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CASE NOTES
Tuesday 17 October 2006, 9.00-9.30pm
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BRITISH BROADCASTING CORPORATION



RADIO SCIENCE UNIT



CASE NOTES

Programme 5. - Nausea



RADIO 4



TUESDAY 17/10/06 2100-2130



PRESENTER:

MARK PORTER



CONTRIBUTORS:

PAUL ANDREWS

KEITH MYERSON

NICOLA STONER

MICHAEL GRESTY




PRODUCER:

ELIANE GLASER



NOT CHECKED AS BROADCAST




PORTER

Hello. Today's programme is all about nausea. What makes us feel sick - and why? And what can we do about it?



I'll be meeting one of the UK's leading lights in the field of motion sickness who, with the help of various machines in his basement, demonstrates how nausea can be induced by the simplest of movements.



CLIP

In a moment I'm going to ask you to just tilt your head down on to your chest and then I'll say quickly back up again. Now tilt down.



Oh oh yeah, that's amazing.



Now you felt almost instant nausea yes?



Yeah.



PORTER

My guest today is Paul Andrews, Professor of Comparative Physiology at St George's, University of London.



Paul, movement aside, what other triggers for nausea are there, and what do they have in common, why do they make us feel sick?



ANDREWS

Well I think the first thing we need to do really is to define what we mean by nausea in distinction from vomiting. Nausea is the unpleasant sensation which is associated with the urge to vomit or the feeling that vomiting is imminent. And that distinguishes it from vomiting which is the actual oral forceful expulsion of material from the stomach. Those - both of them - can be invoked by a wide range of stimuli, we've heard about pregnancy sickness and motion but there are a range of drugs, for example, particularly chemotherapeutic drugs that have nausea and vomiting as side effects, some interventions such as surgery with surgery with post-operative nausea and vomiting, infections, particularly of the gastrointestinal tract, obstruction of the gut but also there are a number of rare syndromes such as cyclical vomiting syndrome which has associated nausea which is particularly common in some children.



PORTER

And what's the relationship between the sensation of nausea and the actual final act of vomiting - is it just a continuum?



ANDREWS

It's not necessarily a continuum, nausea can occur in isolation, as can vomiting, but the normal route is that nausea precedes vomiting. So one hypothesis about why this may be the case is that nausea could be viewed as the warning and therefore is due to low level activation of the pathways which when activated more intensely could lead to full vomiting.



PORTER

You talk about pathways there, is there a part of the brain that's responsible for this sensation of nausea?



ANDREWS

We don't really understand the brain pathway that's finally responsible for the genesis of this conscious sensation. Clearly the signals must reach the higher levels of the nervous system but we really don't know what the pathways are and it's clearly an area we need to understand more.



PORTER

Presumably the fact that there are so many triggers, so many different things that can make us feel sick, and that suggests that there are lots of different pathways involved.



ANDREWS

I think it's likely that there's probably a single area of the brain, of the higher parts of the brain, where the sensation is finally generated but of course there are multiple roots into that final common pathway.



PORTER

Well we talked about early pregnancy being associated with feeling sick and in case you're in any doubt just how awful some pregnant women can feel hear the experience of three mums to be that we met at an antenatal class at the Royal Victoria Infirmary in Newcastle.



VOX POPS

When I first fell pregnant I wasn't physically sick I just felt very nauseous and to help with that I used to buy the ginger fizzy drink and I used to have the ginger biscuits which did help but the thing I think helped the most - a cracker biscuit, plain - and I used to continue to have those throughout the day and it definitely did help, definitely. And then after about three months it disappeared. But the funniest thing was I had a new fitted kitchen put in and every time I went into this new kitchen and me cooker was turned on it used to just make it worse and worse. It was actually the smell of a new cooker which used to turn my stomach, which was quite sad really because I'd waited for this new kitchen for years and when it did eventually come I couldn't sit in it for three months.



