Desflurane

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Desflurane
(RS)-Desfluran Structural Formula V1.svg
Desflurane-3D-balls.png
Clinical data
Pronunciationdes-FLOO-rane
Trade names Suprane
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License data
Pregnancy
category
  • AU:B3
Routes of
administration
Inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Not metabolized
Elimination half-life Elimination dependent on minute ventilation
Identifiers
  • 2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
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UNII
KEGG
ChEBI
ChEMBL
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ECHA InfoCard 100.214.382 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C3H2F6O
Molar mass 168.038 g·mol−1
3D model (JSmol)
  • FC(F)(F)C(F)OC(F)F
  • InChI=1S/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H Yes check.svgY
  • Key:DPYMFVXJLLWWEU-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

Some drawbacks of desflurane are its low potency, its pungency and its high cost (though at low flow fresh gas rates, the cost difference between desflurane and isoflurane appears to be insignificant [2] ). It may cause tachycardia and airway irritability when administered at concentrations greater than 10% by volume. Due to this airway irritability, desflurane is infrequently used to induce anesthesia via inhalation techniques.

Though it vaporizes very readily, it is a liquid at room temperature. Anaesthetic machines are fitted with a specialized anaesthetic vaporiser unit that heats liquid desflurane to a constant temperature. This enables the agent to be available at a constant vapor pressure, negating the effects fluctuating ambient temperatures would otherwise have on its concentration imparted into the fresh gas flow of the anesthesia machine.

Desflurane, along with enflurane and to a lesser extent isoflurane, has been shown to react with the carbon dioxide absorbent in anesthesia circuits to produce detectable levels of carbon monoxide through degradation of the anesthetic agent. The CO2 absorbent Baralyme, when dried, is most culpable for the production of carbon monoxide from desflurane degradation, although it is also seen with soda lime absorbent as well. Dry conditions in the carbon dioxide absorbent are conducive to this phenomenon, such as those resulting from high fresh gas flows. [3]

Pharmacology

As of 2005 the exact mechanism of the action of general anaesthetics has not been delineated. [4] Desflurane is known to act as a positive allosteric modulator of the GABAA and glycine receptors, [5] [6] [7] and as a negative allosteric modulator of the nicotinic acetylcholine receptor, [8] [9] as well as affecting other ligand-gated ion channels. [10] [11]

Stereochemistry

Desflurane medications are a racemate of two enantiomers. [12]

Enantiomeres of desflurane
(R)-Desfluran Structural Formula V1.svg
(R)-Enantiomer
(S)-Desfluran Structural Formula V1.svg
(S)-Enantiomer

Physical properties

Boiling point  :23.5 °C or 74.3 °F(at 1 atm)
Density  :1.465 g/cm3(at 20 °C)
Molecular Weight  :168
Vapor pressure:88.5 kPa672 mmHg(at 20 °C)
107 kPa804 mmHg(at 24 °C)
Blood:Gas partition coefficient:0.42
Oil:Gas partition coefficient :19
MAC  :6 vol %

Physiologic effects

Desflurane induces a dose dependent reduction in blood pressure due to reduced systemic vascular resistance. However, rapid increases in desflurane may induce a transient sympathetic response secondary to catecholamine release. Even though it is highly pungent, it is still a bronchodilator. It reduces the ventilatory response to hypoxia and hypercapnia. Like sevoflurane, desflurane vasodilatory properties also cause it to increase intracranial pressure and cerebral blood flow. However, it reduces cerebral metabolic rate. It also promotes muscle relaxation and potentiate neuromuscular blockade at a greater level than sevoflurane. [13]

Contraindications

It is contraindicated for induction of general anesthesia in the non-intubated pediatric population due to the high risk of laryngospasm. It should not be used in patients with known or suspected susceptibility to malignant hyperthermia. It is also contraindicated in patients with elevated intracranial pressure. [13]

Global-warming potential

Desflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for desflurane is 3714, [14] meaning that one tonne of desflurane emitted is equivalent to 3714 tonnes of carbon dioxide in the atmosphere, much higher than sevoflurane or isoflurane. In addition to global warming potentials, drug potency and fresh gas flow rates must be considered for meaningful comparisons between anesthetic gases. When a steady state hourly amount of anesthetic necessary for 1 minimum alveolar concentration (MAC) at 2 liters per minute (LPM) for Sevoflurane, and 1 LPM for Desflurane and Isoflurane is weighted by the GWP, the clinically relevant quantities of each anesthetic can then be compared. On a per-MAC-hour basis, the total life cycle GHG impact of desflurane is more than 20 times higher than Isoflurane and Sevoflurane (1 minimal alveolar concentration-hour). [15] One paper finds anesthesia gases used globally contribute the equivalent of 1 million cars to global warming. [16] This estimate is commonly cited as a reason to neglect pollution prevention by anesthesiologists. However, this is problematic. This estimate is extrapolated from only one U.S. institution's anesthetic practices, and this institution uses virtually no Desflurane. Researchers neglected to include nitrous oxide in their calculations, and reported an erroneous average of 17 kg CO2e per anesthetic. However, institutions that utilize some Desflurane and account for nitrous oxide have reported an average of 175–220 kg CO2e per anesthetic. Sulbaek-Anderson's group therefore likely underestimated the total worldwide contribution of inhaled anesthetics, and yet still advocates for inhaled anesthetic emissions prevention. [17]

In March 2023, Scotland became the first country to ban its use due to its environmental impact. [18]

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">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">Halothane</span> General anaesthetic

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.

Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, propofol, etomidate, ketamine, pentobarbital, lorazepam and midazolam.

<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">Enflurane</span> Chemical compound

Enflurane is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but is no longer in common use.

<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

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.

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.

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

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.

Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decreased level of consciousness while maintaining the patient's ability to breathe on their own. Airway protective reflexes are not compromised by this process and therefore endotracheal intubation is not required. PSA is commonly used in the emergency department, in addition to the operating room.

Emergence delirium is a condition in which emergence from general anesthesia is accompanied by psychomotor agitation. Some see a relation to pavor nocturnus while others see a relation to the excitement stage of anesthesia.

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.

The following outline is provided as an overview of and topical guide to anesthesia:

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').

References

  1. Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. Varkey JK (October 2012). Cost Analysis of Desflurane and Sevoflurane: An Integrative Review and Implementation Project Introducing the Volatile Anesthetic Cost Calculator (Doctor of Nursing Practice thesis). Texas Christian University.
  3. Fang ZX, Eger EI, Laster MJ, Chortkoff BS, Kandel L, Ionescu P (June 1995). "Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme". Anesthesia and Analgesia. 80 (6): 1187–93. doi: 10.1097/00000539-199506000-00021 . PMID   7762850. S2CID   41150462.
  4. Perkins B (7 February 2005). "How does anesthesia work?". Scientific American . Retrieved 30 June 2016.
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  13. 1 2 Khan J, Liu M (2022). "Desflurane". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   30725791.
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Further reading