Anaesthetics usually knock you out like a light. But by slowing the process down so that it takes 45 minutes to become totally unresponsive, researchers have discovered a new signature for unconsciousness. The discovery could lead to more personalised methods for administering anaesthetics and cut the risks associated with being given too high or too low a dose. It also sheds new light on what happens to our brain when we go under the knife.

Hundreds of thousands of people are anaesthetised every day, yet researchers still don’t fully understand what’s going on in the anaesthetised brain. Nor is there a direct way of measuring when someone is truly unresponsive. Instead, anaesthetists rely on indirect measures such as heart and breathing rate, and monitoring reflexes.

To investigate further, Irene Tracey and her colleagues at Oxford University slowed the anaesthesia process down. Instead of injecting the anaesthetic propofol in one go, which triggers unconsciousness in seconds, the drug was administered gradually so that it took 45 minutes for 16 volunteers to become fully anaesthetised. Their brain activity was monitored throughout using electroencephalography (EEG). The study was then repeated on 12 of these volunteers using functional magnetic resonance imaging (fMRI).

EEG recordings revealed that before the volunteers became completely unresponsive to external stimuli they progressed through a sleep-like state characterised by slow-wave oscillations – a hallmark of normal sleep, in which neurons cycle between activity and inactivity. As the dose of anaesthetic built up, more and more neurons fell into this pattern, until a plateau was reached when no more neurons were recruited, regardless of the dose administered.

Interestingly, the time it took to reach this plateau varied from individual to individual, and seemed to be determined by the number of neurons people possessed – something that decreases as we age.

Meanwhile, fMRI revealed what was happening in different regions of the brain as they lost consciousness. One theory is that an anaesthetic switches off one of the brain’s central relay hubs, the thalamus, meaning it no longer speaks to the cerebral cortex. However, Tracey’s team found that conversations between the cortex and the thalamus continued, even during deep anaesthesia – but there was no propagation of messages to wider regions of the brain.

“The thalamus is actually in a lot of dialogue with the cortex, but because it’s in this lockdown, sensory events that normally come into the cortex and would be routed out to the logical parts of the brain so that you could perceive ‘ouch that hurts’, is not happening,” says Tracey. “To have true perception you’ve got to have all the right bits active and their activity coordinated.”

Importantly, the point at which messages stopped being routed out was the same point at which the slow-wave oscillations reached a plateau. The hope is that this “saturation point” could be used as a measure of when to stop administering drugs, to reduce the risk of side effects such as headaches, dizziness and memory loss.

The next step is to monitor anaesthetised patients while they are undergoing surgery.

Journal reference: Science Translational Medicine, doi.org/ph4