Oxygenation

Categories of ARDS and HFNO

• The committee recommended creating three categories of ARDS to expand the current ARDS definition: non-intubated ARDS, intubated ARDS, and a modified category of ARDS for resource-limited settings.

• The committee recommended including patients who require a minimum level of support with either NIV (as in the Berlin definition) or HFNO in the definition under the category of non-intubated ARDS. This approach, however, limits the definition to care settings in which there is access to these respiratory support devices.

• The committee agreed that the potential to meet diagnostic criteria for a syndrome should not be affected by resource limitations.

• Therefore, a formal adoption of the Kigali modification of the clinical definition of ARDS is recommended for settings in which advanced respiratory support devices are not available.

• Since the publication of the FLORALI trial, the use of HFNO has increased substantially. The COVID-19 pandemic demonstrated that patients treated with HFNO may indeed have ARDS. In one study, 93% of patients with COVID-19 treated with HFNO continued to meet ARDS oxygenation criteria, including criteria for severe ARDS, after intubation and treatment with mechanical ventilation and PEEP. Though the mortality of patients treated with HFNO alone (i.e., who never progressed to invasive mechanical ventilation) was lower, it was similar to those treated with NIV alone, who currently meet the Berlin criteria for ARDS. An important advantage of including patients on HFNO in the revised definition is that ARDS may be recognized earlier, making trials of early interventions more feasible.

• These updates to the current definition will allow researchers to compare treatments and outcomes for patients in each category of ARDS (non-intubated, intubated, resource-limited). The resource-limited option will allow researchers in low-income countries to identify ARDS populations in their hospitals and to conduct clinical studies.

Pulse oximetry and SpO₂/FIO₂ ratio

• The committee agreed on allowing the use of SpO₂/FIO₂ as an alternative to the PaO₂/FIO₂ for the diagnosis of ARDS. Although arterial blood gas (ABG) measurements have been the gold standard for assessing hypoxemia in ARDS, the alternative use of SpO₂/FIO₂was added for two reasons: 1) inconsistent availability of ABGs in resource-limited settings, and 2) declining frequency of ABG monitoring in high income countries. Both linear and non-linear imputations of PaO₂/FIO₂ from SpO₂/FIO₂ demonstrate good performance as long as SpO₂ is ≤ 97% (and a hemoglobin abnormality is not present).

• Recent clinical trials in ARDS have used SpO₂/FIO₂ for patient selection, and patients diagnosed with ARDS using SpO₂/FIO₂ have similar clinical outcomes to those diagnosed by ABG. The committee agreed on using the Rice linear equation to define cutoff values of SpO₂/FIO₂ because its sensitivity and specificity for hypoxemia are comparable to non-linear imputations, and it is simpler to calculate.

• While the availability of a validated, non-invasive, and inexpensive method for evaluating oxygenation has obvious advantages, pulse oximeters may lack adequate sensitivity for hypoxemia in patients with darker skin and patients in shock. These limitations are concerning given the mandate to ensure that an updated definition advances equity in healthcare and is applicable across all patient populations, and because many patients with ARDS have poor systemic perfusion. Nevertheless, the committee thought that the ready availability of pulse oximetry in all healthcare settings outweighed the disadvantage of missing hypoxemia in some patients, because the overall effect will be to increase health equity in settings where ARDS is currently underdiagnosed.

• By using pulse oximetry to evaluate oxygenation, cases of ARDS that might be missed under the Berlin definition due to lack of availability of arterial blood gases or clinician under-recognition will be recognized and treated. However, the committee recommends that arterial blood gas measurement be made if there is uncertainty that would affect patient management. Research related to improving the performance of pulse oximeters in various populations is ongoing and will need to be incorporated into interpretation of SpO₂ as data become available. In addition, the United States Federal Drug Agency is working with manufacturers of oximeters to improve the efficacy of oximeters in people with darker skin.

• Several trials have enriched their populations for higher predicted mortality by including only patients with an enrollment PaO₂/FIO₂ < 150 mmHg, which is not a cutoff specified in the Berlin Definition. Clinical studies have shown that the Berlin severity categories identify increasing mortality with increasing severity, whether using the original PaO₂/FIO₂ ratios, or the SpO₂/FIO₂ imputations. There was no compelling evidence-based reason to change the severity categories, with the exception of allowing for corresponding SpO₂/FIO₂ values to meet the hypoxemia criterion for each category.