by Dr N Shava (SHO Anaesthesia) United Bulawayo Hospitals

1. INHALATIONAL ANAESTHETIC AGENTS
Dr N Shava

2. Definition of General Anaesthesia
• General anaesthesia is described as a medically induced, reversible
state of unconsciousness with inability to respond to a standardized
surgical stimulus
• Achieved in three phases
1. Induction
2. Maintenance
3. Emergence
• The maintenance phase aims to achieve the three components of the
triad of anaesthesia

4. • No single agent can provide all these properties
• A combination of drugs from different categories is used
• Inhalational agents are used mainly to provide hypnosis during the
maintenance phase of anaesthesia- they provide the most common
means of maintaining anesthesia
• They may also be used as induction agents (Halothane and
sevoflurane)
➢Young children
➢ compromised airway – safer than IV because patient continues to breathe
spontaneously – Guedel stages of anesthesia may be used to gauge depth
➢Inaccessible veins

5. History of anaesthesia
• Inhalational anaesthetics – the most innovative medical discovery of
the 19th century
• Evidence of primitive forms of its use in the 12th/13th century
( use of sponges infiltrated with hashish, opium and herbal aromatics
by Arabian alchemists)

7. Diethyl Ether Paracleus in 1540, investigated for human use in 1845 Used first by Clark and Long in 1842,
but first public demonstration by
Morton in 1846
Nitrous Oxide Discovered in 1772 by Priestly and suggested for medical use in
1799
First use in 1844 by Wells
Chloroform First prepared in 1831, discovered as an anaesthetic in 1847 by
Simpson
John Snow administered it to Queen
Victoria in 1853 ( popularized
anaesthesia for child birth in the UK)
Wide use up to 1930
Cyclopropane First manufactured in the 1920s, discovered accidentally as an
anaesthetic agent
First clinical use in the 1930s, very
popular for almost 30 years
Halothane First manufactured in 1951 First clinical use in 1956
Flourexene and
Methoxyflurane
First manufactured in the 1950s
Enflurane and
Isoflurane
Part of the more than 700 compounds synthesized by Ohio
Medical products between 1959 and 1966
Sevoflurane First manufactured in the 1970s Introduced for clinical use initially in
Japan in 1990
Desflurane Part of the compounds synthesized by Terrell and colleagues Approved for clinical use in 1992

8. Delivery of Inhalational anaesthetics
• The goal is to produce the anaesthetic state by establishing a specific
concentration of molecules in the CNS
• The inhalational route is ideal for this because the lung is exposed to
the total cardiac output and as such is the highest perfused tissue
• Also it has a large surface area and high permeability
• When inhalational agents first came into use, primitive delivery
methods were employed
• There was hence little knowledge in terms of how much the patient
was getting versus how much was effective
• Anaesthesia machine – safe and predictable

9. The Anaesthetic Machine
• Accurate and continuous supply of medical gases mixed with
anaesthetic vapour
• Generally a variable concentration gas mixture of oxygen, nitrous
oxide and anaesthetic vapour is obtained from the machine and is
made to flow through the breathing circuit to the patient
• The gas delivery system of the machine itself consists of two
subsystems
i. The gas supply-delivery unit
ii. The anaesthetic vaporizers

10. Gas supply system
• Gases are supplied to the anaesthesia machine from either a
pressurized hospital central supply or from storage cylinders
• From the supply, the gas flows into the into the inlet of the
anaesthesia machine and is directed through the pressure safety
system towards the flow delivery unit

11. Vapour delivery - Vaporizers
• A vaporizer is a device that changes a liquid anesthetic agent into its vapor
and adds a controlled amount of vapor that vapor to the fresh gas flow
• Vaporizers are required because most volatile inhaled agents exist as
liquids at room temperature and pressure
• Pure vapours – too potent to be used alone, need dilution in a carrier gas (
air, oxygen, nitrous oxide)
• Vaporizers produce an accurate gaseous concentration of the volatile liquid
and the carrier gas
• The anaesthetic vapours are picked up from the vaporizer by the carrier gas
that bubbles through or passes over the liquid

