Inhalational anaesthetic
Encyclopedia
An inhalational anaesthetic is a chemical compound possessing general anaesthetic
properties that can be delivered via inhalation. They are administered by anaesthetists (a term which includes anaesthesiologist
s, nurse anaesthetist
s, and anaesthesiologist assistants) through an anaesthesia mask, laryngeal mask airway
or tracheal tube
connected to some type of anaesthetic vaporiser
and an anaesthetic delivery system
. Agents of significant contemporary clinical interest include volatile
anaesthetic agents such as isoflurane
, sevoflurane
and desflurane
, as well as certain anaesthetic gases such as nitrous oxide
and xenon
.
Previously used agents
Although some of these are still used in clinical practice and in research, the following anaesthetic agents are primarily of historical interest in developed countries
:
Future agents
(i.e., as liquids, they are not freely miscible
with water, and as gases they dissolve in oils better than in water). The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of general anaesthesia
with minimal effects on other organ
systems. In addition it is odourless or pleasant to inhale; safe for all ages and in pregnancy
; not metabolised; rapid in onset and offset; potent; and safe for exposure to operating room staff. It is also cheap to manufacture; easy to transport and store, with a long shelf life
; easy to administer and monitor with existing equipment; stable to light
, plastic
s, metal
s, rubber and soda lime
; non-flammable and environmentally safe. None of the agents currently in use are ideal, although many have some of the desirable characteristics. For example, sevoflurane is pleasant to inhale and is rapid in onset and offset. It is also safe for all ages. However, it is expensive (approximately 3 to 5 times more expensive than isoflurane), and approximately half as potent as isoflurane.
es or vapours which produce general anaesthesia by inhalation include nitrous oxide, cyclopropane and xenon. These are stored in gas cylinder
s and administered using flowmeters
, rather than vaporisers. Cyclopropane is explosive
and is no longer used for safety reasons, although otherwise it was found to be an excellent anaesthetic. Xenon is odourless and rapid in onset, but is expensive and requires specialised equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anaesthesia in most persons at standard atmospheric pressure, so it must be used as an adjunct anaesthetic, along with other agents.
s above normal atmospheric pressure
), other gases such as nitrogen
, and noble gas
es such as argon
, krypton
, and xenon become anaesthetics. When inhaled at high partial pressure
s (more than about 4 bar, encountered at depths below about 30 metres in scuba diving
), nitrogen begins to act as an anaesthetic agent, causing nitrogen narcosis
. However, the minimum alveolar concentration
(MAC) for nitrogen is not achieved until pressures of about 20 to 30 atm (bar) are attained. Argon is slightly more than twice as anaesthetic as nitrogen per unit of partial pressure (see argox). Xenon however is a usable anaesthetic at 80% concentration and normal atmospheric pressure.
"Most of the injectable anesthetics appear to act on a single molecular target," says Sonner. "It looks like inhaled anesthetics act on multiple molecular targets. That makes it a more difficult problem to pick apart."
The possibility of anaesthesia by the inert gas argon in particular (even at 10 to 15 bar) suggests that the mechanism of action of volatile anaesthetics is an effect best described by physical chemistry
, and not a chemical bond
ing action. However, the agent may bind to a receptor with a weak interaction . A physical interaction such as swelling of nerve cell membranes from gas solution in the lipid bilayer may be operative. Notably, the gases hydrogen, helium, and neon have not been found to have anaesthetic properties at any pressure. Helium at high pressures produces nervous irritation ("anti-anaesthesia"), suggesting that the anaesthetic mechanism(s) may be operated in reverse by this gas (i.e., nerve membrane compression).
