Nitrous oxide (medication)

Last updated

Nitrous oxide
Entonox set.png
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
  • 50/50 mix of nitrous oxide and oxygen: ℞ (prescription only)
Pharmacokinetic data
Metabolism Not metabolized
Metabolites None
Onset of action 30 seconds [1]
Duration of action 1 minute [1]
Excretion Exhaled
Identifiers
CAS Number
PubChem CID
  • Nitrous oxide: 948
  • Oxygen: 977
DrugBank
ChemSpider
  • Nitrous oxide: 923
  • Oxygen: 952
UNII
ChEBI
ChEMBL
Chemical and physical data
Formula N2O
Molar mass 44.013 g·mol−1
3D model (JSmol)
  • Nitrous oxide: [N-]=[N+]=O
  • Nitrous oxide: InChI=1S/N2O/c1-2-3
  • Key:GQPLMRYTRLFLPF-UHFFFAOYSA-N

Nitrous oxide, as medical gas supply, is an inhaled gas used as pain medication, and is typically administered with 50% oxygen mix. It is often used together with other medications for anesthesia. [2] Common uses include during childbirth, following trauma, and as part of end-of-life care. [2] Onset of effect is typically within half a minute, and the effect lasts for about a minute. [1]

Contents

Nitrous oxide was discovered between 1772 and 1793 and used for anesthesia in 1844. [3] It is on the World Health Organization's List of Essential Medicines. [4] It often comes as a 50/50 mixture with oxygen. [1] Devices with a demand valve are available for self-administration. [5] The setup and maintenance is relatively expensive for developing countries. [6] [7]

There are few side effects, other than vomiting, with short-term use. [1] [2] With long-term use anemia or numbness may occur. [2] It should always be given with at least 21% oxygen. [2] It is not recommended in people with a bowel obstruction or pneumothorax. [2] Use in the early part of pregnancy is not recommended. [1] It is possible to continue breastfeeding following use. [8]

History

Administration of nitrous oxide, 1870 Adminsitration of nitrous oxide Wellcome L0013787.jpg
Administration of nitrous oxide, 1870

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. [10] [11]

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 and New 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 caused hypoxia (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). [11] 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. [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 a relative analgesia machine, which includes several improvements such as flowmeters and constant-flow regulators, an anaesthetic vaporiser, a medical ventilator, and a scavenger system, and delivers a precisely dosed and breath-actuated flow of nitrous 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 a demand-valve inhaler over the nose, which will only release gas when the patient inhales through it.[ citation needed ]

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–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 in managing pain during labor and delivery. [15]

Nitrous oxide has been shown to be an effective and safe treatment for alcohol 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 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 route morphine [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]

Contraindications

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 been scuba 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]

Composition

The gas is a mixture of half nitrous oxide (N2O) and half oxygen (O2). [1] [23] 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). [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]

Inhalation of pure N2O over a continued period would deprive the patient of oxygen, [24] but the 50% oxygen content prevents this from occurring. The two gases will separate at low temperatures (<4 °C), 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.

Administration

The gas is self-administered through a demand 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 an anaesthetist 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.[ citation needed ]

Mechanism of action

The pharmacological mechanism of action of N
2O in medicine is not fully known. However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocks NMDAR and β2-subunit-containing nACh channels, weakly inhibits AMPA, kainate, GABAC and 5-HT3 receptors, and slightly potentiates GABAA and glycine receptors. [25] [26] It also has been shown to activate two-pore-domain K+
 channels. [27] While N
2O affects quite a few ion channels, its anesthetic, hallucinogenic and euphoriant 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 imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties. [28] Nitrous oxide is 30 to 40 times more soluble than nitrogen.

