Oxygen for the FRCA Primary

Gas Gas Gas: Oxygen (FRCA Primary)

Volatiles and Other Assorted Gases: Final Episode

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Introduction: Welcome to Gas Gas Gas

00:00 – 00:46

Please listen carefully.

Hello, Team Anaesthesia. Welcome to Gas Gas Gas. This is the best anaesthetic science podcast for the FRCA Primary exam. Our goal is to fill your brain with all this highly useful information.

Now, you might be in the gym right now, commuting, or ironing your scrubs, and there’s no judgement here. Gas Gas Gas will prime your brain for the monsoon of knowledge you need to imbibe. But regardless, the revision is eventually going to end. For now, expect facts, concepts, model answers, and the odd tangent.

Remember to check out the website, that’s gasgasgas.uk. There are show notes there with all the detail, plus links to foundational reference papers and anything else useful I find for you guys.

Anyway, buckle up, get ready for your mind to be bent into a new shape, and let’s get on with the show.

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Why Oxygen Matters, and What This Episode Covers

00:47 – 03:23

Key points

• Oxygen is mission-critical to life and to the exam, so a lot is expected of you.
• The full syllabus spans supply, delivery, gas exchange, haemoglobin, the alveolar gas equation, oxygen storage and delivery formulae, the haemoglobin-oxygen dissociation curve and V/Q matching.
• This episode covers: physicochemical properties, how oxygen is obtained for medical use, the pathophysiology of excessive oxygen use, and how oxygen is stored in hospitals.

Hello everyone, and welcome to Gas Gas Gas. Here is yet another episode. I’m sure you’ve waited these last two weeks trying to sit on your hands, trying to contain your excitement. But today we are elaborating on the oh-so-critical oxygen.

Now, much like morphine, everyone knows about oxygen, don’t they? We’re all breathing it right now, hopefully. And you could be forgiven for thinking, it’s boring, isn’t it? And we all really know that anaesthetic science is anything but boring, because it is mission-critical to life on Earth as we currently know it, and naturally rather mission-critical for your exams.

Because it’s so important, you are expected to know plenty about it, and this episode will scratch one or two of those itches. Because you need to know what we’re covering today: how you obtain oxygen, deliver it to a hospital, pipe it to your anaesthetic machine, and what the implications of too much or too little are. We’re going to talk about too much today. Too little, well, we all know about that.

But you also need to know how oxygen gets from the atmosphere to your mitochondria, the mechanics of gas exchange. You need to have read West’s respiratory physiology, at least most of it. Understand how haemoglobin works, what the alveolar gas equation is, what blood oxygen storage formulae exist, what oxygen delivery formulae exist, the haemoglobin-oxygen dissociation curve, and ventilation and perfusion matching, which West would cover. It’s basically massive.

We’re not going to do all that today, but one day in the future. Today we are going to cover the physicochemical properties of oxygen that you need to know about, how we obtain oxygen for medical use. We’re going to appreciate the pathophysiology and physiology of subpar oxygen use, and think a little bit about how oxygen is stored in hospitals: vacuum insulated evaporators. There’s a Viva Cast episode that covers just that, alongside a few other bits and pieces.

Naturally, talking about oxygen does follow on nicely from talking about other things that are oxidisers, like our nitrous oxide, and that’s because we touched on explosions in our Christmas special. Hopefully I’m not going to spontaneously combust during the excitement that is within me for this episode, but I think we should get on with it, shouldn’t we?

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Basic Properties and Naming

03:24 – 03:53

Key points

• Named by Antoine Lavoisier in 1777.
• Elemental gas, found in the atmosphere as diatomic O₂.
• No isomers of atmospheric oxygen.
• Colourless, odourless, tasteless.
• Atomic mass 16; molecular weight 32 g/mol.

Oxygen, named as such by Antoine Lavoisier in 1777, is an elemental gas, if you were to try to classify it. You will find it as two atoms bound, O₂, in the atmosphere. There is no such thing as an isomer of atmospheric oxygen, and it is a colourless, odourless and tasteless gas. It has an atomic mass of 16, but as it’s floating around as a diatomic molecule, and diatomic is a fancy way of saying pair, two oxygen atoms, the technical molecular weight is 32 grams per mole.

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Obtaining Oxygen: Fractional Distillation of Liquefied Air

03:54 – 05:21

Key points

• Air is filtered, then cooled to around minus 200 °C.
• This yields a nitrogen vapour phase and a liquid oxygen phase, separated by fractional distillation.
• Argon tags along with the liquid oxygen and must also be removed.
• The product is transported as very cold liquid oxygen.

How do we obtain oxygen to use in our anaesthetic circuits, when we spank it up to 18 litres per minute to really truly wash out that circle circuit, and we’re going nuts? Well, you obtain oxygen through fractional distillation of liquefied air.

I.e. you take air, you filter out the stuff that’s floating around in it, the PM2.5 air pollution et cetera, cool it to minus 200 degrees C, and you’ll end up with a vapour phase of nitrogen and a liquid oxygen phase that are quite happy to be separated from one another and can progressively be decanted out using fractional distillation. You might remember that from chemistry, when they talk about the fractional distillation of crude oil into its variously weighted components in order to have kerosene and petrol and all that sort of stuff.