It started I think it was six weeks exactly and I woke up and I was literally - well I basically vomited continuously for about four or five days. I couldn't get out of bed, it was pretty horrible and it just gradually eased off but I was put on some tablets to help and it stopped at about 22 weeks. They were just like basic - I think they were just like travel sickness tablets. It was absolutely horrible and it was horrible for you wasn't it because it completely took over our lives, it was just horrid. Travelling by car anywhere was horrendous, you could always guarantee I would be sick if I went anywhere in a car, even for 15 minutes. As soon as I got the slightest bit hungry I would be sick, so I had to eat a lot, I still do. Now if I meet any other pregnant person who says they've been sick, you know they've had morning sickness, I have so much more sympathy because before I just assumed it was just something that you just felt - woke up in the morning, felt a bit nauseous and it went and now I realise it's something else completely.



I was never ever sick, I just felt sick, which is worse I think. Because I think if you can actually be sick then you can relieve the feeling but the actual feeling sick is the worst. Your sense of smell is really, really strong, that made me feel sick more than anything just opening the fridge and all the different smells, it really, really puts you off. And it just makes you not want to eat which has a kind of a vicious circle because if you eat you feel better. Sometimes strong smells like people's perfume, sometimes cleaning fluids as well, used to make me feel sick thinking about it. I actually went and got some, from the chemist, some ginger gum which was really good as well and just eating dry biscuits was good. Also in bed first thing in the morning, didn't get out of bed until you've had something to eat, that's my advice.



PORTER

And very good advice it is too.



You are listening to Case Notes, I'm Dr Mark Porter and I am discussing nausea with my guest physiologist Professor Paul Andrews.



Paul, why do so many pregnant women feel sick? Do we understand morning sickness?



ANDREWS

I don't think we understand the exact mechanism by which morning sickness is generated or more correctly I think pregnancy sickness …



PORTER

Yes it's not just in the morning is it no.



ANDREWS

It's not just in the morning and in fact a survey we did a number of years ago showed that in most women it was as common at other times of day as in the morning. We don't know what the basic mechanism is but of course it's likely to be associated with the hormonal changes which occur in early pregnancy.



PORTER

And the fact I suppose that it settles towards - as you get towards the halfway mark in most women it eases doesn't it, does suggest that.



ANDREWS

It does, it spontaneously resolves in the majority of cases.



PORTER

You look them confidently in the eye and say you will feel better soon. I mean there were some common themes from those women in Newcastle there, firstly that paradoxically and while they may not feel like eating they found that if they avoided food, if they didn't eat, they actually felt worse.



ANDREWS

Yes and I think this is quite a common finding. Certainly in a survey that we did about half of the women who experienced nausea felt better if they ate a small amount, I emphasise a small amount, of carbohydrate, such as a biscuit and quite often people are eating - nibbling ginger biscuits and anecdotally people say that that helps.



PORTER

So this is the basis of the current medical advice - that you give little and often really if you have morning sickness. Let's go back to the ginger, I mean all three women there mentioned ginger, is there any evidence to back its use?



ANDREWS

There are a number of studies that suggest that ginger root extract may have some efficacy in early - in sickness in early pregnancy and gradually we're beginning to understand rather more about the pharmacological effects of ginger itself. But of course one always has to be very careful about the safety issues of taking anything in early pregnancy.



PORTER

Any idea how it might be working, any guesses?



ANDREWS

There's some pre-clinical evidence that components of ginger, one called gingerall, may actually work on a receptor, I think we'll hear about later, which is a 5-Hydroxytryptamine3 receptor, which is a neurotransmitter system.



PORTER

In the brain?



ANDREWS

In the brain or probably more likely in the gut but clearly further study needs to be done on this.



PORTER

We'll come back to treatments a bit later but first what about drugs that cause nausea and vomiting? Drugs like painkillers and anaesthetics given to people having operations - Keith Myerson is a consultant anaesthetist at Eastbourne District General Hospital.



Keith - two classes of drugs there that form the backbone of most general anaesthetics. What proportion of patients undergoing surgery develop post-operative nausea?



