Isoflurane is a halogenated methyl ethyl ether that has a pungent odor. It permits rapid induction and recovery from anesthesia due to its intermediate solubility in blood and high potency. It has great popularity due to its virtual absence of serious hepatic toxicity, minimal biotransformation, and ease of administration. Isoflurane causes minimal depression of the cardiovascular system and decreases arterial blood pressure through direct myocardial depression and peripheral arterial vasodilation. It also causes selective coronary vasodilation and decreases cerebral metabolism with low concentrations not changing cerebral blood flow.

1. Amare H.
INHALATIONAL ANAESTHESIA
- 2

2. Isoflurane
1/18/20192
 Isoflurane is a halogenated methyl ethyl ether
that has a pungent, ethereal odor
 Structural isomer of enflurane

3. 1/18/20193
 Its intermediate solubility in blood, combined
with a high potency,
Permits rapid onset and recovery from
anesthesia using isoflurane alone or in combination
with nitrous oxide or injected drugs, such as
opioids.
 Balanced anesthesia ?

4. 1/18/20194
 It has great popularity for a variety of reasons
Virtual absence of serious hepatic toxicity
Minimal biotransformation
Ease of administration

5. Induction
1/18/20195
 Rapid inhalational induction because of low
blood gas solubility
 It is potent
 Does not increase trachea-bronchial secretions

6. Cardiovascular effects
1/18/20196
 Minimal depression of the CV system
 In contrast to halothane & Enflurane, COP is
generally maintained during isoflurane
anesthesia by increasing HR
 Decrease ABP by
-direct myocardial depression
-peripheral arterial vasodilatation

7. 1/18/20197
 It causes selective coronary vasodilatation and
decrease coronary vascular resistance
Concerns regarding its use in patients with
‘coronary steal’
 Increase HR in young patients

8. Central nervous system
1/18/20198
 Decreased cerebral metabolism
 Low conc. No change on CBF
 Doesn’t produce seizure
 ICP increase in spontaneously breathing
patient but this effect is eliminated when the
patient is hyperventilated

9. 1/18/20199
 Some cerebro protective effects during
ischemia or hypoxemia
 Drug of choice for neuro-surgery

10. Respiratory system
1/18/201910
 Like all VAA blunted hypoxic drive leading to
hypercapnia and V/Q mismatching – CO2
narcosis
 Bronchodilator
 Alteration in gas exchange because of
-decreased pulmonary compliance.
-decreased FRC.
-impairment of hypoxic pulmonary
vasoconstriction.

11. The effect of volatile anesthetics on
respiratory system resistance in patients
with COPD – MAC 1.1
1/18/201911

12. Other systems
1/18/201912
 Skeletal muscle relaxation – volatile induction
and laryngoscope with out muscle relaxation
 Relaxation of uterus like halothane - PPH
 Decreased hepatic blood flow but hepatic
oxygen supply better maintained than
halothane and liver function minimally affected
 Enhance the action of GABA

13. Biotransformation
1/18/201913
 Only small amounts are metabolized(0.2%)
 The quantities of this metabolites are insufficient
to cause significant cell injury or toxicity
 Emergence- is prompt after discontinued
-PONV like other IAA
 Complication-increase HR
-trigger MHT
-lack significant cxn. Safe drug

14. Incidence of liver injury
1/18/201914
 Halothane > enflurane > isoflurane >
desflurane and
 Correlates with the extent of their oxidative
metabolism

15. Amare H.15
Advantage Disadvantage
Rapid induction and
onset
High cost, trigger MHT
Minimal
biotransformation with
little risk of hepatic or
renal toxicity
Pungent odor-
coughing, breath
holding
CV stability Coronary
vasodilatation with the
possibility of the
coronary steel

16. Drug Clearance
1/18/201916
 Volatile anesthetics may interfere with the
clearance of drugs from the plasma
Decreased hepatic blood flow or
Inhibition of drug-metabolizing enzymes

17. Desflurane
Amare H17
 Desflurane is a fluorinated methyl ethyl ether that
differs from isoflurane by just one atom: a
fluorine atom is substituted for a chlorine
atom on the ethyl component of isoflurane

18. This fluorination brings about
several effects
1/18/201918
1. It decreases blood and tissue solubility (the
blood: gas solubility of Desflurane equals that
of nitrous oxide)
2. It results in a loss of potency (the MAC of
Desflurane is five times higher than isoflurane)
3. Results in a high vapor pressure

19. Desflurane …
1/18/201919
 The vapor pressure of Desflurane approaches
1 atm at 23°C making controlled administration
impossible with a conventional vaporizer.
 A Desflurane vaporizer is an electronically
controlled pressurized device that delivers an
accurately metered dose of vaporized
Desflurane into a stream of fresh gases passing
through it.

