For today, we're doing by the lovely Dr. Moon of the Duke Hyperbaric Chamber at Duke Medicine and Health. He's also a trained an anesthesiologist. We'll also invite him and I'll spotlight him to talk a little bit about himself and his background, which actually comes from Duke's hyperbaric chamber. Thank you. My pleasure to be here tonight. I am an anesthesiologist also. Half of my job is aestheticizing people for surgery. The other half of my life I spent treating patients with hyperbaric oxygen for various reasons including decompression sickness. I also do research. I also research diving research, and we've done some space research. In fact, just recently we were exposing some new astronauts to high altitude hypoxia to give them a sense of what it feels like to be hypoxic. The lower left, by the way, is the space shot of the East Coast. Several years ago we got in Durham, North Carolina, which hardly ever we get snow. We've got something like 24 inches of snow in 18 hours and to say the least, it shut down the town a bit. It doesn't happen that often, but when it does, it's a big event. Now, many of you may be familiar with the problems of space medicine. There's increased G force during take-off and re-entry and this of course you know this. Sometimes you get out of bed in the morning, all of a sudden, then you feel a little dizzy just for a moment or two. That effect is due to blood essentially redistributing itself into your legs and your cardiac output drops just temporarily. There's something called space motion sickness that is not well understood but many, if not most astronauts experience nausea and vomiting for a couple of days when they first get into space, and then if there's an accident such that the spacecraft becomes decompressed or the spacesuit becomes decompressed, there's a potential for decompression illness or ebullism. Ebullism, by the way, is the situation that exists when the ambient pressure is reduced to the water vapor pressure at body temperature, which is 47 millimeters of mercury. When that happens, blood boils and essentially your body would blow up and you die very quickly. Decompression illness can also occur as a result of EVA, spacewalks because all of the spacesuits that exist in the United States or even the Russian program have an ambient pressure lower than the pressure inside the normal spacecraft or the ISS, the International Space Station. When you enter a spacesuit and go outside to do stuff, there's a potential for decompression illness. Micro meteorites are zinging at 25,000 miles an hour. There aren't that many of them, or at least the density is really small. But if one were to interact with the spacecraft or spacesuit, this could result in severe injury. When you're in space inside an enclosed environment, there's not a whole lot of gas volume and so if somebody spilled something, let's say they open a bottle of anesthetic if you happen to have one and the entire crew is exposed to anesthesia. Then two really big problems are bone calcium loss and muscle atrophy, particularly bone calcium loss. This is something that occurs in general medicine. If you put somebody to bed for whatever reason, for a period of 2, 3, 4 weeks because they have some serious illness, the bone calcium starts dropping. Calcium is leached from the bone by virtue of the fact that there's no gravitational stress anymore when people are walking around and that calcium gets excreted in the urine and it is largely permanently lost. Of course, that occurs in space. Without stressing the bones, the skeleton, calcium is lost from the bones and over the course of a trip to Mars, there might be, for example, a 20 percent loss of bone calcium. Then radiation is a huge problem because here we are on Earth, protected by the Earth's magnetic field from solar radiation and cosmic rays, mostly. Although there is some. But once you get outside the Earth's magnetic field, there's a severe potential problem of getting big doses of radiation and it's not just a matter of putting on a lead apron. Lead doesn't work very well for those kinds of radiation, cosmic rays, or solar-related radiation. I will talk about that in a few minutes. Dr. Moon. I'm sorry. Yeah. Go ahead. You had a question. I can say we have a question to check. Could that bone loss that you were talking about before the bone calcium loss, could that be mitigated through pharmacological measures like bisphosphonate? Yeah. In fact, there's been some work on that. Basically, it's not known whether that would work or not in space, but it's an open question and something that needs to be investigated. A very good question. Reflux, that's heartburn, that's when gastric acid, stomach acid goes and northward it extends into your esophagus and we've all had reflux. You have a big meal then you have a carbonated beverage and you start feeling a little bit of heartburn acid in your chest. One reason that isn't a constant problem is that gravity because we spend most of our life in the upright position. Gravity helps keep stomach acid down in the stomach. But in space of course that can be the gravitational effect doesn't exist, and reflex can be a real problem. Then related to anesthesia. When we anesthetize people, we often put a breathing tube into their trachea, and there are some practical problems in doing that because what you do