Medical oxygen 99.5%

MIMS Revision Date: 01 January 2021

1 Name of Medicine

Oxygen.

2 Qualitative and Quantitative Composition

Contains 99.5% v/v oxygen.
Complies with current British Pharmacopoeial specifications, purity not less than 99.5%.
Purity: Not less than 99.5% v/v.
Carbon dioxide: Not more than 300 ppm v/v.
Carbon monoxide: Not more than 5 ppm v/v.
Water: Not more than 67 ppm v/v.
There are no excipients.

3 Pharmaceutical Form

Compressed medical gas for medicinal use.
Odourless, colourless gas.

4 Clinical Particulars

4.1 Therapeutic Indications

For respiratory delivery where there is a requirement for medical oxygen to treat or prevent hypoxemia.

4.2 Dose and Method of Administration

Medical oxygen is administered by inhalation through the lungs. The major exception is when a metered supply is fed into the oxygenator of an extracorporeal circulation of a cardio-pulmonary bypass system.
Inhaled Medical Oxygen must be administered using an appropriate pressure reduction device and equipment such as mask or nasal prongs to deliver the required inspired concentration of oxygen, between 21% and 100%, as determined by the prescriber after full clinical assessment. Most delivery systems for adults result in an inspired oxygen concentration of 60% or less. Inhaled oxygen may require humidification when treatment duration is longer than an hour.
Standard texts and clinical protocols should be consulted for the oxygen requirements specific to the underlying condition and the clinical status of the individual patient. It is essential to monitor ventilation, arterial oxygen saturation, and the clinical effect of the treatment.
In general, the aim of treatment is to ensure, by adjusting the oxygen fraction in the inhaled air (FiO₂), so that the oxygen partial pressure in arterial blood (PaO₂) does not fall below 60 mmHg or that the oxygen saturation of haemoglobin in arterial blood does not fall below 90%. The dose (FiO₂) must be adjusted according to each patients individual needs, taking into account the risk of oxygen toxicity. The general recommendation is to use the lowest dose necessary to achieve the desired result of treatment. In cases of pronounced hypoxia, oxygen fractions that can involve a risk of oxygen toxicity may be indicated (see Section 4.9 Overdose).
In short-term treatment with oxygen, the oxygen concentration i.e. the fraction in the inhaled gas mixture (FiO₂; avoid > 0.6=60% O₂ in the inhaled gas mixture) should be maintained so as to achieve an arterial oxygen partial pressure (PaO₂) > 60 mmHg.
In patients with chronic respiratory disorders with hypercapnia, there is a risk of reduced respiratory drive with high oxygen concentrations, and low controlled oxygen concentrations (24%-28%) are generally used, with incremental increases based on individual clinical assessment and arterial blood value.
Treatment of neonates with oxygen may be required but must be strictly monitored, so that the oxygen concentration may be reduced when the patient's condition allows. For neonates (full-term and preterm) the appropriate institutional protocols, based on full clinical assessment, should be followed. The lowest effective concentrations should be sought in order to achieve an adequate oxygenation appropriate for neonates.
In the emergency/acute setting, the usual dose for adults to treat or prevent acute oxygen deficiency is 3-4 litres per minute when using nasal prongs or 5-15 litres per minute with a mask.
Oxygen treatment must be continuously evaluated and the effect measured by means of PaO₂ or arterial oxygen saturation.
The use of medical oxygen for hyperbaric oxygen treatment is beyond the scope of this registered therapeutic good. See specialist literature.

4.3 Contraindications

There is no formal contraindication to normobaric oxygen therapy.
Due to the increased risk of fire, patients should not smoke during oxygen therapy.
See Section 4.4 Special Warnings and Precautions for Use.