20. Desflurane …
Amare H20
 Carbon monoxide can be generated under
certain conditions and may accumulate in the
breathing system when in contact with soda
lime
 The MAC of Desflurane (6.5% in adults) is the
highest of any modern fluorinated agent
 It is non-flammable under all clinical conditions

21. Desflurane …
Amare H21
 Desflurane has the lowest blood: gas solubility,
similar to nitrous oxide.
 Desflurane offers a theoretical advantage in long
surgical procedures by virtue of decreased
tissue saturation.

22. Central nervous system effects
1/18/201922
 Reduces cerebral metabolic rate for oxygen
(CMRO2) to a similar extent as isoflurane.
 Desflurane above 1 MAC produce mild
increases in ICP secondary to mild increase in
CBF 2ndary to decreased Cerebral vascular
resistance.

23. Desflurane …
1/18/201923
 Abolishes cerebral auto regulation at 1.5 MAC.
 Alone amongst the agents it increases CSF
production
 Suppresses EEG activity and there is no
evidence of epileptiform activity.

24. Cardiovascular effects = Desflurane
…
1/18/201924
 Similar to those of isoflurane although possibly
less pronounced
 There is a dose-dependent reduction in
myocardial contractility, cardiac output, arterial
blood pressure, and systemic vascular resistance

25. Systemic vascular resistance –
desflurane
1/18/201925

26. Desflurane …
1/18/201926
 Unlike isoflurane, Desflurane may stimulate the
sympathetic nervous system at
concentrations above 1 MAC.
 Sudden and unexpected increases in arterial
blood pressure and heart rate might occur

27. The effects of increasing concentrations (MAC)
of halothane, isoflurane, desflurane, and
sevoflurane on cardiac index (L/min)
1/18/201927

28. Respiratory system effects =
Desflurane …
1/18/201928
 Desflurane causes dose-related respiratory
depression
 Tidal volume is reduced and respiratory rate
increases,
 At induction, high concentrations are irritant
and may provoke coughing or breath-holding.

29. Desflurane …
1/18/201929
 Provoke Laryngospasm, excessive secretions
and apnea.
 Do not have a marked bronchodilator effect
and in cigarette smokers it is associated with
significant bronchoconstriction.

30. Metabolism & toxicity = Desflurane
…
Amare H30
 Desflurane is resistant to metabolism (0.02%) and
serum fluoride levels do not rise even after
prolonged administration
 The potential for Desflurane to cause renal or
hepatic toxicity is small given its minimal bio-
transformation.
 near-absent metabolism to serum
trifluoroacetate, makes immune-mediated
hepatitis extremely unlikely.

31. Neuromuscular effects = Desflurane
…
Amare H31
 Marked depressant effect at the
neuromuscular junction
 Prolongs neuromuscular blockade by both non-
depolarizing and depolarizing relaxants.
 Triggers malignant hyperpyrexia

32. Sevoflurane
Amare H32
 First released for clinical use in Japan in 1990.
 A polyfluorinated isopropyl methyl ether

33. Sevoflurane …
1/18/201933
 MAC ranges from 3.3 in infants to 2.5 in older
children, 1.8 in adults and 1.3 in elderly
patients. { 0.7 – 2.0 in the presence of 65%
nitrous oxide}
 Its low solubility, lack of airway irritability and
moderate potency make it particularly useful for
‘gas induction’ in children.
 Unlike isoflurane it is non-irritant to the airway
and can be given in high concentrations for
anesthetic induction

34. Sevoflurane …
1/18/201934
 The concentration used for induction of
anesthesia is quoted as 5 – 8%.
 Maintenance of anesthesia is usually achieved
using between 0.5 and 3%
 What is the determinant factors for decreasing
the percentage {MAC} of inhalational anesthesia?

35. Cardiovascular effects = Sevoflurane
…
1/18/201935
 Sevoflurane, in common with all volatile agents,
Reduces cardiac output and systemic blood pressure.
 A small increase in heart rate may be observed,
Less pronounced than with isoflurane and Desflurane
 Sevoflurane is associated with a stable heart
rhythm and does not predispose the heart to
sensitization by catecholamine's.

