Hyperbaric Oxygen Therapy and Treatment - An Overview - Part 2 Hayden Dunstan March 2018 Copyright 2018 ?

.../Part 1

Emergency Medicine and Oxygen Administration:

“When in doubt, whip it out!”

One of the many intentionally humorous innuendos encountered on the earliest dive leadership training course I undertook in 1998. A sentiment shared in the first diving medicine textbook I read in 1997 “Diving Medicine for SCUBA Divers. [52] Diving Medicine for SCUBA Divers Edmunds 1992

One of the first editions of this book.

Of course, the instructor was referring to oxygen. When in doubt, give oxygen. A similar ethos is fostered in the US Navy.

“When in doubt, recompress” – Revision 7 USN Diving Manual 2016. [49] United States Navy Diving Manual Diving Medicine and Recompression Chamber Operations 2016

These sentiments both say similar things. If you aren’t sure if your patient needs more oxygen, give it to them anyway. It isn’t going to make them any worse but could well make them better. Recompression does facilitate other physical and physiological mechanisms, though one of those is to increase oxygenation, just as giving oxygen at normal atmospheric pressure (baric oxygen) would do as well.

First, let’s address the reason someone may need emergency medical treatment. And by that, I mean emergency intervention to sustain life or prevent further injury. They either become critically ill, or they may have sustained an injury in some form of accident. In either case immediate care is required to preserve vital function and to preserve life in some cases, until a patient can be transferred to a facility offering more advanced medical help. Intervention also prevents a condition or injury from worsening as a result of any tissue damage sustained. Part of what first responders do is ensure continued oxygen supply to tissues while preventing any further damage, (the rationale behind CPR).

In diving we are taught not to be shy of administering oxygen as a first aid measure. Even recreational diving in benign conditions calls for some form of emergency oxygen to be available. Especially if the patient exhibits signs of decompression sickness or other diving related illness and injury. Even baric oxygen is better than nothing. It is common practice to place a patient on oxygen with no question or consideration for toxicity in emergencies in diving. Why not then in other accidents since end results are the same. A collapse in tissue oxygenation.

Indeed, ambulances not limited to patient transport only, are all equipped with pure oxygen facilities for a reason, and even weekend divers out for a sport dive commonly carry their own emergency oxygen. They too don’t want to have to wait for it to be given at hospital after ponderous consideration when giving it promptly has such an effect on favourable outcomes.

The reason for this, is any injury, or sudden chronic illness that prevents the normal transport and absorption of oxygen can be life threatening. Especially when particularly oxygen sensitive tissues are involved. Or should I say those tissues particularly sensitive to lack of oxygen such as the brain, spinal cord and tissues of other major organ systems, such as the heart and cardiac system.  

As we know, if we stop breathing, life would most certainly cease owing to hypoxia and non-delivery of oxygen to the heart and brain, resulting in cardiac arrest and brain death in minutes. Yet oxygen treatment sometimes is not administered to patients who could have had far better outcomes if it had been administered as an emergency measure. This does touch on the subject of “reperfusion injury” and survivability of neurons, which is a discussion for another article.

The need to make protection of the central nervous system and the circulatory system including cardiac function our priority, is undeniable. Any one-day first-aid-at-work course is geared largely around this very principal and the key component of this training is cardio pulmonary resuscitation. Why would that be? Because it is accepted by mainstream medicine that oxygenation is key to survival and ensures, as far as is possible, better outcomes for the patient. What mystifies me is why the same mainstream medical fraternity hesitate to give more of it when they can.

Preserving cardiac function and oxygen delivery to the brain is of primary importance and immediate intervention is crucial in serious cases. These are the two systems keeping us alive from minute to minute and breath to breath. The adage “time is brain” comes to mind. Because quite literally, for every minute that passes with compromised oxygenation of the brain, more brain cells die.

I quote from the paper entitled “Time is Brain “by Jefferey L Saver, December 2005. [8] Time is Brain Saver 2005

“In each minute, [of ischaemic conditions] 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibres are destroyed. Compared with the normal rate of neuron loss in brain aging, the ischemic brain ages 3.6 years each hour without treatment”.

“Ischaemic” meaning, deprived of oxygen and unable to support proper cell metabolism usually caused by impaired blood flow and poor oxygen delivery.

The paper refers to incidents of ischaemic stroke, but the same principal can be applied to massive blood loss, cardiac arrest, head injury or any other condition compromising oxygen delivery to the brain. We will discuss head injury later, and how brain inflammation (encephalitis) does just that in cases of mild traumatic brain injury, traumatic brain injury and even multiple sclerosis. Whether disease or injury and having read the material I have read, as well as being a first responder and dive supervisor, I see similarities and consider them both a form of head or brain injury.

Once we can agree that preservation of oxygen delivery to the brain and heart is central to survival and better recovery outcomes, we can assess the means of doing this. Ordinarily in cases of stroke, head injury, heart attack and cardiac arrest, etcetera, an ambulance crew will make use of supplemental oxygen in their efforts to maintain saturation of red blood cells as we have previously discussed under oxygen transport. This has been the position for a long time and is of course well advised.

If you recall however, we discussed that haemoglobin can only carry a finite number of oxygen molecules. Once it becomes saturated any additional oxygen you breathe at normal pressure is largely wasted, save for the fact that breathing an increased percentage (fraction) of oxygen will also increase the partial pressure, incidentally resulting in an inward gradient causing plasma to saturate a little more. It may well still not be enough. And this where the disagreement between those for and those against HBOT come into it. The dose. Is the breathing of supplemental oxygen a high enough dose? In some cases, yes. In some cases. Nowhere close to enough. A study of mortality rates and outcomes following serious injury and brain injury will support that.

So, in the event supplemental oxygen it is not enough, what can we do? When supplemental oxygen is simply not enough to guarantee adequate oxygenation, and injury or illness seems too far gone or beyond the reach of conventional means to be remedied, we can make use of hyperbaric oxygenation as a bridge therapy to ensure survival long enough to provide further treatment.

This statement is supported by the results of a paper by Van Meter KW (author) entitled “The effect of hyperbaric oxygen on severe anaemia. [11] The Effect of Hyperbaric Oxygen on Severe Anaemia Van Meter 2012

Quote:

“As a respiratory pigment, haemoglobin allows blood to carry unnaturally high levels of nascent, molecular oxygen at one atmosphere of pressure in chemical solution to capillary beds and post-capillary venules supplying parenchymal cells of all organ systems in the body. When haemoglobin drops to critical levels to disallow proper oxygen delivery, hyperbaric oxygen therapy may be used as bridge therapy to emergently supply oxygen. Hyperbaric-administered oxygen allows oxygen to be dissolved in increased concentration in red blood cell-poor plasma or crystalloid/ colloid-diluted intravascular fluids in a volume-resuscitated patient.”

And:

“Hyperbaric oxygen can reduce oxygen debt decisively in the polar clinical extremes of exsanguination with cardiopulmonary arrest all the way to resuscitation of the severely anaemic patient who cannot be transfused with red blood cells for religious reasons, immunologic reasons, or blood availability problems. A hyperbaric oxygen treatment is equivalent in wholesale cost to a unit of packed red blood cells in the western world. By controversy, but true, hyperbaric oxygen provides a low-technology, cost-competitive means of pharmacologically reducing accumulated oxygen debt in the anaemic, injured or critically ill patient with little side effect. To address severe anaemia in trauma or illness, the future may well afford the use of hyperbaric oxygen therapy in the military far-forward, in pre-hospital EMS settings, in trauma centre emergency departments, in operative and recovery units, and in intensive care units of hospitals.”

There may be a number of reasons baric supplemental oxygen may not be enough. The patient may simply not have enough blood left to transport sufficient oxygen, i.e. not enough red blood cells left. Or there may be chronic inflammation present at the injury site preventing blood perfusion to those tissues. There may also be massive tissue damage preventing haemoglobin from passing through damaged and compromised capillary structures. Red blood cells are not the smallest component of blood. They can easily be prevented from reaching tissues if capillary structure is compromised.

