Inhalation anaesthetic agents

• Inhalational anaesthetic agents


  • Nitrous oxide
  • Ether
  • Halothane
  • Isoflurane
  • Desflurane
  • Sevoflurane
• Properties of ideal inhalational anaesthetic agent

  • Pleasant odour, non-irritant to respiratory tract, allows rapid induction
  • Low blood/gas solubility for rapid induction and recovery
  • Chemically stable, non-flammable, non-explosive
  • Produces unconsciousness with analgesia and muscle relaxation
  • High inspired oxygen concentration capability
  • Non-metabolized, non-toxic, non-allergenic
  • Minimal cardiovascular and respiratory depression, no drug interactions
  • Completely inert and rapidly eliminated unchanged via lungs
• None of the inhalational anaesthetic agents either of historical interest or in current use approaches the standards required of the ideal agents
• Minimum Alveolar Anaesthetic Concentration (MAC)

  The minimum alveolar concentration of an anaesthetic at 1 atmosphere absolute that prevents movement of 50% of the population to a standard stimulus
• Anaesthesia is related to the partial pressure of an inhalational agent in brain rather than its % concentration in alveoli
• MAC has gained widespread acceptance as an index of anaesthetic potency as it is measured
• Factors affecting MAC


  • Premedication
  • Nitrous oxide
  • Disease states (e.g. thyrotoxicosis, myxoedema)
  • Pyrexia
  • Age (higher in infants/neonates, declines with age)
  • Sympathoadrenal stimulation (e.g. hypercapnia)
  • Drugs affecting neurotransmitter release (e.g. ephedrine, amphetamine, reserpine, methyldopa, pancuronium, clonidine)
  • Atmospheric pressure
• For halothane, MAC is 1.1% in neonates, 0.95% in infants, 0.9% at 1-2 years, 0.75% at 40 years, and 0.65% at 80 years
• Ether


  • Colourless, highly volatile liquid with characteristic smell
  • Forms flammable/explosive mixtures in air and oxygen-enriched environments
  • Manufactured by heating ethyl alcohol and concentrated sulfuric acid
• Ether


  • Relatively high blood/gas solubility coefficient of 12, slow equilibration of alveolar with inspired concentration
  • Irritant to respiratory tract, provokes coughing, breath-holding, and profuse secretions
  • Usually administered using an anaesthetic breathing system with non-calibrated (Boyle's bottle) or calibrated (Emo) vaporizer, occasionally using a Schimmelbusch mask
• Halothane


  • Colourless liquid with relatively pleasant smell
  • Decomposed by light, stabilized by addition of 0.01% thymol and storage in amber bottles
  • Relatively low blood/gas solubility coefficient of 2.5, allowing relatively rapid induction
• It may take at least 30 minutes for the alveolar inspired concentration of halothane to reach 50% of the inspired concentration, slower than for enflurane or isoflurane
• Halothane metabolism and effects

  • About 20% metabolized in the liver, usually by oxidative pathways
  • Non-irritant and pleasant to breathe during induction
  • Rapid loss of pharyngeal and laryngeal reflexes
  • Inhibition of salivary and bronchial secretion
  • Antagonizes bronchospasm and reduces airway resistance
  • Arrhythmias are very common, more frequent than with enflurane or isoflurane
  • Relaxes uterine muscle, may cause postpartum hemorrhage
  • Causes skeletal muscle relaxation and potentiates non-depolarizing relaxants
  • Post-operative shivering is common
• Halothane remains the drug of choice for pediatric anaesthesia, in preference to enflurane or isoflurane
• Advantages of halothane


  • Rapid, smooth induction
  • Minimal stimulation of salivary and bronchial secretions, no need for atropine
  • Bronchodilation
  • Muscle relaxation
  • Relatively rapid recovery
• Disadvantages of halothane


  • Poor analgesia
  • Arrhythmias
  • Post-operative shivering
  • Possibility of liver toxicity, especially with repeated administration
• Enflurane


