General anaesthesia

Question 1

What are the two main classes of general anaesthetic?

Answer 1

• intravenous

- inhaled

Question 2

What are the two main classes of anaesthetic generally used for?

Answer 2

intravenous = induction 
inhaled = maintenance

Question 3

What is the triad of anaesthesia?

Answer 3

• hypnosis (unawareness)
• analgesia (lack of physiological response to painful stimuli)
• paralysis (lack of motor response to pain)

Question 4

Why are IV agents suitable for initiation?

Answer 4

very rapid action
they have slow elimination - not used for maintenance as may build up in the body
- an exception to this is propofol which is cleared quickly and can be used for maintenance

Question 5

Examples of IV agent

Answer 5

Propofol

Question 6

Examples of inhaled agent

Answer 6

Isoflurane

sevoflurane

Question 7

Why are inhalation agents commonly used for maintenance?

Answer 7

• arterial blood conc can be rapidly altered by changing the alveolar partial pressure of the drug → can control the degree of anaesthesia

Question 8

What are some factors determining recovery from GAs?

Answer 8

• lower blood solubility → excreted faster via the lungs
• fat solubility → fat soluble agents may accumulate in adipose tissue → after cessation of anaesthesia, may take hours to be cleared

Question 9

What is an important measure of the potency of inhalation anaesthetics?

Answer 9

MAC (minimum alveolar conc) = the alveolar concentration associated with 50% probability of moving in response to a surgical pain stimulus (e.g. skin incision)

Question 10

The lower the MAC, the more…

Answer 10

potent the agent!

Question 11

What are inhaled anaesthetics vaporised with?

Answer 11

O2 or an oxygen-nitrous oxide (N2O) mix
Nitrous oxide is another anaesthetic agent with analgesic effects, but it is not potent enough to be used in surgical anaesthesia on its own

Question 12

Briefly describe proposed mechanisms of GAs (on the RHS of the syllabus so do not need to know)

Answer 12

Thoguht to inhibit the action of excitatory receptors (such as ionotropic glutamate, ACh and serotonin receptors) and potentiate the actions of inhibitory receptors (GABA-A and GlyR)

Question 13

What is an important target in the brain regarding loss of conciousness?

Answer 13

Brainstem arousal nuclei

Question 14

Effects on CV system

Answer 14

Cardiovascular depression, with ensuing hypotension and possible circulatory collapse

• vasodilation
• decrease HR

Question 15

Describe mechanisms underling CV depression

Answer 15

Differ for IV and inhalation agents.

For inhalation:

• peripheral actions are probably significant
• e.g. halothane reduces HR in isolated hearts, indicating action on SAN rather than a central one

For IV:

• central actions
• inhibition of sympathetic outflow

Question 16

What are two exceptions that increase HR and BP?

Answer 16

nitrous oxide and ketamine

Question 17

How can CV depression as a result of GAs be managed?

Answer 17

1. Initial interventions → elavating legs and administering IV fluids
2. Main pharmacological therapy = vasopressors → an indirectly-acting sympathomimetic amine can be used e.g. ephedrine – causes NA
   to leak out through postganglionic sympathetic nerve terminals, thereby increasing
   HR and myocardial contraction, and causing vasoconstriction, elevating BP
3. this may be followed by adrenaline or atropine

Question 18

What does atropine do?

Answer 18

Reduces bradycardia by inhibiting heart M2 Rs

Question 19

Why should B1 activating drugs be carefully considered with several GAs?

Answer 19

because they increase the sensitivity of cardiac
muscle to sympathetic catecholamines in such a way as to increase the risk of arrhythmias
o Normally this is limited to occasional extrasystolic beats; however, in the presence
of large amounts of catecholamines, ventricular fibrillation + death from lack of CO
may occur

Question 20

What effects do GAs have on body temp?

Answer 20

Reduction in body temp

Question 21

What two drugs may be used to reduce anaesthetic shivering?

Answer 21

Doxapram and pethidine

Question 22

What effects do GAs have on the respiratory system?

