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1

Anaesthesia

is the reversible loss of response to noxious stimuli

2

Types of anaesthesia

LOCAL – numbs one small area of the body when
consciousness is maintained;

IV sedation – uses a mild sedative to relax you and pain
medicine to relieve pain. You may stay awake but may not remember the procedure;

Regional anaesthesia – blocks the pain in an area of the
body, e.g. epidural anaesthesia;

General anaesthesia – when anaesthesia is associated with loss of consciousness. It affects your whole body. You go to sleep and feel nothing. You have no memory of the procedure afterwards;

3

Local Anesthetic Mechanisms

Local anaesthetics act by stopping transmission of signals generated by nociceptors
Block Na+ channels: prevents axonal depolarisation and formation of action potential

4

Local Anesthesia Duration

Lidocaine is short acting with a rapid on-set
Mepivacaine is long acting with a rapid on-set
Duration of action can be extended by adding a vasoconstrictor like epinephrine

5

Topical

most are applied to mucous membranes but some
preparations will be absorbed through skin
0.5% Proxymetacaine and 0.4% Oxybuprocaine are
used for ocular anaesthetic
Lidocaine and benzocaine sprays are used to assist in
intubation (OTC in sore throat and dental pain)

6

Infiltration

Multiple intradermal or subcutaneous injections of local
anesthetic along proposed incision line
May contain epinephrine (1:200,000) to increase effect and duration

7

Regional blocks (nerve blocks)

Injection into the connective tissue surrounding a nerve
Can produce loss of sensation and/or paralysis in the region supplied by the nerve
Requires smaller volumes than field blocks, reducing the risk of toxicity

8

Epidurals

Administered alone or in combination with other analgesics
If combined, smaller doses can be used, decreasing risks of adverse effects
Can cause motor deficits at higher doses

9

General Anaesthesia causes

A variety of drugs are given to the patient that have different effects with the overall aim of ensuring
unconsciousness, amnesia and analgesia.

General anesthesia causes:
• loss of consciousness
• analgesia
• amnesia
• muscle relaxation (expressed in different extent)
• loss of homeostatic control of respiration and cardiovascular function

10

General Anaesthesia

Premedication:
–sedation-anxiolytics
»benzodiazepines (diazepam, temazepam, lorazepam)
–Analgesia
»opiates, NSAIDS
–suppress salivation & autonomic reflex (eg bradycardia)
»Cholinergic antagonists –hyoscine
–prophylactic antibiotics
–prophylactic anti-coagulants
–Stop oral hypoglycemics agents, MAOIs, warfarin,

Anaesthetics:
–intravenous – for induction and short procedure
–inhalational – for maintenance
Mechanical ventilation may be necessary
–neuromuscular blockade for tracheal intubation and to
facilitate abdominal surgery

Analgesia

Recovery

11

Anesthesia agents

1. Inhalation anesthetics (volatile anesthetics) - gases : N2O, xenon - Fluids (vaporisers)

2. Intravenous anesthetics - Barbiturans: thiopental
Others : propofol, etomidat

3. Pain killers - Opioids: fentanyl, sufentanil, alfentanil, remifentanil, morphine. NSAID: ketonal, paracetamol

4. Relaxants - Depolarising : succinilcholine –
Non depolarising : atracurium, cisatracurium, vecuronium, rocuronium

5. Adiuvants -benzodiazepins: midasolam, diazepam

12

1. Inhalational Anesthetics

Typically used to maintain unconsciousness
-- Advantage of controlling the depth of anesthesia.
-- Metabolism is very minimal.
-- Excreted by exhalation

•Volatile liquids
Desflurane
Isoflurane
Enflurane
Halothane
Methoxyflurane
Sevoflurane
halogenated

Diethyl ether (out of date)

•Gases: Nitrous oxide – old, weak, used as adjunct
Xenon – lately introduced

13

Mechanism of action of inhalational anaesthetics

• Not fully clear
• Cause generalized depression of CNS temporarily inhibit synaptic transmission a general loss of consciousness, lack of sensation, often muscle relaxation, loss of autonomic reflex
• Lipid solubility theory anaesthesia reflects change in neuronal cell lipid bilayer expands membrane and disrupts protein function
• Membrane receptors
Direct interaction with ion channel?
activation of inhibitory ion channels (eg GABA, Glycine)
inhibition of excitatory ion channels (eg 5HT3, NMDA)

14

General pharmacokinetics

Vapor pressure is expressed as a percentage of barometric pressure at sea level, i.e. 760 mmHg, to determine the maximum concentration, For example, halothane has a saturated vapor pressure of 244 mmHg at 20°C; therefore the maximum concentration of halothane that can be delivered at this temperature is 32% (244/760 × 100 = 32%).
The aim in using inhalation anesthetics is to achieve a partial pressure of anesthetic in the brain sufficient to depress CNS function and induce general anesthesia.
Thus, anesthetic depth is determined by the partial pressure of anesthetic in the brain.
To reach the brain, molecules of anesthetic gas or vapor must diffuse down a series of partial pressure gradients, from inspired air to alveolar air, from alveolar air to blood and from blood to brain:
Inspired air → Alveolar air → Blood → Brain

15

The Minimum Alveolar Concentration - MAC

• CNS partial pressure to monitor the level of anaesthetics;
• the minimum alveolar anesthetic concentration (% of the
inspired air) at which 50% of patients do not respond to a
surgical stimulus;
• MAC value is a measure of inhalational anesthetic potency; inversely related to potency, i.e. high MAC equals low potency; conceptually equivalent to an EC50; MAC values 1.1 to 1.2 used during surgery.

