Magnesium for ectopics and palpitations with Dr Sanjay Gupta

In episode #46, Paul talks with consultant cardiologist Dr Sanjay Guptaon a supplement that he’s found to be beneficial for cardiac patients who experience ectopics and palpitations.

Dr Sanjay Gupta is a Consultant Cardiologist, with specialist ...

And that supplement is Magnesium and in this episode Dr Gupta takes us through what ectopics and palpitations are and why he recommends taking magnesium for them. He talks about the various types of magnesium available and which ones to buy and which ones to avoid.

There’s lots of great help if you are experiencing ectopics or palpitations or just want to know a little more about what goes on in your heart. Another essential listen from this popular YouTube cardiologist.

Available to listen on the link below or Spotify, Apple , Google, YouTube and your favourite podcast player.

#046 Magnesium for ectopics and palpitations with Dr Sanjay Gupta

Paul Swindell: [00:00:10] Hello and welcome to another episode of the life after cardiac arrest podcast with me, your host, Paul Swindell. And today I'm joined by Dr Sanjay Gupta, who is a consultant cardiologist at the York teaching hospital and has a specialist interest in cardiac imaging.

And he has a popular social media presence and can often be seen doing YouTube and Facebook videos on cardiac related matters.

And he's also got a fantastic collection of shirts, which I'm very jealous of actually.

Thank you

He's done a number of videos and all sorts of cardiac issues like palpitations, anxiety, ectopics, AFib, but his most popular one is on magnesium, which has got over one and a half million views on, and that post had 7,000 comments on.

And this is the subject we're going to be talking about today.

So welcome again, Dr Gupta.

Dr Sanjay Gupta: [00:01:05] Thank you for having me Paul.

Paul Swindell: [00:01:07] It's great to speak with you again.

So can you tell me why you did a video on magnesium? Cause it doesn't immediately spring to mind as being a cardiac subject?

Dr Sanjay Gupta: [00:01:17] Yeah. I think it all started because I was interested in talking about heart palpitations. And in particular, one of the commonest, Heart rhythm disorder causing heart palpitations is something called ectopic heartbeats. These are transient extra beats that tend to occur virtually in everyone, but tend to be very much noticed by those people who carry a degree of anxiety.

And when they happen, they can be really, really scary.

The problem well, with these is that, although we recognize them not to be dangerous. They are incredibly scary for patients. When the patient comes to the doctor, the doctor will say, Oh, you've just got a few a topic beads. They're not dangerous. Don't worry about it.

Because the patient can't understand this. He can't understand. He only knows what it feels like. There's very, there was very little support for such patients. You know? No one really talked about ectopics because they were not dangerous. So, in some way they were not important to the medical field because they were not dangerous.

But for patients, and particularly those patients who, who tend to be anxious about their health anyway, it was really something very big, so I felt that I could explain ectopics in a way that made sense to me, and because I did that, I did a video on ectopic heartbeats. A lot of people responded very favourably to that video.

They really felt that I was providing them with information that they hadn't been provided by their own healthcare practitioners. Many of them had been suffering from ectopic beats for 20-30 years. They developed chronic health anxiety as a result.

Really, really terrible stories when you heard them.

As I started doing more videos around ectopic heartbeats, I came across a bunch of people who talked about the fact that magnesium had helped their ectopic heartbeats.

No one had really talked about it on a big scale. These were just anecdotal reports from people who said, well, I took some magnesium and it's really made a big difference. And I thought, well, it'd be interesting to look into this to see whether it really works.

Does it really work?

And do you know?

And if it does, maybe I should talk about it.

I then went and did some reading around the subject and as a doctor, you want to feel like you have some kind of scientific evidence to back up your recommendations.

And I found a very, very small study in Brazil where they used magnesium. They gave magnesium to patients with ectopic heartbeats and they got some really good results and they describe 80 to 90% of patients feeling better.

And although it was a really tiny study and it was in an obscure journal, it gave me enough to be able to feel like I could talk about it.

And I said, well, you know, there is this and here is a study which talked about it. The problem is, the minute you mentioned something like this, people say, well, we want proper studies. We want bigger studies.

Those bigger studies will never be done because magnesium is never going to make money for anyone. And, therefore. Here was something that did have some kind of evidence base. The next step was to try and just recommend it to people, because to my mind, I was confident that it was a safe supplement to use.

So, I thought to myself, well, why dont I talk about it with two people and say, look, there was a small study which suggested it was beneficial. You could try it. It's not dangerous. If suddenly you find that things are better than it's worked for you, and if you don't feel any better then it's maybe not for you.

And on the basis of that video, a lot of people started using magnesium. And I got a ton, a ton of replies, a ton of comments saying, well, you know, when I started taking the magnesium, my palpitations got better. I spoke to my colleagues at work about this and they said, well, how can you recommend this?

There's no really big evidence. And I said to myself, well, do I really need the evidence? Because if the person in front of me who comes to me with a complaint says his problem is better after taking it. Then that's all the evidence I need. We are prescribing this or we are recommending this to improve a person's quality of life, and quality of life is a very individual thing and it has to be measured by that individual's own yardstick.

And so. I started recommending it, and a lot of people responded amazingly to it because they felt, gosh, no one has talked to us about these supplements. when you look, The FDA, the, everywhere. We are chronically depleted of magnesium. This is well-published. It's a well-recognized that three quarters of the population are deficient in magnesium, so it made sense.

When I started recommending it, people said they slept better.

People said that they felt calmer.

People felt that their ectopics got less.

Some people found that their other heart rhythm disturbances, like atrial fibrillation got less anecdotes, that these are not big studies, but how many anecdotes do you need to feel convinced that it's worth trying out?

And that's what's happened with magnesium and me.

Paul Swindell: [00:06:20] Can we just, go over what is exactly a palpitation and what is an ectopic? What is actually going on in our hearts when we, we feel those? I'm I don't think I've ever really had palpitations so much, but after my, cardiac arrest. I was very much aware of what I called missed beats.

Is that what our an ectopic is?

Dr Sanjay Gupta: [00:06:43] The missed beats where you describe a skipping or a fluttering or a miss beat followed by a big thud, those are ectopic beats. So, palpitation is a symptom. Okay. Any time the patient says, my heart feels like it's doing something it shouldn't be doing or it feels odd, that's a palpitation.