This is also evident in damaged tissue such as found in diabetic retinopathy (damage to the capillaries in the retina leading to diabetic blindness, [53] Diabetic Retinopathy Analysis (Introduction) Sivakumar Et al 2005 in which capillaries are damaged by an opening in the blood/tissue barrier causing red blood cells to leak into tissues, resulting in the breakdown of iron and formation of the most dangerous of free radicals. Healing is compromised owing to the damage caused to capillary structure by sustained increased blood glucose levels. Similar of non-healing diabetic wounds on the feet. Incidentally, HBOT causes capillaries to constrict slightly making them less likely to leak at the same time as delivering oxygen in higher concentrations to tissues.

You may also encounter patients who are unable, or indeed unwilling, to receive blood transfusion. For religious objectors and those with immunologic reasons or a lack of blood availability, HBOT is certainly a viable bridge therapy.

In the case of compromised vascularisation (damaged capillaries), there is a component of blood that can pass through very limited pathways in the circulatory system and even perfuse into tissues with severely compromised vascularisation. Plasma.

And as we discussed earlier when we administer hyperbaric oxygenation and HBOT, we don’t aim to saturate haemoglobin, we aim to saturate plasma.

This allows, in the case of emergency treatment, life restoring oxygen to be delivered to tissues in dire need of it. Why would any medical professional deny sufficient oxygen where it is so desperately needed? Would they deny transfusion for exceptional blood loss?  Why restrict the administration of oxygen to baric supplementary oxygen only, when hyperbaric oxygenation would be exponentially more effective in a far shorter time frame?

The use of hyperbaric ambulances is not a new idea. The diving industry have used transportable chambers for many years. Hyperbaric lifeboats have also been in use since the early days of the oil rush in the North Sea in the early 1980’s and the rise of deep diving saturation techniques.

Vickers make, or at least used to make, a hyperbaric incubator for premature infants who suffered from poor oxygenation.  In fact, an entire ambulance could be pressurised safely to a pressure which presents negligible increase in fire risk, but to an extent which would benefit patients.

In a case report published in the book “Oxygen and the Brain – The Journey of Our Lifetime” [1] Oxygen and The Brain – The Journey of Our Lifetime James 2014, the author recounts a case of a low cardiac output patient admitted to the London Chest hospital in 1964. When his condition didn’t improve following surgery, it was decided to try HBOT. In the absence of fixed facilities, he was placed inside a Vickers mobile chamber and removed every 2 hours to allow him to aspirate the considerable bloodied sputum from his bronchial tree. After 12 hours of treatment the patient regained consciousness for the first time since the operation.

To the best of my knowledge the chamber was in the back of an ambulance. There is a great picture of it in the Professors book on page 172 accompanied by another good picture on page 175 of the old hyperbaric chamber that was used on the roof of the Western Infirmary – Glasgow, before its removal some years ago.

It’s almost as though we have taken a step backward since the glory days of hyperbaric medicine in the 60’s and 70’s to a time when over complicated, complex, “look how clever I am” treatments have taken precedence and seem favoured.

Hyperbaric oxygenation should be considered a routine emergency tool and should be a preferred emergency measure to ensure proper oxygenation. Ventilation without tissue saturation is pointless, and after all, is not the objective to do all possible for the benefit of the patient? 

It is quite possible to equip ambulances and emergency vehicles with portable chambers. It is also quite possible to render an entire ambulance patient section, hyperbaric. I’m not suggesting we make ambulances into massive steel tubes but rather make them able to take pressurisation to a lesser degree. Even just raising the internal pressure to 1,3ATA would prove quite safe for all concerned. It’s not enough to run a full protocol on, but for those on the knife edge between life and death, that little bit of extra oxygen may well make the difference between surviving or dying, and it may save their life or prevent debilitating brain injury caused by hypoxia following illness or injury. Time is brain remember. It may save a mother in labour, or an infant born in the back of an ambulance following birth complications from dying, or developing life altering neurological dysfunction.

Certainly, if not ambulances, then at the very least every major A&E, every major ER and emergency unit should have at least some hyperbaric capability or have reasonably immediate access to it. It wouldn’t hurt to have them in every GP surgery either. The cost to benefit ratio is clear, with basic chambers costing a fraction of MRI and X-Ray machines they would unburden government funded healthcare around the world by resolving at least some of the problems that choke the system daily while enabling a population to enjoy better general wellbeing. [54] The applications of hyperbaric oxygen therapy in emergency medicine (Abstract) Weiss Et al 1992

Cellular Metabolism:

I seem to have taken the long way around in getting to the mechanics of how HBOT actually works in the body. It was important though to start at the beginning of the physics and physiology and discuss its origins, the environment in which it is delivered, some of the support it has (and doesn’t have), and the mechanical physical laws that establish this as old science rather than new.

It’s with this that we arrive at the second half of this article dealing with actual conditions and the mechanism by which HBOT helps them. No one is claiming this is a silver bullet cure but rather a potential complimentary therapy. No one is saying HBOT is an outright cure for cancer or cerebral palsy and multiple sclerosis. We are saying though that more research is needed, and a greater level of acceptance by mainstream medicine is crucial, as indications are very good that it can cure a great many things and it can alleviate a wide spectrum of other symptoms, cause reversal and remission in some conditions, and afford patients an improved quality of life if nothing else.

To further understand how the likes of, accelerated healing, anti-inflammatory response, carbon monoxide removal and protection of the blood brain barrier are affected by hyperbaric oxygenation, among others, it is first important to understand where the oxygen goes and what it does following the already discussed gas exchange principals, along with the associated physics which underpins the therapy.

As discussed, the oxygen we breathe dissolves into the blood and then in turn dissolves into tissues and, in turn dissolves into each and every cell in the body’s tissues and systems. Accordingly, this going into solution of oxygen is highly increased when breathed under pressure, as supported by Henry’s Law. This means that the plasma in the blood is saturated to a level far above that of normal (baric) oxygen breathing. The normal level of oxygen in plasma is surprisingly low owing to its poor solubility in water.

In the except below, I quote from a book entitled “Regulation of Tissue Oxygenation” [55] Regulation of Tissue Oxygenation Pitman 2011 The excerpt comes from chapter 4 and while I haven’t read the whole book just yet, the comments inserted below support the oxygen saturation comments made so far.

Where Po2 is again the pressure of oxygen.

As you can see the previously stated haemoglobin saturation of 98% is considered normal and at the top end of saturation of “RBC’s” or red blood cells and according to the above insert, this is where most of the oxygen in blood is carried. This quote also explains that plasma is incredibly poorly saturated in normal baric conditions and as low as only 2% of the oxygen carried in blood is carried in the plasma. That equates to approximately 0.3% by volume or 0.3ml per 100ml of blood. An inarguably insignificant amount.

Hyperbaric oxygenation allows for a far greater saturation of plasma and in turn a far greater saturation of cell cytoplasm when it makes its way downstream into cells, also according to Henry’s law.

Demonstrated here is the ability of hyperbaric conditions to exponentially saturate cells with oxygen, even when normal blood delivery is compromised since we are now delivering oxygen via the plasma. Kind of like using a courier when the post office is on strike.

What happens next is why HBOT actually works. It is rather beautiful in its’ simplicity and yet a rather intricate process. Unfortunately, it is also an overlooked process taught in the very basics of medical training. Furthermore, it is observable, and thus empirical.

 If there is one thing to take away from this article let this be it.

Unlike the inert gas nitrogen, (79% of air), oxygen is active metabolically, and when dissolved into cells reacts and interacts and is used up. This is evidenced in diving decompression theory discussed briefly above. A diver diving on oxygen needn’t make any decompression stops because the oxygen is metabolised and doesn’t come back out of solution. This is the benefit of pure oxygen diving in the navy or spec ops. No decompression required. It is also the basis on which closed circuit rebreathers work. Inert gas is recycled, while only the oxygen, which has been converted to carbon dioxide, (subsequently scrubbed or filtered out), is then replaced into the system. Of the breathing mix the oxygen is the component being used up and constantly being replaced.

What this means for us in HBOT, is that the oxygen is being used in greater amounts proportionate to the environmental pressure, i.e. a greater volume or number of molecules is metabolised by the body under pressure.

In my article on Obesity and Type 2 Diabetes, (February 2017), [6] Dunstan 2017 I discuss in detail the evidence of this when I talk about volume of oxygen which I’ll cover here briefly also.