Society and culture

Nitronox was a registered trademark of the 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]

Research

Investigational trials show potential for antidepressant applications of N2O, especially for treatment-resistant forms of depression, 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]

Related Research Articles

General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Nitrous oxide</span> Colourless non-flammable greenhouse gas

Nitrous oxide, commonly known as laughing gas, nitrous, or factitious air, among others, is a chemical compound, an oxide of nitrogen with the formula N
2O. At room temperature, it is a colourless non-flammable gas, and has a slightly sweet scent and taste. At elevated temperatures, nitrous oxide is a powerful oxidiser similar to molecular oxygen.

<span class="mw-page-title-main">Anesthesia</span> State of medically-controlled temporary loss of sensation or awareness

Anesthesia or anaesthesia 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, paralysis, amnesia, and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized.

<span class="mw-page-title-main">Isoflurane</span> General anaesthetic given via inhalation

Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane. Isoflurane is given via inhalation.

<span class="mw-page-title-main">Sevoflurane</span> Inhalational anaesthetic

Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset. While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.

<span class="mw-page-title-main">Anaesthetic machine</span> Medical device to supply a mix of life-support and anaesthetic gases

An anaesthetic machine or anesthesia machine is a medical device used to generate and mix a fresh gas flow of medical gases and inhalational anaesthetic agents for the purpose of inducing and maintaining anaesthesia.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Horace Wells</span> American dentist who pioneered the use of anesthesia (1815–1848)

Horace Wells was an American dentist who pioneered the use of anesthesia in medicine, specifically the use of nitrous oxide.

<span class="mw-page-title-main">Inhalational anesthetic</span> Volatile or gaseous anesthetic compound delivered by inhalation

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

<span class="mw-page-title-main">Halogenated ether</span> Subcategory of ether used in anesthesiology

Halogenated ethers are a subcategory of ethers—organic chemicals that containan oxygen atom connected to two alkyl groups or similar structures. An example of an ether is the solvent diethyl ether. Halogenated ethers differ from other ethers because there are one or more halogen atoms—fluorine, chlorine, bromine, or iodine—as substituents on the carbon groups.. Examples of commonly used halogenated ethers include isoflurane, sevofluorane and desflurane.

<span class="mw-page-title-main">Methoxyflurane</span> Chemical compound

Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is rapid and of a short duration. Use is only recommended with direct medical supervision.

Veterinary anesthesia is a specialization in the veterinary medicine field dedicated to the proper administration of anesthetic agents to non-human animals to control their consciousness during procedures. A veterinarian or a Registered Veterinary Technician administers these drugs to minimize stress, destructive behavior, and the threat of injury to both the patient and the doctor. The duration of the anesthesia process goes from the time before an animal leaves for the visit to the time after the animal reaches home after the visit, meaning it includes care from both the owner and the veterinary staff. Generally, anesthesia is used for a wider range of circumstances in animals than in people not only due to their inability to cooperate with certain diagnostic or therapeutic procedures, but also due to their species, breed, size, and corresponding anatomy. Veterinary anesthesia includes anesthesia of the major species: dogs, cats, horses, cattle, sheep, goats, and pigs, as well as all other animals requiring veterinary care such as birds, pocket pets, and wildlife.

Dental anesthesia is the application of anesthesia to dentistry. It includes local anesthetics, sedation, and general anesthesia.

The Fink effect, also known as "diffusion anoxia", "diffusion hypoxia", or the "second gas effect", is a factor that influences the pO2 (partial pressure of oxygen) within the pulmonary alveoli. When water-soluble gases such as anesthetic agent N2O (nitrous oxide) are breathed in large quantities they can be dissolved in body fluids rapidly. This leads to a temporary increase in both the concentrations and partial pressures of oxygen and carbon dioxide in the alveoli.

<span class="mw-page-title-main">History of general anesthesia</span>

Throughout recorded history, attempts at producing a state of general anesthesia can be traced back to the writings of ancient Sumerians, Babylonians, Assyrians, Akkadians, Egyptians, Persians, Indians, and Chinese.

Obstetric anesthesia or obstetric anesthesiology, also known as ob-gyn anesthesia or ob-gyn anesthesiology, is a sub-specialty of anesthesiology that provides peripartum pain relief (analgesia) for labor and anesthesia for cesarean deliveries ('C-sections').