General anaesthetic
A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...
properties that can be delivered via inhalation. They are administered by anaesthetists (a term which includes anaesthesiologist
Anesthesiologist
An anesthesiologist or anaesthetist is a physician trained in anesthesia and peri-operative medicine....
s, nurse anaesthetist
Nurse anesthetist
A nurse anesthetist is a nurse who specializes in the administration of anesthesia.In the United States, a Certified Registered Nurse Anesthetist is an advanced practice registered nurse who has acquired graduate-level education and board certification in anesthesia...
s, and anaesthesiologist assistants) through an anaesthesia mask, laryngeal mask airway
Laryngeal mask airway
The laryngeal mask airway is a supraglottic airway device invented by Archie Brain, a British anaesthetist.-Description:Laryngeal masks consist of a tube with an inflatable cuff that is inserted into the pharynx. Laryngeal mask airways come in a variety of sizes ranging from large adult to infant...
or tracheal tube
Tracheal tube
A tracheal tube is a catheter that is inserted into the trachea in order for the primary purpose of establishing and maintaining a patent airway and to ensure the adequate exchange of oxygen and carbon dioxide. Many different types of tracheal tubes are available, suited for different specific...
connected to some type of anaesthetic vaporiser
Anaesthetic vaporiser
An anaesthetic vaporiser is a device generally attached to an anaesthetic machine which delivers a given concentration of a volatile anaesthetic agent.The design of these devices takes account of varying*ambient temperature*fresh gas flow...
and an anaesthetic delivery system
Anaesthetic machine
The anaesthetic machine is used by anaesthesiologists and nurse anaesthetists to support the administration of anaesthesia...
. Agents of significant contemporary clinical interest include volatile
Volatility (chemistry)
In chemistry and physics, volatility is the tendency of a substance to vaporize. Volatility is directly related to a substance's vapor pressure. At a given temperature, a substance with higher vapor pressure vaporizes more readily than a substance with a lower vapor pressure.The term is primarily...
anaesthetic agents such as isoflurane
Isoflurane
Isoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...
, sevoflurane
Sevoflurane
Sevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...
and desflurane
Desflurane
Desflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...
, as well as certain anaesthetic gases such as nitrous oxide
Nitrous oxide
Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
and xenon
Xenon
Xenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...
.
List of inhalational anaesthetic agents
Currently used agents- isofluraneIsofluraneIsoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...
- desfluraneDesfluraneDesflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...
- nitrous oxideNitrous oxideNitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
- sevofluraneSevofluraneSevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...
Previously used agents
Although some of these are still used in clinical practice and in research, the following anaesthetic agents are primarily of historical interest in developed countries
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...
:
- aliflurane
- chloroformChloroformChloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
- cyclopropaneCyclopropaneCyclopropane is a cycloalkane molecule with the molecular formula C3H6, consisting of three carbon atoms linked to each other to form a ring, with each carbon atom bearing two hydrogen atoms...
- diethyl etherDiethyl etherDiethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
- enfluraneEnfluraneEnflurane is a halogenated ether that was commonly used for inhalational anesthesia during the 1970s and 1980s. Developed by Ross Terrell in 1963, it was first used clinically in 1966....
- ethyleneEthyleneEthylene is a gaseous organic compound with the formula . It is the simplest alkene . Because it contains a carbon-carbon double bond, ethylene is classified as an unsaturated hydrocarbon. Ethylene is widely used in industry and is also a plant hormone...
- halothaneHalothaneHalothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
- methoxyfluraneMethoxyfluraneMethoxyflurane is a halogenated ether that was in clinical use as an volatile inhalational anesthetic from its introduction by Joseph F. Artusio et al in 1960 until around 1974. It was first synthesized in the late 1940s by William T...
- methoxypropane
- roflurane
- teflurane
- trichloroethyleneTrichloroethyleneThe chemical compound trichloroethylene is a chlorinated hydrocarbon commonly used as an industrial solvent. It is a clear non-flammable liquid with a sweet smell. It should not be confused with the similar 1,1,1-trichloroethane, which is commonly known as chlorothene.The IUPAC name is...
- vinyl etherVinyl etherVinyl ether, also known as divinyl ether, divinyl oxide, Vinethene and ethenoxyethene , is a clear, nearly colorless, volatile liquid which was briefly used as an inhalation anesthetic...
Future agents
- xenonXenonXenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...
Volatile anaesthetics
Volatile anaesthetic agents share the property of being liquid at room temperature, but evaporating easily for administration by inhalation. All of these agents share the property of being quite hydrophobicHydrophobe
In chemistry, hydrophobicity is the physical property of a molecule that is repelled from a mass of water....