here on Earth is you put a device in, lift up the tongue, and put the tube into the trachea, but in space, if you try and move something in one direction, you go in the opposite direction and you lose all ability to do that sort of thing. Then we'll talk about orthostatic intolerance after re-entry, what this means is the tendency to faint after going back to Earth. Then of course, we don't really know how drugs will work under effects of space. Let's move on. It's very hard to submit people to waitlist conditions here on Earth. There are some so-called models of it. One model in experimental animal is the device you see on the left, which is a harness that allows a rat to walk around on its four paws in the head-down position. What this does is, is redistribute blood towards the head just as it tends to do in space. You can get certain information from that. The middle panel shows immersion. If you choose the temperature of the water very carefully so that it's close to 30 degrees or 32 degrees. Then there's no net heat transfer between the water and the skin. If you ever have a chance to experience this, it's wonderful. It's a terrific feeling, it feels like you're in space because you hardly noticed the water and you get the same redistribution of blood towards the head as you do in space. Then there are some experiments using head-down tilt in humans as shown on the far right. I hope this works. A NASA suit has five, seven pieces. The Russian equivalent is a one-piece. Adjustable arms and legs makes the process of dressing a good deal quicker. It's such a successful design that the next generation of NASA suits are likely to follow their example. The cosmonauts simply climbs into the back. The backpack is locked in the place behind them. Both cosmonauts and astronauts familiarized themselves with their suits and their sense of weightlessness in a control buoyancy tank. This is the NBL in Huntsville, Alabama. Requires an astronauts and cosmonauts to rehearse for in around space station or shallow rock ups minimizing the amount of time spent exposed to the dangers of space itself. That's one way of training astronauts. It's not perfect obviously because in space you don't have the water, you can't swim, but it's better than nothing. Now, another way of simulating microgravity is this. It's going over the sky, it sought of tosses you. The pilot flies the airplane [inaudible] that basically flies around you as you are free falling. You really can't wait for the next gravel. I don't know if this is a throwback to some embryonic recollection that we have or what, but it is very soothing and exonerating and a lot of fun That's real microgravity, but of course it only lasts for a few seconds and then you have to pay back by experiencing high G and then you get the next one a couple of minutes later. Dr. Moon, we have a quick question about the head tilt in microgravity. What is the difference between the four degree head down tilt and the six-degree one used to induce the symptoms of SANS, S-A-N-S? The actual head down tilt angle is a matter of arbitrary choice. For whatever reason, the people doing the experiment that I showed you pick that particular angle. But that's not to say that another angle might not be better. It's unknown what the perfect angle would be. Takeoff, of course, is associated with G force. When you're accelerating from zero miles per hour to 18,000 miles an hour. That's obviously the shuttle taking off, but the newer spacecraft are exactly the same. The high G is experienced by people on board as well. Back in the shuttle era there was actually a plan in case there was an emergency that everybody could get out. Here we are sitting on Earth or standing on Earth. Our muscles are working against gravity and so there is a tendency to be in a perfectly upright position. But of course in space your joint angle relaxes to the point of least stress. So if you're just hanging out or sleeping, you would experience the position like the man in the fourth panel. In fact, people sleep exactly in that position. Somewhere I have a photograph of a bunch of people asleep in space and their arms are up, just like you see there. Since the tendency for gravity to hold blood down into our abdomen and legs is no longer there, this redistribution of blood up into the chest and the head. This is an American astronauts Shannon Lucid. You can see on the left a very attractive young lady on the right. She's got significant facial puffiness from this exact phenomenon. This is a drawing of the venous system. The majority of the blood in our circulation is actually in the veins and it's in largely the leg veins and the so-called splanchnic veins, which are in the abdomen. That forms a large capacitance, if you think of it electrically, there is a lot of volume there. What happens in space is that a large amount of this volume is redistributed up into the heart and the lungs and the body senses that and interprets it as if the blood volume is too high. You have central sensors in the atria of your heart that when the atria become enlarged the system senses that as hypervolemia, excess volume, and causes diuresis. Essentially what happens is you urinate off that extra fluid. Sometimes in real life people who were standing particularly at attention for long periods of time, they get tired, their legs get