GENERAL ANAESTHESIAstudents

Anaesthesia & Analgesia

• Anaesthesia

– State of controllable, reversible

insensibility

• general - loss of consciousness
• local - loss of sensory and motor function

confined to a specific region

• Analgesia

– Temporary abolition or diminution of pain

perception

Anaesthetics may be given

by various routes

• Possible routes are

– Inhalation
– Injection
– Local

• Routes may be combined

– Injectable agent for induction
– Then inhalational anaesthesia for

maintenance

ANAESTHESIA - TYPES

• Local/Regional/Topical Anaesthesia

– Application of local anaesthetic (“Freezing”)

to a specific area of the body

• General Anaesthesia

– Application of an anesthetic drug given by

inhaled gas or by a liquid in an intravenous
form to the entire body and brain

Local anaesthetics - structure

Aromatic group

Amine

Amide or
ester link

HYDROPHOBIC

HYDROPHILIC

Local anaesthetics

• Generally applied locally

• Block nerve conduction of sensory

impulses from the periphery to the CNS

• Abolish sensation (in higher concentration

motor activity) in a limited area of the

body without producing unconsciousness

(e.g. spinal anaesthesia)

Local anaesthetics –

mechanisms of action

• Na

channels exist in activated-open,

inactivated-closed and rested-closed states

• Local anaesthetics selectively bind to Na

channels in inactivated-closed states so are
membrane stabilising

• Reducing Na

ion permeability slows

depolarization so threshold potential is not
reached

Local anaesthetics – onset of action

The onset of action depends on

several factors, including:

• diffusion to the site,
• nerve morphology,
• lipid solubility,
• pH of the tissue and pKa of the

agent.

Local anaesthetics – onset of action

Diffusion to the site

The further away from the nerve the

local anaesthetic is deposited, the longer

it takes for onset of action. Thus, the

onset for the infiltration technique is

quite rapid. The onset for blocks, is

generally longer.

Nerve morphology

The relatively thin pain fibres are blocked with lower

concentrations of local anaesthetics than are the larger

motor fibres.

Concentration

To a very limited extent, increases in the dose

administered result in a more rapid onset.

Lipid solubility

Lipid solubility has only a minor effect on onset of

action, but uptake by the nerve is facilitated with the

more lipid-soluble (lipophilic) agents, as these allow

penetration through the nerve sheath.

Local anaesthetics – onset of action

Lipid solubility and potency

Drug

Relative
potency

Lipid
solubility

Procaine

100

Prilocaine

1.8

129

Lignocaine

366

Bupivicaine

3420

• At physiologic pH local anaesthetics

are charged.

• It is this ionized form that interacts

with Na+ channel and blocks its
action producing local anaesthesia

Local anaesthetics – onset of action

The pH of the tissue and pKa of the agent

• LAs are weak bases pK

7.7 to 8.9

• At ph 7.4, less than 50% of LA exists as lipid

soluble, nonionized form

• This explains poor quality of block when LA

injected into acidic infected tissue

• LAs with pK

closest to physiological pH have

fastest onset of action

Local anaesthetics – onset of action

The duration of action of local anaesthetics

depends primarily on the redistribution of the

drug away from the site of action.

Diffusion away from the site is the most

important factor. It is potentiated by the

property of most local anaesthetics as

inherently vasodilating.

Diffusion away is

reduced by the addition of vasoconstrictor,

usually e.g. noradrenaline.

Local anaesthetics:
diuration of action

Metabolism

• Esters

– plasma cholinesterases

• Amides

– liver metabolism
– most dependent on liver blood flow

because of high extraction ratio

• Action is terminated by redistribution away from

the nerve, not metabolic breakdown.

• Block anaesthesia lasts longer than infiltration

anaesthesia.

• Soft tissue anaesthesia lasts longer than pulpal

anaesthesia.

• Local anaesthetics without a vasoconstrictor

(mepivacaine or prilocaine) provide short duration of
action.

• A vasoconstrictor with articaine, lidocaine,

mepivacaine or prilocaine provides intermediate
duration.

