 Entonox CD cylinder and giving set | |
| Combination of | |
|---|---|
| Nitrous oxide | Analgesic gas (usually 50%) |
| Oxygen | Medical gas (usually 50%) |
| Clinical data | |
| Trade names | Entonox, Nitronox, others |
| Routes of administration | Inhalation |
| Drug class | NMDA receptor antagonist;Dissociative hallucinogen;Analgesic;General anesthetic |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Metabolism | Not metabolized |
| Metabolites | None |
| Onset of action | 30 seconds[1] |
| Duration of action | 1 minute[1] |
| Excretion | Exhaled |
| Identifiers | |
| CAS Number |
|
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII |
|
| ChEBI |
|
| ChEMBL |
|
| Chemical and physical data | |
| Formula | N2O |
| Molar mass | 44.013 g·mol−1 |
| 3D model (JSmol) |
|
| |
| |
Nitrous oxide, asmedical gas supply, is an inhaled gas used aspain medication, and is typically administered with 50% oxygen mix. It is often used together with othermedications foranesthesia.[2] Common uses include duringchildbirth, followingtrauma, and as part ofend-of-life care.[2] Onset of effect is typically within half a minute, and the effect lasts for about a minute.[1]
Nitrous oxide was discovered between 1772 and 1793 and used for anesthesia in 1844.[3] It is on theWorld Health Organization's List of Essential Medicines.[4] It often comes as a 50/50 mixture withoxygen.[1] Devices with ademand valve are available for self-administration.[5] The setup and maintenance is relatively inexpensive fordeveloping countries.[6][7]
There are few side effects, other thanvomiting, with short-term use.[1][2] With long-term useanemia ornumbness may occur.[2] It should always be given with at least 21%oxygen.[2] It is not recommended in people with abowel obstruction orpneumothorax.[2] Use in the early part ofpregnancy is not recommended.[1] It is possible to continuebreastfeeding following use.[8]
Pure N2O was first used as a medical analgesic in December 1844, whenHorace Wells made the first 12–15 dental operations with the gas inHartford.[10][11]
Its debut as a generally accepted method, however, came in 1863, whenGardner Quincy Colton introduced it more broadly at all the Colton Dental Association clinics, that he founded inNew Haven andNew York City.[12]
The first devices used in dentistry to administer the gas consisted of a simple breathing bag made of rubber cloth.[13]
Breathing the pure gas often causedhypoxia (oxygen insufficiency) and sometimes death byasphyxiation. Eventually practitioners became aware of the need to provide at least 21% oxygen content in the gas (the same percentage as in air).[11] In 1911, the anaesthetistArthur 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.[11]
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.[14]
Today the nitrous oxide is administered in hospitals by arelative analgesia machine, which includes several improvements such asflowmeters andconstant-flow regulators, ananaesthetic vaporiser, amedical ventilator, and ascavenger system, and delivers a precisely dosed and breath-actuated flow ofnitrous oxide mixed with oxygen.[citation needed]
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 ademand-valve inhaler over the nose, which will only release gas when the patient inhales through it.[citation needed]
Nitrous oxide (N2O) is itself active (does not require any changes in the body to become active), and so has an onset in roughly thelung–brain circulation time with peak action 30 seconds after the start of administration.[1] 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.[1] It is effective inmanaging pain during labor and delivery.[15]
Nitrous oxide has been shown to be an effective and safe treatment foralcohol withdrawal.[16]
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 withpneumothorax or those who have recently beenscuba diving, and there are cautions over its use with any bowel obstruction.
Its analgesic effect is strong (equivalent to 15 mg ofsubcutaneous routemorphine[1])[17][18] and characterised by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly.[citation needed]
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.[19][20]
N2O should not be used in patients with bowel obstruction, pneumothorax, or middle ear or sinus disease,[1] or who have had a recent intraocular injection of gas[21] and should also not be used on any patient who has beenscuba diving within the preceding 24 hours[22] or in violently disturbed psychiatric patients.[23]There are also clinical cautions in place for the first two trimesters of pregnancy and in patients with decreased levels of consciousness.[1]
The gas is a mixture of halfnitrous oxide (N2O) and halfoxygen (O2).[1][23] The ability to combine N2O and oxygen at high pressure while remaining in the gaseous form is caused by thePoynting effect (afterJohn Henry Poynting, an English physicist).[1] 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.[1]
Since the two substances are homogeneously mixed gases, the cylinder delivers a consistent 50/50 mixture all the way down to empty, even if the cylinder adiabatically cools somewhat from the discharge.[24]
Some N2O may condense into a liquid if the cylinder is cooled to low temperatures (−7 °C or below), which can be dangerous if unaddressed.[24] This occurs most easily with partially used / lower pressure cylinders. Even after warming the contents back into a gaseous state, they may remain nonhomogenous for days. Thus it is typically instructed to warm cylinders in a horizontal orientation (to maximize heat transfer) for a 48 hour period, then rehomogenize the gas by inverting the cylinder three times.[24]
The gas is self-administered through ademand valve, using a mouthpiece, bite block or face mask.[23] 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 ananaesthetist for administration. The 50% oxygen in Entonox ensures the person will have sufficient oxygen in theiralveoli and conducting airways for a short period ofapnea to be safe.[citation needed]
The pharmacologicalmechanism of action ofN
2O in medicine is not fully known. However, it has been shown to directly modulate a broad range ofligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocksNMDAR andβ2-subunit-containingnACh channels, weakly inhibitsAMPA,kainate,GABAC and5-HT3 receptors, and slightly potentiatesGABAA andglycine receptors.[25][26] It also has been shown to activatetwo-pore-domainK+
channels.[27] WhileN
2O affects quite a few ion channels, its anesthetic,hallucinogenic andeuphoriant effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents.[25][28] In addition to its effects on ion channels,N
2O may act to imitatenitric oxide (NO) in the central nervous system, and this may be related to itsanalgesic andanxiolytic properties.[28] Nitrous oxide is 30 to 40 times more soluble than nitrogen[citation needed].
Nitronox was a registered trademark ofthe BOC Group between 1966 and 1999,[29] and was reregistered by Hs Tm Inc since 2005[citation needed] It is also colloquially known as "gas and air" in the United Kingdom.[30]
Investigational trials show potential forantidepressant applications of N2O, especially fortreatment-resistant forms ofdepression, and it is rapid-acting.[31][32][33][34][35] In a phase 2 clinical trial, a treatment with 25% nitrous oxide had comparable efficacy to 50% nitrous oxide but was associated with significantly fewer adverse effects.[33]