tired, and they lock their knees and lose muscle tone. What that does is it causes the veins in the legs to expand and you essentially bleed into your legs. What you see is a faint. Every drill sergeant in the armed forces knows this because particularly young, inexperienced soldiers, marines, when they're training them how to drill, a number of them indeed faint. The trick here is, if you're ever in this situation, to keep contracting your leg muscles to maintain or minimize the blood volume that's trapped in your legs. Now, if you take a blood sample as shown on the left and you put it into a centrifuge, what you'll get and many of you may have seen this. The red cells, which are slightly heavier than plasma, will settle to the bottom and separate from the plasma above. Here's the plasma, and here are the red cells. If you measure the heights of the red cells and divide by the total height, you get a number called the hematocrit. The hematocrit is typically between, say, 35 and 40 for women and between 40 and 45 for men. The sample over on the right has a relatively high hematocrit. Now, if you lose blood, if you donate blood, if you go to the Red Cross, they'll take typically around 500 mLs of blood. You can tolerate this reasonably well. You may feel a little faint when you get up, and that's why they swaddle you off to sit down and relax for a few minutes and then drink some fluid to replace the volume. But some people do faint. If you're seriously injured, and you lose maybe 1,000 mLs of blood, then you'll for sure faint, and you will probably have low blood pressure even when lying down. Now you can actually measure the blood volume by taking a dye such as Indocyanine green. This is the one that's typically used for this purpose. What you do is you dissolve the dye crystals in water. It's a bright green solution. You inject a known amount into a vein and let it recirculate for a few minutes. Then you take a sample of blood and you measure the concentration of green dye in the blood. Since you know how much you put in, you can measure the concentration of what you take out. You can then calculate the blood volume. This is a graph showing three individuals in whom this was done during space flight. This is from Skylab, which was one of the original space stations if you like. What you see here, this goes from zero to about 90 days of spaceflight. You can see at 30 days, these individuals, one person had normal blood volume or normal plasma volume. One person had about a three percent drop. One person had a 10 percent drop in plasma volume. By 80, 90 days, all three individuals had dropped their plasma volume from 12-20 percent. One person actually had these three, and then this one actually had a drop in red cell mass as well. In space, this doesn't really matter because the heart is sensing the appropriate amount of volume for what it needs to maintain circulation. The fact that the plasma volume is lower really has no physiological effect. To test the astronaut's ability to exercise during flight due to reduced blood profusion. That's an attempt to try and maintain blood volume. Not particularly successful. But here's a scenario. Your colleague in space sustains a severe leg injury while performing a repair of a broken valve. His hamstring is severely swollen, and he feels faint. Blood pressure is 90/50, heart rate 120 beats per minute, and you decide that he has to be evacuated back to the Earth's surface. What concerns do you have? What would you think? I'll go fast. It's clear that he suffering from trauma because the hamstring's fairly swollen and he feels faint. The priority would be to make sure that this trauma is dealt with as soon as possible and make sure he doesn't lose too much blood, I guess. That's exactly right. Presumably, he's lost some blood into his leg, and there are minimal medical supplies on the ISS, and so he has to go back home. There are some practical problems of treating this in space. One immediate solution would be to start an IV and infuse some fluid. We have a really good answer in the chat saying that redistribution of the blood on re-entry. So if you're sending a kind of emergency response will compromise the perfusion to vital organs and basically, the shifting blood flows will cause the issue. That's a very good answer and it's right on the money actually. But here in space, if you have a bag of fluid and there is some up there, you need a way of getting all the air out. Of course on land, on the earth's surface, you just hang the bag up and of course the air flows to the surface. If the bag had gotten shaken up, you get what's shown in the lower right, you get micro-bubbles. These have to be filtered out. By the way, there's been some work on doing surgery actually in space. This is Dr. Campbell from Baylor University. This is in the airplane that does those parabolic flights and has looked at the challenges of doing laparoscopic surgery and there are some problems. In space, for example, you have a bleeder, i.e a small blood vessel that's oozing blood and because gravity doesn't take the blood away, it doesn't allow the blood to ooze off the surface of the limb, it builds up and so it obscures your ability to find out where the bleeder is. Just for fun, I'm going to show you this little video. Oh, sorry. [inaudible]. CPR would be challenging and then this