Oxygen for the FRCA Primary

Contents

Introduction
Oxygen Pharmacology
History of Oxygen
Oxygen as a Toxin
COPD and Oxygen excess
Heli-ox and HyperBaric Oxygen Therapy
References

Introduction

Oxygen seems like yet another boring topic, we are asked to prescribe it in hospital and to treat it like a drug. Whilst my obstinate mind worries that I am currently breathing an unprescribed drug – and whether self referral to the police is in my best interests. Getting it wrong has clinical implications that this governance structure helps to avoid

This episode handles:

Physico-chemical properties
Obtaining oxygen for medical use
Pathophysiology and physiology of sub-par oxygen use.

An exciting episode, something to simple, yet not without its challenges!

Oxygen toxicity is a challenge to achieve, but 100% oxygen administration will have a cytotoxic/pulmonary irritant effect which has to be weighed against the odds of death in the ARDS patient cohort (oxygen wins, but we should use 100% O₂ as little as possible.)
Don’t forget the tricky side effect of over oxygenating a sub group of COPD patients, not because they are insensate to O₂ but because of other physiological effects.

Oxygen Pharmacology

Oxygen Physico-Chemical Properties

Name	Oxygen (named by Antoine Lavoisier in 1777)
Class	Elemental Gas
Chemical Make Up	[math]O{_2}[/math]
Isomer Status	Nil
Colour/Appearance	Colourless, odourless, tasteless gas
Pin Index of oxygen	2 - 5 (oxygen, O₂, starts with 2, here the means of recall is here)
Stability/Storage	Stored at 13,800 KPa in Molybdenum Steel tanks (138 Bar) White shouldered nb. there are kevlar wrapped tanks that are lighter to move around with. Unfortunately if a cylinder were to be hit by a stray round the situation is sub-optimal regardless of tank type. A Steel tank will undergo rapid ejection will result in quite a lot of force, which might turn the tank into a projectile, but may also combust some of the tank material and other nearby by materials, if it's a kevlar tank it may unravel, shred and generally prang kevlar shrapnel at a speed incompatible with nearby life. Care should be taken to avoid negligent discharges in the vicinity of all pressurised tanks. For the curious - some folks have done a detailed study of the issue, check it out Youtube, folks shooting things.
Oxygen Cylinder Volumes	CD - 460L - 230 Bar - your common handheld tank in hospital D - 340 - 137 bar E - 680L - 137 bar F - 1360L - 137 bar G - 3400L - 137 bar J - 6800 L - 137 bar nb. remember you won't get absolutely all the oxygen out of the tank as '1 bar worth' will remain as the cylinder will have equalised with atmospheric pressure
Manufacturing	Fractional distillation of liquefied air (Air -200°C yields a vapour phase of nitrogen and a liquid oxygen phase that are separated) which can be progressively decanted out. There are a few other molecules in these distillates - including Argon, Carbon Dioxide and other noble gases. which are eventually removed. Oxygen is transported in liquefied state and stored for hospital use in Vacuum Insulated Evaporators.
Molecular weight	Atomic mass = 16, but its generally floating around as a diatom (pair) -thus it is 32 g/mol
Climate	Peaked at 35% atmospheric O₂ in the carboniferous period 300m years ago.....

Physico-Chemical Properties

Oxygen Boiling Point	-183°C
Critical Temperature of Oxygen	-118°C
Critical Pressure of Oxygen	50 Bar
Comparative diffusion rate	24x less soluble than CO₂

