4. The first public demonstration of inhalation
anaesthetic was nitrous oxide used by Professor
Gardner Q. Colton and dentist Horace Wells on 11
December 1844.
On Oct 16th 1846 William Morton successfully
demonstrated Ether anaesthesia at Massachusetts
general hospital.
6. The goal of delivering inhaled anesthetics is to
produce the anesthetic state by establishing a
specific concentration of anesthetic molecules
in the central nervous system (CNS).
This is done by establishing the specific
partial pressure of the agent in the lungs,
which ultimately equilibrates with the brain
and spinal cord
7.
8. Mechanism of action of inhalational anesthetics remains
obscure, it is assumed that their ultimate desired effect
depends on attainment of a therapeutic tissue concentration
in the CNS
Factors affecting inspiratory concentration (FI):
Fresh gas leaving the anesthesia machine mixes with gases
in the breathing circuit prior to being inspired
Actual composition of the inspired gas mixture depends on
• Fresh gas flow rate
• Volume of the breathing system
• Absorption by the machine or breathing circuit
Higher the fresh gas flow rate, the smaller the breathing
system volume, and the lower the circuit absorption, the
closer the inspired gas concentration will be to the fresh gas
concentration
PHARMACOKINETICS
9. Factors affecting alveolar concentration (FA):
Alveolar gas concentration (FA) would approach inspired gas
concentration (FI) without uptake of anesthetic agent by the
body
Anesthetic agent is taken up by pulmonary circulation during
induction, therefore alveolar concentrations lag behind inspired
concentrations (FA/FI < 1.0)
Greater the uptake, slower the rate of rise of the alveolar
concentration and the lower the FA:FI ratio
Concentration of a gas is directly proportional to its partial pressure,
so that alveolar partial pressure will also be slow to rise
Alveolar partial pressure is important because it determines the
partial pressure of anesthetic in the blood and ultimately, in the
brain
Partial pressure of the anesthetic in the brain is directly proportional
to its brain tissue concentration, which determines clinical effect
10.
11. Increase FA/FI Decrease FA/FI Comment
Low blood solubility High blood solubility As the blood solubility
decreases, the rate of
rise in FA/FI increases.
Low cardiac output High cardiac output The lower the cardiac
output, the faster the rate
of rise in FA/FI
High minute ventilation Low minute ventilation The higher the minute
ventilation, the faster the
rate of rise in FA/FI
High pulmonary arterial
to venous partial venous
partial
Low pulmonary arterial
to venous partial venous
partial
"At the beginning of
induction, PV is zero but
increases rapidly (thus
[PA – PV ] falls rapidly)
and FA/FI increase
rapidly. Later during
induction and
maintenance, PV rises
more slowly so FA/FI
rises more slowly."
12. Three factors determine anaesthetic uptake:
I. Solubility (λ),
II. Cardiac output (Q),
III. Alveolar-to-venous partial pressure difference (PA - Pv).
Uptake equals the product of these factors: λ × Q × (PA - Pv)
divided by barometric pressure.
IF
i. Solubility is low (as in the case of oxygen), or
ii. Cardiac output approaches zero (as in profound myocardial
depression or death), or
iii. Alveolar-to-venous difference becomes inconsequential (as might
occur after an extraordinarily long course of anesthesia),
Uptake would be minimal, and FA/FI would equal 1.
13. Solubility:
• Insoluble agents are taken up by the blood less
readily than are soluble agents; as a result the
alveolar concentrations rise faster and
induction is faster
• Partition coefficients are the relative solubilities
of an anesthetic in air, blood, and tissues
• The higher the blood/gas coefficient, the
greater the anesthetic’s solubility and the
greater its uptake by the pulmonary circulation
• Rise of alveolar concentration toward inspired
concentration most rapid with least blood
soluble agent (N2O) and least rapid with most
blood soluble agents.
14. Alveolar blood flow:
Alveolar blood flow is essentially equal to cardiac output ( CO ).
CO increases
Anaesthetic uptake increases
The rise in alveolar pressure slows
Induction is prolonged
15. • The effect of a change in cardiac output is analogous to
the effect of a change in solubility. As doubling
solubility doubles the capacity of the same volume of
blood to hold anesthetic. Doubling cardiac output
would also double capacity, but in this case by doubling
the volume of blood exposed to anesthetic.
• Low-output states predispose patients to overdosage
with soluble agents.
