Download MBBS Neuroanaesthesia PPT 4 Inhalational Anaesthetics Lecture Notes

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Introduction

? These are the most common drug used for G/A

? Popularity is based on their

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? Ease of administration

? Ability to monitor their effects

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? Relatively inexpensive

? Prevents recalls and provides MR also
History

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? The discovery of anaesthetic properties of N2O, diethyl

ether and chloroform in 1840s

? Long duration of 80 years before other inhaled

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anaesthetic were introduced. In 1950, all were flammable

toxic exception of N2O

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? Halothane was synthesized in 1951
? Introduced for clinical use in 1956
? Due to enhance dysarrhythmogenic effect of epenephrine

led to search for new derivative

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History (contd...)

? Enflurane

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? Introduced in clinical use in 1973

? Nephrotoxicity seems less likely

? Does not enhance dysarrhythmogenic effect of epinephrine

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? It has epileptogenic potential

? Isoflurane, isomer of enflurane, introduced in 1981. Resistant

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to metabolism making organ toxicity unlikely
History (contd...)

? Desflurane was introduced in 1993
? Sevoflurane was introduced in 1995

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? Low blood gas solubility of these agents

? Rapid induction and rapid recovery
? Precise control of anaesthetic concentration

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Inhalational agents

Classification

A. Volatile anaesthetics

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B. Anaesthetic gases

1. Diethyl Ether (CH

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1.

3CH2-OCH2CH3)

Nitroux oxide

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2. Divinyl Ether [(C

2.

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2H3)2 O]

Cyclopropane

3. Ethyl chloride (C

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3.

2H5Cl)

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Ethylene

4. Chloroform (CHCl

4.

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3)

Xenon, Argon

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5. Trichloroethylene (CCl

5.

2CHCl)

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Sulphur hexafluoride

6. Halothane (CF3CHClBr)
7. Methoxyflurane

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8. Enflurane
9. Isoflurane
10. Desflurane
11. Sevoflurane

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Uptake and Distribution

? Liquid anesthetic is vaporized and mixed with oxygen
? Mixture is delivered to the patient via a mask or

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endotracheal tube (ET tube)

? Mixture travels to lungs (alveoli) and diffuses into the

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bloodstream

? Diffusion rate is dependent on concentration gradient

(alveoli/capillary) and lipid solubility of the

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anesthetic gas

? Concentration gradient is greatest during initial induction

ANESTHETIC TRANSFER

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Physical and Chemical Properties

of Inhalant Anesthetics

? Important properties to consider

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? Vapor pressure
? Partition coefficient
? Minimum alveolar concentration (MAC)
? Rubber solubility

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Vapor Pressure

? Is the amount of pressure exerted by the gaseous

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form of a substance when in equilibrium

? i.e. ? it's ability to evaporate

? Determines how readily an inhalation anesthetic

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will evaporate in the anesthetic machine vaporizer

? Dependent upon temperature and anesthetic

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agent
Blood:Gas Partition Coefficient

? The measure of the solubility of an inhalation

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anesthetic in blood as compared to alveolar gas (air)

? Indication of the speed of induction and recovery for

an inhalation anesthetic agent

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? Low blood:gas partition coefficient

? Agent is more soluble in alveolar gas than in blood at

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equilibrium

? Agent is less soluble in blood
? Faster expected induction and recovery

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MINIMUM ALVEOLAR CONCENTRATION

(MAC)

? It is the steady state expired gas concentration of an

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anesthetic

? At 1 atm pressure
? That prevents movement

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? In response to surgical stimulus
? In 50% patients

Analogous to ED 50
? Best measure of anesthetic potency as it mirrors the brain

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partial pressure.

? MAC values of different anesthetic are roughly additive.
MAC

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MAC BAR- MAC that blunts adrenergic response to

noxious stimulus (1.5MAC)

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MAC UNCONSCIOUS- MAC at which pt loses

consciousness (0.4-0.5MAC)

MAC AWAKE- MAC at which patient opens his or her

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eyes to command (0.15-0.5MAC)

Increasing

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Anesthetic Depth

MAC Fraction

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MAC Fraction
MAC

?MAC of inhalational agents
N2O 104

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Halothane 0.75
Isoflurane 1.17
Desflurane 6.6
Sevoflurane 1.8

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? Roughly 1.3 MAC of any of the volatile anesthetic can

prevent movement in 95% pts during surgical stimuli.

