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INHALATION AGENTS

2013/05/28 2Isn’t it romantic…?

Administration

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Physics

� Critical temperature

� Vapour vs. Gas

� Vapour pressure

� Blood–Gas–Partition–Coefficient – BGPC

� MAC

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Critical temperature

� Substance in gaseous phase

� Forced back into fluid phase

� If pressure in container increases

� Except!!!!!!!!!!!!!!!!!!!!

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Critical temperature� If substance in gaseous phase exist

� Above a specific critical temperature

� NO ↑ in pressure will force phase change!

� Will stay a gas

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Critical temperature

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Critical temperature

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Definition of a vapour/gas

� Vapour

– Gaseous phase below critical temperature

� Gas

– Gaseous phase above critical temperature

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Application of Tcrit.

� Oxygen = T crit. of -119ºC

– Quantity in cylinder measured by pressure

gauge

� Nitrous oxide = T crit. of 36,5ºC

– Revert to fluid phase in cylinder

– Quantity in cylinder by weight!

– Is a VAPOUR not a gas!

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Vapour pressure

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Vapour pressure: implications

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INHALATION AGENTS

IDEAL INHALATION AGENT

� Stable (heat, light, metal, soda lime)

� No preservative

� Long shelf life

� Non-flammable, explosive in air, O2, N2O

� Non-irritating to airways

� Atmospherically friendly

� Cheap to synthesize

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INHALATION AGENTS

IDEAL INHALATION AGENT

� Low MAC

� Low blood-gas coefficient

� Not metabolised

� Non-toxic to any organ

� No cardiovascular effects

� No respiratory effects

� Analgesic

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INHALATION AGENTS

IDEAL INHALATION AGENT

� Reversible CNS effects

� No epileptogenic activity

� No drug interaction

� No effect on pregnant uterus or foetus

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INHALATION AGENTS

RATE OF UPTAKE IN BLOOD DEPENDS ON:

� Solubility in blood

� Cardiac output

� Concentration administered

� Alveolar ventilation

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INHALATION AGENTS

Fi FA BGPC

LUNGS PLASMA BRAIN

What makes the patient

sleep?

C.O.

INHALATION AGENTS

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Solubility of vapour in blood

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Solubility of vapours in blood

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INHALATION AGENTS

BLOOD-GAS PARTITION COEFFICIENT

Solubility of vapour in blood:

� The higher the BGPC the more soluble

� The higher the BGPC the slower the action

� The higher the BGPC the slower the recovery

…and the opposite is also true…

INHALATION AGENTS

� Bus vs motorcycle

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INHALATION AGENTS

MINIMUM ALVEOLAR CONCENTRATION:

“MAC50”

Alveolar [vapour] when 50% of people will lie still upon skin incision

(and 50% will move!)

Indication of potency!

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INHALATION AGENTSVAPOUR BGPC MAC

Desflurane 0,42 6%

N2O 0,47 104%

Sevoflurane 0,6 2%

Isoflurane 1,4 1,15%

Enflurane 1,8 1,68%

Halothane 2,3 0,77%

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INHALATION AGENTS↑↑↑↑ MAC ↓↓↓↓ MAC

Chronic C2H5OH Acute C2H5OH

Hyperthyroidism Analgesics

Hyperthermia Sedatives / Opiates

Small children Hypothyroidism

Drug dependency Hypothermia

Narcotic misuse Geriatrics

↑ Cardiac output ↓ Cardiac output

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INHALATION AGENTS� HALOGENATED HYDROCARBONS

– Halothane

� ETHERS

– Enflurane

– Isoflurane

– Sevoflurane

– Desflurane

– Diethylether

� GASSES

– N2O / Xenon

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N2O

� Colourless, odourless, non-flammable

� Colour code = blue

� Critical temperature = 36,5oC

� Vapour pressure = 5500kPa

� Weigh cylinder to determine content

� Below 36,5oC � VAPOUR!! (don’t tell anyone!)

