Oxygen

Oxygen (O₂) is a chemical element. At standard temperature and pressure, two atoms of oxygen bind together to form a colourless and odourless gas with a molecular mass of 32. Together with nitrogen and argon, oxygen is one of the three major constituents of Earth’s atmosphere. 

Medicinal oxygen is an essential medicine with no substitution. Healthcare professionals use it to treat respiratory diseases like COVID-19 and pneumonia. It is administered to patients as an inhalation gas. Solely medicinal oxygen shall be applied to patients. Compared to industrial oxygen, medicinal oxygen is tested to meet authorized specifications for its identity, purity and content and is produced, stored and distributed following good manufacturing practices for patient safety.

International Pharmacopoeia

Oxygen systems must consist of an oxygen source, or production, combined with storage and distribution. Medicinal oxygen can be produced by the air-liquefaction process or by pressure swing adsorption.

Depending on the source and production method, the medical oxygen has the following characteristics: 

1. By the air-liquefaction process – according to the International Pharmacopoeia and to the Revision of the monograph on Oxygen for inclusion in The International Pharmacopoeia (October 2021) medicinal oxygen produced by air-liquefaction must contain not less than 99.5% V/V of O₂. Cryogenically produced liquid oxygen is always generated off-site (not at a medical facility).

2. By Pressure Swing Adsorption (PSA) plants – according to the Revision of the monograph on Oxygen for inclusion in The International Pharmacopoeia (October 2021) and to WHO interim guidance technical specifications for PSA plants (June 2020), pressure swing adsorption technology produces medical oxygen with 93%±3% O₂ from ambient air. A pressure swing adsorption (PSA) oxygen plant serves as a large, central source of oxygen generation that can be located on-site at medical facilities.
3. By oxygen concentrators – according to WHO-UNICEF technical specifications and guidance for oxygen therapy devices (2019) and WHO interim guidance of WHO list of Priority Medical devices for COVID-19 and its associated technical specifications (2020), the concentrator should deliver low-flow, continuous, clean and concentrated oxygen (> 82%) from room air (21%). An oxygen concentrator is a self-contained, electrically powered medical device designed to concentrate oxygen from ambient air using pressure swing absorption process. Oxygen concentrators are mobile and can be moved between clinical areas or for home care and some are even portable.

Oxygen sources and distribution for COVID-19 treatment centres

Oxygen systems must consist of an oxygen source, or production, combined with storage and distribution. Within the hospital oxygen can be distributed using pipeline intra-hospital distribution networks. If no pipeline is available, oxygen cylinders are used. In small health centres or where pipes or cylinders are not available, oxygen concentrators can provide oxygen directly to the patient from the bedside.

Pipeline intra-hospital distribution networks are helpful to supply oxygen at high pressure to equipment such as anaesthetic machines and ventilators. A key advantage of pipeline systems is that they obviate the need for handling and transporting heavy cylinders between hospital wards.

Oxygen gas can be compressed and stored in cylinders. These cylinders are filled at a gas manufacturing plant, either via air liquefaction or a PSA plant, and then transported to health facilities. Additionally, storage or transportation of medical oxygen in cylinders must be done carefully and by trained personnel as the contents are under extreme pressure.

Oxygen sources and distribution for COVID-19 treatment centres

Oxygen Access Scale Up

Within the human body oxygen is tightly regulated to prevent hypoxaemia. Hypoxaemia, or low blood oxygen saturation, is a common complication of a range of clinical conditions. Hypoxemia can lead to acute adverse effects on organs including the brain, heart and kidneys. Oxygen is essential for the treatment of hypoxaemia and should be given to the patient to improve and stabilize blood oxygen saturation levels.

Therefore, oxygen saturation is a crucial component of patient care. Oxygen saturation (commonly referred as oxygen level) is a measure of how much haemoglobin is currently bound to oxygen compared to how much haemoglobin remains unbound. Red blood cells contain haemoglobin, and one molecule of haemoglobin can carry up to four molecules of oxygen. Most of the haemoglobin in blood combines with oxygen as it passes through the lungs.

Technical specifications for oxygen concentrators

WHO’s Science in 5 on COVID-19: Medicinal oxygen

The gold standard for measuring arterial oxygen tension and for calculating oxygen saturation is blood gas analysis. This method is invasive and requires blood gas analysis machine and reagents. Therefore, it is not appropriate in all contexts.

A pulse oximeter can also measure oxygen saturation. It is a non-invasive method that measures light wavelengths to determine the ratio of oxygenated haemoglobin compared to deoxygenated haemoglobin. The use of pulse oximetry is considered a standard of care in medicine. It is often referred as the fifth vital sign. Medical practitioners must know the functions and limitations of pulse oximetry. They should also have a basic knowledge of oxygen saturation.

When arterial haemoglobin oxygen saturation is measured by arterial blood gas analysis, it is known as SaO2, and when it is measured non-invasively by pulse oximetry it is known as SpO2 (haemoglobin oxygen pulsed saturation). SpO2 is therefore often used to define hypoxaemia.