FACTORS AFFECTING MAC

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INCREASING MAC

? CNS metabolism
? CNS neurotransmission

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? Hyperthermia
? Chronic alcohol abuse
? Hyponatremia
? Drugs - MAO I
- Amphetamine

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- Cocaine
- Ephedrine
- L -DOPA
Decreasing MAC

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? CNS metabolism
? CNS neurotransmission

? age

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? Hypothermia

? Acute alcohol

? Hypotension(50mmhg MAP)

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? Hypoxemia(38mmhg)

? Pregnancy

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? Narcotics

? Ketamine

? Benzodiazepines

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? Lithium

? Local anesthetics

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NO EFFECTS ON MAC

?

Gender

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?

Duration of anesthesia

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?

Hypertension

?

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Anemia

?

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Thyroid status

?

Hypo or hypercarbia

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?

Metabolic alkalosis

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?

Hyperkalemia

?

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Magnesium levels


Diethyl Ether (CH3CH2-O-CH2CH3)

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History

? Prepared originally by Valerius Cordus- Sweet oil of vitriol

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? Introduced in profession by W.T.G. Morton of Boston on Oct

16, 1846

? Classic stages and planes of anesthesia described using

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ether

Diethyl Ether (CH3CH2-O-CH2CH3) (contd..)

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Manufacture
? By heating together conc H2SO4 and 95% ethyl alcohol at

130?C
Physical properties

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? Colorless, pungent volatile liquid
? Blood / gas solubility 12, MAC 3.04
? Relatively inert
? Acetaldehyde and ether peroxide as impurities, greater the

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EP Lesser potency

? Stored in dark cool place
? Unaltered in the body 85-90% - Lungs, 15% metabolized in

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liver

? inflammable in air and explosive in O2
EFFECTS ON ORGAN SYSTEM

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A. Circulatory system
? Heart rate First increased Unaltered

Blood pressure

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? Decreased BP after 1st hour ? below phase II
? Vaso Motor Centre paralysis in deep plane
? Functioning Sympathetic Nervous System BP
? Ether increase in sympathetic adrenal activity

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? Cardiac output

? Lighter Plane of Anaesthesia CO increases
? Deep Plane of Anaesthesia CO decreases

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? Arrhythmia ? rare, adrenaline safer with ether

B. Respiratory system

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? RR increase Ist then decrease in deeper plane

? Ether vapour ? Irritant Laryngospasm

? Ether dilates bronchial musculature

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? Hence induction ? Gradual

C.Nervous system

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? Central nervous system

? Induce analgesia Excitement Anaesthesia

? Medullary depression Late, precedes the serious

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cardiac depression

? CBF increases increases CSF pressure
? Sympathetic nervous system

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? Ether

? Central stimulation increase blood catecholamine level

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? Increase in HR

? Increased production of glycogen increased BS level

? Centration of spleen

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? Dilatation ? Gut and inhibition of movements

? Dilatation of coronary arteries

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? Dilation of pupils

? Parasympathetic ? NS central depression

D. Alimentary system

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? PONV (>50% patients)

? Salivary gland stimulation ? Induction and depressed later on

? Gastrointestinal atony

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? Liver function decreased, decreased sec of bile and bile salts
E. Urinary system
? Urine flow ? diminished

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? Dec in plasma volume and renal Vaso-Constriction
Advantages of Ether

? Relatively non-toxic, safe and potent
? Relatively cheap and can be used without sophisticated

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apparatus

? Excellent relaxation
? Respiratory depression not accompanied by serious cardiac

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damage in A/o hypoxia

? Maintained BP, no tendency to arrhythmias
? Thus ether ? very safe, less experienced anaesthetist. Having

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wide safety margin

Disadvantages of Ether

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? Induction and recovery slow
? Mucous secretion from upper airway
? Causes albumin urea
? Inflammable: Explodes, sparks flames
? Ether convulsion : Triad

