Inhaled anaesthetic agents

[Ref: SH4:p43]

• Only HAL and SEVO are not stable in soda lime at 40 degrees
• HAL and SEVO are non-pungent
• Only HAL requires preservative

Carbon monoxide production

Carbon monoxide is produced when AA degrades during interaction with the strong base in desiccated carbon dioxide absorber

• DES produces the highest carbon monoxide
• Then ENF and ISO
• Negligible with HAL and SEVO

Blood:gas partition coefficient

• N2O = 0.46
• HAL = 2.54
• ENF = 1.90
• ISO = 1.46
• DES = 0.42
• SEVO = 0.69
• Xenon = 0.115

MAC values

• N2O = 104%
• HAL = 0.75%
• ENF = 1.63%
• ISO = 1.17%
• DES = 6.6%
• SEVO = 1.80%
• Xenon = 63-71%

Molecular weight

• N2O = 44
• HAL = 197
• ENF = 184
• ISO = 184
• DES = 168
• SEVO = 200

Boiling point (in degrees)

• N2O =
• HAL = 50.2
• ENF = 56.5
• ISO = 48.5
• DES = 22.8
• SEVO = 58.5

Vapour pressure at 20 degrees (mmHg)

• N2O = Gas
• HAL = 244 mmHg
• ENF = 172 mmHg
• ISO = 240 mmHg
• DES = 669 mmHg
• SEVO = 170 mmHg

Anaesthetic agents

[Ref: SH4:p43-p46]

Nitrous oxide (N2O)

Properties

• Low MW
  * MW = 44
• Nonflammable
  * But will support combustion
• Gas at room temperature
• Low potency
  * MAC = 104%
• Low solubility
  * Blood:gas = 0.46

Clinical relevance

• Analgesic
• Minimal skeletal muscle relaxation
• Increased incidence of PONV
• Small increase in P50
• Inactivate vitamin B12
• Mild sympathomimetic effect

Halothane (HAL)

• Halogenated alkane derivative
  * Alkane derivatives can enhance the dysrhythmogenic effects of epinephrine [SH4:p42]

Properties

• Clear, nonflammable liquid
• Intermediate solubility
  * Blood:gas = 2.54
• High potency
  * MAC = 0.75%

Preparation

Requires thymol as preservative
* Thymol prevents spontaneous oxidative decomposition
* Thymol in vapouriser can cause vapouriser turnstiles to malfunction

Chemical structure

• Carbon-fluorine bond decrease flammability
• Trifluorocarbon increase stability
• Carbon-chlorine and carbon-bromine bond with a hydrogen atom
  --> Ensures anaesthetic potency
• Susceptible to decomposition to:
  * Hydrochloric acid
  * Hydrobromic acid
  * Chloride
  * Bromide
  * Phosgene
• Bromide is a potent sedative

Enflurane (ENF)

• Halogenated methyl ethyl ether
• Isomer of ISO
  * Manufactured from chlorotrifluoroethylene

Properties

• Clear, nonflammable liquid at room temperature
• Pungent odour
• Intermediate solubility
  * Blood:gas = 1.90
• High potency
  * MAC = 1.63%
• (???) Good analgesia at subanaesthetic dose

Isoflurane (ISO)

• Halogenated methyl ethyl ether
• Isomer of ENF
  * Manufactured from 2,2,2-trifluoroethanol

Properties

• Clear, nonflammable liquid at room temperature
• Pungent odour
• Intermediate solubility
  * Blood:gas = 1.46
• High potency
  * MAC = 1.17%
• Extremely stable
  * No detectable deterioration after 5 years of storage
  * No detectable deterioration on exposure to CO2 absorbents or sunlight

NB:

• [SH4:p58] Iso may have mild beta-adrenergic agonist property (but not supported by animal data)

Des

• Fluorinated methyl ethyl ether
• Differ from iso by substitution of a fluorine for chlorine on alpha-ethyl of iso

Chemical structure

Fluorinate (rather than chlorination) causes

• Increased vapour pressure
  * Less intermolecular attraction
  * Vapour pressure at 20 degrees is 669 mmHg (cf. 240 mmHg for iso)
• Increased stability
  * Much less metabolism
• Decreased potency
  * MAC = 6.6% (cf. 1.17% for iso)

Properties

• Low solubility
  * Blood:gas = 0.42
• Requires a special heated and pressurised vapouriser which requires electricity
• Pungent smell
  * Cannot be used for gas induction

Clinical relevance

• Increased incidence of salivation, breath-holding, coughing, or laryngospasm when >6% inspired des is used in an awake patient
• Produces highest level of carbon monoxide (of all AAs) when reacting with the strong base in carbon dioxide absorber

Sevo

• Fluorinated methyl isopropyl ether

Properties

• Low solubility
  * Blood:gas = 0.69
• High potency
  * MAC = 1.80%

Clinical relevance

• Fast induction and recovery
• Nonpungent
• Least degree of airway irritation of all AAs

Metabolism and degradation

• More vulnerable to metabolism
  * 3-5% metabolised
• Metabolites include
  * Inorganic fluoride
  * Hexafluoroisopropanol
• Cannot undergo metabolism to form acyl halide
  --> Cannot stimulation formation of anti-trifluoroacetylated protein antibodies
  --> Cannot produce hepatitis
  * Unlike HAL, ENF, ISO, and DES
• Least likely to form carbon monoxide with strong base in carbon dioxide absorber
• Can degrade in presence of the strong bases in carbon dioxide absorber
  --> Fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl-ether (Compound A)
• Compound A is a dose-dependent nephrotoxin in rats
  --> Causes renal proximal tubular injury

Xenon

Prepared by fractional distillation of atmospheric air

Properties

• Low potency
  * MAC = 63 to 71%
  * cf. MAC for N2O = 104%
  * MAC is lower in females
• Very low solubility
  * Blood:gas = 0.115
• Nonexplosive, nonpungent, odourless
• Chemically inert
  * Low toxicity and metabolism

Clinical relevance

• Recovery is very fast
• Potent hypnotic and analgesia
• Does NOT produce haemodynamic depression in adult
• No effect on muscle relaxant effect (rocuronium)
• Some antagonist effect at NMDA receptors (like ketamine)
  --> May be neuroprotective
• No action on dopaminergic pathways
• Can cause air bubble expansion like N2O
• Does NOT trigger malignant hyperthermia