MYERSON

Well a lot of patients unfortunately do feel sick after their operations and this is something anaesthetists are really worried about.



PORTER

And so are patients aren't they, I mean it's one of the side effects that puts patients off?



MYERSON

Well of course we worry on their behalf because not only is it extremely unpleasant for patients to be sick but there are other consequences of it too. It can actually be harmful to patients if they're sick for a long time, actually if they're straining and vomiting it can actually damage the stitches from their operation, it can mean that they're unable to get up and go home, means they have to be admitted to hospital and have economic costs as well. But on the whole it's just so awful for patients that we obviously we want to do our best to try and stop them being sick.



PORTER

And how common is it?



MYERSON

Well we think that probably it's about 1 in 5 people, the studies show, feel sick after operations and 1 in 3 people will actually be sick afterwards. In fact from our own experience these days I suspect it's not quite that high but it's still very high and enough to worry about.



PORTER

It's not just the side effect of the drugs either is it, it varies with the type of surgery that's done.



MYERSON

Well that's right, it's not just the drugs that do it but in fact there are three other things. It's, first of all, who you are, that has an effect, what you're having done - the type of surgery - and also the type of anaesthetic that you get - you're going to be given.



PORTER

Well let's start with who you are.



MYERSON

Well who you are - well first of all women, I'm afraid, are much more likely to be sick after or feel sick after their operations than men. In fact the studies show that post-operative nausea and vomiting is three times more common in women. And interestingly children are also more likely to be sick than adults, although interestingly below the age of six they're actually less likely to be sick. Overweight people are more likely to be sick after their operations as well and people who suffer from migraine may well be sick. People are more likely to be sick after an operation if they have a history of being sick after operations before or indeed get travel sickness. One of the questions anaesthetists may ask you is do you suffer from travel sickness because this may well put you into a high risk category.



PORTER

And what about the type of procedure - how can that make a difference?



MYERSON

Well it's interesting that some types of operations do make you more sick. Gynaecological operations are thought to but maybe that's just because they're only carried out in women who are more likely to be sick anyway. Ear, nose and throat operations can make you sick and that's quite an interesting one because the ancient Romans knew this, they used to have these great feasts where they'd eat too much and then they'd then retire into a side room called the vomitorium and they'd make themselves sick by putting an ostrich quill, a feather, in their ear and tickling their ear and that would make them sick. And this is because of the vegas nerve which supplies part of the ear and when that's stimulated during surgery on your ear that can make you sick too. Eye surgery, is another form of surgery that can make you feel sick and again that's to do with the vegas nerve, pressure on the eyeball we know can actually be used to slow the heart down when there's a normal rhythm, it can be used therapeutically. And operations on the eye can certainly make you more likely to be sick after your operation.



PORTER

What can you do practically to reduce the likelihood of post-operative nausea?



MYERSON

Well first of all anaesthetists can choose not to give you a general anaesthetist and by having an operation performed without actually being asleep, under some kind of nerve block or regional nerve block, an epidural perhaps, these sort of procedures if they can be done that way and most operations can be that makes you much less likely to be sick. Then by a choice of drugs, using short acting drugs that are quickly metabolised, some of the new modern painkillers are very quickly got rid of from the circulation, that makes a difference. Avoiding inhalation agents, these are the gases that anaesthetists have used for a long time, they can make you feel sick. And there is a move now towards avoiding these gases, I mean that's a good idea from many viewpoints.



PORTER

And keeping a patient asleep with a [indistinct word] infusion or something rather than through inhaling the vapour.



MYERSON

Exactly and it's kinder for the environment because a lot of these gases are greenhouse gases anyway.



PORTER

Are you routinely giving them drugs to stop them feeling sick when they wake up?



MYERSON

Well what we do is we categorise patients into the various risk categories, depending on the various patient factors that we talked about, and if the risk is considered high then special techniques will be used and combinations of drugs will be used. Unfortunately we don't have any single ideal drug which can stop the nausea and vomiting so what we have found is that some of the drugs act together - they actually help each other's action and by using mixtures of drugs we can actually have much better results.



