Hypersensitivity of the Anesthesia-Induced Comatose Brain

Increasing levels of anesthesia are thought to produce a progressive loss of brain responsiveness to external stimuli. Here, we present the first report of a state window within anesthesia-induced coma, usually associated with an EEG pattern of burst suppression, during which brain excitability is dramatically increased so that even subliminal stimuli elicit bursts of whole-brain activity. We investigated this phenomenon in vivo using intracellular recordings of both neurons and glia, as well as extracellular calcium and EEG recordings. The results indicate that the bursting activity elicited with mechanical microstimulations, but also with auditory and visual stimuli, is dependent on complex mechanisms, including modulation of excitatory (NMDA) components, gap junction transmission, as well as the extracellular calcium concentration. The occurrence of bursting events is associated with a postburst refractory period that underlies the genesis of the alternating burst-suppression pattern. These findings raise the issue of what burst spontaneity during anesthesia-induced coma means and opens new venues for the handling of comatose patients.