We have all heard of VO2 max. It’s the maximum volume of oxygen our bodies can process under stress or exercise and convert into carbon dioxide. [56] Bruno Et al 2013 It represents a maximum metabolic rate. It varies from person to person based on level of fitness, general health and even body mass index and weight. When we exercise we convert oxygen to carbon dioxide by means of metabolism. As we exercise we convert more of this, increasing metabolism, and creating a surplus of carbon dioxide in our blood. This is why breathing rate increases. Breathing response is not governed by a lowering of oxygen levels, it is governed and triggered by neuroreceptors sensitive to increasing carbon dioxide levels. That’s why free divers hyperventilate before descending. To flush as much CO2 out of their systems before diving. This allows them a longer dive, while staving off the urge to breathe. Carbon dioxide receptors in the brain are what make you feel an urge to breath.

As we consume more oxygen we create an oxygen debt in our tissues which causes our pulse rate to rise. This the body’s way of delivering more oxygen to the areas it is needed. Therefore, stress ECG and pulse rate under stress is a good measure of fitness and cardiac health and is routinely used by medical doctors in aviation and diving medicals to ascertain fitness levels. Fitness referring to … yup… VO2 Max. This is administered as a test during the infamous “Chester Step Test”.

VO2 Max essentially measures the maximum amount of oxygen a body can convert to carbon dioxide. It can be measured by measuring either oxygen consumption or carbon dioxide output in expired breath.

Reasonably stated then, the more oxygen that is consumed in a closed system as pressure increases, the more oxygen the body is using up. Not only is it observable and empirical, it’s calculable.

In diving we are taught to calculate the chamber atmosphere carbon dioxide increase rate using the VO2 of chamber occupants, to ascertain how quickly carbon dioxide builds up in an unfiltered and unvented chamber atmosphere. We routinely use a VO2 rate of 0.25 litres per minutes of oxygen consumed when at rest, and 0.5 litres per minute under stress. This factor is multiplied by ambient pressure since it is subject to increase as the pressure increases. This calculation allows us to determine how often an unfiltered chamber atmosphere should be vented to keep CO2 levels at a safe level. More carbon dioxide means more oxygen has been converted via the metabolic process. How else?

This factor is then multiplied by number of occupants and the ambient pressure in the chamber. It returns a volume of carbon dioxide produced (which is a prime indicator of oxygen metabolised) under pressure, since a greater amount of oxygen for the volume is present under increased pressure according to Boyles Law. We then offset this against the useable volume of the chamber atmosphere, which is arrived at by subtracting the volume the occupants occupy from the total chamber volume. It returns a rate per minute volume of how much carbon dioxide increases.

The question is, where does that extra oxygen go? It gets used up metabolically. If it didn’t, it would behave like inert gas and we would incur a decompression penalty which we don’t, and it doesn’t.

As we know CO2 can be deadly in increased concentration. It’s an important calculation when considering breathing the atmosphere, (as opposed to oxygen via mask), in a chamber. When you don’t breathe from the built in breathing system (BIBS), and breathe the atmosphere, the body produces a proportionate amount of carbon dioxide which can contaminate the atmosphere. We are taught as chamber operators and diving supervisors that pressure is instrumental in determining how much carbon dioxide an individual produces as explained above. Why else would ambient pressure be included in the calculation. [57] Chamber Carbon Dioxide and Ventilation Naval Sea Command Gerth 2004

This, coupled with the fact that breathing oxygen via mask in a chamber incurs no decompression penalty, is absolute proof that more oxygen is consumed by metabolism under pressure, thus raising the VO2 max above that possible in normal baric conditions. [58] Tibbles Et al 1996

Ergo, hyperbaric oxygenation increases cell metabolism (oxidative), proportionate to the ambient pressure.

Cell metabolism is the basis for the argument in favour of HBOT in the treatment of a host of conditions briefly discussed below. Everything from wound healing to healing from disease and indeed life itself, all stems from effective and uncompromised oxidative cell metabolism. Without optimal cell metabolism life simply doesn’t happen like it should, if at all. Wounds do not heal, illness worsens, brains don’t work properly, and quality of life is reduced, and, in some cases, life is lost entirely.

In the presence of additional oxygen, cells metabolise faster as shown above. (VO2 is an expression of metabolism). Increased CO2 production indicates increased volume of oxygen consumed. The excess oxygen oxidises more glucose, and it upregulates the cell energy molecular equivalent of currency, Adenosine Triphosphate (ATP). As ATP is upregulated and the uptake increased, mitochondrial function improves, cell division and mitosis increase, and cell function is supercharged to optimal levels or even higher than that. This stimulates and upregulates the natural repair and rebuild function present in mammalian physiology.

As cells perform better, so do tissues. And as tissues perform better so do the organs and systems they make up, and this is particularly relevant when considering the benefits below. Ever wondered why professional athletes undergo treatment before competition? Or racehorses? They do it in horse racing too. While the ethics of increasing sporting performance is highly debateable it is currently allowed in sporting circles…. for now. What is less debateable is the benefit this can have for injured or ill patients.

If the process of healing is a natural biological function, why not better facilitate this? And in doing so perhaps reduce the need for treatments which cause harmful and detrimental side effects. The risk to benefit ratio in HBOT is far less than most drug therapies. What’s more, stem cell release is upregulated during HBOT. (Stem cell mobilization by hyperbaric oxygen. – Thom SR et al. – April 2006)

The process of mitosis is the duplication of genetically identical daughter cells. What happens if cells are duplicated while functioning optimally with optimal gene expression? An interesting consideration when genetic expression of the new cell is considered.

In simple terms that’s how it works at the cellular level. A more detailed examination of this can be found in my previous diabetes article.

A tool taught to divers and supervisors serves as evidence of increased cell metabolism by virtue of the production of proportionately higher CO2 under pressure. Who would have thought it?

If you take away one thing from this writing, let that be it.

Wound Healing:

Oxygenation is fundamental for tissue repair and rebuilding following illness or injury. It’s what facilitates tissue granulation, collagen release and ultimately tissue re-growth. Under hyperbaric conditions this is stimulated to far higher levels. Along with a demonstrated increase in stem cell release [16] Thom Et al 2006 wound healing is drastically accelerated when hyperbaric oxygen therapy is employed.

In cases of injury the benefits are obvious. An accelerated return to normal activity and significantly shorter periods of convalescence.

For patients who suffer from poor circulation and the subsequent poor oxygenation of tissues this can mean the normal, or close to normal, healing of wounds that would otherwise not heal and potentially lead to amputation.

It is well established that hyperoxygenation increases collagen release into areas of damaged tissue. It is also established that hyperoxygenation increases tissue granulation. [58] Tibbles Et al 1996 [59] Van Neck Et al 2017 [60] Hyperbaric Oxygen Therapy Mediates Increased Nitric Oxide Production Associated with Wound Healing: A Preliminary Study -Boykin Et al 2007

I made mention of race horses above. Hyperbaric oxygenation is widespread in the equine field with hyperbaric oxygen therapy given to increasing numbers of horses, specifically race horses between races, to accelerate their healing after sustaining the injuries they do. While the whole issue of horse racing is highly debateable, the reason horse owners invest the money they do in hyperbaric chambers is clear. It works. It’s as simple as that. Personally, I’m not in favour of any activity in which an animal is literally driven to death but the point being made is that in a situation where accelerated healing is needed it is achieved using hyperbaric oxygenation.

The basic mechanism of HBOT accelerated, or assisted healing of, non-healing wounds is described as follows:

With increased cell metabolism and greater uptake of ATP, cell mitosis and division are accelerated. Type 3 Collagen is also released in greater quantities allowing the formation of the extra cellular matrix developed by fibroblasts. This results in quicker and better granulation in the wound bed, and along the wound margin, and quickens the development of natural scaffolds on which yet more tissue can grow with improved cell division and growth. Eventually, long stranded, stronger type 1 collagen forms on the natural matrix scaffold leaving a scar, i.e. the wound heals as it should but would fail to do, if vascularisation was compromised and hyperoxygenation wasn’t applied.

