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GENERAL

ANESTHETICS

INTRODUCTION

 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.

 OPTIMAL GENERAL ANESTHETIC

reversible CNS depression (with minimal

depression of vital functions)

1. Loss of consciousness

2. Analgesia
3. Muscle relaxation

NO single 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

A.Status of organ system

1) Liver & Kidney 2) Resp. System 3) CVS 4) CNS 5) Pregnancy

B.Concomitant use of drugs

1) Multiple adjunct agents: preanesthetic medication 2) Additional nonanesthetic drugs:

alcohol or opiate
abuse

Induction, Maintenance & Recovery from Anesthesia

A. INDUCTION: the period of time from the onset

of anesthetic agent administration to the development 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 drug

diffuses out from the brain.

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

Each stage is characterized by CNS depression caused by accumulation of the

anesthetic drug in the brain.

They are well defined with ether which

produces a 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 Anesthesia
Stage 1. Analgesia Characteristics - 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. & preserved cough reflex In modern anesthesia, this stage cannot be distinguished. Can be avoided by thiopental. 3. Surgical anesthesia 4. Medullary paralysis - Spontaneous movement, regular respiration & marked muscle relaxation. - Severe depression of Resp. & VM centers - It starts by stoppage of respiration and ends by circulatory failure (death occurs within a few minutes).
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 GENERAL ANESTHETICS:
I. Inhalation Anesthetics II. i.v. Anesthetics

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I.INHALATION

ANESTHETICS

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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 perfusion

b) 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 ALVEOLAR CONC.; 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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Desflurane Sevoflurane

Anesthetic lipid solubility potency

Methoxyflurane Halothane Enflurane

Isoflurane Sevoflurane Desflurane N2O

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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 arterial blood 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-1,1,1trifluoro-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 of hepatic 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 metabolic

release of fluoride (nephrotoxic) rarely

used 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 less toxicity (nephrotoxicity)

It does not induce cardiac arrhythmias nor sensitize the heart to catecholamines.

conc.-dependent hypotension (due to

peripheral & coronary v.d.) suitable for patients with ischemic heart diseases G.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 sarcoplasmic reticulum 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 effective ANALGESIC in concentrations
too low to cause unconsciousness (35%) a

potent analgesic but weak general anesthetic usually used with another
inhaled or i.v. anesthetic for complete

anesthesia
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Inhalation of pure N2O rapid light anesthesia 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.INTRAVENOUS

ANESTHETICS

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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 of inhalation 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

relatively quick redistribution to 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 fetal resp. 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) nonbarbiturate 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 is oil at 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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 Lorazepam is used extensively in cardiac

surgery.

It produces amnesia and is particularly

useful during cardiopulmonary bypass to ensure unawareness of the procedure.

Midazolam has 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 reactive but 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 of movement 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 remains responsive to simple commands and

questions but does not respond to painful

stimuli or retain any memory of the procedure

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A combination of a neuroleptic antipsychotic as droperidol or haloperidol ( a state of quiescence with reduced motor activity) 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 sedation 2. 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 antiemetic properties. 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 secretions 2. Block the reflex vagal effect on the heart 3. Counteract the respiratory depressant actions of morphine

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 Advantages of scopolamine over atropine as

a preanesthetic drug:
1. Being a central depressant sedation & amnesia 2. More potent as antiemetic & antisecretory 3. It counteracts the resp. depression of morphine more efficiently

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V. Skeletal muscle relaxants: To facilitate intubation and suppress muscle tone to the required degree for

surgery
Ex.: succinylcholine, atracurium &

vecuronium

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THANK YOU

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