• Higher than anticipated levels of a volatile anesthetic (
eg, Halothane ) may create a positive feedback loop by
lowering CO even further due to its myocardial
depressant effect
16. Alveolar gas to venous blood partial pressure
difference:
This gradient depends on tissue uptake
Transfer of anesthetic from blood to tissues is determined
by:
• Tissue solubility of agent
• Tissue blood flow
• Partial pressure difference between arterial blood and tissue
Tissues are assigned into four groups based on their
solubility and blood flow for uptake & distribution:
• Vessel-rich group
Brain, heart, liver, kidney, and endocrine organs
• Muscle group
Skin and muscle
• Fat group
• Vessel-poor group
Bone, ligaments, teeth, hair, and cartilage
17. Characteristi
c
Vessel Rich
Group ( VRG
)
Muscle
Group
( MG )
Fat Group
( FG )
Vessel Poor
Group ( VPG
)
% of body
weight
10 50 20 20
% of cardiac
output
75 19 6 0
Perfusion
(mL/min/100g
)
75 3 3 0
Relative
solubility
1 1 20 0
18.
19. Ventilation:
Lowering of alveolar partial pressure by uptake
can be countered by increasing alveolar
ventilation
The effect of increasing ventilation will be most
obvious in raising the FA/FI for soluble
anesthetics
For insoluble agents, increasing ventilation has
minimal effect
Hyperventilation increases rate of rise of FA
Hypoventilation decreases rate of rise of FA
The change is greatest for more soluble
anesthetics
20. A doubling of ventilation increases the methoxyflurane
concentration at 10 minutes of anesthetic administration by
75%, increases the isoflurane concentration by 18%, and
increases the desflurane concentration by only 6%
21. CONCENTRATION EFFECT
Inspired anaesthetic concentration
influences alveolar concentration that may
be achieved and the rate at which that
concentration may be attained
Concentration effect states that with higher
inspired concentrations of an anesthetic,
the rate of rise in arterial tension is greater
22. Concentration:
• Effects of uptake can be lessened by increasing
the inspired concentration
• increasing the inspired concentration not
only increases the alveolar concentration but
also increases its rate of rise (ie, increases
FA/FI). This has been termed the
concentration effect which is really the result
of two phenomena.
a) Concentration effect
b) Augmented inflow effect
23. The FA / FI ratio indicates the percent of
anesthetic removed by uptake.
At 100% inspired concentration, uptake no
longer limits the rise in FA / FI
The concentration effect is more significant with
nitrous oxide than with the volatile anaesthetics,
as the former can be used in much higher
concentrations.
CONCENTRATION EFFECT
24. Factors Affecting Arterial Concentration (Fa)
Normally, alveolar and arterial anesthetic partial pressures are assumed to be equal, but
in fact the arterial partial pressure is consistently less than end-expiratory gas would
predict. Reasons for this may include
i. Venous admixture
ii. Alveolar dead space
iii. Nonuniform alveolar gas distribution
Existence of ventilation/perfusion mismatching will increase the alveolar–arterial
difference.
Mismatch acts as a restriction to flow: It raises the pressure in front of the restriction,
lowers the pressure beyond the restriction, and reduces the flow through the restriction.
The overall effect is an increase in the alveolar partial pressure (particularly for highly
soluble agents) and a decrease in the arterial partial pressure (particularly for poorly
soluble agents).
Thus, a bronchial intubation or a right-to-left intracardiac shunt will slow the rate of
induction with nitrous oxide more than with halothane.
25. Partition coefficient
Partition coefficient is the ratio of the amount of
substance present in one phase compared with
another, the two phases being of equal volume and
in equilibrium
Or it can be defined as the relative concentrations
of anesthetic for two phases when the partial
pressure of two phases is equal.
26. Two important characteristics of
Inhalational anesthetics which govern
the anesthesia are :
Solubility in the fat (oil : gas
partition co-efficient)
Solubility in the blood
(blood : gas partition co-efficient)
27. Oil : gas partition co-efficient :
oIt indicates the amount of gas that is soluble
in oil phase. It is a measure of lipid
solubility of anaesthetic.
oMeyer-Overton hypothesis :which
demonstrated that the potency (expressed
as, MAC) of an anaesthetic agent increased
in direct proportion to its oil: gas partition
coefficient .
