Ageing and anaesthetic sensitivity: the role of inflammaging in the vulnerable surgical brain

Ageing surgical patients demonstrate increased vulnerability to anaesthetic agents, including heightened sensitivity, reduced drug requirements, and delayed emergence, and they are also at increased risk of postoperative complications such as delirium and haemodynamic instability. These phenomena are only partially understood and have traditionally been attributed to the global functional decline associated with ageing. However, emerging preclinical and clinical evidence suggests that inflammaging and related neuroimmune alterations, including peripheral macrophage activation, blood-brain barrier dysfunction, and immune-to-brain signalling, may also modulate anaesthetic response. This narrative review examines current evidence on anaesthetic sensitivity in older adults, the role of macrophage phenotypes in ageing, and the mechanisms by which neuroinflammation may alter neuronal excitability, synaptic function, and electroencephalographic markers of anaesthetic depth. It also reviews methodological approaches ranging from rodent models to biomarkers such as the cerebrospinal fluid to plasma albumin ratio and EEG-derived indices. Overall, the available literature supports a biologically plausible link between age-related immune dysregulation and altered anaesthetic sensitivity, while also suggesting that these same pathways may contribute to broader perioperative brain vulnerability, including postoperative delirium. Direct clinical evidence remains limited, however, and many mechanistic links continue to rely on extrapolation from preclinical models. Further integrative perioperative studies combining immunological profiling, neurophysiological monitoring, and pharmacodynamic modelling are needed to clarify how neuroimmune ageing influences anaesthetic brain sensitivity in older adults.