II. Indications
- General Anesthetic Gas
III. Contraindications
- Malignant Hyperthermia Family History or personal history
IV. Definitions
- Ether
- Organic compounds in which two carbon atoms are linked through an oxygen atom (C-O-C)
- Diethyl ethers have historically been used as inhaled Anesthetics
V. Background
- Newer inhaled Anesthetics (Desflurane, Sevoflurane) are fully fluorinated analogs of Isoflurane
- Isoflurane (partially fluorinated) required a longer recovery period (esp. in obese patients) than these newer analogs
- These newer agents are also not flammable (contrast with Nitrous Oxide)
- Older agents (Halothane, Enflurane) are not in typical modern use in the U.S.
- These older agents were associated with a greater degree of myocardial depression and adverse effects
- First inhalation Anesthetic was ether
- Ether was synthesized in 1540, and was first used for medical Anesthesia in the U.S. in the 1840s
- Nitrous Oxide was also used during this time period, first used in 1772
- Chaturvedi (2011) Med J Armed Forces India 67(4):306-8 +PMID: 27365835 [PubMed]
VI. Mechanism
- Ethers with general Anesthetic (Sedative, hypnotic effects) and Skeletal Muscle Relaxant properties
- Most inhaled Anesthetics are fluorinated
- Inhalational agents are supplied as liquids and are vaporized to gas for inhalation
- CNS concentrations are directly related to alveolar concentrations
- Minimal alveolar concentration (MAC) reflects level at which 50% of patients will not move with painful stimulus
- Blocks release and re-uptake of Neurotransmitters at post-synaptic terminals and decreases conductance
- May affect Neuron ion channels and may also activate GABA Receptors
VII. Medications: Sevoflurane
- Minimum Alveolar Concentration: 1.8%
- Used in the U.S. since the 1990s and is among the most commonly used inhalational Anesthetics for surgery
- Safety
- Pregnancy Category C
- Unknown safety in Lactation
VIII. Medications: Desflurane
- Minimum Alveolar Concentration: 6.0%
- Safety
- Pregnancy Category B
- Considered safe in Lactation
- Precautions
- Laryngospasm is common (avoid in pediatrics)
- Avoid as sole Anesthetic in Coronary Artery Disease
IX. Medications: Isoflurane
X. Pharmacokinetics
- Isoflurane undergoes minimal metabolism (hence fewer adverse effects than Halothane or Enflurane)
- All volatile Anesthetics deposit in fatty tissue
XI. Adverse Effects
- Cardiovascular
- Myocardial Depression, decreased contractility and decreased mean arterial pressure
- Decreased Vascular resistance
- Myocardial Catecholamine sensitization
- Respiratory
- Respiratory depression
- Bronchodilation
- Other Serious Effects
- Malignant Hyperthermia (all volatile Anesthetics)
- Allergic Hepatotoxicity (Halothane)
- Enflurane (Nephrotoxicity)
- Diffuse Alveolar Hemorrhage (Sevoflurane)
XII. Resources
- Desflurane (DailyMed)
- Isoflurane (DailyMed)
- Sevoflurane (DailyMed)
XIII. References
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
- Smith (2023) General Anesthesia for Surgeons, StatPearls, Treasure Island, FL
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Related Studies
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 |