Impaired macroscopic CSF flow by sevoflurane in humans – both during and after anesthesia

Background: According to the model of the glymphatic system, the directed flow of cerebrospinal fluid (CSF) is a driver of waste clearance from the brain. In sleep, glymphatic transport is enhanced, but it is unclear how it is affected by anesthesia. Animal research indicates partially opposing effects of distinct anesthetics but corresponding results in humans are lacking. Thus, this study aims to investigate the effect of sevoflurane anesthesia on CSF flow in humans, both during and after anesthesia. Methods: Using data from a functional magnetic resonance imaging (fMRI) experiment in 16 healthy human subjects before, during, and 45 minutes after sevoflurane mono-anesthesia of 2vol%, we related grey matter blood-oxygenation-level dependent (BOLD) signals to CSF flow, indexed by fMRI signal fluctuations, across the basal cisternae. Specifically, CSF flow was measured by CSF fMRI signal amplitudes, global grey matter (gGM) functional connectivity by the median of inter-regional GM fMRI Spearman rank correlations, and gGM-CSF basal cisternae coupling by Spearman rank correlations of fMRI signals. Results: Anesthesia decreased cisternal CSF peak-to-trough amplitude (median difference Mdn-diff = 1.00, 95% CI [0.17 1.83], p = .013), disrupted the global, cortical BOLD-fMRI-based connectivity (Mdn-diff = 1.5, 95% CI [0.67, 2.33], p < 0.001) and, global grey matter (gGM)-CSF coupling (Mdn-diff = 1.19, 95% CI [0.36, 2.02], p = 0.002). Remarkably, the impairments of global connectivity (Mdn-diff = 0.94, 95% CI [0.11, 1.77], p = 0.022) and gGM-CSF coupling (Mdn-diff = 1.06, 95% CI [0.23, 1.89], p = 0.008) persisted after re-emergence from anesthesia. Conclusions: Collectively, our data show that sevoflurane impairs macroscopic CSF flow via a disruption of coherent gGM activity. This effect persists, at least for a short time, after regaining consciousness. Future studies need to elucidate whether this contributes to the emergence of postoperative neurocognitive symptoms, especially in older patients or those with dementia.