ABSTRACT
The definition of acute respiratory distress syndrome (ARDS) has been updated several times since the syndrome was first described in 1967. The aim of the initial definition was to better study this disease and standardize its care. Each iteration has brought its own set of nuances and challenges. In 2024, a new global definition of ARDS was proposed. This review highlights the evolution of ARDS definitions over the years and discusses the key components of the new proposed global definition.
The diagnosis of ARDS is commonly missed or delayed.
The new global definition of ARDS introduces a new category of nonintubated patients, ie, those receiving oxygen by high-flow nasal cannula or mask, and another category of patients in settings lacking resources such as ventilators, arterial blood gas analyzers, and radiography.
Although the new global definition increases the number of patients who may be diagnosed with ARDS, its impact for the bedside clinician is unknown.
Further studies are required to better understand this new cohort of patients who can now be labeled as having ARDS.
In 2024, a consensus committee of experts from around the world proposed a new global definition of acute respiratory distress syndrome (ARDS)1 that allows it to be diagnosed on the basis of data from tests and treatments that are cheaper, less invasive, and more readily available than the current ones:
Oxygen by high-flow nasal cannula as an alternative to mechanical ventilation
Pulse oximetry as an alternative to arterial oxygen measurements
Ultrasonography as an alternative to chest radiography.
More patients should be identified as having ARDS under the new definition, especially in resource-limited settings, and thus receive potentially life-saving treatment. We hope that it will be useful and practical in both clinical care and research. Still, we will all need to wait and see how it works out in practice.
Here, we review how the definition of ARDS has evolved, how the new definition differs from the old, and the possible implications of the changes.
ARDS IS UNDERRECOGNIZED
ARDS can be precipitated by any of a myriad of direct insults (eg, aspiration, viral, or bacterial pneumonia) or indirect ones (eg, sepsis, pancreatitis, shock, transfusions, or trauma). These lead to systemic inflammation and cytokine release, resulting in bilateral pulmonary parenchymal infiltrates and severe derangements in gas exchange, resulting in ARDS, with high rates of morbidity and mortality.2 Yet, ARDS often goes unrecognized, especially in its mild and moderate forms, and its treatment is inconsistent.3–7
LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure)3 found that clinicians recognized only about 50% of cases of mild ARDS and only about 80% of severe cases. Factors associated with lack of recognition included certain etiologies (eg, postoperative ARDS), patient characteristics (eg, older age, obesity), and understaffing in the intensive care unit.
Underrecognition of ARDS delays timely initiation of best practices, namely lung-protective ventilation (with low tidal volume), positive end-expiratory pressure (PEEP), prone positioning, and conservative fluid management.8–10 This delay has been associated with worse outcomes.4 Conversely, in a single-center study, fewer patients died and more were discharged home after Cleveland Clinic adopted a protocolized approach combined with clinician education, suggesting that both early disease recognition and implementation of evidence-based strategies are important.5
ARDS THROUGH THE YEARS
More than 5 decades ago, Ashbaugh et al11 first described a syndrome of acute respiratory failure in adults (actually, 11 adults and an 11-year-old boy) marked by profound hypoxemia refractory to standard oxygen therapy, with tachypnea and cyanosis; bilateral pulmonary infiltrates on radiography, usually developing within 24 to 48 hours of an inciting event; and markedly reduced lung compliance as evidenced by the need for higher pressures to achieve targeted tidal volumes.
Early studies showed that PEEP could improve the hypoxemia,12 perhaps by preventing alveolar collapse, thereby facilitating efficient gas exchange, and by decreasing congestion and edema within individual alveoli, thereby improving oxygenation.12,13
Observational studies further revealed that ARDS could occur as a consequence of a wide range of diverse etiologies.1–3
Why does a definition matter? Early ARDS definitions
Despite initial advances in the understanding of ARDS, the reported incidence and outcomes varied widely, highlighting the need for a standardized definition. A uniform definition would help address the heterogeneity in presentation and thus aid in conducting and interpreting clinical research. Many attempts were made to address the inconsistencies associated with studying and reporting ARDS, particularly study outcomes and interventions.