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? Deeper ether anaesthesia
? Hyperthermia
? Hypocapnea

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HALOTHANE

? It is halogenated alkene.
? Least expensive

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? 2 bromo-2-chloro 1,1,1-

F

Br

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trifluroethane

? Non-flammable and non explosive
? Non irritant vapors

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F

C

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C

Cl

? Decomposed by light

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(0.01%thymol,amber bottles)

? Absorbed by rubber

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F

H

? Corrodes metals

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? B:G -2.54
? 20-46% metabolized in the liver
? MAC- 0.87-1.19

EFFECTS ON ORGAN SYSTEM

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1. CARDIOVASCULAR:
Dose dependent reduction of arterial blood pressure

by direct myocardial depression.

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It is a coronary artery vasodilator.
It causes slowing of SA node conduction resulting in

bradycardia.

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Sensitizes heart to catecholamine and induces

arrhythmias

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2. RESPIRATORY SYSTEM:
Causes rapid ,shallow breathing.
Decrease in alveolar ventilation and Paco2 elevated.
Potent bronchodilator.
3. CEREBRAL:

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Increased cerebral blood flow
Increased temperature- malignant hyperthermia-

Dantrolene is used for treatment

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4. NEUROMUSCULAR:
? Relaxes skelatal muscle and potentiates non

depolarizing neuro-muscular blocking agents.

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5.RENAL:
? Reduces renal blood flow, glomerular filtration

rate and urinary output.

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6. HEPATIC:
? Decreases hepatic blood flow.

CONTRAINDICATION

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? Unexplained liver dysfunction.
? Intra-cranial mass lesions.
? Hypo-volemic patient with severe cardiac

diseases.

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ISOFLURANE

F

Cl

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F

F

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C

C

O

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C

F

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F

H

H

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? 1-chloro-2,2,2-trifluoroethyl difluoromethyl

ether

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? Colorless volatile liquid
? Pungent
? No preservative
? Does not react with metals

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Isoflurane

? It is non flammable volatile with a pungent
smell.
? Physical Properties

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? High vapor pressure: need a precision vaporizer
? Low blood:gas partition coefficient (1.4): rapid induction and

recovery

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? Good for induction with mask or chamber ?
? MAC = 1.3% to 1.63%: helps determine initial vaporizer setting
? Low rubber solubility
? Stable at room temperature; no preservatives needed = no build

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up in the machine

? Almost completely eliminated through the lungs- 0.2% metabolized

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by the liver
EFFECTS ON ORGAN SYSTEM

CARDIOVASCULAR:
Causes minimal cardiac depression.

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Maintains cardiac output, heart rate, and rhythm
Fewest adverse cardiovascular effects
Rapid increase in MAC lead to increase in HR and BP.
Dilates coronary arteries. (Coronary Steal)
2. RESPIRATORY SYSTEM:

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Respiratory depression .
Irritant to upper airway

3. CEREBRAL:
Maintains cerebral blood flow

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If conc > 1 MAC causes increase in CBF and Intracranial

pressure.

4. NEUROMUSCULAR:

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Induces adequate to good muscle relaxation
5. RENAL:
Decreases renal blood flow , glomerular filtration rate and

urinary output.

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6. HEAPTIC:
Reduces hepatic blood flow.
INDICATIONS
? For Cardiac and Neuro- Surgery

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? In patients with hepatic or renal compromise
CONTRAINDICATION
? No such contraindication.
? Caution in asthmatics

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SEVOFLURANE

? Methylpropylether

F

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? Nonflammable

F C

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pleasant smell

F

H

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? MAC is higher in

children (2.6%in O2

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H

C

O

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C

F

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and 2.0%in
N2O)and neonates

F

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H

(3.3%)

F C

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? Stable

F

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Sevoflurane

High vapor pressure: need a precision vaporizer
Low Blood:gas partition coefficient (0.65)

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= rapid induction and recovery
Good for induction with a mask or chamber. Easier to mask a

patient, more pleasant smelling

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High controllability of depth of anesthesia
MAC = 2.34% to 2.58%
Cost about 10x more than Isoflurane
Eliminated by the lungs, minimal hepatic metabolism- 2-5%
Can react with potassium hydroxide (KOH) or sodium hydroxide