28. Blood – Gas partition co-efficient:
The solubility of a gas in liquid is given by its
Ostwald solubility coefficient. This represents
the ratio of the concentration in blood to the
concentration in the gas phase .
It is a measure of solubility in the blood.
Lower the blood: gas co-efficient faster the
induction and recovery – Nitrous oxide.
Higher the blood: gas co-efficient slower
induction and recovery – Halothane.
30. The second gas effect
The second gas effect usually refers to nitrous
oxide combined with an inhalational agent.
Because nitrous oxide is not soluble in blood, its'
rapid absorption from alveoli causes an abrupt rise
in the alveolar concentration of the other
inhalational anaesthetic agent.
31. Diffusion Hypoxia
At the end of anesthesia after discontinuation of
N2O, N2O diffuses from blood into the alveoli much
faster than N2 diffuses from alveoli into the blood.
Total volume of gas in the alveolus → fractional
concentration of gases in the alveoli is diluted by
N2O → ↓ PaO2 & PaCO2 → hypoxia. This occurs in
the first 5-10 mins of recovery. Therefore it is advised
to use 100% O2 after discontinuation of N2O.
32. On recovery from anesthesia, the outpouring of large volumes
of nitrous oxide can produce what Fink called diffusion
anoxia. These volumes may cause hypoxia in two ways.
First, they may directly affect oxygenation by displacing
oxygen.
Second, by diluting alveolar carbon dioxide, they may
decrease respiratory drive and hence ventilation.
Both these effects require that large volumes of nitrous oxide
be released into the alveoli. Because large volumes of nitrous
oxide are released only during the first 5 to 10 minutes of
recovery, this is the period of greatest concern.
For this reason, administer 100% oxygen for the first 5 to 10
minutes of recovery.
This procedure may be particularly indicated in patients with
preexisting lung disease or in those in whom postoperative
respiratory depression is anticipated (e.g., after nitrous oxide–
narcotic anaesthesia).
33. Elimination
Factors affecting elimination:
Recovery from anesthesia depends on lowering anesthetic
concentration in brain tissue
Elimination accomplished by:
• Exhalation
• Biotransformation
• Transcutaneous loss
Biotransformation usually accounts for a minimal increase in the rate of
decline of alveolar partial pressure. Its greatest impact is on the
elimination of soluble anesthetics that undergo extensive metabolism
(eg, methoxyflurane). The cytochrome P-450 (CYP) group of isozymes
(specifically CYP 2EI) appears to be important in the metabolism of
some volatile anesthetics.
Diffusion of anesthetic through the skin is insignificant.
The most important route for elimination of inhalation anesthetics is
the alveolus.
34. Inhalational Anaesthetic
(Mechanism of action is unknown)
Ultimate desired effect depends on attainment of a therapeutic concentration in
Brain
Inspiratory Concentration
( FI )
1. Fresh gas flow rate
2. Circuit volume
3. Circuit absorption
Alveolar Concentration
( FA )
1. Uptake
2. Ventilation
3. Concentration effect
Arterial concentration
( Fa )
1. Ventilation/ Perfusion
mismatching
Solubility
expressed as Partition
coefficient (Relative
solubility in air, blood,
tissues
Alveolar Uptake
Alveolar blood flow =
Cardiac output
Partial pressure difference of alveoli and
venous blood ( PA – PV ) =Tissue Uptake (
Ut )
Tissue Uptake
1. Tissue Solubility
2. Tissue blood flow
3. Partial pressure difference of
arterial blood and tissue
Tissue group according solubility
and blood flow
1. VRG ( Brain etc. ) 2. Muscle
3. Fat 4. VPG ( Bone etc.)
35. Factors that speed induction also speed recovery:
• Elimination of rebreathing
• High fresh gas flows
• Low anesthetic-circuit volume
• Low absorption by the anesthetic circuit
• Decreased solubility
• High cerebral blood flow
• Increased ventilation
Factors which slow elimination of inhalational
anesthetic agents:
• High tissue solubility
• Longer anesthetic times
• Low gas flows
36.
37. Minimum Alveolar Concentration
(MAC)
“The alveolar concentration of an inhaled
anaesthetic at 1 atm pressure in 100%
Oxygen at equilibrium, that produces
immoblity in 50% of those subjects
exposed to a standardized noxious
stimuli.”
It mirrors brain partial pressure after a
period of equilibration
MAC value is a measure of inhalational
anesthetic potency.
39. Factors Decreasing MAC
Increasing Age.
