Consumer medicine information

Coregas Medical Nitrous Oxide

Nitrous oxide

BRAND INFORMATION

Brand name

Coregas Medical Nitrous Oxide

Active ingredient

Nitrous oxide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Coregas Medical Nitrous Oxide.

What is in this leaflet

Please read this leaflet carefully before you receive this treatment. It provides a summary of the information known about your treatment. If you have any questions or are unsure about anything, ask your doctor.

All medicines have risks and benefits. Your doctor or dentist has weighed the risks of you using Medical Nitrous Oxide against the benefits they expect it will have for you.

If you have any concerns about using Medical Nitrous Oxide, ask your doctor or dentist.

Keep this leaflet with you, as you may want to read it again.

What is Medical Nitrous Oxide used for

Medical Nitrous Oxide is used for general anaesthesia or pain relief.

It is usually given with another anaesthetic and oxygen during surgery, either via a tube placed down your throat by an anaesthetist, or given with oxygen via a mask by your doctor or dentist.

Medical Nitrous Oxide works by causing unconsciousness (deep sleep) before and during surgery and by relieving pain for certain procedures.

Your doctor may prescribe Medical Nitrous Oxide for another purpose. Ask your doctor, if you have any questions about why Medical Nitrous Oxide has been prescribed for you.

This medicine is available only with a doctor's prescription.

Before you take Medical Nitrous Oxide

Do not take Medical Nitrous Oxide if:

  1. You have a condition where air is entrapped within your body and it might expand when given Medical Nitrous Oxide (e.g. bowel obstruction, blocked middle ear, following a recent dive). Ask your doctor for full details of these conditions.
  2. You have been using it for a prolonged period without proper monitoring of your blood.
  3. You are intoxicated.

You must tell your doctor or dentist if:

  1. You are allergic to any other medicines, foods, dyes or preservatives.
  2. You have had a reaction to Medical Nitrous Oxide or any other general anaesthetic or pain relief medication in the past.
  3. You have had a general anaesthetic or surgery in the past.
  4. You have or have had any other health problems or medical conditions, including:
  • Low vitamin B12 levels.
  • Conditions in which air is entrapped within the body.
  • Head injuries with impairment of consciousness.
  • Artificial, traumatic or spontaneous pneumothorax.
  • Air embolism.
  • Decompression sickness.
  • Following a recent dive.
  • Following air encephalography.
  • Sever bullous emphysema.
  • During myringoplasty.
  • Gross abdominal distension.
  • Intoxication.
  • Maxillofacial injuries.
  1. You are pregnant or intend to become pregnant.Pregnant females may experience spontaneous abortion and lowbirth weight babies.
  2. You have had long term usage or been chronically exposed to Medical Nitrous Oxide.

Taking other medicines

Tell your doctor or dentist if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Your doctor may have more information on medicines to avoid while using Medical Nitrous Oxide.

If you have not told your doctor about any of the above, tell them before you start using Medical Nitrous Oxide.

How to use Medical Nitrous Oxide

Medical Nitrous Oxide should only be used under the supervision of your doctor or dentist.

How much to use and how to use it

The amount of Medical Nitrous Oxide given to you will be decided by your doctor or dentist, depending on the amount of pain relief or sleep required. It is usually given to you by breathing it through a mask or by a tube placed down your throat during surgery.

If you are elderly or have lung problems, you may need a lower amount of Medical Nitrous Oxide.

Follow all directions given to you by your doctor or dentist carefully.

These directions may differ from the information contained in this leaflet. If you do not understand the instructions, ask your doctor for help.

How long to use it

Your doctor will decide for how long you need to use Medical Nitrous Oxide.

If you use too much (overdose)

As Medical Nitrous Oxide is most likely to be given to you in hospital under the direction of your doctor or at a dentist’s practice under the direction of the dentist, it is very unlikely you will receive an overdose. However, if this happened, quick action can be taken to maintain your breathing and replace the Medical Nitrous Oxide with oxygen.

If you have any questions then ask your doctor.

While you are taking Medical Nitrous Oxide

Things you must do:

Tell your doctors, dentists and pharmacists who are treating you that you are taking Medical Nitrous Oxide.

Tell your doctor if you become pregnant while taking Medical Nitrous Oxide.