Local anaesthetics - duration of action

2 h

Moderate

Prilocaine

3 h

Moderate

Long

Slow

Bupivacaine

3 h

Moderate

Long

Moderate

Dibucaine

2 h

Rapid

Moderate

Rapid

Lignocaine

30 min

Slow

Short

Moderate

Procaine

Plasma

1/2

Tissue

penetration

Duration

Rate of

onset

Drug

Routes of administration of

local anaesthetics

• Topical (surface) anaesthesia

(cornea,

skin, mucous membranes of bronchial

tree, nose, mouth, genitourinary tract).

• Infiltration

(vasoconstrictor agents may

be used to retard absorption)

• Regional nerve block

• Spinal (subarachnoid) and epidural

(e.g.

for pelvic surgery, child delivery).

Longitudinal spread of LA may cause

hypotension and sometimes respiratory

paralysis.

Cocaine

• Ester, tendency to cause allergy

• Cardiovascular and CNS stimulant

• Addictive

• Possesses vasoconstrictor activity

• Metabolised by plasma esterases

Lignocaine (Lidocaine)

• Amide
• Standard agent against which

others are compared

• Antiarrhythmic
• Vasodilator, increases systemic

toxicity

• Available as 0.5%, 1% and 2%

preparations

Prilocaine

• Sequestered and metabolised in lungs
• Not vasodilating, safest drug in current

use

• Equipotent with lidocaine, slightly longer

duration of action

• Hydrolysed to o-toluidine causing

methaemaglobinaemia at doses over

600mg

Bupivacaine

• Amide
• Long duration of action
• Excellent with catheter based

techniques

• May cause cardiotoxicity before

neurotoxicity

Local anaesthetics –

cardiovascular side effects

• Arteriolar vasodilation

• Myocardial depression

• First degree heart block, conduction

delay

• Pro-arrhythmogenic

Local anaesthetics –

other adverse effects

• Anaphylaxis

• Depress ventilatory response to hypoxia

• Methaemoglobinaemia (prilocaine)

• Tachycardia, hypertension, myocardial

depression, addiction (cocaine)

Choice of agent

Minor Infiltration

0.5%

Intravenous regional

0.5%

Minor nerve block

1.0%

Brachial plexus

1.0-1.5%

Sciatic/femoral

1.0-1.5%

Epidural/spinal

2.0%

Figures are for lidocaine

ANAESTHESIA

Anaesthesia means the absence of sensation.
Anesthesia works in 4 ways:

• As an analgesic (pain reliever)
• It promotes unconsciousness
• It causes immobility of the patient
• Elimination (or reduction) of autonomic

responses such as tachycardia (increased

heart beat), increased hypertension

General anaesthesia

a state of total unconsciousness resulting

from anaesthetic drugs (as for a major

surgical operation)

Neuroleptic analgesia – a state of quiescence,

altered awareness, and analgesia produced by the
administration of a combination of a narcotic
analgesic and a neuroleptic agent

Dissociative anaesthesia – marked amnesia and

profound analgesia (patient is conscious but feels

dissociated from his body)

Anaesthetics

General anaesthetics

Local anaesthetics

Intravenous

Inhaled

Anaesthetics

Adjuncts

to anaesthetics

Preanaesthetic

medication

Muscle

relaxants

Patient factors in selection

of anaesthesia

Liver and kidney

Respiratory system

Cardiovascular system

Nervous system

Status of organ systems:

Stages of anaesthesia

Induction

– time from onset of administration of

anesthetic to the development of effective surgical

anesthesia. Generally induced with an intravenous

anaesthetic like tiopenthal (unconsciousness within 25

sec)

Maintenance

– time during which the patient is

surgically

anesthetized.

Anaesthesia

usually

maintained by inhaled drugs.

Recovery

– time from discontinuation of administration

of anesthesia until consciousness is regained

Depth of anaesthesia

Stage I – analgesia:

loss of pain sensation,

patient is conscious

Stage II – excitement:

delirium, aggression

Stage III – surgical anaesthesis:

surgery may

proceed during this stage

Stage IV

– medullary paralysis:

severe depression

of the respiratory and vasomotor centers

→

death.

