The role of sevoflurane exposure on systemic inflammation and neuroinflammation: a systematic review and meta-analysis of in vivo and in vitro studies

Neuroinflammation induced by anaesthetics may negatively affect neurocognitive functions after surgery in humans. This systematic review and meta-analysis aimed to evaluate the impact of sevoflurane exposure on systemic inflammation and neuroinflammation and to assess alterations in behavioural/cognitive functions in experimental rodent models not exposed to surgery nor to other inflammatory stimuli. Databases were searched for in vivo and/or in vitro studies examining inflammation after sevoflurane exposure compared to control conditions. Inflammatory biomarkers, including interleukin (IL)-6, IL-1β, and tumour necrosis factor alfa (TNFα), at the peak time of production (primary outcomes) were investigated. The secondary outcome was to evaluate the presence of alterations in behavioural/cognitive tests. Subgroup analyses on young and adult rodents were performed for in vivo studies. Thirty-five in vivo and in vitro studies were selected. Results from meta-analyses demonstrated significant increases in the secretion peak of all inflammatory markers in in vivo models. Significantly higher plasma peaks of IL-6 (SMD: 7.97, 95% CI: 4.76-11.17), IL-1β (SMD: 5.71, 95% CI: 1.88-9.55) and TNFα (SMD: 6.64, 95% CI: 3.73-9.56) were found only in adult rodents exposed to sevoflurane. Similar findings were observed in brain tissue homogenates. Rodents exposed to sevoflurane exhibited significant alterations in behavioural/cognitive tests and significance persisted only in adult rodents. Sevoflurane exposure may trigger systemic inflammation and neuroinflammation in experimental rodent models with marked effects in adult rodents. Alterations in behavioural/cognitive tests suggest a potential role of sevoflurane in the development of postoperative cognitive disorders in the elderly, independently of surgery. Further research is needed in humans.