PORTER

Dr Keith Myerson thank you very much.



Well nausea is also a common problem in cancer patients undergoing chemotherapy. Dr Nicola Stoner is the Lead Cancer Pharmacist at Oxford Radcliffe Hospitals NHS Trust .

STONER

Chemotherapy causes certain substances to be secreted that cause nausea and vomiting. And different types of chemotherapy cause different degrees of nausea and vomiting. It's also dependent on individual patients - younger patients are more susceptible to being sick with chemotherapy, also females are more likely to be sick than males.



PORTER

This is one of the side effects that many patients undergoing treatments for cancers dread, would it be fair to say that today's chemotherapy regimes are better tolerated than the ones in the past?



STONER

The chemotherapy regimes today are better tolerated but that's because we've got much better anti-sickness drugs now than we ever used to have.



PORTER

And is there any exciting breakthroughs in the pipeline?



STONER

There are some new antiemetics that have been licensed in this country in the last couple of years. The neurokinin-1 receptor antagonists which have been licensed in the UK for the last two years, they work in a different way to our existing anti-sickness drugs that we use and they work better for a type of sickness that's called delayed sickness. There's anticipatory nausea and vomiting which a patient feels sick before they've even had any chemotherapy and that's often due to them having a bad experience in the past. Then there's what we call acute nausea and vomiting, which is in the first 24 hours after having chemotherapy and then delayed nausea and vomiting, which happens after that first 24 hours. And the newer drugs that have come through they are actually better for delayed sickness.



PORTER

And how well tolerated are these new generation of anti-sickness drugs because of course every drug has a side effect, do they produce side effects themselves?



STONER

Yes, unfortunately, as you said, all drugs do cause side effects and the anti-sickness drugs that we use currently do have side effects. Constipation and headache and if we use some of the older drugs they can have side effects that make them feel a little bit jittery or agitated.



PORTER

Dr Nicola Stoner talking to me from our Oxford studio.



One area we haven't explored is travel sickness - a type of nausea experienced by most of us at some time. Professor Michael Gresty is one of only a handful of experts in the UK working in the field of motion sickness and spatial disorientation. I joined him at his Medical Research Council laboratories in a basement at Imperial College, where we could barely move for machinery.



GRESTY

This is a flight simulator, it's not actually a real flight simulator because of course they'd be fabulously expensive but what we did was take a fairground ride and adapted it by putting our own computers on and our own motors and gearboxes.



PORTER

Your basement here is full of all sorts of machinery, may I say some of it looking a little bit Heath Robinson, you make a lot of this stuff or adapt a lot of this stuff yourself do you?



GRESTY

Yes, we've tried to make situations that people have problems with. So, for example, we've got an escalator over here so we can see the difficulties of patients with balance problems have in negotiating escalators in the store. Now this, for example, one of the latest machines that I'm rather proud that I invented just a year or two ago and as you see it's just a couple of simple hoops which cost nothing - about a hundred pounds. And inside there's a chair.



PORTER

The chair goes round and round and round.



GRESTY

Yes you're sitting on a large electrical motor.



PORTER

So you can drive …



GRESTY

We can drive it with the computer but the hand is just as good, so I can push you round when you're sitting on this chair left or right, very simply. And it's very smooth, so that when you were going round you wouldn't actually know you were turning once we're at a constant velocity.



PORTER

Well let me get into the chair which looks a bit like an electric chair I have to say. I'm going to get into it, there you go and I'm sitting - it's got a headrest behind so I'm sitting absolutely bolt upright with my arms on the arms of the chair.



GRESTY

And lean your head back against the rest.



PORTER

Okay.



GRESTY

And you may feel a little bit dizzy but you shouldn't feel at all sick.



PORTER

No that's not too bad.



GRESTY

Right. Because this is a very simple motion which is a turning with the body maintaining uprightness. Now that's the key concept. Now in a moment I'm going to ask you to just tilt your head down on to your chest and then I'll say quickly back up again. Now tilt down.



