Drugs List

Therapeutic Indications

Uses

Alleviation of pain
Analgesia for painful procedures

Unlicensed Uses

Maintenance of anaesthesia: adjunctive treatment

Administration

For inhalation through a face mask or mouthpiece.

Contraindications

Abdominal distension
Air embolism
Decompression sickness
Head injuries with impaired consciousness
Maxillofacial injuries
Pneumothorax
Severe bullous emphysema

Precautions and Warnings

Anaemia
Vitamin B12 deficiency

Advise patient not to drive or operate machinery for at least 30 minutes
Advise patient not to drive or operate machinery until assessed
Avoid use during myringoplasty
Avoid use following air encephalography
Avoid use following recent intraocular injection of gas
Occupational risk: Use of a scavenging system is recommended
Can cause addiction
Close supervision required if given continuously for more than 24 hours
Close supervision required if used more frequently than every 4 days
Monitor vitamin B12 levels regularly
Perform blood counts on prolonged use of this treatment
Advise patients of fire risk
Avoid use following a recent dive
Strongly supports combustion-avoid naked flames and heat

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.

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

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

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.

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

Gases containing more than 21% oxygen should be avoided in patients that have been exposed to agents that are toxic to the lungs, such as Paraquat.

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.

Pregnancy and Lactation

Pregnancy

Nitrous oxide with oxygen gas is considered safe for use during pregnancy.

Manufacturers advise nitrous oxide with oxygen gas may be used during pregnancy. 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. There is no evidence to suggest that nitrous oxide is toxic to the foetus, although it may depress neonatal respiration if used during delivery. There are no absolute contraindications to the use of nitrous oxide with oxygen gas in the first 16 weeks of pregnancy.

Lactation

Nitrous oxide with oxygen gas is considered safe to use during breastfeeding.

Manufacturers advise nitrous oxide with oxygen gas may be used during the breastfeeding period but not during breastfeeding itself.

Side Effects

Abdominal distension
Addiction
Agranulocytosis
Bloating
Bone marrow depression
Confusion
Disorientation
Dizziness
Ear damage
Ear sensations
Euphoria
Haematological toxicity
Light-headedness
Megaloblastic anaemia
Myelopathy
Nausea
Neurological effects
Neuropathy
Neurotoxicity
Respiratory depression
Sedation
Seizures
Sense of intoxication
Somnolence
Subacute combined degeneration
Tingling sensation
Vomiting

Presentation

Compressed medicinal gas containing nitrous oxide and oxygen.

Drugs List

Therapeutic Indications

Uses

Alleviation of pain
Analgesia for painful procedures

Unlicensed Uses

Maintenance of anaesthesia: adjunctive treatment

Dosage

Nitrous oxide with oxygen gas should not be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring.

Adults

Children

Neonates

Administration

For inhalation through a face mask or mouthpiece.

Contraindications

Abdominal distension
Air embolism
Decompression sickness
Head injuries with impaired consciousness
Maxillofacial injuries
Pneumothorax
Severe bullous emphysema

Precautions and Warnings

Anaemia
Vitamin B12 deficiency

Advise patient not to drive or operate machinery for at least 30 minutes
Advise patient not to drive or operate machinery until assessed
Avoid use during myringoplasty
Avoid use following air encephalography
Avoid use following recent intraocular injection of gas
Occupational risk: Use of a scavenging system is recommended
Can cause addiction
Close supervision required if given continuously for more than 24 hours
Close supervision required if used more frequently than every 4 days
Monitor vitamin B12 levels regularly
Perform blood counts on prolonged use of this treatment
Advise patients of fire risk
Avoid use following a recent dive
Strongly supports combustion-avoid naked flames and heat

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.

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

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

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.

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

Gases containing more than 21% oxygen should be avoided in patients that have been exposed to agents that are toxic to the lungs, such as Paraquat.

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.

Pregnancy and Lactation

Pregnancy

Nitrous oxide with oxygen gas is considered safe for use during pregnancy.

Manufacturers advise nitrous oxide with oxygen gas may be used during pregnancy. 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. There is no evidence to suggest that nitrous oxide is toxic to the foetus, although it may depress neonatal respiration if used during delivery. There are no absolute contraindications to the use of nitrous oxide with oxygen gas in the first 16 weeks of pregnancy.

Lactation

Nitrous oxide with oxygen gas is considered safe to use during breastfeeding.

Manufacturers advise nitrous oxide with oxygen gas may be used during the breastfeeding period but not during breastfeeding itself.

Side Effects

Abdominal distension
Addiction
Agranulocytosis
Bloating
Bone marrow depression
Confusion
Disorientation
Dizziness
Ear damage
Ear sensations
Euphoria
Haematological toxicity
Light-headedness
Megaloblastic anaemia
Myelopathy
Nausea
Neurological effects
Neuropathy
Neurotoxicity
Respiratory depression
Sedation
Seizures
Sense of intoxication
Somnolence
Subacute combined degeneration
Tingling sensation
Vomiting

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 ).

Further Information

Last Full Review Date: December 2021

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Entonox. BOC Ltd. Revised October 2019.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 03 December 2021