HBOT also triggers new vascularisation (neovascularisation), angiogenesis and vascular growth. [58] Hyperbaric Oxygen Therapy (Review) Tibbles Et al 1996 Mention was made above of the Hypoxia Inducible Factor Gene Alpha 1. HIF1A as the master regulator gene responsible for the upregulation of around 60 other hypoxia triggered genes. One of those factors is the Vascular Endothelial Growth Factor or the VEGF. This is a signal protein responsible for triggering new vascular growth and angiogenesis following the presence of poor tissue oxygenation caused by injury, or illnesses, such a diabetes for example. New capillary growth is triggered to facilitate improved oxygen delivery to healing tissue without which granulation and cell growth would not be possible. It is well established that HBOT upregulates the VEGF allowing accelerated healing.

What’s more, in areas of severely compromised vascularisation, oxygen just cannot make it to the wound. Severe diabetic ulcers, crush injuries, burns and so on simply don’t allow for the normal passage of red blood cells. This where oxygenation can be achieved by better saturating the plasma which can pass through far smaller structures and even increase oxygenation in other bodily fluids that can reach the site. Again, as a bridging therapy for injury this allows tissue to survive long enough for new capillaries to grow, without which crush injuries and sever diabetic ulceration almost always lead to amputation. Neovascularisation isn’t a particularly fast acting process by the body to in response to the hypoxia induced response. HBOT allows the body time to grow the vessels, and accelerates the growing of these vessels, while salvaging as much tissue as possible. Especially important when oxygen sensitive tissue is concerned.

HBOT also causes a massive increase in stem cell release facilitating healing on many fronts. I explain this further in the article on diabetes and obesity management.

Note: In type 2 diabetics, the patient life span following a first amputation is reported to be as little as 5 years in some cases.

Oxygen as an Anti-Inflammatory and Multiple Sclerosis:

Any discussion about wound healing wouldn’t be complete without mention of inflammation. Inflammation is the bane of all recovery efforts the body makes. Yet it is a crucial mechanism in the body’s natural immune response and repair-rebuild processes. When an injury occurs, in addition to the hypoxia induced reactions within the body, inflammation also occurs. As tissue and capillaries become damaged, fluid leaks out into those tissues surrounding an ulcer or injury and prevents the absorption and transport of oxygen. Since oxygen is poorly dissolved in water (leaked fluid), cells and tissues eventually die due to localised hypoxia. This is further aggravated by the bodies response to low oxygen. It is the natural auto immune response to assume infection and to despatch neutrophils, one of the white blood cell types, along with other white blood cells types such as leucocytes and phagocytes, to an area of low oxygenation such as an injury or diseased tissue. The programmed function of these cells is to ingest and break down foreign matter and pathogens. Following an injury, hypoxic tissue is interpreted as foreign or pathogenic material and is deconstructed. This is evidenced by observing swelling.  Redness and heat are generated by quicker blood throw through the core as the body attempts to restore blood flow to the area, leading to yet more fluid leakage into the tissues creating a rather vicious circle of further inflammation injury. Inflammation being the swelling part of it owing to additional fluid being present at an injury site. [1] Oxygen and The Brain – The Journey of Our Lifetime James 2014

Tissue that otherwise would have survived if it were adequately oxygenated until vascularisation could be restored, is lost. HBOT facilitates a sustained elevated tissue oxygen tension even after a patient returns to normal pressure, giving tissue that extra helping hand to survive and in doing so also relieves inflammation by controlling the body’s inflammatory response when it goes into overdrive. When this happens, the inflammation becomes the new mechanism of injury and it becomes imperative to control it. HBOT can and does do just that.

To simplify the differentiation between injured hypoxic tissue and diseased hypoxic tissue and thus avoid a lengthy paragraph, they are much the same for the purposes of this discussion. Disease could even be described as microscopic internal injury.

For example: In diabetic patients, sustained elevated blood glucose causes damage to the internal lining of capillaries. It sticks to them and prevents the adequate transport of oxygen through the capillary wall. This leads to local hypoxia and in essence, a microscopic injury to the blood/tissue barrier. Similar can be said of micro emboli in the brains vascular system making up the blood/brain barrier. Emboli cause an opening of the blood brain barrier resulting in local inflammation following the leaking of fluid into those tissues reducing oxygen saturation triggering hypoxia response. Unarguably far more serious than wounds on the feet, brain disease, (micro-injury), of this nature can be very serious very quickly.

Hence the principal for accelerated injury healing is similar to the principal of accelerated diseased wound healing.

In many cases, pain caused by an injury is twofold. It stems from obvious nerve damage occurring in the incident causing the injury and it is perpetuated by inflammation. So, while oxygen is not a pain killer per se. It will undoubtedly reduce pain where inflammation is present. This has been personally observed in the recompression of injured divers.

Multiple Sclerosis, (M.S.), can be described as a condition of the central nervous system resulting from inflammation and subsequent de-myelination, and sclerosing, of the nerves of the brain and spinal cord. When separate incidents leading to these detectable scarred or sclerosed areas are disseminated in time, the label M.S. is handed down. It’s not so much a diagnosis as it is a descriptive label. The words “Multiple Sclerosis” simply means “Many Scars”. The cause in yet unknown but it is blamed on auto-immune disease in which the immune system inexplicably attacks brain tissue.

Some disagree though, citing one potential cause as being a compromise of the blood/brain barrier, which triggers the fluid/inflammation response already discussed. The immune response is involved, but not inexplicably. It comes into action when the tissues surrounding a blood/brain barrier compromised, becoming inflamed, following fluid leakage. The hypoxia induced response then kicks in as discussed in this writing under wound healing. It’s the causes of these incidents of blood/brain barrier compromise that may well at a future time offer up a better understanding of M.S. Something as seemingly benign as a remote site injury, leading to micro emboli, could very well be involved. The accepted mechanism of de-myelination is inflammation. MS cannot be cured with HBOT, but it is certainly a great management tool, and indeed there are over 66 charity units operating across the UK under the auspices of The Hyperbaric Oxygen Treatment Trust, and, Multiple Sclerosis National Therapy Centres. These are charitable centres run by volunteers and have assisted in millions of safely executed treatments over recent years. M.S. warrants a thorough detailed article though and shall be re-visited soon for a more detailed examination of it’s mechanisms and how HBOT interacts with those mechanisms. [1] Oxygen and The Brain – The Journey of Our Lifetime - James 2014

Orthopaedic Conditions:

Orthopaedic injury, like the injuries described above, benefit in the same way. Accelerated healing for broken bones, strained tendons, other fractures, bruising to bones and so on, can all be readily healed in less time than a normal healing would take. [10] Hyperbaric Oxygen Effects on Sports Injuries Barata Et al 2011

Bone healing occurs in a similar fashion to soft tissue healing, in that a broken bone, after bleeding has been stopped by vasoconstriction, begins to heal following the formation of fibroblastic granulated tissue which later turns into chondroblast tissue. Periosteal cells in other parts of the fracture develop into osteoblasts. Ultimately the two grow in size until they unite with their counterparts elsewhere in the fracture forming woven bone, ultimately culminating in a new mass of heterogeneous tissue known as a fracture callus.

This process is hastened by the use of HBOT and bone healing can be accelerated.

A great many sports teams worldwide own their own chambers and many in the UK visit hyperbaric chambers following injury to radically shorten recovery times. Many high-end athletes have them installed at home to improve performance, as well as soft tissue and orthopaedic healing.

There are even reports of South African Rugby captain Fran?ois Pienaar having received treatment following a fractured wrist around the time of the famous 1995 world cup. He was reportedly able to return to the field after just 5 days of treatment.

Oxygen as an Anti-Bacterial Agent:

Wound healing is supported by the prevention of infection. Infection doesn’t only exist in wounds though. It is a common component of illness, viral and bacterial infection, some kinds of poisoning and any occurrence that allows a pathogen or foreign element to take root in the body resulting in infection.

In addition to its anti-inflammatory properties oxygen also exhibits anti-bacterial, anti-viral and anti-biotic properties and can be used as a complimentary treatment to help control resistant infection. [58] Hyperbaric Oxygen Therapy (Review) Tibbles Et al 1996

(Hyperbaric oxygen in the treatment of post-operative infections – A. Larsson et al. 2011 concludes that HBOT is a useful adjuvant for deep post-operative infection). Post-operative infection follows similar principals to other foreign body infection hence the relevance of the conclusion noted in the publication. [61] Hyperbaric oxygen in the treatment of postoperative infections in paediatric patients with neuromuscular spine deformity A. Larsson et al. 2011

Also quoted from the conclusion of “Not Just Full of Hot Air: Hyperbaric Oxygen Therapy Increases Survival in Cases of Necrotizing Soft Tissue Infections” 2014 by Joshua J Shaw Et al. – June 2014. [15] Not Just Full of Hot Air: Hyperbaric Oxygen Therapy Increases Survival in Cases of Necrotizing Soft Tissue Infections Shaw Et al. – June 2014.