Hypothermia.
Other anesthetic (Opioids).
Acute drug intoxication (Ethanol).
Pregnancy.
Hypothyroidism.
Other drugs ( Clonidine ,Reserpine).
40. No Effect on MAC
Gender
Duration of anesthesia
Carbon dioxide tension (21-
95 mmHg)
Metabolic Acid base status
Hypertension
Hyperkalemia
41. AGENT MAC POTENCY
Methoxy-flurane 0.16% Most potent
Halothane 0.74%
Isoflurane 1.17%
Enflurane 1.7%
Sevoflurane 2.05%
Desflurane 6.0%
Nitrous oxide 104% Least potent
42. Factors determining how quickly
the inhalational agent reaches the
alveoli?
1-Increasing the delivered
concentrations of anesthetic
2- The gas flow rate through the
anesthetic machine
3-Increasing minute ventilation
MV = Respiratory Rate × Tidal
volume
43. Factors determining how quickly the inhalational
agent reaches the brain from the alveoli in order to
establish anesthesia?
1- The rate of blood flow to the brain
2- The solubility of the inhalational agent in the
brain
3- The difference in the arterial and venous
concentration of the inhalational agent
44. Anesthetic B:G PC MAC Features Notes
Halothane 2.3 0.74% PLEASANT Arrhythmia
Hepatitis
Hyperthermia
Enflurane 1.9 1.69% PUNGENT Seizures
Hyperthermia
Isoflurane 1.4 1.17% PUNGENT Widely used
Sevoflurane 0.62 1.92% PLEASANT Ideal
Desflurane 0.42 6.1% IRRITANT Cough
Nitrous 0.47 104% PLEASANT Anemia
47. Recent research suggests that inhalational agents may act on
specific membrane proteins and alter ion flux or receptor
function.
Interruption of Neuronal Transmission: the action of the
inhaled agents on synaptic transmission may be due to
alteration of either,
a. presynaptic transmitter release
b. reuptake of transmitter following release
c. binding to post/pre-synaptic receptor sites
d. membrane conductance following receptor
activation
GABA A receptors - potentiation of GABA receptor occurs
with halothane, isoflurane and sevoflurane.
Glycine receptors potentiation
48. All of the potent agents increase CBF in a dose-
dependent manner.
Halothane is a very potent cerebral vasodilator and
causes the greatest increase in CBF per MAC-
multiple.
↓ EEG wave frequency and ↑ amplitude
Higher conc. (2 MAC): Isoelectric EEG and burst
suppression
Protect against ischemia by ↓ CMRO2
Cerebral vasodilation leading to ↑ ICP
Enflurane and sevoflurane to a lesser extent can
cause convulsions
Dose related ↓ amplitude and ↑ latency of evoked
potentials
49. PULMONARY EFFECTS
Inhaled anesthetics produce dose-dependent
increases in the frequency of breathing.
Respiratory depression leading to decreased
tidal volume, ↓ MV and ↑pCO2:
The net effect of these changes is a rapid and
shallow pattern of breathing during general
anesthesia.
Depress ventilatory responses to hypercarbia
and hypoxia in a dose dependent manner.
50. An anesthetic-induced depression of
ventilation, as reflected by increases in
the PaCO2, most likely reflects the direct
depressant effects by these drugs on the
medullary ventilatory center.
Preferential dilatation of distal airways
as compared to proximal airways.
51. Functional residual capacity is decreased in
general anesthesia is bcoz of-
Decrease in the intercostal muscle tone,
Alteration in diaphragm position,
Changes in thoracic blood volume, and
The onset of phasic expiratory activity of
respiratory muscles
Inhaled anesthetics, including nitrous oxide, also
produce dose-dependent attenuation of the
ventilatory response to hypoxia
Halothane the most potent bronchodilator.
52. Systolic and Diastolic Function:
Dose related negative inotropic effect
Halothane=Enflurane>Isoflurane=Desflura
ne=Sevoflurane
Dose related prolongation of isovolemic
relaxation, early LV filling and filling
associated with atrial systole
53. Cardiac Protection (Anesthetic Preconditioning)
Brief episodes of myocardial ischemia occurring
before a subsequent longer period of myocardial
ischemia provide protection against myocardial
dysfunction and necrosis. This is termed ischemic
preconditioning (IPC).
The opening of KATP channels is critical for the
beneficial cardioprotective effects of IPC.