<span class="mw-page-title-main">Inhalation sedation</span>

Inhalation sedation is a form of conscious sedation where an inhaled drug should:

  1. Depress the central nervous system (CNS) to an extent that surgeons can operate with minimal physiological and psychological stress to the patient
  2. Modify the patient's state of mind such that communication is maintained and the patient can respond to verbal command
  3. Carry a margin of safety wide enough to render the unintended loss of consciousness and loss of protective reflexes unlikely.
<span class="mw-page-title-main">Peter Baskett</span> Northern Irish physician

Peter John Firth Baskett (1934–2008) was a Northern Irish physician, specializing in anaesthesia. He was responsible for the introduction of paramedics into the United Kingdom, created specialist ambulances for delivering on-scene pain relief to patients, and was the first chairman of the European Resuscitation Council.

Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Anaesthesia UK : Entonox". www.frca.co.uk. 26 January 2009. Archived from the original on 31 October 2007. Retrieved 15 December 2016.
  2. 1 2 3 4 5 6 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 20. hdl: 10665/44053 . ISBN   9789241547659.
  3. ↑ Myers RL (2007). 100 Most Important Chemical Compounds, The: A Reference Guide: A Reference Guide. ABC-CLIO. p. 198. ISBN   9780313080579. Archived from the original on 2016-12-20.
  4. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  5. ↑ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 878. ISBN   9780857111562.
  6. ↑ Gregory GA, Andropoulos DB (2012). Gregory's Pediatric Anesthesia, With Wiley Desktop Edition. John Wiley & Sons. p. 1148. ISBN   9781444333466. Archived from the original on 2016-12-20.
  7. ↑ WHO model prescribing information : drugs used in anaesthesia. World Health Organization. 1989. hdl: 10665/41014 . ISBN   92-4-140101-X.
  8. ↑ "Nitrous Oxide use while Breastfeeding". Drugs.com. Archived from the original on 21 December 2016. Retrieved 15 December 2016.
  9. ↑ Thomas FR (1870). "Manual of the discovery, manufacture, and administration of nitrous oxide, or laughing gas in its relations to dental or minor surgical operations, and particularly for the painless extraction of teeth". Philadelphia : S.S. White. Retrieved 17 December 2018.
  10. ↑ Erving HW (May 1933). "The Discoverer of Anæsthesia: Dr. Horace Wells of Hartford". The Yale Journal of Biology and Medicine. 5 (5): 421–430. PMC   2606479 . PMID   21433572. Archived from the original on 2012-12-23.
  11. 1 2 3 "History of Entonox". BOC Gases. Archived from the original on 2009-07-05. Retrieved 2009-04-11.
  12. ↑ Sneader W (2005). "Part 1: Legacy of the past, chapter 8: systematic medicine". Drug Discovery –A History. John Wiley and Sons. pp. 74–87. ISBN   978-0-471-89980-8 . Retrieved 21 April 2010.
  13. ↑ Miller AH (1941). "Technical Development of Gas Anesthesia". Anesthesiology. 2 (4): 398–409. doi: 10.1097/00000542-194107000-00004 . S2CID   71117361.
  14. ↑ Baskett PJ (April 1970). "Use of Entonox in the ambulance service". British Medical Journal. 2 (5700): 41–43. doi:10.1136/bmj.2.5700.41. PMC   1699783 . PMID   5440577.
  15. ↑ Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. (March 2012). "Pain management for women in labour: an overview of systematic reviews". The Cochrane Database of Systematic Reviews. 2012 (3): CD009234. doi:10.1002/14651858.CD009234.pub2. PMC   7132546 . PMID   22419342.
  16. ↑ Gillman M.A, Lichtigfeld, F.J. 2004 Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal, Addictive Behaviors, Volume 29, Issue 6, Pages 1183–1187
