Drugs List

Therapeutic Indications

Uses

Nitrous oxide may be used when an inhalational anaesthetic is required. Nitrous oxide administration is usually accompanied by simultaneous administration of a volatile agent such as halothane, etc.

Relief of severe pain, usually in emergency situations (by inhalation with 50% oxygen).

Relief of pain in short term procedures, such as wound and burn dressing, wound debridement and suturing (usually administered with 50% oxygen)

Provide short-term analgesia in dental work, such as during tooth extraction and other brief procedures (by inhalation with 50% oxygen).

Insufflating agent in laparoscopy

Refrigerant in cryosurgery.

Administration

For inhalation.

Nitrous oxide is administered through a face mask or tracheal tube by means of an anaesthetic apparatus.

Handling

Care is needed in the handling and use of nitrous oxide cylinders. Nitrous oxide is stored in high pressure gas cylinders as a liquid under pressure. Rapid opening of the valve can cause the gas to re-liquefy and this can lead to cold burns if skin contact occurs.

Cylinders should only be used in the vertical position with the valve uppermost. If not, liquid may be discharged when the valve is opened.

Do not use oil based creams when moisturising preparations are required for use with a facemask. Also check hands are clean and free from any oils or greases.

Where alcohol gels are used to control microbiological cross contamination, ensure that all alcohol has evaporated before handling nitrous oxide cylinders or equipment.

Contraindications

Nitrous oxide should not be used in any condition where air is trapped within the body as its expansion may be dangerous. These conditions include:
Head injury with impaired consciousness
Pneumothorax (artificial, traumatic or spontaneous)
Air embolism
Decompression sickness
Severe bullous emphysema
Gross abdominal distension
Intoxication
Maxillofacial injuries
After a recent intraocular injection of a gas (such as sulfur hexafluoride)

Precautions and Warnings

Hypoxia can occur if no oxygen is administered with nitrous oxide.

Nitrous oxide should not be used as an analgesic or anaesthetic agent for more than 24 hours without monitoring of peripheral blood for signs of megaloblastic anaemia and leukopenia.

Routine blood cell counts should be performed if nitrous oxide is administered more frequently than every 4 days.

Nitrous oxide can lead to an inactivation of vitamin B12 (a cofactor of methionine synthase). As a result, prolonged (either by continuous or by intermittent administration) or frequent administration of nitrous oxide can cause disruption of folate metabolism, impairment of DNA synthesis, megaloblastic marrow changes, megaloblastic anaemia myeloneuropathy and subacute combined degeneration of the spinal cord. Assessment of vitamin B12 levels should be considered in patients with vitamin B12 deficiency or risk factors for vitamin B12 deficiency prior to use of nitrous oxide. These include the elderly, those with a history of anaemia and those with a poor or vegetarian diet. Theatre staff should also take precautions to minimise their exposure to nitrous oxide for the same reason.

In patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after a single exposure to nitrous oxide during general anaesthesia.

Haematological assessment should include a assessment for megaloblastic change in red blood cells and hypersegmentation of neutrophils. Neurological toxicity can occur without anaemia or macrocytosis and with B12 levels in the normal range.

Pregnancy - see Pregnancy section

Avoid use following a recent dive

Avoid use following air encephalography

Avoid use during myringoplasty

Concomitant administration of nitrous oxide with other centrally acting medical products such as morphine derivatives and/or benzodiazepines) may result in increased sedation and consequently have effects on respiration, circulation and protective reflexes.

Do not use oil based creams when moisturising preparations are required for use with a facemask. Also check hands are clean and free from any oils or greases.
Where alcohol gels are used to control microbiological cross contamination, ensure that all alcohol has evaporated before handling nitrous oxide cylinders or equipment.

Withdrawal of the mask at the end of a nitrous oxide/oxygen anaesthesia leads to an outpouring of nitrous oxide from the lung 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.

Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and treatment room levels to below 100ppm of ambient nitrous oxide.

Smoking is prohibited when using nitrous oxide.

Advise patients not to drive or operate machinery for 12 hours after nitrous oxide anaesthesia.