16

BLOOD : GAS PARTITION CO-EFFICIENT

It is a measure of solubility in the blood.
It determines the rate of induction and recovery of Inhalational anesthetics.

17

OIL: GAS PARTITION CO-EFFICIENT

It is a measure of lipid solubility

Higher the Oil: Gas Partition Co-efficient, lower the MAC. E.g., Halothane

Lipid solubility - correlates strongly with the potency of
the anesthetic.
Higher the lipid solubility – potent anesthetic

18

Metabolism and Elimination

Inhalation anesthetics are eliminated primarily through the lungs, i.e. they are exhaled. Nonetheless, these agents are not totally inert and undergo biotransformation, primarily in the liver, to a variable degree. Metabolism
might be expected to promote recovery from anesthesia. However, for the newer inhalation agents any contribution to recovery is slight. Of more direct importance is the potential production of toxic metabolites.

19

Isoflurane

Isoflurane is a less soluble isomer of enflurane, and is widely use. It potentiates the action of neuromuscular blockers. It produces dose-dependent peripheral vasodilatation and hypotension but with less myocardial depression than enflurane and halothane.

Cerebral blood flow is little affected by isoflurane which
makes it an agent of choice during neurosurgery.
Uterine tone is well maintained as compared with halothane or enflurane, and thereby isoflurane reduces postpartum hemorrhage.

20

Halothane

• Used for many years with good effect
• First non-flamable volatile fluid anesthetic
• MAC high
• Now-a-days used only in pediatric anesthesia

• Moderate muscular relaxation is produced, but insufficient for major abdominal surgery. It potentiates the action of neuromuscular blockers.
• Increased myocardial excitability (ventricular tachycardia, and fibrillation).
• Blood pressure usually falls, due to CNS depression
and myocardial depression.
• Cerebral blood flow is increased which is an contraindication for use in head injury and intracranial tumors.
• Halothane is not good analgesic and also may lead to convulsions.
• It can produce massive hepatic necrosis or subclinical hepatitis following anesthesia.
• Halothane can cause malignant hyperthermia (which needs treatment with Dantrolene i.v.), uterine atony and postpartum hemorrhage.
• It has a teratogenic activity.

21

Nitrous Oxide (N2O)

• Old
• Weak
• Used as adjuvant
• Used to reduce pain during child birth
• Concomitant administration of N2O with one of the volatile GAs reduces the MAC value of the volatile drug by up to 75%.
• Risk of bone marrow depression occurs with prolonged administration of N2O.

22

2. Intravenous Induction Agents

These are used for induction of anesthesia.
• Rapid onset of action.
• Recovery is mainly by redistribution.
• Also reduce the amount of inhalation anesthetic for
maintenance.
• Commonly used IV induction agents include Propofol, Sodium Thiopental and Ketamine

23

Propofol

• Most commonly used IV anesthetic
• They modulate GABAergic neuronal transmission.
• Unconsciousness in ~ 45 sec The duration of action of IV induction agents is generally 5 to 10 minutes, after which
time spontaneous recovery of consciousness will occur.
• Anti-emetic in action
• Non-irritant to airways
• Suited for day care surgery - residual impairment is less marked
• A/E- pain during injection, fall in BP

24

Sodium thiopental

• Rapid-onset ultra-short acting barbiturate, it binds to GABAA receptor, increases the duration of time for which the Clionopore is open;
• Rapidly reaches the brain and causes unconsciousness within 30–45 seconds;
• The short duration of action is due to its redistribution away from central circulation towards muscle and fat;
• The dose for induction is 3 to 7 mg/kg.
• Causes hypotension, apnoea and airway obstruction

25

Ketamine

• Ketamine is a general dissociative anaesthetic
• Ketamine is classified as an NMDA Receptor Antagonist Dissociatives are a class of hallucinogen, which distort perceptions of sight and sound and produce feelings of detachment – dissociation – from the environment and self. This is done through reducing or blocking signals to the conscious mind from other parts of the brain
• Produce - profound analgesia, immobility, amnesia
with light sleep
• Heart rate and BP are elevated due to sympathetic
stimulation
• Respiration is not depressed and reflexes are not
abolished
• Can be associated with post-operative hallucination

26

General anaesthetics eg

• Sample gases: Nitrous oxide and Xenon
• Halogenated hydrocarbons: Isoflurane
• Barbiturates: Thiopental

All either suppress excitatory synaptic transmission or enhance inhibitory transmission

27

Local anaesthetics eg

• Ester: Cocaine, Procaine, Tetracaine
• Amide: Lidocaine, Bupivacaine

All work via inhibition of sodium channel