Different heart rhythm disturbances can cause palpitations. So, you you may even get palpitation when your heart is not doing anything funny, but it just feels like your heart's doing something funny.

So, for example, if someone comes and scares you, you know, from behind your heart will beat really hard and really fast and that would be a palpitation.

But at that time your heart's not doing anything odd. It's just responding to all the adrenaline that's suddenly been produced in your body. Then you have other heart rhythm disturbances, which may manifest as palpitation, and the commonest by far are ectopic heartbeats. Where what tends to happen there is that your heart will beat and then it relaxes for a certain amount of time.

When it relaxes for a certain, let's say it relaxes for a second and then it beats, so it'll fill up with a seconds worth of blood whilst it's relaxing, and then it will contract and push out that seconds worth of blood. Then it will start relaxing. Now if before it reaches that second of relaxation, let's say after half a second, an extra beat comes in from somewhere.

Then this time. The heart is only pumped out half a seconds worth of blood because the extra beat came in after half a second so it only had half a second. So that will feel like a missed beat. Then to compensate, the normal beat comes in later after one and a half seconds, and now the heart has had to fill up with one and a half seconds worth of blood, which it pumps out, and that then feels like a big thud.

So that's traditionally what ectopics feel like.

They feel like boom, boom, boom, boom, boom.

Paul Swindell: [00:08:35] Yeah.

I've definitely had those.

You said several times that they're not considered dangerous, why is that? Because it sounds like it could be a problem or could it not lead into a, further arrhythmia?

Dr Sanjay Gupta: [00:08:47] Well, we, the reason they're not dangerous usually is because they're non-sustained ectopics by definition, tend to be followed by normal beats.

Paul Swindell: [00:08:59] So what you just get them in isolation.

Dr Sanjay Gupta: [00:09:02] Yeah, definitely. So you'll get that extra beat. And then after a little while you get that big thud, which is the normal beat.

So, because the heart is a pump and when you have an ectopic, any heart rhythm disturbance, means one thing and one thing only. It means that the heart is a pump is not as as efficient. Okay?

So, the efficiency of the heart is compromised during that heart rhythm disturbance.

So, if you've got something which is only going on for a second, followed by normal beats, the inefficiency is non-sustained inefficiency.

It's followed by normal beats, the heart becomes efficient again.

Sustained heart rhythm disturbances are where you get one abnormal beat, followed by another abnormal beat, followed by another abnormal beat for, let's say, you know, 10 minutes there, you've got 10 minutes worth of inefficiency.

So that's why ectopics in general are not dangerous because they represent a non-sustained heart rhythm disturbance as opposed to things like atrial fibrillation, ventricular tachycardia, which are sustained.

Paul Swindell: [00:10:03] I see.

So are ectopics a symptom of an underlying problem, whether that be in the heart muscle or elsewhere in the body?

Dr Sanjay Gupta: [00:10:11] Sure. I mean, I think the first thing to say is that ectopics happen.

So if you take a hundred people off the street and do a 24 hour monitor on them, you will find that on their monitor, 60 out of the hundred, will have some ectopics in a 24 hour period. So they're very, very common. These are people who don't feel a thing.

They're just getting about their own, their lives. Normally they have no symptoms, but if you do a monitor, you'll see some ectopics. So they occur normally. It is true to say that if you have a diseased heart, if you have a structural problem with your heart, let's say you have a cardiomyopathy, let's say you have scar in your heart.

Let's say you have weaker heart, then the heart is more likely to be more irritable and therefore you may get even more ectopics. Significantly more ectopics, and that is why the first thing we do when we have a person who is getting ectopics is to make sure that the heart is structurally normal. We do that by doing an ECG and doing an echocardiogram, a heart scan, and if those are fine, then we turn around and say, we think you have a structurally normal heart.

Therefore, your ectopics are not, a symptom of a diseased heart. The next question then is, if they're not a symptom of a diseased heart, what else could they be?

And the answer is that there was some interesting studies done, the where they took a bunch of people who suffered from health related anxiety and they strapped them to a monitor and they proceeded to make them more anxious.

And as these people got more anxious, they got more ectopics on their monitor. So yes, you know, it's interesting. For example, you mentioned that you know, after, after you were unwell, you got some missed beats. That can simply, of course, it could be due to the fact that if you had a cardiomyopathy or something like that, you may get ectopics as a result of that, but more likely because of the trauma and the stress and anxiety that this whole thing may have caused you.

Paul Swindell: [00:12:05] I see. I see. Yeah, that makes sense. Because, they have dissipated over time and, I've become more relaxed and chilled about what happened as it were.

Dr Sanjay Gupta: [00:12:16] Yeah .

Paul Swindell: [00:12:17] Okay. So, can we look at the actual magnesium?

What is magnesium and why is it important to the body and the heart?

Dr Sanjay Gupta: [00:12:25] Okay, so, magnesium is a essential mineral.

It's a mineral and an electrolyte. It's, I think the fourth most abundant mineral in the body. It's necessary for electrical activity in the heart and the brain. It's a cofactor in more than 300 reactions within the body.

The daily recommended daily allowances, 400 to 420 milligrams for men and 310 to 360 milligrams for women.

But our daily intake is far less than this, most people take between 240 and 370 milligrams at most, and therefore, 75% of the population in the Western world takes in less magnesium than is recommended.

Once we have ingested the magnesium, 30 to 40% is absorbed from our gut and our bowel and some is excreted through our kidneys, but then our kidneys try and reabsorb it when we're deficient.

The other thing to say about magnesium, which is really, really important, is that the blood tests we have for it or not very accurate, and they don't give a true reflection of how much to total body magnesium we have. And that is why a lot of people will come to me and say, well, I've had my magnesium levels checked.

They're okay and I say to them, well, it's still worth trying a magnesium supplement because you can't rely on the blood test. And we are magnesium deficient because we now take in less than we should.

This is because of modern farming methods, which just serve to deplete the magnesium in soil, processing of food depletes magnesium further, we absorb less of it from our stomach because, you know, a lot of patients, for example, are on proton pump inhibitors, for their stomach, and, that reduces acid production and acid is necessary for absorption of magnesium.

And so by far and away, the commonest medication that is prescribed these days are PPIs, Losec, Metrazole, that kind of stuff.

And, they reduce magnesium absorption.

