LOCAL & GENERAL
ANAESTHESIA
Professor Jolanta B. Zawilska
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
N
R
R
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)
Benzocaine
Cocaine
Procaine
Articaine
Bupivacaine
Lidocaine
Mepivacaine
Prilocaine
Esters
Amides
Classification of Local Anaesthetics
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 –
mechanisms of action
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
=1
100
Prilocaine
1.8
129
Lignocaine
2
366
Bupivicaine
8
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
a
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
a
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
Moderate
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
t
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 –
CNS side effects
• Tongue and circumoral tingling
• Agitation, vertigo and tinnitus
• Slurred speech
• Skeletal muscle twitching
• Seizures
• Coma
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
„For there was never yet
philosopher that could endure
the toothache patiently"
- Shakespeare
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)
Analgesia
Amnesia
Unconsciousness
Muscle relaxation
Suppression of undesirable reflexes
General anesthesia
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
is
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
4
Surgical anaesthesia
Dead drunk
3
Uninhibited response to
stimuli
Drunk and disorderly
2
Amnesia and analgesia
Dizzy and delightful
1
General Anaesthesia
Alcoholic
Intoxication
*
Stage
*
modified from Gaddum's
Pharmacology
1950
Intravenous anaesthetics
Barbiturates
Ketamine
Propofol
Etomidate
Often used for rapid induction of anaesthesia,
which is then maintained with inhalation agent
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
Inhalation anaesthetics
Used primarily for the maintenance
of anaesthesia after administration
of iv agent
Mechanism of action
Influence on lipid membranes
Allosteric regulation of membrane
receptors
•
excitatory:
ionotropic glutamate receptors (NMDA, AMPA)
nicotinic ACh receptors
•
inhibitory
GABA
A
receptors
glycine receptors
K
+
-channels (anesthesia activated)
α
2
-adrenergic receptors
Potency of inhalation anaesthetics
Minimum alveolar concentration (MAC)
–
concentration
of
anesthetic
gas
needed to eliminate movement among
50%
patients
challenged
by
a
standarize skin incision.
MAC for anaesthetic gases
Halothane
Isoflurane
Enflurane
Ether
Nitrous
oxide
0
1
2
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”)
N
2
O (do not confuse with EDRF
NO, nitr
ic
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.