Conclusion: “At HBOT-capable centres, receiving HBOT was associated with a significant survival benefit. Use of HBOT in conjunction with current practices for the treatment of NSTI can be both a cost-effective and life-saving therapy, in particular for the sickest patients.” [15] Not Just Full of Hot Air: Hyperbaric Oxygen Therapy Increases Survival in Cases of Necrotizing Soft Tissue Infections Shaw Et al. – June 2014.

Mentioned above is the upregulation of tissue repair processes and this paradoxically includes the release of granulocytes and phagocytes. (polymorphonuclear leukocytes or neutrophils).

Their role is to trap and destroy microorganisms by ingestion and the breaking down of bacterial cell walls, as well as deploying intra cellular bacterial protein destroying enzymes. This deconstructs pathogens as well as damaged cells or debris. Healing following injury or infection cannot take place without this removal of damaged cells and debris.

A certain level of local tissue hypoxia is necessary to trigger the inflammatory response and begin the healing process, but when this hypoxia is excessive and out of control, healing ceases and a vicious cycle of inflammation, poor oxygen transport and cell/tissue death occurs.  Inflammation and infection become the new injury mechanism. [1] Oxygen and The Brain – The Journey of Our Lifetime – James 2014[58] Hyperbaric Oxygen Therapy (Review)Tibbles Et al 1996

Incidentally this response is commonly given as a diagnosis in cases where no obvious explanation is available. The “label”, auto immune disease is one of those “cop-out” diagnoses that allow a label to be applied to an elusive cause to a problem. Interestingly, recognised as a cause of illness when it’s convenient.

This is not to say HBOT should be used for all injuries. Although they would heal quicker. Injuries without complication heal owing to this natural process when it operates in a naturally controlled manner. But when this process contributes to the worsening of an infection or injury then HBOT can break the cycle.

Certainly, a balance must be decided based on benefit to the patient. Some inflammation is healthy, but excessive inflammation is damaging.

Seemingly the use of HBOT would be contra indicated because it would appear to slow or stop the release of neutrophils associated with inflammation and local hypoxia. Not strictly true. It does slow the release of neutrophils as advocated above but the administration of HBOT would be delayed beyond the point of the triggering of the HIF1A and natural inflammatory responses. A patient arriving at hospital would most certainly have been ill for long enough for this process to already have been triggered and be well under way.  Natural response would have been triggered at the time of the injury.

In the case of out of control inflammation, these neutrophils attack normal tissue interpreted as a pathogen or a damaged cell, or even debris and micro emboli. If this goes unchecked, blood flow ultimately stops due to ongoing inflammation and cells die. When excessive inflammation is present, this can result in more tissue loss than is necessary. Phagocytes, neutrophils, etc, attack and deconstruct more than just the damaged cells because of local tissue hypoxia perpetuated by inflammation. Poor oxygen transport and perfusion then in turn support the inflammation response and a nasty cycle develops.

The paradox is that these are necessary elements of the body’s immune response to infection, but they also, in a secondary process, release oxygen free radicals into tissue causing further damage, low blood flow, poor oxygenation and inflammation. It is important to prevent this cycle of inflammation, poor oxygen transport and perfusion, low blood flow and inflammation, from perpetuating.

Beyond the inflammatory response, which is far better described in the aforementioned book “Oxygen and The Brain – The Journey of our Lifetime” – Prof. Phillip B James 2014, the author also agrees that oxygen also directly compromises the ability of any pathogen, virus etc to proliferate, that doesn’t like oxygen.  [1] Oxygen and The Brain – The Journey of Our Lifetime – James 2014

Many bacteria’s and viruses are described as anaerobic, i.e. they proliferate under anaerobic (low oxygen) conditions. High concentrations of oxygen have a direct effect on these micro-organisms which can help regain control of infection which has spiralled out of control as is the case with sepsis and non-healing wounds.

Inflammation, infection and wound healing go hand in hand, in hand, and when a balance is struck between potentially slowing the natural healing process and re-starting it when it has stalled, HBOT certainly shows itself to be a valuable tool in the toolbox, for saving viable tissue that could otherwise be lost. This is of utmost importance when oxygen sensitive tissues are involved.

A Word on Sports Injuries:

In closing on wound healing and injury I would like to cite another paper dealing with the subject of sport injury. The paper as quoted below is cautiously supportive of the arguments presented here. While not entirely in favour of widespread HBOT for all sports injuries and noting the importance of blood perfusion in low perfusion tissues such as bone and ligaments, it still looks favourably on this as a potential for improved modality of therapy. I quote their conclusion: [10] Hyperbaric Oxygen Effects on Sports Injuries – Barata Et al 2011

Dosage:

A word on dose comes into the discussion here, (briefly mentioned already), which takes us back to the aforementioned JS Haldane, the father of decompression theory. In his work on decompression theory, Haldane proposed what are called tissue compartments. These are essentially theoretical “tissues” or more accurately described, “compartments”, represented by a mathematical algorithm. In his compartment algorithm he includes mathematically represented theoretical tissue based on gas absorption rates according to Henry’s law. He represents the slowest possible rate and the fastest possible rate, and then intermittent rates, thus theoretically covering and accounting for any possible tissue likely to exists in mammalian biology. Any diving manual will be quite clear in their affirmation that these theoretical tissues or compartments and are not actual tissues.

Over the years, since his original 5 compartment model, with tissue half times of 5, 10, 20, 40, and 75 minutes (half time to saturation), and 2 to one gradient safety suggestion, dive computers and dive tables began representing more “tissue” half times, such as found in the Buhlmann ZHL-16 algorithm (16 compartments), (Uwatec Aladin computers used this in the 1990’s), with some research models now representing as many as 256 compartments. Divers, and students of diving, increasingly tend to casually assign specific tissues to the various compartments although not strictly academic. Slower tissues generally refer to tissues such as bone which is slow, adipose tissue which is fairly slow but faster than bone, and at the fast end, blood, which will saturate faster than bone. Brain tissue is also a fast tissue. Blood flow to specific tissues is the determining factor when considering their half times.

A good explanation of tissue halftimes can be read on the NHS Scottish Diving Medicine website here: https://www.sdm.scot.nhs.uk/dive_tables/index.htm.

While decompression theory is primarily involved with inert gas in-gassing and out-gassing, oxygen saturation into plasma and tissue will occur based on the same underlying principal of gas diffusion in tissue/liquid under pressure, (Henry’s Law).

This is how dose is considered.

For treatments involving slow tissue such as bones, in the case of fractures, a higher-pressure gradient is needed to saturate that tissue to an effective extent. Higher pressure shortens the saturation half-life with a steeper inward gradient facilitating shorter treatment times. For faster tissues such as brain tissue, a lower inward gradient is needed to achieve a similar saturation level, owing to their naturally shorter half times. There is no need to push the half time with a higher pressure.

In many cases a slightly longer duration at lower pressure will achieve a relatively deep saturation level in faster tissues owing to faster half times. High gradient dosage such as found in a 3ATA treatment protocol, will of course be shorter treatment times than a lower dose of say, 1.75ATA when oxygen tolerance is considered.

In the case of sports injury’s, it is normally slower tissues that are injured such as tendons and ligaments. These usually require shorter duration and higher-pressure treatments as opposed to something like brain injury, which can benefit from as low as 1,3ATA to 2ATA for longer periods, with chronic ongoing neuro-degenerative conditions benefitting from ongoing multiple low pressure – longer duration treatments. White brain matter differs also from grey matter, experiencing lower circulation and drainage. Accordingly, a moderately higher pressure may be required than that for grey matter conditions, to facilitate a shorter tissue half time.

While Decompression sickness and decompression theory may seem like another topic the crossover is obvious. Henry’s Law is the underlying scientific principal at play. Whether dealing with inert or metabolically active gas, the saturation into tissue is governed by the same principal. Decompression theory also deals with the coming out of solution of inert gas, which we don’t have a need to observe in the case of pure oxygen breathing.

