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Nitrous oxide, commonly known as happy gas or laughing gas, is a chemical compound with the chemical formula N2O. At room temperature, it is a colorless non-flammable gas, with a pleasant, slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic effects. It is known as "laughing gas" due to the euphoric effects of inhaling it, a property that has led to its recreational use as a dissociative drug. It is also used as an oxidizer in rocketry and in motor racing to increase the power output of engines. At elevated temperatures, nitrous oxide is a powerful oxidizer similar to molecular oxygen. For example, nitrous oxide in a test tube will re-ignite a smoldering splint.

Nitrous oxide reacts with ozone and is the main naturally occurring regulator of stratospheric ozone. Nitrous oxide is also a major greenhouse gas and air pollutant. Considered over a 100 year period, it has 298 times more impact per unit weight than carbon dioxide.

"Laughing gas" (name)

Scientist Humphrey Davy introduced nitrous oxide to the public (primarily the British upper class) as a recreational drug at "laughing gas parties" in 1799, 36 years before it was used medically. The effects of the gas can makes the user feel stuperous, dreamy, and sedated. Some people, in a state of induced euphoria by the gas, can sometimes "get the giggles" and erupt in laughter and overall amusement. Davy called it "laughing gas" because at his parties, everyone laughed and had a good time watching the user's "nitrous oxide capers", which included stumbling around, slurred speech, and falling down.

Manufacture

Nitrous oxide is most commonly prepared by careful heating of ammonium nitrate, which decomposes into nitrous oxide and water vapor. The addition of various phosphates favors formation of a purer gas at slightly lower temperatures. One of the earliest commercial producers was George Poe in Trenton, New Jerseymarker.

NH4NO3 (s) → 2 H2O (g) + N2O (g)


This reaction occurs between 170 - 240°C, temperatures where ammonium nitrate is a moderately sensitive explosive and a very powerful oxidizer. Above 240 °C the exothermic reaction may accelerate to the point of detonation, so the mixture must be cooled to avoid such a disaster. Superheated steam is used to reach reaction temperature in some turnkey production plants.

Downstream, the hot, corrosive mixture of gases must be cooled to condense the steam, and filtered to remove higher oxides of nitrogen. Ammonium nitrate smoke, as an extremely persistent colloid, will also have to be removed. The cleanup is often done in a train of 3 gas washes; namely base, acid and base again. Any significant amounts of nitric oxide (NO) may not necessarily be absorbed directly by the base (sodium hydroxide) washes.

The nitric oxide impurity is sometimes chelated out with ferrous sulfate, reduced with iron metal, or oxidised and absorbed in base as a higher oxide. The first base wash may (or may not) react out much of the ammonium nitrate smoke, however this reaction generates ammonia gas, which may have to be absorbed in the acid wash.

Other routes

The direct oxidation of ammonia may someday rival the ammonium nitrate pyrolysis synthesis of nitrous oxide mentioned above. This capital-intensive process, which originates in Japan, uses a manganese dioxide-bismuth oxide catalyst:
2 NH3 + 2 O2 → N2O + 3 H2O


Higher oxides of nitrogen are formed as impurities. In comparison, uncatalyzed ammonia oxidation (i.e. combustion or explosion) goes primarily to N2 and H2O.

Nitrous oxide can be made by heating a solution of sulfamic acid and nitric acid. Many gases are made this way in Bulgaria.

HNO3 + NH2SO3H → N2O + H2SO4 + H2O


There is no explosive hazard in this reaction if the mixing rate is controlled. However, as usual, toxic higher oxides of nitrogen form.

Nitrous oxide is produced in large volumes as a by-product in the synthesis of adipic acid; one of the two reactants used in nylon manufacture. This might become a major commercial source, but will require the removal of higher oxides of nitrogen and organic impurities. Currently much of the gas is decomposed before release for environmental protection. Greener processes may prevail that substitute hydrogen peroxide for nitric acid oxidation; hence no generation of oxide of nitrogen by-products.

Hydroxylammonium chloride can react with sodium nitrite to produce N2O as well:
NH3OH+Cl + NaNO2 → N2O + NaCl + 2 H2O
If the nitrite is added to the hydroxylamine solution, the only remaining byproduct is salt water. However, if the hydroxylamine solution is added to the nitrite solution (nitrite is in excess), then toxic higher oxides of nitrogen are also formed.

Uses

Rocket motors

Nitrous oxide can be used as an oxidizer in a rocket motor. This has the advantages over other oxidizers that it is non-toxic and, due to its stability at room temperature, easy to store and relatively safe to carry on a flight. As a secondary benefit it can be readily decomposed to form breathing air. Its high density and low storage pressure enable it to be highly competitive with stored high-pressure gas systems.

In a 1914 patent, American rocket pioneer Robert Goddard suggested nitrous oxide and gasoline as possible propellants for a liquid-fueled rocket. Nitrous oxide has been the oxidizer of choice in several hybrid rocket designs (using solid fuel with a liquid or gaseous oxidizer). The combination of nitrous oxide with hydroxyl-terminated polybutadiene fuel has been used by SpaceShipOne and others. It is also notably used in amateur and high power rocketry with various plastics as the fuel.

Nitrous oxide can also be used in a monopropellant rocket. In the presence of a heated catalyst, N2O will decompose exothermically into nitrogen and oxygen, at a temperature of approximately 1300 °C. Because of the large heat release the catalytic action rapidly becomes secondary as thermal autodecomposition becomes dominant. In a vacuum thruster, this can provide a monopropellant specific impulse (Isp) of as much as 180s. While noticeably less than the Isp available from hydrazine thrusters (monopropellant or bipropellant with nitrogen tetroxide), the decreased toxicity makes nitrous oxide an option worth investigating.

Specific impulse (Isp) can be improved by blending a hydrocarbon fuel with the nitrous oxide inside the same storage tank, becoming a Nitrous Oxide Fuel Blend (NOFB) monopropellant. This does not incur the danger of spontaneous ignition, since N2O is chemically stable. When the nitrous oxide decomposes by a heated catalyst, high temperature oxygen is released and rapidly ignites the hydrocarbon fuel-blend. NOFB monopropellants are capable of I greater than 300 seconds, while avoiding the toxicity associated with hypergolic propulsion systems. Its low freezing point also eases thermal management as compared to hydrazine and dinitrogen tetroxide—a valuable property on a spacecraft which may contain quantities of cryogenic propellant.

Internal combustion engine

In vehicle racing, nitrous oxide (often referred to as just "nitrous" or as NOS after the name of the brand Nitrous Oxide Systems) allows the engine to burn more fuel and air, resulting in a more powerful combustion. The gas itself is not flammable, but it delivers more oxygen than atmospheric air by breaking down at elevated temperatures.

Nitrous oxide is stored as a compressed liquid; the evaporation and expansion of liquid nitrous oxide in the intake manifold causes a large drop in intake charge temperature, resulting in a denser charge, further allowing more air/fuel mixture to enter the cylinder. Nitrous oxide is sometimes injected into (or prior to) the intake manifold, whereas other systems directly inject right before the cylinder (direct port injection) to increase power.

The technique was used during World War II by Luftwaffe aircraft with the GM-1 system to boost the power output of aircraft engines. Originally meant to provide the Luftwaffe standard aircraft with superior high-altitude performance, technological considerations limited its use to extremely high altitudes. Accordingly, it was only used by specialized planes like high-altitude reconnaissance aircraft, high-speed bombers, and high-altitude interceptor aircraft.

One of the major problems of using nitrous oxide in a reciprocating engine is that it can produce enough power to damage or destroy the engine. Very large power increases are possible, and if the mechanical structure of the engine is not properly reinforced, the engine may be severely damaged or destroyed during this kind of operation. It is very important with nitrous oxide augmentation of internal combustion engines to maintain proper operating temperatures and fuel levels to prevent "preignition", or "detonation" (sometimes referred to as "knocking" or "pinging"). Most problems that are associated with nitrous do not come from mechanical failure due to the power increases. Since nitrous allows a much denser charge into the cylinder it dramatically increases cylinder pressures. The increased pressure results in heat, and heat will cause many problems from melting the piston, valves or warping the head/cracking or predetonation.

Aerosol propellant

An 8g canister of nitrous oxide intended for use as a whipped cream aerating agent
The gas is approved for use as a food additive (also known as E942), specifically as an aerosol spray propellant. Its most common uses in this context are in aerosol whipped cream canisters, cooking sprays, and as an inert gas used to displace bacteria-inducing oxygen when filling packages of potato chips and other similar snack foods.

The gas is extremely soluble in fatty compounds. In aerosol whipped cream, it is dissolved in the fatty cream until it leaves the can, when it becomes gaseous and thus creates foam. Used in this way, it produces whipped cream four times the volume of the liquid, whereas whipping air into cream only produces twice the volume. If air were used as a propellant, oxygen would accelerate rancidification of the butterfat; nitrous oxide inhibits such degradation. Carbon dioxide cannot be used for whipped cream because it is acidic in water, which would curdle the cream and give it a seltzer-like 'sparkling' sensation.

However, the whipped cream produced with nitrous oxide is unstable, and will return to a more or less liquid state within half an hour to one hour. Thus, the method is not suitable for decorating food that will not be immediately served. Similarly, cooking spray, which is made from various types of oils combined with lecithin (an emulsifier), may use nitrous oxide as a propellant; other propellants used in cooking spray include food-grade alcohol and propane.

Users of nitrous oxide often obtain it from whipped cream dispensers that use nitrous oxide as a propellant (see above section), for recreational use as a euphoria-inducing inhalant drug. It is non-harmful in small doses, but risks due to lack of oxygen do exist (see Recreational use below).

In medicine

Nitrous oxide has been used for anesthesia in dentistry since the 1840s. The most common use is as a 50:50 mix with oxygen, commonly known as Entonox or Nitronox delivered through a demand valve, and frequently used to relieve pain associated with childbirth, trauma and heart attacks.

Professional use can involve constant supply flowmeters which allow the proportion of nitrous oxide and the combined gas flow rate to be individually adjusted. Nitrous oxide is typically administered by dentists through a demand-valve inhaler over the nose that only releases gas when the patient inhales through the nose.

Because nitrous oxide is minimally metabolized, it retains its potency when exhaled into the room by the patient and can pose an intoxicating and prolonged-exposure hazard to the clinic staff if the room is poorly ventilated. Where nitrous oxide is administered, a continuous-flow fresh-air ventilation system or nitrous-scavenging system is used to prevent waste gas buildup.

Nitrous oxide is a weak general anesthetic, and so is generally not used alone in general anesthesia. In general anesthesia it is used as a carrier gas in a 2:1 ratio with oxygen for more powerful general anesthetic agents such as sevoflurane or desflurane. It has a MAC (minimum alveolar concentration) of 105% and a blood:gas partition coefficient of 0.46. Less than 0.004% is metabolised in humans.

Recreational use

Nitrous oxide (N2O) is a dissociative drug that can cause analgesia, depersonalization, derealization, dizziness, euphoria, and some sound distortion. Research has also found that it increases suggestibility and imagination.

Since the earliest uses of nitrous oxide for medical or dental purposes, it has also been used recreationally as an inhalant, because it causes euphoria and slight hallucinations. Only a small number of recreational users (such as dental office workers or medical gas technicians) have legal access to pure nitrous oxide canisters that are intended for medical or dental use. Most recreational users obtain nitrous oxide from compressed gas containers which use nitrous oxide as a propellant for whipped cream or from automotive nitrous systems.

Users typically inflate a balloon or a plastic bag with nitrous oxide from a tank or a one-use 'charger', and then inhale the gas for its effects. Highly compressed liquid expelled from a tank or canister is extremely cold, and should not be inhaled directly, thus for medical and recreational use it is decompressed into something else, such as a balloon, first. Mis-cracked canisters can cause skin damage due to freezing temperatures. Users may also inhale nitrous oxide directly from pre-packaged whipped cream canisters, where it is used as propellant.

Recreational users typically do not mix it with air or oxygen and thus may risk injury or death from anoxia if they tie plastic bags around their heads or otherwise obstruct their breathing.

