Neuroinflammation, neuronal damage or cognitive impairment associated with mechanical ventilation: A systematic review of evidence from animal studies

Purpose: Long-term cognitive impairment is a complication of critical illness survivors. Beside its lifesaving role, mechanical ventilation has potential complications. The aim of this study is to systematically review the evidence collected in animal studies that correlate mechanical ventilation with neuroinflammation, neuronal damage and cognitive impairment. Methods: We searched MEDLINE and EMBASE databases for studies published from inception until August 31st, 2020, that enrolled mechanically ventilated animals and reported on neuroinflammation or neuronal damage markers changes or cognitive-behavioural impairment. Results: Of 5583 studies, 11 met inclusion criteria. Mice, rats, pigs were used. Impact of MV: 4 out of 7 studies reported higher neuroinflammation markers in MV-treated animals and 3 studies reported no differences; 7 out of 8 studies reported a higher neuronal damage and 1 reported no differences; 2 out of 2 studies reported cognitive decline up to 3 days after MV. Higher Tidal volumes are associated with higher changes in brain or serum markers. Conclusion: Preclinical evidence suggests that MV induces neuroinflammation, neuronal damage and cognitive impairment and these are worsened if sub-optimal MV settings are applied. Future studies, with appropriate methodology, are necessary to evaluate for serum monitoring strategies. Trial registration number: CRD42019148935.