12. Vaporizers – Basic design
• Fresh gas flow (carrier gas ) enters vaporizer
• Splitting of gas flow
• Some amount is allowed to enter the vaporizing chamber
• Majority is allowed to bypass
• Gas saturated with vapor exits the chamber
• Mixing with the bypassed gas takes place
• Diluted Gas + Vapor mixture leaves to the C.G.O
• Finally delivered to the patient

14. Characteristics of modern vaporizers
1. Use flow over technique
2. Employ variable bypass ( alternative is the flow meter control
method)
3. Temperature compensated
4. Agent specific
5. Safety measures – only one vaporizer used at a time
-- locked into the gas circuit
- keyed filling system

15. Vaporizer output calculation - Physics related to
vaporizers
• Vapor =gaseous phase of a substance which is normally a liquid at
room temperature and atmospheric pressure
• Vapor pressure = pressure exerted by a vapor on its surroundings – it
solely depends on the liquid characteristics and the temperature
• Saturated vapor pressure = the pressure exerted by a vapor pressure
when it is at equilibrium with its associated liquid
• Vapor behaves like a true gas – mixes freely with other gases in a
given space and gives a partial pressure ( Dalton’s Law)
• Boiling point = temperature at which the vapor pressure is equal to
the atmospheric pressure

18. • Three flow streams are considered when calculating vaporizer output
i. Vaporizer inflow – the volume of fresh gas delivered into the vaporizer
chamber per minute
ii. Diluent flow – the volume of fresh gas that bypasses the vapor chamber
iii. Vapor outflow
• Splitting ratio – ratio of bypass flow ( z ) to the flow to the flow through the
vaporizing chamber ( y ) – it depends on ratio of resistances in the two
pathways
- the resistance depends on the adjustable orifice present at the inlet and
outlet, size of orifice varies according to the concentration set by the dial
setting

20. • SVP/Total pressure = Agent vapor(ᵡ) / Carrier gas (y) + Agent vapor
(ambient pressure) (total volume exiting vaporizer)
• In accordance with Boyle’s law:
P₁V₁ = P₂V₂

22. Vaporizer output calculation

24. • The anaesthetic vaporizer output may be expressed either as
absolute pressure (mmHg), or in volume percentages
• Volume percent – the number of units of volume of gas in relation to
a total of 100 units of volume the of the total gas mixture
• The volume percent expresses the relative ratio of gas molecules in a
mixture, whereas partial pressure expresses an absolute value
• Anaesthetic uptake and potency are related directly to partial
pressure and only indirectly to volume percent

25. PHARMACOKINETICS
Definition: What the body does to the drug (how the drug moves
through the body)
• The objective is to obtain a certain concentration of anaesthetic in the
brain
• The uptake of the anaesthetic agent into the brain is preceded by
passage through various physiologic compartments
• Movement between these compartments depends on equilibration of
partial pressures

27. Factors affecting inspired gas concentration (Fi)
• This is the fractional anaesthetic concentration that leaves the circuit and enters the respiratory system
i. How much the vaporizer is set at
- the dial setting on the vaporizer determines the percentage of agent delivered to the alveoli
ii. Volume of breathing circuit –
- Increased volume of breathing circuit increases dead space, hence increases dilution of anesthetic gases
iii. Fresh gas flow rate (FGF) –
- Increased FGF increases speed of induction (and recovery)
iv. Absorption of agent by breathing system
- Rubber tubing absorbs more than plastic and silicon

28. Factors affecting alveolar concentration (Fᴀ)
• The rate of rise of the alveolar partial pressure (Fᴀ - measured by the
gas analyser as the end-tidal value) towards the inspired fractional
concentration (Fi) is equal to the net difference between input into
the alveoli and uptake by the arterial blood

