II. Indications

  1. General Anesthetic Gas

III. Contraindications

IV. Definitions

  1. Ether
    1. Organic compounds in which two carbon atoms are linked through an oxygen atom (C-O-C)
    2. Diethyl ethers have historically been used as inhaled Anesthetics

V. Background

  1. Newer inhaled Anesthetics (Desflurane, Sevoflurane) are fully fluorinated analogs of Isoflurane
    1. Isoflurane (partially fluorinated) required a longer recovery period (esp. in obese patients) than these newer analogs
    2. These newer agents are also not flammable (contrast with Nitrous Oxide)
  2. Older agents (Halothane, Enflurane) are not in typical modern use in the U.S.
    1. These older agents were associated with a greater degree of myocardial depression and adverse effects
  3. First inhalation Anesthetic was ether
    1. Ether was synthesized in 1540, and was first used for medical Anesthesia in the U.S. in the 1840s
    2. Nitrous Oxide was also used during this time period, first used in 1772
    3. Chaturvedi (2011) Med J Armed Forces India 67(4):306-8 +PMID: 27365835 [PubMed]

VI. Mechanism

  1. Ethers with general Anesthetic (Sedative, hypnotic effects) and Skeletal Muscle Relaxant properties
    1. Most inhaled Anesthetics are fluorinated
  2. Inhalational agents are supplied as liquids and are vaporized to gas for inhalation
    1. CNS concentrations are directly related to alveolar concentrations
    2. Minimal alveolar concentration (MAC) reflects level at which 50% of patients will not move with painful stimulus
  3. Blocks release and re-uptake of Neurotransmitters at post-synaptic terminals and decreases conductance
  4. May affect Neuron ion channels and may also activate GABA Receptors

VII. Medications: Sevoflurane

  1. Minimum Alveolar Concentration: 1.8%
  2. Used in the U.S. since the 1990s and is among the most commonly used inhalational Anesthetics for surgery
  3. Safety
    1. Pregnancy Category C
    2. Unknown safety in Lactation

VIII. Medications: Desflurane

  1. Minimum Alveolar Concentration: 6.0%
  2. Safety
    1. Pregnancy Category B
    2. Considered safe in Lactation
  3. Precautions
    1. Laryngospasm is common (avoid in pediatrics)
    2. Avoid as sole Anesthetic in Coronary Artery Disease

IX. Medications: Isoflurane

  1. Older agent, replaced by Desflurane and Sevoflurane
  2. Minimum Alveolar Concentration: 1.15%
  3. Safety
    1. Pregnancy Category C
    2. Unknown safety in Lactation
  4. Adverse Effects
    1. Longer recovery period than newer agents (esp. in Obesity)

X. Pharmacokinetics

  1. Isoflurane undergoes minimal metabolism (hence fewer adverse effects than Halothane or Enflurane)
  2. All volatile Anesthetics deposit in fatty tissue

XI. Adverse Effects

  1. Cardiovascular
    1. Myocardial Depression, decreased contractility and decreased mean arterial pressure
    2. Decreased Vascular resistance
    3. Myocardial Catecholamine sensitization
  2. Respiratory
    1. Respiratory depression
    2. Bronchodilation
  3. Other Serious Effects
    1. Malignant Hyperthermia (all volatile Anesthetics)
    2. Allergic Hepatotoxicity (Halothane)
    3. Enflurane (Nephrotoxicity)
    4. Diffuse Alveolar Hemorrhage (Sevoflurane)
      1. Ahmed-Khan (2023) Arch Clin Cases 10(1): 29-31 [PubMed]

XIII. References

  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
  2. Smith (2023) General Anesthesia for Surgeons, StatPearls, Treasure Island, FL
    1. https://www.ncbi.nlm.nih.gov/books/NBK493199/

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Related Studies

Ontology: Enflurane (C0014277)

