Science Questions

How does chloroform work to make you unconscious?

Tue, 22nd Mar 2016

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Question

Deeksha Hegde asked:

How exactly does chloroform make you unconscious? How does a slightly larger dose cause death?

Answer

We put Deeksha's question to resident chemist Ben Pilgrim... chloroform

Ben - The first thing to say is that the movies definitely have it wrong with regards to chloroform.  Chloroform has been used as an anesthetic for about 150 years and the kind of misconception that you have from watching movies is that by breathing a chloroform soaked rag you’ll knock someone out within a second or so.  This isn’t the case, you need to be breathing it for several minutes in order to make someone pass out and they need to be breathing it constantly in order to keep them passed out.  In fact, about 150 years ago, a famous medical journal, The Lancet, published a paper asking the criminal classes whether any one of them could divulge their supposed secret of being able to knock people out so quickly because it would be very, very useful for medicine.  Needless to say, no-one has come forward to this date.

Chris - It was called a blow to the head probably, wasn’t it rather than chloroform.  I think Queen Victoria was the first monarch to undergo a cesarean…

Ben - Yes for a couple of her last pregnancies.  How does it work - this is something of debate and, indeed, in all anesthetics there is considerable debate about how they actually cause someone to pass out.  Obviously they affect the nervous system.  One idea is they affect the flux of potassium irons and this affects the body’s response to nerves.  Another idea is that the chloroform interferes with the cell membranes and slows down the passage of nerves which makes people less likely to feel pain.  So there’s a couple of ideas about how it might work.  I should say, it was replaced because it was dangerous.  Dangerous for a couple of reasons; one is actually you just breath too much of the gas in your lungs and this fills up your lungs and stops your lungs getting enough oxygen and so you just die from not having enough oxygen.  But also, if you start fiddling around with the nervous system, then it can also cause people’s hearts to fail because hearts rely on electrical impulses to work and if you mess around with that, you can die of a heart attack.

Chris - So don’t do it is the bottom line because people do abuse other kinds of solvents like butane out of gas refills and glue because there are solvents in there, all because the work the same way…

Ben - Yes, very dangerous to breath in.

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As far as I understand it, the precise mechanism of action of small molecule anesthetics (like ethanol, chloroform, diethyl ether, triethylamine, Halothane, and even various solvents, xenon or high pressures of nitrogen) is not known. There is evidence that these molecules dissolve in the membranes and hydrophobic residues of neurons, thereby changing the activity of those neurons. GABA and NMDA pathways appear to be particularly important, but none of these molecules appears to be selective for one type of neuron over others--these are "general" anesthetics, and don't behave like targeted drugs such as opiates or benzodiazepines etc.

There have been some studies that showed that the effects of anesthetics to be essentially reversed in hyperbaric chambers (for instance http://www.ncbi.nlm.nih.gov/pubmed/2840107 and http://www.ncbi.nlm.nih.gov/pubmed/655442), but it is not exactly clear why this happens either. See also: https://en.wikipedia.org/wiki/Theories_of_general_anaesthetic_action

As to how these can lead to death--the extent to which these compounds inhibit neural activity is very much dose dependent: higher doses → less neural function. This includes the neural pathways that control breathing (and I think heart rate as well, though I could be mistaken), so too little neural activity leads to failure to breathe... chiralSPO, Tue, 23rd Feb 2016

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