Now, you don’t just have oxygen and nitrogen in air. There’s also argon, which tags along with the liquid oxygen. This needs to be removed as well. We’re not going to go into that.

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Hospital Storage and Pipeline Supply

05:22 – 06:20

Key points

• Liquid oxygen is pumped into vacuum insulated evaporators (VIEs) at the hospital.
• BOC on the side stands for British Oxygen Company.
• Pipelines operate at 4 bar, then pressure is down-regulated at the anaesthetic machine to one atmosphere.
• Without down-regulation, pipeline pressure would damage the machine.

Now, this oxygen is subsequently transported in its very cold liquid state and is pumped into vacuum insulated evaporators at your hospital. You’ve walked past them, you’ve seen them, you’ve stared gloriously up at them. It may say BOC on the side, B-O-C. That’s the company, and that actually just stands for British Oxygen Company.

And that’s all well and good. We know that that is piped to our anaesthetic machines down pipelines that operate at 4 bar, delivered into our anaesthetic machine, and then down-regulated in pressure to one atmosphere of pressure, which the anaesthetic machine operates with. Without that down-regulation, that pressure would damage our anaesthetic machine. We’re not talking Schrader valves and non-interchangeable connectors this time round. We’ll have to wait.

But that’s not the only way you can get oxygen to a patient. Through your anaesthetic machine we’ve got the flowmeters, then the walls, and then we also have tanked oxygen, or cylinder oxygen.

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Cylinder Sizes, Volumes and Pressures

06:21 – 07:53

Key points

• Size E (back of the anaesthetic machine): 680 L at 137 bar.
• Size F (under the resus trolley): 1360 L at 137 bar.
• Size CD (handheld, white): 460 L at 230 bar, because the cylinder wall is stronger.
• You cannot extract the full stated volume. A 10 L cylinder retains 10 L of 100% oxygen once equilibrated to atmospheric pressure.

Tanks you will see: on the back of your anaesthetic machine, you will see a size E tank, 680 litres of oxygen in there at 137 bar. Underneath resus trolleys you will probably see a size F tank. That’s 1360 litres, again 137 bar.

But now, if you were to go and pick up a full handheld oxygen cylinder, and you all know the one I’m talking about, it’s often white and you can indeed pick it up. If you look on that, it is defined as a CD tank, and this has 460 litres in it, and it is pressurised to 230 bar. So it’s a bit of an outlier, and this is because the nature of the tank is stronger. Therefore you can carry a convenient amount of oxygen around in a convenient form factor, you know, the size of the cylinder.

Now, it’s important to remember that if you were to try and get 460 litres of oxygen out of that tank, you wouldn’t succeed. Those tanks are about 10 litres, therefore you would have 10 litres knocking around as a remainder in your tank, which is 100% oxygen. But now that it’s equilibrated to atmospheric pressure, that’s just what’s in there. You wouldn’t be able to get it out unless you squirted something else in there to displace it.

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Cylinder Materials: Steel versus Kevlar

07:54 – 10:20

Key points

• Steel cylinders are made of molybdenum steel alloy.
• Kevlar-wrapped cylinders are aluminium with a Kevlar composite wrap: lighter and more convenient, but weaker.
• A pierced steel cylinder vents at high pressure, can become a projectile, and the oxygen plus steel supports oxidation and flame formation that enlarges the hole.
• A struck Kevlar/aluminium cylinder does not simply perforate. It fails catastrophically and fragments.

More oxygen tank fun. These tanks are made of molybdenum steel, which is an alloy of steel. You also have Kevlar-wrapped tanks. These are aluminium with a Kevlar wrapping to provide greater strength, and this is a composite material which is lighter and more convenient.

But now we’ve got to think, which is the better tank to use? And my mind naturally goes to what happens if you were to shoot one of these tanks. Some Americans, I think, have done this, at least to the steel tank. There’s a link to that in the show notes, it’s on YouTube. But there are two sides to this coin.

If your steel tank was to unfortunately get hit by a stray round, and by the sounds of it, looking at this video, not just a 9 mm prang from a Glock, but a robust rifle round or something larger, not NATO 5.56 but something bigger, you will pierce this tank and you will rapidly eject 137, well, 136 bar worth of oxygen out of that hole. Now that’s a lot of oxygen travelling quite quickly. This can convert your oxygen cylinder into a projectile, but also that amount of oxygen concentrated, plus the steel, causes a degree of oxidation and flame formation that can make that hole bigger as well. Check out the video.

So you’ve got a hole in a tank that converts the tank to a projectile, ejecting very oxidising gas at high speed that would support significant combustion if, for example, that was pierced inside an environment that was already on fire, where there was material to combust. Sounds suboptimal.

So now we look at our Kevlar tank and we’re trotting through the battlefield, but then that gets hit by a round. And this is Kevlar and this is aluminium, so it is far more susceptible to lower energy projectiles. But Johnny Squaddy running around with a lighter tank on his back, he might be able to avoid said projectiles a bit quicker, because he can move faster. But that tank is hit. It doesn’t just put a hole in it. The tank fails. It undergoes rapid unscheduled disassembly and prangs off aluminium and Kevlar shrapnel at a speed incompatible with nearby life.

This ultimately means that if you want to take oxygen to a casualty, one, do it when there are not rounds pranging around the place, and two, take a steel tank and keep your head down. Hopefully that’ll help you remember what these oxygen tanks are made of.