Note: The similarity between decompression sickness and micro emboli in the brain is discussed in Professor James’s book already mentioned above. The professor explains that even micro bubbles, (emboli), that pose no threat to the circulatory system and pose no threat of obstruction in blood flow, and which also cause no detectable symptoms of decompression illness, do indeed make it across the lungs and enter the arterial blood supply. Dive manuals call these micro-bubbles and explain them as harmless. The lungs, as filters are extremely effective at sieving out larger emboli, including gas and fat emboli as well as other debris, but some micro emboli do make it across in some cases. These emboli, it is argued, go on to interrupt the normal functioning of the blood brain barrier, causing an opening in the barrier, resulting in fluid leakage into the surrounding tissue. This triggers the inflammatory response along with the despatch of neutrophils causing tissue damage. This can result in damage or symptoms seemingly from an “unknown” cause at a later time and would likely be labelled or “diagnosed” as auto immune disease when they do present at seemingly an un-related time.

These areas of inflammation present as bright spots on MRI and are similar in nature to sub concussion injury in imaging. Also, very similar in nature to one of the argued causes of multiple sclerosis as explained in the chapter dedicated to this subject in his book.

Decompression sickness is not just about the obvious massive circulatory blockage, tissue bubbles, neurological bubbles or tissue damage. It can present in very subtle ways which may only manifest into problematic conditions some time after an undetected incident. Certainly, worth a read – (Oxygen and The Brain – The Journey of our Lifetime – Prof Phillip B James - 2014).

Other Conditions:

This excerpt comes from the NHS Commissioning policy prepared by the NHS Commissioning Board Clinical Reference Group for Hyperbaric Oxygen Therapy, first published in April 2013. [4] NHS Commissioning of HBOT - NHS Commissioning Board Clinical Reference Group for Hyperbaric Oxygen Therapy - 2013

The three permissible conditions for which HBO may be commissioned, are laid out above and the document deals with the evidence the NHS would like to see in order to amend which conditions are commissioned for treatment.

That’s all very well, the NHS simply cannot afford to fund every new theory. Earlier in this article I distance this modality from the many snake oil remedies toted on today’s market. Demonstrated here is solid science, not fancy. And old science at that, dating back centuries to the big names in physics. This is not hypothetical or wishful thinking. This is real undisputable science. To be honest, it would be better not having the fringe support. It costs by association. This is not fringe science.

The call for triple blinded, randomised trials is unreasonable though, to say the least. It is practically impossible to run a trial of accident victims close to death, or indeed perinatal humans. Likewise, dementia sufferers all exhibit very different conditions from person to person, which vary to such a degree that no one patient could serve as control to another. It’s almost as though patients with a long list of conditions are all unique. Many conditions present uniquely in individuals. Ask the family of a handful of dementia sufferers and you will see how variable their presentation is. Or the parents of a child with cerebral palsy. Not all patients are the same and therefore cannot be matched to control subjects for trials.

You may ask then why trials are so universally recognised for the approval of drugs into the market. You’re not alone. Anyone with an aptitude for mathematics will appreciate that choosing the “right” sample of a population and, making that sample big enough, can return almost any desired result. How else do we get “science” both in favour and against smoking for example?

Tobacco lobbyists pay their scientists to analyse the “right” sample of the population, as do their opposition anti-tobacco lobbyists. A huge number of harmful drugs are on the market because of this process. While this is a valid method for many medications in use today, it simply isn’t reasonable to conduct this kind of study en-masse for HBOT. That said, some evidence does exist in this form in some instances. Evidence which is routinely ignored and dismissed. There is some progress though, albeit slow, but progress nonetheless.

In fact, it would violate ethical standards today to run trials on unborn babies or infants suffering birth injury, not to mention the resistance from the medical fraternity over any such admission. It would amount to experimentation surely? It is also impossible to accurately match control placebo subjects with those in the group receiving HBOT. How does one justify a placebo group of suffering infants being given a placebo while an active treatment is withheld?

Mentioned above is the body’s response to even just an analgesic. Papers have been written on this. A google search will find them. Patients respond as much as 700% differently to rates of absorption for drugs such as non-steroidal anti-inflammatory drugs or NSAIDS. So how is it fair, to then assume that a matched control is a fair match? [1] Oxygen and The Brain – The journey of Our Lifetime – James 2014 Pg159

In the case of emergency conditions such as severe brain injury, severe blood loss and other traumatic conditions, it simply isn’t reasonable to strike up a study. That would require an unethical delay in life altering emergency treatment. That’s how trials work, by withholding all other treatment during the trial. Obviously not an option in emergency medicine. Accepted practice establishes that any treatment that can be observed to assist the patient should not be withheld, i.e. blood transfusion for severe blood loss, giving water for dehydration, oxygen in ambulances for oxygen deprived patients.

Why then is the observational method so easily dismissed? If it is shown to help, give it. Why, when HBOT is observed to improve outcomes, as it is in divers, stroke victims, head injury victims, etc, is it withheld? It is withheld on the basis that not enough randomised double blinded placebo-controlled studies exist. This seems absurd. Requiring trials where it isn’t ethically possible to provide them, and therefore withholding a potentially beneficial treatment for want of evidence not ethically possible to obtain or provide. This amounts to the same ethical failing that would be evident if trials were to be applied to critically ill patients while withholding other effective treatments for the sake of evidence. It’s a bit of self-defeating argument.

In most cases of injury and illness, it has been demonstrated. And is reasonable to conclude, that at a cellular level, oxygen delivery is compromised in one way or another, or normal oxygen levels are just not enough to optimise the healing response naturally evolved into mammalian physiology. Surely the remedy for not enough oxygen is to give oxygen? Why then deny the administration of more oxygen than is current practice?

HBOT should be a commonplace first response rather than a reluctant last resort. There should not be a requirement for “Exceptional Clinical Circumstances” before it is considered. A great many patients would retain otherwise lost function and vitality if it were, and outcomes would be far better for those who finish up with loss of brain function and other loss of function following illness or injury.

Many more observational studies exist than triple blinded, randomised trials. Although those do exist as well. And the evidence is good that patients do indeed benefit yet, at the time of this writing, a consultation was underway to close hyperbaric units within the NHS in the UK. A low cost, effective, non-invasive, largely benign, (with no side effects), and almost risk free non-drug therapy and modality, that can be administered to many patients simultaneously in large multi place chambers. Bearing in mind that airplanes are essentially pressure vessels themselves. Something along those lines could be designed for large numbers.

The UK is not alone though. Many countries are yet to acknowledge the effectiveness and importance of this modality. It’s worth a mention that China, Japan and Russia have a far greater acceptance of HBOT and have done since the days of the Cold War. (One of the reasons why information has not been shared.) A massive resource of information is available in these countries.

It’s a simple case of choosing which evidence to deem credible by the political powers that be. Surely political positioning is less important than patient well-being? To my mind, observational study is just as valuable as trials. More so in cases of emergency treatment because it simply remains the only method of validation for HBOT.

If a patient improves, it is reasonable to conclude that, if nothing else has been changed, the introduction of a specific therapy, on a balance of probability, was responsible. It is the most basic duty of a physician not to withhold a potentially beneficial treatment regardless of prevailing politically correct views.

What’s more, matched controls don’t necessarily represent an entirely reliable representation for comparison with trial subjects. The best control for a trial subject is themselves. Patients are their own best controls. There can be no better match for a patient than themselves. After years of suffering, when some ailment is suddenly relieved upon administration of HBOT, then surely its reasonable to conclude it was the HBOT that did it?

Below is a list of conditions currently being treated worldwide by private clinics and treatment centres with a brief paragraph or so on each. I hope to extend these paragraphs into full articles in time.

Beginning with three that are indicated for treatment in the UK.

Decompression Sickness:

The primary principal and motivation for approving treatment of decompression sickness/illness (DCI) with HBOT is simply that it squashes the bubble and forces it back into solution according to Boyles Law and Henry’s Law. This removes the cause of the problem allowing successful and uncomplicated treatment of any injuries or conditions which arose as a result of the first instance.