Answer 22

tend to cause respiratory depression and airway obstruction

Question 23

What is increased risk of airway obstruction caused by?

Answer 23

The central mechanism involves reduced outflow to pharyngeal dilator muscles, reducing
their ability to maintain a patent upper airway during the negative pressure of inspiration

The non-central mechanism involves spastic muscle contraction:
- Loss of the cough reflex allows saliva + mucus to fall back on the vocal cords,
causing laryngospasm, or into the trachea and lungs, causing bronchospasm

Question 24

What does the respiratory depression manifest as?

Answer 24

• decrease in minute ventilation volume → caused by reduction in respiratory rate or tidal volume

Question 25

What do these respiratory symptoms lead to?

Answer 25

Hypercapnia – which can have significant effects in the postoperative patient including
tachycardia, arrhythmias, headache, confusion

Hypoxemia may occur, with resulting ischaemic effects on a variety of organs

Question 26

How may the respiratory symptoms be managed?

Answer 26

• if an opioid is being used, naloxone may be administered to reduce respiratory depression
• intubation & external ventilation
• before surgery antimuscarinics may be administered to reduce saliva and mucus production

Question 27

What is one of the most significant consequences of GA use? what agents can it be triggered by? What is it caused by? Treatments

Answer 27

• malignant hyperthermia
• can be triggered by halogenated inhalation anaesthetics and sux
• Excess release of Ca2+ from skeletal myofibre SR → intense contraction & increasing ATP use dramatically → lots of heat generated → hyperthermia
• cooling and administration of dantrolene → drug that blcoks RyR1

Question 28

What mutation causes susceptibility to malignant hyperthermia?

Answer 28

• mutations in RyR1

Question 29

What are the stages of general anaesthesia?

Answer 29

1 - analgesia
2 - excitement (loss of pain perception, unconscious but retained reflexes )
3 - surgical
4 - paralysis - BAD

Question 30

What is MAC? Define it

Answer 30

MAC defined as the concentration of the vapour in the lungs needed to prevent a motor response in 50% of patients in response to surgical (pain) stimuli; > 90% all patients become anesthetized following the administration of 1.3 MAC, and, presumably, 1.5 to 2 MAC is required to ensure anaesthesia in all patients 

Question 31

List adjuvant drugs used in GA and their actions

Answer 31

-Anxiolytics e.g. temazepam → pre-operative, GABA-A R agonist

Antiemetics e.g. ondansetron → 5-HT3 antagonist

Opiate analgesics e.g. morphine → stopping pain perception by binding to opioid receptors

Non-steroidal anti-inflammatories e.g. ibuprofen → COX inhibitors

Neuromuscular blocking agents e.g. vecuronium, suxamethonium → used to induce flaccid paralysis

Cholinesterase inhibitors e.g. neostigmine.

Local anaesthetics e.g. lidocaine, bupivacaine.

Muscarinic antagonists e.g. atropine → increase HR and inhibit secretions

Question 32

Effect of halothane on cardiovascular system?

Answer 32

Halothane slows the heart rate by prolonging the RR interval by acting on SAN, not linked to sympathetic regulation, may also prolong PR interval at higher doses – ANV

Question 33

General principles of management of effect on other body systems

Answer 33

Fluid therapy, vasoconstrictors (e.g. α1-agonists such as phenylephrine); increase blood pressure

Parasympathoytics (e.g. muscarinic antagonists such as glycopyrrolate);

Oxygen supplementation, airway maintenance, assisted ventilation; assist in management of airway collapse.

Active warming

Anaesthetics and opiates depress minute ventilation and the hypoxic ventilatory response via actions on afferent sensor and the central pressor (respiratory centre): net effect is diminished efferent output of the phrenic nerve. Drugs that depress the ventilatory drive also suppress in parallel the efferent output to the pharyngeal dilators to various degrees.

Question 34

What does halothane do to the Frank Starling curve?

Answer 34

Causes it to fall and droop - plateau is faster → shows that contractility is reduced in the myocardium itself