Whether mechanical ventilation (MV) induces neurotoxicity that can trigger or accelerate chronic cognitive disorders is controversial. The relationship between MV and neurocognitive impairment, that persisted at hospital discharge and at 1-year follow up, was first reported in 1999 in MV-treated ARDS patients. Since then, several preclinical and clinical studies have investigated the mechanisms, localization, and timing of brain damage induced by MV and possible preventive/therapeutic strategies.

Growing preclinical and clinical evidence suggest that MV induces harmful effects on neurocognitive functions. It is not easy to discriminate whether these changes should be interpreted as direct MV-induced damage or as result of perioperative/critical care environment and preexisting frailty.

Given the importance to preserve patient’s cognitive functions, we consider it necessary to define a work-up dedicated to monitor neuroinflammation during MV that might include neuroinflammatory scavengers, immune modulation, DRD2-blockers, and lung “neuroprotective” MV management. The latter should encompass optimal MV setting, including low tidal volume, the lowest FiO2 needed, to maintain—when possible—PaCO2 within normal values and to warrant the shortest MV exposure.

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