Tell your doctor if you have taken a general anaesthetic.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Things you must not do:

Following a general anaesthetic:Do not drive a vehicle or operate machinery for at least 24 hours after using Medical Nitrous Oxide.

General anaesthetics may cause a slight decrease in intellectual function and alertness for 2 to 3 days in some people.

Do not stop taking Medical Nitrous Oxide without first checking with your doctor.

Side effects

Tell your doctor or dentist as soon as possible if you do not feel well while you are using Medical Nitrous Oxide.

Medical Nitrous Oxide may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor any questions you may have.

Tell your doctor or dentist if you notice any of the following and they worry you:

  • Nausea, vomiting.
  • Headache, dizziness.

These side effects are usually mild.

Tell your doctor or dentist immediately if you notice any of the following:

  • Confusion, excitation, depression.
  • Breathing problems.
  • Heart problems.
  • Pins and needles, changes in sensation.
  • Bleeding, fits.
  • Abdominal pain, bloating.
  • Addiction.
  • Paraesthesiae in the legs.
  • Hyper-reflexia.
  • Weakness of the intrinsic hand muscles.

These are serious side effects. You may need urgent medical attention. Serious side effects are rare. Other side effects may occur as a result of your operation or other medications and anaesthetics received, so check with your doctor or dentist if you have any concerns.

If any of the above happen, tell your doctor or dentist immediately or go to casualty at your nearest hospital

Other side effects not listed above may also occur in some patients. Tell your doctor or dentist if you notice anything else that is making you feel unwell.

Ask your doctor or dentist if you do not understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Medical Nitrous Oxide

Storage

Medical Nitrous Oxide is supplied to the hospital or clinic or doctor and they will be responsible for ensuring the container is stored in accordance with the manufacturer’s instructions.

Disposal

Medical Nitrous Oxide is supplied to the hospital or clinic or doctor and they will be responsible for ensuring the container is returned to the manufacturer.

Product Description

What it looks like

Medical Nitrous Oxide is a clear, colourless, slightly sweet smelling, non-irritating gas supplied in a pressurised gas cylinder with a valve. The gas cylinder contains only Medical Nitrous Oxide.

The gas cylinders’ colour code is a white body with an ultramarine shoulder, as determined by AS4484.

Cylinder sizes include: 2.8L, 9.5L, 23L, 50L, 6 Pack 300L, 12 Pack 600L as measured by nominal water capacity.

Ingredients

Active
Nitrous oxide 100% v/v.

Manufacturer/Distributor/ Supplier:

Coregas Pty. Ltd.
66 Loftus Road.
Yennora. NSW. 2161
Australia

AUST R 27183

This leaflet was prepared in June 2013.

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Coregas Medical Nitrous Oxide

Active ingredient

Nitrous oxide

Schedule

S4

 

1 Name of Medicine

Nitrous oxide.

2 Qualitative and Quantitative Composition

Nitrous oxide 100% v/v.

3 Pharmaceutical Form

Compressed medical gas (for medicinal use only).

4 Clinical Particulars

4.1 Therapeutic Indications

Nitrous oxide is used:
1. General anaesthesia: when an inhalation anaesthetic is required, the administration is usually accompanied by simultaneous administration of a volatile agent such as halothane, ethrane, etc.
2. Analgesia with oxygen:
relief from severe pain, usually in emergency situations, by inhalation with oxygen;
useful also in short-term procedures which inevitably involve pain, such as wound and burn dressing, wound debridement and suturing. Administration with oxygen;
in dental work to provide short-term analgesia for tooth extraction and other brief procedures. Administration with oxygen.
3. Others:
occasionally as an insufflating agent in laparoscopy;
in cryosurgery as a refrigerant.

4.2 Dose and Method of Administration

Where the clinical indication is the production of general anaesthesia it should be noted that:
In the average adult, nitrous oxide is administered by inhalation through a suitable anaesthetic apparatus in concentrations up to 80% with oxygen as the balance.
As people age, there is a steady reduction in the indices of cardiac and respiratory function evidenced by a lowering of cardiac output and in lung ventilation and perfusion. In addition, there is an increase in dead space in the lung which increases minute ventilation. Cerebral blood flow is reduced by up to 30%. The result of these changes mean that susceptibility to anaesthesia is increased. Nitrous oxide is, therefore, more useful in the elderly and the depressant effects of added agents are reduced.
There are no essential differences in clinical indications between the adult and child.
Nitrous oxide is strongly recommended in the anaesthesia of neonates.
In obstetrical anaesthesia, the nitrous oxide level is kept below 70% to allow a substantial oxygen level to be provided. Nitrous oxide plays a major role because injected agents depress the breathing of the infant and volatile agents depress uterine contraction.
As a general rule, the more ill the patient, the more susceptible is the patient to other anaesthetic agents and the more nitrous oxide is relied upon.