Also, this is well accepted [worldwide] as the only indicated treatment for DCI. [4] NHS Commissioning of HBOT - NHS Commissioning Board Clinical Reference Group for Hyperbaric Oxygen Therapy – 2013[17} United States Navy Diving Manual Volume 5 - 2016

Indeed, it is globally accepted as a treatment which can be administered by divers on each other, even without extensive medical training. Even the law allows this in most countries. That’s how accepted it is.

It has been accepted because it has been observed to do the trick in decades of diving research and the treatment of actual humans as opposed to trial mice and rats. Millions upon millions of dives have been recorded and collated to contribute to decompression theory studies and the development of safe dive tables. Millions of successful treatments have been observed to resolve cases of DCI. The observational method is accepted in this case backed by solid scientific theory. The outcomes satisfy the evidence requirements in this case.

In short, the one condition unequivocally accepted as only being treatable with HBOT achieved that status by statistical and observational data and studies, and theoretical reasoning.

Gas Embolism:

Gas embolism is also globally indicated for treatment with HBOT for the same reasons mentioned above. Bubble squashing reduces the embolus size and it is then re absorbed into the body’s tissue according to Boyles Law and Henry’s Law. [25] [26]

Whether this is an embolus from a ruptured lung causing bubbles to cross into the arterial blood circulation, or an incident of DCI, it is universally recognised that Boyles Law, and subsequently Henry’s Law, provides the physics for reducing the air embolus size and absorption into the body in solution. This reduces the chance of a retinal, or even brain embolism causing potential visual issue or ischemic stroke or transient ischemic attack and even death respectively.

This too is indicated because it is shown to work in emergency situations. That is, by observation of success and by observing established physics common to diving.

Acute Carbon Monoxide Poisoning (CO):

Of the three indicated and accepted conditions for routine treatment this one is the most confusing in how it’s treated. The condition must be acute before HBOT is indicated and commissioned for use.

When CO enters the lungs, it passes through the alveolar wall, as we discussed above under gas exchange. Owing to a far greater affinity for haemoglobin, it then displaces the oxygen attached to haemoglobin and attaches itself with voracity. Because this affinity is so high, oxygen cannot easily displace the CO and the blood carries less oxygen as a result. Even normal baric oxygen mask breathing is relatively unsuccessful in removing CO from haemoglobin or re-saturating it with oxygen. CO becomes the gate keeper and doesn’t allow oxygen saturation of red blood cells (RBC’s). Removal requires a higher inward pressure gradient than that exhibited by the CO, i.e. hyperbaric oxygenation.  Oxygen must have a higher pressure compared to the CO binding onto haemoglobin in order to displace it. In the same way helium displaces nitrogen in trimix mixes because of a higher affinity, so CO displaces oxygen and requires increased pressure to reverse the carboxyhaemoglobin bond. Oxygen must be at a higher pressure to become the favoured compound for haemoglobin bonding. [63] Hyperbaric oxygen therapy for carbon monoxide poisoning –Weaver 2014

What’s more, a higher pressure of oxygen can also make use of the plasma as a means of transport as discussed, thus proving a bridging and potentially lifesaving therapy, in that it continues to supply vital systems and organs with oxygen despite “bogged down” haemoglobin. When the haemoglobin has been successfully “scrubbed” of the CO, HBOT can cease as natural recovery will support itself.

It would eventually rectify naturally in mild cases, but takes a long time, all the while depriving the body of oxygen. Why deprive the body of oxygen? In cases where death is unlikely, it can still cause ill effects. Long term cognitive dysfunction among them. Why else would authorities insist on the compulsory placing of CO alarms almost everywhere in modern society. It’s that serious that even in mild cases it’s regarded as serious. The body simply doesn’t get the oxygen it has evolved to thrive with. This can continue for days or longer after a poisoning incident. Oxygen sensitive tissue can’t sustain that length of deprivation and recover fully. Low oxygen should be regarded as serious as no oxygen. Duration of affliction becoming the deciding factor in determining the extent of cellular damage suffered.

The real danger with CO is that it is odourless and tasteless in and of itself. A victim could well have no idea that they are being poisoned and become unconscious suddenly, which, without help could very well lead to death. Usually however headache and maybe some nausea may be present. Also, a reddening of the nail beds, as taught in first aid class. Similar could be said for carbon dioxide poisoning, although CO2 is easier to remove or scrub from the blood stream than CO. Ordinarily, unless life threatening, baric oxygen would alleviate and successfully treat carbon dioxide poisoning but not so for carbon monoxide.

CO is that effective at depriving the brain and body of oxygen it has become a well-favoured suicide method. The hose in the car exhaust and through the window will be successful in ultimately displacing all the oxygen attached to haemoglobin causing hypoxia (hypoxia being the same resulting end condition suffered in low pressure altitude sickness), but rather a somewhat more irreversible form of hypoxia. Ultimately leading to death by asphyxia in the case of untreated serious carbon monoxide poisoning.

If we treat hypoxia in altitude sickness with increased pressure of oxygen why not with all cases of CO poisoning, with maybe the exception of the mildest cases. The expected response for altitude sickness is to bring the victim to a place of higher pressure to resolve low oxygenation. Why does it have to be “Acute” with death being imminent in CO poisoning? The reason is that few hospitals have hyperbaric chambers or facilities, and often transporting a patient to a facility is ill advised, or such facility doesn’t meet the prescribed standard. Surely it is more cost effective to treat a victim of CO poisoning with HBOT over a shorter period than to have them as an in-patient for an extended period?

Nonetheless, it is an indicated condition for the use of HBOT. One complication being the bureaucracy of requiring treatment in a type 1 or type 2 chamber, i.e. a hospital. In the case of a suicide attempt, even locked wards are preferred. A shame since there are a great many facilities which don’t have this capability and hence are not allowed to administer HBOT to a victim of CO poisoning. It is agreed that a patient should receive hospital treatment, however provision should be made for ANY chamber to at least be able to offer immediate emergency treatment of victims followed then by proper hospitalisation. This early stage intervention can make the difference between retaining full brain function or not. Or indeed survival or death.

Non-Indicated Off-Label Conditions:

I have had occasion recently to become acquainted with the term “off-label” conditions. Not a particularly friendly term when used the way it is. And I have heard it from more than a few sources lately. Unfortunately, despite a continuing uphill battle by proponents of HBOT, there exists a great division in the discipline all over the world.

There are those who advocate the use of HBOT only for indicated conditions and those who advocate treatment for a greater number of conditions. These, I am told are two very separate camps with much antagonism between the two. Despite growing evidence in favour of wider use, many limit the use of HBOT to the few indicated conditions claiming a lack of sufficient evidence of benefit. It seems the two sides disagree on much.

How on earth can we expect progress in favour of HBOT when we cannot even agree among ourselves which is the best way forward?

Surely the industry would benefit from a unified approach with concession made on both sides with regard to operating procedure, modified safety and risk analysis for milder dose protocols, standard protocols, indicated conditions, training, accreditation and so on? Surely combined resources would go a long way to providing the evidence the political powers call for?

It does the industry no good when opinions are so divided on certain issues.

Safety seems to be one of the key issues as well as proven benefit from treatment. There is only one way to see if a specific condition benefits, and that’s to treat it. HBOT will not make it worse and has no problematic side effects. It can hardly be seen as experimentation when all this is doing is proving more oxygen within safe limits to optimise natural function. It wouldn’t hurt in other words but could well help. Why not make and accept more observational studies? Not anecdotal studies, but actual observational studies of measurable improvement in real patients.

Seemingly not however. Seemingly, never the twain shall meet. It amazes me to be honest, that two sides whose goals are so similar are so far apart. What are known as type 3 chambers in the UK are unregulated and easily run by volunteers. Maybe this has something to do with it. Outside of the “framework” so to speak.

The following conditions are currently considered “off-label”, however good evidence, studies, both observational and randomised blinded trials exist in support of their indication for hyperbaric oxygen therapy/treatment.

I for one am a supporter of a wider, and more mainstream application of this modality and relatively low tech, cost effective alternative, facilitative, supportive and complimentary therapy.

I too am a safety nut coming from the diving world, but accommodation can and really should be made to expand the conditions indicated for treatment and include all organisations in the mainstream.

Cerebral Malaria:

In 1999 I was unfortunate enough to suffer a severe case of malaria whilst living and working in Tanzania, East Africa. I was a diver as well as a chef in those days. If you look it up I’m in a medical journal somewhere. At least at the time, it was the highest recorded survived parasite count in East Africa with a P Falciparum count exceeding 8000 parasites in 200 blood cells. They stopped counting above that as they expected me to die anyway and it wouldn’t really matter just how bad it was. The outcome was going to be the same regardless.

