31-10-23 - General anaesthesia Flashcards
Learning outcomes
- Define “general anaesthesia”, “balanced anaesthesia” & “MAC”
- Outline the current understanding of the pharmacodynamics of anaesthetic agents
- Compare and contrast the commonly used intravenous induction agents
- Compare and contrast the following commonly used inhalational agents
- Explain the role of pharmacokinetics in general anaesthesia
What is general anaesthesia? What are the 4 stages of anaesthesia depth (in picture)?
- General anaesthesia is reversible, drug induced loss of consciousness, usually to allow a surgical procedure to be performed
- 4 stages of anaesthesia depth (in picture)
What are IV induction agents used for anaesthesia?
How quickly do they work?
What are 4 examples of IV induction agents?
- IV induction agents used for anaesthesia are agents which will induce loss of consciousness in one arm brain circulation time
- It is the time required to circulate back to the heart and then up to the brain (usually less than 1 minute).
- 4 examples of IV induction agents:
1) Propofol
2) Thiopentone (thiopental)
3) Etomidate
4) Ketamine
What are Inhalational anaesthetic agents?
What are they used for?
What are 4 examples of inhalation anaesthetic agents?
- Inhalational anaesthetic agents are gas or vapour, delivered to the patient via a breathing circuit.
- May be used to induce anaesthesia (children)
- More commonly used to maintain anaesthesia
- 4 examples of inhalation anaesthetic agents:
1) Nitrous oxide
2) Isoflurane
3) Sevoflurane
4) Desflurane
Why did there used to be more awake c-sections?
- There used to be more awake c-sections performed
- This is because we didn’t want to anesthetise the baby, so we couldn’t use anaesthetics that would cross the blood-placental barrier
- Thiopental was found to induce anaesthesia in c-sections, which lead to less awake c-sections being performed
What is Entonox?
What are 3 cases where Entonox might be used?
- Entonox is 50:50 nitrous oxide: oxygen
- 3 cases where Entonox might be used:
1) Analgesic
2) Labour
3) Trauma
What is MAC?
Why do we want to exceed MAC?
What is MAC measure of?
How is it linked to potency?
- MAC is the Minimum alveolar concentration at which 50% of the population fail to respond to surgical stimulus
- We want to exceed MAC to ensure patients wont response to surgical stimulation
- MAC is a measure of how well drugs are able to dissolve in oil (how lipophilic / fat soluble they are)
- The higher the MAC, the worse the drug is at dissolving in oil (lipids)
- The higher the MAC, the lower the potency the drug is as a general anaesthetic
How does blood and lipid solubility affect the properties of an inhalational agent as a general anaesthetic?
What are examples of this?
- For inhalational agent as a general anaesthetic:
- The more lipid soluble: the more potent: the lower the MAC
- The more blood soluble: the slower the onset – drug won’t be leaving the blood to get to compartments and tissues where it will have an effect
- Examples:
1) Nitrous Oxide (NO)
* NO has a MAC that exceeds 100%, meaning by even giving 100% NO, we can’t fully anaesthetise a patient (NO is given is a 50/50 mix with oxygen in Entonox)
* We will get an anaesthetic effect, but won’t have an unconscious effect
* NO also has a low blood/gas coefficient, meaning it is poorly absorbed in the blood
* All of these factors mean that NO has a low potency, but a rapid onset
2) Isoflurane
* Isoflurane has a low MAC, meaning it is very potent
* Isoflurane also has a high blood/gas partition coefficient, meaning it is well absorbed into blood, giving it a slow-onset
How can anaesthetic enantiomers have the same general formula and solubility, but different potencies?
- Anaesthetic enantiomers can have the same general formula and solubility, but different potencies
- This is due to their interaction with GABAA receptors
What are GABAA receptors?
What type of arrangement do GABAA receptors have?
How many subunits do they have?
How do general anaesthetics bind to GABAA receptors?
What does allosterically mean?
How does general anaesthetic binding affect neuronal excitability?
