The scene is set from the series so far – healthcare systems in a complex balancing act, political distractions at play, a new virus emerging from origins evidently unknown, and the understanding of a century of pandemics and epidemics in our collective back pockets. 

So what of the product that would go on to be at the heart of coronavirus therapies the world over – oxygen? How did we get to such severe shortages seen in various parts of the world throughout 2020 and now, 2021 too?

To better understand the complexities behind those questions, it is first beneficial to understand the product itself and how it came to be. Here in Part 5 of this Covid-19 Oxygen Crisis series we explore the discovery of oxygen and its role in society and healthcare systems the world over.

’Dephlogisticated air’ 

For something so fundamental to human life, it seems strange to write that oxygen was only discovered in recent centuries and yet, that is the case. 

It is widely credited that oxygen was first ‘discovered’ by the English chemist Joseph Priestley. He believed that air mixed with carbon created electricity and, in 1774, he used a 12 inch-wide glass ‘burning lens’ to focus sunlight on a lump of mercuric oxide. During this experiment, he observed that mercuric oxide broke down under the extreme temperature and formed beads of elemental mercury. The mercuric oxide also emitted a strange gas that facilitated flames and opened the respiratory tract, making it easier to breath when inhaled. At the time, Priestley named this gas ‘dephlogisticated air’69

Thankfully for the title of this series of articles if nothing else, it was not a term that would endure. In 1774 the French chemist Antoine-Laurent Lavoisier then met with Priestley, who told him of this discovery, and Lavoisier began to conduct his own experiments with Priestley’s ‘pure form of air’. In his experimentation he observed that the element was part of several acids and incorrectly assumed that it was needed to form all acids. Based on this thought, Lavoisier used the Greek words oxy (acid) and gene (forming) to create the French word ‘oxygene’ which was subsequently translated to ‘oxygen’ in English, around 1779.

Depending on your source, the roots of oxygen’s discovery do in fact predate Priestley. It is said that oxygen was isolated by Michael Sendivogius before 160470 but commonly believed to have discovered as an element independently by Carl Wilhelm Scheele, in Uppsala, Sweden in 1773 or earlier and by Priestley in 1774. Priestley is often acknowledged, however, as his work was the first to be published. 

The next meaningful steps in the history of oxygen would not come until the late 19th century, when scientists began to realise that air could be liquefied and its components isolated by compressing and cooling it. Various scientists are credited as having undertaken pioneering efforts in this field, but not to any tangible scale. It is documented that oxygen was liquefied in a stable state for the first time on 29th March 1883 by Polish scientists Zygmunt Wróblewski and Karol Olszewski from Jagiellonian University71 and later produced in a quantity sufficient for study by Scottish chemist James Dewar in 189172. The first commercially viable process for producing liquid oxygen, however, was independently developed in 1895 by German engineer Carl von Linde and British engineer William Hampson. Both men lowered the temperature of air until it liquefied and then distilled the component gases by boiling them off one at a time and capturing them separately73

Air separation

This cryogenic distillation process, widely credited to Carl von Linde and combined with his later separation of the constituent gases in 1902, is the backbone of the air separation process that we know today. 

During this same period, French engineer George Claude had also successfully developed a new air liquefaction process and along with his business partner, Paul Delorme, launched the public company Air Liquide in 1902 to research Claude’s processes74. Whether intentional or not, the race to the modern air separation process was on.

Carl von Linde actually sought to promote the internationalisation of his discoveries and budding business in Europe and had not only sold the patent rights to his refrigeration and ice machines to German-American Friedrich Wolf in Chicago, but would also go on to market his air liquefaction plants in the US. Before he could so, he would need to have the American patents and, after what would become years of lengthy hurdles and patent disputes, eventually decided to found his own company in the country. 

December 1906 would see von Linde travel to Buffalo to purchase land and set in motion the construction of an oxygen factory, culminating in the founding of Linde Air Products. Opened on Thanksgiving Day in November 1907, the factory became the first oxygen production plant in the US75.

Over a century later and air separation units (ASU’s) are integral to the production of all industrial gases such as argon, oxygen and nitrogen by separating air into their constituent components. Without ASU’s in modern industry, it would not be possible to produce these molecules in the quantities required today and in such a cost-effective manner. Although other technologies exist to produce these molecules, the processes they harness are considered more costly76

Nitrogen and argon extracted from the air separation process are normally produced directly from modern ASU’s at a purity suitable for most industrial and specialty gas applications. When extracted from an ASU, oxygen can generally be used without further purification for many medical and industrial applications, but specially designed ASU’s are required to produce the high purity oxygen needed for specialty gases applications. 