4.4 Special Warnings and Precautions for Use

Domiciliary oxygen therapy is not indicated for adult patients with severe airflow limitation whose main complaint is dyspnoea but who maintain a PaO₂ > 60 mmHg and who show no secondary effects of chronic hypoxia, or who have not received adequate therapy of other kinds (e.g. bronchodilators and corticosteroids, treatment for right ventricular failure, or for any respiratory infection). (See Section 4.2 Dose and Method of Administration.)
Oxygen therapy may affect the level of consciousness in a patient with hypercapnia and reduced respiratory drive. (Section 4.2 Dose and Method of Administration.)
General. Warning. Oxygen aids and increases combustion.
Oxygen strongly supports combustion. Smoking is prohibited and no naked flame is allowed.
Oxygen in contact with oils, greases and tarry substances creates a highly dangerous environment due to the risk of spontaneous combustion.
Electrical equipment capable of sparking or generating extreme heat should not be used in the vicinity of patients receiving oxygen.
Check the following before use. Oxygen cylinders must be fitted with an appropriate and lawfully supplied pressure-reducing device dedicated to use with medical oxygen and complying with Australian Standards (See Section 4.2 Dose and Method of Administration; Section 6.4 Special Precautions for Storage). Where this device is separate, it must match the cylinder valve pin index outlet. Where the dispensing equipment connection is separate, this must be connected by an oxygen-specific coupling.
Cylinder pressure may be used as an indicator of the quantity of gas remaining in the cylinder.
Use of gas cylinders. Medical oxygen is stored in high pressure gas cylinders at ambient temperature. Care is needed in the handling and use of compressed medical oxygen gas cylinders.
Under no circumstances should oils or grease be used to lubricate any part of the compressed gas medical oxygen cylinder or the associated equipment used to deliver the gas to the patient. Cylinders must not be exposed to extremes of temperature.
Always ensure hands are clean and free from any oils or grease.
See Section 4.2 Dose and Method of Administration; Section 6.4 Special Precautions for Storage. Additional information is contained in the Material Safety Data Sheet for medical oxygen from the Sponsor.
Oxygen toxicity may occur with prolonged exposure to high inspired oxygen levels. High oxygen concentrations should be given for the shortest possible time required to achieve the required clinical outcome, and reduced as soon as possible to the lowest concentrations needed to prevent or treat hypoxia.
There is evidence in the literature that the risk of oxygen toxicity can be minimised if the treatment follows these guidelines (oxygen fraction in the inhaled air/gas mixture = FiO₂):
Oxygen in concentrations up to 100% (FiO₂ 1.0) should not be given for more than 6 hours.
Oxygen in concentrations above 60-70% (FiO₂ 0.6-0.7) should not be given for more than 24 hours.
Oxygen in concentrations above 40-50% (FiO₂ 0.4-0.5) should not be given during the next 24 hours.
Oxygen concentrations > 40% (FiO₂ > 0.4) can potentially cause damage after 2 days.
Premature infants are excluded from these guidelines because retrolental fibroplasia may occur with a much lower FiO₂. The lowest effective concentrations should be sought in order to achieve an adequate oxygenation appropriate for neonates (also see Section 4.2 Dose and Method of Administration).
The response to oxygen varies depending on the underlying disorder, cause of hypoxia, and clinical status of the individual patient. The clinician should consider all relevant factors in selecting the inspired oxygen concentration, flow rate, and duration of therapy, taking into account the risk of oxygen toxicity. The general recommendation is that the lowest dose - FiO₂ - to achieve the desired result of therapy, a safe PaO₂ must be the aim. Careful monitoring of oxygen therapy is required, with repeated clinical assessment and monitoring of inhaled oxygen concentration (FiO₂) and checks of arterial oxygenation e.g. by arterial blood gas measurements (PaO₂), or arterial oxygen saturations (SaO₂) via pulse oximetry, as clinically appropriate.
If oxygen is mixed with other gases, its concentration in the gas mixture inhaled (FiO₂) must be maintained at least at 21% in the inhaled gas. Oxygen inhaled fraction can be increased up to 100%.
Use in the elderly. Use in the elderly is determined by clinical assessment and course of the illness. Some elderly patients with chronic severe obstructive airways disease may rely on hypoxic drive for respiration and require relatively low inspired oxygen concentrations: see Section 4.2 Dose and Method of Administration.
Paediatric use. Special care must be observed when administering oxygen to neonates. Preterm infants are more susceptible to the direct and indirect potentially toxic effects of oxygen exposure, including retinopathy of prematurity. Clinical protocols appropriate to the condition and age of the infant should be followed, including advice for appropriate arterial oxygen saturation monitoring. Ongoing monitoring is required to achieve the targeted arterial saturation using the lowest possible inspired oxygen levels. See Section 4.2 Dose and Method of Administration.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

High oxygen fraction may further impair the damages caused by lung toxic agents.
Bleomycin. Potentially fatal pulmonary toxicity can develop in patients treated with bleomycin who are exposed to conventional oxygen concentrations during anaesthesia. It is recommended that oxygen concentration in bleomycin-treated patients should where possible be limited to less than 30% (FiO₂ < 0.3), with use of low concentrations (25%, FiO₂ 0.25) during surgery and post-operative recovery, and avoidance of pulmonary interstitial oedema by careful choice and monitoring of fluid replacement (see bleomycin Product Information).
Amiodarone. High dose oxygen may increase the risks of amiodarone-induced post-operative adult respiratory distress syndrome (see amiodarone Product Information).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. Medical oxygen has not been shown to adversely affect fertility when used as clinically required.
Use in pregnancy. (Category A)
When oxygen is used in pregnancy as clinically required, to treat intercurrent illness and avoid hypoxemia, at the lowest concentration for the shortest possible time.
Hyperbaric oxygen treatment during gestation in mice, rats, hamsters and rabbits led to increased resorptions and foetal abnormalities, and decreased foetal body weights. Category A does not relate to hyperbaric oxygen treatment and specialist literature should be consulted.
Pregnant women should not be exposed to hyperbaric oxygen.
Use in lactation. Oxygen can be used during breast-feeding as clinically required, to treat intercurrent illness and avoid hypoxemia, at the lowest concentration for the shortest possible time.

