham T, et al. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis. Lancet Respir Med, 10(4):367-377 (2022).

Each working group considered the five overall goals for the definition as well as specific questions regarding its topic.