General Anaesthetics

Question 1

Uses of GA:

Answer 1

• Produce unconsciousness and lack of responsiveness to all painful stimuli – inhibit sensory and autonomic reflexes
• causes hypnosis, amnesia and analgesia
• allow for skeletal muscle relaxation

Question 2

GA stages:

Answer 2

1. Pre-assessment/premed
2. Induction of anaesthesia
3. Airway management
4. Maintenance of anaesthesia
5. Reversal/emergency
6. Post-operative care

Question 3

Traits of ideal GA:

Answer 3

• Unconsciousness
• Analgesia
• Muscle relaxation
• Amnesia
• Brief and pleasant
• Depth of anesthesia can be increased or decreased with ease
• Minimal adverse effects
• Large margin of safety

Question 4

Drugs commonly used in combination in GA:

Answer 4

• inhalation and intravenous anaesthetics
• Short-acting barbiturates (induction)
• NM blocking agents (muscle relaxation)
• Opioids and nitrous oxide (analgesia)

Question 5

What is MAC:

Answer 5

index of inhalation anaesthetic potency (the lower the MAC, the more potent it is)

• Defined as minimum concentration of drug in alveolar air that will produce immobility in 50% of patients exposed to painful stimulus
• Values alter with age, condition, concommitant administration of other drugs etc.

Question 6

Examples of inhalation anaesthetics:

Answer 6

volatile liquids: halothane, enflurane, desflurane, isoflurane, sevoflurane
Gases: nitrous oxide

Question 7

Possible MoA of Inhaled GA:

Answer 7

1. enhance neurotransmission at inhibitory synapses via allosterically increasing GABA receptor sensitivity to action by GABA itself (positive allosteric modulator)
2. Depress neurotrransmission at excitatory synapses via blocking glutamate neurotransmitter acting on NMDA receptor – prevent activation (negative allosteric modulator)

Question 8

Factors affecting absorption of Inhaled GA:

Answer 8

1. Concentration of anaesthetic in inspired air
2. Solubility of GA in blood
3. Blood flow through lungs

Question 9

Factor affecting distribution of inhaled GA:

Answer 9

Regional blood flow – determines which tissues receive GA – highly perfused tissues will have the anaesthetic levels equilibrating with those in blood quickly after administration

Question 10

mechanism of elimination of inhalation anaesthetics:

Answer 10

exported in expired breath
eliminated almost entirely via lungs
minimal hepatic metabolism

Question 11

Metabolites of inhalation anaesthetics

Answer 11

• Inorganic fluorides(isoflurane and enflurane) – nephrotoxic
• Halothane – hepatotoxic

Question 12

Adverse effects of halothane:

Answer 12

• Respiratory depression (dose-dependent)
• decreased BP due to depression of cardiac output
• Arrhythmia
• halothane-associated hepatitis
• (May be a use as well) relaxes skeletal muscle and potentiates skeletal muscle relaxants

Question 13

Adverse effects of isoflurane:

Answer 13

• dose-dependent respiratory depression
• decreased BP due to decrease in systemic/vascular resistance
• less hypotension and arrhythmia compared to halothane

Question 14

MAC of inhaled anaesthetics:

Answer 14

Halothane: 0.75%
Isoflurane: 1.4%
Sevoflurane: 2%
Nitrous oxide: 105-110%

Question 15

mechanism of nephrotoxicity in sevoflurane:

Answer 15

metabolised in liver to release inorganic fluoride

Question 16

Rank the time needed for onset and recovery of inahled anaesthetics:

• Isoflurane
• Halthane
• Nitrous Oxide
• Sevoflurane

Answer 16

nitrous oxide < sevoflurane < isoflurane and halothane

Question 17

limitations of use of nitrous oxide in GA: :

Answer 17

give analgesia and amnesia but not complete unconsciousness/surgical anaesthesia
- used to supplement analgesic effects of primary anaesthetic

Question 18

Major concern in use of nitrous oxide

Answer 18

post-operative nausea and vomiting

Question 19

Things to take note of in the use of sevoflurane:

Answer 19

degrade to compound that is potentially nephrotoxic when exposed to carbon dioxide absorbants in anaesthetic machines

Question 20

Types of intravenous anaesthetics

Answer 20

thiopentane, etomidate, propofol, ketamine, midazolam

Question 21

Purpose of IV anaesthetics. Comment on its duration of action

Answer 21

• induce unconsciousness

- does not keep you asleep for very long – effects on its own is not very long

Question 22

Advantages of using a combination of inh and iv anaesthetics:

Answer 22

1. permit dosage of inhalation agent to be decreased

2. produce effects that cannot be achieved with an inhalation GA alone

Question 23

advantage of thiopentone:

Answer 23

extremely high lipid solubility – enters brain easily and rapidly for rapid onset of action – unconsciousness occurs 10-20 sec after IV

Question 24

pk of thiopentone:

Answer 24

• Large Volume of Distribution
• Active metabolite Pentobarbital – liver cirrhosis can result in prolongation of clinical action
• Extensively bound to plasma proteins – small amount of free drug excreted by glomerular filtration + reabsorption in tubules
• Less than 1% excreted unchanged

Question 25

MoA of thiopentone:

Answer 25

Cause CNS depression by potentiating action of GABA on GABA-A receptor-gated chloride ion channels - Does not replace neurotransmitter but allow for more effective binding - lead to greater entry of chloride ions as channel is open, making it difficult to depolarise

Question 26

What is Propofol used for in patients who require anaesthesia?