Pregnancy and Lactation

Pregnancy

May depress neonatal respiration if used during delivery.

No increased incidence of foetal malformation has been seen in epidemiological studies or case reports in humans.

There is no evidence to suggest that nitrous oxide is toxic to the foetus.

Mild skeletal teratogenic changes have been observed in animal studies where the female was exposed to high concentration of nitrous oxide during the organogenesis period.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

No reports describing the use of nitrous oxide during breastfeeding have been located.
The solubility in blood and tissue is low and the plasma half-life is very short (less than 3 minutes) therefore, it is unlikely that a nursing infant would be exposed to the agent in milk or that it would be orally bioavailable to the infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Megaloblastic anaemia
Bone marrow depression
Myeloneuropathy
Abdominal distension
Ear damage
Addiction
Malignant hyperthermia
Neurological effects
Haematological toxicity
Euphoria
Disorientation
Sedation
Nausea
Vomiting
Dizziness
Tingling sensation
Agranulocytosis
Neurotoxicity

Presentation

Compressed medical gas containing nitrous oxide

Cylinder sizes available
450 litres size C
900 litres size D
1800 litres size E
3600 litres size F
9000 litres size G
18000 litres size J

Drugs List

Therapeutic Indications

Uses

Nitrous oxide may be used when an inhalational anaesthetic is required. Nitrous oxide administration is usually accompanied by simultaneous administration of a volatile agent such as halothane, etc.

Relief of severe pain, usually in emergency situations (by inhalation with 50% oxygen).

Relief of pain in short term procedures, such as wound and burn dressing, wound debridement and suturing (usually administered with 50% oxygen)

Provide short-term analgesia in dental work, such as during tooth extraction and other brief procedures (by inhalation with 50% oxygen).

Insufflating agent in laparoscopy

Refrigerant in cryosurgery.

Dosage

Nitrous oxide should only be administered by medical personnel trained in the appropriate techniques.

Cylinders can only be used in conjunction with medical nitrous oxide gas pressure regulators.

Nitrous oxide must be administered with oxygen. At the end of nitrous oxide/oxygen anaesthesia, diffusion hypoxia occurs which should be counteracted by giving 100% oxygen for a few minutes when the flow of nitrous oxide is stopped.

As a general rule, the more ill the patient, the more susceptible they are to other anaesthetic agents, and the more nitrous oxide is required.

Nitrous oxide should not be used for more than a total of 24 hours, or more frequently than every four days, without clinical supervision and haematological monitoring.

Nitrous oxide is usually not sufficient to create an adequate anaesthetic effect on its own and should therefore be used in combination with appropriate doses of another anaesthetic when used for general anaesthesia. Nitrous oxide as additive interaction with most other anaesthetics.

Adults

Elderly

Children

Neonates

Administration

For inhalation.

Nitrous oxide is administered through a face mask or tracheal tube by means of an anaesthetic apparatus.

Handling

Care is needed in the handling and use of nitrous oxide cylinders. Nitrous oxide is stored in high pressure gas cylinders as a liquid under pressure. Rapid opening of the valve can cause the gas to re-liquefy and this can lead to cold burns if skin contact occurs.

Cylinders should only be used in the vertical position with the valve uppermost. If not, liquid may be discharged when the valve is opened.

Do not use oil based creams when moisturising preparations are required for use with a facemask. Also check hands are clean and free from any oils or greases.

Where alcohol gels are used to control microbiological cross contamination, ensure that all alcohol has evaporated before handling nitrous oxide cylinders or equipment.

Contraindications

Nitrous oxide should not be used in any condition where air is trapped within the body as its expansion may be dangerous. These conditions include:
Head injury with impaired consciousness
Pneumothorax (artificial, traumatic or spontaneous)
Air embolism
Decompression sickness
Severe bullous emphysema
Gross abdominal distension
Intoxication
Maxillofacial injuries
After a recent intraocular injection of a gas (such as sulfur hexafluoride)

Precautions and Warnings

Hypoxia can occur if no oxygen is administered with nitrous oxide.