(i.e., as liquids, they are not freely miscible
Miscibility
Miscibility is the property of liquids to mix in all proportions, forming a homogeneous solution. In principle, the term applies also to other phases , but the main focus is usually on the solubility of one liquid in another...
with water, and as gases they dissolve in oils better than in water). The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of general anaesthesia
General anaesthesia
General anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...
with minimal effects on other organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
systems. In addition it is odourless or pleasant to inhale; safe for all ages and in pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
; not metabolised; rapid in onset and offset; potent; and safe for exposure to operating room staff. It is also cheap to manufacture; easy to transport and store, with a long shelf life
Shelf life
Shelf life is the length of time that food, drink, medicine, chemicals, and many other perishable items are given before they are considered unsuitable for sale, use, or consumption...
; easy to administer and monitor with existing equipment; stable to light
Light
Light or visible light is electromagnetic radiation that is visible to the human eye, and is responsible for the sense of sight. Visible light has wavelength in a range from about 380 nanometres to about 740 nm, with a frequency range of about 405 THz to 790 THz...
, plastic
Plastic
A plastic material is any of a wide range of synthetic or semi-synthetic organic solids used in the manufacture of industrial products. Plastics are typically polymers of high molecular mass, and may contain other substances to improve performance and/or reduce production costs...
s, metal
Metal
A metal , is an element, compound, or alloy that is a good conductor of both electricity and heat. Metals are usually malleable and shiny, that is they reflect most of incident light...
s, rubber and soda lime
Soda lime
Soda lime is a mixture of chemicals, used in granular form in closed breathing environments, such as general anaesthesia, submarines, rebreathers and recompression chambers, to remove carbon dioxide from breathing gases to prevent CO2 retention and carbon dioxide poisoning.It is made by treating...
; non-flammable and environmentally safe. None of the agents currently in use are ideal, although many have some of the desirable characteristics. For example, sevoflurane is pleasant to inhale and is rapid in onset and offset. It is also safe for all ages. However, it is expensive (approximately 3 to 5 times more expensive than isoflurane), and approximately half as potent as isoflurane.
Gases
Other gasGas
Gas is one of the three classical states of matter . Near absolute zero, a substance exists as a solid. As heat is added to this substance it melts into a liquid at its melting point , boils into a gas at its boiling point, and if heated high enough would enter a plasma state in which the electrons...
es or vapours which produce general anaesthesia by inhalation include nitrous oxide, cyclopropane and xenon. These are stored in gas cylinder
Gas cylinder
A gas cylinder is a pressure vessel used to store gases at above atmospheric pressure. High pressure gas cylinders are also called bottles. Although they are sometimes colloquially called "tanks", this is technically incorrect, as a tank is a vessel used to store liquids at ambient pressure and...
s and administered using flowmeters
Flow measurement
Flow measurement is the quantification of bulk fluid movement. Flow can be measured in a variety of ways.Positive-displacement flow meters acumulate a fixed volume of fluid and then count the number of times the volume is filled to measure flow...
, rather than vaporisers. Cyclopropane is explosive
Explosive material
An explosive material, also called an explosive, is a reactive substance that contains a great amount of potential energy that can produce an explosion if released suddenly, usually accompanied by the production of light, heat, sound, and pressure...
and is no longer used for safety reasons, although otherwise it was found to be an excellent anaesthetic. Xenon is odourless and rapid in onset, but is expensive and requires specialised equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anaesthesia in most persons at standard atmospheric pressure, so it must be used as an adjunct anaesthetic, along with other agents.
Hyperbaric anaesthesia
Under hyperbaric conditions (pressurePressure
Pressure is the force per unit area applied in a direction perpendicular to the surface of an object. Gauge pressure is the pressure relative to the local atmospheric or ambient pressure.- Definition :...
s above normal atmospheric pressure
Atmospheric pressure
Atmospheric pressure is the force per unit area exerted into a surface by the weight of air above that surface in the atmosphere of Earth . In most circumstances atmospheric pressure is closely approximated by the hydrostatic pressure caused by the weight of air above the measurement point...