Routes of administration.

Use as a gas.

Nitrous oxide administered through a face mask or tracheal tube by means of an anaesthetic apparatus. The gas is breathed in by the patient and absorbed through the lungs.
Nitrous oxide should only be administered by medical personnel trained in the appropriate techniques.
Cylinders should only be used in conjunction with medical nitrous oxide gas pressure regulators.

Use as a liquid refrigerant in cryosurgery.

Aluminium cylinders with dip tubes are used for extracting liquid nitrous oxide. A hose is attached to the cylinder, and the liquid applied topically.

4.3 Contraindications

All these effects are well documented, extremely rare and may follow prolonged exposure to levels of nitrous oxide over 5,000 ppm or to frequent (more than once every two days) exposure to analgesic concentrations. Vitamin B12 inactivations have been reviewed by Nunn.
Hypersensitivity to nitrous oxide or any other component in the gas is a contraindication.
Nitrous oxide should not be administered without the required level of oxygen (see Section 4.4 Special Warnings and Precautions for Use, Use with caution in the following circumstances).
Nitrous oxide should not be used with any condition where air is entrapped within a body and where its expansion might be dangerous, such as:
the presence of intracranial air;
severe head trauma;
head injuries with impairment of consciousness;
pneumopericardium;
artificial, traumatic or spontaneous pneumothorax;
air embolism;
gas embolus;
decompression sickness;
following a recent dive;
following cardiopulmonary bypass or air encephalography;
severe bullous emphysema;
during myringoplasty;
occluded middle ear;
cysts;
gross abdominal distension;
intoxication;
maxillofacial injuries;
after intraocular gas injection in ophthalmic surgery, for example with sulphur hexafluoride (SF6) or perfluoropropane (C3F8), until the intraocular gas had been completely absorbed, due to the risk of further expansion of the gas bubble possibly leading to blindness.
Nitrous oxide should not be used on intoxicated patients.
Medicinal nitrous oxide is also contraindicated:
In patients with cardiac failure or severely impaired cardiac function (e.g. after cardiac surgery), since the mild myocardio-depressive effect may cause further deterioration in cardiac function.
In patients presenting persistent signs of confusion, changed cognitive function or other signs that could be related to increased intra-cranial pressure, as nitrous oxide may further increase the intra-cranial pressure.
In patients presenting decreased consciousness and/or co-operability, when used in analgesia, because of the risk for loss of protecting reflexes.
In patients presenting with a vitamin B12 or folic acid deficiency or genetic perturbation in this system.
Nitrous oxide should not be used as an analgesic or anaesthetic agent for more than 24 hours without monitoring of peripheral blood for features of megaloblastic anaemia and leukopenia. (See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

4.4 Special Warnings and Precautions for Use

General.

Coregas nitrous oxide is a simple asphyxiant in the absence of oxygen.

Occupational exposure to nitrous oxide.

Nitrous oxide is classified as hazardous according to criteria of Worksafe Australia. Worksafe exposure standard TLV TWA is 25 ppm.
Reduced fertility in medical and paramedical personnel has been reported after repeated exposure to nitrous oxide in inadequately ventilated rooms. It is not currently possible to confirm or exclude the existence of any causal connection between these cases and nitrous oxide exposure. It is important that the nitrous oxide content in the ambient air is kept as low as possible and well below the nationally set limit value (see Section 4.6 Fertility, Pregnancy and Lactation, Effects on fertility).
Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and equivalent treatment room levels to a level below 25 ppm of nitrous oxide gas.
Rescue personnel are advised to monitor nitrous oxide concentration before entering confined spaces and poorly ventilated areas which have been contaminated by a nitrous oxide gas leak.
Chronic occupational exposure to nitrous oxide may lead to bone marrow or neurological impairment (see also below Interference with vitamin B12 metabolism leading to neurological and bone marrow toxicity).
Suitable manual handling equipment should be used to transport cylinders.