Definition (NCI) A fluorinated ether and very potent and stable general anaesthetic agent. The mechanism through which enflurane exerts its effect is not clear, it probably acts on nerve cell membranes to disrupt neuronal transmission in the brain, probably via an action at the lipid matrix of the neuronal membrane. Enflurane may also enhance the activity of the inhibitory neurotransmitter gamma-aminobutyric acid on synaptic transmission. Enflurane may also inhibit glutamatergic excitatory transmission.
Definition (MSH) An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate.
Definition (CSP) extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D004737
SnomedCT 32313007, 387176008
LNC LP18610-3, MTHU004794
English Enflurane, enflurane, Ethane, 2-chloro-1-(difluoromethoxy)-1,1,2-trifluoro-, Methylflurether, 2-Chloro-1,1,2-trifluoroethyl difluoromethyl Ether, 2-Chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane, Enflurane [Chemical/Ingredient], ENFLURANE, Enflurane (product), Enflurane (substance)
Swedish Enfluran
Czech enfluran
Finnish Enfluraani
Russian ENFLURAN, ЭНФЛУРАН
Japanese エンフルラン
Polish Enfluran
Spanish enflurano (producto), enflurano (sustancia), enflurano, Enflurano
French Enflurane
German Enfluran
Italian Enflurano
Portuguese Enflurano

Ontology: Halothane (C0018549)

Definition (NCI) A nonflammable, halogenated, hydrocarbon and general inhalation anesthetic. Although the exact mechanism of action is unknown, halothane provides relatively rapid induction of anesthesia by depressing the central nervous system, thereby producing a reversible loss of consciousness and sensation. (NCI05)
Definition (MSH) A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)
Definition (CSP) potent inhalation anesthetic widely used for induction and maintenance of general anesthesia.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D006221
SnomedCT 387351001, 63682003
LNC LP18067-6, MTHU003330
English 1,1,1-Trifluoro-2-Chloro-2-Bromoethane, Halothane, halothane, Ethane, 2-bromo-2-chloro-1,1,1-trifluoro-, 1,1,1-Trifluoro-2-bromo-2-chloroethane, Halothane [Chemical/Ingredient], Halothane (product), Halothane (substance), HALOTHANE
Swedish Halotan
Czech halothan
Finnish Halotaani
Italian 1,1,1-Trifluoro-2-cloro-2-bromoetano, Alotano
Russian FTOROTAN, GALOTAN, ГАЛОТАН, ФТОРОТАН
Japanese フルオタン, フローセン, ハロセン, ハロタン
Croatian HALOTAN
Polish Halotan
Spanish halotano (producto), halotano (sustancia), halotano, Halotano
French Halothane
German Halothan
Portuguese Halotano

Ontology: Isoflurane (C0022180)

Definition (NCI) A fluorinated ether with general anesthetic and muscle relaxant activities. Although the exact mechanism of action has not been established, inhaled isoflurane, appears to act on the lipid matrix of the neuronal cell membrane, which results in disruption of neuronal transmission. This agent enhances the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), thereby increasing the activity of the inhibitory neurotransmitter on synaptic transmission. Isoflurane may also both inhibit glutamatergic excitatory transmission by increasing glutamate re-uptake, and potentiate glycine receptor activity, which decreases motor function. In addition, isoflurane may alter certain pro- and anti-inflammatory cytokines, including interleukin-6 and -10 (IL-6, IL-10), possibly through the activation of the nuclear factor kappa B (NF-KB) pathway, which may affect immune responses during surgery.
Definition (MSH) A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
Definition (CSP) F2CHOCHCl-CF3; used as an inhalation anesthetic; may act via beta adrenergic or muscarinic receptors; adverse side effects are hypotension and risk of myocardial ischemia and cardiac arrest.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D007530
SnomedCT 387368002, 66492008
LNC LP17885-2, MTHU024731
English Isoflurane, isoflurane, Ethane, 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-, ISOFLURANE, Isoflurane [Chemical/Ingredient], 1-Chloro-2,2,2-trifluoroethyl Difluoromethyl Ether, 2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane, Isoflurane (product), Isoflurane (substance)
Swedish Isofluran
Czech isofluran
Finnish Isofluraani
Russian IZOFLURAN, ИЗОФЛУРАН
Croatian IZOFLURAN
Polish Izofluran
Spanish isoflurano (producto), isoflurano (sustancia), isoflurano, Isoflurano
French Isoflurane
German Isofluranum, Isofluran
Italian Isoflurano
Portuguese Isoflurano