Brief exposure to a volatile anesthetic (isoflurane,
sevoflurane, desflurane) can activate KATP channels
and result in cardioprotection.
54. RENAL EFFECTS
Volatile anesthetics produce similar dose-related
decreases in renal blood flow, glomerular filtration rate,
and urine output.
These changes most likely reflect the effects of volatile
anesthetics on systemic blood pressure and cardiac
output.
Preoperative hydration attenuates or abolishes many of
the changes in renal function associated with volatile
anesthetics.
55. NEUROMUSCULAR SYSTEM
The inhaled anesthetics, in addition to the direct
effects of relaxing skeletal muscle, also potentiate
the action of neuromuscular blocking drugs.
Although the mechanism of this potentiation is
not entirely clear, it appears to be largely because
of a postsynaptic effect at the nicotinic
acetylcholine receptor located at the
neuromuscular junction
All of the potent volatile anesthetics serve as
triggers for malignant hyperthermia in genetically
susceptible patients.
56. UTERINE AND FETAL EFFECTS
Dose dependent relaxation of uterus
Increased blood loss during Caesarean
Delivery.
Lower concentrations (=0.5MAC safer)
Inhaled anesthetics cross placenta
Higher concentration: Fetal cardiovascular
depression
Reduction of CBF and O2 delivery to brain
57. Effect Of Volatile Agents On Hepatic
Blood Flow
Halothane: Causes hepatic arterial constricton,
microvascular vasoconstriction
Enflurane: Increase in hepatic vascular resistance
Isoflurane: Increase in microvascular blood velocity
Sevoflurane & Desflurane: Preservation of hepatic blood
flow & function
58. Carbon Monoxide and Heat
CO2 absorbents degrade sevoflurane, desflurane,
enflurane, and isoflurane to carbon monoxide when
the normal water content of the absorbent (13 to 15%)
is markedly decreased below 5%.
The degradation is the result of an exothermic reaction
of the anesthetics with the absorbent. Although
desflurane produces the most CO with anhydrous CO2
absorbers, the reaction with sevoflurane produces the
most heat. The strong exothermic reaction has caused
significant heatproduction, fires, and patient injuries.
59. Fluorination
Addition of fluorine have resulted in decreased
flammability and increased stability of volatile
anaesthetics.
The exclusion of all halogens except fluorine
results in nonflammable liquids that are poorly
lipid soluble and extremely resistant to
metabolism. Desflurane, a totally fluorinated
methyl ethyl ether, was introduced in 1992, and it
was followed in 1994 by the totally fluorinated
methyl isopropyl ether, sevoflurane.
60. Fluorination
The low solubility in blood of these newest anesthetics was
desirable, because it would facilitate the rapid induction of
anesthesia, permit precise control of anesthetic
concentrations during maintenance of anesthesia, and favor
prompt recovery at the end of anesthesia independent of the
duration of administration.
New risks [airway irritation, sympathetic nervous system
stimulation, carbon monoxide production, complex
vaporizer technology, fluoromethyl-2,2-difluro-1-
(trifluoromethyl) vinyl ether or compound A production]
and increased expense are associated with the administration
of these new drugs.
61. Ether
Cheap
High CVS stability
No blunting of Hypoxic drive
Slow Induction and Recovery
Pungent smell
Inflammable,so cautery cant be used
63. PHARMACOLOGY:
- Good Analgesic
- Weak anesthetic
- Excreted via lungs
- MAC = 104%
- Lower water solubility
- Not Metabolized in the body
Nitrous Oxide (N2O)
64. Nitrous oxide
N2O is a liquid gas .
Colour coding = french blue.
Gas cylinders are made of molybdenum
steel.
Blood gas partition coeficient is 0.47.
Pin index is 3;5
65. With a MAC value of 104%, nitrous oxide, by itself is
not suitable or safe as a sole anesthetic agent.
Nitrous oxide is an effective analgesic.
Nitrous oxide has minimal effects on the circulation
compared to the other inhalational agents with which it
is co-administered.
Nitrous oxide by itself has minimal effects on respiratory
drive.
Minimal skeletal muscle relaxation.