Nitrous oxide should not be used as an analgesic or anaesthetic agent for more than 24 hours without monitoring of peripheral blood for signs of megaloblastic anaemia and leukopenia.

Routine blood cell counts should be performed if nitrous oxide is administered more frequently than every 4 days.

Nitrous oxide can lead to an inactivation of vitamin B12 (a cofactor of methionine synthase). As a result, prolonged (either by continuous or by intermittent administration) or frequent administration of nitrous oxide can cause disruption of folate metabolism, impairment of DNA synthesis, megaloblastic marrow changes, megaloblastic anaemia myeloneuropathy and subacute combined degeneration of the spinal cord. Assessment of vitamin B12 levels should be considered in patients with vitamin B12 deficiency or risk factors for vitamin B12 deficiency prior to use of nitrous oxide. These include the elderly, those with a history of anaemia and those with a poor or vegetarian diet. Theatre staff should also take precautions to minimise their exposure to nitrous oxide for the same reason.

In patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after a single exposure to nitrous oxide during general anaesthesia.

Haematological assessment should include a assessment for megaloblastic change in red blood cells and hypersegmentation of neutrophils. Neurological toxicity can occur without anaemia or macrocytosis and with B12 levels in the normal range.

Pregnancy - see Pregnancy section

Avoid use following a recent dive

Avoid use following air encephalography

Avoid use during myringoplasty

Concomitant administration of nitrous oxide with other centrally acting medical products such as morphine derivatives and/or benzodiazepines) may result in increased sedation and consequently have effects on respiration, circulation and protective reflexes.

Do not use oil based creams when moisturising preparations are required for use with a facemask. Also check hands are clean and free from any oils or greases.
Where alcohol gels are used to control microbiological cross contamination, ensure that all alcohol has evaporated before handling nitrous oxide cylinders or equipment.

Withdrawal of the mask at the end of a nitrous oxide/oxygen anaesthesia leads to an outpouring of nitrous oxide from the lung 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.

Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and treatment room levels to below 100ppm of ambient nitrous oxide.

Smoking is prohibited when using nitrous oxide.

Advise patients not to drive or operate machinery for 12 hours after nitrous oxide anaesthesia.

Pregnancy and Lactation

Pregnancy

May depress neonatal respiration if used during delivery.

No increased incidence of foetal malformation has been seen in epidemiological studies or case reports in humans.

There is no evidence to suggest that nitrous oxide is toxic to the foetus.

Mild skeletal teratogenic changes have been observed in animal studies where the female was exposed to high concentration of nitrous oxide during the organogenesis period.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

No reports describing the use of nitrous oxide during breastfeeding have been located.
The solubility in blood and tissue is low and the plasma half-life is very short (less than 3 minutes) therefore, it is unlikely that a nursing infant would be exposed to the agent in milk or that it would be orally bioavailable to the infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Advise patients not to drive or operate machinery for 12 hours after nitrous oxide anaesthesia.

Counselling

Advise patients not to drive or operate machinery for 12 hours after nitrous oxide anaesthesia.

Advise patients of fire risk.

Side Effects

Megaloblastic anaemia
Bone marrow depression
Myeloneuropathy
Abdominal distension
Ear damage
Addiction
Malignant hyperthermia
Neurological effects
Haematological toxicity
Euphoria
Disorientation
Sedation
Nausea
Vomiting
Dizziness
Tingling sensation
Agranulocytosis
Neurotoxicity

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store in a well ventilated area, protected from extreme temperatures
away from flammable materials
Keep away from ignition sources (including static discharges)

Nitrous oxide is non-flammable but strongly supports combustion and will cause substances to burn vigorously, including some materials that do not normally burn in air. Nitrous oxide is highly dangerous in the presence of oils, grease, tarry substances and many plastics due to the risk of spontaneous combustion in the presence of nitrous oxide in relatively high concentrations. Warning notices prohibiting smoking and naked lights must be clearly posted in the cylinder store. Inform emergency services of the location of the cylinder store.

Further Information

Last Full Review Date: September 2011

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Medical nitrous oxide. BOC Ltd. Revised September 2009.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 September 2017