General anaesthesia Flashcards
What is general anaesthesia ?
Reversible, drug induced loss of consciousness, usually to allow a surgical procedure to be preformed
Different stages (from away to commence surgery)
Stage 1 - Analgesia;
- Analgesia (depends on agent)
- Amnesia
- Euphoria
Stage 2 - Excitement;
- Excitement
- Delirium
- Combative behaviour
Stage 3 - Surgical Anaesthesia;
- Unconsciousness
- Regular respiration
- Decreasing eye movement
Stage 4 - Medullary Depression (Gone too far!);
- Respiratory arrest
- Cardiac depression and arrest
- No eye movement
What are some commonly used anaesthetic agents (drugs)?
Intravenous induction agents:
- Agents which will induce loss of consciousness in ‘one arm brain circulation time’
- Propofol
- Thiopentone (thiopental)
- Etomidate
Inhalation anaesthetic agents;
- Gas or vapour, delivered to the patient via a breathing circuit
- May be used to induce anaesthesia (children)
- More commonly used to maintain anaesthesia
- Sevoflurane
- Nitrous oxide
- Isoflurane
- Desflurane
What is the most common induction agent ?
Propofol used in 91.8% cases that had an induction agent
What is the most common maintenance agent ?
Sevoflurane used in 71.3% cases that has a maintenance agent during general anaesthesia
What is the most common induction and maintenance agents in C-sections
C-section
Most common induction agent;
- Thiopental (then propofol)
Most common maintainance agent;
- Sevoflurane (nitrous oxide close second)
Thiopental - Due to people waking up during surgery, reduces likelihood of recovery during surgery and reduced risk of getting into circulation and influencing the baby before being born
What is the SECOND most common induction agent for children?
Most common - Propofol
Second most common - Sevoflurane
What is and when might you us Entonox?
Entonox is 50:50 nitrous oxide and oxygen
Uses;
- Analgesic
- Labour
- Trauma (e.g hip broken - moving transport)
Unlikely to make patient unconscious, short action, numbs a little of what is going on
How can very different molecular structures cause the same affect?
Overton & Meyer (the ‘old skull’ explanation);
- Originally thought was due to lipid solubility
- Correlation between MAC score and solubility
- MAC score is what alveolar concentration that 50% of population failed to respond to a surgical stimulus to (lowest effective dose and escalating up from there)
Minimum Alveolar Concentration (MAC) = At which 50% of the population fail to respond to surgical stimulus
- More lipid soluble = More potent = Lower MAC score
- More blood soluble = Slower the onset
Higher MAC harder it is to put patient into respiratory distress and medullary shut down, kinda like therapeutic index.
The most soluble in blood is Isoflurane ! (slowest onset)
NO2 is least soluble, so less potent, higher MAC and quicker onset
However ! There are some black swans!;
- Drugs like Ketalar and hypnomidate have structural isomers (mirror images of each other), have same lipid solubility but different potencies and effects, so lipid solubilities aren’t the only effect
What occurs in chemical synaptic transmission ?
1980’s discovered that anaesthetics interact with proteins, moved us from lipid solubility and graphs to more classic pharmacology of receptors being involved
1). Synthesis of neurotransmitter and formation of vesicles
2). Transport of neurotransmitter down axon
3). Action potential travels down the axon
4). Action potential causes calcium to enter evoking release of neurotransmitter
5). Neurotransmitter attaches to receptor exciting or inhibiting postsynaptic neuron
6). Separation of neurotransmitter molecules from receptors
7). Reuptake of neurotransmitter to be recycled
8). Vesicles without neurotransmitter transported back to cell body
What receptors do General Anaesthetics interact with ?
Transmitter (ligand) gated ion channels !
Interact with a range of receptors, GABA interaction is most common though!
How do Benzodiazepines work on receptors ?
Benzodiazepines act on a separate receptor binding site on the GABA(a) receptor subtypes than GABA
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 action of existing GABA molecules
This is what we reckon with anaesthetics
Allosteric modulator - binds to not the receptor but different site on receptor but modifies function and changes channel
What are the features of GABA(a) receptors ?
