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Nitrous oxide, is an inhaled gas used as a pain medication and together with other
medications A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
for
anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
. Common uses include during childbirth, following trauma, and as part of
end-of-life care End-of-life care (EoLC) refers to health care provided in the time leading up to a person's death. End-of-life care can be provided in the hours, days, or months before a person dies and encompasses care and support for a person's mental and emotio ...
. Onset of effect is typically within half a minute, and the effect lasts for about a minute. There are few side effects, other than vomiting, with short-term use. With long-term use anemia or numbness may occur. It should always be given with at least 21% oxygen. It is not recommended in people with a
bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...
or pneumothorax. Use in the early part of pregnancy is not recommended. It is possible to continue breastfeeding following use. Nitrous oxide was discovered between 1772 and 1793 and used for anesthesia in 1844. It is on the World Health Organization's List of Essential Medicines. It often comes as a 50/50 mixture with oxygen. Devices with a
demand valve A diving regulator is a pressure regulator that controls the pressure of breathing gas for diving. The most commonly recognised application is to reduce pressurized breathing gas to ambient pressure and deliver it to the diver, but there are al ...
are available for self-administration. The setup and maintenance is relatively expensive for developing countries.


Medical uses

Nitrous oxide (N2O) is itself active (does not require any changes in the body to become active), and so has an onset in roughly the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
brain circulation time. This gives it a peak action 30 seconds after the start of administration; Entonox should thus be used accordingly, i.e. inhalation should start 30 seconds before a contraction becomes painful in labour. It is removed from the body unchanged via the lungs, and does not accumulate under normal conditions, explaining the rapid offset of around 60 seconds. It is effective in managing pain during labor and delivery. Nitrous oxide is more soluble than oxygen and nitrogen, so will tend to diffuse into any air spaces within the body. This makes it dangerous to use in patients with pneumothorax or those who have recently been scuba diving, and there are cautions over its use with any bowel obstruction. Its analgesic effect is strong (equivalent to 15 mg of
subcutaneous Subcutaneous may refer to: * Subcutaneous injection * Subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The ...
route morphine) and characterised by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly. When used in combination with other anesthetics gases, nitrous oxide causes a dose dependent increased respiratory rate and decreased tidal volumes, the net effect is a lower minute ventilation. Like volatile anesthetics, it increases cerebral blood flow and intracranial pressure. However, contrary to volatile anesthetics, it leads to an increase in cerebral metabolic rate of oxygen.


Contraindications

N2O should not be used in patients with bowel obstruction, pneumothorax, or middle ear or sinus disease, and should also not be used on any patient who has been scuba diving within the preceding 24 hours or in violently disturbed psychiatric patients. There are also clinical cautions in place for the first two trimesters of pregnancy and in patients with decreased levels of consciousness.


Composition

The gas is a mixture of half nitrous oxide (N2O) and half oxygen (O2). The ability to combine N2O and oxygen at high pressure while remaining in the gaseous form is caused by the Poynting effect (after John Henry Poynting, an English physicist). The Poynting effect involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporisation of the liquid to form a gaseous O2/N2O mixture. Inhalation of pure N2O over a continued period would deprive the patient of oxygen, but the 50% oxygen content prevents this from occurring. The two gases will separate at low temperatures (<4
°C The degree Celsius is the unit of temperature on the Celsius scale (originally known as the centigrade scale outside Sweden), one of two temperature scales used in the International System of Units (SI), the other being the Kelvin scale. The d ...
), which would permit administration of hypoxic mixtures. Therefore, it is not given from a cold cylinder without being shaken (usually by cylinder inversion) to remix the gases. File:Entonox Shoulder.png, Distinct blue and white cap of an Entonox cylinder File:Entonox schrader valve.png, Typical Schrader valve attachment, making the gas usable only with demand based giving sets


Administration

The gas is self-administered through a
demand valve A diving regulator is a pressure regulator that controls the pressure of breathing gas for diving. The most commonly recognised application is to reduce pressurized breathing gas to ambient pressure and deliver it to the diver, but there are al ...
, using a mouthpiece, bite block or face mask. Self-administration of Entonox is safe because if enough is inhaled to start to induce anaesthesia, the patient becomes unable to hold the valve, and so will drop it and soon exhale the residual gas. This means that unlike other anaesthetic gases, it does not require the presence of an anaesthetist for administration. The 50% oxygen in Entonox ensures the person will have sufficient oxygen in their
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
and conducting airways for a short period of
apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...
to be safe.