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The Pin Index System

10:21 – 11:20

Key points

• The pin index system prevents a cylinder of one gas being attached to the wrong port.
• The oxygen pin index is 2 and 5.
• Mnemonic: oxygen is O₂, so it starts with the 2.

The last FRCA fun fact that those swines may ask you to recall is the pin index of oxygen. Now, the pin index system is a means of preventing inadvertent attachment of one sort of gas-containing cylinder to an incorrect port, i.e. you wouldn’t want to put your nitrous on your oxygen line, or your CO₂ on your oxygen line, for example. We don’t use CO₂ any more, but they used to.

We have pin indexes which mean that you cannot successfully attach one thing to the other. The oxygen pin index is 2 and 5. Now remember, oxygen, O₂, therefore it starts with the 2, so at least you’re halfway there. I couldn’t tell you a clever way to remember that it’s 5, but if you start with 2, you’re already halfway to a right answer. I do not envy you.

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The History of Oxygen

11:21 – 14:40

Key points

• Second century BC: Philo of Byzantium observes water rising into a sealed vessel as a candle or a mouse consumes something in the air.
• Leonardo da Vinci notes that combustion and respiration consume the mass of air.
• 1604: Michael Sendivogius describes cibus vitae, “food of life”, and shows the same gas is produced by thermal decomposition of potassium nitrate.
• The prevailing framework was phlogiston theory.
• Three individuals identified oxygen at around the same time. Joseph Priestley is credited as the first to publish.
• Named by Antoine Lavoisier in 1777.

So on that depressing, despondent thought of all the bothersome things you may be expected to memorise and be able to regurgitate in an exam, I think we should just take a pause and think about the history of oxygen.

Now, oxygen obviously has been around since the somewhat early aspects of the universe. But what about humans? Because, you know, that’s where we’re really interested. One of the first recorded notions towards there being something in the air that was involved in combustion, and was consumed, occurred in the second century BC. It was by a curious Greek person called Philo, or Philo, who knows how to pronounce it, of Byzantium. They had noted that if they were to put a candle inside a container that was sealed with water around the bottom of the container, or a mouse in the container, you would see the height of the water climb up the inside of the container as something inside was consumed. At the time, they thought this was the so-called elemental air that was converted to elemental fire.

These observations continued to occur here and there. Leonardo da Vinci seemingly made an observation that combustion and respiration consumed the mass of air. And in 1604, a Polish physician-cum-gentleman-scientist type named Michael Sendivogius described a substance in the air as cibus vitae, or food of life. They subsequently also managed to demonstrate that this same gas was produced when potassium nitrate was thermally decomposed. Thermal decomposition is different to combustion. This is where you apply heat to something and it breaks down.

There are suggestions that a few other people also came to a somewhat similar conclusion at the time, but they struggled to align their findings with the prevailing opinions of the time. They failed to shout loud enough. They failed to challenge their colleagues. And therefore we remember Michael Sendivogius a tad more.

What was the prevailing opinion of these times? Well, it was the phlogiston theory, which we mentioned in our last episode on nitrous oxide, when it was described as a phlogisticated nitrous air [see changelog]. The phlogiston theory alludes to the fact that they presumed there was something in a material which burns off, and the remainder of that material is dephlogisticated, i.e. the bit that burns has been removed.

So science continued to bash on the door of this theory. And whilst three individuals around the same time formally identified oxygen in air, understood the role of combustion, as well as devising means of liberating oxygen from other reactions, our pal Joseph Priestley, who also attached his name to nitrous oxide quite successfully, is defined as the first person to publish about oxygen. He was a busy man, discovering nitrous oxide and oxygen. I’d be lucky if I discovered a £5 note under the carpet.

So there you go, a tad of oxygen history. And remember, named in 1777 by Antoine Lavoisier.

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Sponsor: Teach Me Anaesthetics

14:41 – 16:12

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Physicochemical Properties: Boiling Point, Critical Temperature and Critical Pressure

16:13 – 18:09

Key points

• Boiling point: minus 183 °C.
• Critical temperature: minus 118 °C. Above this, no amount of pressure will liquefy oxygen.
• This is why a VIE must operate below minus 118 °C.
• Critical pressure: 50 bar, the pressure required at the critical temperature to liquefy it.
• For the exam, prioritise boiling point and critical temperature. You can hang the whole VIE explanation off those two numbers.

What about the physicochemical properties of oxygen? Well, oxygen boils at negative 183 degrees C, i.e. if you have liquid oxygen at minus 184 degrees C, it’ll be happily a liquid. If you warm it up one degree more, it’ll boil off quite happily.

What is the critical temperature of oxygen? Above which any amount of pressure will not liquefy that material. So if you’ve got oxygen that’s at minus 100 degrees C, you could crush it in the centre of the earth and it would remain a gas. Too much energy. Whereas if it’s less than negative 118 degrees C, it will acquiesce and become a liquid. This is why you will find vacuum insulated evaporators must operate below negative 118. Check out that Viva Cast episode for more chat about the seemingly rather clever VIE that every hospital has.

You’ve had critical temperature, therefore we should also talk critical pressure. Now, critical pressure is the pressure you must apply to that material at its critical temperature in order to liquefy it. So if you’ve got some oxygen at minus 118 degrees C, you have to apply 50 bar, i.e. 50 atmospheres of pressure to it in order to press it back into liquid form.