is a shuttle landing. Good job. [inaudible] a few seconds before landing, the pilot will pull the nose up to create a lot of lift and let the tires just [inaudible] one way. [inaudible]. The point here is that now you're landing, you have to pay back that acceleration in form of deceleration and you're exposed to, again, high G. This manifests itself even in normal people as a tendency to faint. [inaudible] carried out of their return vehicle, put into a reclining chair and kept there for three or four. When astronauts land, they have to sit down and relax and drink some fluids just as you had to in the blood bank. Now, this is just to show you a change in heart size. This is heart volume, end-diastolic volume and stroke volume immediately post-flight. In fact, it lasts even for a week or two post-flight. There's a 20-30 percent drop in the heart's mechanical function due to reduction in fluid volume. Now, if you're starting off as the fictitious patients a few slides ago, if you're starting off hypovolemic, then who knows what might happen to blood pressure during re-entry and landing? These should have been zeroed out. This is an issue. This is bone calcium loss. What you see here is change in calcium level in the calcaneus bone, which is your heel bone essentially, and the green dots represent controls. These are people living their everyday life on earth. Of three Skylab astronauts, one person maintains bone calcium in the normal range, but two others had significant loss over the course of 80 or 90 days. The gray squares represent what happens in bed rest. It's exactly the same thing as being in space. Another scenario, you're on the way to Mars and a leak is discovered in the spacecraft causing loss of pressure, and your companions are acting strangely, what could be the cause? What happens is that hypoxia causes encephalopathy. If your oxygen partial pressure is too low, your brain doesn't work. This is an example of that. This is an individual at 25,000 feet altitude who is breathing oxygen. Then they took his mask off and asked him to write down numbers, subtracting by one each time from 1,000. You can see the top line of 1000, 999, 998 and so on. Within a minute, he's still doing okay except the numbers are becoming a little large, and within two minutes, obviously a big problem. Within three minutes is just hieroglyphics. Hypoxia is a very insidious thing. He probably doesn't even realize, or didn't even realize what was happening. Now, this is a a video of exposure of a flight attendant to 30,000 feet altitude in a hyperbaric chamber. The steam is just condensation as the pressure is reduced. The attendant is breathing oxygen, of course. Her task is to put nuts and bolts together. You can see initially she's doing perfectly fine. Now she's having a little bit of problem. Now she can't even get the nut out of the well. He's going to put the oxygen back on. You'll notice that she doesn't say, okay, I get it. Let's go back home. She just carries on carrying on and she probably isn't even aware that there's a problem. Now she's breathing oxygen for a few breaths, she's back to normal. Now, this is from the 1950s. This one's a little bit sexist. Her job is to put makeup on. There is a condensation from the reduction in pressure that change in temperature. Again, just carries on, carrying on. Now this has had tragic consequences. Payne Stewart, the golfer who won the US Open, was flying across country in a Learjet. The plane over flew its destination. They send up an Air Force jet to see what was going on. It appeared that the pilot in the cockpit eyelids were not conscious and eventually it ran out of gas and it crashed, killing everybody on board. Another example was a flight from Cyprus to Athens in 2005. There were a number of checklists that were overlooked. What happened was the pressurization was set to manual, and so when the plane took off, the aircraft just lost pressure as it send it. They put it on autopilot, and then of course the pilots lost consciousness the same thing and a plane crashed a little later and killed everybody on board. Now, what do you do medically when things go wrong? One thing that is likely to happen on a long interplanetary trip, like a trip to Mars. Bone calcium is being lost. That calcium ends up in the urine, and it's highly likely that somebody may develop a kidney stone. That one potential idea for dealing with that is for somebody on the spacecraft to put in an instrument into the bladder and visualize the ureter. Then have a urologist on Earth manipulate it and attempt to take out the stone. This concept was tested back in 2001 where a surgeon in New York removed the gallbladder from a patient in France, in Strasbourg. It worked perfectly fine. The link, of course, was perfectly good. The problem here is that the delay that is when the surgeon in New York moved his hands it took a finite amount of time for that signal to go to France, for the movement to occur, and then to have the visual feedback come back. It was only about 155 milliseconds. Now it was felt at the time that the allowable lag time is about a third of a second. It was well within the lag time, so I'm sure you could operate on somebody in Australia from New York. But in terms of Mars, the delay time is now potentially up to several minutes. It's not feasible to do an operation in