History

Pure N2O was first used as a medical analgesic in December 1844, when Horace Wells made the first 12–15 dental operations with the gas in Hartford. Its debut as a generally accepted method, however, came in 1863, when
Gardner Quincy Colton Gardner Quincy Colton (February 7, 1814, Georgia, Vermont – August 10, 1898, Geneva, Switzerland) was an American showman, medicine man, lecturer, and former medical student who pioneered the use of nitrous oxide, or laughing gas, in dentistr ...
introduced it more broadly at all the Colton Dental Association clinics, that he founded in New Haven and New York City. The first devices used in dentistry to administer the gas consisted of a simple breathing bag made of rubber cloth. Breathing the pure gas often caused
hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...
(oxygen insufficiency) and sometimes death by asphyxiation. Eventually practitioners became aware of the need to provide at least 21% oxygen content in the gas (the same percentage as in air). In 1911, the anaesthetist
Arthur Ernest Guedel Arthur Ernest Guedel (June 13, 1883 – June 10, 1956) was an American anesthesiologist. He was known for his studies on the uptake and distribution of inhalational anesthetics, as well for defining the various stages of general anesthesia. The gu ...
first described the use of self-administration of a nitrous oxide and oxygen mix. It was not until 1961 that the first paper was published by Michael Tunstall and others, describing the administration of a pre-mixed 50:50 nitrous oxide and oxygen mix, which led to the commercialisation of the product. In 1970, Peter Baskett recognised that pre-mixed nitrous oxide and oxygen mix could have an important part to play in the provision of pre-hospital pain relief management, provided by ambulance personnel. Baskett contacted the Chief Ambulance Officer for the Gloucestershire Ambulance Brigade, Alan Withnell, to suggest this idea. This gained traction when Baskett negotiated with the British Oxygen Company, the availability of pre-mixed nitrous oxide and oxygen mix apparatus for training. Regular training sessions began at Frenchay Hospital (Bristol) and a pilot study was run in Gloucestershire (in which ambulances were crewed by a driver and one of the new highly trained ambulance men), the results of this trial were published in 1970. Today the nitrous oxide is administered in hospitals by a
relative analgesia machine A relative analgesia machine is used by dentists to induce inhalation sedation in their patients. It delivers a mixture of nitrous oxide ("laughing gas") and oxygen. A relative analgesia machine is simpler than an anaesthetic machine, as it does not ...
, which includes several improvements such as flowmeters and constant-flow regulators, an anaesthetic vaporiser, a medical ventilator, and a
scavenger system {{Unreferenced, date=March 2009 A scavenger system is a medical device used in hospitals. It is used to gather gas or aerosolized medication after it is exhaled from the patient or left the area of the patient. Often used to collect anesthesia, ...
, and delivers a precisely dosed and breath-actuated flow of nitrous oxide mixed with oxygen. The machine used in dentistry is much simpler, and is meant to be used by the patient in a fully conscious state. The gas is delivered through a demand-valve inhaler over the nose, which will only release gas when the patient inhales through it.


Society and culture

Nitronox was a registered trademark of the BOC Group between 1966 and 1999, and was reregistered by Hs Tm Inc since 2005 It is also colloquially known as "gas and air".


Research

Investigational trials show potential for
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
applications of N2O, especially for treatment-resistant forms of depression, and it is rapid-acting.


References


Further reading

*


External links


BabyCentre entry on Entonox


{{DEFAULTSORT:Nitrous Oxide And Oxygen Breathing gases Emergency medical equipment First aid General anesthetics Oxygen Pain management World Health Organization essential medicines Wikipedia medicine articles ready to translate