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(NaOH) in desiccated CO2 absorbent to produce a chemical

(Compound A) that causes renal damage

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EFFECTS ON ORGANS

1. CARDIOVASCULAR SYSTEM:
? Mildly depresses myocardial contractility.
? May prolong QT interval, but no significance.

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2. RESPIRATORY SYSTEM:
? Depresses respiratory rate.
? It reverses broncho-spasm

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3. CEREBRAL:
? Maintains cerebral blood flow
? Increases CBF and intra-cranial pressure.
? Some paddling and excitement during recovery
? No post-op analgesia

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4. RENAL SYSTEM:
? Slightly decreases renal blood flow. Higher Conc

Causes Nephro-toxicity

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5. HEPATIC:
? Decreases portal vein blood flow but increases

hepatic artery blood flow thus maintaining total

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hepatic blood flow.

6.NEUROMUSCULAR:
? Adequate muscle relaxation.

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INDICATION
? For induction
? Especially useful in children
? In patients with reactive upper airway
CONTRAINDICATION

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? No such contraindication
? Caution in severe hypo-volemia.


DESFLURANE

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? Fluorinated methyl

ethyl ether

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F

F

F

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? Colorless, without

preservative

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F

C

C

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O

C

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F

? Non flammable
? Special heated

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F

H

H

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vaporizer

Desflurane

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Structure much similar to that of isoflurane.
Recovery time are approximately 50 % less than those of

Isoflurane.

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Pungent Smell
? Expensive
? Lowest blood:gas partition coefficient: very rapid induction and

recovery

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? Used with a special heated electronic precision
vaporizer (TEC 6)
? MAC = 7.2% and 9.8%

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? Least potent inhalant agent

? Eliminated by the lungs- 0.02% metabolized in liver
EFFECTS ON ORGAN SYSTEM

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1. CARDIOVASCULAR SYSTEM:
? Similar to Isoflurane ( Increases HR and BP when increased

MAC rapidly)

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? Dilates coronary arteries.
2. RESPIRATORY SYSTEM:
? Causes decrease in tidal volume and increase in resp rate.
? Pungency and airway irritation so causes coughing and

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sometime bronchospasm.

? Strong vapors cause coughing and holding the breath=

difficult to mask

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2. 3. CEREBRAL:
? Increases CBF and Intracranial pressure.
4. NEUROMUSCULAR:
? Relaxes skeletal muscle.

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5. RENAL AND HEPATIC SYSTEM:
? No any evidence has been documented.

INDICATION- For Hepatic and Renal Surgery
CONRAINDICATION ? Same as isoflurane

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NITROUS OXIDE

Physical properties:
?It is a laughing gas.
?It is only inorganic anesthetic gas in clinical use.

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?Colorless and odorless
?Non Explosive and Non Infammable
?Gas at room temperature and can be kept as a

liquid under pressure.

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?It is relatively inexpensive.

Effects of Nitrous Oxide on Organ System

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1. CARDIOVASCULAR SYSTEM
? Stimulate sympathetic nervous system.
? Directly depresses myocardial contractility.
? Arterial blood pressure ,heart rate and cardiac

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output are slightly increased.

2. RESPIRATORY SYSTEM:
? Increases respiratory rate with decreases tidal volume.
? Minimal change in minute ventilation.

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3. CEREBRAL:
? Increases CBF thus increasing intracranial pressure.
4. RENAL SYSTEM:
? It decreases renal blood flow thus leads to drop in

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glomerular filtration rate and urinary output.

5. HEPATIC SYSTEM:
? Decreases the Hepatic blood flow but to a lesser

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extent than other inhalation agents.

6. GASTROINTESTINAL:
? It causes post operative Nausea and Vomiting.

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CONTRAINDICATION OF N2O

? Air embolism
? Pneumothorax
? Acute Intestinal Obstruction

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? Tension Pneumocephalus
? Tympanic membrane grafting
Uses of N2O

Mixed with oxygen at 40-67%, then delivered

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to patient

Reduces MAC 20-30%

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Used with Halothane and Methoxyflurane
to reduce the adverse effects of these gases