4.7 Effects on Ability to Drive and Use Machines

Under normal conditions, oxygen does not interfere with consciousness, however patients who require continuous oxygen support will require individual assessment, taking their entire medical situation into account for evaluating their ability to drive or operate machinery. Also see Section 4.4 Special Warnings and Precautions for Use.

4.8 Adverse Effects (Undesirable Effects)

Oxygen toxicity depends upon both inspired partial pressure of oxygen (a function of concentration and barometric pressure) and duration of exposure, the safe duration decreasing as the pressure increases. With 100% normobaric oxygen, symptoms of pulmonary toxicity are cough, substernal chest pain, mild dyspnoea, malaise, nausea, or transient paresthesia after 6-24 hours, substernal distress, atelectasis, decrease in vital capacity (after 18 hours) and acute respiratory distress syndrome (after 24-48 hours). Up to 2 atmospheres, pulmonary toxicity occurs before CNS toxicity; at higher pressures, the reverse applies. Symptoms of CNS toxicity include nausea, mood changes, vertigo, twitching, convulsions and loss of consciousness.
Adverse effects of oxygen exposure as described in standard texts include:
Eye disorders. Retinopathy of prematurity, retrolental fibroplasia in neonates, tunnel vision, myopia with hyperbaric oxygen.
ENT. Mucosal dryness and irritation, ear or sinus trauma, tympanic membrane rupture with hyperbaric oxygen.
CNS disorders. Drowsiness/carbon dioxide narcosis if given in high concentrations to patients with reduced sensitivity to carbon dioxide tension in arterial blood; effects of hyperbaric oxygen toxicity include vertigo, convulsions, loss of consciousness.
Respiratory. Chest tightness, dry cough, pain on inspiration; decreased vital capacity; pneumonitis; atelectasis bronchopulmonary dysplasia in neonates; carbon dioxide retention when given in high concentrations to patients with reduced sensitivity to arterial CO₂ tension. Pneumothorax or air embolism has been reported with hyperbaric oxygen.
Gastrointestinal. Nausea.
General. Haemolysis of red blood cells; lipid peroxidation and cell membrane damage due to chemical toxicity in any metabolising cells.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

In oxygen intoxication there may be pulmonary symptoms of chest tightness, dry cough, and pain on inspiration. Care must be taken where symptoms cannot present (e.g. intensive care) since the onset of objective evidence for pulmonary oxygen toxicity occurs late in its development (see Section 4.8 Adverse Effects (Undesirable Effects)).
The oxygen therapy should be reduced or, if possible, stopped, and symptomatic treatment should be started in order to maintain vital functions (e.g. artificial ventilation/assisted ventilation should be given if the patient shows signs of failing respiration).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: GASMED, Gas, Medical. ATC Code: V03AN01.
Mechanism of action. Oxygen is present in the atmosphere at 21% and is essential for cellular metabolism. The therapeutic use of oxygen is intended to improve, or prevent a reduction in, the oxygen content of blood leaving the lungs (or the oxygenator of a heart-lung machine).
The basal oxygen consumption in humans is approximately 250 mL/min for a body surface area of 1.8 m². It is reduced by about 10% during anaesthesia and natural sleep and by about 50% for a 10°C fall in body temperature. Under normal conditions, alveolar air contains about 14% oxygen (105 mmHg) and the arterial blood has an oxygen tension of 97 mmHg. The difference, known as the alveolar arterial oxygen tension gradient, increases with age and may be as great as 30 mmHg in a healthy elderly individual. Oxygen in the blood is primarily bound to haemoglobin. The oxygen saturation of haemoglobin in arterial blood is approximately 97%. Each gram of haemoglobin binds approximately 1.34 mL of oxygen, giving a maximum capacity of about 20 mL per 100 mL of blood. A small amount, 0.3 mL, exists in solution in the same volume of blood.
The concept of "oxygen availability" can be used to quantify the amount available to the body. It can be expressed as product of cardiac output and the oxygen content of the blood. This is estimated by (cardiac output) x (Hb concentration) x (amount of oxygen carried by one gram of haemoglobin) x (% saturation of haemoglobin), plus the amount in solution.
The average healthy individual with basal oxygen consumption has no more than four minutes supply of oxygen circulating in the blood.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