  • Clear, colourless, pleasant ethereal smell
  • Non-flammable in clinical use
  • Stable with soda lime and metals, does not require preservative
  • Blood/gas solubility coefficient of 1.9
  • About 2.5% of absorbed dose is metabolized, predominantly to fluoride
• Enflurane is non-irritant and does not increase salivary or bronchial secretions
• Enflurane is associated with a much smaller incidence of arrhythmias than halothane and much less sensitization of the myocardium to catecholamines
• Bronchial stimulation


  Prior administration of atropine is unnecessary
• Bronchodilation


  • Muscle relaxation
  • Relatively rapid recovery
• Enflurane


  (2-chloro-1,1,2-trifluoroethyl difluro methyl ether)
• Synthesized and first evaluated clinically 1966

  1963
• First introduced into clinical practice in the USA


  1971
• Enflurane


  • Clear, colourless, pleasant ethereal smell
  • Non flammable in clinical
  • Stable with soda lime and metals and does not require preservative
  • Blood/gas solubility coefficient is 1.9
  • About 2.5% of the absorbed dose is metabolized, predominantly to fluoride
• Enflurane


  • Non irritant and does not increase salivary or brondual secretions
  • Associated with much smaller incidence of arrhythmias than halothane and much less sensitization of the myocardium to catecholamines either endogenous or exogenous
• Enflurane


  • Produces dose-dependent depression of EEG activity, but at moderate to high concentration (more than 3%) it produces epileptiform paroxysmal spike activity and burst suppression
  • Should be avoided in epileptic patient
• Isoflurane


  (1-chloro-2,2,2-trifluoroethyl difluro methyl ether)
• Synthesized


  1965
• Clinical studies undertaken


  1970
• Approved by the food and drug administration in the USA

  1980
• Isoflurane


  • Colourless, slightly purgent odour
  • Stable and does not react with metal or other substances and does not require preservatives
  • Non-flammable in clinical concentration
  • Least soluble blood/gas solubility co-efficient is 1.4
  • Due of pungency, the incidence of coughing or breath holding on induction is significantly greater with isoflurane than with halothane
  • Only 0.17 of the absorbed dose is metabolized
• Isoflurane


  • Coronary steal syndrome due to coronary vessel vasodilatation at the stenosed area not perfussed
  • Low concentration of isoflurance do not cause any changes in the cerebral blood flow at normocapnia
  • Higher inspired concentrations of isoflurance cause vasodilation and increase cerebral blood flow
  • It does not cause seizure activity on EEG
• Sevoflurane


  Methylpropyl ether
• Isolated


  Early 1970
• First used in humans

  1981
• Sevoflurane


  • Non-flammable, with pleasant smell, blood/gas co-efficient 0.6
  • Oil-gas partition co-efficient of 55 and MAC value of 2.0%
  • Does not appear stable in sodalime
  • Does not sensitize the myocardium to cathecolamine and it appears to have relatively little effect on the cardio vascular and respiratory system
  • Its physical properties suggests that it may be useful for gaseous induction of anaesthesia in children
• Desflurane


  • 1st used in humans in 1988
  • The structure differs from isoflurane only in the substitution of fluorine for chlorine
  • Blood/gas solubility co-efficient of or 0.42, oil-gas partition co-efficient of 18.7
  • Because of the boiling point of 23.50C, it cannot be used with conventional vapourizers
  • No preservatives
• Desflurane


  • Stable with sodal lime
  • Has ethereal but much less pungent odour than isoflurane
  • Undergoes minimal biodegradation and does not sensitise the myocardium to cathecolamus
  • Uptake and elimination of desflurance are virtually identical to those of nitrous oxide and the drug therefore has theoretical advantage over the conventional volatile anesthetic agent
• Nitrous Oxide (N2O)


  • Produced commercially heating ammonium nitrate to a temperature of 245-2700C
  • After production the higher oxide of nitrogen dissolve in water to form nitrous and nitric acid
  • These substances are toxic and produce met hb and pulmonary oedema if inhaled
  • In the past these have been several reports of death occurring during anesthesia as a result of the inhalation of nitrous oxide contaminated with higher oxide of nitrogen