Acute Respiratory Distress Syndrome Definitions

OVERVIEW

Definitions of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have varied over time

• ARDS was first described by Ashbaugh and Petty in 1967 in a case series of 12 ICU patients who shared the common features of unusually persistent tachypnea and hypoxemia accompanied by opacification on chest radiographs and poor lung compliance, despite different underlying causes
• for more than 20 years, there was no common definition of ARDS
• inconsistent definitions led to the published prevalence in ICU ranging from 10 to 90% of patients
• The 1994 AECC definition became globally accepted, but had limitations
• This was superseded by the ‘Berlin Definition’ published in 2013, which was created by a consensus panel of experts convened in 2011 (an initiative of the European Society of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)
• In 2023 an new “global definition of ARDS” was published based on a consensus conference of 32 critical care ARDS experts followed by input from members of several critical care societies.

2023 GLOBAL DEFINITION OF ARDS

Conceptual model (Matthay et al, 2023):

ARDS is an acute, diffuse, inflammatory lung injury precipitated by a predisposing risk factor, such as pneumonia, nonpulmonary infection, trauma, transfusion, burn, aspiration, or shock. The resulting injury leads to increased pulmonary vascular and epithelial permeability, lung edema, and gravity-dependent atelectasis, all of which contribute to loss of aerated lung tissue. The clinical hallmarks are arterial hypoxemia and diffuse radiographic opacities associated with increased shunting, increased alveolar dead space, and decreased lung compliance. The clinical presentation is influenced by medical management (position, sedation, paralysis, positive end-expiratory airway pressure, and fluid balance). Histological findings vary and may include intraalveolar edema, inflammation, hyaline membrane formation, and alveolar hemorrhage.

Criteria that apply to all ARDS categories (Matthay et al, 2023):

Risk factors and origin of edema		Precipitated by an acute predisposing risk factor, such as pneumonia, nonpulmonary infection, trauma, transfusion, aspiration, or shock. Pulmonary edema is not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload, and hypoxemia/gas exchange abnormalities are not primarily attributable to atelectasis. However, ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS is also present.
Timing		Acute onset or worsening of hypoxemic respiratory failure within 1 week of the estimated onset of the predisposing risk factor or new or worsening respiratory symptoms.
Chest imaging		Bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on ultrasound not fully explained by effusions, atelectasis, or nodules/masses.

Criteria That Apply to Specific ARDS Categories (Matthay et al, 2023):

Nonintubated ARDS	Intubated ARDS	Modified Definition for Resource-Limited Settings
PaO2:FiO2 ⩽ 300 mm Hg or SpO2:FiO2 ⩽ 315 (if SpO2 ⩽ 97%) on HFNO with flow of ⩾30 L/min or NIV/CPAP with at least 5 cm H2O end-expiratory pressure	Mild: 200 < PaO2:FiO2 ⩽ 300 mm Hg or 235 < SpO2:FiO2 ⩽ 315 (if SpO2 ⩽ 97%)	SpO2:FiO2 ⩽ 315 (if SpO2 ⩽ 97%). Neither positive end-expiratory pressure nor a minimum flow rate of oxygen is required for diagnosis in resource-limited settings.
	Moderate: 100 < PaO2:FiO2 ⩽ 200 mm Hg or 148 < SpO2:FiO2 ⩽ 235 (if SpO2 ⩽ 97%)
	Severe: PaO2:FiO2 ⩽ 100 mm Hg or SpO2:FiO2 ⩽ 148 (if SpO2 ⩽ 97%)

Summary of key changes from 2012 Berlin Definition:

Berlin Definition	Rationale for Updating Criteria	How This is Addressed in the Global Definition
Acute onset within 1 week of known insult or new or worsening respiratory symptoms	Onset may be more indolent for some insults, such as COVID-19	The inclusion of patients with HFNO will capture patients with more indolent courses, and therefore the timing criterion has not been changed
Bilateral opacities on chest radiography or computed tomography not fully explained by effusions, lobar/lung collapse, or nodules	Chest radiography and computed tomography not available in some clinical settings	Ultrasound can be used to identify bilateral loss of lung aeration (multiple B lines and/or consolidations) as long as operator is well trained in the use of ultrasound
Three severity categories defined by PaO2:FiO2	Pulse oximetric measurement of SpO2:FiO2 is widely used and validated as a surrogate for PaO2:FiO2	SpO2:FiO2 can be used for diagnosis and assessment of severity if SpO2 is ⩽97%
Requirement for invasive or noninvasive mechanical ventilation such that PEEP ⩾ 5 cm H2O is required for all categories of oxygenation severity except mild, which can also be met with CPAP ⩾ 5 cm H2O	HFNO increasingly being used in patients with severe hypoxemia who otherwise meet ARDS criteria	New category of nonintubated ARDS created for patients on HFNO at ⩾30 L/min who otherwise meet ARDS criteria
	Invasive and noninvasive mechanical ventilation not available in resource-limited settings	Modified definition of ARDS for resource-limited settings does not

2012 BERLIN DEFINITION OF ARDS

ARDS is an acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue…[with] hypoxemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space and decreased lung compliance.