Oxygen therapy for children

Pulse oximetry is the most accurate non-invasive method for detecting hypoxaemia. It is used to measure the percentage of oxygenated haemoglobin in arterial blood (SpO2). The pulse oximeter consists of a computerized unit and a sensor probe, which is attached to the patient’s finger, toe or earlobe. The pulse oximeter measures oxygen saturation of haemoglobin in the blood by comparing the absorbance of light of different wavelengths across a translucent part of the body. The oximeter displays the SpO2 with an audible signal for each pulse beat, a pulse rate and, in most models, a graphical display of the blood flow past the probe (the plethysmography or pulse wave). The technology is robust and the cost quite low. Pulse oximeters can be used to both detect and monitor hypoxaemia, make more efficient use of oxygen supplies and improve patient monitoring; they are cost-effective for district hospitals.

Priority medical devices list for the COVID-19 response and associated technical specifications

WHO-UNICEF Technical specifications and guidance for oxygen therapy devices

Oxygen therapy for children

Arterial oxygen saturation is referred to as SaO2 when measured by gas analysis and as SpO2 when measured by pulse oximetry. The normal range of SpO2 at sea level is 97–99%, with a lower limit (mean minus 2 standard deviations) of 94%. Oxygen saturation values drop with increase of altitude (Figure 1).

Figure 1 Mean Spo₂ and threshold of hypoxaemia at different altitudes.

Oxygen therapy for children

Oxygen therapy or supplemental oxygen is the provision of medical oxygen as a healthcare intervention. Only medicinal-grade oxygen that complies with current quality standards, as for example described by The International Pharmacopoeia (Medicinal Oxygen (Oxygenium Medicinalis), Draft proposal for revision in The International Pharmacopoeia, 5 (October 2021) ), should be given to patients. The current standard of care for oxygen therapy includes proper monitoring and training of clinical staff regarding when and how to administer therapy. Pulse oximeters are an important low-cost technology and the accepted standard for detecting hypoxaemia and monitoring oxygen therapy. When combined with an appropriate oxygen supply, pulse oximetry can promote the efficient use of oxygen.

Oxygen therapy is a highly effective intervention for reducing global mortality. WHO guidelines emphasize the importance of oxygen and its broad indications for neonates, paediatrics, obstetrics, internal medicine, emergency care, triage, anaesthesia, surgery, trauma, survival services, and pandemic preparedness and treatment of other common medical conditions and illnesses affecting patients of all ages.

Oxygen sources and distribution for COVID-19 treatment centres

The sources of oxygen, its distribution and delivery depend on the facility and the availability of resources. The most common sources of oxygen are air liquefaction process, pressure swing adsorption and oxygen concentrators (see question 3). Effective oxygen delivery systems should be a universal standard of care and should be made more widely available.

The methods used to deliver oxygen to the patient should be safe, simple, effective and inexpensive. They could be non-invasive (through a face mask, tent or holding tubing close to the face) or semi-invasive (insertion of prongs or catheters into the upper airway). Semi-invasive delivery methods require a low oxygen flow and are cheaper than non-invasive methods, which require high oxygen flow.

Nasal prongs and nasal and nasopharyngeal catheters are the most efficient means for delivering oxygen. Nasal prongs are the preferred oxygen delivery method in most circumstances for an optimal balance between safety, efficacy and efficiency. Humidification is necessary only with methods of oxygen delivery that bypass the nose; it is generally not necessary when oxygen is delivered through a nasal catheter or nasal prongs. Humidification is essential when cold oxygen is delivered from a cylinder through a nasopharyngeal catheter or when high oxygen flows are used.

Oxygen therapy for children

Oxygen sources and distribution for COVID-19 treatment centres

COVID-19 Clinical management: living guidance

WHO defined the severity of COVID-19 using the following criteria:

The definition of severe COVID-19 includes oxygen saturation SpO₂ < 90% on room air. However, the panel noted that the oxygen saturation threshold of 90% to define severe COVID-19 was arbitrary and should be interpreted cautiously. For example, clinicians must use their judgment to determine whether a low oxygen saturation is a sign of severity or is normal for a given patient with chronic lung disease. Similarly, a saturation > 90–94% on room air is abnormal (in patients with normal lungs) and can be an early sign of severe disease if the patient is on a downward trend. Generally, if there is any doubt, the panel suggested erring on the side of considering the illness as severe.

COVID-19 Clinical management: living guidance

Ideally, all patients with COVID-19 are cared for in a healthcare facility. Home care does not replace healthcare by professionals. Those patients who receive homecare should be regularly monitored by health workers. However, there may be some circumstances where patients may not require hospitalization or inpatient care is unavailable or unsafe, such as when capacity is insufficient to meet the demand for healthcare services. Patients should be assessed on a case-by-case basis by the health worker to determine where their care needs can best be met.

Use of pulse oximetry at home is a safe, non-invasive way to assess oxygen saturation in the blood and can support the early identification of low oxygen levels in patients with initially mild or moderate COVID-19 or silent hypoxia, when a patient does not appear to be short of breath but his or her oxygen levels are lower than expected. Home pulse oximetry can identify individuals in need of medical evaluation, oxygen therapy or hospitalization, even before they show clinical danger signs or worsening symptoms.

Home care for patients with suspected or confirmed COVID-19 and management of their contacts