66. Toxicities – Nitrous Oxide
Hematologic:
N2O antagonizes B12 metabolism
inhibition of methionine-synthetase
Decreased DNA production
RBC production depressed post a 2 hr N2O exposure
Leukocyte production depressed if > 12 h exposure
Megoloblastic anemia. Aplasia in bone marrow
Neurologic:
Long term exposure to N2O is hypothesized to result in
neurologic disease similar to B12 deficiency
Dif hypoxia
Sec gas
67. 35 times more soluble in blood than nitrogen,
N2 so fills and expands any air-containing
cavities:
air embolism
pneumothorax
intracranial air
lung cysts
intraocular air bubbles
tympanoplasty
endotracheal tube cuff (monitor and reduce
pressure periodically)
May exacerbate pulmonary hypertension
68. XENON
Most ideal inhalational agent.
Blood gas partition co-efficient is 0.14. least of all .least
soluble. so fastest induction and fastest recovery.
MAC is 70% so can be given with 30%O2.
Most cardiostable.
No metabolism in body –least side effects non tertogenic.
Non inflamble,does not deplete ozone layer.
Disadvantages = costly, needs special equipment for
delivary, bronchospasm.
Acts on NMDA receptor
69. Entonox
50% N2O + 50% O2
Colour coding = blue body with blue &white
quarters.
Pin index = 7
Poyinting effect: normally N2O is liquid at 2400
psig. But If N2O is mixed with O2 it remains in
gaseous state called poyinting efect.
Use: 1)labour analgesia.
2)field analgesia(wars)
70. Methoxy-flurane
Most potent inhalational agent is M-F(mac-0.16%).
Slowest induction and recovery is M-F(b:g – 15).
Most nephro-toxic agent – M-F (high output renal
failure,highest fluride toxicity).
Cyclopropane
Most inflamable & explosive agent – Cp.
Liquid gas-Orange cylinder.
Cyclopropane shock.
71. Trichloroethylene (trilene)
Most potent analgesic agent - tcl. 2-xenon 3-N2O.
Reaction with sodalime :-
dichloroacetylene – neurotoxic- V, VII.
phosgene - pulmonary toxicity(ARDS)
CHLOROFORM
1st agent used for labour analgesia.
Cardiotoxic- death due to ventricular fibrillation.
Hepatotoxic.
Profound hyperglycemia.
76. Halothane: (2-bromo-2-chloro-1,1,1-
trifloroethane)
Synthesized in 1951.
* Volatile liquid easily vaporized, stable, and
nonflammable
* Most potent inhalational anesthetic
•MAC of 0.75%
•Colorless liquid , pleasant smell , decomposed by
light. So should be stored in container away from
light and heat
• It has low blood/gas solubility coeffient of 2.5 and
thus induction of anasthesia is relatively rapid.
•Stored in Amber-colored bottles because it is
susceptible to oxidative decomposition. To prevent
this THYMOL is added as a preservtive.
77. Halothane
2-chloro,bromo 1-trifluro ethane.
•Amber colored bottled – red colour coding
• It is a potent anesthetic.
• Induction is pleasant.
• It sensitizes the heart to catecholamines.conc of adrenaline
• It dilates bronchus – preferred in asthmatics.
• It inhibits uterine contractions.
• Halothane hepatitis and malignant hyperthermia can occur.
78. Halothane causes unconsciousness; however, does not
provide adequate analgesia.
Halothane does not provide adequate muscle
relaxation for surgery
Halothane is associated with reversible reduction in
glomerular filtration rates (GFR)
Halothane (Fluothane) is a myocardial depressant, an
effect which is particularly apparent in children,
especially in hypovolemic patients.
79. HALOTHANE
Metabolism
20% metabolized in liver by
oxidative pathways.
Major metabolites : bromin, chlorine,
Trifloroacetic acid,
Trifloroacetylethanl amide.
80. Dosage and Administration
The induction dose varies from patient
to patient. The maintenance dose varies
from 0.5 to 1.5%.
Halothane may be administered with
either oxygen or a mixture of oxygen and
nitrous oxide.
HALOTHANE
82. Respiratory system:
Halothane anesthesia progressively depresses
respiration.
Its cause inhibition of salivary & bronchial
secretion.
Its may cause tachypnea & reduce in tidal
volume and alveolar ventilation .
Its cause decrease in mucocillary function
which lead to sputum retention.
It causes bronchodilation. Hypoxia, acidosis, or
apnea may develop during deep anesthesia.
83. HALOTHANE
Effect on systems
Cardiovascular system:
Halothane anesthesia reduces the blood pressure, and
cause bradycardia.(atropin may reverse bradycardia.).
