Towards Novel BIOmarkers to Diagnose SEPsis on the Emergency Room

Study Overview
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Brief Summary
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Objectives: To compare the immune response of patients with or without sepsis presenting to the ED with a(n) (suspected) infection. To determine immune response aberrations that are associated with an increased risk of developing sepsis in patients presenting to the ED with a(n) (suspected) infection without sepsis. To determine the long term cognitive and physical sequelae of sepsis after admission.

Detailed Description
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Sepsis will be defined in accordance with the current Sepsis 3.0 criteria as a(n) (suspected) infection with evidence of organ failure, as reflected by a SOFA (Sequential Organ Failure Assessment) score of ≥2. Notably, a molecular definition of sepsis does not exist and there is no pathological gold standard; therefore, in accordance with the current international consensus, the investigators consider the commonly used clinical organ failure (SOFA) criteria as the best option. The SOFA score is composed of six organ dysfunctions (cardiovascular, pulmonary, renal, hepatic, coagulation and neurological). The SOFA score was developed for ICU patients, but its components can be easily scored in an ED (and hospital ward) setting with the exception of the pulmonary component; this pulmonary dysfunction score is based on the PaO2/FiO2 (PF) ratio, wherein PaO2 is the partial pressure of oxygen in arterial blood and FiO2 the fraction of inspired oxygen. Measurement of the PaO2 requires an arterial blood puncture, which is not routinely done on the ER or hospital ward. Therefore, the investigators will use an alternative method to determine the respiratory SOFA by determining the SpO2/FiO2 (SF) ratio, wherein SpO2 is peripheral oxygen saturation. SpO2 is routinely measured by finger pulse oximeter in patients with suspected infection; FiO2 is 21% when breathing room temperature and increases by 4% with each liter of oxygen provided per minute to a patient via a nasal cannula. Cut-off values for SF ratios correlating with SOFA pulmonary scores based on PF ratios have been validated in large data sets.

Official Title
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Towards Novel BIOmarkers to Diagnose SEPsis on the Emergency Room

Conditions
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Infection, Bacterial, Infection Viral, Infections, Respiratory, Sepsis, Septic Shock, Sepsis, Severe, Infections

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or higher Presentation at the Emergency Department (ED) Clinical suspicion of infection or earlier confirmed infection Modified Early Warning Score (MEWS) of 2 or higher Exclusion Criteria: No informed consent given

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with infection<br>Patients with an (suspected) infection and a MEWS score 2 or higher | Other: No intervention<br>* There is no intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final diagnosis for hospitalization | Adjudicated diagnoses for hospitalization | 4 years | 
| Disease severity | Sequential Organ Failure Assesment (SOFA) score (minimum 0, maximum 24) collected during admission | During hospitalization (up to day 180) | 
| Mortality | Mortality at day 30 | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay | Both hospital and ICU stay | During hospitalization (up to day 180) | 
| Mortality | Hospital, ICU, 28-day, 90-day and 1 year mortality | 5 years | 
| Post-sepsis sequelae | Up to 1 year post sepsis, e.g. decreased executive functions, weakness, fatigue etc.) | Up to 1 year after sepsis episode | 
| Readmissions | All cause readmissions in the first year after discharge | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Emergency Room, A&E, Accident & Emergency