Carbonated beverages, reduce the absorption of magnesium and can make the problem worse.

We're using up a lot more magnesium than we were.

So, things like sugar, a lot more sugar in our foods, and magnesium is required to break the sugar down.

So, we're using a lot more magnesium that way. Stress, sleep disturbance, we'll all get rid of magnesium from the body. And, things like coffee, tea will make us excrete more magnesium in our urine. So, there's loads of reasons why so many of us are deficient in magnesium.

Paul Swindell: [00:14:57] You mentioned about, the food that we eat and the farming methods, depleting the amount of magnesium in our food, but what, what foods should we be looking for?

Because obviously I'll guess food is the best way of getting magnesium into your body, rather than necessarily taking a supplement.

Dr Sanjay Gupta: [00:15:14] I think greens are an important way to get magnesium.

Nuts are an important way to get magnesium in our body, you know, so almonds, spinach, cashew nuts, peanuts.

Trying to eat organically grown foods, whatever, you know, whether you can rely on what is organic or not is another matter, but avoiding processed foods and eating as far as you're aware, organically grown foods from local growers is a good way to get the magnesium into the body, but to my mind, most people benefit from taking a supplement as well.

Paul Swindell: [00:15:46] You mentioned that a blood test is not a good way of telling whether you are deficient is, is there any other way of telling if you're deficient?

Are there any obvious signs?

Dr Sanjay Gupta: [00:15:57] You know, the reality is, it's one of those deficiencies, which isn't reflected in outwardly major, major issues. But, there are some tests that are more accurate, so you can measure something called the red cell magnesium content, but very few places offer that test.

So most places they just do a blood test, and if you go to, you know, local doctors, et cetera, they'll just do the blood test for magnesium, which has no good at all.

I think it's one of those things where the symptoms of a deficiency of very kind of nonspecific, and this is only once you start taking a supplement, if you suddenly find out, gosh, you know, I'm feeling calmer and I'm sleeping better, and a lot of people will say that they get cramps in their legs at night and that they take a magnesium supplement, the cramps go away.

Paul Swindell: [00:16:44] What confused me when I was looking is that there are so many different types of magnesium. are you able to run through sort of some of the main types and the ones that perhaps, heart patients should be looking for in particular?

Dr Sanjay Gupta: [00:16:57] Yeah, there were a lot of different preparations. The common preparation you will come across as something called magnesium oxide and magnesium oxide is is not a good preparation to take because the bioavailability is only 4%.

So, what you take in you only absorb about 4% of what you're taking in, and it has a propensity to cause a loose stomach.

And so, one of the side effects of taking magnesium is loose stool.

So, magnesium oxide is one that I recommend against taking, but there are other preparations like magnesium citrate, magnesium glycinate, magnesium taurate. Any other form of magnesium is fine. You can, you don't actually have to take it orally.

You can take it topically, so you can have oil and rub oil into your skin, and it can be absorbed trans dermally as well.

In my experience, I recommend magnesium citrate or magnesium taurate as a really good supplement for heart palpitations.

Paul Swindell: [00:17:53] Is there any price difference in those products or those types of magnesium?

Dr Sanjay Gupta: [00:17:58] The way it started with me was a lot of people came to me and said, well, can you recommend a preparation?

And the preparation that was studied in the study from Brazil is no longer in production. So, no one seems to be producing that, particular, preparation. So, I decided to recommend magnesium taurate, and a lot of people came back to me and said, you know. That magnesium taurate it's done me a lot of good, I feel better. So, I said, look, that's the one to go for.

Unfortunately, then I discovered that the, company that was making it to raise their prices greatly, and I started recommending magnesium citrate. In the UK we have a health food store called Holland and Barrett, and you can buy magnesium citrate and it's about five or six pounds, something like that.

So, it's not too expensive at all. And, and that seems to work as well as any other preparation.

Paul Swindell: [00:18:48] But what form would that come in, is that a tablet or a powder?

Dr Sanjay Gupta: [00:18:52] I think it's a, I think it's a capsule.

Paul Swindell: [00:18:55] And for people who don't like taking tablets or have got a handful of tablets to take anyway, do you know, are there any other ways to ingest?

Dr Sanjay Gupta: [00:19:03] You can buy magnesium aspartet sachets so that you can mix them in water. And that�s a reasonable way to do it. You can open the capsules and put the powder in and mix it with water and that's another way to do it. Or topical magnesium, magnesium oil.

Paul Swindell: [00:19:21] And what sort of dosage should people will be taking of this? Would it be one size fits all or does it depend on your symptoms?

Dr Sanjay Gupta: [00:19:30] I generally say start with the recommended dose on the tin.

You know, so the preparation you buy, take the recommended dose because we know that at that dose that's going to be safe.

Now, the reality is with magnesium, you know, it has a, you can take a higher doses and not come to harm as opposed to something like potassium, for example.

With potassium, potassium has a very narrow, kind of normal range in the body.

If you go very high, it can be dangerous.

If you go low, it can be very dangerous.

But magnesium has a much wider scope.

So, I normally start off by magnesium citrate, 200 milligrams daily. Magnesium taurate 125 milligrams twice a day.

But any of the preparations, if you take the recommended dose on the box, then that's great place to start.

Paul Swindell: [00:20:23] You mentioned with magnesium oxide that you could get loose stools. Are there any other sort of side effects that you might get from some of the other types of magnesium?

Dr Sanjay Gupta: [00:20:33] I haven't come across any, is the truth. It is just the loose stool that I've come across. Obviously, people who have kidney damage or you know, in those people, you want to be a little bit more careful because they're not treating as well as they should.

But it is mainly the loose stools that have come across as a problem. Having said that, most people tolerate the other forms of magnesium really well. Magnesium glycinate is probably the easiest on the stomach.

Paul Swindell: [00:21:00] As I mentioned earlier, people are probably taking a handful of medications already if they've had a serious heart issue, are there any contra-indictions that it shouldn't be taken with any of these tablets. And should they be going to their, GP or cardiologist before starting on something like this?

Dr Sanjay Gupta: [00:21:21] It's always a good idea for everyone , to get the consent of their, healthcare provider before starting anything. Because everyone's different. And, you know, when I sort of make a recommendation, it's impossible to know the specifics for every person who may be thinking about it.