this manner. Now there are some cardiovascular changes as we've mentioned. Really quick, I wanted to bring up one question from the chat that maybe you're able to add a little bit more too, which is on both those videos the person kept on carrying on their task as they were becoming more and more hypoxic, which is weird because they lose consciousness, tunnel vision, and maybe it goes away. I know that there are air force trainings for this very same reason that the first time you experience it, you don't actually notice it. Is there maybe more to add to that too? Yeah, that's right. The Air Force and the Navy-Marine pilots all have hypoxia training. The idea is, this is what it's like, and if you start feeling this way then you have to make sure that your oxygen supply is working or you better get the aircraft down to a lower altitude. If it were actually to happen in real life, you hope that you remember what it felt like. That's the idea of the training and they have to do it every so often. Now, one thing, when you're on a commercial jet, they always tell you if you're traveling with a child make sure you put your own mask on before you put the child's mask on which is the opposite of what you might intuitively want to do. The reason, of course, is the child has absolutely no interest in having a mask on his or her face. By the time you struggle and get it looped up, you may lose consciousness yourself. But you have to act quickly because if you're 30,000 feet, you'll lose consciousness within 90 seconds or so. It doesn't actually take very long, and hence the training for military pilots. Just to summarize, cardiovascular changes, increase in preload means simply redistribution of venous blood up into the heart so that it gets bigger. Cardiac output increases and that is sensed by the body as volume overload. Therefore there's diaphoresis loss of fluid through the urine to bring what it senses as the appropriate blood volume back to normal. But of course, during re-entry, that blood volume is now inadequate. In fact, before landing, astronauts are given salty liquids to drink. There are other ideas on what might work. This is a lower body negative pressure suit. Which was tried. The idea here is that you'd get into it periodically, perhaps every day, certainly before re-entry. There's a negative pressure vacuum, a slight vacuum applied to the lower part of the body, which tends to redistribute blood back into the lower half of the body and then induce the heart and the kidneys to retain fluid rather than get rid of it. Whether this would work in practice has not really been fully tested. Now, another scenario. You're in Earth orbit, your companion has just returned from EVA spacewalk and she reports elbow and knee pain. What would you do? It sounds like she may be experiencing some decompression illness. I'm not sure if you're able to re-pressurize anything greater than one atmosphere, but maybe putting her back in the spacesuit to re-pressurize. Yeah. Well, that's exactly right. This situation is due to the reduction in ambient pressure while in the space suit. Your partial pressure of nitrogen inside the space station is on the order of 0.8 atmospheres and then in the suit, the total pressure is about a third of an atmosphere and so the partial pressure of nitrogen is 0.8 times that, or potentially initially 0.8 times that and so you can get bubble formation. Bubbles tend to form in various places in the body. They often produce joint pain, is not certain why that is and in fact, this has been reported. Michael Collins, who was a Gemini astronaut, reported in the Smithsonian many years after he was actually in space. We've had a hell of a day. On top of everything else, my left knee has been aching for the past couple of hours, an indication that my preflight nitrogen purge did not work 100 percent. I have a mild case of the bends. Of course, if you have a cool job like an astronaut, probably the last thing you want to do is complain of a little knee pain. He didn't. This is the only case that we know of that has actually occurred in space and we didn't find out about it until over a decade later. How do you treat decompression sickness? You administer oxygen and you increase the ambient pressure in a hyperbaric chamber. The oxygen is administered because what that does is it washes out nitrogen and therefore increases the diffusion gradient from the bubble into the surrounding tissue. In space, there are no hyperbaric chambers, but there is a mini hyperbaric chamber, if you like, which is a space suit. You can increase the ambient pressure to 1.3 atmospheres roughly, which is probably better than nothing and indeed that's exactly what would happen. There's no DCS, decompression sickness, reported in NASA or Russia EVAs. Again, we don't know if there was any or they just aren't reporting it. But during ground-based EVA simulations with the same decrease in ambient pressure, but there's 20-50 percent decompression sickness. There's a mismatch between what happens in space and what happens on the ground. Again, is this reporting or is this some biological difference? We don't know. Really good question from Zoe in the chat. Why can the air lock itself not be used as a hyperbaric chamber standing? Well, it could except the amount of pressure that you can actually increase it to is minimal. The