PHYSICAL PROPERTIES OF INHALED ANESTHETICS AND GASES

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PHYSICAL PROPERTIES OF INHALED ANESTHETICS AND
GASES

• HARRY SINGH, MD
• DEPT. OF ANESTHESIOLOGY
• UTMB

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PHYSICAL PROPERTIES

• Chemical Structure
• Boiling Point and Vapor Pressure
• Solubility
• Meyer Overton Hypothesis
• Interaction with Bases
• N2O and Xenon
• Effects on the Environment

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Structure of Diethyl Ether
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What are Inhaled Anesthetics

• Halothane Alkane
• Enflurane Methyl-ethyl ether
• Isoflurane Methyl-ethyl ether
• Sevoflurane Methyl-isopropyl ether
• Desflurane Methyl-ethyl ether
• Nitrous oxide Inorganic gas
• Xenon Noble gas

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Effect of Chemical Structure on Physical
Properties

• Halogenation reduces flammability
• Fluorination reduces solubility
• Fluorination decreases potency
• Substitution of Cl for F (isoflurane vs.
  desflurane)
• ?Solubility
• ?Potency
• ? Vapor Pressure and ? Boiling Point
• Substitution of Cl for H/Br increases potency
• Progression of potency H/Br gt Cl gt F

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Vapor Pressure and Boiling Point

• All inhaled anesthetics liquid at 20 0C
• Vapor Pressure Pressure exerted by the molecules
  of the vapor phase at equilibrium of molecules
  moving in and out of liquid phase
• Vapor Pressure dependent on temperature and
  physical characteristics of liquid, independent
  of atmospheric pressure
• ? Temperature?? Vapor Pressure
• Boiling Point Temperature at which vapor
  pressure equals atmospheric pressure

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BP and VP of Inhaled Anesthetics
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Significance of Boiling Point

• Variable Bypass Vaporizer Halothane, enflurane,
  isoflurane, sevoflurane Datex Ohmeda Tec
  4,5,7 or North American Drager Vaporizer 19.n and
  20.n
• Tec 6 Vaporizer Desflurane Electronically
  heated, thermostatically controlled, pressurized,
  electromechanically coupled, dual circuit
  gas-vapor blender

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Solubility of Inhaled Anesthetics

• Ideal inhaled anesthetics should have low
  blood/gas and low tissue/blood solubility and low
  solubility in plastic and rubber
• Low solubility means rapid induction and
  emergence and more precise control
• Anesthesia related to partial pressure of gas in
  brain
• More molecules of a soluble gas/agent required
  before increasing partial pressure in brain
• Induction/recovery DesfluranegtSevofluranegt
  Isoflurane

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Solubility of Inhaled Anesthetics

• Solubility is defined in terms of the partition
  coefficient
• Partition coefficient is the ratio of the amount
  of substance present in one phase compared with
  another, the two phases being of equal volume and
  in equilibrium
• Or it can be defined as the relative
  concentrations of anesthetic for two phases when
  the partial pressure of two phases is equal.

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Partitioning of Nitrous Oxide
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Partition Coefficients of Inhaled Anesthetics
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FA/FI Ratio of Inhaled Anesthetics
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Partition Coefficients of Inhaled Anesthetics
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Effect of Rubber and Plastic Components

• Rubber or plastic components may remove agents
• Significant problem with obsolete
  agent-methoxyflurane
• Minor problem-halothane and isoflurane
• No problem-N2O, desflurane, sevoflurane

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Meyer Overton Hypothesis
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Compounds that Disobey Meyer Overton Hypothesis

• Meyer Overton Constant 1.820.56 atm
• Alkanols More potent than lipophilicity
• Transitional Compounds Less potent than
  lipophilicity predicts
• Nonimmobilizers Lipophilic nonanesthetic alkanes
  and ethers
• Anesthetic potency defined by MAC is a function
  of both polar and nonpolar characteristics

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MAC vs Oil/Gas Partition Coefficient
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Meyer Overton Constant vs Saline/Gas Partition
Coefficient
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Odor

• Halothane Sweet
• Isoflurane Pungent, ethereal
• Enflurane Pungent, ethereal
• Desflurane Pungent, ethereal
• Sevoflurane None, sweet
• Nitrous Oxide None, sweet
• Xenon None

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Respiratory Irritation

• 2 MAC Desflurane 75
• 2 MAC Isoflurane 50
• 2 MAC Sevoflurane 0
• 1MAC No irritation with any of three
• Sevofluane Agent of choice for induction

