How Coronavirus Kills_ Acute Respiratory Distress Syndrome (ARDS) & Treatment (Coronavirus Lecture 4)
Welcome to another MedCram lecture. So I hear this question a lot. How does the coronavirus actually kill people? There was a recent article in the Lancet that showed that of 41 people that were admitted to the hospital, six of them died, and all of them were on ventilators, and they died with something called ARDS, and ARDS is how the coronavirus kills. It’s not just the coronavirus, but many other viruses including the influenza virus that we have every year.
How is it that this happens? It’s through acute respiratory distress syndrome, and I’m going to explain to you how that happens. So you first have to understand lung anatomy, and to understand that I like to show you a tree. So a tree has a tree stump, and then it branches, and then those branches branch, and then further those branches branch until finally you get to the leaves. And these leaves capture the sun’s rays, and that’s what gives you photosynthesis, and that’s how the tree lives.
And so what happens is that this tree and the branches increase the surface area of the leaves on the tree so that if you were to pluck off all of the leaves, and you were to put them on the ground next to each other, the surface area that is represented by those leaves would be larger than the shadow that is produced by the sun on that tree.
Well, it’s the same exact thing that happens with your lungs. You’ve got an airway, and then that airway divides into a right mainstem bronchus and into a left mainstem bronchus, and then you have a right upper lobe, you have a right middle lobe, right lower lobe, left upper lobe, and you have a left lower lobe. So this is the left side; this is the right, because you’re looking at the patient.
And then these things of course divided into much smaller branches, and instead of leaves at the end of all of these things what you have is something called an alveoli, which is a tiny, little, small grape-like structure that the air gets into, and the air of course has oxygen.
So what does this look like on a large scale? Here’s what an alveolus looks like. How many alveoli are there in the human body? Well, there’s about 600 million of them. These are very very small. So what happens is deoxygenated blood comes by, and its job is to pick up the oxygen that comes into the alveoli. And then when that oxygen comes in, it oxygenates the blood, and then that blood goes back to the heart, and then to the body, and all your muscles. That’s how you get oxygen. And so you can imagine that this is very very thin because the oxygen which comes down here has to diffuse into the bloodstream.
So far so good. But what happens? Well, just like when you hit your finger in the door, your finger swells. That’s because there’s inflammation occurring where you hit your finger in the door, and inflammation causes a leakage of fluids into the tissue space. So what happens here is that you get a viral infection. The virus affects your lungs, and with ARDS the entire lung becomes inflamed, not just in one area like you would have with a pneumonia, or one particular area, for instance, on your finger. And it would just stay in one particular finger, and your whole hand won’t swell.
No. With ARDS, the entire lung goes crazy with inflammation. And so what happens here, instead of having a nice thin area, inflammation goes everywhere, and you get a large barrier a fluid that goes into the interstitial space.
Furthermore, these capillaries start to become leaky, and fluid starts to leak into the alveolar space as well. And this starts to fill up with liquid, proteinaceous liquid, liquid that prevents oxygen from getting into the bloodstream. So instead of having nice oxygenated blood, this blood becomes hypoxic, and you become hypoxic if you have ARDS, and you have a hard time breathing, and that’s when you get placed on the ventilator.
There’s really nothing you can do to speed this up. There’s nothing that you can do to slow it down. You have to be supported on the ventilator so that you’re getting enough oxygen, and that the machine can breathe for you until, just like everything else after you hit your finger in the door, and the swelling goes away. This fluid will eventually go away as well.
The key though is keeping you supported during that period of time until the fluid goes away. And then once again, the oxygen will be able to go back into the system, and you will get oxygen back to your tissues.
So here’s another look at that. We get oxygen that’s going down into these terminal structures called the alveoli. They go into these alveoli, and they cause deoxygenated blood to turn into oxygenated blood, and then go back to the heart.
So I’m going to show you three things today that we have learned in the last 20 years that can improve survival in these patients who are on ventilators, to help them beat coronavirus or for that matter any other virus, whether it be influenza, whether it be respiratory syncytial virus, any other kind of virus for beating and getting better if you have ARDS, and you’re on the ventilator.
So the first thing that we’re going to look at is what they noticed back in 2000, and actually before, is that when we put people on the ventilator, and the ventilator puts a breath into their airways, what we were trying to do is we’re trying to make sure that we were ventilating patients well.
And that’s important in some situations because the blood that is poor in oxygen also has carbon dioxide, which is given up from the muscles. Well, this carbon dioxide would need to be ventilated to be taken out on exhalation, so CO2 will be coming out. Well in order to do that, we have to make sure that enough volume of air was going back and forth, back and forth.
The problem with that though is that we were inflating these alveoli, and then when we were releasing the pressure and letting the air out, these alveoli would collapse down, and nothing was keeping them open. So there would be opening and closing, opening and closing, shutting and opening. And so that was causing a lot of shear stress.
And of course, what’s the whole problem here that we’ve got? Inflammation is what’s causing the whole problem here in the first place, and that’s causing these membranes to become very thick, and the oxygen can’t get in there. And so by ventilating these patients with large tidal volumes, we were causing the inflammation to actually get worse than it would have been if we hadn’t done that.
And so the scientists started to look at this and say wait a minute. What happens if we just put a lot of pressure down here to keep these alveoli open and only use a small amount of tidal volume to ventilate these patients? And yes, we won’t be able to get as much carbon dioxide out of them, but we don’t really care so long as we’re not adding more inflammation to it. And so the first thing that we looked at this is back in the early 2000s. That this came out is low tidal volume and that would almost certainly cause the PCO2, that is the partial pressure of carbon dioxide in the blood, to go up. So this was called a low tidal volume strategy.
And sure enough, paper was published in 2000 in the New England Journal of Medicine, that showed that we could affect change, and we could decrease the mortality at the time from 40 percent down to about 31 percent mortality. So that was a huge drop in mortality, and all we did was we just ventilated people differently using low tidal volume.
Now, when you’re ventilating people with low tidal volume, it’s not very comfortable. They’re trying to breathe more because they don’t like that increased carbon dioxide levels. And so they would try to breathe over the ventilator, and they would try to breathe differently than what the ventilator was telling them to do. And in these cases, we would usually sedate the patients. But if we sedated them too much, bad things could happen to them. They could get blood clots; their blood pressure would go down.
And so the second thing that they came up with was actually paralyzing these patients using medications so that they were in perfect sync with the ventilators. And so that was paralysis. Paralysis requires pre-intensive care and intensive care unit. You need good ancillary services, you need respiratory therapist. You need good nursing. Something that you might not get if there’s a huge outbreak, but you could get if attention was made to this.
So this paper, also published in the New England Journal of Medicine, (And by the way, I’m going to give links to all of these papers in the description below) they were able to drop the mortality from 41% down to 32%, and this paper was published in 2010.
So far so good. What we also started to realize is that patients in the hospital for whatever particular reason. If you ever look at them in bed, they’re always on their back, and what we decided to do was flip them over, and there were a number of reasons for this, so that their belly was down, and that their back was up. We call this prone Positioning.
And if you do this for about 17 to 18 hours a day, you can actually decrease the mortality, they found, from 33% down to 16%, and this paper was published back in 2013. And so you can see here three breakthroughs in the treatment of ARDS: the final common pathway for morbidity, and mortality in the coronavirus we were talking about.
But the other thing about this, that’s interesting, is we can do a lot if we catch it early, and we get people into the hospital, and we get them in the Intensive Care Unit, and we get them on ventilators, and we’re able to appropriately treat them with good-quality medical care. And three things that really make a difference, then we’ve got a good chance so that they’re not another statistic of mortality, but they survive this.