  17. ↑ Gao HX, Zhang JJ, Liu N, Wang Y, Ma CX, Gao LL, et al. (January 2021). "A fixed nitrous oxide/oxygen mixture as an analgesic for patients with postherpetic neuralgia: study protocol for a randomized controlled trial". Trials. 22 (1): 29. doi: 10.1186/s13063-020-04960-5 . PMC   7787626 . PMID   33407845.
  18. ↑ Parbrook GD (December 1967). "The levels of nitrous oxide analgesia". British Journal of Anaesthesia. 39 (12): 974–982. doi: 10.1093/bja/39.12.974 . PMID   4865545.
  19. ↑ Clar DT, Patel S, Richards JR (2022). "Anesthetic Gases". StatPearls. PMID   30725698. NBK537013.
  20. ↑ Knuf K, Maani CV (2022). "Nitrous Oxide". StatPearls. PMID   30422517. NBK532922.
  21. ↑ "Entonox: The essential guide" (PDF). BOC online. Retrieved 2023-12-24.
  22. ↑ Komesaroff D (1998). "Oxygen administration in diving accidents". South Pacific Underwater Medicine Society Journal. 28 (3 Supplement).
  23. 1 2 3 Fisher J, Brown S, Cooke M (2006). UK Ambulance Service Clinical Practice Guidelines (PDF). Joint Royal Colleges Ambulance Liaison Committee. ISBN   978-1-84690-060-0. Archived (PDF) from the original on 2011-06-05.
  24. ↑ "Breathing Nitrous Oxide". Nitrous Oxide Supplies. Archived from the original on 2009-02-16.
  25. 1 2 Yamakura T, Harris RA (October 2000). "Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol". Anesthesiology. 93 (4): 1095–1101. doi: 10.1097/00000542-200010000-00034 . PMID   11020766. S2CID   4684919.
  26. ↑ Mennerick S, Jevtovic-Todorovic V, Todorovic SM, Shen W, Olney JW, Zorumski CF (December 1998). "Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures". The Journal of Neuroscience. 18 (23): 9716–9726. doi:10.1523/JNEUROSCI.18-23-09716.1998. PMC   6793274 . PMID   9822732.
  27. ↑ Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP (February 2004). "Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane". Molecular Pharmacology. 65 (2): 443–452. doi:10.1124/mol.65.2.443. PMID   14742687. S2CID   7762447.
  28. 1 2 Emmanouil DE, Quock RM (2007). "Advances in understanding the actions of nitrous oxide". Anesthesia Progress. 54 (1): 9–18. doi:10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2. PMC   1821130 . PMID   17352529.
  29. ↑ "NITRONOX Trademark Information". trademarkia. Archived from the original on 2017-09-10. Retrieved 2017-07-11.
  30. ↑ "Entonox (gas and air)". Baby Centre. Archived from the original on 2006-11-11.
  31. ↑ Nagele P, Duma A, Kopec M, Gebara MA, Parsoei A, Walker M, et al. (July 2015). "Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial". Biological Psychiatry. 78 (1): 10–18. doi: 10.1016/j.biopsych.2014.11.016 . PMID   25577164.
  32. ↑ Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB (October 2015). "Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression". The American Journal of Psychiatry. 172 (10): 950–966. doi: 10.1176/appi.ajp.2015.15040465 . PMID   26423481.
  33. 1 2 Nagele P, Palanca BJ, Gott B, Brown F, Barnes L, Nguyen T, et al. (June 2021). "A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression". Science Translational Medicine. 13 (597): eabe1376. doi:10.1126/scitranslmed.abe1376. PMID   34108247. S2CID   235381316.
  34. ↑ Mozes A (2021-06-10). "'Laughing Gas' May Help Tough-to-Treat Depression". WebMD. Retrieved 2021-06-15.
  35. ↑ de Leon VC, Kumar A, Nagele P, Palanca BJ, Gott B, Janski A, et al. (August 2023). "Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis". The Journal of Clinical Psychiatry. 84 (5): 48436. doi:10.4088/JCP.22br14725. PMC   11097146 . PMID   37585253.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.