1. General Anesthesia

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GENERALANESTHETICS

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INTRODUCTION

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ANESTHESIA: absence of sensation

General anesthetics are used as an

adjunct to surgical procedures to render

the patient unaware&unresponsive to

painful stimuli.

They are given systemically.

They exert their main effect on the CNS.

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OPTIMAL GENERAL ANESTHETICreversible CNS depression (with minimal

depression of vital functions) 1. Loss of consciousness

2. Analgesia

3. Muscle relaxation

NOsingle agent can produce such aims

rapidly and safely.

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Anesthetic medication includes:1) Preanesthetic medication

2) Potent general anesthetics

3) Skeletal muscle relaxants

Inhalation anesthetics are volatile liquids

except nitrous oxide (N2O)

i.v. Anesthetics rapid induction

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A.Status of organsystem

1) Multiple adjunct

agents: preanestheticmedication

2) Additional non-

anesthetic drugs:

alcohol or opiate

abuse

1) Liver & Kidney

2) Resp. System

3) CVS

4) CNS

5) Pregnancy

B.Concomitant use ofdrugs

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Induction, Maintenance & Recovery from

Anesthesia

A. INDUCTION: the period of time from the onset

of anesthetic agent administration to thedevelopment of effective surgical anesthesia

It depends on how fast effective conc. of the

anesthetic drug reaches the brain.

B. MAINTENANCE: sustained surgical anesthesia

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C. RECOVERY: the time from the discontinuation

of administration of the anesthetic until

consciousness and protective physiologic

reflexes are gained

It is the reverse of induction.

It depends on how fast the anesthetic drugdiffuses out from the brain.

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D. DEPTH (STAGES) OF ANESTHESIA (4 STAGES):

Each stage is characterized by CNSdepression caused by accumulation of the

anesthetic drug in the brain.

They are well defined withetherwhich

producesa slow onset of anesthesia. G.R.

With newer agents, the stages are difficult to

characterize(rapid onset of anesthesia). G.R.

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Stages of AnesthesiaStage Characteristics

1.Analgesia - The subject is conscious but drowsy.- Responses to painful stimuli It is pronounced with ether, N2O, but not with halothane.

2.Excitement - It is a dangerous stage.- There is loss of consciousness, delirium and violent

combative behavior.- The subject does not respond to non-painful stimuli, but

responds to painful ones.

- Rapid respiration (irregular), irregular B.P. & preservedcough reflex

In modern anesthesia, this stage cannot be distinguished.

Can be avoided by thiopental.

3.Surgicalanesthesia

- Spontaneous movement, regular respiration & markedmuscle relaxation.

4.Medullaryparalysis

- Severe depression of Resp. & VM centers

- It starts by stoppage of respiration and ends by circulatoryfailure (death occurs within a few minutes).

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GENERAL ANESTHETICS:

I. Inhalation Anesthetics

II. i.v. Anesthetics

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I.INHALATIONANESTHETICS

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Used for maintenance of anesthesia after an

i.v. anesthetic agent

Advantages:

1) Minute-to-minute control of the depth of

anesthesia by changing the conc. of the

delivered anesthetic gas

2) Reversible; rapidly eliminated by

exhalation

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Common features of inhalation anesthetics

1) Non-flammable & non-explosive

2) Smooth muscle relaxation a) Cerebrovascular resistance (cerebral

v.d.) brain perfusionb) Bronchodilation

3) Their movement from the lungs to body

depends on their solubility in blood &tissues

and blood flow.

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POTENCY(MINIMUM ALVEOLARCONC.; MAC)

It is the conc. of anesthetic gas needed to

eliminate movement among 50% of patients

challenged with standardized skin incision.

It is expressed as the % of anesthetic gas

in a mixture required to achieve the effect.

It is small for potent anesthetics (e.g.halothane) & large for less potent ones (e.g.

N2O)

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Anesthetic lipid solubility potency MethoxyfluraneHalothaneEnflurane

IsofluraneSevofluraneDesfluraneN2O17

DesfluraneSevoflurane


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Enflurane

Methoxyflurane

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Pharmacokinetics:

Very rapid absorption from the lungs

(enormous surface area & efficient blood

supply of the alveolar surface)G.R.