), other gases such as nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
, and noble gas
Noble gas
The noble gases are a group of chemical elements with very similar properties: under standard conditions, they are all odorless, colorless, monatomic gases, with very low chemical reactivity...
es such as argon
Argon
Argon is a chemical element represented by the symbol Ar. Argon has atomic number 18 and is the third element in group 18 of the periodic table . Argon is the third most common gas in the Earth's atmosphere, at 0.93%, making it more common than carbon dioxide...
, krypton
Krypton
Krypton is a chemical element with the symbol Kr and atomic number 36. It is a member of Group 18 and Period 4 elements. A colorless, odorless, tasteless noble gas, krypton occurs in trace amounts in the atmosphere, is isolated by fractionally distilling liquified air, and is often used with other...
, and xenon become anaesthetics. When inhaled at high partial pressure
Partial pressure
In a mixture of ideal gases, each gas has a partial pressure which is the pressure which the gas would have if it alone occupied the volume. The total pressure of a gas mixture is the sum of the partial pressures of each individual gas in the mixture....
s (more than about 4 bar, encountered at depths below about 30 metres in scuba diving
Scuba diving
Scuba diving is a form of underwater diving in which a diver uses a scuba set to breathe underwater....
), nitrogen begins to act as an anaesthetic agent, causing nitrogen narcosis
Nitrogen narcosis
Narcosis while diving , is a reversible alteration in consciousness that occurs while scuba diving at depth. The Greek word ναρκωσις is derived from narke, "temporary decline or loss of senses and movement, numbness", a term used by Homer and Hippocrates...
. However, the minimum alveolar concentration
Minimum alveolar concentration
Minimum alveolar concentration or MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours; in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus...
(MAC) for nitrogen is not achieved until pressures of about 20 to 30 atm (bar) are attained. Argon is slightly more than twice as anaesthetic as nitrogen per unit of partial pressure (see argox). Xenon however is a usable anaesthetic at 80% concentration and normal atmospheric pressure.
Neurological theories of action
The full mechanism of action of volatile anaesthetic agents is unknown and has been the subject of intense debate. "Anesthetics have been used for 160 years, and how they work is one of the great mysteries of neuroscience," says anaesthesiologist James Sonner of the University of California, San Francisco. Anaesthesia research "has been for a long time a science of untestable hypotheses," notes Neil L. Harrison of Cornell University."Most of the injectable anesthetics appear to act on a single molecular target," says Sonner. "It looks like inhaled anesthetics act on multiple molecular targets. That makes it a more difficult problem to pick apart."
The possibility of anaesthesia by the inert gas argon in particular (even at 10 to 15 bar) suggests that the mechanism of action of volatile anaesthetics is an effect best described by physical chemistry
Physical chemistry
Physical chemistry is the study of macroscopic, atomic, subatomic, and particulate phenomena in chemical systems in terms of physical laws and concepts...
, and not a chemical bond
Chemical bond
A chemical bond is an attraction between atoms that allows the formation of chemical substances that contain two or more atoms. The bond is caused by the electromagnetic force attraction between opposite charges, either between electrons and nuclei, or as the result of a dipole attraction...
ing action. However, the agent may bind to a receptor with a weak interaction . A physical interaction such as swelling of nerve cell membranes from gas solution in the lipid bilayer may be operative. Notably, the gases hydrogen, helium, and neon have not been found to have anaesthetic properties at any pressure. Helium at high pressures produces nervous irritation ("anti-anaesthesia"), suggesting that the anaesthetic mechanism(s) may be operated in reverse by this gas (i.e., nerve membrane compression).
See also
- A.C.E. mixtureA.C.E. mixtureA.C.E. mixture is an old anaesthetic agent for general anaesthesia, which was first suggested by Dr. George Harley and first used in England around 1860, and in 1864 it was recommended for use by the Royal Medical and Surgical Society’s Chloroform Committee...
- a mixture of ethanolEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, chloroform and diethyl ether - Anaesthetic