Vital centre depression

Dangerously deep

Surgical anaesthesia

Dead drunk

Uninhibited response to
stimuli

Drunk and disorderly

Amnesia and analgesia

Dizzy and delightful

General Anaesthesia

Alcoholic
Intoxication

Stage

modified from Gaddum's

Pharmacology

1950

Barbiturates

Thiopental (thiopentone), thiamylal, metohexital

Potent anaesthetic, weak analgesic
Highly lipophilic:

•

rapid distribution in the CNS

quick onset of action (1 min)

•

rapid redistribution in skeletal muscles and adipose tissue

ultra-short acting,

slowly metabolised

Minor effect on cardiovascular system

but may

contribute to severe hypotension in hypovolemic or
shock patients!!!

AE – apnea, coughing, chest wall spasm, laryngo- or
bronchospasm

thiamylal, metohexital

Propofol

Rapidly induces anaesthesia, similar to thiopental.

Duration of propofol anaesthesia can be increased by

repeated administration or by combination with inhalational
agents, nitrous oxide, or opioids.

Causes peripheral vasodilation

Propofol does not adversely affect hepatic or renal function.

Emergence from propofol anesthesia is rapid with minimal

postoperative confusion.

Postoperative GI upset occur at a similar frequency to that

of thiopental.

Propofol is now commonly used in ambulatory surgery settings

and first choice drug for induction of anaesthesia.

Ketamine

Short-acting, nonbarbiturate anesthetic
Induces

dissociated state

in which patient is

unconsious but appears to be awake and does not
feel pain

Stimulation of the heart, increase in blood pressure

and plasma catecholamies

Highly lipophilic – quickly enters the brain, quick

redistribution

Employed mainly in children and young adults for

short procedures. Also common in veterinary med.

Closely resembles phencyclidine, a „street-drug”

with a pronounced effect on sensory perception.
Awakening may be associated with bad dreams and
hallucinations which may recur.

Etomidate

• Similar to thiopenthal, but more quickly

metabolized

• Lacks analgesic activity
• Less risk of cardiovascular depression
• May cause involuntary movements during

induction

• Possible risk of adrenocortical suppression

Mechanism of action

Influence on lipid membranes

Allosteric regulation of membrane

receptors

•

excitatory:

ionotropic glutamate receptors (NMDA, AMPA)
nicotinic ACh receptors

•

inhibitory

GABA

receptors

glycine receptors
K

-channels (anesthesia activated)

-adrenergic receptors

Potency of inhalation anaesthetics

Minimum alveolar concentration (MAC)

–

concentration

anesthetic

gas

needed to eliminate movement among

50%

patients

challenged

standarize skin incision.

MAC for anaesthetic gases

Halothane

Isoflurane

Enflurane

Ether

Nitrous

oxide

100

MAC

Pharmacokinetic properties of

inhalation anaesthetics

• Rapid induction and recovery
• Speed of induction and recovery depends on

solubility in blood and lipid solubility

• Agents with low blood:gas partition coefficients

produce rapid induction and recovery; agents
with high coefficients show slow induction and
recovery

• Agents with high lipid solubility accumulate

gradually in the body fat, and may produce a
prolonged hangover if used for a longer time.

Halothane

Potent anaesthetic, relatively weak analgetic

May not adequately suppress visceral reflexes or

provide adequate muscle relaxation for surgery

Has a relaxant effect on the uterus, which limits its

usefulness for obsteric purposes

Now largely replaced by other inhalations

anaesthetics in USA.

Halothane

Reversible reduction in glomerular filtration rates

Hypotensive, induces arrythmias

Metabolised to tissue -toxic hydrocarbons

Malignant hypertermia (dramatic increase in

intracellular calcium). Probably due to excitation-

contraction coupling defect. Treatment: dantolene +

reduce the body temperature (ice poultice)

Enflurane

Less potent that halothane, but produces rapid

induction and recovery

Partially metabolised to fluoride ion, excreted by

the kidney

In comparison with halothane – fewer arrytmias,

less sensitization of the heart to catecholamines,
greater potentiation of muscle relaxants

Some risk of epilepsy-like seizures!