- Pentameric arrangement
- Central ion channel pore
- 18 possible subunits (approx 30 forms receptor)
- Some subunits location-specific
General anaesthetics Allosterically activate the receptor;
- IV GA’s probably acting on B subunits
- Inhalation GA’s probably at links between A and B subunits
Research using knock-in mice shows;
- intravenous anaesthetics are mediated by B3 subunit,
- B2 subunit mediating IV hangover
- However, unlikely to be any new anaesthetics … due to economics (cost to make new and no demand)
What General Anaesthetics affect which channels and what do those channels cause?
Drugs;
- Etomidate, Propofol, Barbiturates STIMULATE GABA(a) receptors
- Volatile Anaesthetics STIMULATE GABA(a) receptors and Background Potassium Channels and INHIBITS Sodium Channels
- Nitrous oxide STIMULATE Background Potassium Channels and INHIBIT NMDA receptors
- Ketamine INHIBITS NMDA receptors
Receptors;
- GABA(a) Receptors INHIBIT Neuronal Excitability
- Sodium Channels STIMULATE Neuronal Excitability and Excitatory Neurotransmitter-transmission
- Background Potassium Channels INHIBIT Neuronal Excitability and Excitatory Neurotransmitter-transmission
- NMDA Receptors STIMULATE Excitatory Neurotransmitter-transmission
BOTH Neuronal Excitability and Excitatory Neurotransmitter-transmission STIMULATE Consciousness and Movement (AKA we don’t want this in anaesthesia)
What is Special K and its features?
Special K is Ketamine’s street name - Drug misuse;
- Sniffed / snorted
- Increasing misuse
- Reclassified as Class B drug
- Bladder problems (stone bladder)
- Dissociative ‘K-Hole”
How may Nitrous Oxide be mis-used?
Nitrous oxide;
- Increasing number of users present with neurological complications
- Inactivates Vitamin B12 leading to myelopathy (spinal cord injury) and paraparesis
What are the clinical implications of the pharmacokinetics ?
Most of recovery is based upon the maintenance drug
When stop adding drug it will redistribute in different tissues and high concentrations in nervous system drops off (patient will wake up!)
Patient “waking up” tends to happen with drug redistribution in the body, so when we keep supplying in CNS and stop will allow for it to redistribute and come around (see image where after time it decreases in blood and brain and is redistributed to fats and less-well-perfused tissues)
How do anaesthetics affect the heart + vasculature?
Virtually all antetheic agents will to a greater or lesser effect have a negative effect on the heart and will reduce systemic vascular resistance (this was discover from Pearl Harbor)
EXCEPT - KETAMINE - Increases Cardiac performance
All anaesthetic have effect on heart and cause BP to drop apart from Ketamine - used in field stuff now, increases cardiac performance
Gave to those kids trapped in cave in Thailand, as increased cardiovascular performance and could swim for longer
How do anaesthetics affect the airways?
Any drug causing loss of consciousness may lead to obstruction of the airway
Respiratory depression is common with nearly all anaesthetic agents. With intravenous agents this tends to be a fall in respiratory rate with inhalational agents a fall in tidal volume
Happened to Michael Jackson as he was prescribed Propofol to go to sleep, too much respiratory depression and died and doctor was sued
What are some features of Anaesthetic agents we have?
There is no perfect anaesthetic agent
Propofol - least bad, big decrease in Heart function, decrease in everything else (Inc or Decrease in SVR) (Pain injection)
Ketamine - increase respiratory + Cardio (inc everything but SVR stays same)
Etomidate - everything in middle, respiratory depression (pain injection)
Thiopentone - everything decrease apart from HR (SVR can go up or down)
*Systemic vascular resistance (SVR)
What are the 4 main inhalation and 4 main intravenous anaesthetics ?
Inhalation;
- Desflurane;
- Nitrous oxide
- Isoflurane
- Sevoflurane
Intravenous;
- Thiopental
- Ketamine
- Fentanyl
- Propofol