Lung injury score. In 1988, in the first attempt to standardize the definition of ARDS and stratify its severity, Murray et al14 developed a lung injury score based on the number of lung quadrants showing radiographic infiltrates, the ratio of arterial oxygen tension to the fraction of inspired oxygen (P/F ratio), the level of PEEP required, and respiratory system compliance (Table 1).1,11,14–16
Timeline of acute respiratory distress syndrome (ARDS) definitions
The American-European Consensus Committee definition,15 published in 1994, defined acute lung injury and ARDS based on timing (acute onset for both), oxygenation (a P/F ratio ≤ 300 mm Hg in acute lung injury and ≤ 200 mm Hg in ARDS), chest radiographic features (bilateral infiltrates), and either pulmonary capillary wedge pressure less than 18 mm Hg or no clinical evidence of left atrial hypertension.
This definition allowed us to study ARDS-related outcomes and specific interventions for the first time, based on a consistent patient population. But it had limitations: Ferguson et al17 reported that in more than half of patients screened for ARDS clinical trials in which ventilator settings were standardized, the P/F ratio improved enough within 30 minutes of putting the patient on the ventilator that the patient no longer met the criteria for ARDS.
Berlin definition.16 The European Society of Intensive Care Medicine, American Thoracic Society, and Society of Critical Care Medicine convened in 2011 to develop a new definition for ARDS focusing on feasibility, reliability, and validity. Acute timing was defined as onset within 1 week of a known inciting event or new or worsening hypoxemia. ARDS was categorized as mild, moderate, or severe based on the P/F ratio at a PEEP level of at least 5 cm H2O. Bilateral infiltrates on chest radiography remained part of the definition, but with a caveat advising clinicians to think of noncardiogenic causes of pulmonary edema and to consider using echocardiography if no clear ARDS etiology was apparent to rule out hydrostatic pulmonary edema. The use of pulmonary capillary wedge pressure was eliminated.
This expert opinion definition was then tested using empirical data from 2 large databases and was found to better predict mortality compared with the earlier definition. In 2012, these revisions were published and named the Berlin definition.16
BUT WHAT IF YOU DON’T HAVE A VENTILATOR?
Although the Berlin definition addressed the limitations of the earlier definition, Riviello et al18 pointed out that it required access to mechanical ventilators to administer PEEP, arterial blood gas analyzers to measure arterial oxygen tension, and chest radiography to detect lung infiltrates, which many resource-constrained hospitals of the world do not have. These limitations may lead to underestimating the true incidence of ARDS in these settings and present an obstacle to treatment.
Therefore, Riviello et al18 proposed the Kigali modification, which defined hypoxemia as a ratio of peripheral oxygen saturation to fraction of inspired oxygen (S/F ratio) of 315 or less (only applicable if the peripheral oxygen saturation is ≤ 97%) without a PEEP requirement, and said that lung opacities could be detected on ultrasonography as an alternative to chest radiography. Using the Kigali modification, 4% of hospitalized patients were found to have ARDS, with a hospital mortality rate of 50% in a prospective study in Rwanda.18 None of these patients would have been identified by the Berlin criteria, emphasizing the importance of a modified definition in areas where resources are limited.
Mechanical ventilation can be given invasively by endotracheal tube or noninvasively by face mask to provide continuous or bilevel positive airway pressure. An alternative to both is to give oxygen by high-flow nasal cannula, a strategy that has become more prevalent in the care of acute hypoxemic respiratory failure since the publication of the FLORALI (High-Flow Nasal Oxygen Therapy in Resuscitation of Patients With Acute Lung Injury) trial.19 It found even more use during the COVID-19 pandemic, in which patients required high levels of oxygen support but intensive care unit beds and mechanical ventilators were in short supply. These patients with severe hypoxemia requiring high-flow nasal oxygen technically did not meet the Berlin diagnostic criteria for ARDS, given their method of oxygen delivery with a lack of PEEP.
Patients who meet all other criteria of the Berlin definition except for the requirement of mechanical ventilation have been found to have a similar mortality rate, and the degree of hypoxemia itself relates more to the overall patient trajectory.20–22 Kangelaris et al23 found the 60-day mortality outcomes were similar between patients meeting diagnostic criteria for ARDS who were initially not intubated vs those who were intubated early.