Oxygen Pharmacodynamics & Side Effects

Mechanism of Action	Facilitates oxidative phosphorylation at the electron transport chain level - found on the inner mitochondrial membrane of eukaryotic cells.
Chief Effect / Actions	One oxygen atom accepts two hydrogen ions and 2 electrons at Complex IV in the electron transport chain - ultimately forming a water molecule.
Dose	21% + as fraction inspired. Hypoxic mixtures are not recommended. Note once upon a time, such notions were less robustly applied Quote: The subjects were anesthetized for one hour, at as nearly a constant depth of surgical anesthesia as possible; the induction was started with a mixture of approximately 85 parts of ethylene and 15 parts of oxygen, and maintained as near this concentration as the patient would permit. BRUMBAUGH JD. see ref
Cardio-Vascular Side Effects	Increased Systemic vascular resistane
Respiratory Side Effects	Parenchymal effects: Absorption atelectasis at the bases once they have had their delightfully splinting nitrogen washed out.
Central Nervous System Side Effects	ICP : Cerebral Vasculature: Vasoconstriction leading to reduced cerebral blood flow. CMRO₂: Seizure Threshold: can trigger seizures Nausea and vomiting: Induces Nausea
Ophthalmic	Transient loss of peripheral vision Retinopathy of the pre-term infant due to oxygen administration
Mucosal	Oxygen from the pipeline is devoid of moisture, it will dry nose, and tracheal mucosa, and eventually the alveoli. This impairs cilia function, and eventually gas exchange. Anyone who is expected to be stuck on higher oxygen flows should be considered for a humidified circuit.

History of Oxygen

There were many a rumbling about there being something in the air consumed by flame and life (a candle or mouse in a container sealed with water, the height of the water climbing up the inside of the container as oxygen was consumed. the first record of this was in the 2nd century BC by a curious Greek, Philo of Byzantium. Naturally they thought it was assumed that the elemental air was converted to elemental fire…
Leonardo Da Vinci seemingly also made the observatoin that combustion and respiration consumed the mass of the air.

In 1604 - a Polish physician come gentleman scientist type, Michael Sendivogius described a substance in air as ‘cibus vitae’ - ‘food of life’ and managed to demonstrate that this same gas was produced when potassium nitrate was thermally decomposed (heated so it breaks down), others at the time came to similar conclusions but struggled against the prevailing errors of the time.

I mentioned nitrous oxide was initially described as a type of phlogisticated air during the nitrous oxide episode, and this phlogiston theory hampered progress [Phlogiston theory being all about the two parts of a material the phlogiston which burns off and the dephlogisticated remainder) air was irrelevant to this theory.

Science continued to bash on the door of phlogiston theory, and three individuals around the same time formally identified oxygen in air required for combustion, and devised means of liberating oxygen from other reactions - ultimately our pal Joseph Priestley who also discovered nitrous oxide got himself published first.

Oxygen as a Toxin

Headline : Administering too much oxygen is a sub-optimal

60%+ FiO₂ = Pulmonary changes seen in 24 hours

Introducing…

Oxygen as we know, critical to life, once upon a time far more of it in the atmosphere, now less. It is highly reactive which is useful when the goal is to operate a chemical reaction that ultimately provides utilisable energy, minimally reactive molecules would be ‘chemically’ harder to work with.

Reactive oxygen species

Previously known as an oxygen free radical, have 1+ unpaired electrons, making them free to zip around and react with other molecules in their vicinity. Hydrogen peroxide and Superoxide are the two most abundant, that can end up being generated (routine oxidative phosphorylation can kick out the odd escapee, and the immune system uses hydrogen peroxide in peroxisomes to murder/main/mangle offending bacteria.

Nb, species plural,

Hydrogen peroxide and superoxide can cause mischief by reactive together, to build an even more injuries set of reactive oxygen species. Forming hydroxyl (OH) and a singlet oxygen molecules 1O₂.

Antioxidants

There are many to be found in cells:

Non-enzymatic vitamin C and + beta-carotene.
Enzymatic: uric acid, bilirubin, (and others)

Hyperoxia increases ROS formation, more heavily burdening intracellular anti-oxidant systems (leading to oxidative stress upon the cell) in the lung it can lead to acute lung injury (ALI) and potential fibrosis.

Oxidative Stress

Don’t forget, that whilst once upon a time, someone having a myocardial infarction would of been put on oxygen as part of emergent treatment, it has been identified that this reduces blood flow to the myocardium through this vasoconstrictive process. in myocardial infarct, aim for SPO₂ >94%. I don’t think the evidence can tease out if it increases oxidative stress in marginally perfused tissues.

Oxygen Toxicity

Sub divided into normobaric and hyperbaric hyperoxia.

