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TERRY GROSS, host:

This is FRESH AIR. I'm Terry Gross.

Do you know what happens to your brain while you're under general anesthesia? Well, anesthesiologists aren't completely sure either. My guest, Dr. Emery Brown, is an anesthesiologist who's studying bring image who's using brain imaging to study what happens when you go under. Along with a sleep expert and an expert on coma, Dr. Brown co-authored a study on general anesthesia and its relationship to sleep and coma that was published last December in The New England Journal of Medicine.

What they're learning can help doctors better understand consciousness and sleep, and could lead to new treatments for pain and insomnia.

Brown is a professor of anesthesia at Harvard Medical School and a practicing anesthesiologist at Massachusetts General Hospital. He's also a professor in the department of brain and cognitive science at MIT.

Dr. Emery Brown, welcome to FRESH AIR.

When you say that anesthesia, when it puts you under you're not in a sleep-like state, you're in a state more closely resembling a coma. I get scared, because to me coma is something terrible. Coma is like when you're really ill or you've been in a terrible accident. So first of all, calm me down about the comparison to coma.

Dr. EMERY BROWN (Harvard Medical School): Well, I think you've hit at one of the key point of why it's been a challenge to explain exactly what we do.

When anesthesiologists typically talk with patients, we very often say - well, we virtually never say we're going to put you in a state of coma. We say we're going to have you go off to sleep. The only difficulty with that is that sleep is not the state you're going to be in, nor would it be the state in which someone could actually perform an operation on you.

So let's just define general anesthesia clearly. So it has, let's say, five components. So you're supposed to be unconscious, you're not supposed to hurt, you're not supposed to have pain, you're not supposed to remember, and we want to not move while someone is operating on you. And in addition to that, we want you be in stable physiologically - stable heart rate, stable blood pressure, temperature, breathing.

So the anesthesiologist takes over the physiology of the patient and controls it for the duration of the time that the patient is having surgery. Then by titrating very carefully the way the medications are given, when the surgery is over we can reverse the coma.

GROSS: So you've been doing imaging studies on the brain under anesthesia. The brain's under anesthesia, not you.

(Soundbite of laughter)

Dr. BROWN: Yes, exactly. Right, right.

GROSS: So what are you learning about what anesthesia actually does to the brain - which parts of the brain are shut down, which parts of the brain are still active?

Dr. BROWN: One of the most interesting things that we've noticed is that in addition to certain areas being turned off, certain other areas are, let's say, you know, turned on or more active. So for example, imagine to communicate between two brain regions you have like feedback loops. One area talks to the other and vice versa. So if you decrease the activity in one, what you may end up doing, if one area was inhibiting the other, once the first area's activity is decreased, the second area's activity could increase because it's no longer receiving that inhibition.

By the same token, you could have noise. In other words, you've turned off so many things that now there's effectively noise going between different brain regions and you couldn't communicate.

GROSS: Do different anesthetic drugs create different patterns in the brain?

Dr. BROWN: Oh, they certainly do. So let me just give you a couple of examples. So the standard drug, propofol, that is probably the most used anesthetic...

GROSS: Could we stop and say that's the one that Michael Jackson was using to, quote, sleep?

Dr. BROWN: That's the one that, as I understand it, he was supposedly taking to sleep. It is a very, very potent drug, and when you look at how it affects the brain, low doses of it actually cause a state of excitation. Then what you actually see next is the brain start to slow. So a period where the brain is actually active and then with higher doses, the brain starts to slow. All right?

So let's contrast that with ketamine. Ketamine is a drug that we use a lot in anesthesia and it's especially useful for reducing the amount of drugs that we have to give, let's say like the opioids to treat pain. In this case, ketamine actually causes an excited state, even at higher doses.

GROSS: I should say that ketamine is also used as a street drug, and as a street drug it's known as Special K.

Dr. BROWN: That's right.

GROSS: What kind of effect do people using it as a street drug get from this anesthetic drug?

Dr. BROWN: Well, that's just it. You see, it works by causing this excited state in the brain. So the level of the state of unconsciousness that you get with ketamine is created by making the brain active. Well, as you transition through this active state, you very frequently hallucinate. And it's these hallucinations or sense of euphoria or sometimes what's called a dissociative state that people who are using it a drug of abuse are seeking.

GROSS: Ketamine is also being researched for having possibilities with treating depression and chronic pain. How is ketamine being used in those settings now?

Dr. BROWN: Seemingly(ph) low doses of ketamine can be quite effective in treating patients that have chronic depression. And you know, if this turns out to be reproducible, you know, and every indication is that it will be, this could change tremendously how chronic depression is managed. Chronic depression is a very challenging disease because it takes often several months to get improvement in symptoms. And the thinking is it takes several months for the drug levels to reach where they need to be in order for the patient to feel better.