But, as discussed above, concerns were raised that requiring invasive or noninvasive mechanical ventilation with a PEEP of at least 5 cm H2O to make a diagnosis of ARDS may delay its recognition and hence potentially life-saving treatment, underscoring the need to further revise the Berlin definition.21
A NEW GLOBAL DEFINITION OF ARDS—2024
The consensus committee separated ARDS into 3 categories: nonintubated, intubated, and a modified category that would allow ARDS to be diagnosed in resource-limited settings.1
Nonintubated. Patients on noninvasive ventilation or high-flow nasal oxygen with a P/F ratio of 300 mm Hg or less or an S/F ratio of 315 or less (if the peripheral oxygen saturation is ≤ 97%) with at least 30 L/minute if on a high-flow nasal oxygen cannula or at least 5 cm H2O of PEEP if receiving positive airway pressure with a mask are now classified as having nonintubated ARDS. The criterion of 30 L/minute was agreed upon in view of studies that showed that this level of support actually generated low levels of PEEP.24 This modification to the Berlin criteria allows ARDS to be recognized earlier and provides additional information on the evolution of the disease.
Intubated. The S/F ratio can also be used in intubated patients. The previous Berlin criteria for severity of hypoxemia based on the P/F ratio remains the same. If the peripheral oxygen saturation is less than or equal to 97%, hypoxemia is classified as follows:
Mild if the S/F ratio is greater than 235 but less than or equal to 315
Moderate if it is greater than 148 but less than or equal to 235
Severe if it is less than or equal to 148 (Figure 1).
A new global definition of acute respiratory distress syndrome.1
P/F = ratio of arterial oxygen tension (Pao2) to fraction of inspired oxygen (Fio2); PEEP = positive end-expiratory pressure;
S/F = ratio of peripheral oxygen saturation (Spo2) to fraction of inspired oxygen (Fio2)
Resource-limited. A third category uses the Kigali modification for intended use in resource-limited settings. This modification would address the barriers to obtaining arterial blood gasses and using mechanical ventilators that are present in resource-limited areas. The consensus committee agreed on a S/F ratio of 315 or less (with peripheral oxygen saturation ≤ 97%) to define ARDS.1 Studies have shown that the S/F ratio is a satisfactory method for determining the degree of hypoxemia as compared with the P/F ratio if the patient does not have a hemoglobin disorder and if the peripheral oxygen saturation is 97% or less.25–27
It is important to note that pulse oximetry may not be entirely accurate in shock states or in patients with darker skin.28,29 Keeping this in mind, some situations may require validation with an arterial blood gas measurement, especially for research studies. For these reasons, the consensus committee did not recommend using this modified definition in settings that are not resource-limited. Nonetheless, this modification removes social and economic gaps in identifying patients with ARDS who would benefit from early intervention and therapeutic strategies. It also provides another area for future research to prospectively compare the Berlin definition with the global definition of ARDS.
Preliminary retrospective cohorts have shown that the new global definition captures a higher proportion of ARDS patients than the Berlin definition in resource-limited settings30 and helps with earlier detection of this disease syndrome.31 However, larger prospective epidemiologic studies need to be carried out to fully understand the new definition’s clinical relevance and impact.
While the new global definition has focused on identifying ARDS early in its course and consequently will include many patients with mild forms of the disease, it remains unclear at this point whether these changes would translate into better recognition, changes in processes of care, and improved outcomes.
HOW WILL THE CHANGES AFFECT CARE?
The new global definition of ARDS has far-reaching potential implications beyond simply characterizing a disease state—it can have both clinical relevance and investigative applicability. These modifications, however, have not been clinically studied, and their impact will likely become more apparent over the next few years. At first glance, high-flow nasal oxygen, pulse oximetry, and chest ultrasonography, now included in the new global ARDS definition, are attractive options, as they provide additional diagnostic tools to help detect ARDS early. Unfortunately, they also add a layer of complexity and diagnostic uncertainty to an already poorly understood syndromic definition.
The new global definition was developed to bolster and standardize research enrollment in future studies. Its higher sensitivity will capture more patients at an earlier point in the disease process. Studying the disease process at an earlier stage will enable further understanding of patients’ clinical trajectories, assist with phenotyping, and ultimately aid the development of therapeutic strategies.
A boost to research
The delineation of 3 separate groups in the broader definition—nonintubated, intubated, and those in resource-limited settings—paves the way for future research into the outcomes of each of these distinct patient cohorts. It also provides a chance to critically analyze how the timing of certain therapeutic interventions may affect the patient’s overall clinical trajectory.