PORTER

Oh, oh yeah. That's amazing.



GRESTY

Now you felt almost instant nausea yes?



PORTER

Yeah.



GRESTY

Although the whole of your body is rotating from left to right by tilting your head you brought the balance organs of the inner ears into a new plain of motion and suddenly you're getting a very complex motion signal fed to the brain from your balance organ. This is disorienting and because the brain finds it difficult to unscramble these messages it starts to make you feel first of all an experience of malaise and then sick.



PORTER

Yeah it's almost - I mean - oh yeah, feeling a bit strange. I mean that's the feeling you get that I've experienced in a car as a passenger when you bend down to pick something up off the floor, turn round to tell all the children off in the back seat.



GRESTY

Precisely that's just what we've simulated.



PORTER

But why - why do we feel nauseous, why do we get that sort of response, how might that have helped us in an evolutionary way?



GRESTY

Well this is a very highly contested issue but the initial stages are not really nausea, the initial stages are just feeling a bit uncomfortable or a little bit strange and this is a warning sign that there's something wrong about your organisation of behaviour in space and you've got to do something about it because the most important thing you have as a biological organism is orientation in space, to know where you are and what's happening around you, without that you couldn't even pick up a cup of tea and put it to your lips. So when something goes wrong with this orientation in space the brain says listen you have to get this right quickly to protect yourself. The next stage is nausea which is a very strong warning sign, I mean soldiers get this, for example, and anxiety before going into battle, that's a very strong warning sign to get the body geared up for action. And eventually through to vomiting, if the motion continues long enough, the provocative motion, you will vomit.



PORTER

It's the alarm that makes you act.



GRESTY

Yes.



PORTER

Looking at the test that you did here on the chair would it be possible for me to become accustomed to that, I mean would I be able to get my equivalent, I suppose, of sea legs?



GRESTY

Oh yeah. In a car the best thing to do is to close your eyes, tilt backwards gently and keep immobile. The next best thing to do is look ahead through the window of the car at the oncoming scenery, that's fine because you can predict what's happening, but do not wiggle your head about.



PORTER

Reading is the classic - children sitting in the back reading their comics, it makes them feel ill, what's happening there?



GRESTY

Well that's what we call a sensory conflict because when you ride along in the car and you look at the road ahead the car is actually vibrating, it's moving up and down and side to side and all the natural reflexes that control the stability of vision, they're called the vestibulo-ocular reflexes stabilise the eyes on the horizon, so you can see clearly, you can read road signs. But when you try to look at something that's moving with you you've got to shut down all these reflexes and then start your, what we call, visual following movements and scanning movements to try to read the newspaper or the book. So you have two rather important kinds of visual reflexes working against each other, again there's a conflict here.



PORTER

It's a common theme this, it's sort of - when the brain's in conflict or confused that's when this feeling of nausea arises.



GRESTY

Yes, yes absolutely.



PORTER

Now I noticed in the device that I'm sitting in that there's a curtain that goes round the - a striped curtain that goes round the outside, now what's that there for?



GRESTY

Well the curtain actually gives us the impression that the environment is moving round you.



PORTER

So I can sit still and you move the curtain around.



GRESTY

Yes, now let's think of trains, if you look out through the window of the train you see the scenery going past you, you may get the illusion that you're moving, you know when you see another train going past …



PORTER

Particularly in the station.



GRESTY

Yes that's right, particularly in the station. So this curtain allows us to simulate visual motion.



PORTER

So we've already shown that if you spin me round and I tilt my head while I'm sitting in this chair that's spinning round it'll make me feel very …



GRESTY

Are you susceptible to motion sickness?



PORTER

Yeah I am yeah, I can't go on a boat. If I were to sit still and you were to spin the environment and I was to tilt my head I might feel the same?



GRESTY

You'd get sick just the same way, perhaps not as fast, it's not as strong, but it's a definite factor.



PORTER

Well can we try that? Okay. So I'm sitting in the chair, you're drawing the curtain. I presume I have to keep my eyes open for this one.



