Inhalational Anaesthetic Agents.

Dr Amupitan.

Introduction.

• Volatile and gaseous anaesthetic agents remain popular for maintenance of anaesthesia and, under some circumstance for induction of anaesthesia.
• Three factors affect anaesthetic uptake; solubility in the blood, the alveolar blood flow and the difference in the partial pressure between alveolar gas and venous blood.

• Chloroform, ether and nitrous oxide were the first universally accepted general anaesthetics.
• Chloroform and ether however are no longer in use.

Stages of Anaesthesia.

• Historically , the stages of anaesthesia was described using diethyl ether.
• First stage: this is from beginning of induction to the loss of consciousness. Also known as stage of analgesia.
• Second stage. This is from loss of consciousness to onset of regular breathing. Also known as stage of excitement.

• Third stage: this is from onset of regular breathing to onset of diaphragmatic paralysis. This is the stage of surgical anaesthesia.
• This is from diagphragmatic paralysis to apnea and death. It is the stage of anaesthetic overdose.
• It should be noted that these classical stages are not as clearly with current inhalational agents.

Properties of an ideal inhalational agent.

• It should have a pleasant odour ,be non –irritant to the respiratory tract and allow peasant and rapid induction of anaesthesia.
• It should possess a low blood/ gas solubility which permits rapid induction and rapid recovery.
• It should be chemically stable in storage and should not interact with the material of anaesthetic circuit e.g soda lime.

• It should be capable of producing unconsciousness with analgesia and some degree of muscle relaxation.
• It should be neither flammable or explosive.
• It should be non toxic and not provoke allergic reactions.
• It should produce minimal cardiovascular and respiratory symptoms.

• It should be easy to administer using standard vaporizers.
• It should not be epileptogenic or raise intracranial pressure.
• None of the inhalational anaesthetic agents approaches the standards required of the ideal agent.

Minimum Alveolar Concentration (MAC)

• MAC is the alveolar concentration of an inhaled anaesthetic that prevents movement in 50% of patients in response to a standardized surgical stimulus.
• Factors that lead to a reduction in MAC include; sedative agents e,g premedication agents, nitrous oxide, increasing age, hypotension, hypothermia etc.

• Factors which increase MAC includes decreasing age, pyrexia ,presence of ephedrine, hypercapnia and chronic alcohol ingestion.
• MAC has gained widespread acceptance as an index of anasthetic potency which can be measured.

• Although the mechanism of action of inhalation anaesthetics remains unknown,it is assumed that their ultimate effect depends on attainment of a therapeutic tissue concentration in the CNS.
• The most important route for elimination of inhalational agents is the alveolus.

Uptake of Inhalational Anaesthetics.

• Can be divided into two phases: pulmonary and circulatory.
• Pulmonary phase: affected by

1) inhaled concentration of the agent- the higher the concentration, the more rapid the induction.

2)alveolar ventilation – the uptake of inhalational is proportional to alveolar ventilation

• Hypoventilation or airway obstruction will slow down induction while hyperventilation will make induction more rapid.
• 3) Blood / gas partition coefficient- the less soluble an anaesthetic is in blood, the more rapid is induction because alveolar tension of the anaesthetic will build up faster.

• 4) Pulmonary blood flow: when this is reduced, as in shock, induction is more rapid because alveolar tension of anaesthetic builds up faster.
• 5) Second gas effect- induction is faster if e.g nitrous oxide ( the second gas) is given with the inhalational agent rather than oxygen alone.

• 6) Alveolar membrane- diffusion and hence uptake will be reduced in the presence of pulmonary oedema or fibrosis.
• Circulatory phase: affected by the following
• 1) Cardiac output- a high cardiac output slows down inhalational induction by reducing the rate of increase in alveolar tension of the anaesthetic agent.

• 2) Cerebral blood flow- a greater cerebral blood flow is associated with a more rapid induction of anaesthesia.
• 3) Ventilation/ perfusion ratio – ventilation perfusion mismatch can slow down inhalational induction.

Inhalational Agents.