- GABAA receptors are transmitter (ligand) gated ion channels with a central ion pore
- They have a pentameric arrangement
- 18 possible sub units, with approximately 30 forms of receptor (some subunits location-specific)
- General anaesthetics allosterically activate the receptor, with IV GAs probably acting at links between α and β subunits
- Allosterically means they bind to somewhere other than the active site
- When general anaesthetics bind, this leads to an enhanced binding of GABAA, leading to greater entry of Cl- ions to the cell
- This hyperpolarizes the cell, making it more difficult to depolarize, reducing neuronal excitability
How can GAs promote a loss of consciousness?
- GAs potentiate (increase the power, effect, or likelihood) GABAergic transmission in the reticular activating system to produce an increased inhibitory input there to promote loss of consciousness.
Where do benzodiazepines bind to GABA receptors?
What does this site control?
What happens when Benzodiazepines are bound?
- Benzodiazepines act on a separate receptor binding site on the GABAA receptor subtype than GABA (allosteric binding)
- This site controls the ability of GABA to open the channel
- When benzodiazepines are bound, GABA can open the channel more often
- Benzodiazepines therefore only enhance the action of existing GABA molecules.
Describe the predominant mechanism of action of general anaesthetics.
Describe the mechanism of action for Nitrous oxide.
- The predominant method of action of general anaesthetics is activation of GABAA receptors
- Nitrous oxide inhibits NMDA receptors, which decreases excitatory neurotransmission
- It also increases the activity of background potassium channels, which hyperpolarizes cells and decreases excitability
How is ketamine taken?
What class of drug is it?
What type of problems can it lead to?
- Ketamine is sniffed/snorted
- It has been Reclassified as class B]
- It can lead to bladder problems, such as stone bladder, where the bladded doesn’t contract/relax but remains in a refractory period
- Patients may need to get their bladders removed
What can users of NO present with?
What does NO inactivate?
What is myelopathy and paraparesis?
- Increasing number of NO users presenting with neurological complications
- NO inactivates vitamin B12 leading to myelopathy and paraparesis
- Myelopathy is an injury to the spinal cord due to severe compression that may result from trauma, congenital stenosis, degenerative disease or disc herniation
- Paraparesis is partial paralysis of the lower limbs.
How does blood solubility affect induction and emergency/resolution of GAs?
- GAs that are poorly blood soluble will have a rapid induction, and rapidly resolve (fast emergence) e.g NO
- GAs that are very blood soluble will have a slower induction, but a longer emergence, as they take longer to get out of the system e.g isoflurane
Describe the following in fatty and lean tissues:
1) Perfusion rate
2) Partition coefficient
3) Rate of equilibration
- Lean tissues (e.g brain mass and CNS)
1) Fast perfusion
* Rapidly get blood to location
2) Small partition coefficient
* There is not much fat either side of the barrier to cause partitioning
3) Rapid equilibration
* As a result of having a small partition coefficient
* This tissue will clear rapidly of anaesthetic
- Fat tissues
1) Slow perfusion
* Doesn’t receive as much cardiac output
2) Large partition coefficient
* Drug leaches out into the lipophilic environment where it wants to be
3) Slow equilibration
* The slow perfusion and large partition coefficient means there will be slow equilibration
* This means there will be slow clearance of GAs from fat
- Although there will be fast clearance from lean tissues, there will still be traces left in the fat
How does ‘waking up’ from GAs typically occur?
- ‘Waking up’ from GAs typically occurs via redistribution rather than the drug clearing from the body
- Drug will move away from the brain and CNS quicker than it will be metabolised and removed from the body
IV anaesthetics
- Describe the effect of thiopentone, propofol, ketamine, and etomidate on the following factors (in picture):
1) BP
2) CO
3) HR
4) SVR (systemic vascular resistance)
5) Respiration rate
6) ICP
7) Pain on injection - Which one might we want to use for septic shock?
- IV GAs (in picture)
- In septic shock, we want a GA that won’t reduce BP, so ketamine of etomidate
What are side-effects of certain inhaled GAs?
- Inhaled GAs:
- Isoflurane causes cough and laryngospasm
- Patients wake up very quickly from desflurane - increased use as maintenance for long operations
Describe therapeutic advantages and disadvantages of the following GAs (in picture):
* Inhaled anaesthetics:
1) Desflurane
2) NO
3) Isoflurane
4) Sevoflurane
- IV anaesthetics
1) Thiopental
2) Ketamine
3) Fentanyl
4) Propofol