GRESTY

Interestingly patients with balance disorders tend to become very sensitised to this so they can feel as though they're moving and off balance when they see traffic or crowds in supermarkets or go to a cinema and see a moving visual scene like on a James Bond movie or something.



PORTER

Yeah well the curtain's started moving, it's going clockwise and for a minute I thought I was going anticlockwise. Now my eyes are starting to flicker, now I have no idea what's happening to me, I've got a feeling that my chair's spinning quite rapidly round to the left now.



GRESTY

Now I'm going to ask you just to keep looking at the drum but tilt your head about.



PORTER

Okay, so tilting my head to the right now and to the left and oh urgh, I can feel beads of sweat breaking out on my forehead. I guess I'm the wrong guy to be doing this.



GRESTY

And now I've stopped the drum because I don't want to prolong your misery.



PORTER

Yeah. So your ability to fix on the environment that's around you, that you're travelling through, is important?



GRESTY

In a normal train you don't really get sick, you get thrown about a bit you don't feel very sick. But in a tilting train when you look through the window and it goes round the bend the environment swings widely from being depressed to being elevated and when you look at this, and particularly if you make any head movements while you're looking at it, then you get very sick indeed. And the first tilting trains made about a third of all the passengers really rather ill. So now they've limited the amount of tilt on trains.



PORTER

Michael Gresty and his very effective nausea inducing machine.



Physiologist Paul Andrews is still with me - Paul, how do travel sickness pills help dampen down that type of nausea?



ANDREWS

The predominant mechanism is by blocking one or two of the neurotransmitters, acetylcholine and histamine, that connect the balance system into the emetic pathways.



PORTER

Essentially dampening down the signals that are coming …



ANDREWS

Essentially dampening down the signals and that's probably also why tablets that have those effects on transmitters may also have an effect on other types of emesis, other than purely motion sickness.



PORTER

What about some of the non-drug approaches, how might these things be working, could it be simply that they're distracting people?



ANDREWS

I think in general distraction, relaxation - all of these - are likely to help with some degree of alleviation because we know that stress and anticipation of being sick are likely to make it more likely to occur so I think relaxation is probably the ...



PORTER

And we heard about the anticipation didn't we, with the chemotherapy, people who've had a bad experience are almost expecting another bad experience.



ANDREWS

That's right yes, so I think generally once you've had one bad experience anything that you can do to distract you from thinking about that experience in the same setting may well help.



PORTER

What's happening at the physiological level in terms of identifying the causes of nausea, do you think we're going to see a breakthrough in the pipeline, if we can understand more about why people, for instance why some drugs make people sick?



ANDREWS

I think we've already seen some advances as we've gradually begun to understand the underlying mechanisms, particularly in the area of chemotherapy where we know fairly well the pathways which are activated by the anti-cancer drugs and hence we've been able to find approaches for blocking them.



PORTER

I suppose the other way of looking at it coming with a bit of lateral thinking is that it could help us develop drugs that don't actually have nausea as a side effect in the first place.



ANDREWS

That's exactly right and this is I think a very important area of understanding, is firstly to understand why nausea and also vomiting are common side effects of many different types of drugs and in fact in some cases have prevented development of very promising types of treatment. So we must understand the basic mechanism by which these drugs and potential drugs cause this side effect and also of course if we can't filter out these effects in development then we need to find ways of blocking after the event using drugs specifically targeted to block nausea and of course vomiting as well. But in general nausea is the problem that's of much more concern to patients and is generally less well dealt with than is vomiting.



PORTER

I am afraid we must leave it there. Professor Paul Andrews, thank you very much.



Don't forget if you would like to listen to any of the programme again then you can do so via the website, that's at bbc.co.uk/radio4. And if you don't have access to the net, but would like more details of the issues we've discussed today, then do try the Action Line on 0800 044 044.



Next week's programme looks at the burgeoning problem of allergies, and we meet chef Giorgio Locatelli's daughter Dita who, in a cruel twist of fate, is seriously allergic to nearly all his favourite ingredients.




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