Sepsis, Septic Shock
Conditions
Keywords
Sepsis, Delirium, Post intensive care syndrome, Biomarkers, NSE, NFL
Brief summary
To evaluate the value of biomarkers of neuronal and glial injury for predicting cognitive impairment (memory impairment assessed by a MoCA score \< 26/30) at 3 months in patient admitted in the intensive care unit for a sepsis or a septic shock.
Detailed description
Sepsis is a major cause of admission to intensive care units and is responsible for approximately 11 million deaths worldwide each year. It may be complicated by an acute brain dysfunction known as sepsis-associated encephalopathy (SAE), which affects about 50% of patients and typically manifests as delirium or coma. The diagnosis of SAE is primarily clinical, with EEG and brain MRI providing supportive information. Risk factors for SAE are mainly related to patient characteristics, including advanced age, chronic kidney disease, and pre-existing neurodegenerative or cognitive disorders. The pathophysiology of SAE involves three major mechanisms: neuroinflammation, endothelial dysfunction with blood-brain barrier disruption, and mitochondrial dysfunction leading to neuronal injury. These mechanisms likely explain both acute neurological symptoms and long-term psycho-cognitive sequelae. Following sepsis, 30-60% of patients develop psychiatric disorders and cognitive impairments comparable to those observed after moderate traumatic brain injury or early Alzheimer's disease. These sequelae are part of post-intensive care syndrome (PICS), supporting the need for structured post-ICU follow-up. However, the optimal target population and organization of such follow-up remain unclear, as some studies have reported reduced quality of life in patients receiving long-term follow-up. Identifying early biomarkers predictive of psycho-cognitive outcomes is therefore crucial, as current data on neuronal and glial biomarkers remain limited. Such biomarkers could improve prognostication, guide cognitive rehabilitation and psychological support, and contribute to the development of future neuroprotective strategies. Primary objective: To evaluate the value of biomarkers of brain injury for predicting cognitive impairment (memory impairment assessed by a MoCA score \< 26/30) at 3 months. Secondary objectives: * To evaluate the value of brain injury biomarkers for predicting delirium in the ICU, including hypoactive, hyperactive, and mixed phenotypes * To assess the association between brain injury biomarkers and the duration of delirium in the ICU * To evaluate the value of brain injury biomarkers for predicting psychological sequelae (anxiety, post-traumatic stress disorder, and depression) at 3 months * To evaluate the value of brain injury biomarkers for predicting functional neurological outcomes using the Glasgow Outcome Scale-Extended at ICU discharge and at 3 months * To assess the association between brain injury biomarkers and Post-Intensive Care Syndrome (PICS) * To assess the association between brain injury biomarkers and EEG abnormalities in the ICU * To assess the association between brain injury biomarkers and MRI abnormalities at 3 months
Interventions
BIOLOGICALSerum
Neurofilament light chain NfL, brain-derived tau, GFAP, UCHL1, p-tau217, s100B, neurone specific enolase NSE, sTREM2, YKL-40
Sponsors
Assistance Publique - Hôpitaux de Paris
URC-CIC Paris Descartes Necker Cochin
ANR and Ministry of Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18-80 years. * Admission to a medical or mixed ICU. * Sepsis or septic shock according to Sepsis-3 criteria. * ICU admission for less than 24 hours. * Need for invasive or non-invasive mechanical ventilation and/or vasopressor support. * Informed consent obtained from the patient or legal representative.
Exclusion criteria
* Moribund patients. * Age \>80 years. * Patients under legal guardianship. * History of schizophrenia or bipolar disorder. * Pregnancy. * No health insurance coverage. * Previous inclusion in the study. * Refusal to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive function impairment assessed by the Montreal Cognitive Assessment (MoCA) score at 3 months | 3 months | Montreal Cognitive Assessment (MoCA) ranges from 0 to 30 points, with higher scores indicating better cognitive performance. Cognitive impairment will be defined as a MoCA score \<26/30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coma- and/or delirium-free days | Day 10 after inclusion | — |
| Duration of delirium in the intensive care unit (ICU) | 3 months | — |
| Type of ICU delirium: hypoactive, hyperactive, or mixed | 3 months | — |
| Psychiatric disorders (anxiety, depression : ( 0 =min; 21 =max) , or PTSD) | 3 months | — |
| Glasgow Outcome Scale-Extended (GOSE) | 3 months | — |
| Delirium duration | 3 months | Number of ICU days with delirium assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Delirium duration will be reported as the cumulative number of ICU days with at least one positive CAM-ICU assessment. Higher values indicate longer delirium duration. |
| Delirium phenotype | 3 months | ICU delirium phenotype classified as hypoactive, hyperactive or mixed according to CAM-ICU and RASS assessments. Results will be reported as the proportion of patients in each category. |
| Psychiatric outcomes | 3 months | Symptoms of anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS; higher scores indicate greater symptom severity). PTSD assessed using the PTSD Checklist (PCL-5). Results will be reported as continuous scores and proportions of patients above validated thresholds |
| Functional outcome | 3 months | Functional neurological outcome assessed using the Glasgow Outcome Scale-Extended (GOSE; range 1-8, higher scores indicate better functional recovery). |
| PICS : Post-Intensive Care Syndrome (PICS) | 3 months | PICS is defined by the presence of cognitive impairment, psychiatric symptoms and/or physical disability at 3 months. Results will be reported as the proportion of patients fulfilling at least one PICS domain. |
| Neurological, psychiatric, or rehabilitation follow-up proposed to the patient | 3 months | Referral for specialized follow-up after ICU discharge. This outcome will be reported as the proportion of patients referred to neurological consultation, psychiatric consultation, cognitive rehabilitation, physical rehabilitation and/or a multidisciplinary post-ICU clinic. |
Countries
France
Contacts
CONTACTSarah BENGHANEM, Dr
CONTACTAdèle BELLINO
PRINCIPAL_INVESTIGATORSarah BENGHANEM, Dr
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed