Since its discovery Nitrous Oxide has found a wide variety of uses in many areas of modern life. It is perhaps most famous for use as NOS an oxidiser for boosting engine power and as “laughing gas” the anaesthetic used by dentists and in hospitals.

This website draws upon many sources of information to present everything you are likely to need to know about Nitrous Oxide gas.

What is Nitrous Oxide?

Nitrous oxide is a colourless gas, with a vaguely sweet taste and smell (one of its popular names is in fact sweet gas), which is composed by two parts nitrogen and one oxygen (N2O). It is widely known as laughing gas due to provoking euphoric effects when inhaled, additionally also provokes memory loss and hallucinations, characteristics that made popular as a recreational drug.  Nitrous oxide is neither inflammable nor explosive, but it supports combustion (meaning it is an oxidizer) as actively as oxygen when mixed in specific concentrations with anaesthetic or flammable materials.

Nitrous oxide is widely used in surgery and dentistry for its anaesthetics and analgesic properties. It also used in rocket and internal combustion engines as an oxidizing agent, due it to providing increases in the power output of this type of engines.

Nitrous oxide is also a critical greenhouse gas. It generates nitric oxide (NO) when it reacts with oxygen atoms, and consecutively the nitric oxide reacts with ozone, being the prime natural regulator of stratospheric ozone. Given that nitrous oxide has 298 times a much impact as carbon dioxide in terms of “global warming potential” it is also considered a major pollutant.

Buying Nitrous Oxide

Depending upon its purpose you would buy Nitrous Oxide from different sources – the food  grade gas can be bought as cream chargers from here – for whipping cream and mini-rockets. Automotive Nitro has added chemicals that make it toxic and can be bought from places like here. Carefully read any suppliers terms and conditions before ordering there may be special restrictions regarding the sale and delivery of the gas.

Presence in Nature

Most of the atmospheric air is composed by nitrogen, which bacteria present in oceans and soils (mainly tropical soils) use as nutrient, producing nitrous oxide, as part of a series  of processes that are known as the nitrogen cycle. The natural occurrence of nitrous oxide described above amounts to 70% of the nitrous oxide released into the atmosphere, with the remaining 30% being released due to human activity, mainly due to agricultural and livestock activity.  The microbial processes that occur naturally in the soil are:

• Nitrification
• Denitrification
• Nitrifier denitrification
• Aerobic autotropic nitrification
• Anaerobic heterotrophic denitrification
• Heterotropic nitrification
• Aerobic denitrification
• Fungal denitrification
• Chemodenitrification by non-biological processes

Emissions of nitrous oxide in the soil are attributed to chemical and physical characteristics of the soil. These include the presence of the mineral N, the soil’s PH, the presence of organic matter and the type of soil, as well as climate related characteristics such as soil temperature and water content.

Discovery

The discovery of nitrous is credited to English scientist Ioseph Priestley, in 1772, although it seems he was not aware of its anaesthetics properties or possible uses. In 1775 he published his discovery in Experiments and Observations on Different Kinds of Air, where he details the production of nitrous oxide, or “nitrous air diminished” as he named it, by heating iron fillings dampened with nitric acid.

Production

Apart from the natural sources outline above, nitrous oxide can also be produced by chemical methods for human use, which will be outlined later. The most common method for its production is:

• Ammonium nitrate decomposition by heat

This is the most common method for the production of nitrous oxide at an industrial scale and consists in heating ammonium nitrate (NH4NO3) up to 240º Celsius. The decomposition of the nitrate by this process creates a mixture of nitrous oxide and extremely hot vapour. At the same time, this process also produces impurities, including ammonia, nitrogen and other nitrogen oxides. Water vapour and other impurities cleaned with a mixture of water, caustic soda and sulphuric acid, with any traces of nitrogen being removed from the storing place of the nitrous oxide, after this being compressed.

• Direct oxidation of ammonia

This method is costlier than the one outline above, but may someday be competitive with it.  It uses as a catalyst manganese dioxide-bismuth oxide to produce nitrous oxide and was developed in Japan. In this process creates impurities in the form of higher oxides of nitrogen. The result of the uncatalyzed ammonia oxidation is manly nitrogen and water.

• Heating of a solution of sulfamic acid and nitric acid

This method, widely used in Bulgaria, is produced by heating a solution of sulfamic acid and nitric acid. Given that the mixing rate is closely controlled there is no explosive danger in this reaction.

• By-product in the synthesis of adipic acid

Large quantities of nitrous oxide are produced as a by-product in the synthesis of adipic acid (adipic acid is one of reactants used in the production of nylon). This method as the potential to become a major commercial source, but requires the removal of impurities in the form of higher oxides of nitrogen and organic materials. At this time most of the gas decomposes before release due to environmental reasons. More environment friendly, which replace hydrogen peroxide with nitric acid oxidation, may succeed given that they do not generate nitrogen oxide by-products.

• Hydroxylammonium chloride reacting with sodium nitrite

When the nitrite is mixed into a hydroxylamine solution, nitrous oxide is produced with the by-product of salt water. If the reverse happens, hydroxylamine mixed into a nitrite solution and thus the nitrites in excess, there is the forming of additional higher oxides of nitrogen.

First uses

Thomas Beddoes and James Watt where responsible in 1794 for the first notable usage of nitrous oxide due to their joint publishing of the volume Considering on the Medicinal Useage and on the New Production of Semi-Factitious Air. The importance of this book is two sided, as it described the innovative device to produce a quantity of “Factitious Airs”, the name given at the time to nitrous oxide, and a new form of “ventilator” used to breathe in the gas, created James Watt. The book also published and highlighted Beddoes theories on the medical uses of nitrous oxide, namely in the treatment of tuberculosis and further respiratory diseases.  Watt’s machine was made of three different components:

• A furnace to combust the required materials
• A receptacle with water, through which there processed gas would pass through a curling pipe, to remove the impurities.
• A gas cylinder furnished with a gas-o-meter, thru which the produced gas could be transported into the movable air bags.

The ventilator was a simple mouthpiece connected by a tube to the movable air bags mentioned above.

In 1794, with the machine and the ventilator being constructed and then manufactured, the basis for the clinical trials were set, which started after Beddoes instituted the “New Pneumatic Original Institution for Relieving of many Diseases by the use of Medical Airs” in Bristol. Working with a bigger version of James Watt’s machine, located at its basement, was Humphry Davy. He was responsible for the production of gas, as well as stimulated into testing new gases to treat the patients. This lead to Humphry Davy’s first notable work, the investigation of nitrous oxide, which was subsequently published in his 1800’s book Researches, all about Chemical and also the Modern Philosophical.  In this book, Davy’s describes the analgesic consequences of the gas and the possible medical uses in surgical operations. In spite of Humphry Davy’s discoveries, 47 long years would pass before doctors experimented with this gas as a form of anaesthesia.

As an interesting aside, the recreational use was an instant hit among the British wealthiest, as soon as 1799. The then named “laughing gas and fun parties” explored one of the most known effects of nitrous, the euphoric state provoked by the inhaling of the gas.

As for nitrous oxide’s adoption as an anaesthetic, it didn’t happen until 11 December 1844, when the Horace Wells performed a dental extraction, with the patient demonstrating insensitivity to any form of pain or discomfort. Horace Wells continued using this method, during the next weeks, in as much as 12 to 15 patients, and according to his personal reports, the effects of the nitrous oxide only were unsuccessful in a pair of cases. Although these results, indicating the potential of nitrous oxide as an anaesthetic in dental surgeries, were reported as soon as December 1844 to the Boston’s medical society, nitrous oxide adoption did not happen straightway. This is possibly because in the first public showing to the medical community in Boston did not a total success, resulting in an obvious reluctance of his peer in adapting this new methodology, doubting its effectiveness and security of the patient.

As for the usage in hospitals, it was not potent enough for anaesthetic use in any major operations. The more potent sulphuric ether was tested and admitted into use by October 1846 and, later in 1847, so was chloroform.  However, it became a common practice using the “gas-ether inhaler”, created by Joseph Thomas Clover in 1876, to start anaesthetic procedures with a minor stream of nitrous oxide, adding gradually the more potent ether or chloroform, in order to increase the anaesthesia. Joseph Thomas Clover’s device was planned to deliver a mixture, controlled by a member of staff, of nitrous oxide and ether. It was used in many medical facilities until the mid-1930s and, although hospitals now use much more advanced anaesthetic devices, many of these machine are still based on Clover’s inhaling device, using nitrous oxide to start the anaesthesia before the usage of an additional, more potent, anaesthetic.

Pharmacology

Nitrous oxide is highly insoluble in blood and other tissues, providing a fast absorption of the anaesthesia and after that a fast recovery after the patient stops inhaling the gas.  The lungs, with a minimal dispersion through the skin, eliminate nitrous oxide completely. It is though that nitrous oxide is disintegrated in the interaction with vitamin B12, present in intestinal bacteria. This results in lowering of the synthesis of methionine, creating signs of vitamin B12 deficiency (megaloblastic anemia, peripheral neuropathy), when using nitrous oxide for a long period of time. Due to that it is not used an anaesthetic for long periods of time or as sedative in cases of intense care.

Nitrous oxide in high concentrations has been known to provoke death by asphyxiation due to the lack of oxygen. However, it should be noted that the gas mixture used of anaesthesia should always contain at least 21% oxygen, which is the proportion of oxygen in breathable air. The incorrect and badly controlled use of nitrous oxide is the reason for these deaths.  Incorrect and continued use during pregnancy can also lead to medical complications for the baby.

Effects of long-term exposure to small doses are not known, but have been studied in some professions that are routinely exposed, as anaesthetists in operating rooms.

Anaesthetic effects

Nitrous oxide is an anaesthetic, this mean that it provokes a loss of sensation when inhaled. The prevailing theory of the molecular mechanism that contributes for the anaesthetic action of nitrous oxide is the non-competitive inhibition of glutamate receivers of the subtype NMDA. This way, the inhibition of the neurotransmission glutamate-induced excitotoxicity is central to the thesis of the anaesthetic effects of nitrous oxide.  Other prime target that contributes to the anaesthetic action of the nitrous oxide is potassium channels, like the TREK-1 channel that, when activated, enhances the conductivity of potassium and therefore hyperpolarizes the neurons, changing their firing rates.  Even considering the importance of GABAa receptors in anaesthesia through intravenous anaesthetics (propofol, etomidate and pentobarbital) and volatile halogenated anaesthetics is well established, nitrous oxide has an insignificant effect on these antagonist (that inhibit) receptors.

Analgesic effects

Nitrous oxide has also known analgesic effects; this meaning it can relieve pain. Nitrous oxide induces analgesia by activating opioid neurons in the periaqueductal grey matter and in the adrenergic neurons in locus ceruleus, areas 5 and 7 of the brain (somatosensory cortex). The corticotrophin release factor, released by the hypothalamus, seems to be critical to the activation of the locus ceruleus, a fact that might be provoked the inhibition by NMDA receptors.

Anxiolytic effect

Nitrous oxide has widely known anxiolytic effect, meaning that it has a calming effect. For this reason, it is widely used in dentistry to calm the patient before applying local anaesthesia and during the procedure.  The patient retains conscience and is relaxed, often reporting a losing track of time. After the procedure, the effects wear off quickly. The anxiolytic effect of nitrous oxide is linked with heightened activity of GABAa receptors.

Euphoria

In studies conducted on mice, it was found nitrous oxide arouses the mesolimbic reward path by the inducement of dopamine and the activation of dopaminergic neurons in the ventral tegmental area and nucleus accumbens. It is theorized that this happens due to the inhibition of NMDA receptors present in the brain. This has been pointed as the reason for the euphoria effects of nitrous oxide, as well as appearing to enhance the analgesic characteristics of nitrous oxide. One interesting result of these studies on mice is nitrous oxide seems to block amphetamine-induced carrier-mediated dopamine release, which blocks addiction to opioids like cocaine or morphine. This might be the reason of its positive effects when dealing with addiction, although studies in humans, through clinical trials, have returned mixed results.

Toxicity

Nitrous oxide can have a series of potential negative effects, specifically:

• Cardiovascular
  • Hypotension
  • Cardiac dysrhythmia
  • Cerebral oedema (also known as cerebral edema)
  • Etc.
  • Central Nervous System
    • Depression of central nervous system
    • Ataxia
    • Etc.
    • Other effects
      • Headaches
      • Nausea
      • Vomiting
      • Etc.

 

Nitrous oxide can provoke nausea and post-operating vomiting, but this can be easily prevented. Another negative effect of nitrous oxide is known ability to scatter into body cavities filled with air. This can produce an increase in pressure or volume of the cavity, when the nitrous oxide is administered incorrectly. Specific examples of these effects are:

• Increase in intraocular pressure
• Increase in intra-cranial pressure
• Increase in abdominal distension (in the case of intestinal obstruction)
• Increase in pressure of the pleural space

When the flow of nitrous oxide is interrupted, it diffuses form the blood to the cavities as rapidly as it diffused to the bloodstream during the inhaling. If the patients is allowed to breath atmospheric air (“normal air”) an occurrence known as “diffusion hypoxia” might develop. Diffusion hypoxia is responsible for the majority of reported headaches, nausea and lethargy following inhaling nitrous oxide – a state similar to a hangover.

Immunological Effects

Nitrous oxide has been associated to several effects at the level of the immunological system, as the lowering in the proliferation of mononuclear cells in the peripheral blood and the build-up and lowering of the chemotaxis of neutrophils.

Blood toxicity

The inhibition of methionine synthetase can lead to complications like megaloblastic anemia (also known as megaloblastic anaemia). In fact, even during short period of exposure (two to six hours) can provoke megaloblastic changes in the bone marrow in critical patients. Another group vulnerable to the suppression of methionine synthetase are the elderly, as aproximatly 20% are cobalamin deficient.

Neurological effects

The reduction in the functioning of methionine synthetase can lead to the Subacute combined degeneration of spinal cord, an effect that has been reported as result of long-term abuse of nitrous oxide.  Another field relevant to the study of the neurological effects of nitrous oxide is paediatrics, as brain development is a focal point in paediatric anaesthesiology. Recent studies in the field have directed their focus to the impact of anaesthetics in brain development. Human brain development continues at a fast pace after birth, during a period of synaptogenesis, which prolongs for several years. It is during this phase that neurons rearrange themselves forming synaptic connections, and in this phase happens that some unnecessary neurons die out, in a process of apoptosis. This leads to fearing that anaesthetics such as nitrous oxide might accelerate the process of apoptosis, leading to o neurotoxic effect.  Nitrous oxide has been in use for many years without the observation of negative effects in children, but some new evidence as show that nitrous oxide might be damaging to the developing brains of children.

Dangers

Nitrous oxide as several associated threats, as dissociative anaesthetic, as compressed liquefied gas, and it also poses an asphyxiation risk. There are several adverse effects associated with exposure to nitrous oxide, such as short-term decreases in mental acuteness, visual and audio perception, and eye–hand coordination. As for long-term effects deriving from exposure to nitrous oxide, we can name B12 deficiency, reduction in reproductive health in pregnant females, among other questions.

Chemical and Physical Dangers

Nitrous oxide, as other heavy-duty oxidizing agents, has been considered the reason for several accidents with rockets. In these cases, the mixing of small amounts of nitrous oxide and fuel explode, because of a “water hammer” effects. These effects are sometimes known as “dieseling”, meaning the increase in temperature triggered by adiabatic compression of gases until they reach decomposition temperatures. This kind reaction can also happen with common building materials, such as stainless steel and aluminium, with these acting as fuel ignited by the presence of nitrous oxide.