N2O 0,47 104%

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N2O

- 2nd gas effect

- Diffusion hypoxia

N2O 0,47 104%

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N2O

- Expand air filled cavities

- Bone marrow suppression

- Teratogenic

- ↑ PVR

- ↓ Myocardial contractility

N2O 0,47 104%

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HALOTHANE

� ↑ Cerebral blood flow – ↑ intracranial pressure – ICP

Halothane 2,3 0,77%

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HALOTHANE

�Cardiac effects� Decreased myocardial contractility

– Ca++ antagonist

– SVR remains normal

� Sensitizes myocardium for catecholamines

� Suppresses conduction (whole conduction system)

• Bradycardia

• Re-entry phenomena

Halothane 2,3 0,77%

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HALOTHANE

�Respiratory system

– Bronchodilator

– Hypoventilation

Halothane 2,3 0,77%

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HALOTHANE

�Liver

– 20% metabolised by liver

– Halothane hepatitis:

� Immunologic reaction

� Toxic reductive metabolites– Tri-fluoro acetic acid (TFA)

� Ischaemic conditions

– Rare 1:35000 but mortality risk 90%

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HALOTHANE

� Halothane hepatitis predisposing factors:

– Female

– Middle age

– Obesity

– Multiple administrations

– Enzyme induction

– ↓ Glutathione (fasting)

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HalothaneSmells OK

Relatively low BGPC.

Relatively rapid induction and recovery

CVS

↓HR↓CO↓BP

Dysrhythmias↓ ConductionCatecholamine sensitivity

↓VO2

RESP

↓ Breathing Bronchodilation

↑Secretions

Hepatitis

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ENFLURANE

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ENFLURANE

� Irritating to the awake airway

� Less dysrhythmogenic than Halothane

� 2% metabolised by liver

� Increased ICP by increased CSF

– ↑ production and ↓ reabsorption

� Epileptogenic changes on EEG (with ↓CO2)

� ↓BP more due to vasodilation (less ↓CO)

� Potentiate skeletal muscle relaxants

Enflurane 1,8 1,68%

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EnfluranE

EEGLow BGPC

Rapid InductionXSmells Bad

CVS

↓BP less than HaloNo dysrhyhtmias

RESP

Bronchodilator

↓Breathing

Finorg

EXPENSIVE

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ISOFLURANE

� CNS

– Maintains autoregulation up to 1 MAC

– Non-epileptogenic

– ↓ CSF production & ↑ CSF absorption

– Least ↑ CBF

– Least ↑ ICP

– Most ideal for neuro-anaesthesia

Isoflurane 1,4 1,15%

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ISOFLURANE

� CVS

– Potent vasodilator

– Mild tachycardia?

– Less myocardial suppression compared to halothane

– Coronary steal? (steal-prone anatomy)

– Not dysrhythmogenic

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ISOFLURANE

� Irritating to the awake airway

� Potent muscle relaxant

� 0,2% metabolised by the liver

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Isoflurane

BGPC=1.4

CVS

Vasodilatation

CoronarySTEAL

↓BP

Drug of choice:

NEURO

LIVER

EXPENSIVE

Bronchodilator

PUNGENT

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SEVOFLURANE

� Non-irritating to the airways (SMELLS NICE!)

� Ideal agent for inhalation induction

(second choice is Halothane)

� CNS = same as isoflurane

� CVS = small drop in BP

= not dysrhythmogenic

Sevoflurane 0,6 2%

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SEVOFLURANE

� 2-5% metabolised by the liver

– Hexa-fluoro-isopropanol � hepatotoxic

– Inorganic fluoride

� Decomposes 6% per hour in soda lime at 22oC

Sevoflurane 0,6 2%

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SEVOFLURANE

SEVOFLURANE

Desiccated soda lime

BREAKDOWN

COMPOUND A

Sevoflurane 0,6 2%

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SEVOFLURANE

COMPOUND A

ββββ-lyase

Nephrotoxic substance

Sevoflurane 0,6 2%

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Sevoflurane

BGPC=0.6Fast onsetFast emergence

CVS

Vasodilatation

NO STEAL

↓BP

Drug of choice:

NEURO

Gas induction

VERY EXPENSIVE

Renal –Compound A

Pleasant smell

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DESFLURANE

� BGPC = 0,42

� High vapour pressure (681mmHg at 20oC)

� New technology vapouriser

� Tachycardia for few minutes

� Produces CO in desiccated soda lime

(so does enflurane, isoflurane)

Desflurane 0,42 6%

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DIETHYLETHER

� BGPC = 12

� Respiratory depression precedes cardiovascular depression

� Good analgesic

� Highly flammable

� Nausea and vomiting

� ↑ Secretions

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Desflurane

BGPC=0.42Rapid onsetRapid emergence

CVS

Vasodilatation

Sympatheticresponse

↓BP

Drug of choice:

LIVER

Short cases

VERY EXPENSIVE

RESP irritant

VERY PUNGENT

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