So, I would always say, you know, there's no harm in trying it. But just make sure that your doctor's happy with you trying it. I have not really found a major contraindication. My patients take all sorts of medications and they can take a magnesium supplement. And I've not really come across anyone, who has suffered, adversely as a result of taking the magnesium.

Some people worry that it has a slight, a very tiny anticoagulant effect. And if you're taking anticoagulants, people worry about that. But again, a lot of my patients do, and they've not come to any harm.

But again, as you know, I would always reiterate that before taking any kind of supplements, make sure your doctor is happy with you doing so.

Paul Swindell: [00:22:19] So have you got anything else to sort of, to sum up

Dr Sanjay Gupta: [00:22:22] Yeah, I think so.

I think the reason I recommend magnesium is for quality of life.

I don't know whether, you know, I don't recommend it because I think, Oh, this will make you live longer, I don't know.

There is no evidence, we don't know, but, I think that try and get out and seeing if your quality of life improves in some way.

And if it does, then that is what you were taking it for.

And if it doesn't, then maybe it's not for you.

But you know as again, you know, if, if for example, you don't sleep well and you start taking a magnesium supplement and you sleep better, well that just is good for you.

It improves your quality of life, it makes you a healthier person.

If you're getting ectopic beats and you take some magnesium supplements and the ectopics get less, well, that's just improved your quality of life.

So, in that sense, I think it's worth trying, and if you feel better, then great.

You know, the problem is very few people are going to go out and say, oh, take magnesium. You know, we are sort of a largely pharma driven industry now.

And, so it is all the, kind of the newest and most expensive medications, and the research and the kind of evidence base that we all crave for, will never, be accumulated for things like magnesium because there's no money.

Paul Swindell: [00:23:41] Okay, my final question would be, if someone starts taking it, how soon would they notice any effect if there is going to be some for them?

Dr Sanjay Gupta: [00:23:50] Usually, you know, within a week or two weeks, a lot of people come back and say, look, that's worked. I definitely think that's helped. So one to two weeks.

Paul Swindell: [00:24:00] And what's the sort of maximum time they should take it for? And if they haven't seen any, effect, and then?

Dr Sanjay Gupta: [00:24:07] Four weeks,

Paul Swindell: [00:24:09] Four weeks.

Dr Sanjay Gupta: [00:24:10] If you've not noticed a benefit in four weeks, and I don't think it's working for you then.

Paul Swindell: [00:24:16] Okay.

That's an absolutely brilliant session on magnesium Dr Gupta, thank you for that. And I'll speak to you next time.

Dr Sanjay Gupta: [00:24:24] Thank you.

If you enjoyed this podcast please do leave a positive review on Apple or other podcast providers as it helps us to spread the word.

Presented and edited by Paul Swindell.

Recorded March 2020. 

The ultimate survivor with Jonathan Jenkyn

Jonathan Jenkyn tell his story on episode 45 of the Life After Cardiac Arrest podcast

In episode #45, Paul talks with the very remarkable Jonathan Jenkyn who has not only survived a sudden cardiac arrest but also a potentially fatal kidney condition and he has recently beaten an aggressive form of cancer.

Jonathan maybe extremely unlucky in having had the Grim Reaper have 3 attempts at him, and although he defeated this wiley foe he did not escape entirely unscathed from the experiences.

Dad diagnoses himself with cancer while helping daughter revise ...

However, he is wiser and more upbeat than many and has a positive outlook and attitude to life that many of us would do well to take note of. He takes us through both his cancer and cardiac arrest experiences, his running, his loss of ability to play the guitar, the benefits of giving back and he imparts some very interesting information about ICD’s along the way.

He also compares the two experiences and the impact that they have had on him and his family.

An amazing story of survival, told in an eloquent and engaging way from someone who has earned the right to the accolade of “the ultimate survivor.”

An essential listen to survivors of all types and beyond!

P.S. A few days after recording this episode Jonathan fulfilled one of his bucket list by recording a song with his daughter and he released it on Youtube, it’s rather good and will inspire all those who may have lost some musical ability after an event like an SCA.

Available to listen on the link below or Spotify, Apple , Google, YouTube and your favourite podcast player.

If you enjoyed this podcast please do leave a positive review on Apple or other podcast providers as it helps us to spread the word.

Presented and edited by Paul Swindell.

Recorded May 2020. 

Post arrest cooling with Professor Tobias Cronberg

In episode #44, Paul talks with Professor Tobias Cronberg from Lund University in Sweden who is a consultant in Neurology and has a deep interest in brain injury after a cardiac arrest.

Hur kan vi veta vem som kommer att vakna? - Vad händer vid ...

Professor Cronberg has been working with cooling technologies for over 20 years and is a senior member of the team behind the world wide Targeted Temperature Management 2 (TTM2) trial. The trial is a continuation of the original TTM trial and with almost 2000 patients enrolled, it will supercede it as the largest trial on temperature management as a post-cardiac arrest intervention.

Professor Cronberg talks about the history of cooling and what the study hopes to achieve and where it currently is. A fascinating overview of this intervention that many cardiac arrest patients will have received as part of their treatment.

Available to listen on the link below or Spotify, Apple , Google, YouTube and your favourite podcast player.

#044 Post arrest cooling with Professor Tobias Cronberg

Paul Swindell: [00:00:00] Hello, and welcome to another episode of the life after cardiac arrest podcast with me, your host, Paul Swindell.

Today I'm joined by professor and consultant in neurology at Lund University, Tobias Cronberg, who has a special interest in cardiac induced brain injuries.

Welcome to the show, Tobias, and it's great to talk to you.

Professor Tobias Cronberg: [00:00:32] Thank you, Paul. Very nice to be here.

Paul Swindell: [00:00:35] And just to say that you're in Sweden at the moment, aren't you? How's life there?

Professor Tobias Cronberg: [00:00:41] Well, the sun is blue, and the sky is up, but of course we are suffering from the pandemic as everybody else. So, it's an extraordinary situation,but it hasn't hit the Southern part of Sweden very much. Yeah. So, we are still very, and much business as usual.

Paul Swindell: [00:01:01] Yeah. So, you're just saying before we started recording your life seems not quite normal, but it's not as drastically hit as it is in the UK.

Professor Tobias Cronberg: [00:01:11] That's right.

Paul Swindell: [00:01:11] And I just wonder if you could briefly introduce yourself and tell me a little bit about your interest in neurology and in particular, cardiac arrest induced brain injury. How did you come into that?

