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.
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:
Volatile anaesthetic agents share the property of being liquid at room temperature, but evaporating easily for administration by inhalation. The volatile anesthetics used in the developed world today include: Desflurane, isoflurane and sevoflurane. Other agents widely used in the past include ether, chloroform, enflurane, halothane, methoxyflurane. All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with water, and as gases they dissolve in oils better than in water). [3]
The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of general anaesthesia with minimal effects on non-target organ systems. In addition it is odorless or pleasant to inhale; safe for all ages and in pregnancy; not metabolised; rapid in onset and offset; potent; safe for exposure to operating room staff; and has a long shelf life. It is also cheap to manufacture; easy to transport and store; easy to administer and monitor with standard operating room equipment; stable to light, plastics, metals, rubber and soda lime; and 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. [4]
Other gases or vapors which produce general anaesthesia by inhalation include nitrous oxide, carbon dioxide, cyclopropane, and xenon. These are stored in gas cylinders 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 odorless (odourless) and rapid in onset, but is expensive and requires specialized equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anaesthesia in most people at standard atmospheric pressure, so it must be used as an adjunct anaesthetic, along with other agents.
Under hyperbaric conditions (pressures above normal atmospheric pressure), other gases such as nitrogen, and noble gases such as argon, krypton, and xenon become anaesthetics. When inhaled at high partial pressures (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. [5] [6] However, the minimum alveolar concentration (MAC) for nitrogen is not achieved until pressures of about 20 to 30 atm (bar) are attained. [7] 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. [8]
Endogenous analogs of inhaled anesthetics are compounds that the body produces and that have the properties and similar mode of action of inhaled anesthetics. [9] Among the gases in the human body, carbon dioxide is among the most abundant and produces anesthesia from insects to humans. [10] CO2 anesthesia was first demonstrated to the king of france in the early 1800s by Henry Hill Hickman. Initially CO2 was thought to work through anoxia, but in the early 1900, increased CO2 in the lung showed a dramatic increase oxygenation of the brain disproving the anoxia argument. [11] Prior to the development of modern anesthetics, CO2 was used extensively by psychiatrists in a treatment called carbon dioxide inhalation therapy. [12]
 | Parts of this article (those related to Important research from Scripps Research misses here.) need to be updated.(October 2021) |
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. [13]
"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 bonding 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). Also, some halogenated ethers (such as flurothyl) also possess this "anti-anaesthetic" effect, providing further evidence for this theory.
Paracelsus developed an inhalational anaesthetic in 1540. [14] He used sweet oil of vitriol (prepared by Valerius Cordus and named Aether by Frobenius): [14] used to feed fowl: “it was taken even by chickens and they fall asleep from it for a while but awaken later without harm”. [14] Subsequently, about 40 years later, in 1581, Giambattista Delia Porta demonstrated the use of ether on humans although it was not employed for any type of surgical anesthesia. [14]
In modern medicine, Dr. Horace Wells used nitrous oxide for his own dental extraction in 1844. However his attempt to replicate these results at Massachusetts General Hospital (MGH) resulted in a partial anesthetic and was deemed a failure.
William T.G. Morton is credited with successfully demonstrating surgical anesthesia for the first time on October 16, 1846, at MGH. Following this event, the use of ether and other volatile anesthetics became widespread in Western medicine. [15]
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.
Nitrous oxide, commonly known as laughing gas, nitrous, nitro, or nos, 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.
Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful in those who are difficult to intubate. It is given by 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.
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.
Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a triangular ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself is mainly of theoretical interest but many of its derivatives - cyclopropanes - are of commercial or biological significance.
A breathing gas is a mixture of gaseous chemical elements and compounds used for respiration. Air is the most common and only natural breathing gas, but other mixtures of gases, or pure oxygen, are also used in breathing equipment and enclosed habitats. Oxygen is the essential component for any breathing gas. Breathing gases for hyperbaric use have been developed to improve on the performance of ordinary air by reducing the risk of decompression sickness, reducing the duration of decompression, reducing nitrogen narcosis or allowing safer deep diving.
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.
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.
Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.
Nitrous oxide is an inhaled gas used as a pain medication and together with other medications for anesthesia. Common uses include during childbirth, following trauma, and as part of end-of-life care. Onset of effect is typically within half a minute, and the effect lasts for about a minute.
A halogenated ether is a subcategory of a larger group of chemicals known as ethers. An ether is an organic chemical that contains an ether group—an oxygen atom connected to two (substituted) alkyl groups. A good example of an ether is the solvent diethyl ether. What differentiates a halogenated ether from other types of ethers is the substitution (halogenation) of one or more hydrogen atoms with a halogen atom. Halogen atoms include fluorine, chlorine, bromine, and iodine.
Minimum alveolar concentration or MAC is the concentration, often expressed as a percentage by volume, of a vapour in the alveoli of the lungs that is needed to prevent movement in 50% of subjects in response to surgical (pain) stimulus. MAC is used to compare the strengths, or potency, of anaesthetic vapours. The concept of MAC was first introduced in 1965.
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.
Flurothyl (Indoklon) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.
Throughout recorded history, attempts at producing a state of general anesthesia can be traced back to the writings of ancient Sumerians, Babylonians, Assyrians, Egyptians, Indians, and Chinese. Despite significant advances in anatomy and surgical technique during the Renaissance, surgery remained a last-resort treatment largely due to the pain associated with it. However, scientific discoveries in the late 18th and early 19th centuries paved the way for the development of modern anesthetic techniques.
Blood–gas partition coefficient, also known as Ostwald coefficient for blood–gas, is a term used in pharmacology to describe the solubility of inhaled general anesthetics in blood. According to Henry's law, the ratio of the concentration in blood to the concentration in gas that is in contact with that blood, when the partial pressure in both compartments is equal, is nearly constant at sufficiently low concentrations. The partition coefficient is defined as this ratio and, therefore, has no units. The concentration of the anesthetic in blood includes the portion that is undissolved in plasma and the portion that is dissolved. The more soluble the inhaled anesthetic is in blood compared to in air, the more it binds to plasma proteins in the blood and the higher the blood–gas partition coefficient.
Nitrous oxide, desflurane, and isoflurane are the most commonly used anesthetic gases. They may cause some complications due to their leakage and storage failure.
Endogenous anesthetics are analogs of anesthetics the body makes that have the properties and similar mode of action of general anesthetics.
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