So with ketamine, for 70 to 80 percent of these patients, they felt better almost immediately and its effect could have lasted seven to 10 days. And this is an exciting finding because right now there is no way to make a chronically depressed patient feel better, you know, immediately.

GROSS: Now, some people who have had surgery under general anesthesia or who have had colonoscopies with - in a sedated state - swear that they were actually awake during the surgery or during the procedure, that they were in pain but they weren't able to communicate that because they were paralyzed by the drug.

And I always wonder, do they dream that, or did that really happen? And how often does that really happen, and how do you know whether it actually happened or whether it was a dream?

Dr. BROWN: Now, that's a good question, and in fact I think it's one of the major concerns that patients, you know, often have. Now, does it happen despite our best effort sometimes? Yes, I think that's the case. The times when it happens more predictably is usually in emergency settings. So perhaps, you know, maybe a woman coming to have an emergency cesarean section, and there's concern about how to titrate the level of anesthesia so you can take care of the mother, as well as the baby.

Or another case is, someone comes in with, you know, massive trauma, maybe from a car accident, maybe a gunshot wound. And again, you're trying to balance the perhaps side effects of the anesthetic on the heart, maybe the lungs, against trying to give the person appropriate level of anesthesia so he or she would be, you know, can tolerate the surgery that's necessary.

Now, there is one situation where historically there had been a fair amount of recall or awareness under anesthesia, and that was with heart surgery, because up until, you know, a few years ago it was done primarily using large doses of opioids. And even though patients were quite comfortable and there was no evidence of stress overtly, they would report having recall or having been aware of parts of the surgery.

GROSS: Well, if you're just joining us, my guest is Dr. Emery Brown. He's an anesthesiologist at Massachusetts General Hospital and a professor of anesthesia at Harvard Medical School. And he's using imaging to study how anesthesia affects the brain to produce a coma-like state.

Let's take a short break here, and then we'll talk some more. This FRESH AIR.

(Soundbite of music)

GROSS: We're talking about anesthesia and what we're learning about the brain and how the brain responds to anesthesia. My guest is Dr. Emery Brown. He's an anesthesiologist at Massachusetts General Hospital and a professor of anesthesia at Harvard Medical School. And he's been doing studies using imaging to see how anesthesia affects the brain to produce a coma-like state.

When you're administering anesthesia, do you have the patient count down backwards from a hundred?

Dr. BROWN: You know, actually I do, because I've been using it recently to demonstrate to the residents how quickly people lose consciousness under anesthesia and to give them a sense of how profoundly it occurs. So it sounds like something you see in the movies, but I actually do it because it's fairly impressive, and people rarely get beyond 90.

GROSS: And besides impressing people, why do you have them count down from a hundred?

Dr. BROWN: Oh, because - in other words, you can actually get a sense of how the drug - it's a little bit crude. But you can start to get a sense of how the drugs are actually affecting the brain. So some people start counting. They'll go 100, 99, 98, 97, um, um, 95, 94, 90. So they'll stop remembering. And so if you think about it, counting we think of as a very simple process, but it's actually fairly complex because you have to remember what you just said and to remember what the next number in sequence is and actually say it. So you can actually start to see the memory process even in that small time frame break down.

GROSS: Since you've been the studying the anesthesia-produced coma-like state, what are you learning about what happens to people in a coma-like state? And I guess what I'm specifically interested in hearing about here is, you know, a lot of people visit patients, visit loved ones who are in the hospital, in the coma, and want to know like if I talk to them, will they hear me? If I hold their hand, will they know I'm present? And I don't think we have any real evidence one way or another, but a lot of people just feel like they know, they know I'm here.

Dr. BROWN: Uh-huh.

GROSS: During the studies that you're doing, have they given you any insights?

Dr. BROWN: Well, when people have brain injuries, not all of the brain is damaged. And the brain is a very plastic entity, so areas that are not damaged may be able to take over, you know, certain functions, and certain functions can be rerouted. So what you could imagine is that if you had some sort of innovative way of communicating with a person, first looking to see what areas may be damaged and what areas are still functional, you might have some new ways of probing them so that you could communicate.

And there was a study that was done a few years ago in which a patient who used to be a tennis player was, you know, in a you know, one of the various levels of coma and they learned what areas of the brain are activated when let's say a serving motion is executed. And what they did was, with the same sort of perception you were talking about before, the perception that maybe this person was understanding the people around him, they asked him to think about executing the serve.

And they did a series of studies to understand like when they asked him to think about executing the serve, that was different from, let's say, you know, driving a car, executing some other motor task. And then they looked at other people doing the same thing and they were able to use that to demonstrate that they could communicate with this person because reliably on cue they could get this person to think about that particular activity and then demonstrate that he was understanding what the request was.