On that applications front, oxygen is used for a wealth of key end-user sectors, not least in the production of steel, plastics and textiles, in the manufacture of various cut and welded products, as a rocket fuel/propellant, for oxygenation in water treatment applications, and of course as a medical gas in healthcare and a multitude of life support/sustaining systems aboard aircraft, submarines, space flight and deep sea diving. 

This brings us to arguably that most precious of applications – medical oxygen for saving and sustaining life.

shutterstock_1455103604

Oxygen in health and wellbeing 

Supplemental oxygen – or oxygen therapy – is the use of oxygen as a medical treatment. In short-term procedures or treatments, this might include the use of oxygen to remedy low blood oxygen levels, to overcome carbon monoxide poisoning or to maintain a patient’s oxygen levels while under an anaesthetic during an operation. 

In long-term cases, oxygen treatment has been increasingly called upon in the fight against known and ongoing respiratory diseases like COPD (chronic obstructive pulmonary disorder) or other lung diseases where chronically low oxygen levels are restrictive at best and life-endangering at worst. Portable oxygen delivery devices to meet these needs have been a fast-growing application for those in the gas and equipment business. This is more a reflection of improving healthcare and quality of life than advances in oxygen itself. Oxygen treatment of respiratory diseases has existed for a very long time; there has, however, been significant increases in the understanding and willing treatment of diseases such as COPD, while the increased development of portable oxygen devices has largely been driven by a desire to improve the quality of life of those suffering from these diseases.

On a more technical level, oxygen is required for normal or healthy cell metabolism, the set of life-sustaining chemical reactions in organisms. For humans, the intake of oxygen from the air is the essential purpose of respiration – the inhalation of oxygen from the outside environment to the cells within tissues and the exhalation of carbon dioxide in the same process – so oxygen supplementation is used in various branches of medicine. 

Treatment not only increases oxygen levels in the patient’s bloodstream, but has the secondary effect of decreasing resistance to blood flow in many types of diseased lungs, easing the workload on the heart. Oxygen saturation is key and can vary on the treatment being given; just as oxygen is required for core functions and to overcome the presence of carbon dioxide or carbon monoxide in a given circumstance, excessively high concentrations can cause oxygen toxicity or lung damage77

For the first half of the 20th century, pressurised oxygen therapy was being used to treat numerous medical issues such as emphysema, asthma and pneumonia, a medicinal form of oxygen that was generally kept in heavy steel cylinders78. Access to oxygen therapy for pneumonia is still essential and a significant challenge in low and middle-income countries (LMICs) today, in 2021. The Every Breath Counts Coalition is the world’s first public-private partnership to support national governments to end pneumonia deaths by 2030. The coalition of UN agencies, businesses, donors and NGOs has committed to supporting governments in countries with some of the highest burdens of pneumonia. 

It supports ‘double-burden’ countries across Africa, Asia and Latin America that are struggling with heavy burdens of Covid-19 and child pneumonia deaths and aims to close the critical gaps in pneumonia prevention, diagnosis and treatment. It states, “Pneumonia is the world’s biggest infectious killer of adults and children – claiming the lives of 2.5 million, including 672,000 children, in 2019. Pneumonia deaths are falling. But too slowly to achieve the Sustainable Development Goal of ending preventable child deaths by 2030. Covid-19 has already added 1.9 million to the death toll from respiratory infections in 2020, increasing all-cause pneumonia mortality by 75%.

home healthcare oxygen

While children suffer far less from the direct impact of Covid-19, the potential secondary impact caused by the disruption of health services, as well as increased rates of wasting, might account for up to 2.3 million additional deaths among children under the age of five – more than a third from pneumonia and newborn sepsis alone.” 79 Among the products and critical gaps the Every Breath Counts Coalition includes in its mission is oxygen; a relatively basic, fundamental and yet often difficult to procure medicinal treatment. 

Hyperbaric oxygen therapy uses medical oxygen at a pressure higher than atmospheric. Such therapy requires a patient to lie down inside a chamber filled with 100% pressurised oxygen and is thought to remedy a whole host of ailments. The 100% pressurised oxygen stimulates the growth of new blood vessels and improves the flow of blood to areas with reduced circulation. It is understood to reduce the injurious effects of systemic gas bubbles by physically reducing their size and providing improved conditions for the elimination of bubbles and excess dissolved gas80.

HBOT found early use in the treatment of decompression sickness and is perhaps most synonymous with treating divers, but is also thought to have shown effectiveness in treating conditions such as carbon monoxide poisoning. More recent research is reported to have examined the possibility that HBOT may also have value for other conditions such as cerebral palsy and multiple sclerosis, but no significant evidence has been found. In fact, there is a degree of caution urged with HBOT, with many of its benefits said to be not medically proven; it is not currently a common feature of hospitals and healthcare centres. It should also be noted that the relevance of HBOT to the Covid story is limited; it was not widely used and largely the subject of trial treatments.