Now, in an exam they’re probably more interested in you knowing what the boiling point and, very much so, what the critical temperature of oxygen is, because you can hang the conversation of how a VIE works off those numbers. Critical pressure, less important, but just remember 50 bar.

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Mechanism of Action

18:10 – 19:39

Key points

• Oxygen facilitates oxidative phosphorylation at the electron transport chain, on the inner mitochondrial membrane of eukaryotic cells.
• Oxygen is electronegative and readily accepts electrons.
• Its role is at the end of the chain, at complex IV, accepting two hydrogen ions and two electrons to form water.

So we are trying to shoehorn oxygen into some sort of pharmacodynamic and pharmacokinetic concept, although it’s somewhat challenging, because it’s not really a drug, is it? Even though we’re meant to prescribe it. I always feel quite anxious walking into the hospital knowing that I need a prescription for oxygen. Should I hold my breath? Should I breathe? Should I refer myself to the GMC or the police? Ultimately, I decide that I will cope without prescribing myself oxygen whilst I’m on hospital premises. And whilst I jest, there are very strong and robust reasons why we should actually prescribe oxygen to patients, which we’re going to get ourselves into in a little bit.

But what is the mechanism of action of oxygen? What does the body actually really use it for? Oxygen facilitates, as you might expect, oxidative phosphorylation. This occurs at the level of the electron transport chain. This is found on the inner mitochondrial membrane of eukaryotic cells.

What actually does it do? So an oxygen atom is electronegative. It’s got extra space compared to the number of protons it has in its electron fields, electron shells around it. Therefore it’s quite happy to accept electrons, or things that would offer up an electron. So oxygen’s role is at the end of the electron transport chain. Remember, this is complex IV in this. And it merely accepts two hydrogen ions and two electrons to form a molecule of water. Very hydrating stuff.

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Dose, and the Ethylene Anaesthesia Aside

19:40 – 21:08

Key points

• Normal inspired oxygen is 21%. Hypoxic mixtures are not recommended.
• Early 20th century ethylene anaesthesia used an 85% ethylene / 15% oxygen mix.
• Volunteer doctors and technicians reported unchanged heart rate, a pleasant experience, nausea, vomiting and headache. Nobody recorded cyanosis, and there were no saturation probes then.

What’s the dose of oxygen? Well, hopefully we’re all breathing 21% oxygen. I thoroughly would not recommend hypoxic mixtures. However, once upon a time, anaesthesia did involve the odd hypoxic mixture, accidentally or intentionally.

Now, there’s a link to an article that describes, in the early 20th century, the use of ethylene gas as an anaesthetic agent. And these very sensible folks, at I think the Letterman District General Hospital somewhere in the United States, thought, well, we best obtain some approval from the board before we do this, which was duly given. And then some of the doctors and some of the technicians agreed to be anaesthetised, to really suss out how good ethylene anaesthesia was. However, their mix was 85% ethylene and 15% oxygen.

And if you read the article, it is behind a paywall, but you might be able to figure out how to obtain it. They describe the patients’ heart rate not changing, them finding it somewhat pleasant. Most of them were nauseous afterwards, and several of them were sick after. Most of them had a headache. But at no point did anyone mention that they’d turned blue. Back then they didn’t obviously have sats probes, and you had to kind of wing it, didn’t you? I think we’re perhaps in slightly more sensible days, where we don’t just find an anaesthetic gas, think, this works quite well but we’re not quite sure, so should we just anaesthetise a bunch of ourselves and suss it out. Madness, right?

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Side Effects of Oxygen

21:09 – 24:05

Key points

• Cardiovascular: raises blood pressure. It is a vasoconstrictor and raises systemic vascular resistance.
• Respiratory: absorption atelectasis. Nitrogen is washed out of the FRC and replaced by oxygen, which is then absorbed, collapsing poorly ventilated alveoli.
• Mucosal drying of nose, mouth and trachea. Wall oxygen carries no moisture, as humidity would corrode the pipework.
• Retinopathy of prematurity in premature infants.
• CNS effects at greater than atmospheric pressure: cerebral vasoconstriction, headache, nausea, seizures.
• Quoted threshold: 60% oxygen at atmospheric pressure produces parenchymal change within 24 hours.

Side effects of oxygen. Interestingly, oxygen increases your blood pressure when you’re given more than you need. That’s its chief cardiovascular effect.

Respiratory side effects depend on what you’re doing to the patient. If you were to breathe 100% oxygen, eventually your lungs would perhaps think about trying to collapse, particularly at the bases. You’ve lost the nitrogen mass down in your functional residual capacity. That mass is replaced by oxygen. That oxygen is absorbed in these less ventilated areas of lung, leading to collapse of your alveoli.

Another important effect is on the mucosa. Nose, mouth, trachea, and the alveolar membranes, which themselves are not mucosal, remember, they’re an epithelial membrane, will get dried out, especially with wall oxygen. Because oxygen that’s come from the VIE, that’s piped across the hospital and comes out of your flowmeter, has no moisture in it, because it would cause things to rust and gum up, wouldn’t it? So it comes out bone dry. If you’re just inhaling that because you’re on 15 litres, sat in resus for two days because of the state of the NHS, you’re going to end up with very, very dry lungs.