So in that sense now that you realize that you could, you know, that's one way, you know, one way of perhaps communicating with someone who is in a coma-like state if, again, there are areas which could be sufficiently activated or used, you know, to carry out that communication.

GROSS: So let me see if I understand this. You're saying if you said to this patient, imagine that you're serving the ball, and the part of their brain would light up on the imaging that they would use if they were serving a ball.

Dr. BROWN: Exactly.

GROSS: And you'd be able to see that so that you'd know that they were comprehending what you were saying when you said imagine you're serving a ball. And you'd know that some part of their brain is actually functioning and that they could hear you and interpret you.

Dr. BROWN: Right. Exactly. So now you could use that even just as set of binary choices. You could say, think about serving a ball if you would like me to call your mom, or something like that. Think about serving a ball to tell me that you want me to leave you alone. So now you have a way of actually - in sort of a binary sense - of being able to carry out a conversation to communicate with this person.

GROSS: In conducting this interview, I'm thinking about - the first time I was under anesthesia was when I had my tonsillectomy. I think I was probably around 10. And I was knocked out with ether, and I still remember what it smells like.

Dr. BROWN: Oh, really? Uh-huh.

GROSS: Yeah. And do they still use ether for...

Dr. BROWN: Well, we don't use...

GROSS: ...surgeries like that? Yeah.

Dr. BROWN: ...we don't use ether itself, but we do have inhaled drugs. And the inhaled drugs that we use today are derivatives of ether.

GROSS: Uh-huh.

Dr. BROWN: So in that sense we still do use ether-like compounds. You know, they've been made more stable, they are actually far less flammable than ether was. But we still use ether-like compounds.

GROSS: So ether was the first real anesthetic drug. You tell a great story about how ether was discovered.

Dr. BROWN: The first public demonstration of ether anesthesia took place at Mass General Hospital. That was October 16, 1846, by William Morton. What was transpiring at the time was that Morton himself was a dentist who was looking for a way to take care of his patients if he give them like a full set of dentures. But to do that he had to remove all their teeth.

So he was looking for a way to provide anesthesia for that. And you know, at the time ether was - it was around. In fact, there is a practice called ether follies, in which people would sniff ether for the purpose of getting high. And Morton, you know, realized that someone had gone too far at one point and had a cut and didn't perceive the cut because of the ether and he reasoned that perhaps he could use this as an anesthetic. And he proposed it to John Collins Warren, who was the surgeon at Mass General at the time, and he proposed trying this.

And so this is the famous, you know, public demonstration of ether that took place in 1846, where Morton built this flask, which is this sort of glass structure with a sponge inside and which, you know, he used to deliver the ether vapors to Gilbert Abbott, who was a gentleman who had a tumor on his neck that Dr. Warren wanted to remove. And he did this, he delivered the ether, the surgery was a success, and afterwards Dr. Warren said this is no humbug, and that was heralded in as the start of the use of the practice of ether for anesthesia.

GROSS: So have you ever been in state of general anesthesia for surgery?

Dr. BROWN: No, I haven't.

GROSS: Aren't you curious?

Dr. BROWN: Uh...

GROSS: I don't mean that you should have surgery.

(Soundbite of laughter)

Dr. BROWN: No, I mean I see it enough. I mean, so...

(Soundbite of laughter)

Dr. BROWN: I see it enough to have a good perspective on what's going on. I mean, I am part of the over 50 club, so I have had a colonoscopy. So I've had the sedation.

GROSS: Now, in an interview with you in The Boston Globe, you were asked why you chose anesthesia as your specialty, and you said you always knew you wanted to be a physician, and then you added: I know this sounds corny but some of the best times I had as a child was going to see my pediatrician. And I thought, what? I never enjoyed that. What did you like about seeing your pediatrician?

Dr. BROWN: Oh, my pediatrician in particular, ironically his name was Dr. Butcher(ph).

(Soundbite of laughter)

Dr. BROWN: He didn't spell it as butcher. There was actually an extra S in there.

GROSS: Uh-huh.

GROSS: But what just - I remember to this day he always listened. I mean, he made me feel like I was, you know, a young adult, as opposed to a kid coming to see him. And as well, his partner, Dr. Richardson, who was exactly the same way. I mean, I just have very, very vivid memories of that. (Unintelligible) that little tidbit - one of my true confessions there.

GROSS: All right. With that concession, I want to thank you so much for talking with us. It's really been interesting.

Dr. BROWN: Oh, thank you very much for having me.

GROSS: Dr. Emery Brown is a professor of anesthesiology at Harvard Medical School and is a practicing anesthesiologist at Massachusetts General Hospital. On or website you'll find a complete text of the article he co-authored, "General Anesthesia, Sleep and Coma," which was published in The New England Journal of Medicine. That's freshair.npr.org.

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