• The modern volatile inhalational agents in use now include halothane, isoflurane, sevoflurane, enflurane and desflurane.
• Inhalational anaesthetic agents can be divided into 2:
• 1) Ethers – isoflurane, sevoflurane, enflurane, desflurane and diethyl ether.
• 2)Halogenated hydrocarbon - halothane

Halothane

• Synthesized in1951 and introduced into clinical practice in the UK in 1956.
• Physical properties.
• Halogenated alkane
• Colourless liquid with a relatively pleasant smell
• The addition of thymol preservative and storage in amber- coloured bottles renders it stable.

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• Has a MAC of 0.75
• Blood /gas solubility coefficient of 2.5
• Non – irritant to the airway and therefore inhalational induction relatively fast.
• Recovery from halothane anaesthesia is slower than with other gases because of its high blood/ gas solubility.

• Metabolism and excretion
• Approximately 20% metabolized in the liver usually by oxidative pathway.
• Major metabolite is trifluoroacetic acid.
• Metabolized by isoenzyme of cytochrome P-450.
• End products excreted in the urine.

Effect of halothane on organ systems.

• Cardiovascular :
• Dose dependent reduction of blood pressure due to myocardial depression
• Hypotension due to peripheral vasodilation
• Bradycardia may occur usually reversible by atropine.
• Arrhythmias may occur with local infiltration with adrenaline- tarchycardia, ventricular extrasystole or even cardiac arrest.

• Respiratory system:
• Non – irritant and pleasant to breath during induction.
• Has bronchodilator effect.( good in asthmatics)
• In unpremedicated patients, associated with an increases ventilatory rate and decreased tidal volume.

• Rapid loss of pharygeal and larngeal reflexes.
• Inhibition of salivary and bronchial secretions by depressing clearance of mucus from respiratory tract causing postoperative hypoxia and atelectasis.

• Central nervous system:
• Produces anaesthesia without analgesia
• Cerebral blood flow and intracranial pressure increased.
• No seizure activity on EEG.

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• Uterus
• Relaxes uterine muscle and may cause postpartum haemorrhage
• GIT – minimal nausea and vomiting, gastric motility may be inhibited
• Liver – halothane induced hepatitis especially with repeated doses. Should be avoided inpre existing liver dysfunction.

Isoflurane

• Physical properties :
• Colourless,volatile liquid with slightly pungent odour.
• Stable and does not react with other metals or substances.
• Does not require preservatives.
• Non – flammable in clinical concentrations
• MAC 1.2%

• Has blood /gas solubility of 1.4 and tha alveolar concentration with inspired concentration.
• Pungency of vapour limits rate of induction.
• Not an ideal agent for induction.
• Approximately 0.17% of absorbed dose is metabolised.
• Metabolism is predominately by oxidation.

Effect of Isoflurane on organ systems

• Cardiovascular:
• Myocardial depressant effect, however less than with halothane
• Less depression of cardiac output
• Respiratory system:
• Dose dependent ventilatory depression
• Decreased tidal volume but increased ventilatory rate.

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• Causes respiratory irritation.
• Cental nervous system:
• Low doses does not cause any change in cerebral blood flow.
• However, high concentrations may cause vasodilation and increased cerebral blood flow
• No seizure activity on EEG.

• Uterus –similar as halothane.
• Advantages of isoflurane- rapid recovery,low risk of hepatic or renal toxicity, low risk of arrthymias and muscle relaxation.

Sevoflurane

• Non flammable
• Pleasant smell
• MAC 2%
• Blood /gas solubilty coefficient 0.69
• Stable and stored in amber colouredbottle.
• Rapid induction
• Metabolised in the liver.

Desflurane

• Structure similar to isoflurane.
• MAC 6%
• Pungent and not suitable for induction
• Rapid recovery.

Nitrous oxide

• Colourless, non irritating
• A good analgesic but weak anaesthetic agent
• Non flammable but supports combustion.
• Insoluble in comparison with other inhalational agent.
• Can be used with oxygen during maintenance of anaesthesia
• Causes marrow supression , agranulocytosis, diffusion hypoxia and expansion of air filled spaces.

Ether

• Colourless, highly volatile liquid
• Flammable and explosive in oxygen.
• Use of ether has been abandoned widely due to its flammability
• High blood /gas solubility of 12. MAC 105
• Induction of anaesthesia with ether is slow
• Irritant to the airway and provokes coughing and breath holding.

• Causes profuse secretions from mucous secreting glands.
• Premedication with anticholinergic agent is essential.
• Myocardial depression.