There is a story of a mountaineer, obviously high up a mountain where the air is really, really dry, true or not, whose mucosal lining dries out so much that he basically coughs it out, but it obstructs his airway as he’s trying to cough and splutter, and something’s going on, and he throws himself against a rock repeatedly to try and exert enough pressure in his chest to displace a wodge of mucosa that had sloughed off, because it was so dry and desiccated that it failed. I’m yet to see that in a hospital. There’s probably one day soon.

So oxygen messes with your splinting, causes absorption atelectasis, and is also irritant to the lung parenchyma itself. And we’re going to get into that in a moment.

Oxygen therapy is detrimental to eyeballs in premature infants. They can get retinopathy. And oxygen delivered to a person at higher than atmospheric pressures can lead to CNS effects. Remember, oxygen raises your systemic vascular resistance. It’s a vasoconstrictor. It vasoconstricts your cerebral circulation, impairing perfusion, and ultimately can make you feel headachy, nauseous, sick, unwell, and develop seizures. And again, more detail in a moment.

By this virtue, it sounds a little bit like oxygen could be a toxin in the wrong hands. Giving too much to the wrong person is suboptimal, and the quoted line is: if you’re delivering 60% oxygen to someone at atmospheric pressure, you will see changes in their lung parenchyma in 24 hours.

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Oxygen Toxicity: Reactive Oxygen Species

24:06 – 26:35

Key points

• Approximately 2% of oxygen molecules escape the electron transport chain to become reactive oxygen species (ROS).
• Formerly called oxygen free radicals. ROS is the clearer umbrella term.
• ROS carry one or more unpaired electrons. First species: hydrogen peroxide (H₂O₂) and superoxide anion (O₂⁻).
• These react on to form the hydroxyl radical (OH) and singlet oxygen, which is extremely reactive.
• Antioxidant defences are enzymatic and non-enzymatic. Non-enzymatic: vitamin C (ascorbic acid), beta-carotene. Uric acid and bilirubin also have an influence.
• Hyperoxia increases ROS formation, burdening the antioxidant apparatus and producing oxidative stress. In lung this can cause acute lung injury and fibrosis.

Now, we know oxygen is critical to life, but it is also a very reactive molecule. It’s electronegative, and that reactivity is useful in a controlled manner, to facilitate the reactions that occur in our mitochondria to power us. But there are challenges with operating with such feisty chemicals, and it is suggested, supposed, that about 2% of your oxygen molecules that are meant to be behaving themselves escape the electron transport chain and become reactive oxygen species.

Now, ROS, reactive oxygen species, were once upon a time called oxygen free radicals. But then that nomenclature is a bit weird, because is it a radical with no oxygen? Or is it a free oxygen that’s radical? So reactive oxygen species as an umbrella term is clearer.

Reactive oxygen species will generally have one or more unpaired electrons in its probabilistic cloud of electroniness that is surrounding the nucleus of that atom. They can knock around causing mischief, oxidising stuff. The first two that you might expect to see are hydrogen peroxide molecules, that’s H₂O₂, and a superoxide anion, that is O₂⁻, whereby your oxygen, normally O₂, floating around, but it is short just one electron. These can then subsequently react, forming a hydroxyl, OH, and a singlet oxygen molecule that is very, very reactive. There’s a good BJA article linked in the show notes that goes into that in more detail.

But all these reactive oxygen species would go off and cause mischief, messing up your DNA, et cetera. So there are a number of antioxidant mechanisms within a cell. These can be broken down into enzymatic and non-enzymatic. Non-enzymatic: your vitamin C, ascorbic acid, great antioxidant, as well as beta-carotene. And then enzymatic. Uric acid and bilirubin seem to have an influence there.

More oxygen, i.e. hyperoxia, increases reactive oxygen species formation. It leads to a greater burden upon the intracellular antioxidant apparatus. Ultimately you could describe this as causing oxidative stress to the cell. If we wind ourselves to looking at our lungs again, this can lead to an acute lung injury and potentially cause fibrosis.

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Hyperoxia and the Myocardium

26:36 – 27:35

Key points

• Routine 15 L non-rebreathe in myocardial infarction did not improve outcomes.
• Excess oxygen raises systemic vascular resistance, so more work for the heart.
• It constricts epicardial vessels, reducing coronary blood flow.
• It increases the ROS burden in already marginal myocardium.

And think about other bits of the body. We know that once upon a time we used to put 15 litres non-rebreathe on everyone having a myocardial infarction. Ultimately it transpires they didn’t need that. It didn’t improve outcomes. But also, that excess oxygen increases systemic vascular resistance, so more work on the heart. It causes the epicardial vessels of the heart to constrict, so less blood flow to the heart, and arguably increases the burden of reactive oxygen species you will find inside those cells. And if your cell is hanging on by the skin of its teeth in that hypoperfused element of myocardium, and then you make it work harder, well, it might just tip over the edge and necrose.

So by that virtue we can infer that oxygen isn’t great if you have too much of it.

