Inhalational Anaesthetic Pharmacology

Question 1

1. What are the most commonly used inhalational anaesthetic agents?
2. What spp. are they used for?
3. Why are other previously used inhalational anaesthetic agents not used anymore?
4. Name agents they are being used less or not at all.

Answer 1

1. Isoflurane and sevoflurane.
2. Cats and dogs w/ some variations.
3. They have been associated w/ increased risk of anaesthesia related death and have environmental impacts.
4. Halothane (difficult to obtain and recent withdrawal of MA), desflurane (no MA), nitrous oxide (environmental impacts), ether, methoxyflurane, cyclopropane.

Question 2

Ideal properties for inhalational agent.

Answer 2

Non-irritant to MMs.
Minimal effects on CV and resp. function.
Rapid uptake and elimination.
Non-toxic.
Non-flammable and chemically stable.
Easily vaporised.
Good analgesia and muscle relaxation.

Question 3

1. What is MAC?
2. How is MAC determined?

Answer 3

1. Minimum alveolar concentration = minimum anaesthetic conc. required to prevent a purposeful movement in response to a supramaximal noxious stimulus in 50% of subjects.
2. Determined experimentally to compare the potency of agents. The subjects do not receive any injectable anaesthetic agents, pre-meds, they are mask induced.
   Once anaesthetised, clamp or electrical stimulus applied, usually to a digit.
   Anaesthetic agent conc. altered and stimulus applied again to see if any withdrawal reflexes.
   Series of measurements obtained, allowing MAC to be calculated.

Question 4

1. What reduces MAC?
2. What increases MAC?

Answer 4

1. Other drugs e.g. pre-meds, LAs; hypothermia; pregnancy; geriatric and neonatal animals; and hypothyroidism.
2. Hyperthermia, youth, hyperthyroidism, administration of catecholamines and sympathomimetics.

Question 5

Physical properties of…
1. Vapour.
2. Gas.
Define…
3. Partial pressure.
4. Partition coefficient.

Answer 5

1. Gaseous state of a substance that at ambient temp. and pressure is a liquid.
2. Exists in gaseous form at room temp. and sea level.
3. Pressure that individual gas exerts un a mixture of gases.
4. Ratio of the concentration of a compound in two solvents at equilibrium.

Question 6

1. Inhalational agent site of uptake.
2. Inhalational agent site of action.
3. What enhances uptake of the inhalational agent and the recovery from anaesthesia?
4. Relationship between blood gas solubility and speed of onset and recovery?
5. Relationship between CO and speed of onset of anaesthesia. – + consideration.
6. What impact does the blood tissue solubility have on the effects of anaesthetic inhalational agents?

Answer 6

1. Lungs.
2. Brain.
3. Good and effective alveolar ventilation.
4. The lower the blood gas solubility, the faster the onset of anaesthesia and recovery from it.
5. Lower CO, faster onset of anaesthesia. – Care when anaesthetising sick animal w/ lower CO.
6. It impacts on how widely distributed anaesthetic agent is w/in body.

Question 7

What is done to reduce the dose-dependent resp. and CV depression caused by inhalant anaesthetics?

Answer 7

Balanced anaesthesia by the use of combo of drugs aiming to benefit from their desired effect while minimising adverse effects.
Anaesthetic triad considered vital.
Detailed monitoring of patient.
Supportive therapies incl. fluids and facilities for ventilation.

Question 8

1. State of nitrous oxide.
2. Nitrous oxide MAC.
3. Analgesia?
4. Speed of uptake and elimination? – why?
5. Rations in breathing systems. Recommendation?

Answer 8

1. Liquid in cylinders, administered as gas.
2. > 100% – used to supplement anaesthesia.
3. Good analgesia.
4. Rapid. – Insoluble
5. 1:2 in non-rebreathing, 1:1 in circle.
   O2 monitoring recommended.

Question 9

1. Irritation of isoflurane and sevoflurane?
2. Iso and sevo CV and resp. effects.
3. Uptake and elimination of sevo and iso?

Answer 9

1. Iso can be irritant to MMs.
   Sevoflurane better tolerated for induction than iso, but not recommended.
2. Iso can cause CR depression which is dose-dependent.
   Same for sevo.
3. Iso rapid. Primarily via lungs w/ <1% biotransformed by liver. Blood gas solubility (aka partition) coefficient 1.4.
   Sevo rapid. Primarily via lungs w/ 3% biotransformed by liver. Blood gas solubility coefficient 0.69 so faster uptake and elimination than iso.

Question 10

1. Iso and sevo toxicity.
2. Flammability and chemical stability of iso and sevo.
3. Vaporisation of both.
4. Analgesia of iso and sevo.
5. Muscle relaxation of iso and sevo.

Answer 10

1. Both non-toxic.
2. Both non-flammable and chemically stable but sevo can produce compound A by reacting w/ soda lime.
3. Both easily vaporised.
4. Both no analgesia, only unconsciousness.
5. Both cause muscle relaxation that us adequate for most procedures.

Question 11

Effects of inhalation agents (iso and sevo) on CNS.

Answer 11

• Both decrease cerebral metabolic rate, decreasing cerebral O2 consumption demand, subsequently decreasing cerebral blood flow.
• Both can cause cerebral vasodilation so there is an overall balance between decreased O2 demand and cerebral vasodilation w/ general increase in blood flow.
  – Both increase intracranial blood vol so consideration for head trauma or intracranial pathology patients.
• Sevo may preserve cerebral perfusion better than iso at equipotent levels.
• Deflurane associated w/ greater degree of cerebral vasodilation so should use w/ caution in patients w/ increased intracranial pressure.

Question 12

CV effects of inhalation agents (iso, sevo, des).

Answer 12

• Both cause CV depression.
• Hypotension common and via many mechs.
• Reduced myocardial contractility and vasodilation respectively cause reduced CO and systemic vascular resistance.
• Desflurane may cause hypotension primarily through reduced myocardial contractility.
• Effects on HR inpredictable.
  – Tends to increase but not enough to offset hypotensive effects.
• Desflurane particularly causes tachycardia when inspired conc. increased rapidly but this response is blunted when potent opioids also administered.
• Limit use of IPPV can reduce CR so limit use, but IPPV may be necessary to offset respiratory depression and ensuing hypercapnia and respiratory acidosis.

Question 13

Respiratory effects of iso and sevo.

Answer 13

• Dose-dependent respiratory depression w/ consequent hypercapnia.
  – Caused by decrease in minute volume due to decreased tidal volume and/or decreased RR.
  – Hypoventilation may be less obvious if only monitoring RR as tidal vol also a factor.
  – Tidal volume harder to assess as is monitored subjectively.
• Tidal volume tends to be reduced initially and then the RR decreases.
• Reduced resp. drive so blunted response to CO2.
• Relaxation of resp. muscles.
• Ventilation-perfusion mismatch.
• Hypoxaemia uncommon as O2 used in carrier gas for VAs.
• RR better maintained w/ sevo and des but no guarantee of adequate ventilation.
• Resp. arrest will occur at 2.5 x MAC for iso and just over 3x MAC for sevo.
• Both cause bronchodilation so an increase in VA conc. could help w/ bronchospasm, nut this increase likely to cause undesirable cardiopulmonary depression – poss. detrimental.
  Sevo smell generally better tolerated than iso or des – beneficial for inhalation induction by face mask or chamber – disadvantageous in many ways (workplace pollution, personnel exposure, lack of rapid airway control, increased stress).