Sevoflurane
Encyclopedia
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. It is often administered in a mixture of nitrous oxide
and oxygen. After desflurane
, it is the most volatile anesthetic with the fastest onset and offset. Though desflurane has the lowest blood/gas coefficient of the currently used volatile anesthetics, sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.
First reports of sevoflurane appeared in the literature in 1971. The agent was developed by scientists at Baxter Laboratories.
It was introduced into clinical practice initially in Japan in 1990. Its name comes from having seven fluorine atoms. The rights for sevoflurane in the US and other countries are held by Abbott Laboratories
.
Sevoflurane forms at least two degradation products, compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] also called PIFE (pentafluoroisopropenyl fluoromethyl ether) and Compound B [1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane], also called PMFE (pentafluoromethoxy isopropyl fluoromethyl ether) on contact with the soda lime
in a rebreathing apparatus
, which absorbs exhaled carbon dioxide
, especially at higher temperatures and when the soda lime is desiccated. Hydrofluoric acid is formed in the same reaction as compound A. Compound A has been shown to cause renal necrosis in rats. In humans, direct histological evidence of renal toxicity has not been demonstrated, although there is dose-related proteinuria
, glycosuria
and enzymuria. During low-flow anaesthesia, when the lower fresh gas flow leads to decreased flushing of the circuit and increased temperature of the soda lime, compound A may build up to clinically significant levels, although there have never been any reports of adverse events in humans. As a result, sevoflurane is sometimes administered with a minimum fresh gas flow of 2 liters per minute, making it a relatively expensive choice for maintaining general anesthesia. Only two countries currently maintain mandatory minimum flow rates of 2L/min; Canada and Australia. Recent generic competition in select markets has also significantly lowered the unit cost of sevoflurane, making it more cost effective.
Sevoflurane has been implicated in neuronal degeneration in infant mice. This activity is thought to occur via blockade of NMDA
receptors or hyperactivity of GABA
neurotransmission. In one, the researchers showed exposure of infant mice to inhaled sevoflurane resulted in learning deficits and abnormal social behaviour
Sevoflurane raises the intracranial tension and can cause respiratory depression.
Wallin, Richard F., Regan, Bernard M., Napoli, Martha D., Stern, Ivan j. (Nov.-Dec. 1975). "Sevoflurane: A New Inhalational Anesthetic Agent". Anesthesia and Analgesia, 84(6), 58-766.
Halogenated ether
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 alkyl groups...
used for induction and maintenance of general anesthesia. Together with 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...
, it is replacing 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...
and halothane
Halothane
Halothane 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...
in modern anesthesiology. It is often administered in a mixture of 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 oxygen. After 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...
, it is the most volatile anesthetic with the fastest onset and offset. Though desflurane has the lowest blood/gas coefficient of the currently used volatile anesthetics, sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.
First reports of sevoflurane appeared in the literature in 1971. The agent was developed by scientists at Baxter Laboratories.
It was introduced into clinical practice initially in Japan in 1990. Its name comes from having seven fluorine atoms. The rights for sevoflurane in the US and other countries are held by Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
.
Sevoflurane forms at least two degradation products, compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] also called PIFE (pentafluoroisopropenyl fluoromethyl ether) and Compound B [1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane], also called PMFE (pentafluoromethoxy isopropyl fluoromethyl ether) on contact with the 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...
in a rebreathing apparatus
Rebreather
A rebreather is a type of breathing set that provides a breathing gas containing oxygen and recycled exhaled gas. This recycling reduces the volume of breathing gas used, making a rebreather lighter and more compact than an open-circuit breathing set for the same duration in environments where...
, which absorbs exhaled carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
, especially at higher temperatures and when the soda lime is desiccated. Hydrofluoric acid is formed in the same reaction as compound A. Compound A has been shown to cause renal necrosis in rats. In humans, direct histological evidence of renal toxicity has not been demonstrated, although there is dose-related proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
, glycosuria
Glycosuria
Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to...
and enzymuria. During low-flow anaesthesia, when the lower fresh gas flow leads to decreased flushing of the circuit and increased temperature of the soda lime, compound A may build up to clinically significant levels, although there have never been any reports of adverse events in humans. As a result, sevoflurane is sometimes administered with a minimum fresh gas flow of 2 liters per minute, making it a relatively expensive choice for maintaining general anesthesia. Only two countries currently maintain mandatory minimum flow rates of 2L/min; Canada and Australia. Recent generic competition in select markets has also significantly lowered the unit cost of sevoflurane, making it more cost effective.
Sevoflurane has been implicated in neuronal degeneration in infant mice. This activity is thought to occur via blockade of NMDA
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
receptors or hyperactivity of GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
neurotransmission. In one, the researchers showed exposure of infant mice to inhaled sevoflurane resulted in learning deficits and abnormal social behaviour
Sevoflurane raises the intracranial tension and can cause respiratory depression.
Physical properties
| Boiling point Boiling point The boiling point of an element or a substance is the temperature at which the vapor pressure of the liquid equals the environmental pressure surrounding the liquid.... : |
58.6 °C | (at 101.325 kPa) | |
| Density Density The mass density or density of a material is defined as its mass per unit volume. The symbol most often used for density is ρ . In some cases , density is also defined as its weight per unit volume; although, this quantity is more properly called specific weight... : |
1.517–1.522 g/cm³ | (at 20 °C) | |
| MAC 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... : |
2 vol % | ||
| Molecular Weight: | 200 u | ||
| Vapor pressure Vapor pressure Vapor pressure or equilibrium vapor pressure is the pressure of a vapor in thermodynamic equilibrium with its condensed phases in a closed system. All liquids have a tendency to evaporate, and some solids can sublimate into a gaseous form... : |
157 mmHg (20.9 kPa) | (at 20 °C) | |
| 197 mmHg (26.3 kPa) | (at 25 °C) | ||
| 317 mmHg (42.3 kPa) | (at 36 °C) | ||
| Blood:Gas Partition Coefficient: | 0.68 | ||
| Oil:Gas Partition Coefficient: | 47 |
Additional reading
Wallin, Richard F., Regan, Bernard M., Napoli, Martha D., Stern, Ivan j. (Nov.-Dec. 1975). "Sevoflurane: A New Inhalational Anesthetic Agent". Anesthesia and Analgesia, 84(6), 58-766.