• Conference Reports and Expert Panel
• Open Access
• Published: 16 June 2023

ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies

Grasselli, G., Calfee, C.S., Camporota, L. et al.

Intensive Care Med (2023). https://doi.org/10.1007/s00134-023-07050-7

Domain 1: ARDS definition

Domain 2: ARDS phenotyping

Question 2.1: How do we define an ARDS sub-phenotype?

Based on the currently available literature and consensus within the working group, the following definitions were established:

1. A phenotype is a clinically observable set of traits resulting from an interaction of genotype and environmental exposures (i.e., ARDS is a phenotype).
2. A subgroup is a subset of patients within a phenotype, which may be defined using any cut-off in a variable. This cut-off can be arbitrary, and frequently patients fall just on either side of it, resulting in patients switching subgroups (e.g., PaO₂/FiO₂ severity classification of ARDS).
3. A sub-phenotype is a distinct subgroup (of ARDS patients) that can be reliably discriminated from other subgroups based on a set or pattern of observable or measurable properties. Discrimination is typically based on a data-driven assessment of a multidimensional description of traits. Subphenotypes should also be reproducible in different populations.
4. An endotype is a sub-phenotype with distinct functional or pathobiological mechanism, which preferably responds differently to a targeted therapy.

Question 2.2: How do we identify or operationalize an ARDS sub-phenotype?

Question 2.3: What is the evidence for heterogeneity of treatment effect (predictive enrichment) between sub-phenotypes?

Question 2.4: How does sub-phenotyping relate to patient outcome (prognostic enrichment)?

Question 2.5: What are the research questions related to the use of sub-phenotyping for future trials?

Domain 3: High-flow nasal oxygen

Question 3.1: In non-mechanically ventilated patients with acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema or acute exacerbation of chronic obstructive pulmonary disease (COPD), does HFNO compared to conventional oxygen therapy (COT) reduce mortality or intubation?

Recommendation 3.1
We recommend that non-mechanically ventilated patients with AHRF not due to cardiogenic pulmonary edema or acute exacerbation of COPD receive HFNO as compared to conventional oxygen therapy to reduce the risk of intubationStrong recommendation; moderate level of evidence in favor
We are unable to make a recommendation for or against the use of HFNO over conventional oxygen therapy to reduce mortalityNo recommendation; high level of evidence of no effectThis recommendation applies also to AHRF from COVID-19Strong recommendation; low level of evidence in favor for intubation and no recommendation; moderate level of evidence of no effect for mortality, for indirectness.

Question 3.2: In non-mechanically ventilated patients with AHRF not due to cardiogenic pulmonary edema or acute exacerbation of COPD, does HFNO compared to non-invasive ventilation reduce mortality or intubation?

Recommendation 3.2
We are unable to make a recommendation for or against the use of HFNO compared to continuous positive airway pressure (CPAP)/NIV to reduce intubation or mortality in the treatment of unselected patients with acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema or acute exacerbation of COPD.No recommendation; moderate level of evidence for mortality, low level of evidence for intubation, not in favor nor against.
We suggest that CPAP/NIV can be considered instead of HFNO for the treatment of AHRF due to COVID-19 to reduce the risk of intubation (weak recommendation, high level of evidence), but no recommendation can be made for whether CPAP/NIV can decrease mortality compared to HFNO in COVID-19.No recommendation; high level of evidence of no effect.

Domain 4: CPAP/NIV

Question 4.1: In non-mechanically ventilated patients with AHRF not due to cardiogenic pulmonary edema, obesity hypoventilation or acute exacerbation of COPD, does CPAP/NIV, as compared to conventional oxygen therapy reduce mortality or intubation?

Recommendation 4.1
We are unable to make a recommendation for or against the use of CPAP/NIV compared to conventional oxygen therapy for the treatment of AHRF (not related to cardiogenic pulmonary edema or acute exacerbation of COPD) to reduce mortality or to prevent intubation.No recommendation; high level of evidence for mortality, moderate level of evidence for intubation.
We suggest the use of CPAP over conventional oxygen therapy to reduce the risk of intubation in patients with acute hypoxemic respiratory failure due to COVID-19.Weak recommendation; low level of evidence in favor.
In this population, we are unable to make a recommendation for or against the use of CPAP over conventional oxygen therapy to reduce mortality.No recommendation; moderate level of evidence of no effect.

Question 4.2: In patients being treated with CPAP/NIV for AHRF, does the use of a helmet interface as compared to face mask reduce intubation or mortality?

Recommendation 4.2
We are unable to make a recommendation for or against the use of helmet interface for CPAP/NIV as compared to face mask to prevent intubation or reduce mortality in patients with acute hypoxemic respiratory failure.No recommendation; very low level of evidence in favor.

Question 4.3: In patients with AHRF, does NIV as compared to CPAP reduce mortality or intubation?

Recommendation 4.3
We are unable to make a recommendation for or against the use of NIV compared to CPAP for the treatment of AHRF.No recommendation; no evidence.

Domain 5: Low tidal volume ventilation

Question 5.1: In adult patients ARDS and COVID-19-related ARDS, does low tidal volume ventilation alone compared with more traditional approaches to ventilation decrease mortality?

Recommendation 5.1
We recommend the use of low tidal volume ventilation strategies (i.e., 4–8 ml/kg PBW), compared to larger tidal volumes (traditionally used to normalize blood gases), to reduce mortality in patients with ARDS not due to COVID-19.Strong recommendation based on expert opinion despite lack of statistical significance; high level of evidence.
This recommendation applies also to ARDS from COVID-19.Strong recommendation; moderate level of evidence for indirectness.