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Formulation

• Isoflurane, Desflurane-Branded product-Baxter
• Sevofluane-Branded product-Abbot
• Sevoflurane-Generic product-Baxter
• Branded Sevoflurane-Glass containers-Lewis acid
  sites?HF?Pulmonary damage
• Water not less than 0.03(300 ppm) but not more
  than 0.1 for Branded Sevoflurane
• Generic Sevoflurane-Aluminium containers-water
  content 130 ppm-stable as no Lewis acid sites

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Absorbent Bases and Anesthetic Degradation
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Absorbents

• Baralyme Ca(OH)2 80 Ba(OH)2 15 KOH 4.6
  Water
• SodaLime Ca(OH)2 80 NaOH 3 KOH 1 Water
• SodaSorb Ca(OH)2 75 NaOH lt5 Water
• Amsorb/Amsorb Plus Ca(OH)2CaCl2
  
• No monovalent
  bases

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Products of Anesthetic Degradation
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Compound A / BCDFE

• Pentafluoroisopropenyl fluoromethyl ether (PIFE,
  C4H2F6O)
• Extraction of acidic proton in presence of strong
  base (KOH, NaOH)
• Baralyme gt Soda lime
• Production inversely related to FGF
• Production directly related to absorbent
  temperature
• Deprotonation of halothane by soda lime-BCDFE
  (2-bromo-2-chloro-1,1-difluoro ethylene)

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FGF vs Compound A
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Temperature vs CompoundA
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Nitrous Oxide

• Clear, colorless, odorless gas
• Molecular weight 44
• Supplied through pipeline or pressurized
  cylinders
• BP -890C
• Critical temperature 36.5 0C
• Critical Pressure 73 bars
• Specific gravity 1.53 at 0C
• Filling ratio 0.65

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Isotherms for Nitrous Oxide
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Effect of Nitrous Oxide on Closed Gas Spaces

• Nitrogen Blood/gas partition coefficient 0.015
• Nitrous Oxide 0.47
• N2O leaves blood 34 times faster than N2 is
  absorbed
• Theoretical limit to increase in volume is a
  function of alveolar nitrous oxide concentration.
• At equilibrium, concentration of N2O in closed
  gas space equal alveolar concentration.
• Alveolar concentration of 50 N2O may double
  volume of gas space

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Xenon

• Inert gas with anesthetic properties
• Normal constituent of atmospheric air at a
  concentration of lt0.086 ppm
• Removed by fractional distillation of liquefied
  air
• Highly insoluble
• Blood/gas Partition Coefficient 0.14
• Oil/gas Partition Coefficient 1.9
• Environment friendly
• Density 5.8 gm/L (N2O 1.53 Air 1).
• Greater density? ? Airway resistance

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Effects on the Environment

• Ozone Depletion ? ? Ultraviolet radiation
• Inhalational anesthetics account for only 0.25
  of global production of ClFCs
• Degradation of halothane, enflurane, isoflurane
  releases ozone destroying Cl and Br moiety
• Ozone destruction 0.36, 0.02, 0.02, 1 for
  halothane, enflurane, isoflurane, ClFCs
• Sevoflurane, desflurane Environment friendly
• Anesthetic vapors account for lt 0.01 ozone
  depletion

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Effects on the Environment

• Greenhouse Effect (Global Warming)
• Prevention of loss of infrared energy
• Greenhouse gases Carbon dioxide, methane,
  nitrous oxide
• Medically used N2O lt 2 of total N2O emission
• Anesthetic usage of N2O accounts for 0.05 of
  total greenhouse effect

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Suggested Readings

• Physical Properties of Inhaled Anesthetics in The
  Pharmacology of Inhaled Anesthetics by Edmond I
  Eger II, James B Eisenkraft, Richard B Weiskopf.
• Inhaled Anesthetics in Millers Anesthesia (Vol
  I), Editor Ronald D Miller, Churchill
  Livingstone.
• Koblin D, Laster MJ, Ionescu P, et al.
  Polyhalogenated Methyl Ethyl Ethers Solubilities
  and Anesthetic Properties. Anesth Analg
  199988(5)1161-67.
• Basic Physics and Measurement in Anaesthesia,
  Editors Paul D Davis and Gavin NC Kenny,
  Butterwoth-Heinemann Medical.
• Singh H. Can we as Anesthesiologists Contribute
  to a Better Environment. J Clin
  Anesth199810354-5.

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