Professor Tobias Cronberg: [00:01:24] Well, I tried to make a long story short, it started actually during my, my early years in Lund from, the middle of the 1990s when I was working in a laboratory doing my PhD in experimental brain research. And we worked a lot with stroke models and with a models of cardiac arrest, and the basic mechanisms of cell injury after cardiac arrest and stroke, which is rather similar diseases in the sense that the blood it gets a loss of blood flow for a period, and then we have a reperfusion of the brain and then we have a damage, and the mechanisms are quite similar, actually.

So, it started then and when I, I had done my dissertation, I was working full time clinics and I got interested in the cardiac arrest population.

I started a collaboration with Hans Freberg, who was intensive care physician at that time, and he was a professor there and now, we started, with hypothermia treatment early in 2003 when, when the two important studies were published, showing that cooling patients after cardiac arrest had a protective effect.

And we were strong believers of hypothermia and we wanted to, to study outcome in those patients long-term outcome, and also to look at different methods to try to diagnose brain injury and to try to decide the prognosis for the patients, in the ICU, when the patients were still unconscious, and we started working with different methods, mainly biomarkers in the blood, clinical neurological examination and, electrophysiology, where we could work would continous EEG, for example, as a method to look at the brain activity after cardiac arrest, we started publishing our results about this and, gradually, we got more and more international collaboration. Nicholas Nielson, who is intensive care physician in Helsingborg became part of the team and he was very important for us building up a big network of international sites in the hyperthermia register, which was the foundation for the first TTM trial. After that, which we did in 2010 until 2013, studying the effects of, temperature management in patients.

Paul Swindell: [00:04:04] When was it sort of first realized that hypothermia could be sort of therapeutic and be a useful tool in the medical toolkit as it were. I mean, I guess people have known for quite a long time. I mean, when I used to play sports as a youngster and I, if I got a strain on my leg, you get an ice pack put on your, on your knee or the muscle or whatever, and that would help alleviate any inflammation there.

And you get back to playing the sport quicker, but when was it sort of the light bulb moment, if you like that, Hey, we can use this in a bigger way for something like the brain?

Professor Tobias Cronberg: [00:04:43] Well, that has been known for the, for the brain. It has been known for many years, that it's possible to cool a patient, for example, to, be able to do thoracic surgery in the main aortic vessel, to be able to stop the blood flow to the brain you have to cool the patient very much all the way down to two 19 degrees.

At that level it's, it's almost like putting the brain into the refrigerator and all biological processes slow down, very much. Very similar to what happens in your knee, actually. You slow down all the biological processes, all the damaging, degrading processes are being slowed down and, for a patient operated and, thoracic surgery, you could, you could do, keep operating for approximately one hour at the temperature of 19 degrees.

And during that period, you have basically no activity in the brain. If you, if you look at the cortical activity with an EEG, it's completely silent and then you could rewarm the patient and they will be functioning, more or less normally after that, maybe some, some minor problems, but most patients could return to normal life.

And, comparing that with a cardiac arrest, it would be completely impossible to have a human who, who is without any circulation and normal body temperature for one hour. After that time, you're certainly dead. There's no chance to, revive that person, if the body temperature is normal. So, it has been very obvious and it has been known, for a long, long time.

But, there were, early research, on this, I'm not sure about the exact years, but there were pioneering research done in, in the U S in Pittsburgh at the Safar Institute, and then it was more or less abandoned until the 1970s, when this, when there was some major new focus on hypothermia in experimental settings and a lot of experimental done.

In, in animals, with mild hypothermia, not down to 19 degrees, but only two 33 to 32 33, or maybe 34 degrees, and it was shown that this was effective in different models, experimental models of cardiac arrest and stroke. So, when I got to the lab laboratory and started my research in 1995, it was very well known.

I mean, that laboratory here in Lund, a lot of the pioneering work had also been done on hypothermia in experimental animals. And for me it was very clear. Also, I worked with the whole animal models, and I also worked with cell cultures and when we did this scheme in the cell cultures, and we just lowered the temperature.

The cells didn't get damaged. So it was, it was sort of a concept that was, very much for all the researchers. Very, very clear concept that hypothermia works. And then we had these two trials in 2013 showing in a clinical setting that it worked also in patients. And that led to a major implementation over the whole world, of hypothermia treatment.

But unfortunately, those two trials were not, very good trials, they were small trials. One Australia trial from, from, Bernard and his collaborators, which we'd only less than 100 patient, I think it was 77 patients. And then as European trial, which was stopped early because they didn't have enough funding and they had, I think, 200 and, and 73 patients, which is not very much in these suction circumstances. So, so for us later, it became evident that we need more information in patients, to know whether it is effective or not. We need to do large clinical trials to study, temperature management, hypothermia treatment in patients.

Paul Swindell: [00:09:09] Could I just take you back to one of the things you were saying when you were doing your study and your PhD, you were saying you were looking at animals.

Do animals though, that they have, a lot of them have a natural ability to hibernate anyway, don't they? So how does that come into the picture and do humans have anything like that?

Professor Tobias Cronberg: [00:09:26] No, humans don't have that ability to hibernate, and, and the animals used, in the experiments for hypothermia, don't have that ability. So a rat, which is the most common laboratory experimental animal, it can�t hibernate, and pigs has also been used, but not very much.

But the animals, rats and mice, they don't, they don't hibernate.

Paul Swindell: [00:09:51] And, and also, as I mentioned to you just before we came on, on the air,

There was a, famous case at the end of the nineties, which featured a, a Swedish doctor Ana Bagenholm, who I believe, experienced a case of hypothermia for a couple of hours, I believe it was, cause she was skiing in Norway and, fell into a river.

Do you know much about that?

Professor Tobias Cronberg: [00:10:14] Yes, I remember. I know I've seen a program on television about her.

Professor Tobias Cronberg: [00:10:19] This, this is a very, very interesting case and it's sort of a proof of principle case. With Ana Bagenholm because what happened was that she was skiing, and down a slope and she went out on the ice at the end of the slope and was sliding out on quite thin ice, actually, and got trapped with her head into the water, and was, and drowned, on the ice with her head being put into the water, and then she had a cardiac arrest, if I've understood it correctly. So, so this is not an unusual situation with cardiac arrest, in the circumstance of drowning, of course.