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CNS Oxygen Toxicity, and Oxygen in Spaceflight

27:36 – 29:33

Key points

• At 2 atmospheres of near-100% oxygen, CNS oxygen toxicity begins: headache, discomfort, then visual disturbance, muscle twitching and seizures.
• Named after Paul Bert, described as the father of aviation medicine.
• Mercury and Gemini crews breathed 100% oxygen for days without notable effect, because cabin pressure was 5 psi (34 kPa), roughly one third of an atmosphere, similar to the summit of Everest.
• Low pressure also made the vessel easier to engineer against vacuum.
• The Apollo 1 fire: three astronauts died in a 100% oxygen cabin pressurised at sea level. NASA subsequently used a nitrogen/oxygen mix at atmospheric pressure on the pad, switching to oxygen once clear of Earth.

So we’re just going to finish up on oxygen toxicity. I mentioned earlier that you get lung effects, you get blood pressure effects with hyperoxia at normal pressure. But if you were to go to two atmospheres and find yourself in an environment that is near 100% oxygen, you will start journeying down the process of CNS oxygen toxicity. This begins with headaches and feeling uncomfortable and unsettled, and progresses to visual disturbance, muscle twitching and then seizures. This is named after Paul Bert, who’s a bloke, link in the show notes, who is described as the father of aviation medicine for his studies of pressure and gas on human physiology.

Now, that’s oxygen at high pressure. But what about oxygen that’s at 100% at low pressure? Has this ever happened? And yes, it did. In the very, very early missions, those space cowboys took off of our planet up into the reaches of the stars. In the Gemini and Mercury missions, they were breathing 100% oxygen for several days as they tottered around the Earth, with no notable side effects. This is because the pressure inside was five pounds per square inch, or in our money, 34 kilopascals, which is approximately a third of atmospheric pressure, which is roughly similar to being on top of Everest. Because they were breathing 100% oxygen, they weren’t getting hypoxic. You really don’t want a hypoxic astronaut, do you, when they’re trying to make decisions. And the pressure was low because it meant it was easier to engineer something that would tolerate the vacuum, if the pressure inside wasn’t so high.

However, there was a disaster at NASA in one of the build-ups to the Apollo 1 mission, where three astronauts burnt alive inside a capsule they couldn’t escape, that was 100% oxygen pressurised at sea level, where a spark ignited flames that burned them alive. They subsequently changed their gas mixes at atmospheric pressures to nitrogen, and would switch to an oxygen mix once out of the pull of Earth. They also made a number of engineering modifications to make it less likely to cause fire in the first place.

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Oxygen in COPD: Debunking Hypoxic Drive

29:34 – 31:02

Key points

• The taught explanation, obliterating hypoxic drive, has been debunked.
• Minute volume in severe COPD patients given 100% oxygen does not change, yet CO₂ still rises in a subset.
• Two mechanisms are posited: altered hypoxic pulmonary vasoconstriction affecting dead space, and the Haldane effect.
• Reference: British Thoracic Society emergency oxygen guidelines, linked in the show notes.

Okay, now, how about when we accidentally give someone too much oxygen in the hospital when they’ve got bad COPD? Now, I was taught at medical school that you would obliterate their hypoxic drive, because they’re only bothering to breathe because they’re blue. This doesn’t really work when you’re a pink puffer as opposed to the so-called blue bloater that are mentioned in textbooks of yore. And this has subsequently been debunked, because we’ve measured the minute volumes of patients with severe COPD, administered them 100% oxygen, and then witnessed that their minute volume remains the same, therefore obliterating that as a reason for why their CO₂ may go up.

And their CO₂ sometimes does go up. There is a subset cohort of COPD patients who are incompatible with excesses of oxygen. Now, for the full lowdown of this, get on the British Thoracic Society website, there’s a link in the show notes, looking at their emergency oxygen administration guidelines. There’s a PowerPoint in there as well that has loads of interesting information.

But ultimately there are two things that are posited to have an effect. Alterations in your hypoxic pulmonary vasoconstriction, messing with your physiological dead space, leading to bother. And then the Haldane effect.

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Hypoxic Pulmonary Vasoconstriction and Shunt

31:03 – 32:01

Key points

• A hypoxic alveolus vasoconstricts its capillary bed. Oxygen reverses that.
• Dilating poorly ventilated units lowers pulmonary vascular resistance, easing right heart work.
• But once the oxygen in that diseased alveolus is consumed, shunt fraction rises and saturations may fall.
• The speaker considers this a weak explanation for the CO₂ rise, since minute ventilation is unchanged.

Now, the crux of the V/Q mismatching is in the name: hypoxic pulmonary vasoconstriction. An alveolus that’s hypoxic will vasoconstrict. So if you give someone loads of oxygen and get some oxygen in there, it’s going to cause dilation of that capillary bed. Now, these alveoli are still poorly ventilated. What are the effects of dilating them? Well, one, you’re going to reduce your pulmonary vascular resistance, so the right side of the heart might have to work a bit less. That’s nice. However, once you’ve consumed the oxygen in that alveolus that is challenging to ventilate because it’s knackered and diseased, you’re going to increase your shunt fraction, so you might see a drop in someone’s sats. Maybe.

I feel like the hypoxic pulmonary vasoconstriction argument for this is on thin ground. I’ve read a number of papers and it doesn’t really stretch to suggesting truly why it causes the CO₂ to go up, because the patient’s minute ventilation hasn’t changed.

