Acute Hypoxemic Respiratory Failure, Acute Respiratory Distress Syndrome
Conditions
Keywords
critical illness, intensive care unit, endotypes, phenotypes, emergency department, trajectory, mechanical ventilation, elderly, ageing
Brief summary
We attempt to perform dynamic endotyping of critically ill patients presenting in the emergency department with de novo acute hypoxemic respiratory failure (AHRF). We also attempt to identify what clinical, radiological, physiological and biological variables collected early in the course of AHRF correlate with subsequent mortality and/or persistent severe hypoxemia.
Detailed description
Rationale: Even before the pandemic of the new coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS), the most severe form of acute hypoxemic respiratory failure (AHRF), constituted a public health challenge. Despite the intense research on identifying targeted pharmacological therapies for ARDS, there is no available treatment for the syndrome. The failure of clinical trials exploring pharmacological therapies for ARDS has been attributed to incomplete understanding of the pathogenesis and heterogeneity of the syndrome. As examples of the heterogeneity of ARDS, our recent work has identified differential outcomes of patients with ARDS depending on whether hypoxemia is rapidly improving or persistent severe or associated with non-identifiable risk factors or associated with neutropenia. It is advocated that the heterogeneity of ARDS can be tangled by a precision approach, which identifies endotypes of ARDS; i.e., subtypes characterized by a distinct biological profile that might share mortality risk, clinical course, or treatment responsiveness. Notwithstanding their contributions, current research efforts on endotyping ARDS might be limited by the fact that they are based on the current conceptual framework of the syndrome, which has been widely questioned. Indeed, for reasons such as high interobserver variability of radiological criteria of ARDS and exclusion of patients requiring high-flow nasal oxygen, influential experts have even suggested to completely abandon the term. Objective: Accordingly, in the current study, we attempt to perform endotyping of critically ill patients presenting in the emergency department with de novo AHRF, which is a simpler and more reliable phenotype than ARDS. The approach for endotyping will be dynamic rather than static; i.e, two blood samples with a 24-hour interval will be used for endotyping to trace trajectories of biomarkers (over 1500 unique human proteins). In addition, we attempt to identify what clinical, radiological, physiological and biological variables collected early in the course of AHRF correlate with subsequent mortality and/or persistent severe hypoxemia. Thus, the research protocol is organized as 3 aims. Aim#1 will organize a registry and biobank of critically ill patients presenting in the emergency department with de novo AHRF. Aim#2 will build a predictive model to identify what variables among those collected in Aim#1 are associated with subsequent mortality and/or persistent severe hypoxemia. Aim#3 will use an agnostic discovery approach to explore novel proteomic biomarkers-based dynamic endotypes in critically ill patients presenting in the emergency department with de novo AHRF. Also, Aim#3 will create a multiprotein model of biomarkers associated with subsequent mortality and/or persistent severe hypoxemia and will determine whether inclusion of this multiprotein panel in the predictive score developed in Aim#2 improves risk prediction.
Interventions
None listed
Sponsors
Evangelismos Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (aged \>18 years) presenting in the emergency department * De novo acute hypoxemic respiratory failure (requiring oxygen flow rate of 5 liters per minute or more to maintain SpO2 of 90% or more)
Exclusion criteria
* Age \<18 years * Not admitted to the hospital * Postoperative acute respiratory failure (within one week from surgery) * Chronic hypoxemic respiratory failure (requiring long term oxygen therapy at home) * Hypercapnic respiratory failure * Transferred from another hospital or facility * Pregnant women * Admitted to the hospital purely to facilitate comfort care * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of dynamic endotypes of acute hypoxemic respiratory failure | Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department | Mutually exclusive subgroups of patients (clusters) characterized by a distinct biological profile that might share mortality risk, clinical course, and/or treatment responsiveness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department | To determine what variables among those collected, including protein biomarkers, are associated with subsequent all-cause mortality. |
| Persistent severe hypoxemia | Until 28 days following presentation to emergency department | To determine what variables among those collected, including protein biomarkers, are associated with persistent severe hypoxemia. We will consider that persistent severe hypoxemia is present in endotracheally intubated individuals receiving positive pressure ventilation and having a PaO2:FiO2 ratio of equal to or less than 100 mmHg at 48 hours following intubation. |
| Intensive care unit-free days | Until 28 days following presentation to emergency department | Intensive care unit-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not in the intensive care unit. |
| Vasopressor-free days | Until 28 days following presentation to emergency department | Vasopressor-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not receiving vasopressors. |
| Ventilator-free days | Until 28 days following presentation to emergency department | Ventilator-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not on a ventilator. |
| Continuous renal replacement therapy-free days | Until 28 days following presentation to emergency department | Continuous renal replacement therapy-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not receiving continuous renal replacement therapy. |
| Bacteremia | Until 28 days following presentation to emergency department | Bacteremia is determined by a positive blood culture. |
Countries
Greece
Contacts
CONTACTEleni D. Papoutsi, MD
PRINCIPAL_INVESTIGATORIlias I. Siempos, MD, DSc
Evangelismos Hospital
Outcome results
None listed