Nitrous oxide, is an inhaled gas used as a

pain medication An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

and together with other medications for anesthesia. Common uses include during

childbirth Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births glob ...

, following

trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...

, and as part of end-of-life care. 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 Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, with short-term use. With long-term use

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as num ...

may occur. It should always be given with at least 21%

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

. It is not recommended in people with a bowel obstruction or

pneumothorax A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve i ...

. Use in the early part of

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

is not recommended. It is possible to continue

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

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 The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It often comes as a 50/50 mixture with

. Devices with a demand valve are available for self-administration. The setup and maintenance is relatively expensive for

developing countries A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...

Medical uses

Nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...

(N₂O) is itself active (does not require any changes in the body to become active), and so has an onset in roughly the lung–

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

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

or those who have recently been

scuba diving Scuba diving is a mode of underwater diving whereby divers use breathing equipment that is completely independent of a surface air supply. The name "scuba", an acronym for " Self-Contained Underwater Breathing Apparatus", was coined by Chr ...

, and there are cautions over its use with any bowel obstruction. Its analgesic effect is strong (equivalent to 15 mg of subcutaneous route

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

) 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

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 Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...

(N₂O) and half

(O₂). The ability to combine N₂O and oxygen at high pressure while remaining in the gaseous form is caused by the

Poynting effect The Poynting effect may refer to two unrelated physical phenomena. Neither should be confused with the Poynting–Robertson effect. All of these effects are named after John Henry Poynting, an English physicist. Solid mechanics In solid mecha ...

(after

John Henry Poynting John Henry Poynting FRS (9 September 185230 March 1914) was an English physicist. He was the first professor of physics at Mason Science College from 1880 to 1900, and then the successor institution, the University of Birmingham until his deat ...

, 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 ...

), 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 The Schrader valve (also called American valve) is a type of pneumatic tire valve used on virtually every motor vehicle in the world today. The Schrader company, for which it was named, was founded in 1844 by August Schrader. The original Schra ...

attachment, making the gas usable only with demand based giving sets

Administration

The gas is self-administered through a demand valve, 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 Anesthesiology, anaesthesiology, or anaesthesia is the medical specialty concerned with the total perioperative care of patients before, during and after surgery. It encompasses anesthesia, intensive care medicine, critical emergency medicine ...

for administration. The 50% oxygen in Entonox ensures the person will have sufficient oxygen in their alveoli and conducting airways for a short period of apnea to be safe.

History

Adminsitration of nitrous oxide Wellcome L0013787

Pure N₂O was first used as a medical analgesic in December 1844, when

Horace Wells Horace Wells (January 21, 1815 – January 24, 1848) was an American dentist who pioneered the use of anesthesia in dentistry, specifically the use of nitrous oxide (or laughing gas). Early life Wells was the first of three children of H ...

made the first 12–15 dental operations with the gas in

Hartford Hartford is the capital city of the U.S. state of Connecticut. It was the seat of Hartford County until Connecticut disbanded county government in 1960. It is the core city in the Greater Hartford metropolitan area. Census estimates since t ...

. Its debut as a generally accepted method, however, came in 1863, when Gardner Quincy Colton introduced it more broadly at all the Colton Dental Association clinics, that he founded in

New Haven New Haven is a city in the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound in New Haven County, Connecticut and is part of the New York City metropolitan area. With a population of 134,023 ...

and

New York City New York, often called New York City or NYC, is the most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the most densely populated major city in the Un ...

. 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 (oxygen insufficiency) and sometimes death by

asphyxiation Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that ca ...

. 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 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, which includes several improvements such as

flowmeter Flow measurement is the quantification of bulk fluid movement. Flow can be measured in a variety of ways. The common types of flowmeters with industrial applications are listed below: * a) Obstruction type (differential pressure or variable area) ...

s and constant-flow regulators, an

anaesthetic vaporiser An anesthetic vaporizer (American English) or anaesthetic vaporiser (British English) is a device generally attached to an anesthetic machine which delivers a given concentration of a volatile anesthetic agent. It works by controlling the vap ...

, a

medical ventilator A ventilator is a piece of medical technology that provides mechanical ventilation by moving breathable air into and out of the lungs, to deliver breaths to a patient who is physically unable to breathe, or breathing insufficiently. Ventilators ...

, and a scavenger system, 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 BOC Ltd is a British based multinational, industrial gas company, more commonly known as BOC, now a part of Linde plc. In September 2004, BOC had over 30,000 employees on six continents, with sales of over £10.6 billion. BOC was a constituent ...

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 applications of N₂O, especially for treatment-resistant forms of depression, and it is rapid-acting.

References

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