But the key factor that clinicians and researchers need to acknowledge and identify is that these are very distinct cohorts of patients, and currently studied therapies in ARDS may not apply broadly across them. For example, corticosteroids are beneficial in severe pneumonia and COVID-19 but not in later stages of ARDS or other ARDS etiologies.32–34 Changes in the definition affect the ability to study and apply interventions, given the heterogeneity in the included patients, in both timing of the disease process and severity. Prospective validation is required before we can apply these recommendations across the individual cohorts.
Earlier recognition and treatment
Prior to this expanded definition, a patient on high-flow nasal oxygen with bilateral opacities and a predisposing risk factor that occurred within approximately 1 week of the development of acute hypoxemic respiratory failure would not have met the ARDS criteria, because they were on high-flow nasal oxygen. This expanded definition can help identify patients with ARDS much earlier in their disease trajectory and engage care teams outside the intensive care unit to consider early supportive care that could improve the clinical trajectory of patients.
Physicians, advanced care clinicians, and nurses working on hospital general medical wards have traditionally not been involved in the care of patients with ARDS, but this broader definition brings this disease into their realm with the opportunity for earlier identification and management.
Clinicians need to think about noncardiogenic pulmonary edema in patients with risk factors for it (eg, influenza-like illness, sepsis, trauma) and rule out volume overload due either to decompensation in patients with underlying cardiac dysfunction or to initial volume resuscitation.3 Early recognition of noncardiogenic pulmonary edema should prompt the clinician to think about strategies that are beneficial in this disease process while on the general wards, such as diuretics, and targeted echocardiography to assess the right side of the heart to screen for hypoxemia-associated right ventricular failure and cor pulmonale.35 It may also help facilitate earlier transfer to the intensive care unit for potential need for mechanical ventilation if noninvasive strategies are failing or the patient has significant work of breathing despite these early interventions.
Education will be needed
However, without additional education, this broader definition may not have its intended benefits. Although a broader definition suggests potential benefits for both early recognition and future research studies, it may pose a challenge to clinicians in making distinctions between early vs severe forms of ARDS.
For example, a patient receiving 60% oxygen at 60 L/minute by high-flow nasal cannula who has a P/F ratio of 210 mm Hg and a respiratory rate of 20 breaths per minute may be very different from another patient on the same settings with the same P/F ratio but with a respiratory rate of 30 breaths per minute. The amount of oxygen delivery is the same, the P/F ratios are identical, but the second patient’s higher breathing rate suggests a diminished lung compliance or decreased ventilatory efficiency leading to increased dead space and consequently a more severe form of the disease process.
This definition may allow for a larger number of patients to be identified as having “mild” or “moderate” ARDS. But we must not be falsely reassured if a patient is categorized as having mild ARDS if they have other clinical features, such as increased work of breathing, that would point to a more severe form of the disease process. Maintaining a low threshold for escalating care to the level of an intensive care unit and promptly implementing proven treatments such as lung-protective ventilation, paralysis if desynchrony is present, and prone positioning are vital to patient outcomes.
The new global definition does not change anything for those with severe ARDS, which has been the subject of most of the trials over the past 2 decades.36–38 As we study early identification of ARDS with this new definition, it is important for clinicians to remember that targeted multidisciplinary care including lung-protective ventilation, PEEP titration, prone ventilation, and extracorporeal membrane oxygenation remains a core need for patients with severe ARDS.4,5,37
Hence, apart from offering educational initiatives, hospital systems may consider creating an infrastructure conducive to both early recognition and appropriately timed internist-initiated escalation with active involvement of pulmonary and critical care teams in the care of these patients. Given the identified gap between what is recommended and what doctors actually do in practice, it is crucial to consider how the new definition will affect these efforts and how hospital systems will address the risk of such variability.
Although the global definition has expanded the patient population that may be diagnosed as having ARDS, it remains to be seen whether it will identify patients with the same syndromic disease process, which itself lacks clarity. Thus, its impact for the bedside clinician is unknown. Unlike the Berlin definition, which was validated using large, multicenter, prospective cohorts of patients and compared with its preceding definition, the global definition is foremost a prelude to further research. And until then, clinicians and hospitals need to be mindful of its adoption in the clinical setting.
DISCLOSURES
Dr. Duggal has disclosed being an advisor or review panel participant for Alung Technologies. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
- Copyright © 2025 The Cleveland Clinic Foundation. All Rights Reserved.
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