Upon inhalation, the anesthetic passes

through the alveolar membrane arterialblood various body tissues esp. the CNS

Excreted mostly unchanged through the

lungs

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A. Diethyl ether (Ether; (C2H5)2O)

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B. Chloroform

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C. Halothane (Fluthane)

2-bromo-2-chloro-1,1,1-trifluoro-ethane

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It is the anesthetic of choice in children

because(1) its pleasant odor, (2) lacking

airway irritation, and (3) non-hepatotoxic in

children G.R.

Halothane hepatitis:

20-30% of halothane undergo hepatic

metabolism trifluoroaacetic acid & bromide(a reaction common in females) fever,anorexia, N & V & jaundice hepatitis

50%of those patients die ofhepatic necrosis

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D. Enflurane (2-chloro-1,1,2,-trifluoroethyl-difluoromethyl ether)

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E. Methoxyflurane

It is the most potent inhalation anesthetic

(high lipid solubility).

Prolonged administration metabolicrelease offluoride (nephrotoxic) rarelyused outside of obstetrics G.R.

It is used in child-birth because it does not

relax the uterus when briefly inhaled. G.R.

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F. Isoflurane (isomer of enflurane)

A halogenated anesthetic that has low

biotransformation & low organ toxicity

It is a very stable molecule that undergoes little

metabolism less fluoride is produced lesstoxicity (nephrotoxicity)

It does not induce cardiac arrhythmias nor

sensitize the heart to catecholamines.

conc.-dependent hypotension (due toperipheral & coronary v.d.) suitable forpatients with ischemic heart diseasesG.R.

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G. Desflurane (isomer of enflurane)

It has the most rapid onset and offset of the

inhalation anesthetics (low blood solubility).

Its potency is lower than the above

mentioned halogenated anesthetics

At the conc. used for induction (10%)

resp. irritation cough & bronchospasm

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H. Sevoflurane

It resembles desflurane but more potent.

It is less likely to cause resp. irritation suitable for children

Metabolism

fluoride

nephrotoxicity

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Malignant hyperthermia:

A pharmacogenetic disorder It results from excessive metabolic heat

production in skeletal muscle due to excessive

release of Ca2+

from the sarcoplasmicreticulum a dramatic in body temp.,muscle contractions & acidosis

It can be fatal unless treated promptly.

Rx: dantrolene; a muscle relaxant, which

blocks these Ca2+channels

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I. Nitrous Oxide (laughing gas; N2O)

Inorganic colorless, odorless, tasteless gas.

It has a MAC of 105% !!!

It is effectiveANALGESIC in concentrationstoo low to cause unconsciousness (35%) a

potent analgesic but weak general

anesthetic

usually used with anotherinhaled or i.v. anesthetic for complete

anesthesia

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Inhalation of pure N2

O rapid lightanesthesia

Induction is rapid, the patient is joyful

euphoric, and consciousness is lost in 20-30 seconds.

Continued N2O administration 2 min signs of severe anoxia (cyanosis, BP &muscle twitches)

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I. Nitrous Oxide (Laughing gas) N2O

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II.INTRAVENOUSANESTHETICS

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1) Anesthetics

unconsciousness in 20 sec Ex.: ultrashort-acting barbiturates (e.g.

thiopental), etomidate & propofol

2) Basal Anesthetics

They act less rapidly to produce sedation

prior to anesthesia

the amount ofinhalation anesthetics

Ex.: ketamine & diazepam

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A. Ultrashort-Acting Barbiturates

Ex.: thiopental, methohexital &thiamylal

They are ultrashort-acting.

Their rapid entry to the CNS is followed by a

relativelyquick redistributionto different

body tissues.

A single IV dose of thiopental unconsciousness within 10-20 sec that lasts

for 5-10 min

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NO analgesic effect

Thiobarbiturates cross the placenta fetalresp. depression

They are useful in:

1) Induction of anesthesia

2) Maintenance of short surgical procedures

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Uses:

1. Brief general anesthesia for minor operations

2. Induction of anesthesia which is then

completed by another anesthetic, e.g. N2O

3. Basal anesthesia (given rectally in doses

lower than those required to produce full

anesthesia)

4. Anticonvulsants

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B. Etomidate

A potent ultrashort-acting (5-10 min) non-barbiturate anesthetic hypnotic amnesic agent

NO analgesia

Similar pharmacological properties to those of

barbiturates

A wide safety margin

Used for induction and supplement to maintain

anesthesia

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C. Propofol

It isoilat room temp.