Key components

1. acute, meaning onset over 1 week or less
2. bilateral opacities consistent with pulmonary edema must be present and may be detected on CT or chest radiograph
3. PF ratio <300mmHg with a minimum of 5 cmH20 PEEP (or CPAP)
4. “must not be fully explained by cardiac failure or fluid overload,” in the physician’s best estimation using available information — an “objective assessment“ (e.g. echocardiogram) should be performed in most cases if there is no clear cause such as trauma or sepsis.

Severity

• ARDS is categorized as being mild, moderate, or severe:

ARDS Severity	PaO2/FiO2*	Mortality**
Mild	200 – 300	27%
Moderate	100 – 200	32%
Severe	< 100	45%
*on PEEP 5+;  **observed in cohort

Changes from the 1994 AECC definition

• the term acute lung injury was abandoned
• measurement of the PaO2/FIO2 ratio was changed to require a specific minimum amount of PEEP
• 3 categories of ARDS were proposed (mild, moderate, and severe) based on the PaO2/FIO2 ratio
• Radiographic criteria were changed to improve interrater reliability
• PCWP criterion was removed and additional clarity was added to improve the ability to exclude cardiac causes of bilateral infiltrates

Issues with the Berlin definition

• ability to predict mortality is still poor, but slightly better (based on meta-analysis of 4188 patients): Berlin ROC AUC = 0.577 compared to 0.536 for AECC
• 4 ancillary variables for severe ARDS were assessed but did not have additional predictive value, so were not included in the definition:
  • 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)
• Berlin definition doesn’t include underlying aetiology and lacks a direct measure of lung injury
• use of vasopressors at the time of diagnosis of ARDS is associated with a much higher mortality regardless of the PF ratio (not accounted for in the Berlin definition)
• Does not allow early identification of patients who may be amenable to therapies before ARDS becomes established
• unclear how the Berlin definition will affect diagnosis and management in the real world
• Berlin definition still allows CXR to be used for diagnosis, which compared poorly with CT chest when studied by Figueroa-Casa et al, 2013:
  • Sensitivity 0.73; specificity, 0.70; positive and negative predictive values 0.88 and 0.47
• The Berlin definition has low sensitivity when compared to autopsy findings:
  • Thille et al (2013) found that the Berlin Definition had a sensitivity of 89% and specificity of 63% to identify ARDS, based on autopsies of 356 patients with clinical criteria for ARDS using evidence of diffuse alveolar damage as the gold standard

1994 AECC DEFINITION OF ARDS

Now obsolete

Four key components must be present for the diagnosis of ARDS:

• the syndrome must present acutely
• hypoxemia, measured as PaO2/FIO2 ratio <200 (the ratio is >450 in healthy persons)
•  bilateral infiltrates on chest radiograph
• cannot be due to cardiac failure (elevated left atrial pressure), as evidenced by either clinical examination or a PCWP >18 cm H2O

The AECC also introduced the concept of acute lung injury:

• defined similarly to ARDS, except that the PaO2/FIO2 ratio needed only be <300

Pros

• cited by thousands of papers
• defined the entry criteria into the practice changing ARDsnet ARMA trial that led to the widespread adoption of protective lung ventilation
• incorporated into practice bundles

Cons

• other definitions such as the Lung Injury Score and the Delphi definition have a greater sensitivity when matched against autopsy evidence
• acute is ill defined
• PF ratio can be manipulated by adjusting PEEP
• CXR interpretation is unreliable
• PACs are rarely used
• PCWP may oscillate above and below the cut-off and may be elevated for reasons other than heart failure
• ALI  was used inconsistently, just PF ratio 200 to 300, or all patients <300 including ARDS?

These cons led to the development of the 2012 Berlin definition

References and Links

Journal articles

• ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. PMID: 22797452.
• Angus DC. The acute respiratory distress syndrome: what’s in a name? JAMA. 2012 Jun 20;307(23):2542-4. doi: 10.1001/jama.2012.6761. PMID: 22797455.
• Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet (London, England). 2(7511):319-23. 1967. [pubmed]
• Figueroa-Casas. Accuracy of the chest radiograph to identify bilateral pulmonary infiltrates consistent with the diagnosis of acute respiratory distress syndrome using computed tomography as reference standard. J Crit Care 2013;  [Article Link]
• Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, Gong MN, Gotts JE, Herridge MS, Laffey JG, Liu KD, Machado FR, Martin TR, McAuley DF, Mercat A, Moss M, Mularski RA, Pesenti A, Qiu H, Ramakrishnan N, Ranieri VM, Riviello ED, Rubin E, Slutsky AS, Thompson BT, Twagirumugabe T, Ware LB, Wick KD. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2024 Jan 1;209(1):37-47. doi: 10.1164/rccm.202303-0558WS. PMID: 37487152; PMCID: PMC10870872.
• Phillips CR. The Berlin definition: real change or the emperor’s new clothes? Crit Care. 2013 Aug 1;17(4):174. PMC4057493.
• Thille AW, Esteban A, Fernández-Segoviano P, Rodriguez JM, Aramburu JA, Peñuelas O, Cortés-Puch I, Cardinal-Fernández P, Lorente JA, Frutos-Vivar F. Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med. 2013 Apr 1;187(7):761-7. PMID: 23370917. [Article Link]

FOAM and web resources

• ICN — ARDS: An Evidence-based Update by Rob Mac Sweeney at smaccGOLD (2014)
• PulmCCM.org — Meet the New ARDS: Expert panel announces new definition, severity classes (JAMA) (2013)