Answer 26

For both induction and maintenance (by infusion)

Question 27

Onset and duration of propofol:

Answer 27

``` rapid onset ( unconsciousness develops within ~60 sec) short duration of action (~3-5 min following single injection) rapid distribution from brain to other tissues ```

Question 28

use of propofol:

Answer 28

extensively used in day surgeries, need continuous, low dose infusion for extended effects

Question 29

benefits of using propofol over using other anaesthetic agents

Answer 29

- reduced postoperative vomiting (anti-emetic action)

Question 30

side effects of propofol:

Answer 30

significant CV effects during induction: lowered BP and negative inotropic --> hypotension

Question 31

caution for use of propofol:

Answer 31

used with caution in elderly patients, patients with compromised cardiac function, hypovolemic patients

Question 32

what makes ketamine different from other IV anaesthetic

Answer 32

- only IV anaesthetic possessing analgesic property - produce state of dissociative anaesthesia -- patient dissociated from environment, commonly used in vet practice/antidepressant with fast onset

Question 33

Effects of ketamine:

Answer 33

Sedation, immobility, analgesia, amnesia

Question 34

PK of ketamine:

Answer 34

- metabolised in liver to less active metabolite, excreted in bile - Large volume of distribution, rapid clearance -- suitable for continuous infusion without lengthening duration of action

Question 35

benefits of using ketamine:

Answer 35

rapid induction, responsiveness to pain is lost -- good analgesic effects

Question 36

Adverse effects of ketamine:

Answer 36

unpleasant psychologic reactions (hallucination, disturbing dreams, delirium) may occur during recovery

Question 37

Methods to reduce adverse effects of ketamine:

Answer 37

premedication of diazepam/midazolam

Question 38

Types of anaesthetic adjuncts:

Answer 38

1. Benzodiazepines (IV midazolam) 2. a2 adrenergic agonists (IV dexmedetomidine) 3. Analgesics (NSAIDs/Opioids) 4. Neuromuscular blockers (succinylcholine, vecuronium)

Question 39

use of BZDs as anaesthetic adjuncts:

Answer 39

used for sedation during procedures not requiring GA as anxiolytics, for amnesia and sedation prior to induction of anaesthesia

Question 40

benefits of using BZDs as anaesthetic adjuncts:

Answer 40

- rapid onset when used for induction (unconsciousness develops in 80 seconds) - High therapeutic index

Question 41

metabolism of IV midazolam:

Answer 41

metabolised in liver -- people with liver issues will be more sensitive

Question 42

adverse effects of IV midazolam:

Answer 42

CV and respiratory depressing effect (less compared to other IV anaesthetics) -- compounded by use with other agents

Question 43

how to mitigate adverse effects of IV midazolam:

Answer 43

inject midazolam slowly (2 or more mins) and wait another 2 more mins for full effects before dosing again -- side effects minimised by dragging out administration duration

Question 44

how is IV dexmedetomidine used in GA:

Answer 44

- sedation prior to and/or during procedures in non-intubated patients - short-term sedation (<24 hours)

Question 45

benefits in use of IV dexmedetomidine:

Answer 45

- little respiratory depression - has sedative and analgesic effects - Tolerable decrease in bp and HR

Question 46

Side effects of IV dexmedetomidine:

Answer 46

nausea, dry mouth, hypotension, bradycardia

Question 47

list of possible analgesics that can be used during/post operation:

Answer 47

``` fentanyl morphine sufentanil remifentanil alfentanil ```

Question 48

Why and when are analgesics used with GA:

Answer 48

- to decrease anaesthetic requirement | - for minor surgical procedures (cox-2 inhibitors, paracetamol and opioids for perioperative period)

Question 49

Metabolism and excretion of analgesics:

Answer 49

metabolised in liver (remifentanil hydrolysed by tissue and plasma esterases) excretion in urine and bile

Question 50

Use of NM blockers in GA:

Answer 50

used during induction of anaesthesia to relax muscles to facilitate laryngoscopy and endotracheal intubation - aids many surgical procedures and provide additional insurance of immobility

Question 51

two NM blockers commonly used:

Answer 51

depolarising: succinylcholine | non-depolarising: vecuronium

Question 52

caution when using IV NM blockers:

Answer 52

barbiturates will precipitate when mixed with muscle relaxants -- should be allowed to clear from IV line

Question 53

Reason for ultra-short duration of action of thiopentone

Answer 53

redistributes to less vascularised tissues