It is supplied as 1% emulsion for IV

anesthesia.

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A short-acting IV sedative/hypnotic used in

the induction or maintenance of anesthesia

It induces anesthesia as rapidly as does

thiopental.

NO analgesia

Anesthesia may be maintained by continuous

infusion of propofol combined with opioids &

N2O.

Safe (no liver or kidney toxicity)

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D. Benzodiazepines

Useful for induction & maintenance of

anesthesia and in pre-anesthetic medication

Diazepam(orally, IM & IV) is used for

preanesthetic medication.

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Lorazepamis used extensively in cardiacsurgery.

It produces amnesia and is particularly

useful during cardiopulmonary bypass to

ensure unawareness of the procedure.

Midazolamhas a slower onset of action than

all drugs.

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E. Ketamine

In dissociative anesthesia, the patient is

dissociated from his environment, the eyes

remain open and the patient appears awake

and reactivebut does not respond to sensory

stimuli.

It blocks NMDA-receptors.

It is used by IM and IV routes.

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Ketamine analgesia, amnesia &paralysis ofmovement without actual loss of

consciousness.

Following a single dose, consciousness is lost

for 10-15 min &analgesia persists for 40 min.

There is no muscle relaxation (a state of

catalepsy; muscular rigidity and fixity of

posture regardless of external stimuli) + sensitivity to pain

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The main side effect is emergence

phenomenon: unpleasant hallucination,

delirium, irrational behavior (scream and

cry) during recovery. These effects are less

marked in children.

Ketamine is often used in conjunction with

BDZs (diazepam) for minor procedures in

pediatrics as they prevent the emergence

phenomenon.

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Neuroleptanalgesia

A combination of neuroleptic drugs and

analgesics a state of deep sedation and

analgesia in which the patient remainsresponsive to simple commands and

questions but does not respond to painful

stimuli or retain any memory of theprocedure

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A combination ofa neuroleptic

antipsychotic as droperidol or haloperidol

( a state of quiescence with reduced motoractivity) and a potent opioid analgesic as

fentanyl.

It is used in diagnostic procedures (e.g.

endoscopy & radiological studies) or minor

surgical procedures (e.g. burns dressing).

It can be converted to neuroleptanesthesia

by administration of 65% N2O in O2.

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III.PREANESTHETIC

MEDICATION

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It is the use of drugs prior to administration

of an anesthetic to:

1. Anxiety & fear and production of sedation2.

Dose of general anesthetic

3. Relieve of preoperative pain (if present)

4. Minimize the undesirable complications of

anesthetics such as salivation, bradycardia,

postoperative vomiting,

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I. Sedative-hypnotics & anxiolytics:

A. BDZs of short duration of action amnesia(diazepam, lorazepam & midazolam)

B. Barbiturates: orally or I.M., 1 hour before

operation sedation and relief anxiety(pentobarbital & secobarbital)

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C. Antihistamines: sedative anticholinergic

properties (hydroxyzine & diphenhydramine)

D. Phenothiazines: tranquilizing and antiemeticproperties. They are combined in reduced

dosage with barbiturates or opioids, e.g.

promethazine and propiomazine

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II. Analgesics

Surgical pain is often severe, and even minor

preoperative pain is deleterious to smooth

induction of anesthesia

Opioids are frequently used i.m. 1 hour

before anesthesia

Examples: morphine, meperidine&fentanyl

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III.Antiemetics

Droperidol, hydoxyzine&ondansetron

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IV. Anticholinergics Atropine or scopolamine is used i.m. 1 hour

before anesthesia to:

1. Salivary & bronchial secretions2. Block the reflex vagal effect on the heart

3. Counteract the respiratory depressantactions of morphine

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Advantages of scopolamine over atropine asa preanesthetic drug:

1. Being a central depressant sedation &amnesia

2. More potent as antiemetic & antisecretory

3. It counteracts the resp. depression ofmorphine more efficiently

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V. Skeletal muscle relaxants:

To facilitate intubation and suppress

muscle tone to the required degree forsurgery

Ex.: succinylcholine, atracurium&

vecuronium

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1. General Anesthesia