For three consecutive days we were told I wouldn’t survive the night. Needless to say, this had a massive effect on my family if not me. Psychologists came to see me, and I was prepared for the eventuality of my death by them in the way of discussion and suggestions made to fly home to South Africa in a Leer jet air ambulance and die with my family, rather than in developing Africa. It was in my central nervous system and just about every other system was affected. How I survived is still an unknown. When I left the IST International Clinic in Dar es Salaam after days of crazy hallucinations and intensive treatment, one of the nurses who cared for me said to me, “it is only by the grace of God you leave here today”. She then filled me on a rather amusing horse race that went on on my chest and being put back in bed by the security guard when I stormed off down the road to go home almost completely naked. I still have no memory of much of that 3 or 4 days outside of not being convinced I was going to die.

I received help from the Kenya malaria team of the time, the Tanzania based experts, as well as the tropical disease centres input from Switzerland and the UK I believe.

In any event, if you’re still reading you’ll notice I’m alive and well. Although, after donating blood I did receive a letter from the NHS in 2016 suggesting I go see my doctor if I feel unwell. I was further asked to please not donate blood anymore since I shall test perpetually positive for malaria parasite and it could lead to an infection in someone receiving my blood.

This little anecdote is merely to demonstrate how seriously I personally view malaria. This serves to introduce a short paper I have recently come across entitled:

“Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria” by Yara C. Blanco,  Alessandro S. Farias, Uta Goelnitz, Stefanie C. P. Lopes, Wagner W. Arrais-Silva, Bruna O. Carvalho, Rogério Amino,  Gerhard Wunderlich,  Leonilda M. B. Santos, Selma Giorgio, and Fabio T. M. Costa. – 2008.

The paper can be read online but I’ll quote from their conclusion:

“The data presented here is the first indication that HBO treatment

could be used as supportive therapy, perhaps in association

with neuroprotective drugs, to prevent CM clinical outcomes, including death.” [9] Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria Yara Et al 2008

Interesting to say the least. It certainly warrants further research and in the case of someone like me, who was scheduled and certain to die. What is there to lose? If it had been offered even as an outside chance of helping I know that I would have been happy to try it. I was a diver even then and was in the early stages of learning about diving medicine and would no doubt have considered it better than dying. Who really wants to die just for the sake of being right? Sounds like the making of a Kris Kristofferson song.

Over a million people die annually from falciparum malaria. If a supportive or complimentary therapy could be developed to improve outcomes even by some margin, then surely the medical fraternity have a responsibility to investigate further. Hyperbaric oxygenation is relatively simple to deploy without the need for extensive medical training. Containerised chamber systems have been used in diving for a long time and could prove beneficial in endemic and remote areas around the world.

Cancer and Radiotherapy:

In 2012 a review of HBOT and cancer studies was undertaken by Ingrid Moen and Linda E. B. Stuhr entitled:

 

Hyperbaric oxygen therapy and cancer—a review from Targeted Oncology. – Moen Et al. – 2012 [7]

The review concluded that despite previous beliefs that HBOT was a cancer promoter and tumour grower, it was in fact safe and patients reviewed that had undergone HBOT suffered no significant growth in tumours. The insert confirms:

The same year (2012), I was asked by a family member if HBOT would help her stage 4 liver cancer. I said no, it would grow the tumours. Accordingly, she never investigated it further. Pursuant to that, I followed up and made enquiries and discovered that my original thought of increased vascularisation would cause tumours to grow more rapidly was indeed wrong.

If only I had been aware of the review sooner.

The report establishes that no evidence exists that HBOT promotes angiogenesis in cancer tissue, contrary to former beliefs that it would accelerate vascularisation of tumour tissue resulting in accelerated growth. It does do in normal tissue and wounds which are aerobic tissues. However, the cited studies in this paper establish that an anti-angiogenesis effect is noted in tumour tissue, which is anaerobic, with incidents of inhibitory effects in mammary tumours and at least one glioma model. Angiogenesis and vascular recruitment (neovascularisation) is not evident in tumours following HBOT.

The reason is that cancer and tumour growth is anaerobic. Similar to what we discussed regarding anaerobic viruses and bacteria.

Cancer cells reproduce in an anaerobic (low oxygen) environment. It has been suggested and studied since 2012 that HBOT can actually inhibit tumour growth and could potentially, along with other therapies, be a cancer cell killer.

Additionally, HBOT is routinely used, “off-label”, for the treatment of tissue damage caused by radio therapy. Especially in cases of oesophageal cancer, which too, I am very personally familiar and acquainted with. Head and neck cancers benefit greatly in preserving as much tissue as possible following radiotherapy on the basis discussed under wound healing. The preservation of this tissue, if not a life saver, is certainly a quality of life provider. If patients can avoid some tissue damage at least they can retain better functions such as speech, breathing and so forth, providing an improvement in quality of life. HBOT will also effectively manage inflammation and as a knock-on effect, pain, as already discussed, reducing the need for debilitating pain medications.

Additionally, HBOT is considered a chemo-facilitator. Pre-conditioning is fast becoming a topic of research. Before operations, radio therapy and so on, patients are pre-conditioned with a HBOT session prior to tissue damage. The increased oxygen tension in tissues following treatment aids healing and reduces damage. HBOT is easily given hours prior to surgery or radiation therapy. It’s easier than taking an X-ray for example, or other relatively routine procedures. It’s low tech by comparison. As a chemo-facilitator, HBOT pre-conditions the body for chemotherapy to be better targeted and more effective.

Hypoxia is described as an important factor in chemotherapy resistance. Hypoxia mediated response to chemotherapy has been ascribed to: altered cellular metabolism reducing drug cytotoxicity; the redox state, meaning that oxygen is required to generate ROS to be maximally cytotoxic. Additionally, cytoxicity is important in achieving maximal effect. Tumour tissue anatomy affects transport of intravenously administered substances to the cancer cells determing the efficacy of the drug (Moen Et. al. 2012). [7]

As a potential cancer cell killer surely early stage treatment could be beneficial and improve survivability?

A Word on Immunotherapy:

Recently newspapers around the world featured a story of a patient with advanced breast cancer, who, after being given three years to live, was declared cancer free for 2 years, following new immunotherapy treatments. An amazing story to say the least, considering the cancer had moved into many other areas in her body.

https://www.theguardian.com/science/2018/jun/04/doctors-hail-world-first-as-womans-advanced-breast-cancer-is-eradicated 

This research too is not new research and has been around for some years now. It is now slowly becoming a potential treatment for many cancers, including prostate cancer in men. It too was considered “fringe”, not long ago, and dismissed by many.

I have also seen other articles claiming a loss of weight in patients in the days and weeks following treatment as the cancer cells are deconstructed and leave the body. As much as a few kilograms even.

In the UK some versions of this are slowly becoming available on the NHS with reported success rate of around 10% in patients.

As we know, the reason cancer is not supressed by the immune system is that the immune system recognises cancer cells as the body’s own cells and is not up-regulated as it would be in the case of a pathogen or other foreign body.

From what I’ve read, T-cells are harvested from individual patients and then reprogrammed to recognised cancer cells, and then re -introduced into the body. [64] CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers 2014 [65] Driving CAR T-Cells Forward [Abstract] – Jackson 2016

In some cases, seemingly miraculous recoveries are noted. That said the “hit-rate” is still low.

Under the discussion above on chemo facilitation, I mention the sensitizing of cancer cells and tissues, making them more susceptible to the toxicity of chemo therapy drugs, thus facilitating more effective, and targeted chemotherapy.

Little more than a theory, is it not worth considering that a similar sensitization of cancer cells, (given to their intolerance of hyper-oxygenation and anaerobic nature), may better facilitate the targeting of this therapy?

Is it worth considering, and surely the question now needs to be asked, can we better target reprogrammed T-cells to better seek out and deconstruct cancer cells? Thus, perhaps increasing the efficacy of this ground-breaking therapy?

I can hear the reply already. “More data are needed”. I agree whole heartedly. There exists then a responsibility of the medical profession to go out and generate these data.

.../ Part 3