``Types of inhalational agents

• Gaseous: Nitrous oxide

• Volatile liquid: Halothane, enflurane, isoflurane

Mechanism of action

• Increase the threshold of cells to firing, thereby resulting in decreased activity

• Reduce rate of rise of action potential by interfering with sodium influx

• Effect in cell membrane via anaesthetic molecule dissolving in lipid neuronal membrane

Pharmacokinetics

• Depth of anaesthesia is determined by concentration of anaesthetic in CNS

• Rate at which an effective brain concentration is reached [rate of induction of anaesthesia] depends on pharmacokinetic factors that influence the uptake & distribution of the anaesthetic

Uptake & distribution

• Concentration of an anaesthetic gas [or any gas] in a mixture of gases is proportional to its partial pressure or tension

• Achievement of an adequate brain concentration to cause anaethesia requires transfer of anaethetic from alveolar air to blood to brain

• The rate at which a given concentration of anaethetic in the brain is reached is dependent on:

1) Solubility properties of anaesthetic

- influences transfer of anaesthetic from lungs to blood

- blood:gas partition coefficient defines relative affinity of anaesthetic for blood compared to air [higher value indicates increased affinity for blood]

- eg nitrous oxide with a low solubility in blood, reaches arterial tensions rapidly, which results in more rapid equilibration with the brain and faster induction of anaethesia

Anaesthetic	Blood:Gas Partition Coefficient
Nitrous oxide	0.47
Isoflurane	1.4
Enflurane	1.8
Halothane	2.3

2) Anaesthetic concentration in Inspired Air

- Concentration of inhaled anaethetic in inspired gas has direct effects on:

- i) Maximum tension achieved in alveoli

ii) Rate of increase in its tension in blood

Increase in inspired anaethetic concentration will increase rate of induction of anaethesia by increasing rate of transfer into blood [according to Fick’s law]

3) Pulmonary Ventilation

- Rate of rise of anaesthetic gas tension in blood is directly dependent on both rate & depth of ventilation

4) Pulmonary Blood Flow

- An increase in pulmonary blood flow [increased CO] slows the rate or rise in arterial blood tension

- therefore in patients with reduced cardiac output [shock], the decreased pulmonary blood flow may accelerate induction of anaesthesia

Elimination

- The time to recovery from an inhalational anaesthetic depends on the rate of elimination of anaesthetics from the brain after the inspired concentration of anaesthetic has been decreased

- The increase in solubility of anaesthetic in blood and brain, the longer time is required for elimination

- Increased duration of exposure to volatile anaesthetic prolongs time for recovery, especially with more soluble anaesthetics

Minimum Alveolar Anaesthetic Concentrations [MAC]

- During general anaesthesia, the partial pressure of an anaesthetic in the brain equals that in the lung when steady state is achieved: at this point measurement of alveolar concentrations of different anaesthetics provides a comparison of their relative potencies

- MAC of an anaesthetic is defined as the concentration that results in immobility in 50% of patients when exposed to a noxious stimuli

- Individual patients may require from 0.5 - 1.5 MAC

- Dose response curve is steep: over 95% of patients may fail to respond to stimulus at 1.1x MAC

- MAC is not affected much by sex, height & weight

- MAC values decrease with age

- MAC is decreased with analgesics and sedatives-hypnotics

- note that nitrous oxide is the least potent

Anaesthetic	MAC [%]
Nitrous oxide	> 100
Isoflurane	1.4
Enflurane	1.68
Halothane	0.75

- note: reaction of isoflurane with polycarbonate plastics

Anaesthetic	Summary
Isoflurane	Potent, expensive, reacts with polycarbonates (& to a much lesser degree PVC); may cause coronary ‘steal’ if CPP too low
Enflurane	Not associated with jaundice and does not react with plastics; but lower therapeutic index than isoflurane & halothane
Halothane	Potentially associated with hepatitis: jaundice