But what was very special with Anna Bagenholm and ideal for her was that her body, and particularly her head was cooled before she had the cardiac arrest.

And we also know that from experimental settings that the most protective effect of cooling is if you could the brain of the animal or of the human in this case before the heart stops. Because then all the damaging processes will be much slower.And for her, they couldn't rescue her because of the thin ice.

So, her friends couldn't, couldn't rescue her, and they eventually got a helicopter and somehow they rescued her and she was transported and put on, on, artificial circulation in the helicopter. And slowly rewarmed and very, very slowly, her heart started beating again.

And it was so remarkable because she had at least, I'm not sure how long, but at least one hour of circulatory arrest. And that's very similar to these thoracic surgery patients. And, and that explains why her brain didn't get damaged or more damaged, by the cardiac arrest.

Paul Swindell: [00:12:19] I understand that she was like, over two hours in arrest and her body temperature went down to 13.7 degrees, which apparently was the lowest ever recorded. And it's pretty amazing. But I don't know if you saw the news last year, towards the end of last year, there was a report of a British lady who had a similar case who suffered hypothermia in the mountains of Spain.

And she arrested for, six hours, I think it was. But they managed to bring her back, and they always say, "they made a full recovery", but of course, we're never really know whether she has made a full recovery.

Professor Tobias Cronberg: [00:12:59] No, but it's, I think it's a very, very strong and important message here. And that is if you are cooled before you have the arrest, then you have a very favorable situation.

And that's also very well known to doctors that you cannot decide that the person is dead.

Before the person has been rewarmed, because there's always the chance that the cooling or the chill has had a protective effect and not the patient will survive.

Paul Swindell: [00:13:31] There's a saying isn't there?

You're not dead until you're warm and dead.

Professor Tobias Cronberg: [00:13:35] Exactly, exactly. And it's also interesting, we did a meta-analysis of the experimental data on hypothermia after cardiac arrest, all the animal research we put together. And looked at the evidence in favour of hypothermia. And it showed that the strongest evidence is for, prearrest cooling or intra arrest cooling of the small animals.

And we have actually. All too few data on large animals with post cardiac arrest cooling, which is what we do with the humans. When, when we are cooling after arrival to hospital.

Paul Swindell: [00:14:17] Obviously we don't know for My cohort, for people like myself, we don't know. The majority of them are going to go into an arrest. So, we can't really put us into a cooling situation firsthand unless you, you're there by chance. But do you think it would, I don't know if the technologies are there, but, in first aid situations with paramedics and things like that, would they have cooling apparatus with them?

Would that be a practical scenario for them to adopt in the future if they know that, you know, as well as getting a defib and doing CPR that we get a cooling pack, whatever that looks like? I don't know. But is that something that you could see perhaps coming in the future?

Professor Tobias Cronberg: [00:15:02] Well, we can certainly, we can't exclude it, but there have been studies trying that approach because it's so obvious for, from, from experimental studies that it would be a great advantage. So there has been a big study looking at the prehospital cooling with intravenous cold fluids, but that did not show any benefit, some signal towards harm, because cold fluids will give you a load on the heart.

So, there's a risk of, cardiogenic shock. The patients will go to shock because of the fluids. So that was not a good approach. And then there was a, study, which was, centered from Stockholm in Sweden, with, with nasal cooling, where they try to call through the, nose. Most of the patients with a special technique, uh, with preparation and, that didn't show any effect. however, a small signal to boards possible effect, at least the context included that it may have some effect, but it was not a significant can't affect anyway. And I, it may tell us that it's the main, main thing if a person has a cardiac arrest, is to get the heart restarted.

And if we start doing other things, maybe we won't be as successful restarting the heart.

Paul Swindell: [00:16:30] That�s true, that�s true.

Professor Tobias Cronberg: [00:16:31] So there are, there are problems with any approach. And if we compare a human to a mice or a rat, well, it's much more difficult to cool a human. You can't just put a few ice packs. It won't too much difference to lower the body temperature of such a big animal, lesser human.

It takes a lot of time and a lot of effort and a lot of cooling power.

Paul Swindell: [00:16:59] Okay.

So, can we go back to sort of the turn of the century? It sounds a funny sort of phrase. So back, back at the early two thousands, you said, you noticed that, it was obvious that cooling worked for you. So, you started doing that in your hospital then presumably.

Professor Tobias Cronberg: [00:17:14] Yeah, that's true.

Paul Swindell: [00:17:19] What did you start seeing?

Professor Tobias Cronberg: [00:17:21] Well, it was a great enthusiasm. And the big thing I, I think at that time was a shift in favour of the cardiac arrest patients. They became a very interesting patient group in the ICU because suddenly the cardiac arrest went from being a condition where we could do nothing, to become a condition where we could do a lot because we could do cooling with the cooling machines, fancy new apparatus.

I think that was very good for the cardiac arrest patients. And, and, it was shown in, in many registers that, survival, went up after the introduction of, cooling. I think that's important too, to remember as well that, probably many things improved for the cardiac arrest patients because before that time, it wasn't obvious that a cardiac arrest patient would go to the ICU.

They may go even go to a regular ward without any artificial ventilation, and now because they needed to be sedated and not officially ventilated during the cooling process, they probably got very good intensive care, in the package, so to say.

Also, we started with a more advanced methods to diagnose brain injury, to, to be able to do a more advanced prognostication to decide which patients would have a good outcome eventually in which patients had such severe brain injury that it wouldn't be beneficial to continue treatment.

And that was also probably very good for the patient. It made it the care more safe and the decisions around life sustaining therapy more safe, I think.

Paul Swindell: [00:19:10] What would these patients, in hospital cardiac arrest victims or were they out of hospital or were they both?

Professor Tobias Cronberg: [00:19:17] Both. Both. we didn't make any difference whether it was in the hospital or out of hospital. for in hospital cardiac arrest patients, they often have more significant comorbidities because they're in the hospital for a reason. And that may be a reason not to. To give full intensive care, for example, for a patient with advanced, cancer of some kind, may not be of benefit for the patient to have that care path.

But those decisions have to come later. When a patient have a cardiac arrest, it's a full action and full intensive care from the beginning. And then you can, you can sometimes have to back off.

Paul Swindell: [00:20:02] What was the scenario in Sweden at that time?