Isoflurane

Initially, until deeper levels of anesthesia are

reached, isoflurane stimulates airway reflexes
with attendant increases in secretions, coughing
and laryngospasm.

May provide adequate muscle relaxation greater

than seen with halothane which may be adequate
for abdominal procedures

Not sensitize the heart to catecholamines

Reported tendency to increased incidence of

coronary ischaemic attacts

Very stable molecule

Methoxyflurane

The most potent inhalation anesthetic
High solubility in lipids
Metabolised with releasing of fluoride
Useful in obstetrics

Sevoflurane

Low pungency – suitable in children
Low solubility in blood
Rapid uptake and excretion

Nitrous oxide

(„laughing gas”)

O (do not confuse with EDRF

NO, nitr

oxide)

Potent analgesic, weak anesthetic
Very rapid onset and recovery, little or no toxicity
No skeletal muscle relaxation
Post-anesthesia hypoxia
Not suitable as a sole anesthetic agent

Inhibition of methionine synthetase (risk of bone
marrow depression)

Preanaesthetic Medication

Primary Goals:

Anxiety relief without excessive sedation
Amnesia during perioperative period
Relief of preoperative pain

Secondary Goals:

Reduction in the requirement for inhalational agents
Reduction in side effects associated with some inhalational

agents.

Side effects include salivation, bradycardia, postanesthetic

vomiting.

Reduction in acidity and volume of gastric contents.
Reduction of stress in perioperative period

Multiple adjuct agents given to

surgical patient

• Benzodiazapines

– to allay anxiety and facilitate

amnesia

• Antihistaminergics (diphenhydramine)

- to

prevent allergic reactions

• Antiemetics (ondasetron)

- to prevent possible

aspiration of stomach contents

• Opioids

– for analgesia

• Antimuscarinics

– to prevent bradycardia and

secretion of fluids into respiratory tract, also

antiemetic effect

• Muscle relaxants

(neuromuscular agents)

Intravenous anaesthetics

Adjuncts to anesthesia:

•

benzodiazepines

•

opioids

•

neuroleptic drugs

neuroleptoanalgesia

Fentanyl and related agents

i.v. fentanyl causes analgesia and unconsciousness

Fentanyl is often combined with a muscle relaxant

and nitrous oxide or low dose inhalational agent for
anesthesia.

Alfentanil and sufentanil are more potent than

fentanyl and produce analgesia and, at higher
concentrations, anesthesia.

Remifentanil is a new potent agent which produces

analgesia very rapidly. It is readily metabolized
resulting in a rapid recovery time.

Innovar

Innovar is a combination of droperidol and

fentanyl

Innovar produces slight circulatory effects, but can

cause significant respiratory depression.

Droperidol can cause neuroleptic malignant syndrome

(rarely).

The low incidence of extrapyramidal side effects

associated with droperidol use may be effectively
treated with the anti-cholinergic (anti-muscarinic)
drug, benztropine

Benzodiazepines

Diazepam, Midazolam, Lorazepam

Benzodiazepines are effective in promoting sedation and

reducing anxiety

Drowsiness occurs several minutes after i.v. administration

of Diazepam. Lorazepam slightly slower and Midazolam
slightly faster onset compared to diazepam

Used alone benzodiazepines have limited depressant effects

on the cardiovascular/respiratory system

Benzodiazepines are not analgesic

May be used alone for procedures not requiring analgesia

Neuroleptoanalgesia

Combinations: Neuroleptic + Opioids

Useful for minor surgical procedures, some radiological

procedures, burn dressing, and endoscopy

Neuroleptic agents such as droperidol cause a reduction in

anxiety and a state of indifference

When combined with an opioid such as fentanyl a state of

neurolept analgesia results.

Addition of nitrous oxide can transition neurolept analagesia to

neurolept anesthesia.

Neurolept analgesia/anesthesia may be especially useful in the

elderly, debilitated or seriously ill patient.