Ontology: desflurane (C0063252)

Definition (NCI) A fluorinated ether with general anesthetic and muscle relaxant activities. Although the exact mechanism of action has not been established, desflurane, administered by inhalation, appears to act on the lipid matrix of the neuronal membrane, resulting in disruption of neuronal transmission in the brain. This agent may also enhance the synaptic activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C053562
SnomedCT 108393001, 386841003
English desflurane, Ethane, 2-(difluoromethoxy)-1,1,1,2-tetrafluoro-, Ethane, 2-(difluoromethoxy)-1,1,1,2-tetrafluoro-,(+-)-, DESFLURANE, desflurane [Chemical/Ingredient], Desflurane, Desflurane (product), Desflurane (substance)
Spanish desflurano (producto), desflurano (sustancia), desflurano

Ontology: sevoflurane (C0074414)

Definition (NCI) A fluorinated isopropyl ether with general anesthetic property. Although the mechanism of action has not been fully elucidated, sevoflurane may act by interfering with the release and re-uptake of neurotransmitters at post-synaptic terminals, and/or alter ionic conductance following receptor activation by a neurotransmitter. Sevoflurane may also interact directly with lipid matrix of neuronal membranes, thereby affecting gating properties of ion channels. In addition, this agent may activate gamma-aminobutyric acid (GABA) receptors hyperpolarizing cell membranes. This results in a general anesthetic effect, a decrease in myocardial contractility and mean arterial pressure as well as an increased respiratory rate.
Definition (PDQ) A fluorinated isopropyl ether with general anesthetic property. Although the mechanism of action has not been fully elucidated, sevoflurane may act by interfering with the release and re-uptake of neurotransmitters at post-synaptic terminals, and/or alter ionic conductance following receptor activation by a neurotransmitter. Sevoflurane may also interact directly with lipid matrix of neuronal membranes, thereby affecting gating properties of ion channels. In addition, this agent may activate gamma-aminobutyric acid (GABA) receptors hyperpolarizing cell membranes. This results in a general anesthetic effect, a decrease in myocardial contractility and mean arterial pressure as well as an increased respiratory rate. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=524061&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=524061&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C47717" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C009250
SnomedCT 386842005, 255735002, 108395008
English fluoromethyl hexafluoroisopropyl ether, fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether, sevoflurane, 1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propane, Ether, Fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl-, FluoroMetrifltriflMeethyl eth, Fluoromethyl 2,2,2-trifluoro-1-(trifluromethyl)ethyl ether, SEVOFLURANE, sevoflurane [Chemical/Ingredient], sevorane, Fluoromethyl 2,2,2-trifluoro-1-(trifluromethyl)ethyl ether (substance), Sevoflurane, Sevoflurane product, Sevoflurane (product), Sevoflurane (substance)
Spanish fluorometil 2,2,2-trifluoro-1-(trifluorometil)etil éter, fluorometil 2,2,2-trifluoro-1-(trifluorometil)etil éter (sustancia), sevoflurano (producto), sevoflurano (sustancia), sevoflurano

Ontology: Forane (C0306242)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
English Forane

Ontology: Volatile liquid anesthetic agent (C0592957)

Concepts Pharmacologic Substance (T121)
SnomedCT 372645001, 356269009
English Volatile liq anaesthetic agent, Volatile liq anesthetic agent, Volatile agent, Volatile liquid anesthetic agent, Volatile liquid anaesthetic agent, Volatile liquid anesthetic agent (product), Volatile liquid anesthetic agent (substance)
Spanish agente anestésico líquido volátil (producto), agente anestésico líquido volátil (sustancia), agente anestésico líquido volátil

Ontology: Fluothane (C0701981)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D006221
English Fluothane