Pulmonary Effects: Causing respiratory epithelial damage presenting as retrosternal chest pain, dyspnoea and pleuritic pain

In hyperbaric environments 2Atm+ CNS Effects are seen.

note: Hyperoxia causes cerebrospinal vasoconstriction

This can lead to irritability, headache, nausea, visual disturbance and progress to muscle twitching and seizures. (the so called Paul Bert effect)

Space cow boys

Don’t forget that early space faring (projects Gemini and Mercury and Apollo 1 involved being in a 100% oxygen atmosphere for several days, with no notable effects… because the pressure inside the capsule was 5 psi - aka 34kPa so the quantity of oxygen molecules knocking around is not the same as 100% O₂ at 101kPa (sea level)

After the disasters fire in the cockpit of Apollo 1 - an air mix was used as well as a number of engineering alterations to reduce the risk of being burnt alive.

COPD and Oxygen excess

Oxygen: severe COPD incompatibility

Debunked concept: oxygen therapy inhibits a patients hypoxic drive leading to their disinclination to breathe resulting in a climbing in PaCO2

However, giving oxygen to a certain subset of COPD patient does lead to hypercapnia. It would be remiss to refuse oxygen to these patients, a lower target oxygen saturation is generally recommended by BTS a spo2 <85% is too low, and a low of 88% as target is safe.

The resultant hypercapnia is much more likely in severe COPD patients who have an exacerbation of COPD.

Studies have found that the minute ventilation in this patient cohort who are inappropriately exposed to oxygen did not alter, thus where does the elevated PaCO2 originate from?

Physiological basis for COPD:O₂ excess incompatibility:V:Q

Oxygen exposure to an alveolus that is not accustomed to such an oxygen fraction due to terribly knackered lung parenchyma will lead to a loss of hypoxic pulmonary vasoconstriction (HPV) this was defending the passing red blood cells from tottering past a feckless alveolus.

Note that oxygen is the most potent influencer of pulmonary capillary vasoconstriction, the clue is in the name… (volatiles can impair HPV)

The vascular relaxation of poorly ventilated alveoli increases physiological dead space, this may alter shunting of blood leading to increased deoxygenated admixture in the pulmonary veins but also reduce right ventricular after load.

COPD:O₂ excess incompatibility is a component of these alterations, but all patients differ.

Physiological basis for COPD:O2 excess incompatibility: Haldane Effect

CO₂ + Haemoglobin = carbaminohaemoglobin

Deoxygenated Haemoglobin is far better at stowing away CO₂ than oxygenated Hb

Recall there is a hb O₂ disassociation curve - there also exists a hb co2 disassociation curves, and much like co2 shifts the former, oxygen shifts the latter, to the right impairing affinity to CO2 - elevating blood oxygen co2 tension. This right shift is the Haldane Effect.

This becomes pertinent in a patient who is unable to increase their minute ventilation.

In short - you give oxygen, you take a patient who has been knocking about with a pa02 of 7-8-9kPa, and make it 30+Kpa dissolved O₂ and the rest…
Their Hb which had been buffering a tonne of CO₂ in the patient (who’s generally mildly full of CO₂ to begin with given their lungs) now is unable to do so, liberating said CO₂ from carbaminohaemoglobin and raising blood CO₂ Tension!

High CO₂ can render this patient group less conscious - despite them generally being more tolerant given the underlying chronic disease process.

Avoiding excessive O₂ tensions, defends their diseased gas exchange interface and their very hard working haermaglobin.

Have a read of the BTS guidelines for emergent oxygen therapy if you’ve the time, there is an excellent set of powerpoint slides also!

Bleomycin

Someone who has had Bleomycin chemo for lymphoma etc, Is at risk of developing a fibrosing alveolitis on exposure to oxygen later in their life - target their sats 88-92%, and be as cheap as safely possible with the oxygen.

Combustion

Oxygen supports combustion (aka oxidation) because it is electronegative, and keen to accept electrons from other atoms.
There are other elements that support oxidation, check out this video from University of Nottingham where they are fiddling around with fluorine, which is feisty stuff! they also mention the lewis acid glass issue too.