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The Haldane Effect

32:02 – 34:30

Key points

• Deoxygenated haemoglobin carries CO₂ better than oxygenated haemoglobin, as carbaminohaemoglobin.
• This increase in CO₂ affinity when haemoglobin is deoxygenated is the Haldane effect.
• Oxygenating a chronically hypoxaemic COPD patient displaces CO₂ off haemoglobin into plasma, raising PaCO₂.
• A significant spike crosses the blood-brain barrier, reduces consciousness, and starts a downward spiral.
• Clinically: if someone is blue, give oxygen. If you have control of the situation, titrate. Unconscious, 15 litres. Conscious and talking with sats of 70, nudge it up gently.

But now let’s look at the Haldane effect, and this feels to me quite a bit more convincing. What happens when a patient has CO₂ in their blood and haemoglobin in their blood, and this is venous blood, so let’s say the sats are 92%? Well, that haemoglobin that’s a bit deoxygenated has bound carbon dioxide. It’s buffered it, sucked it up, tidied it away, and we call this carbaminohaemoglobin. We know deoxygenated haemoglobin is better at carrying CO₂ than oxygenated haemoglobin. That makes sense, because you’re delivering oxygen to the tissues and trying to pick up CO₂ at the tissues to then return it.

There is also a haemoglobin-oxygen dissociation curve, and when there’s not so much oxygen knocking around, the affinity for CO₂ goes up. There is a right shift. This CO₂ affinity increase of haemoglobin that’s deoxygenated is called the Haldane effect. So if someone is not so good at clearing CO₂ because their lungs are diseased and they’re walking around a little bit hypoxic, their haemoglobin is actually doing quite a good job of squirrelling away CO₂. Great.

But now the F1 doctor rushes to the blue patient, panics in a fit of madness, puts 15 litres on their face. Not the end of the world if you take it off promptly. Might cause some mischief if you leave it. If someone is blue, I still err on the side of give them oxygen. If you have control of a situation, titrate the oxygen. If they’re unconscious, 15 litres. If they’re conscious and able to talk to you and their sats are 70, just gently nudge it up.

That’s not the focus of this podcast. The focus of this podcast is: we’ve given that patient loads of oxygen. We’ve oxygenated their haemoglobin. Therefore that CO₂ has nowhere to go but plasma. And it does. And this leads to an increase in CO₂. Now, most of these patients are probably knocking around somewhat resilient to high CO₂s and their obtunding effects. But if it were to spike significantly in a patient who has an exacerbation of their COPD, they’re fatigued, their CO₂ is creeping up, their sats are 88, and then they inadvertently get a load of oxygen. Now their sats are 100%, they’ve displaced all that CO₂ from their haemoglobin, their CO₂ in the plasma spikes, that CO₂ crosses your blood-brain barrier, it pickles your CNS, they become less conscious, then you’re in a downward spiral of badness.

This sounds more convincing than some jiggery-pokery with V/Q mismatch. If I’m wrong on that V/Q mismatch malarkey, email me and I will pop a correction in here. That’s fine. Naturally, all personal opinion.

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Hyperbaric Oxygen and Carbon Monoxide Poisoning

34:31 – 35:31

Key points

• At 3 atmospheres of 100% oxygen, dissolved oxygen alone can meet tissue demand.
• This keeps a severely carbon monoxide poisoned patient alive while CO is displaced from haemoglobin.
• Category 1 hyperbaric chambers accepting such patients exist in the UK.

We could literally talk about oxygen until the cows come home, and as soon as I don’t own any cows, we would be doing it for a very long time. But there are just a few more fun things to talk about.

What happens if someone has shut themselves in their garage, turned on the car and tried to kill themselves with carbon monoxide, and their carbon monoxide level is through the roof and they are sick as a parrot, and you just so happen to be near a category one patient-accepting hyperbaric oxygen chamber in the United Kingdom? Well, you could take that patient and put them in there. If you take them to three atmospheres of pressure in 100% oxygen, you can deliver enough oxygen to their tissues to keep them alive just by the amount of oxygen dissolved in their blood. Three atmospheres, 100% oxygen, you will achieve sufficient oxygen delivery and save their life whilst you slowly but surely displace carbon monoxide from the haemoglobin.

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Heliox and the Density of Gases

35:32 – 38:00

Key points

• Heliox is 21% oxygen and 79% helium.
• Air, oxygen and helium have similar viscosity. Heliox works by reducing gas density by a factor of 1.73.
• Lower density means less turbulent flow (Reynolds number), so less work of breathing.
• Useful in upper airway narrowing, not in gas exchange failure such as pneumonia.
• Side effect: a higher-pitched voice, from the higher flow rate across the vocal cords.
• The reverse holds for dense gases such as sulphur hexafluoride: a lower voice and difficulty exhaling.

And now, what about other oxygeny type mixes? We mentioned saturation diving, I think, in one of the previous episodes. One of the mixes that divers sometimes breathe is Heliox. We’ve all probably heard about Heliox.

You could find yourself feeling very clever with a patient with airway obstruction secondary to narrowing, who has high work of breathing, and say, ah, give them Heliox. This is 21% oxygen and 79% helium, and oh, that makes them better. It only makes them better if they’ve not got a gas exchange issue, obviously. So if they’ve got obstruction and pneumonia, because they haven’t been able to cough and clear their lungs, it’s not for you or them.

