1. Halothane and
Sevoflurane
Verna Thomas, RN, BSN, SRNA
Leah Baumgardner, RN, BSN, SRNA
Tuesday, March 26, 13

2. Halothane
History
Initially introduced in the mid 1950’s Halothane became
the most widely used inhalational anesthetic.
Today, its prevalence in modern medicine has
diminished to use in Third World countries and
veterinary surgery.
The arrival of safer anesthetics and better
pharmocokinetics in the 1980’s and 1990’s was a
substantial contributor to its elimination in American
medicine.
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3. Halothane
Functional Group
2-bromo-2-chloro-1,1,1,triflouroethane
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4. Halothane
Metabolism
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5. Halothane
Halothane Sevoflurane HALOTHANE HEPATITIS
Boiling Point (°C) 50.2 58.5 Type I (mild): Benign hepatotoxicity,
Vapor Pressure @ 20°C (mmHg) 243 120
transient ↑ in serum transaminase
Molecular Weight (Da) 197.4 200 and glutathione S-transferase
Specific Gravity (g/mL) 1.87 1.50 concentrations, no jaundice or
Blood:Gas Partition Coefficient 2.4 0.66 hepatocellular disease evident.
Oil:Gas Partition Coefficient 224 53.4 Type II (fulminant halothane
MAC (vol%) 0.75 2.05 hepatitis): Massive centrilobular liver
Metabolism (% approx) 20 5 necrosis, 50% mortality, fever,
jaundice, and marked ↑↑serum
transaminase levels, immune
Cardiac: ↓BP, ↓HR, ↓CO mediated.
Respiratory: ↓VT, ↑RR, ↑PaCO2
Cerebral: ↑CBF, ↑ICP, ↓cerebral
metabolic rate, ↓seizures
Renal: ↓GFR, ↓renal blood flow,
↓UO
Hepatic: ↓hepatic blood flow
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6. Sevoflurane
Inhalation Anesthetic
Use: Induction and maintenance of general anesthesia
Adult and Pediatric
Effects on Organ Systems:
Cardiac: moderate reduction in SVR and MAP but
myocardial contractility and heart rate unchanged
Respiratory depressant but most effective bronchodilator
and least irritant of the inhaled anesthetics
Relaxes Muscles and attenuates response to noxious
stimuli
Causes less cerebral vasodilatation and maintains cerebral
autoregulation well
Contraindications: Malignant Hyperthermia
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7. Sevoflurane
Naming: Functional Group
ETHER: R-O-R
IUPAC : 1,1,1,3,3,3,-Hexafluoro-2-(fluoromethoxy)-propane
Molecular Formula: C4H3F7O
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8. Sevoflurane
PROPERTIES
STRUCTURE: Non-polar
more polar than alkanes (because of
Oxygen) but less polar than alcohols
Very slightly water soluable
HALOGENATED: with Flourine
BOILING POINT: Low - 58.5 degrees Celsius
ODOR: Pleasant
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9. Sevoflurane
Oil/gas partition coefficient: 47.2
MAC (Vol%) [in patients aged 30-60y]: 2.05
Blood/gas partition coefficient: 0.69
- low solubility in the blood results in rapid induction,
improved control of depth of anesthesia, and fast emergence/
recovery
pKa (Acidic and Basic) are not provided but PubChem lists
H-Bond Donor: 0 H-Bond Acceptor: 8
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10. Sevoflurane
Metabolism
95-98% is eliminated through the
lungs
- rapidly because of low blood/gas
solubility
The remaining 2-5% is metabolized...
Cytochrome P450 System - LIVER
- defluorinated to
hexaflouroisopropanol (HFIP) with
release of inorganic flouride and
carbon dioxide
- HFIP conjugated with glucuronic acid
to HFIP-glucuronide and excreted in
the urine
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11. Sevoflurane
Degradation
- in the presence of CO2 absorbents used in
anesthesia circuits i.e. Baralyme or soda lime
Loss of Hydrogen Fluoride produces Compound A
fluoromethyl-2,2-difluoro- 1- (trifluoromethyl)
vinyl ether (CF2 = C(CF3) OCH2F)
Compound A has been shown to be nephrotoxic
in rats but not shown in humans
- dose related proteinuria, glycosuria, and
enzymuria
Reduce amount of Compound A by using fresh gas
inflows >2L/min
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12. Sevoflurane
1. Formation of Compound A is directly/inversely proportional
to fresh gas inflow???
2. What characteristic of Sevoflurane is responsible for rapid
induction and rapid elimination??
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13. References
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14. References
Behne, M., Wilke, H. J., & Harder, S. (1999). Clinical pharmacokinetics of sevoflurane. Clinical
pharmacokinetics, 36(1), 13-26.
Eger II, E. I. (1991). Metabolism of Sevoflurane. Anesthesia & Analgesia, 73(5), 671-671.
Hemmings, H. C., & Hopkins, P. M. (2006). Foundations of anesthesia: basic sciences for clinical practice.
Mosby Incorporated.
Sevoflurane. In (2012). Drugs.com. Retrieved from http://www.drugs.com/pro/sevoflurane.html
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