Acute respiratory distress syndrome (ARDS) is characterized by pathological pulmonary edema caused by direct or indirect damage to the alveolar-capillary membrane.
Its management relies on etiological treatment, invasive mechanical ventilation, and the use of sedatives and neuromuscular blockers, depending on the patient's condition.
Improvements in patient care have led to an improved prognosis. However, in-hospital mortality remains high (between 35% and 45%). Notably, morbidity among surviving patients is very high and is largely dominated by neuropsychological sequelae. Attention and executive function disorders, confusion, disorientation, or memory impairment are thus found in 70 to 100% of patients following ARDS. These disorders are still present in 46 to 80% of surviving patients one year after ARDS and in 20% of them five years later.
Although essential to treatment, mechanical ventilation carries a risk of significant complications. Beyond the risk of infection and complications related to sedation and neuromuscular blockade, the use of mechanical ventilation is associated with a risk of ventilator-induced lung injury (VILI).
The use of so-called protective ventilation reduces the risk of VILI and improves patient outcomes. However, analysis of relevant physiological parameters shows that the risk of VILI may still exist even when ventilator settings comply with recommendations and the concept of protective ventilation. Driving pressure (which represents Strain) is a good marker of VILI; it represents the distension of the lung with each breath relative to the initial lung volume. Values above 14 cmH₂O are associated with high mortality in patients with ARDS. Inspiratory transpulmonary pressure represents Stress-that is, the pressure that distends the alveoli at the end of inspiration-and is also associated with the risk of VILI. Finally, mechanical power represents the amount of energy delivered to the lung by the ventilator and has been validated as a marker of VILI. The advantage of mechanical power over the other indices described is that it incorporates all components that can lead to VILI.
Among the various sources of neurological damage during ARDS, inflammatory processes appear to play a major role. Numerous inflammatory mediators (TNF-α, IL-6, IL-8, IL-1β) are secreted during ARDS, and animal studies have demonstrated a link between inflammation and hippocampal damage. Furthermore, cerebral ischemic lesions, exacerbated by systemic inflammation and endothelial activation leading to coagulation activation with thrombus formation, may also contribute to the development of cognitive impairments.
In addition to the inflammatory processes associated with ARDS, mechanical ventilation itself may have a significant impact on neuroinflammatory damage. Recently, the term "ventilator-associated brain injury" (VABI) has been proposed to describe these secondary neurological lesions induced by mechanical ventilation. Studies in mouse and pig models have demonstrated a relationship between the dose and duration of VILI, apoptosis, neuroinflammation, and neuronal damage. An animal study in mice also showed an association between the duration of mechanical ventilation and the onset of cognitive impairments.
During brain injury, proteins and neurotransmitters are released and serve as biomarkers of brain damage. Elevated plasma levels of S100B protein indicate astrocyte damage caused by traumatic, anoxic-ischemic, or inflammatory mechanisms. It correlates with neurological prognosis following cardiac arrest, in ischemic or hemorrhagic strokes, in neurodegenerative diseases, and in patients with traumatic brain injury.
Clinical studies have shown a negative correlation between elevated S100B protein levels, the MoCA (Montreal Cognitive Assessment) score, and the MMSE (Mini-mental state evaluation ) in patients with OSA (Obstructive Sleep Apnea) or COPD (chronic obstructive pulmonary disease), respectively, indicating an association between this protein and cognitive impairment.
The investigators therefore hypothesize that mechanical ventilation associated with high mechanical power is linked to a significant risk of brain injury, reflected by elevated serum S100B protein levels and the presence of neurocognitive disorders long after ARDS.
Adult patient
Patient admitted to the intensive care unit less than 48 hours ago
Mild ARDS: 200 < PaO₂/FiO₂ < 300 mmHg
Moderate ARDS: 100 < PaO₂/FiO₂ < 200 mmHg
Patients with a history of central nervous system disorders resulting in cognitive impairment
Patients on ECMO
Patients admitted for symptomatic central nervous system disorders
Patients admitted for acute respiratory distress syndrome following cardiorespiratory arrest.
Single group
Blood test scores calculations
Other interventioncollection of oesophageal pressure data, mechanical power calculation, MOCA score collection and blood sample collection for S100B protein dosage
association between the mechanical power between Day 1 and Day 3 (reflecting the risk of VILI)
mechanical power calculation
S-100B serum protein level between Day 1 (H0) and Day 3 (H72).
S-100B protein dosage
association between serum S100B protein concentrations from day 1 to day 3 and neurological outcome at 3 months and 12 months
Correlation coefficient between S-100B protein levels from Day 1 to Day 3 and the MOCA (Montreal Cognitive Assessment) score at 3 and 12 months (no neurocognitive impairment if MOCA ≥ 26/30, neurocognitive impairment if \< 25/30).
association between other VILI markers (inspiratory transpulmonary pressure and driving pressure) and serum S100B protein concentrations from day 1 to day 3.
Correlation coefficient between inspiratory transpulmonary pressure and driving pressure, and serum S-100B levels between Day 1 and Day 3, whilst accounting for potential confounding factors in a multivariate model
association between these other VILI markers and neurological outcomes at 3 months and 12 months.
Correlation coefficient between mechanical power, inspiratory transpulmonary pressure and driving pressure (average of values measured between J1 and J3) and the MOCA score at 3 and 12 months, taking potential confounding factors into account in a multivariate model
association between the occurrence of delirium during a stay in the intensive care unit and neurological outcomes at 3 and 12 months.
The occurrence of neurocognitive impairment, defined as a MoCA score of \<25/30 at the 3- and 12-month assessments, in patients who experienced delirium in the intensive care unit compared with those who did not.
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