Interference with vitamin B12 metabolism leading to neurological and bone marrow toxicity.

Nitrous oxide causes inactivation of Vitamin B12 (a co-factor of methionine synthesis), which interferes with folic acid metabolism. Nitrous oxide inhibits methionine synthetase which contributes to the conversion of homocysteine to methionine. The inhibition of this enzyme affects/reduces the formation of thymidine, which is an important part of DNA formation. Thus, DNA synthesis is impaired following prolonged nitrous oxide administration. These disturbances can result in megaloblastic bone marrow changes and possibly polyneuropathy and/or subacute combined degeneration of the spinal cord (see Section 4.8 Adverse Effects (Undesirable Effects)). The effect on DNA synthesis is one of the probable reasons for the influence of nitrous oxide on blood formation and the foetal damage seen in animal studies.
Nitrous oxide should be used with caution in patients at risk of vitamin B12 or folic acid deficiency. See Section 4.3 Contraindications.
Risk factors include the elderly, those with poor or vegetarian diet, and previous history of anaemia. Nitrous oxide should therefore not be used for prolonged periods of time.
See also Chronic exposure below.
In patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after single exposures to Nitrous Oxide gas during general anaesthesia. Other analgesic therapies should be considered in patients showing signs of vitamin B12/folate deficiency (see Section 4.3 Contraindications).

Chronic exposure.

Care should be taken with long term usage of nitrous oxide. Chronic exposure to nitrous oxide, such as in abuse, can inactivate vitamin B12 with resulting neurological and haematological side effects such as polyneuropathy, megaloblastic anaemia, bone marrow depression and reproductive side effects (see Section 4.8 Adverse Effects (Undesirable Effects)).
A polyneuritic type of neuropathy and spinal cord sclerosis can appear during chronic administration of high concentrations of nitrous oxide gas.
Administration of nitrous oxide more frequently than every four days should be accompanied by routine blood cell counts for evidence of megaloblastic change in red blood cells and hypersegmentation of neutrophils.
A full blood examination should also be performed in abusers and professionals chronically exposed for evidence of megaloblastic change in red blood cells and hypersegmentation of neutrophils.

Use with caution in the following circumstances.

Nitrous oxide gas should never be given with less than 21% oxygen but a maximum of 30% oxygen should be used during anaesthesia and more at altitude and in the presence of disorders affecting oxygenation.
Nitrous Oxide gas passes into gas containing spaces in the body faster than nitrogen passes out.
Prolonged anaesthesia may result in bowel distension, middle ear damage, rupture of ear drums and expansion of other non-vented gas containing cavities. Nitrous oxide gas administration may increase the pressure in catheter balloons e.g. in tracheal intubation.
Addiction to and abuse of nitrous oxide has been reported. Delirium has been reported upon withdrawal.
Due to the potential for myocardial depression, nitrous oxide should be used with caution in patients with mild to moderate cardiac dysfunction and is contraindicated in patients with severe cardiac dysfunction or pronounced cardiac failure (see Section 4.3 Contraindications).
In patients taking other centrally acting medicinal products, such as morphine derivatives and/or benzodiazepines, concomitant administration of nitrous oxide may result in increased sedation, and consequently have effects on respiration, circulation and protective reflexes. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Nitrous oxide gas in high concentration can lead to the loss of laryngeal reflexes and reduce consciousness. In higher concentrations it often causes unconsciousness and the risk for impairment of the laryngeal reflexes increases.
When nitrous oxide gas is used in conjunction with other volatile or intravenous anaesthetic agents, the MAC of those agents may be reduced.
Nitrous oxide should not be used during laser surgery in the airways due to the relative risk for explosive fire.
At the end of nitrous oxide/oxygen anaesthesia, withdrawal of the mask leads to an outpouring of nitrous oxide from the lungs and consequent dilution of oxygen in the incoming air. This results in diffusion hypoxia and is counteracted by giving 100% oxygen for a few minutes when the flow of nitrous oxide is stopped.
Nitrous oxide should be used with caution in patients with severe hypotension.

Check the following before use.

Nitrous oxide is non-flammable but strongly supports combustion (including some materials which do not normally burn in air) and should not be used near sources of ignition. It is highly dangerous when nitrous oxide comes into contact with oils, greases, tarry substances and many plastics due to the risk of spontaneous combustion.
Operability of oxygen mixing apparatus and availability of oxygen.
Dispensing equipment connection matches cylinder valve outlet.
Cylinder pressure is not a true indicator of quantity remaining in cylinder until all liquid has vapourised. Measure contents by weight.

