Sedation as an Immunomodulator of Inflammatory Responses in the Lung–Brain Axis of ARDS

Acute respiratory distress syndrome (ARDS) is characterized by systemic inflammation, immune dysregulation, oxidative stress, and frequent extrapulmonary organ involvement. Neurological complications of ARDS, such as neuroinflammation, cognitive impairment and delirium, are common and worsen outcomes. Early evidence highlights bidirectional communication between the lungs and brain, the lung–brain axis, through which inflammation may amplify both pulmonary and cerebral injury. This narrative review synthesizes recent experimental and clinical data on the immunomodulatory and neuroprotective effects of commonly used sedative agents in ARDS, focusing on their influence on inflammatory mediators (IL-1β, IL-6, IL-8, IL-10, TNF-α) and neuronal injury biomarkers (S100B, neuron-specific enolase). Sedative agents seem to exert effects beyond sedation by modulating systemic and neuroinflammatory responses. Evidence suggests they can influence cytokine profiles and reduce biomarkers associated with neuronal injury, potentially mitigating neuroinflammation and delirium in ARDS patients. Sedatives may modulate lung–brain crosstalk in ARDS through immunoinflammatory pathways, integrating sedative and neuroprotective effects. Mechanistic clarification may enable targeted sedation strategies to improve pulmonary and neurological outcomes.