Nitrous oxide can be habit-forming because of its short-lived effect (generally from 0.1 – 1 minutes in recreational doses). Long-term use in excessive quantities has been associated with vitamin B12 deficiency anemia due to reduced hemopoiesis, neuropathy, tinnitus, and numbness in extremities, unless vitamin B12 supplements are taken to counteract this. Pregnant women should not use nitrous oxide as chronic use is teratogenic and foetotoxic. One study in rats found that long term exposure to high doses of nitrous oxide may lead to Olney's lesions that may become persistent.

Neuropharmacology

Medical grade nitrous oxide tanks used in dentistry


Nitrous oxide shares many pharmacological similarities with other inhaled anesthetics, but there are a number of differences. Nitrous oxide is relatively non-polar, has a low molecular weight, and high lipid solubility. As a result, it can quickly diffuse into phospholipid cell membranes.

Like many other classical anesthetics, nitrous oxide's exact mechanism of action is still open to some conjecture. It acts as an NMDA receptor antagonist at partial pressures similar to those used in general anaesthesia. The evidence on the effect of N2O on GABAA receptor currently is mixed, but tends to show a lower potency potentiation via acting as a positive allosteric modulator of the receptor. N2O, like other volatile anesthetics, activates twin-pore potassium channels, albeit weakly. These channels are largely responsible for keeping neurons at the resting (unexcited) potential. Unlike many anesthetics, however, N2O does not seem to affect calcium channels.

Unlike most general anesthetics, N2O appears to affect the GABA receptor. In many behavioral tests of anxiety, a low dose of N2O is a successful anxiolytic. This anti-anxiety effect is partially reversed by benzodiazepine receptor antagonists. Mirroring this, animals which have developed tolerance to the anxiolytic effects of benzodiazepines are partially tolerant to nitrous oxide. Indeed, in humans given 30% N2O, benzodiazepine receptor antagonists reduced the subjective reports of feeling “high”, but did not alter psycho-motor performance.

The effects of N2O seem linked to the interaction between the endogenous opioid system and the descending noradrenergic system. When animals are given morphine chronically they develop tolerance to its analgesic (pain killing) effects; this also renders the animals tolerant to the analgesic effects of N2O. Administration of antibodies which bind and block the activity of some endogenous opioids (not beta-endorphin), also block the antinociceptive effects of N2O. Drugs which inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of N2O. Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of N2O, but these drugs have no effect when injected into the spinal cord.

Conversely, alpha-adrenoreceptor antagonists block the antinociceptive effects of N2O when given directly to the spinal cord, but not when applied directly to the brain. Indeed, alpha2B-adrenoreceptor knockout mice or animals depleted in noradrenaline are nearly completely resistant to the antinociceptive effects of N2O. It seems N2O-induced release of endogenous opioids causes disinhibition of brain stem noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signaling (Maze, M. and M. Fujinaga, 2000). Exactly how N2O causes the release of opioids is still uncertain.

Safety

The major safety hazards of nitrous oxide come from the fact that it is a compressed liquefied gas, an asphyxiation risk, and a dissociative anaesthetic. Exposure to nitrous oxide causes short-term decreases in mental performance, audiovisual ability, and manual dexterity.

A study of workersand several experimental animal studies indicate that adverse reproductive effects for pregnant females may also result from chronic exposure to nitrous oxide.

The National Institute for Occupational Safety and Health recommends that workers' exposure to nitrous oxide should be controlled during the administration of anesthetic gas in medical, dental, and veterinary operators.

Chemical/physical

At room temperature (20°C) the saturated vapor pressure is 58.5 bar, rising up to 72.45 bar at 36.4°C — the critical temperature. The pressure curve is thus unusually sensitive to temperature. Liquid nitrous oxide acts as a good solvent for many organic compounds; liquid mixtures may form shock sensitive explosives.

As with many strong oxidizers, contamination of parts with fuels have been implicated in rocketry accidents, where small quantities of nitrous / fuel mixtures explode due to 'water hammer' like effects (sometimes called 'dieseling' — heating due to adiabatic compression of gases can reach decomposition temperatures). Some common building materials such as stainless steel and aluminum can act as fuels with strong oxidisers such as nitrous oxide, as can contaminants, which can ignite due to adiabatic compression.

There have also been accidents where nitrous oxide decomposition in plumbing has led to the explosion of large tanks.