Oxygen ‘Storage’ in blood

Transported by haemoglobin 1.34g/dl (in vivo, recall its quoted as 1.39 in vitro)- plus 0.23 ml/100ml/kPa of O₂ dissolved in plasma. We have covered oxygen storage in the hospital in greater detail with Dr Lewis,

Heli-ox and HyperBaric Oxygen Therapy

HyperBaric Oxygen therapy

In an emergency, there are a few hyper basic chambers associated with intensive care services, so called category 1 accepting chambers, they can be found in Hull, the Wirral, Chichester, derriford whips cross, James Paget and near Rugby. The British Hyperbaric Association has more!

Generally used to manage decompression sickness. severe carbon monoxide poisoning in a patient lacking oxygen delivery, or those with severe infection (osteomyelitis / necrotising infection).

If you put someone at 3x ATM in 100% O₂ - you will deliver enough oxygen to tissues in the plasma dissolving fraction alone.

Heli-Ox

Why does it make breathing easier? Oxygen Air and Helium are similarly viscous, but the goal is to reduce the density of the gas being inhaled, less dense = less heavy and therefore less work required to displace it. and by virtue of reduced density is less prone to turbulence and more likely to flow in a laminar fashion.

Heli-Ox vs Air, 0.5g/L vs 1.25 g/L

Remember Heli-Ox is 21% oxygen only! If someone is very blue, it is not a sensible course of action.

Heliox improves flow by 1.73x

Reynolds number = density x velocity x length / viscosity of fluid

Nitrous Oxide, is a denser carrier gas and will make turbulence associated breathing difficulty worse!

Speech becomes higher as gas can flow across vocal cords more quickly.

Inhaling a really Heavy gas

So, a bloke on the internet took it upon themselves to inhale some rather heavy gases, and its with the momentary watch to appreciate the tone, but also how hard it was to clear it out of the lungs! (he must have inhaled an air: sulphur hexafluoride mix, and/or de-nitrogenated himself first (who knows!? Because he didn’t go blue - Link to the Vid!

Just one more thing!

In 1250 - a boffin hailing from Damascus called Ibn Al-Nafīs reaached the conclusion that venous blood crosses the lungs and attends the left atrium, clearly this points out that Galenic school was barking up the wrong tree Ibn challenged several ’ concepts that did not bear out in reality (pores in the IV septa of the heart as an example.) It would be another 400 years until alveolar capillary beds were seen. at the time the prevailing opinion was there were pores in the heart - despite them not being visible either.

Have a read of this - Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden Age

He was a discerning thinker, not being trapped by the prevailing opinions of the age. This should remind us that whilst we think we know we are right in medicine, we do not know everything, yet and you may be proven wrong or right in 400 years time (give or take considering the technology of today. Let’s keep our minds open to the oddities we come across and think in a physicianly manner - perhaps you will come across something you can name!

Summary

Oxygen is manufactured by fractional distillation of liquefied air and stored in hospitals as a liquid in vacuum insulated evaporators or as compressed gas in cylinders at 137 bar (white shoulder, pin index 2-5). At the cellular level, oxygen facilitates oxidative phosphorylation at Complex IV of the electron transport chain, accepting electrons and hydrogen ions to form water.

Whilst essential for life, oxygen has pathological potential. High inspired fractions (>60%) cause pulmonary toxicity within 24 hours through reactive oxygen species formation, overwhelming cellular antioxidant systems and leading to epithelial damage as well as absorption atelectasis, and potential acute lung injury. In hyperbaric environments (>2 atm), CNS toxicity manifests as the Paul Bert effect—seizures, visual disturbance, and muscle twitching. Hyperoxia also causes cerebral vasoconstriction, reducing cerebral blood flow, and can worsen outcomes in myocardial infarction (target SpO₂ >94%, not the historic routine high-flow oxygen).

In severe COPD patients, excessive oxygen causes hypercapnia—not through loss of hypoxic drive, but via two mechanisms: loss of hypoxic pulmonary vasoconstriction (worsening V/Q mismatch) and the Haldane effect (oxygenated haemoglobin releases bound CO₂). BTS guidelines recommend targeting SpO₂ 88-92% in this cohort. Bleomycin-exposed patients risk fibrosing alveolitis with oxygen and require similar conservative targets.

For the FRCA Primary: know oxygen manufacture, storage pressures, toxicity mechanisms, COPD physiology, and clinical applications. Oxygen is prescribed as a drug—prescribe it wisely.