Use of gas cylinders.

Cylinder should be kept out of the reach of children.
Smoking should be prohibited when using nitrous oxide.
Under no circumstances should oils or grease be used to lubricate any part of the Nitrous Oxide cylinder or the associated equipment used to deliver the gas to the patient.
Where moisturising preparations are required for use with a facemask, oil based creams should not be used.
Check that hands are clean and free from any oils or grease.
Where alcohol gels are used to control microbiological cross-contamination ensure that all alcohol has evaporated before handling.
Care is needed in the handling and use of medical nitrous oxide gas cylinders. Nitrous oxide is stored in high pressure gas cylinders as a liquid under pressure at ambient temperature.
Most containers are designed to deliver product in gaseous form, however, rapid opening of the valve and sustained high flow rates can cause the discharged gas to re-liquefy. Special cylinders with dip tube are designed to deliver liquid nitrous oxide for cryosurgery. This liquid can cause cold burns if in contact with the eyes and skin.
Gas cylinders should be used in the vertical position with the valve uppermost. If not, liquid may be discharged when the valve is opened. Cylinders with dip tube are designed to administer liquid nitrous oxide and must not be used for gas administration.
Additional information is contained in the Material Safety Data Sheet for Medical nitrous oxide.

Cold burns.

Burns should not occur if the product is administered correctly (see Section 4.9 Overdose, Accidental contact with liquid nitrous oxide (cold burns) - symptoms and signs).

Use in hepatic impairment.

No data available.

Use in renal impairment.

No data available.

Use in the elderly.

Elderly patients are more susceptible to the effects of nitrous oxide.

Paediatric use.

Paediatric neurotoxicity.

Some published studies in children have observed cognitive deficits after repeated or prolonged exposures to anaesthetic agents early in life. These studies have substantial limitations, and it is not clear if the observed effects are due to the anaesthetic/analgesic/sedation drug administration or other factors such as the surgery or underlying illness.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy. The clinical significance of these nonclinical findings is yet to be determined.
With inhalation or infusion of such drugs, exposure is longer than the period of inhalation or infusion. Depending on the drug and patient characteristics, as well as dosage, the elimination phase may be prolonged relative to the period of administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Nitrous oxide inactivates vitamin B12. There are no major incompatibilities with nitrous oxide.
Nitrous oxide reduces the amount of volatile anaesthetics required for anaesthesia when administered concomitantly.
Nitrous oxide and CNS depressants may lead to increased CNS depression, increased respiratory depression and increased hypotensive effects.
Nitrous oxide and opioids together may lead to further circulatory depression. High dose fentanyl with nitrous oxide may decrease heart rate and cardiac output.
The uptake of an inhalational anaesthetic from the lungs is accelerated by the uptake of nitrous oxide when administered concomitantly. This is known as the second gas effect.

Methotrexate.

Nitrous oxide potentiates the effect of methotrexate on folate metabolism, yielding increased toxicity such as severe, unpredictable myelosuppression, stomatitis and neurotoxicity with intrathecal administration. Avoid concomitant use of nitrous oxide in patients receiving methotrexate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.4 Special Warnings and Precautions for Use, Occupational exposure to nitrous oxide.
(Category A)
Medicinal nitrous oxide interferes with vitamin B12/folic acid metabolism (see Section 4.4 Special Warnings and Precautions for Use).
Inhibition of the methionine synthase may cause adverse effects during early stages of pregnancy.
Pregnant females may experience spontaneous abortion and low birth weight babies.
Epidemiological studies suggest an increased risk of spontaneous abortion and low birth weight in off-spring in female workers employed in operating theatres and dental surgeries. These findings are controversial.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy.
Animal studies have demonstrated that high concentration or prolonged exposure during particular stages of pregnancy can induce teratogenic effects. The potential risk for humans is unknown.
All general anaesthetics carry the potential to produce central nervous system and respiratory depression in the newborn infant. However, in the compromised foetus, careful consideration should be given to this potential depression and to the selection of particular anaesthetic drugs, doses and techniques.
Inhalation anaesthetics cross the placenta.
Published studies in pregnant and juvenile animals demonstrate that the use of anaesthetic/analgesic/sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of rapid brain growth or synaptogenesis may result in neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis when used for longer than 3 hours. These studies included anaesthetic agents from a variety of drug classes.
Mild skeletal teratogenic changes have been observed on pregnant rat embryos when the dam has been exposed to high concentrations of nitrous oxide during the period of organogenesis.
There is no published material which shows that nitrous oxide is toxic to the human foetus, however, no increased incidence of foetal malformation has been discovered in 8 epidemiological studies and case reports in human beings.
See Section 4.4 Special Warnings and Precautions for Use, Occupational exposure to nitrous oxide.
 It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitrous oxide is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