During the pandemic of Covid-19, medical oxygen has been used in its most critical form – in assisted respiration, incident response and life support. It has been very much about getting that oxygen into patients struggling to breathe and suffering from dangerously low oxygen levels, and keeping their vital functions active. 

Medical oxygen production 

As gasworld explored at length last year (2020), oxygen produced by the cryogenic distillation process is typically produced at greater than 99% purity so that it can be used for essentially all applications, including for medical purposes. Medical oxygen, is, however considered as a drug or pharmaceutical product in the healthcare sector.81 

Oxygen produced by air separation is acceptable as medical oxygen without any additional purification steps. The air separation process itself removes contaminates to levels typically below those required to meet medical oxygen specifications. Although some air separation facilities may divert a portion of the oxygen they produce into dedicated medical oxygen tanks, this is not a universal practice, nor is it necessary; oxygen produced by air separation is, by nature of the process, acceptable as medical oxygen. It is, however, heavily regulated, and in some regions it is necessary as the regulations require separate storage.

Many air separation facilities produce oxygen into a common tank, then use in-facility testing equipment to verify the product meets the specification for its intended use. In the case of medical oxygen, this in-facility testing equipment is also used to produce the test results that allow a qualified person to release the product as acceptable for use as medical oxygen. To be able to sell medical oxygen, plants must have the required licenses and ensure the stringent specifications to be met – some describe this as a ‘red tape’ process, but others rightly observe that with oxygen considered a medicine that enters the human body, it is fundamental to have the necessary quality control and assurance processes in place for patient safety. There cannot be any instances of sub-standard product being supplied and administered.

Oxygen in the medical field has traditionally been produced centrally at the ASU(s) and then distributed in liquid form, or as a gas via cylinders, to the customer. European hospitals, for example, have typically relied upon these two choices for supplying medical oxygen to their medical gas network – depending on their consumption they could either purchase liquid oxygen stored in on-site in bulk cryogenic tanks and fed into the facility via its pipelines, or purchase cylinder supply and the regular refills required. 

Bulk supply via storage tanks and pipeline into the wards is generally the most popular or required means of supply, such is the volume of medical oxygen required. However, it is not uncommon to find a combination of bulk and cylinder supply – this has long been used to ensure continuity of supply. Central banks of cylinders are connected automatically to a hospital’s piped system to provide security of supply to liquid, in the event of any problems. This was especially the case during the circumstances of pandemic, whereby the amount of oxygen required could feasibly outstrip the capabilities of the pipelines to deliver it. Cylinder supply can both complement the piped capacity and also provide a relatively mobile means of supply.

shutterstock_1960070674

Source: Exposure Visuals / Shutterstock

An alternative and increasingly popular means of oxygen generation exists in the medical market, however, in the form of pressure swing adsorption (PSA). Though commercialised in the 1970s, PSA oxygen concentrators for the supply of medical gas distribution systems have grown on the worldwide market in the last 20-25 years in particular. As the oxygen is produced onsite, without delivery and storage, medical oxygen generators have convinced many hospitals and healthcare facilities in North America, Africa, Middle East, Asia, and in recent years Europe, that they are able to supply medical oxygen at a competitive price compared to liquid oxygen or cylinders. 

PSA systems utilise commonly available components that can greatly reduce the initial capital required compared to the cryogenic production of oxygen, for example, and offer the kind of mobility that address the varying requirements of the hospital and healthcare sector; their rise in this area has been facilitated by ‘monographs’ that deem the use of oxygen in the range of 90-96% purity acceptable. 

Gaps in the oxygen supply chain during the Covid-19 pandemic have shone the spotlight on this means of onsite oxygen production, via generators and concentrators, as a third means of oxygen supply in addition to traditional means of delivery via bulk liquid and packaged gases. Those in the PSA systems space claim it has opened the door to this mode of supply, but there are of course counter-claims and questions over PSA systems when viewed as a long-term resource.

Liquid suppliers will question not only quality control and assurance, where a lack of contaminants in the supply is concerned, but also the security of supply in the event of an unforeseen failure. For example, is there a back-up supply to the PSA unit in the event of a system failure? It is in this context that the well-practiced combination of pipeline and cylinder supply is a valuable example. Another question might concern the back-up power supply status for those PSA systems, particularly so in less developed regions where power outages are common, if not unheard of; regions where PSA supply has been more prevalent. gasworld understands there have also been questions raised about the long-term maintenance of an installed base of PSA systems.

All of these factors become less of a potential issue in the event of major shortage situations, as has been seen over the last year, but must not be overlooked in the long-term view of the medical oxygen markets.