But how does it work? So air, oxygen and helium are similar in their viscosity, but what we’re trying to do is reduce the density of the gas being inhaled. Because remember, when we think about Reynolds number, turbulence and all that jazz, the denser the thing, the more likely you are to have turbulent flow. Turbulent flow, more work of breathing, a challenge. Therefore, Heliox reduces the density of the gas you’re inhaling by a factor of 1.73. Cracking. That person might start talking in a bit of a higher voice, because you get a higher rate of flow across the vocal cords.

And now we’ve thought, well, that’s a less dense gas. What about a denser gas? Well, a denser gas will make you talk in a very low voice. And for anyone who’s desperate for some entertainment, there is a link to a video in the show notes of a bloke, naturally on the internet, who took it upon themselves to inhale some rather heavy gases. It’s good because you can appreciate the tonal changes of his voice, but also he describes it actually being quite hard to breathe the gas out that he breathed in. Now, it doesn’t mention if he also inhaled that as an oxygen mix, or if it was like 50% sulphur hexafluoride, 50% oxygen, so he didn’t get hypoxic. Because if you were to just breathe 100% sulphur hexafluoride, you can imagine that you would go blue and possibly even pass out, and you’d really kind of struggle to clear it. It’s quite funny, watch the video.

That will hopefully help embed in your mind the nature of the density of the gas being the thing we are interested in, as opposed to the viscosity of the gas, when we’re thinking about turbulent flow in lungs.

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Episode Summary

38:01 – 38:40

That was actually quite a fun episode, wasn’t it? With lots of interesting points made and stuff around the edges of oxygen.

We talked a little bit about the history of oxygen, who named it, how it was approximately figured out and discovered, and who really stamped their name on it as a discovery: Joseph Priestley, by the looks of it. We’ve handled oxygen toxicity, when you give too much to a normal person, oxygen toxicity in the context of severe COPD patients with an exacerbation, and dabbled on the physicochemical properties and side effects of oxygen.

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Closing Thought: Ibn al-Nafis and the Prevailing Opinion

38:41 – 41:00

Key points

• Around 1250, Ibn al-Nafis of Damascus concluded that venous blood crosses the lungs and returns to the left atrium.
• This contradicted the accepted model of blood passing through invisible pores in the interventricular and interatrial septa.
• Neither the pulmonary vessels nor the pores were visible at the time. He followed the reasoning rather than the consensus.
• The alveolar capillary beds were not seen for another 400 years, vindicating him.
• The lesson: medicine should hold its conclusions open, and stay curious about the oddities it cannot yet name.

I want to close out this episode with just one more thing, and this is when I was moseying around with the history of oxygen. I’ve read a number of history books for medicine, because it’s just interesting, and there’s often an allusion to a bit of a dark age where the Hippocratic or Galenic school of medical teaching kind of got stuck for 1400 years.

However, in 1250, a boffin, by no other name frankly, hailing from Damascus, called Ibn al-Nafis, reached the conclusion that venous blood crosses the lungs and subsequently attends the left atrium to get pumped out around the body. This was absolutely contrary to the prevailing opinion of the time, because no one could find the blood vessels in the lungs. The blood got from the left to the right side of the heart through pores in the heart itself, between the interventricular septum and the interatrial septum. But whilst no one could find these blood vessels in the lungs, the pores also weren’t visible in the heart. But the prevailing opinion everyone was stuck with was that this was the case. Ibn al-Nafis went contrary to that, stating what he thought was right.

Now, there’s a link to an article about him and the golden age of Islamic endeavour that occurred in this timeframe, and it’s less recognised in the history of medicine and writings that come about, or you might find in a bookshop. It wasn’t for a further 400 years that the alveolar capillary beds were seen, and subsequently this chap was vindicated.

But this person was a discerning thinker. They had not allowed themselves to become trapped by the prevailing opinions of the age. We should use this to remind ourselves that whilst we think we know we’re right about stuff, we do not know everything yet. We, you, I, medicine, may well be proven right or wrong in 400 years’ time or less, because we have better technology now. Medicine should keep its mind open. Not just purely think what the textbook says is right, but think about what the textbook is missing. Perhaps when you come across an oddity in clinical practice, think about it in a physicianly manner. Hmm, is this something I could name if I could see more of it? And allow your curiosity to exist, because that’s the thing that makes life interesting.

Anyway, let’s not get too philosophical.

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Next Episode

41:01 – 41:40

Thank you very much for listening to this oxygen episode of Gas Gas Gas. And I think we have succeeded in concluding the chapter on volatiles and other assorted gases that we might fiddle with.

The next few episodes are going to tidy up a few more things to finalise a few more chapters. We’re going to handle mivacurium and pancuronium, paracetamol, and non-steroidals. Paracetamol, again, more than you might want to believe is present to talk about with that. And non-steroidals, because they love to ask about the pKa of aspirin, and there’s that pathway of chemical action that often could come up as well.

We shall see you next week. Thanks for listening.

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Outro

41:41 – 42:36

[…] the costs of Gas Gas Gas. From buying me a coffee, to venturing forth via an affiliate link, to the hoard of joyful SBA questions from Teach Me Anaesthetics. Those links are on the website and in the show notes.

Speaking of the website, definitely check out gasgasgas.uk for the show notes, diagrams, details and the references.

Now, we all know, guys, that this is a bucket of content to consume, and it is like drinking from a fire hose. So I want to finish by saying: take it day by day, don’t overcook yourself, don’t freak out, and keep studying.