airlock is not designed for high pressure. The spacesuit obviously is, because when the astronaut is performing EVA, the pressure is 1/3 of an atmosphere. So the differential pressure is 0.33 and therefore, when the spacesuit is inside the ISS, you can obviously get 1.33, but that's about it. There has been over the years talk of putting a hyperbaric chamber in space, but to date, that hasn't happened. Does it also have to do a little bit with the amount of gas you need to pressurize the whole chamber versus an individual suit or no? Yeah. Well, that's right. There are a couple of problems. One is that, let's say you put a hyperbaric chamber up that you could pressurize to a standard pressure which would be 2.8 atmospheres or 1.8 atmospheres above ambient. It does require a significant amount of gas and oxygen for the victim to breathe, but also the weight of getting it up there. Somebody told me years ago, I don't know how many dollars per pound of payload, but it's extraordinarily expensive and to date the money has been spent, the space hasn't been allotted onboard the ISS and there is no recompression facility other than putting the person back in a spacesuit. Now, another problem is radiation. There are a couple of sources of radiation. One is cosmic radiation that's more or less constant. It comes from distant galaxies. It's all particle or mostly particle radiation, so it's much more destructive than X-rays or gamma rays. Just to show you on the left, if you can see the mouse. The other source of radiation is solar flares. When these occur, the amount of radiation is potentially lethal. These red arrows represent different moon expedition. This is Apollo 8, Apollo 9, Apollo 10, Apollo 11, Apollo 12. These vertical lines represent solar flares. You can see that NASA was just very lucky back in those days that those astronauts were up in space when there wasn't a solar flare. Now on the right is some radiation doses. The average US background radiation, we're all exposed to radiation is 2.2 millisieverts per year. But the units don't really matter. But getting a chest X-ray gives you 0.2 millisieverts. Airline crew are exposed to a little bit more because they're up at higher altitude. They may be up to 6 millisieverts per year. The average dose, as it turned out from Apollo mission was about 12 millisieverts, about six times the baseline. Then here, a two-point five-year mission to Mars would be around 1000 millisieverts. Now, this is a big deal because the higher your radiation dose, 1000 millisieverts is not going to kill you, but it does increase the risk of cancer. As I recall, the space program has decided that the maximum allowable dose is one that would increase your risk of cancer no more than about 20 percent above baseline. For a 45 year-old man, this is around 1500 millisieverts. For 45 year old woman is about 900 millisieverts. If you go to Mars and back, you've already used up those exposure limits. Now, what do you do if there's a solar flare? Because that increases the radiation dose hugely and potentially a single flare could be lethal. LED doesn't actually work very well, but one idea is to surround the living compartment with water. This is a cartoon of a design. The water shield has a thickness of about 0.3 meters, which would absorb most of the incoming particle radiation. Polystyrene is another reasonable absorbent, but you have to have a lot of it. Whereas water you can use, polystyrene is really just a waste at space. The advantage of water is you could recycle it. Of course you need 2, 3 years of drinking water when you go from here to Mars. But of course everybody's making urine. The idea then would be recycle it. Urine would be converted back into usable water by reverse osmosis and you can see in the lower right, a recycling device. This would be people urinate. It would be put through one of these devices and then pumped back into the water shield and then used as drinking water. Just to summarize, we've talked about various practical issues which I'm not going to overdue. But onboard physicians, if there are any physicians maybe unskilled at performing whatever procedures there are. If you put a physician on board, he or she may not be skilled at performing surgery that might be required. GE reflux, airway difficulties. There's a limited quantity of medical supplies. If you're in the hospital emergency room, there's virtually an infinite inexhaustible supply of intravenous fluids, drugs, you name it, but certainly not on the way to Mars. What you take with you is what you have. In orbit there's a delayed returned to work. It takes at least 12 hours to get someone back. On the way to Mars there's nothing you can do once you're headed in that direction, you got to keep going and you can't come back until you get there and then turn around. Postural hypotension is an issue and certainly if you've had blood loss for whatever reason, it would be much worse and could be lethal and then decompression sickness. I'm going to stop there and please fire away if you have any questions. Thank you for your attention. [inaudible] speaking with you. Actually, perfect timing. First off, can we give a big round of applause to Dr. Moon for coming in and giving this incredible guest lecture. It actually wraps up everything that we'll be talking about or have talked about already.