Nitrous oxide

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structure

nitrous-oxide_3d_mid.jpg


Contents

Introduction

Nitrous oxide (N2O is a colourless, odourless, sweet tasting gas which has been widely used as a general anaesthetic drug. Its molecular weight is 44, the same as that of carbon dioxide). It is stable and inert at room temperature.

It is a weak anaesthetic agent (MAC 101%) so can not be used alone to induce 'surgical anaesthesia'. In most cases, its use is supplemented by other more potent anaesthetic agents, such as IV anaesthetics, or volatile anaesthetics.

It was one of the first anaesthetic agents used and still remains in wide use. Over the last 20 years, an increased awareness of the adverse effects associated with its use, and the availability of alternative drugs and techniques has resulted in a decline in its popularity and clinical use.

Nitrous oxide is not metabolised (except perhaps to a minute degree) in the body.

The mechanism of action is often described as unknown, but recent evidence suggests it acts predominantly as an NMDA receptor antagonist.

Nitrous oxide is also available in cylinders in a pre-mixed 50:50 mixture with oxygen known as Entonox

History

Joseph Priestley, an English scientist, discovered nitrous oxide in 1793. He prepared the gas by heating ammonium nitrate (with some iron filings) and then passed the gas through water to remove toxic byproducts.

Humphrey Davy (at the Pnuematic Institute, Bristol, UK) studied the gas to test for physiologic properties. He invented the common name "laughing gas" because inhalation of the gas induced a state of giddiness and laughter. The gas was subsequently used predominantly as an amusement for this effect.

nitrous-oxide.jpg

In the 1840s, Gardner Quincy Colton, a failed medical student, travelled to various places giving exhibitions of the effects of nitrous oxide.

During such an event in Hartford, Connecticut, USA, a local dentist, Horace Wells was impressed by the the analgesic qualities of nitrous oxide when a man under the influence of nitrous oxide did not display any pain after sustaining a leg injury. Wells used the gas as an analgesic in his dental practice. A demonstration of the use of nitrous oxide at the Harvard Medical School was a failure primarily because of the low anaesthetic potency of the gas. He suffered public humiliation and later committed suicide. The popularity of nitrous oxide in dental practice waned for a while after this but later became widely used.


Physical Properties

N2O is supplied as liquid/gas in French blue cylinders. The pressure in the cylinder is the saturated vapour pressure of N2O at that temperature, provided that some liquid remains within the cylinder. For example, the pressure is 40 atm at 15 degrees C and 54 atm at room temp. The pressure in the cylinder remains constant (provided the temperature remains constant) until the liquid has all evaporated, after which the pressure falls as gas is removed from the cylinder.

N2O1a.jpg Nitrous oxide cylinder

The significance of this is that the content remaining in the cylinder cannot be determined by measuring the cylinder pressure. In contrast, O2 cylinders contain only compressed gas so their content of oxygen is proportional to the cylinder pressure.

Nitous oxide is a colourless, odourless, sweet tasting gas with a molecular weight of 44 (=14+14+16).

It has a low blood-gas partition coefficient of 0.47 and consequently onset and offset of action are rapid (few minutes). It is a nonflammable gas, but will support combustion and will detonate at temperatures > 650C.

Other properties:

  • Oil/gas partition coefficient: 1.4
  • Boiling point: -88.46C
  • Melting point: -90.81C
  • Critical temperature: 36.6C
  • Critical pressure 71.7 atm
  • MAC 105%

Chemical Properties

Nitrous oxide is produced by heating of ammonium nitrate at 170-180C in the presence of a catalyst. This thermal decomposition process was invented by Berthollet in 1785 and is now widely used.


  • formula
  • impurities
  • stability & preservatives; exclusion of light; decomposition products & their effects; tests for decomposition
  • class of the compound; acid, base, ester, simple compound
  • structure-activity relationships - ionised (water-soluble), unionised (lipid soluble); molecular size; similarity to other drugs


Pharmacokinetics

  • Administration, absorption
  • Distribution, incl VD , plasma protein binding, tissue affinities
  • Elimination - Biotransformation, metabolic products & their actions
  • Elimination - Excretion
  • Special features - enzyme induction, cumulation, effects of age


Pharmacodynamics

Initial

  • Target organs/desired effects
  • side effects
  • toxic effects

System effects

  • CNS
  • Autonomic nervous system
  • CVS
  • Respiratory system
  • Skeletal system
  • GIT
  • Blood
  • Metabolism
  • Genitrourinary system
  • Endocrine system
  • Immune system

Clinical Uses

  • Dosage, administration
  • Blood levels, expected duration
  • Advantages, disadvantages, side effects, toxic effects
  • Indications, contraindications
  • Antagonists
  • Interactions
  • Controversies, recent research

Miscellaneous

Other uses of nitrous oxide are:

  • injector system to provide a power boost for racing cars or motor bikes. (In racing, this is illegal.)
  • use in sparklets for whipped cream production

Nitrous oxide is a greenhouse gas. About 10 million tons are added to the atmosphere each year from natural sources (predominantly from the soil and oceans) and 8 million tons are added each year as a consequence of the activities of man. The majority of the man-made contribution is from agricultural soils (fertilisers). Only a very small amount is due to anaesthetic use.

Related Material

  • links to relevant online material

References

  • Myles PS, Leslie K, Silbert B, Paech MJ, Peyton P. (2004) A review of the risks and benefits of nitrous oxide in current anaesthetic practice. Anaesth Intensive Care. 2004 Apr;32(2):165-72. PMID 15957712
  • Smith I (2006) Nitrous oxide in ambulatory anaesthesia: does it have a place in day surgical anaesthesia or is it just a threat for personnel and the global environment? Curr Opin Anaesthesiol. 2006 Dec;19(6):592-6. PMID 17093360
  • Hopkins PM (2005) Nitrous oxide: a unique drug of continuing importance for anaesthesia. Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):381-9. PMID 16013688
  • Jahn UR, Berendes E (2005) Nitrous oxide--an outdated anaesthetic. Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):391-7 PMID 16013689
  • Yentis SM, Hirsch NP, Smith GB. Anaesthesia and Intensive Care A-Z An Encycopledia of Principles and Practice 3rd Edition. p371
  • Nitrous oxide (Need password from ANZCA library page)
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