36. The effects of increasing concentrations (MAC)
of halothane, isoflurane, desflurane, and
sevoflurane on heart rate (beats/minute)
1/18/201936

37. Sevoflurane …
1/18/201937
 Sevoflurane not appear to cause the “coronary
steal” phenomenon in man.
 Dose related decrease in myocardial contractility
and MAP, systolic pressure decreases to a
greater degree than diastolic pressure

38. Respiratory system effects =
Sevoflurane …
1/18/201938
 Sevoflurane causes dose-related respiratory
depression.
 Decrease in tidal volume and an increase in
respiratory rate with a net decrease in minute
ventilation.
 Produces the same degree of bronchodilation
as isoflurane and Enflurane.

39. Sevoflurane …
1/18/201939
 Sevoflurane causes the least amount of
subjective airway irritation and inhalational
induction can be swift and effective in the most
testing of circumstances.
 At equi-MAC concentrations, respiratory
resistance is reduced by sevoflurane >
halothane > isoflurane

40. The effect of volatile anesthetics on
respiratory system resistance in patients
with COPD – MAC 1.1
1/18/201940

41. Central nervous system effects =
Sevoflurane …
1/18/201941
 Sevoflurane preserves cerebral auto regulation
better than the other agents
 Has a dose-dependent effect on cerebral blood
flow and intracranial pressure;

42. Sevoflurane …
Amare H42
 Sevoflurane above 1 MAC produce mild
increases in ICP, paralleling Its mild increases in
CBF
 One potential advantage of sevoflurane is that its
lower pungency and airway irritation may
lessen the risk of coughing and bucking and the
associated rise in ICP as compared to Desflurane
or isoflurane.
 It reduces the cerebral metabolic rate for oxygen
(CMRO2) by approximately 50% at
concentrations approaching 2 MAC.

43. Gastrointestinal & other effects
= Sevoflurane …
1/18/201943
 A higher incidence of nausea and vomiting
after sevoflurane anesthesia. – prophylactic
treatment?
 Sevoflurane reduces renal blood flow and leads
to an increase in fluoride ion concentration {12-
90umol/l in anesthesia lasting 1 to 6hrs
respectively.} – no evidence of gross changes
in renal function
 In animal models, the drug decreases liver
synthesis of fibrinogen, transferrin, and
albumin.

44. Metabolism and toxicity =
Sevoflurane
1/18/201944
 Approximately 5% of a given dose of sevoflurane
is metabolized with cytochrome P-450, a higher
proportion than with isoflurane or Enflurane
 CYP450 may be induced by chronic exposure to
ethanol and isoniazide
 Produces more fluoride ions than Enflurane
 It should be used with caution in patients with
renal dysfunction, but not a universal
contraindication for its use.

45. Sevoflurane …
1/18/201945
 Elimination of sevoflurane is rapid, again due to
its low solubility, resulting in a fast wash-out rate
 Unlike halothane, its metabolism does not result
in the formation of trifluoroacetylated liver
proteins and subsequent production of anti-
trifluoroacetylated protein antibodies

46. Special points = Sevoflurane
…
1/18/201946
 Sevoflurane potentiates the action of co-
administered depolarizing and non-depolarizing
muscle relaxants to a greater extent than
either Halothane or Enflurane.
 As with other volatile anesthetic agents, the co-
administration of N2O, benzodiazepines, or
opioids lowers the MAC of sevoflurane.

47. Advantages = Sevoflurane …
1/18/201947
 For inhalational induction of anesthesia in
children.
In adults, 8% sevoflurane is well tolerated and,
provides rapid induction of anesthesia without
adversely affecting hemodynamic stability.
 For dental procedures as there is a lower risk of
cardiac arrhythmias than with halothane.
 In children with congenital heart disease.

48. Emergency = Sevoflurane …
1/18/201948
 Agitation in the early postoperative period has
been noted in young children.
 Self-limiting or may require by Premedication with
midazolam or similar benzodiazepine

49. Enflurane
1/18/201949
 A halogenated methyl ethyl ether which is a
geometric isomer of isoflurane
 Presentation
As clear, colorless liquid {that should be protected
from sunlight} with a characteristics of sweet smell
 The MAC of enflurane is 1.68{0.57 in 70% nitrous
oxide}

50. Cardiovascular effects
1/18/201950
 Enflurane is a negative ionotrope and it also
cause a decrease in systemic vascular resistance
Decrease in MAP
 Unlike halothane, enflurane produces a slight
reflex tachycardia
 Enflurane is not markedly arrhythmogenic, but
does sensitize the myocardium to the effects of
circulating catecholamine's

51. Respiratory system effects
1/18/201951
 It is a powerful respiratory depressant, markedly
decreasing tidal volume although RR may increase.
 The drug also decrease respiratory response to
hypoxia and hypercapnia
 Enflurane is non-irritant to the RT; it causes
bronchodilatation and no increase in secretion
 The drug inhibits pulmonary macrophage activity
and mucociliary transport