Cause there's sort of general consensus from the UK is that the Scandinavian countries are ahead of us in the curve. As it were, regarding having AEDs in the community and encouraging people to do CPR and having the equipment and the processes in the hospital once you get there.

Professor Tobias Cronberg: [00:20:23] I wouldn't say, I think, I think at this that the curve is lifting around that time around 2000, around 2000 or even, even later. So, I think you could see the real surge in, in survival rates in Sweden comes after the introduction of hypothermia. But at the same period, there is a lot of training in CPR in the community, and there is a public movement of, lay people, CPR.

it's around that time and, and we have seen very clearly in the Swedish cardiac arrest register, how survival and the use of bystander CPR are parallel curves.

Paul Swindell: [00:21:21] So you've been doing, therapeutic treatments for a while then, and then, had that been spreading around to other hospitals and to other parts of the world? And then what, what was the motivation for coming up with the TTM, trial? The initial one.

Professor Tobias Cronberg: [00:21:37] Yeah. So, so the, the introduction or the implementation of therapeutic hypothermia was a global movement. And, a lot of believers, who had been doing experimental research perhaps, or were just doing clinical research. We're implementing these treatment all over the world in a parallel process.

So, it wasn't something that spread from Lund to a other places, certainly not, but it spread from many places. And there is still a very much of a movement and a great interest in hypothermia all over the world. But the TTM. So, we were also part of the believers, because we had so much evidence from the experimental research.

As we, as we thought, at least, and then Nicholas Nielsen, he did a meta-analysis, of the clinical evidence for therapeutic hypothermia, together with the clinical trials unit in Copenhagen. Copenhagen is very close to Lund, it's just over the sound here. And we have a lot of collaborations. And Nicholas works with very good statisticians and clinical trialists in Copenhagen, and they could show that the evidence, for therapeutic hypothermia in humans were insufficient, and that, it could be a benefit or it could be no benefit, or it could even be harm.

We couldn't tell from the studies that were performed. And I think that changed something fundamentally for us, in the group. And we decided to, do a large international trial and we started to, form the group around the TTM. The first TTM trial when we were discussing the TTM trial, we first thought that we would just redo the previous trial.

Test whether coding is better than no coding, but since the guidelines at that time, they recommended cooling for these patients. We many people thought it would be unethical to randomize patients to know cooling. Since, since a lot of people all over the world thought that it was shown. That cooling was working and the guidelines stated that it was shown or there was evidence, strong evidence in favour of hypothermia.

So that therefore, the first TTM tried was a bit of a compromise where we decided to, just to compare two different targeted temperature, 33 degrees and 36 degrees. Temperature where 36 was quite similar to no treatment or as far as we could go in that direction. And then we did this very large trial with 950 patients, so it's much more than the other trials together.

And we saw absolutely no difference between 33 and 36 degrees. And I think that was very, very surprising for many people in the field because from the experimental research, we should certainly have a very big difference between 33 and 36 but we didn't, and we looked at a lot of different outcomes for the patients.

Of course, survivor level, of cause neurological function at six months after the cardiac arrest, and we looked at cognitive functioning detail, we looked at biomarkers of brain injury in the blood. And we saw no differences between the groups. So, so that led to a change in the recommendations from the international organizations that, 33 or 36 degrees is just, just as good.

Paul Swindell: [00:25:22] You still felt that cooling was better than no cooling?

Professor Tobias Cronberg: [00:25:27] Well, I felt that we needed to take it all the way. I didn't feel that, I personally, I didn't feel very strongly that cooling was better than no cooling. I felt that the may be in effect still, but I'm, I'm not sure. And I'm still not sure because we are still doing the TTM 2 trial. I think it's a, I think it's equally possible that there is no effect of cooling.

That there is, is an effect.

Paul Swindell: [00:26:01] Oh, interesting. So what, what is it the people who, say that cooling works, what is it they think is actually happening with the, with the brain and with the body when you actually call someone? What, what processes are we changing?

Professor Tobias Cronberg: [00:26:14] Well, we are certainly doing a lot of things in the brain when we see, when we cool a patient that's no doubt about it. I mean, we. We slow down all the biological processes. It's just the same as when you take your milk package of milk and put it in the refrigerator. You protect the milk from, from breakdown, and you protect the brain from, from breakdown and damage due to a lot of different processes that has been shown in the experimental animals.

And we have proof of principle. Well, w with this, physician who went into the cold water, as you, as you referred to, and, we have from patients being cooled for thoracic surgery, we know that it's very a very potent, treatment, but we don't know if. When we do it in a delayed fashion as we do with the patients today, if that is effective.

And that's my major doubt. I'm doubt that, that we do it early enough, I think we would need to be much faster, and have some kind of method to very effectively, without any side effect cool the patient, on the scene.

I doubt that it is effective to do it, as, we do it.

Paul Swindell: [00:27:35] So you think that the damage is already done as it were?

Professor Tobias Cronberg: [00:27:39] Exactly, exactly

That's what I'm afraid of. At least that we are not, we are not, protecting the brain early enough

Paul Swindell: [00:27:49] And I guess that comes back to what we briefly talked about earlier, getting the paramedics, equipment to be able to do that. But then, as you said, that adds another, another job to be done, as well as trying to restart the heart, which is obviously the most important thing to do.

So, its a tricky one isn�t it really?

Professor Tobias Cronberg: [00:28:08] Yeah.

So, this would, with hypothermia treatment or targeted temperature meat treatment is something that we will be living with for many years to come, I'm sure. And we will have to work with it and try to refine it to get as much as possible out of the treatment. But I'm not sure that what we are doing today, is effective

Paul Swindell: [00:28:31] are most hospitals these days might do most cardiac arrest patients say in, developed nations, will they experience the calling that, you�ve been talking about?

Professor Tobias Cronberg: [00:28:41] Yes, I would say so. Certainly, in the Scandinavian countries, but it varies over Europe and it varies globally as well. I think it's a lot more variations in the in the U S but there's big variations within Europe as well.

Paul Swindell: [00:28:59] you're currently undertaking a TTM 2, so how does that differ from your original trial.

Professor Tobias Cronberg: [00:29:05] Yeah.

So, in the TTM two we are taking the question one step further. We are now trying to evaluate whether hypothermia to 33 degrees as in the TTM one trial compared to no cooling unless the patient gets fever.