It cause myocardial relaxation & Hypotenstion.
Its also causes dilation of the vessels of the skin and
skeletal muscles
Halothane maybe advantages In pts with CAD , bcz of
decrease of oxygen demand.
Arrhythemias are very common .(especially with
epinephrine).
◦To minimize effects :
Avoid hypoxemia and hypercapnia
Avoid conc. Of adrenaline higher than 1 in
10000
84. HALOTHANE
Effect on systems
Gastro intestinal tract:
Inhibition of gastrointestinal motility.
Cause sever post. Operative nausea & vomiting
Uterus:
Halothane relaxes uterine muscle, may cause postpartum
hemorrhage .
Concentration of less than 0.5 % associated with increase
blood loss during therapeutic abortion.
Skeletal muscle:
Its cause skeletal muscle relaxation .
Postoperatively , shivering is common , this increase oxygen
requirement>>> which cause hypoxemia
85. Halothane - Hepatic Toxicity
All inhaled AA can cause hepatic injury in animal
studies
All inhaled AA have immunohistochemical
evidence of binding to hepatocytes
Thought that Trifluoroacetic acid metabolites are
root cause
Another theory is due to Hypoxia as halothane causes
Hepatic arterial constriction
86. Halothane Hepatitis
The incidence of fulminant hepatic necrosis terminating
in death associated with halothane was found to be 1 per
35,000.
Demographic factors ; It’s a idiosyncratic reaction,
susceptible population include Mexican Americans
,Obese women, , Age >50 yrs, , Familial
predisposition,Severe hepatic dysfunction while Children
are resistant.
Prior exposure to halothane is a important risk factor &
multiple exposure increases the chance of hepatitis.
87. Mechanism of Toxicity
There are various proposed mechanisms:
• Metabolite-mediated direct toxicity
• Immunologically-mediated damage to liver cells
a proportion is biotransformed by hepatic microsomal enzyme CYP 2E1
to a trifluoroacetic acid which can be detected in the urine, but which
also can trifluoroacetylate hepatic proteins, some of which may be
immunogenic and induce cytotoxic reactions.
• Hypoxia alone
88.
89. Main advantages of halothane:
Rapid smooth induction .
Minimal stimulation of salivary &
bronchial secretion.
Brochodilatation.
Muscle relaxant .
Relatively rapid recovery.
90. Main disadvantages are:
Poor analgesia.
Arrhythmias.
Post operatively shivering.
Possibility of liver toxicity.
91. Contraindication
Malignant hyperthermia.
susceptibility unexplained liver dysfunction after
previous halothane exposure
intracranial mass lesion
hypovolemia
aortic stenosis
pheochromocytoma
with aminophylline has been associated with severe
ventricular dysrhythmias
92. Isoflurane
2-chloro 1-trifluro methyl-
ethyl ether.
Isomer of enflurane
Clear, Nonflammble, Pungent odour .
Physically stable- No preservative.
MAC is 1.17 % & B:G p co-ef is 1.46.
Only agent that preserves baroreceptor reflex –isof.
So that relex tachycardia occurs in response to
decrease B.P mantaining cardiac output.
Coronary steal
93. Isoflurane
Initially, until deeper levels of anesthesia are
reached, isoflurane stimulates airway reflexes
with:
increases in secretions
coughing
laryngospasm.
94. Isoflurane
CNS:
Generalized CNS depression; Rapid emergence
Increased ICP
Agent of choice for neuro anaesthesia is isoflurane
Cardiovascular:
Little effect on cardiac output
Decreased systemic vascular resistance
Decreased MAP
Increased heart rate
Agent of choice for cardiac anaesthesia is isoflurane
95. Coronary steal phenomenon
Isoflurane induced coronary artery vasodilatation can
lead to redistribution of coronary blood flow away
from diseased areas where arterioles are maximally
dilated to areas with normal responsive coronary
arteries. This phenomenon is called the coronary
steal syndrome
97. Sevoflurane
Methyl –isopropyl ether.
Non-pungent, bronchodilation similar to isoflurane
Non flammable,
MAC- 1.80, B:G Coff. – 0.69
Stable-No preservative
Least airway irritation among current volatile anesthetics,
thereby allowing direct anesthesia induction
98. • Pleasant smell , non irritant and bronchodilatation makes
it agent of choice for paediaric anaesthesia.
• 2nd agent of choice for
• Neuro anaesthesia.
