Wake up!

Confession time. Each way when I go to work, I don’t entirely know what I’m doing. Yes, that’s right, when I’m doing that whole “helping kids sleep through their surgery” thing there’s a big black hole at the centre of my practice. Now, before anyone contacts the Tele so they can place a screeching headline at the top of their website (“BLACK HOLES IN THE OPERATING THEATRE”; “BEST GUESS: DOCTORS TESTING DRUGS ON KIDS”), that’s actually the reality of where we’re up to with anaesthesia.

After more than a decade of training, I am well qualified to assess a patient’s clinical condition, figure out what options are available to keep them comfortable and safe through the operative period and administer a combination of medicines to induce a level of unconsciousness so the patient isn’t aware of what is going on. That in itself feels like magic. Each work day I deliver anaesthesia to patients and it quite literally feels like seeing a miraculous phenomenon take place time after time.

What I’m struggling with is the exact mechanism of how the medicines induce that anaesthetised state. That’s not because it was one of those factoids I learnt for a period of 20 minutes around the exam and promptly let fall on the pavement outside (I refer to those factoids as “statistics”). It’s also not because no one can be bothered looking. People have proposed various mechanisms, such as specific receptors being the target for anaesthetic agents, or that they change the composition of cell membranes, thereby altering how key cells within particular brain pathways work. The problem has been that not all anaesthetic medications interact with the same receptors or pathways, which is disappointing if you’re the type of person who yearns for the certainty of a single unifying theory for any concept up for discussion.

So if you’re a gas geek, this week was particularly exciting. A group combining bright sparks from the University of Michigan and Asan Medical Centre, South Korea have published a paper which brings us a big step closer to knowing how anaesthetic agents produce their magic. It’s big news for anaesthesia, but I sort of think for our broader understanding of consciousness itself.

Anaesthesia has been around for a pretty decent amount of time now. Although there are earlier reports of anaesthetic use, modern inhalational anaesthesia is generally described as originating with the demonstrations of William Thomas Morton (a dentist probably quite happy showing his face in any media format). Having performed a painless tooth extraction on September 30, 1846 he was invited to perform a demonstration in the operating theatre at the Massachusetts General Hospital. This allowed Dr John Collins Warren to painlessly remove a neck tumour on October 16, 1846 after which he famously declared “Gentlemen, this is no humbug”.

Since then, anaesthesia has become a vital component of interventional medicine. While I’m obviously biased, it is one of the most important discoveries in medicine over the last couple of centuries, allowing progress in surgical science, whole new fields of treatment and the injection of a whole bunch of humanity into perioperative care. (I should point out that I am not suggesting that anaesthetics don’t have their side effects or bad bits, but this is the glass half full post.) Of course, anaesthesia is so well accepted as part of the furniture, there are plenty of people who aren’t entirely sure that anaesthetists are medically trained (we are), or assume that we got into it so we could avoid interaction with normal awake humans (mostly untrue) or that we spend most of our time doing crosswords (please, we have tablets now).

Now, to this discovery and a bit of background (stick with me, it won’t be that rough). One of the reasons that previous proposed mechanisms have faltered is that there are agents that work in distinctly different fashions. Many of the agents that produce anaesthesia potentiate the action of a particular neurotransmitter called gabba-aminobutyric acid (GABA). This has always made intuitive sense because, when binding with certain receptors, GABA produces neurones that are less able to get excited. Less excited equals less active equals more sleepy, right?

The problem is that some other agents in use, particularly ketamine, don’t do this at all. Ketamine (yep, Special K) is the classic example of a drug that interacts with N-methyl-D-aspartate (NMDA) receptors. So if you do an electroencephalogram (EEG) to monitor electrical activity in the cortex of the brain, unlike the GABA drugs, ketamine leaves you with a cortex that still looks busy.  Hmmm …

Now, a little about the brain. You probably know that jobs of the brains are associated in particular areas. Well, information flows between these areas. Information travelling from the frontal cortex to other bits of the cortex is sometimes called “feedback” or recurrent processing (at least in the anaesthetic literature). This feedback is thought to mediate conscious experience. Information flow from the posterior to anterior direction is thought to be key in sensory processing.

Now, the same group releasing their work this week previously showed that in a conscious person, the information flowing from the frontal lobe back to the parietal lobe dominates the information heading in the other direction. They also showed that this dominance is decreased by the anaesthetic agents that interact with GABA receptors. What they have now demonstrated is that this information flow is altered in the same way by ketamine. So the cortex might look busy, but the flow of information between the two areas is still disrupted. (I’m hyperventilating a little here, it’s really exciting.)

This story is great for a few reasons. One is that from the point of view of a purist, the application of a different form of analysis (Normalised Symbolic Transfer Entropy) to evaluate this association is interesting all on its own (although I’m not going to pretend all of the details have immediately washed in). It’s also a great example of the long, quiet pursuit for an answer finally coming a little closer to reality.

More broadly though, I quite like the idea that the consciousness of the individual is predicated on the flow of talk from one part of the brain to another, in the same way that our collective understanding of the world is so profoundly dependent on the way information flows from one group to another.

In the meantime, I can stop worrying quite so much about that black hole.


5 thoughts on “Wake up!

  1. Pingback: Total (Embellished) Recall and Anaesthetic Nightmares | The Flying PhD

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