Inhaled oxygen is transported via the airways to the lung with the inspired air. Oxygen is absorbed in the alveoli by gas exchange resulting from the difference in partial pressure from the inspired air/gas mixture to the capillary blood. Increasing the inhaled oxygen concentration, (i.e. inspired gas oxygen fraction, FiO₂), is intended to compensate for problems of ventilation, diffusion and ventilation/perfusion mismatch, by increasing the alveolar partial pressure of oxygen. Oxygen is transported mainly bound to haemoglobin. A small amount though is free and dissolved into plasma.
The uptake of oxygen by the blood in the lungs and discharge to the tissues is determined by the oxygen dissociation curve. The characteristic sigmoid curve ensures that, at tensions between 40 and 15 mmHg, the oxygen carried in the blood from the lungs can be readily given up to the tissues. See Figure 1.

The uptake from the lungs is rapid, because blood flow through the capillaries, where exchange takes place, occurs in about 0.5 seconds. The uptake of oxygen is favoured by simultaneous loss of carbon dioxide, which is excreted in the expired air. Conversely, the entry of carbon dioxide into the blood from the tissues facilitates oxygen transfer to the cells.
At rest, mixed venous blood returning to the lungs contains 13-14 mL of oxygen per 100 mL, but with severe exercise, the oxygen content may fall to 3-4 mL. In very active tissue, there is almost complete extraction of oxygen.

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medical product. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

Shelf life is according to appropriate Australian Standards.

6.4 Special Precautions for Storage

Storage is according to appropriate Australian Standards.
Medical Oxygen cylinders should be:
stored under cover in a well ventilated area, kept dry and clean and not subjected to extremes of heat or cold;
not stored near stocks of combustible materials or near sources of heat;
stored separately from industrial and other non-medical cylinders;
stored to maintain separation between full and empty cylinders;
used in strict rotation so that cylinders with the earliest filling date are used first;
stored separately from other medical cylinders within the store.
Warning notices prohibiting smoking and naked lights must be posted clearly in the cylinder storage area and the Emergency Services should be advised of the location of the cylinder store.
Handling and instructions for use. Warning. Medical Oxygen increases burning and the risk of fire. Do not use medical oxygen if:
a. You are smoking;
b. You are near open flames.
Cylinders must be fitted with an appropriate pressure-reducing device; see Section 4.4 Special Warnings and Precautions for Use. Consult the information provided by the Sponsor about operating procedures for the cylinders.
Do not use medical oxygen if the cylinder is damaged or has the tamper evident plastic seal removed. All personnel handling medical oxygen should have adequate knowledge of:
Properties of the gas.
Correct operating procedures for the cylinder.
Precautions and actions to be taken in the event of an emergency.
Under no circumstances should oils or grease be used to lubricate any part of the compressed gas medical oxygen cylinder or the associated equipment used to deliver the gas to the patient. Always ensure hands are clean and free from any oils or grease.
Where moisturising preparations are required for use with a facemask or in nasal passages etc., avoid using oil based creams. If in doubt, check with the manufacturer to ensure that the product of choice is suitable for use with oxygen.
When Compressed Medical Oxygen cylinders are in use, ensure that they are:
Only used for medicinal purposes;
Only moved with the appropriate size and type of trolley or handling device;
Handled with care and not knocked violently or allowed to fall;
Firmly secured to a suitable cylinder support when in use;
Not used in the vicinity of persons smoking or near naked lights.
When the Compressed Medical Oxygen cylinder is empty, ensure that:
The cylinder valve is closed using moderate force only and the pressure in the regulator or tailpipe released, and the valve outlet cap, where fitted, is replaced;
Empty cylinders are immediately returned to the empty cylinder store for return to BOC.

6.5 Nature and Contents of Container

Presentation. Medical Oxygen (gas code 400) is supplied as a compressed gas in the following cylinder sizes (see Table 1):

Cylinders and valve outlets must comply with relevant Australia Standards.

6.6 Special Precautions for Disposal

Empty cylinders are immediately returned to the empty cylinder store for return to BOC.

6.7 Physicochemical Properties

Chemical structure. O = O.
CAS number. 7782-44-7.
Physical characteristics. Molecular weight: 32.
Boiling point: -183.1°C (at 1 bar).
Density: 1.335 kg/m³ (at 15°C).
Combustion characteristics: Non-flammable. Strongly supports combustion.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Date of First Approval

14 March 2008

Date of Revision

09 November 2020

Summary Table of Changes