Biological

Nitrous oxide inactivates the cobalamin form of vitamin B by oxidation. Symptoms of vitamin B deficiency, including sensory neuropathy, myelopathy, and encephalopathy, can occur within days or weeks of exposure to nitrous oxide anesthesia in people with subclinical vitamin B deficiency. Symptoms are treated with high doses of vitamin B , but recovery can be slow and incomplete. People with normal vitamin B levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B levels should be checked in people with risk factors for vitamin B deficiency prior to using nitrous oxide anesthesia.

Nitrous oxide has also been shown to induce early stages of Olney's lesions in the brains of rats. However none of the lesions found were irreversible.

Environmental

Nitrous oxide is a greenhouse gas, accounting for around 6% of the heating effect of greenhouse gases in the atmosphere. According to 2006 data from the United States Environmental Protection Agency, industrial sources make up only about 20% of all anthropogenic sources, and include the production of nylon, and the burning of fossil fuel in internal combustion engines. Human activity is thought to account for 30%; tropical soils and oceanic release account for 70%. However, a 2008 study by Nobel Laureatte Paul Crutzen suggests that the amount of nitrous oxide release attributable to agricultural nitrate fertilizers has been seriously underestimated, most of which would presumably come under soil and oceanic release in the Environmental Protection Agency data. Atmospheric levels have risen by more than 15% since 1750. Nitrous oxide also causes ozone depletion. A new study suggest that N O emission currently is the single most important ozone-depleting substance (ODS) emission and is expected to remain the largest throughout the 21st century.

Legality

In the United Statesmarker, possession of nitrous oxide is legal under federal law and is not subject to DEA purview. It is, however, regulated by the Food and Drug Administration under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of human consumption.

Many states have laws regulating the possession, sale, and distribution of nitrous oxide. Such laws usually ban distribution to minors or limit the amount of nitrous oxide that may be sold without special license.

In some countries, it is illegal to have nitrous oxide systems plumbed into an engine's intake manifold. These laws are ostensibly used to prevent street racing and to meet emission standards.

Nitrous oxide is entirely legal to possess and inhale in the United Kingdom, although supplying it to others to inhale, especially minors, is more likely to end up with a prosecution under the Medicines Act.

In New Zealandmarker, the Ministry of Health has warned that nitrous oxide is a prescription medicine, and its sale or possession without a prescription is an offense under the Medicines Act. This statement would seemingly prohibit all non-medicinal uses of the chemical, though it is implied that only recreational use will be legally targeted.

In Indiamarker, for general anaesthesia purposes, nitrous oxide is available as Nitrous Oxide IP. India's gas cylinder rules (1985) permit the transfer of gas from one cylinder to another for breathing purposes. This law benefits remote hospitals, which would otherwise suffer as a result of India's geographic immensity. Nitrous Oxide IP is transferred from bulk cylinders (17,000 liters capacity gas) to smaller pin-indexed valve cylinders (1,800 liters of gas), which are then connected to the yoke assembly of Boyle's machines. Because India's Food & Drug Authority (FDA-India) rules state that transferring a drug from one container to another (refilling) is equivalent to manufacturing, anyone found doing so must possess a drug manufacturing license.

History

The gas was first synthesized by English chemist and natural philosopher Joseph Priestley in 1775 [6377], who called it phlogisticated nitrous air (see phlogiston). Priestley describes the preparation of "nitrous air diminished" by heating iron filings dampened with nitric acid in Experiments and Observations on Different Kinds of Air (1775). Priestley was delighted with his discovery: "I have now discovered an air five or six times as good as common air... nothing I ever did has surprised me more, or is more satisfactory."

Humphry Davy in the 1790s tested the gas on himself and some of his friends, including the poet Samuel Taylor Coleridge. They realized that nitrous oxide considerably dulled the sensation of pain, even if the inhaler were still semi-conscious. After it was publicized extensively by Gardner Quincy Colton in the United States in the 1840s, it came into use as an anaesthetic, particularly by such dentists as Horace Wells, who was one of the first dentists to use it on his patients. This was because dentists did not typically have access to the services of anesthesiologists and might benefit from patients who could respond to verbal commands.

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