So, we're in the control group. We will only treat those patients who develop fever, which is about a temperature above 37.8.

So, if a patient gets 37.8, we will take them down to 37.5 and, and keep them there with the cooling device, for the first, 24 hours.

Paul Swindell: [00:29:45] Do people naturally go into a fever after they've had a cardiac arrest?

Professor Tobias Cronberg: [00:29:50] Yes, many people develop a fever of the cardiac arrest, and that's part of probably part of the global, systemic organ damage with a global, inflammatory process in the body.

So, it's common that you develop fever and the more fever you develop, the worst is your prognosis. It's related to worst prognosis to have fever.

So that's a, the reason why there is a recommendation to treat fever, and it's the same in stroke. Actually, there's a recommendation to treat fever because there is an association with the worst outcome.

However, whether we are actually doing something good by cooling, we don't know, because it may be that it's just a marker of a more severe damage.

So, so we don't, we don't even know that for sure, but we thought that in the TTM 2 trial, we will take it just one step further and decide whether cooling for patients who do not develop fever, whether that is any good or not.

Paul Swindell: [00:30:54] Yeah, that's interesting. And so how far along are you in this trial?

Professor Tobias Cronberg: [00:31:00] The TTM two trial has included 1900 patients just as planned. It's the largest cardiac arrest trial ever performed, and we are now performing the follow-up, the six months follow up and trying to complete it. It has been, a problem with the covert pandemic of course, because we can't see the patients face to face.

We have to do follow ups, with telephone instead. But we are, are pressing on with our, schedule and we believe we will be able to publish the results in the end of this year or the beginning or next year.

Paul Swindell: [00:31:39] Okay that�s great.

So, what are the outcomes you're looking for? Is, is it just, not that they survive, but they survive with particular or better neurological outcome, is it?

Professor Tobias Cronberg: [00:31:46] Yeah, certainly we are looking at different things, but the primary outcome is survival. And that's because it's a very robust thought. I'll come off the cardiac arrest. You can't really, you can't, you can never manipulate survival, either you survive or not, and if you can't get any, any kind of influence from your own perceptions into that, but the secondary outcomes is quality of life.

Of the survivors and also their neurological function in more detail. And then we have a lot of exploratory outcomes where we are looking at their cognitive function, their physical activity, and how they are, are participating in, in the community, et cetera, et cetera.

Paul Swindell: [00:32:35] Okay. So, you say you'd be publishing next year, and then do you get a feel for whether this is, been a, a benefit doing TTM two as opposed to TTM one?

Professor Tobias Cronberg: [00:32:47] Yes, I think. I mean, it will have a fundamental impact. If we can show that hypothermia is, or cooling to 33 degrees is effective, then I think a lot more centers will start using this treatment all over the world. That will be a very, very strong signal for, for working, to refine, hyperthermia treatment as well.

But if we don't show any effect, that will be to the other side. People will probably stop doing hyperthermia for patients who don't have fever, that will also have a fundamental effect. So, I think the world is sort of rather much, the or the cardiac arrest community's rather much waiting for the results of the TTM to try and.

Paul Swindell: [00:33:33] Yes. Yes. I can understand that. A lot A lot of weight on your shoulders.

Professor Tobias Cronberg: [00:33:38] Yes, yes, it is.

Paul Swindell: [00:33:41] I'd just like to finish off this, conversation about, therapeutic management is, it's sort of throw you a left field type question.

Do you think we can use this sort of technology, to put humans into a sort of pseudo hibernation so that maybe it can be used in other fields like space travel or preserving people so there life span is longer?

Professor Tobias Cronberg: [00:34:04] No, I don't think so, no.

Paul Swindell: [00:34:08] No?

Professor Tobias Cronberg: [00:34:09] I don't know, but to slow down, your metab, metabolism may be good for you. It may make you live longer. There are some, I mean, some, some data that the starving is slow grade starving will make you live somewhat longer. Cooling down the body and then re awake patient or a person, I don't know. It's signed. It's sort of a scientific future that I don't, I don't want to be part of, at least I think we are so many people on the world anyhow so we should leave space for those coming after us, but that's more ethical issue I guess.

Of course, I mean, hypothetically cooling down somebody and putting them in a spaceship and having some, some, machine to thaw them when they arrive. It's, yeah, theoretically you may be right. Maybe, maybe possible for long travel is extending over a hundred years or something like that.

Paul Swindell: [00:35:13] Or maybe, even though I don't know if for shorter periods, like getting to Mars or coming back from, there can be a couple of years, I believe, if, if you, leave at the wrong time in the orbit,

Professor Tobias Cronberg: [00:35:25] Yes, yes. I think you could, I mean, probably you could extrapolate from, from the, from your package of milk again, that putting the milk in a refrigerator will buy you some time, but not a lot of time. A few days, for, it gets sour, but putting it in the freezer would buy you a lot more time, I mean, it's still a limited time and putting a human in a freezer. I don't think we will be able to thaw them afterwards because there is so much cell damage.

Paul Swindell: [00:35:59] It�s not all good news being in the freezer.

Professor Tobias Cronberg: [00:36:02] No, I don't think so.

Paul Swindell: [00:36:08] Okay. Tobias, thank you very much, has been a really interesting conversation about this subject, which is, you know, it's, it's played a part in my recovery and I'm sure that played a part in many other people's recovery as well. And I'm, really glad that you guys are looking at this subject and that you did back in.

Back at the end of the nineties, last century. And it's going to be really interesting to see the results of the TTM 2 and where that takes us.

So, good luck with it all and I hope we speak again soon

Professor Tobias Cronberg: [00:36:38] Thank you, Paul. I just want to say a last word and that is that even if we would, show that therapeutic hypothermia is ineffective in the way we use it today, it wouldn't mean that the treatment has not been beneficial for the patients. I think it has been tremendously beneficial. Because a lot of things came with the package, had a lot more focused on the cardiac arrest patient in the ICU.

A lot more, more, artificial ventilation of focus on that, sedation regimes, EEG, surveillance, et cetera. And we will talk more about that

Paul Swindell: [00:37:15] Yes, it's very valid points and yeah, thanks for raising them.

Alright, Thanks a lot. Bye. Bye.

Professor Tobias Cronberg: [00:37:18] Bye

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Presented and edited by Paul Swindell.

Recorded April 2020.