Nitrous oxide is rapidly eliminated but it is recommended that driving, use of machinery and other psycho-motor activities should not be undertaken until 12 hours have elapsed after nitrous oxide anaesthesia and until the patients have returned to their initial mental status as judged by attending healthcare professional.
General anaesthetics may cause a slight decrease in intellectual function following anaesthesia.

4.8 Adverse Effects (Undesirable Effects)

Nitrous oxide is an asphyxiant in the absence of oxygen.

Other adverse effects (frequency and seriousness).

The adverse effects listed are derived from public domain scientific medical literature and post marketing safety surveillance.

Cardiovascular.

Cardiovascular depression, hypotension, arrhythmia, increased pulmonary vascular resistance.

Gastrointestinal.

Bowel distension following prolonged anaesthesia.

General.

Cold burns (see Section 4.9 Overdose, Accidental contact with liquid nitrous oxide (cold burns) - symptoms and signs).
Addiction to and abuse of nitrous oxide have been reported.

Haematological.

The use of nitrous oxide causes inactivation of vitamin B12 which is a co-factor of methionine synthase. Folate metabolism is consequently interfered with and DNA synthesis is impaired following prolonged nitrous oxide administration. This results in symptoms similar to vitamin B12 deficiency and megaloblastic bone marrow changes. Bone marrow depression with resultant leukopenia, thrombocytopenia and severe megaloblastic anaemia, including fatal cases, have been noted.
Exceptionally heavy occupational exposure and addiction have resulted in myeloneuropathy and subacute combined degeneration.
These effects include rarely: drowsiness, confusion, paraesthesia in the legs, hyper-reflexia and weakness of the intrinsic hand muscles.
If these effects occur, usage of nitrous oxide should be stopped and daily vitamin B12 replacement administered. Effects should then be expected to be reversed gradually.
All these effects are well documented, extremely rare and may follow prolonged exposure to levels of nitrous oxide over 5,000 ppm or to frequent (more than once every two days) exposure to analgesic concentrations.

Neurological.

CNS excitation and depression, raised intracranial pressure, anxiolytic effects, neuropathy, seizures, convulsions, drowsiness. Exceptionally heavy or frequent use, including occupational exposure and addiction, have resulted in myeloneuropathy (including polyneuropathy) and subacute combined degeneration of the cord.

Fertility, pregnancy and lactation.

See Section 4.4 Special Warnings and Precautions for Use; Section 4.6 Fertility, Pregnancy and Lactation. It has been suggested that prolonged occupational exposure to high levels of nitrous oxide may affect a woman's ability to become pregnant.

Respiratory.

Hypoxia, diffusion hypoxia, asphyxia.
Nitrous oxide gas passes into all gas containing spaces in the body faster than nitrogen passes out. The main contraindications which follow from this are listed in Section 4.3 Contraindications, but in addition prolonged anaesthesia may result in bowel distension, middle ear damage and rupture of ear drums. See Table 1.

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

Inhalation - symptoms and signs.

Inappropriate, unwitting or deliberate inhalation of nitrous oxide will ultimately result in unconsciousness, passing through stages of increasing lightheadedness and intoxication, and, if the victim were to be within a confined space, death from anoxia could result.
Other signs may include: bradycardia, respiratory depression, cardiovascular depression and severe hypotension.

Inhalation - treatment.

The treatment is fresh air, mouth-to-mouth resuscitation and, if necessary, the use of an oxygen resuscitator.

Accidental contact with liquid nitrous oxide (cold burns) - symptoms and signs.

Local pain usually warns of freezing, but sometimes no pain is felt or is short lived. Frozen tissues are painless and appear waxy, with a pale yellowish colour. Thawing of the frozen tissue can cause intense pain.
Shock may occur if the area is large.