52. Central nervous system effects
1/18/201952
 Same like others on increasing ICP and CBF, but
decrease cerebral oxygen consumption
 The drug may induce tonic/ clonic muscle
activity and may also produce epileptiform EEG
traces, especially in the presence of hypocapnia

53. Other effects
1/18/201953
 Enflurane decreases renal blood flow and
glomerular filtration rate
 The drug reduces the tone of pregnant uterus
 The drug causes a fall in body temperature
predominantly by cutaneous vasodilatation
 Enflurane depress white cell function for 24hr
postoperatively

54. Toxicity & adverse effects
1/18/201954
 Triggering agent for the development of
malignant hyperthermia
 The drug may also cause myocardial
dysarrythmia, particularly in the presence of
hypoxia, hypercapnia and excessive
catecholamine secretion
 Shivering occurs mostly in postoperative period
– Mgt?
 Hepatotoxicity and renal toxicity after repeated
exposure to enflurane

55. Metabolism
1/18/201955
 2.4% of the administered drug metabolized by the
liver cytochrome p450, principally by oxidation
and degradation
Plasma fluoride concentration may reach 10 times
observed after use of halothane or isoflurane.

56. Special points
1/18/201956
 Potentiate the action of co-administered non-
depolarizing muscle relaxant
 Caution when using adrenaline like halothane

57. Nitrous oxide
1/18/201957
 It is used for
As an adjuvant to the induction and
maintenance of GA
As an analgesic during labour and other painful
procedures
 Presentation
 As liquid in cylinders at a pressure of 44 bar at
15˚c
 The cylinders are French blue and are available
in six sizes {C-J, containing 450-18000 lit,
respectively}

58. 1/18/201958
 The gauge pressure does not correlate with
cylinder content until all N2O is in gaseous state.
 It is sweet-smelling colorless gas and non-
flammable, but supports combustion
 The MAC of nitrous oxide is 105 and blood gas
partition coefficient is 0.46{compared to 0.015 for
nitrogen} – Denitrogenation?

59. 1/18/201959
 Entonox - 50:50 mixture of oxygen and nitrous
oxide and is produced by bubbling oxygen
through liquid nitrous oxide
 It is available in cylinders which are French blue
with white and blue shoulders in the following four
sizes: SD, D, F, G containing 440 – 5000L
respectively.
 The cylinder pressure is 137 bar at 15˚c

60. Cardiovascular effects
1/18/201960
 Nitrous oxide decreases myocardial contractility,
But the MAP is usually well maintained by reflex
increase in peripheral vascular resistance.
 Deterioration in left ventricular function occurs
when nitrous oxide is added to a high dose opioid
oxygen anesthetic sequence, volatile agents, or
Propofol infusion{TIVA}

61. Respiratory system effects
1/18/201961
 The gas causes slight depression in respiration
with a decrease in tidal volume and in
increases in respiratory rate.
 Nitrous oxide is non irritant and does not cause
bronchospam

62. Central nervous system
1/18/201962
 Nitrous oxide is a CNS depressant and, when
administered in a concentration of 80%, will
cause LOC.
 The gas is a powerful analgesics in a
concentration > 20%
 Its administration causes a rise in ICP
 Anti-hypoxic device?
 N2O has no effect on uterine tone

63. Toxicity / side effects
1/18/201963
 15% of patients receiving N2O will experience
nausea & vomiting
 The gas is 35 times more soluble than nitrogen in
the blood, therefore, cause
An increase in air-filled spaces { eg. Pneumothorax,
intestine, air cysts in the middle ear} in the body.
Fink effect{diffusion hypoxia}

64. 1/18/201964
 Prolonged use of high concentration of
N2O{>6hr} leads to inactivation via oxidation of
the cobalt ion of the cobalamin {vitamin B12}
The resulting cobalt ion prevents cobalamin from
acting as coenzyme for methionine synthase,
which involves in the synthesis of DNA, RNA,
myelin and catecholamine's.
 Pernicious anemia, megaloblastic anemia and
pancytopenia
20% of elderly patients are deficient in cobalamin

65. Special points
1/18/201965
 The concentration effect
 Second gas effect
 66% nitrous oxide in oxygen decreases the MAC
of halothane to 0.29, of isoflurane to 0.5, of
sevoflurane to 0.66, desflurane to 2.8 and of
enflurane to 0.6.
 The use of nitrous oxide is safe in patients
susceptible to malignant hyperpyrexia.