• Cardiac anaesthesia .
• asthamatics
Sevoflurane
99. Sevoflurane
Advantages and Disadvantages
Advantages
1. Well tolerated (non-irritant, sweet odor), even at
high concentrations, making this the agent of choice
for inhalational induction.
2. Rapid induction and recovery (low blood:gas
coefficient)
3. Does not sensitize the myocardium to
catecholamines as much as halothane.
4. Does not result in carbon monoxide production
with dry soda lime.
100. Disadvantages
1. Less potent than similar halogenated agents.
2. Interacts with CO2 absorbers. In the presence of
soda lime (and more with barium lime) compound A
(a vinyl ether) is produced which is toxic to the brain,
liver, and kidneys.
3. About 5% is metabolized and elevation of serum
fluoride levels has led to concerns about the risk of
renal toxicity.
4. Postoperative agitation may be more common in
children then seen with halothane.
Sevoflurane
Advantages and Disadvantages
101. Sevoflurane and Compound A
Sevoflurane forms a degradation product, compound
A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] on
contact with the soda lime in a rebreathing apparatus.
Compound A is a dose-dependent nephrotoxin in rats,causing
renal proximal tubule injury.
A proposed mechanism for nephrotoxicity is the metabolism of
compound A to a reactive thiol via the β-lyase pathway.
Because humans have less than one-tenth of the enzymatic
activity for this pathway compared to rats, it is possible that
humans should be less vulnerable to injury by this mechanism.
102. SEVOFLURANE
Sevoflurane can also be degraded into hydrogen
fluoride by metal and environmental impurities
present in manufacturing equipment, glass bottle
packaging, and anesthesia equipment. Hydrogen
fluoride can produce an acid burn on contact with
respiratory mucosa. The risk of patient injury has been
substantially reduced by inhibition of the degradation
process by adding water to sevoflurane during the
manufacturing process and packaging it in a special
plastic container
103. Desflurane
2-fluro,1-trifluro methyl ethyl ether.
MAC-6.6 ;B:G coff. -0.42
No need to add preservative
Agent that boils at room temperature(22.8*c)-DF.
Agent of choice for day care (fastest induction)- DF.
Agent of choice for geriatric (old) patients – DF.
Agent of choice for hepatic failure
Agent of choice for renal failure
104. Desflurane
Pungent odor --desflurane less likely to be used for
inhalation induction compared to halothane or
sevoflurane.
Airway irritation, breath-holding, coughing,
laryngospasm when >6% inspired desflurane
administered to an awake patient.
Significant salivation
Carbon monoxide: Secondary to desflurane
degradation by strong base present in carbon dioxide
absorbants.
106. It was created specifically for the agent desflurane
Desflurane boils at 23.5 ºC, which is very close to room
temperature. This means that at normal operating
temperatures, the saturated vapour pressure of desflurane
changes greatly with only small fluctuations in
temperature.
A desflurane vaporiser (e.g. the TEC 6 produced by Datex-
Ohmeda) is heated to 39C and pressurised to 200kPa (and
therefore requires electrical power).
.
107. Morgan, G.E., Mikhail, M.S., and Murray, M.J. (2006). Clinical
Anesthesiology. (4th Ed.) New York, NY: McGraw-Hill.
Nagelhout, J.J. and Zaglaniczny, K.L. (2005). Nurse Anesthesia. (3rd Ed.).
St. Louis, MO: Elsevier- Saunders.
Stoelting, R.K. (1999). Pharmacology & Physiology in Anesthetic Practice.
(3rd Ed.) Philadelphia, PA:
J.B. Lippincott Company.
Steven L. Shafer, M.D : Inhalational Anesthetics : Uptake and
Distribution , July 24, 2007.
Read Eger's The Pharmacology of Inhaled Anesthetics.
Miller's Anesthesia, Seventh Edition.
Barash : Handbook of Clinical Anesthesia (6th Ed. 2009)
Anesthesia and Anesthesiology Teaching Site:
http://www.anesthesia2000.com/
Edmond I Eger II, MD : Illustrations of Inhaled Anesthetic Uptake,
Including Intertissue Diffusion to and from Fat. Anesth Analg
2005;100:1020–33.
B.Korman and W.W.Mapleson: Concentration and second gas effects:
Can the accepted explanations be improved? British Journal of
Anaesthesia 1997;78:618-625
REFERENCES