29. Factors affecting input
1. Inspired fractional concentration( Fi)
– increasing the Fi not only increases the alveolar concentration but also the rate of its rise,
and hence the speed of induction ( the concentration effect)
- The ‘second gas effect’ is essentially another concentration effect
2. Alveolar ventilation
– increased alveolar ventilation, like Pi, promotes input of anaesthetic agent to offset
output
- more influential on more soluble anaesthetic agents
- induction is slowed by hypoventilation (respiratory depression, airway obstruction)
- a larger functional residual capacity results in slower onset of anaesthesia

30. Factors affecting uptake
a. Cardiac output
- Influences agent uptake and therefore Pᴀ by carrying away either more or
less anesthetic from the alveoli (e.g. CCF, elderly patients)
b. Arterial concentration of anesthetic agent (Fа)
- The partial pressure of agent reaching the systemic circulation is not always
the same as that in the pulmonary capillaries, there may be some degree of
shunting
c. Alveolar to mixed venous partial pressure difference
- This gradient depends on the amount of agent removed by the tissues, as
tissues get saturated, more agent returns to the lungs reducing the pressure
gradient

32. Factors affecting input – Impact of solubility
• Solubility of inhaled anesthetics in blood and tissue is denoted by
partition coefficients - a distribution ratio describing how the gas
distributes itself between two phases at equilibrium
• The partition coefficient depicts a relative capacity of each phase to
absorb the anesthetic agent

34. Blood- gas partition coefficient
• The rate of increase of the Pᴀ is inversely proportional to the
solubility of the anesthetic in blood
• The more soluble the agent is in blood, the longer it will take to
increase alveolar partial pressure
• Blood is a pharmacologically inactive reservoir

37. • Question ?
Blood- gas partition coefficients:
Methoxyflurane – 15
Desflurane - 0.42
Xenon – 0.14
Which one has the fastest induction time ?

38. Tissue uptake
• The uptake of anesthetic agents by tissues depends on
1. Tissue solubility – denoted by the tissue- blood partition
coefficient, determines the time necessary for equilibration of
tissues with Pa
2. Tissue blood flow – highly perfused tissues (brain, heart, kidneys,
liver- vessel rich group) , receive 75% of the cardiac output –
equilibrate rapidly
- once equilibrium is reached in this group, the muscle group will
equilibrate (1-3hrs), then finally the adipose tissue

40. Uptake by the brain
• The brain is the end target organ for inhalational anesthesia
• The concentration of agent at the brain level is mirrored by the end-
tidal concentration in the alveoli
• Uptake into the brain is determined by lipid solubility- which is
denoted by the oil : gas partition coefficient
• Lipid solubility is related to potency

42. Recovery from anesthesia
• Directly related to the rate of decrease of drug partial pressure in the brain
• At the conclusion of anesthesia, the concentration of agent in tissues
depends highly on the solubility of the anesthetic and the duration of its
administration
• Elimination of the anaesthetic agent occurs mainly through the alveoli,
and so the same factors that speed up induction also speed up recovery
• Factors influencing rapid emergence – high FGF
- lower tissue solubility
- shorter anaesthesia times

43. Metabolism
• Volatile agents are rapidly removed from the body via the lungs and
this is the most important route of elimination
• They are also metabolized by the cytochrome P450 enzymes to a
varying degree
• Some metabolites may be harmful
• Sevoflurane is the most metabolized

44. PHARMACODYNAMICS
• DEFINITION – The study of drug action, including toxic responses, i.e.,
‘how the drug affects the body’
• Theories of mechanism of action
• Potency – Minimal Alveolar Concentration (MAC)
• Effects on different organ systems and toxicities – individual drugs

45. MECHANISM OF ACTION
• Still largely unknown
• The effects of inhaled anesthetics cannot be explained by a single
molecular mechanism. Rather, multiple targets contribute to the
effects of each agent
• The immobilizing effect of inhaled anaesthetics involves a site of
action in the spinal cord, whereas sedation and amnesia involve
supraspinal mechanisms
• No comprehensive theory describes the sequence of events leading
from the interaction between an anaesthetic molecule and its targets
to the behavioral effects

46. Proposed mechanisms
• Disruption of normal synaptic transmission by interfering with the release
of neurotransmitters from presynaptic nerve terminals
-altering the uptake of neurotransmitters
-changing the binding of neurotransmitters to pot-synaptic receptor sites
- influencing the ionic conductance following activation of the post-synaptic
receptor
• Direct interaction with the neuronal plasma membrane
• Indirect interaction via production of a second messenger
• The high correlation between lipid solubility and potency suggests a
hydrophobic site of action
• Inhalational agents may bind to both membrane lipids and proteins, hence
both lipid based and protein based theories have been suggested

47. Lipid- based theories of mechanism of action
Meyer-Overton Theory
• supported by the fact that the anesthetic potency correlates directly
with lipid solubility
• Anaesthesia results from molecules dissolving at specific lipophilic
sites resulting in the disturbance of physical properties of cell
membranes in the CNS
• It is the number of molecules which are present at the site of action
which is important, not their type
• Supports an additive nature of effects of anaesthetic agents

48. Lipid- based theories of mechanism of action
Critical volume hypothesis
• Bulky and hydrophobic anaesthetic molecules accumulate inside the
hydrophobic regions of the cell membrane causing its distortion and
expansion due to volume displacement
• This expansion distorts channels necessary for sodium ion flux and
therefore disrupts development of action potentials –thus providing
anesthetic effect

49. Lipid- based theories of mechanism of action
Modern lipid hypothesis
• solubilization of the general anaesthetic in the lipid bilayer causes
redistribution of membrane lateral pressures
• Most ligand gated ion channels are sensitive to this change in lateral
pressures
• General anaesthesia likely involves inhibition of the opening of an ion
channel in a postsynaptic ligand-gated membrane protein

50. Protein receptor hypothesis
• Postulates that protein receptors in the CNS are responsible for the
mechanism of action of inhaled anaesthetics
• Supported by the steep dose-response curve for inhaled anaesthetics
• Unclear if they disrupt ion flow through membrane channels by an
indirect action on the lipid membrane or via a second messenger or
by direct and specific binding to channel proteins

51. Activation of GABA receptors
• This is another proposed theory
• Volatile agents may activate GABA channels and hyperpolarize cell
membranes
• In addition they may inhibit certain calcium channels and therefore
prevent the release of neurotransmitters and inhibit glutamate
channels
• Volatile anaesthetics therefore may share common cellular actions
with other sedative, hypnotic and analgesic drugs

52. MINIMUM ALVEOLAR CONCENTRATION – MAC/MAC₅₀
DEFINITION: The minimum alveolar concentration , at equilibrium, at 1 Atm
pressure, which produces immobility in 50% of subjects exposed to a
standard noxious stimulus, (surgical incision of skin of 1cm width and depth)
• MAC may also be estimated using the equation: MAC x λ = 1.82 Atm
(where λ is the olive oil-gas partition coefficient)
• it is an index to measure the potency and relate the potency of other
agents, and provides a standard for experimental evaluations
Rational for this measure of anaesthetic potency:
• Alveolar concentration can be easily measured
• The high cerebral blood flow produces rapid equilibration
• Near equilibrium, alveolar and brain tensions are virtually equal

54. • The lower the MAC, the more potent the agent
• 1.3 MAC of any of the volatile anaesthetics prevents movement in 95% of
subjects
( MAC₉₅ = 1.3 x MAC₅₀ )
• Nitrous oxide alone (MAC -104% ) is unable to produce adequate
anaesthesia
• The MAC values for different anaesthetics are roughly additive. For
example, a mixture of 0.5 MAC of nitrous oxide and 0.5 MAC of
halothane approximates the degree of CNS depression of 1.0 MAC of
isoflurane

55. MAC VARIANTS
MAC Awake = MAC of anaesthetic that would allow opening of eyes
on verbal commands during emergence from anaesthesia (0.3 – 0.4
MAC)
MAC Intubation = MAC that would inhibit movement and coughing
during endotracheal intubation ( 1.3 MAC )
MAC Bar = MAC of anesthetic necessary to Block Autonomic Response
to nociceptive stimuli as measured by concentration of catecholamine
in venous blood ( 1.5 MAC )
• When different agents are compared the ratio of MAC skin incision to
MAC intubation or MAC awake is relatively constant

56. Factors that affect MAC
Increased MAC
• Hyperthermia – if > 42⁰ C
• Hypernatremia
• Drug induced CNS elevation of catecholamine stores (amphetamine,
cocaine, ephedrine, MAO inhibitors, Levodopa)
• Chronic alcohol/ opioid abuse

57. • Decreased MAC
• Increased age ( 6% decrease in MAC per decade)
• Hypothermia
• Hyponatremia
• Hypoxaemia
• Hypotension (MAP < 40mmHg)
• Anaemia (haematocrit < 10%)
• Pregnancy
• Acute alcohol abuse
• CNS depressant drugs ( opioids, benzodiazepines, TCAs)
• Other drugs ( lithium , lignocaine, magnesium)

58. • No effect on MAC
• Gender
• Duration of anaesthesia
• Weight, BSA
• Hypo/Hyperkalaemia
• hypertension

60. The ideal inhalational anaesthetic
• The compound should have molecular stability
• Maintain stability over a long period of time
• It should not form flammable or explosive mixtures with air, oxygen
or nitrous oxide
• It should be reasonably potent, allowing use with high concentrations
of oxygen
• It should have low solubility in blood in order that induction of, and
emergence from anaesthesia are rapid
• No metabolism – fewer toxic effects

61. • No long term effects – no toxicity to personnel, patients or the
environment
• Non-irritant odour – pleasant smell and easy inhalational induction
• no respiratory depression
• No cardiovascular depression
• Hypnotic and analgesic
• Readily reversible, neuroprotective and non-excitatory

62. MALIGNANT HYPERTHERMIA
DEFINITION: - A rare inherited syndrome characterized by a life
threatening acute hypermetabolic state triggered by exposure to a
‘triggering’
• All volatile anaesthetics and Suxamethonium are potential triggers
• Caused by a defect in a receptor on the sarcoplasmic reticulum called
the Ryanodine receptor - a calcium channel receptor
• Once exposed to the trigger, the receptor stays open and floods the
cell with calcium with a resultant persistent contractile state
• Hyperthermia is defined as a core temperature of > 38⁰C – a late sign

63. Clinical features
• Tachycardia
• Tachypnoea
• Increased oxygen consumption, and eventually cyanosis
• Hypercapnia
• Masseter muscle spasm
• Whole body skeletal muscle rigidity
• Metabolic and respiratory acidosis
• Hyperkalaemia
• Hyperthermia – a late sign
• Myoglobinuria
• Multiple organ failure and coagulopathy if left untreated

64. Management protocol
• Discontinue volatile anesthetics and suxamethonium
• Call for Help
• Hyperventilate with 100% oxygen at high flows
• Mix dantrolene sodium with sterile water and administer 2.5mg/kg IV
ASAP
• Institute cooling measures
• Treat complications ( dysarhythmias, hyperkalaemia, acidosis)
• Transfer to ICU

65. HALOTHANE
Colour Code- Red
MAC = 0.75%
• A halogenated alkane
• It is a colourless liquid which is
decomposed by light and must be
stored in amber bottles with 0.01%
Thymol as stabilizer
• Non-flammable and non-explosive
• Non- irritant with pleasant smell
• 1-2% for induction (0.8% with 65%
N₂O)
• 0.5 – 0.75% for maintenance

66. Halothane – Effects on organ systems
CARDIOVASCULAR EFFECTS
• Causes hypotension due to vasodilation and direct myocardial depression
( interferes with sodium-calcium exchange and intracellular calcium
utilization)
• Dilates coronary arteries – however decreased coronary blood flow due to
hypotension
• Blunts physiologic (vagal) response to hypotension
• Dysrhythmias, especially sinus bradycardia and nodal rhythm are common
and dose-related
• Halothane sensitizes the heart to arrhythmogenic effects of epinephrine –
avoid doses > 1.5mcg/kg (lidocaine reduces the risk of arrythmias)

67. RESPIRATORY
• Halothane normally causes rapid, shallow breathing and a decrease in tidal
volume - decreased alveolar ventilation
• Resting PaCo₂ is elevated
• Hypoxic drive is reduced
• Respiratory changes are increased in pre-existing lung disease
• Halothane is a potent bronchodilator- may reverse asthma induced
bronchospasm
• Inhibits salivary and bronchial secretions
• Promotes post-operative hypoxia and atelectasis by depressing mucociliary
action

68. CEREBRAL
• Dilates cerebral vessel – lowers cerebral vascular resistance and
increases blood volume and flow
• Blunts autoregulation
• Increases intracranial pressure, which may be minimized by
hyperventilation
• Decreased cerebral activity – EEG slowing and some reduction in
metabolic oxygen demand
• Potent anesthetic, but no analgesic effects. Slow recovery with
noticeable ‘hangover effect’

69. Neuromuscular
• Produces some muscle relaxation
• Post operative shivering is common
• May trigger malignant hyperthermia like most volatile anesthetics
Renal
• Reduces renal blood flow, GFR, and urinary output
• Preoperative hydration limits these changes
Uterus
• Uterine relaxation and risk of bleeding if used in high concentrations during c/s
(>0.5%)

70. LIVER
• 20% is metabolized in the liver – end products are excreted in the urine
• Mild elevation in liver enzymes is common post-op
• Post operative liver dysfunction has several causes ( infectious, impaired perfusion,
hypoxia. Post-op intrahepatic cholestasis)
• Halothane hepatitis is very rare ( 1 in 35000) – an idiosyncratic allergic phenomenon
which results in fulminant necrosis with 50-75% mortality- risk factors include:
- exposure to halothane in multiple occasions at short intervals - (avoid repeated
exposure within 3 months)
- middle aged, obese women
- family or personal history of toxicity

71. Contraindications to halothane
• Unexplained liver dysfunction following previous anaesthetic
exposure
• Should not be used in patients with cardiac arrythmias
• Caution in patients with possible raised intracranial pressure
• Concomitant epinephrine administration
• Pheochromocytoma
• May have adverse effects in patients who have recently used
aminoglycosides
• Caution should be exercised in patients on phenobarbitone and
other hepatic enzyme inducers

72. Isoflurane
Colour code – Purple
MAC = 1.15% Vapour pressure 238mmHg
1-chloro-2,2,2-triflouroethyl diflouromethyl
ether
• Colourless, halogenated ether
• Less potent than halothane, but faster induction
and recovery due to relative insolubility (blood-gas
partition coefficient – 1.4)
• Depth of anaesthesia is easy to control
• 2-4% for induction, 1-2% for maintenance
• Analgesic properties at subanaesthetic
concentrations (0.5%)
• Non-flammable,stable, not decomposed by light
• Pungent odor
• Relatively cheap

73. Isoflurane – Organ effects
Cardiovascular
• Minimal myocardial depression, anaesthetic concentrations only
cause a slight fall in myocardial contractility and stroke volume
• No sensitization to catecholamines – epinephrine may be
administered in doses up to 4.5mcg/kg
• Theoretic possibility of ‘coronary steal’- but effect not clinically
relevant
• Good peripheral vasodilator, causing a drop in blood pressure
• Reflex sympathetic activity is increased, maintaining cardiac output,
with a tendency to tachycardia in young patients

74. Respiratory
• Vapour is irritant to the airways, so inhalational induction not recommended
• Slightly more of respiratory depressant than halothane (↑RR, ↓ Tv, ↓min. volume )
• Good bronchodilator. But not as potent as halothane
Cerebral
• Most potent of the volatile anesthetics in clinical use
• Least effect on cerebral blood flow and intracranial pressure of all agents
• Agent of choice in neuroanesthesia
• Some degree of hyperventilation necessary in patients with increased intracranial
pressure
• Decreases cortical EEG activity and does not induce abnormal electrical activity or
convulsions

75. Skeletal muscle
• Muscle relaxant, potentiates non-depolarizers
• Also may precipitate malignant hyperthermia
Uterus
• Relaxation, but less than halothane
• Use in low concentrations ( 0.5 – 0.75%)
Hepatic
• Only 0.2 % is metabolized by hepatic enzymes
• Total hepatic blood flow may be reduced but to a less extent than with halothane
• Liver function tests usually not affected
Renal
• Reduction in blood flow, GFR, urinary output, triflouroacetic acid metabolite may raise serum
fluoride levels, but nephrotoxicity unlikely

76. SEVOFLURANE
Colour code – Yellow
MAC = 2% SVP 160mmHg
1-trifluoromethyl-2,2,2-triflouroethyl
monoflouromethyl ether
• Fluorinated derivative of Methyl isopropyl
ether
• Relatively weak volatile agent and less
potent than isoflurane, but with low
solubility (0.65)- faster induction and
recovery
• Less soluble than isoflurane in plastic and
rubber- useful for low flow systems
• Great for inhalational induction because
of pleasant odour
• Induction 5-7%, maintenance 1-3%
• Relatively expensive

77. Sevoflurane – Organ effects
Cardiovascular
• Little or no direct effect on the heart
• Mild depression of myocardial contractility
• Systemic vascular resistance and blood pressure decline slightly – less than with
isoflurane
• Lack of compensatory increase in heart rate may lead to impaired maintenance of
cardiac output
• May prolong QT interval (infants)
Respiratory
• Non- irritant to the airways
• Depresses respiration and reverses bronchospasm to an extent similar to
isoflurane

78. Cerebral
• Slight increase in CBF and intracranial pressure (effect minimal with normal maintenance doses)
• High concentrations may impair autoregulation
• No excitatory effects on the EEG
• Higher risk of emergence agitation compared to isoflurane
Neuromuscular
• Produces adequate muscle relaxation for intubation following inhalational induction
• Uterine muscle relaxation
• May trigger malignant hyperthermia
Renal
• Slightly decreases renal blood flow, metabolism in the liver produces inorganic fluoride (compound A ) which
is potentially nephrotoxic- but clinical significant effects have not been seen
Contraindications:
• severe hypovolemia, intracranial hypertension

79. DESFLURANE
Colour code – sky blue
MAC = 6% SVP – 664mmHg
• Differs from isoflurane only in the
substitution of fluorine for chlorine
• Extremely volatile with boiling point of
23.5⁰C, with need for a sophisticated
vaporizer
• Non-flammable and non-explosive
• Minimal biotransformation with little toxic
potential
• Most insoluble, produces rapid induction and
recovery (BGPC- 0.42%), but irritant and
unpleasant and therefore not used for
induction
• Less potent
• CVS, Respiratory and CNS effects are similar
to isoflurane

80. XENON
MAC = 71%
• Noble gas that Has been long known to have anesthetic effects
• Odorless, non-explosive,
• Very fast onset and emergence
• Works via NMDA inhibition
• Little effect on CVS, hepatic and renal systems
• Protective against neuronal ischemia
• Cost and limited availability limit widespread use

81. REFERENCES
• Morgan and Mikhail’s Clinical anesthesiology
• Pharmacology for Anaesthetists, Norman Calvey and Norton Williams
• Anesthetic Pharmacology, Basic Principles and Clinical Practice
• Medical Pharmacology online
• Wikipedia