Accidental contact- treatment.

Skin.

Loosen any clothing that may restrict circulation and seek immediate hospital attention for all but the most superficial injuries. Do not apply direct heat to the affected parts, but if possible, place the affected part in lukewarm water. Sterile dry dressings should be used to protect damaged tissues from infection or further injury, but they should not restrict circulation. Alcohol and cigarettes should not be given.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Nitrous oxide is not very soluble in water but is fifteen times more soluble than oxygen. Water dissolves nitrous oxide, taking 100 volume % and blood plasma 45 volume %.
Nitrous oxide is an inhalational anaesthetic.
Nitrous oxide is an analgesic and a weak anaesthetic. Pain reduction is achieved at a concentration of around 25%. Induction with nitrous oxide is relatively rapid, but a concentration of about 70% is needed to produce unconsciousness. Endorphins are probably involved in the analgesic effect; a concentration of 25% nitrous oxide is usually adequate to provide a marked reduction in pain.
Nitrous oxide alone may increase pulse rate and have depressant effects on respiration.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

No data available.

Distribution.

Nitrous oxide is a low potency inhalation anaesthetic and only slightly soluble. The advantage of this is that concentrations not greater than 70% are used and induction of anaesthesia and recovery occur quickly.
At a constant inspired concentration, the rise time of alveolar concentrations is faster than that of any other anaesthetic agent.
The blood/gas partition coefficient of nitrous oxide at 37°C is 0.46 compared with that of nitrogen of 0.015, causing nitrous oxide to expand into internal gas spaces.
Under normal anaesthesia, the adult body contains 25 litres of gaseous nitrous oxide (this gives some notion of its essential safety and lack of acute toxicity).

Metabolism.

Not applicable.

Excretion.

The elimination of nitrous oxide is faster than that of any other anaesthetic.
Nitrous oxide is eliminated unchanged from the body mostly by the lungs.
The flow of nitrous oxide out from the tissues through the lungs at the end of anaesthesia may lead to a degree of transient hypoxia.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

No excipients present.

6.2 Incompatibilities

There are no major incompatibilities with nitrous oxide.

6.3 Shelf Life

Not applicable.

6.4 Special Precautions for Storage

Nitrous oxide will decompose at temperatures above 400°C and the speed of decomposition increases with increasing temperature. Explosive decomposition can occur at 650°C at atmospheric pressure.
The normal precautions required in the storage of medical gas cylinders as described below are applicable.
Cylinders should be stored away from sources of ignition, poisons, flammable or combustible materials. They should be secured upright, in a secure area, below 45°C, on a dry well ventilated area constructed of non-combustible material with a firm, level floor (preferably concrete) away from heavy traffic and emergency exits.
Cylinders should be kept out of the reach of children.

6.5 Nature and Contents of Container

Gas cylinders are supplied in steel or aluminium cylinders and fitted with pin index, valve outlet.
The cylinder colour code is: white body with ultramarine shoulder as per AS4484.
Cylinder size (nominal water capacity, Litres): C (2.8 L), D (9.5 L), E (23 L), G (50 L), 6 pack (300 L); 12 pack (600 L).
For cryoablation liquid withdrawal the cylinders composed of aluminium (sizes C, D, E, G), contain a dip tube and the valve outlet is different to that of the gas valves, to avoid operator error.
All cylinders and outlets comply with the relevant Australian Standards.
AUST R: 27183.

6.6 Special Precautions for Disposal

The cylinder pack should not be disposed of but must be returned to the supplier.

6.7 Physicochemical Properties

Nitrous oxide is a sweet smelling colourless gas. Nitrous oxide is not very soluble in water but is fifteen times more soluble than oxygen. Water dissolves nitrous oxide, taking 100 volume % and blood plasma 45 volume %. Boiling point: -88.6°C (at 1 bar). Specific gravity at 15°C and 101.3 kPa is 1.53. Density at 115°C and 101.3 kPa is 1.875 kg/m3. Nitrous oxide is an oxidising substance which will support combustion of materials which may not normally burn in air. The molecule is stable and comparatively unreactive at ordinary temperatures. At elevated temperatures it decomposes to nitrogen and oxygen.

Chemical structure.

A linear but unsymmetrical molecule of the form N-N-O.
Molecular Formula: N2O.
MW: 44.01.

CAS number.

10024-97-2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes