General Anaesthesia Flashcards
What are the anaesthesia techniques?
Local Anaesthesia
General Anaesthesia
Conscious sedation (IHS and IV)
What is the goal of anaesthesia?
Hypnosis (unconsciousness)
Amnesia
Analgesia
Immobility/decreased muscle tone (relaxation of skeletal muscle)
Inhibition of nociceptive (pain) reflexes
Reduction of certain autonomic reflexes (gag reflex, tachycardia, vasoconstriction- increase blood pressure)
What are the desired effects of general balanced anaesthesia?
Rapid induction
Sleep
Analgesia
Secretion control
Muscle relaxation
Rapid reversal
What are the delivery techniques of anaesthesia?
Inhalation anaesthesia
Intravenous anaesthesia
Inhalation plus intravenous
Inhalation plus intravenous anaesthesia is also referred to as…
Balanced anaesthesia
What is the MOA of inhalation anaesthesia?
The MOA is still largely unknown
There is a strong linear correlation between lipid solubility of inhalation anaesthesia and ____________.
Anaesthesia potency
(minimum alveolar concentration)
The potency of inhalation anaesthesia can also be referred to as ________.
minimum alveolar concentration (MAC)
What is the effect of the lipid solubility on anaesthetic effect?
The more soluble the agent, the better the anaesthetic effect ???
What is the minimum alveolar concentration (MAC)?
This is the concentration of the gas that prevents patient movement in response to a stimulus (e.g. skin incision) in 50% of subjects
Why is MAC accepted as a valid measure of potency of inhalation GA?
This is because it remains fairly constant for a given species even if it is given under varying conditions
MAC is ______ in infants and _________ in the elderly.
Higher in infants
Lower in the elderly
What is the implication of a higher MAC in children/ infants?
lower concentration is required to get the same effect
What is the implication of a lower MAC in the elderly?
a higher concentration is required to get the same effect
What can MAC be used for?
It can be used to titrate the level of volatile anaesthetic to achieve and maintain a safe level of anaesthesia
What is the implication of factors that cause MAC to decrease?
It means that less volatile LA is required to prevent patient response to stimulus (e.g. surgical incision)
What is the implication of factors that cause MAC to increase?
It means that more volatile LA is required to prevent patient response to stimulus (e.g. surgical incision)
What factors can cause MAC to increase?
hyperthermia
Alcoholism
thyrotoxicosis (more thyroid hormones; overactive thyroid)
What factors can cause MAC to decrease?
Hypothermia
Hypotension
Pregnancy
Decrease in T4 hormone (hypothyroidism)
Hyponatraemia (decrease in Na+)
Opioids
TCAs
Tranquilizers
Benzodiazepines
In these situations; less volatile anaesthetic is required to prevent patient response to stimulus
What is the effects of opioid analgesics and sedative hypnotics often used as adjuvants to anaesthesia?
The decrease MAC
which means that less of anaesthetic is required to prevent patients response to stimulus (e.g. surgical incision)
MAC values can be described to be ____________. Give an instance of this characteristic
Additive
Anaesthetic with MAC of 0.7 and NO with a MAC of 0.3
means that that combination anaesthetic has a MAC of 1
What is the use of nitrous oxide in anaesthetics?
NO is often used as a carrier gas to decrease the anaesthetic requirement of other drugs
What are the proposed theories for how inhalation anaesthesia work?
Membrane stabilisation theory
Promiscuous Receptor agonist theory
General anaesthetics exist in what forms?
gases or volatile liquids that evaporate when inhaled
What is the object of inhalation anaesthesia?
to obtain a partial pressure in the brain that is sufficient to reach the desired level of anaesthesia
!!! Briefly explain the membrane stabilisation theory!!
The site of action in the lipid phase of cell membranes (membrane stabilising effect)
The propagation of action potentials is stopped by changes the ion channels?
OR
Anaesthesia could bind to the hydrophobic regions of the membrane bound proteins which may induce the transition from gel to the liquid crystalline state of the phospholipids. This therefore stabilises the membrane and prevents action potentials from being propagated
!!!Briefly explain the promiscuous receptor agonist theory!!!
Anaesthetias may act at GABA /NMDA/other NT receptors
They may act directly on the ion channels associated with these receptors
They may act in the hydrophobic pouches of proteins associated with receptors
They may effect allosteric interaction to alter the affinity of the receptor ligands
Although the MOA of inhalation anaesthesia is still not fully understood, the potency of an anaesthetic is thought to correlate with its…
lipid solubility
They may produce the effects by dissolving in the lipid bilayer of the cell membrane and expanding or increasing its fluidity
It is thought that anaesthetics bind to the __________ region of proteins (ion channels/receptors) and inhibit its normal function
hydrophobic region
the inhibit the propagation of the action potential
What are volatile anaesthetics?
These are anaesthetics that are present as liquids at room temperature and pressure but are vaporised into gases for administration
NO is present in what state at room temperature and pressure?
gaseous state
How is NO supplied ?
supplied as compressed gas
The depth of inhalation anaesthesia is dependent on…
the MAC (minimum alveolar concentration)
Partial pressure of the gas in the brain
Briefly state the pathway for anaesthetics.
Alveoli
Arterial blood
other tissues/metabolism/brain
Give examples of agents used in inhaled anaesthetics (general inhalation anaesthesia)
Nitrous Oxide (decreases MAC so less volatile LA is required to prevent patient response to stimulus)
Halothane (fluothane)
Methoxyflurane (penthrane)
Enflurane (ethrane)
Isoflurane (forane)
Desflurane (suprane)
Sevoflurane
Other anaesthetic gases have even lower MACs which means that even less volatile LA is required to prevent patient response to stimulus (surgical incision)
What in general inhaled anaesthetic is not readily used and difficult to manage?
Desflurane (Suprane)
What is the least potent anaesthetic gas?
Nitrous Oxide
Has a MAC of 105
What is the least potent anaesthetic gas?
Nitrous Oxide
Has a MAC of 105
What is the MAC percentage of NO?
105
What is the MAC percentage of halothane?
0.75
What is the MAC percentage of methoxyflurane?
0.16
What is the MAC percentage of of enflurane?
1.7
What is the MAC percentage of isoflurane?
1.2
What is the MAC percentage of desflurane?
6.0
What is the MAC percentage of
2.0
What is the current most potent anaesthetic gas?
Isoflurane
This is because it has the lowest MAC value
Why has the use of halothane been phased out?
this is because of the potential to cause respiratory depression
Does NO have analgesic properties?
No it does not
What hypnotic agent used in anaesthesia has the fasted elimination?
Nitrous Oxide
Give some characteristics of nitrous oxide?
colourless and inorganic agent
it has a pleasant odour
it is non-irritating to the body
it is non-explosive and not flammable; but will support combustion as well as oxygen
What is the MAC of nitrous oxide?
110%
105%?
High MAC means that more of the volatile anaesthetic is required prevent response to stimulus (e.g. surgical incision)
What is the MAC asleep for nitrous oxide?
68-73%
this means that asleep, less N2O is required to prevent response to stimulus (e.g. surgical incision)
How is nitrous oxide excreted from the body? State the form it is excreted in
It is excreted unchanged almost exclusively by the lungs
Nitrous oxide depresses the CNS mainly in the ___________ centres
respiratory centres
What is the benefit of nitrous oxide as a second gas in inhaled anaesthetic ?
A high concentration of NO2 (70%) can be used to promote the rapid uptake of gas
Why is a high concentration of Nitrous oxide beneficial for the second gas in the inhaled anaesthetic?
The second gas is drawn much faster into the lungs than if it were administered alone
This is because a high concentration of Nitrous oxide will mean that alveolar pressures are reached quickly , there is little decrease in the concentration of the gas and due to the negative pressure produced, more gas is drawn into the lungs decreasing the volume
What is the benefit of the second gas effect?
it allows minimal amount of a more potent anaesthetic to be administered simultaneously with nitrous oxide
Halothane (fluothane) is the first _________ ether. This makes it _____________.
halogenated
this makes it non-flammable
How is halothane metabolised?
Metabolised by P450, induction of hepatic microsomal enzyme
What is halothane metabolised into?
TFA (trifluoroacetic acid), chloride, bromide
What is the effect of halothane on the CVS?
it is a myocardial depressant; has effects on the SA node
causes sensitisation of the myocardium to catecholamines (adrenaline)
can cause dose dependent hypotension
Halothane is hepatotoxic. True or false
True
this is more likely after repeated doses
Isoflurane undergoes a lot of metabolism. True or false
False
very little metabolism (0.2%)
What characteristic of isoflurane inhaled anaesthetic is particularly beneficial in dentistry?
it potentiates muscle relaxants
Allows mouth muscles to relax under anaesthetic for dental procedures
What is the effect of isoflurane on the CNS ?
controls cerebral blood flow and intracranial pressure
What is the meaning of a coronary steal?
it is a condition that occurs due to the vasodilation of coronary arteries in the presence of CAD (this is where there is partial or complete blockage of the lumen in another artery)
What is the effect of isoflurane on coronary vessels?
they can cause preferential vasodilation of small coronary vessels which can lead to a coronary steal
dose dependent hypotension
Vasodilation increases the lumen of blood vessels and therefore lowers the blood pressure
There are no reports of hepatotoxicity and renotoxicity for isoflurane. True or false
True
What is the most widely employed inhaled anaesthetic?
isoflurane
Sevoflurane is used more often in _____________.
Paediatrics
What are the implications of the low solubility and pungency observed in sevoflurane?
acts as an early induction agent
rapid recovery means patient may need early post-operative pain-relief
Briefly describe metabolism of sevoflurane.
undergoes significant metabolism (5% metabolism)
10x more than isoflurane
What are the metabolic produces of sevoflurane?
inorganic fluoride
hexafluoroisopropranolol
Why is sevoflurane indicated for use in children?
very pleasant to breath
good choice if an inhalation agent is required for induction
What is induction ?
This is a preoperative stage where patients have been given medication and may begin to feel its effects but remain conscious
Sedated but conscious
Due to rapid recovery from sevoflurane, what must be reinforced?
analgesic
What is malignant hyperthermia (MH)?
This is a pharmacogenetic hypermetabolic state of the skeletal muscle in susceptible individuals by inhalation anaesthesia and/or succinylcholine (and maybe by stress or exercise)
What are the causes of malignant hyperthermia?
Genetic susceptibility of the Ca+ channel defect (CACNA 1S) or RYR1 (ryanodine receptor)
Stress
Exercise (high performance athletes)
What are the effects of malignant hyperthermia?
excess calcium ions leads to excessive ATP breakdown/depletion, lactate production, increased CO2 production. Increased VO2 and eventually, myonecrosis and rhabdomyolysis , arrhythmias and renal failure
MH causes excessive muscle contraction which causes rigidity
calcium binds to troponin and tropomyosin? which are the proteins which mediate muscle contraction
What is a serious contraindication for inhaled GA use?
malignant hyperthermia
How can malignant hyperthermia be treated?
Dantrolene
What is the MOA of dantrolene?
increases the reuptake of calcium ions in the sacroplasmic reticulum
What are the signs of malignant hyperthermia?
Tachycardia
Tachypnea (rapid and shallow breathing)
ETCO2 increasing
Metabolic acidosis
Hyperthermia
Muscle rigidity
Sweating
Arrhythmias
What is the MOA of most intravenous anaesthetics?
potentiating the GABA receptor
GABA inhibitory NT
The GABAnergic actions of IV anaesthetics may be similar to those of the volatile (inhaled) anaesthetics, how do they differ?
They act on different sites of the receptors
What can you also employ when using IV anaesthetics?
High efficacy opioids such as fentanyl
Malignant hyperthermia is a factor with IV anaesthetics. True or false
False
What is the effect of IV anaesthetics on GABA receptors?
They prolong the ion channel opening of GABA receptors
Therefore the activity of the GABA receptors increase
What are the organ effects of IV anaesthesia?
decrease cerebral metabolism and intracranial pressure
(often used in the treatment of patients at risk for cerebral ischaemia or intracranial hypertension)
May cause respiratory depression
May cause apnea (starting and stopping of breathing when you are asleep) after induction of anaesthesia hence the importance of establishing the airway soon after delivery
Benzodiazepines (diazepam), barbiturates and propofol are _________.
sedatives
Hyponotic sedatives ?
What is the effect of benzodiazepines (diazepam), barbiturates and propofol on the CVS?
they can cause cardiovascular depression
Drugs which typically do not depress the cardiovascular system can do so in what kind of patients ?
patients who’s CVS is compromised but compensating by increasing sympathetic nervous system activity
Why are barbiturates considered ideal IV anaesthetics?
short acting
rapid onset
What was the most common IV anaesthetic used?
Thiopental (penthathol)
Barbiturate
Give examples of IV barbiturates used in IV anaesthetics
Suritol (thiamylal)
Brevital (methohexital)
What is the MOA of barbiturates?
act on GABA receptors
potentiate endogenous GABA activity at receptor
has direct effect on Cl- channels at higher concentrations
When GABA acts on GABAa receptors, activated GABA receptors become more permeable to chloride ions
Barbiturates do not bind to the GABAb receptors
How are the physiological effects of barbiturates terminated?
By redistribution and not metabolism
What is the danger with repeated administration or prolonger infusion of barbiturates?
Redistribution to terminate the effects become ineffective as it can lead to approached equilibrium at distribution sites which renders redistribution ineffective in terminating the action
Barbiturates can build up in _________ tissue. Therefore, it can cause __________
adipose tissue
long emergence (delayed emergence) where it takes a long time to gain consciousness
What is the onset of propofol?
onset within 1 minute of injection
What is the MOA of propofol?
thought to enhance activity of GABA receptors
Propofol has no ____________ action
analgesic
Does not bind to opioid receptors
What are the side effects of propofol?
vasodilation
respiratory depression
apnea (25-40% of cases) - breathing stops and starts during sleeping
What is the use of propofol in IV anaesthesia?
induction and maintenance of anaesthesia or sedation
Briefly describe emergence from anaesthesia with propofol use
rapid emergence from anaesthesia
Propofol has a anti-emetic effect. What does this mean?
can prevent nausea and vomiting
Propofol can be used for what kind of surgery?
Ambulatory surgery/outpatient surgery
this is surgery that does not require overnight stay
What causes pain on injection of etomidate (amidate)?
not soluble in water so formulated in 35% propylene glycol
Etomide has little respiratory depression and minimal CV effects. True or false
True
Etomidate has a ______ induction.
Rapid (from arm to brain)
duration of 10-15 minutes
What is etomide commonly used for?
induction of anaesthesia in patients with CV compromise or where cardiovascular stability is most important
Etomidate is metabolised into ___________ and excreted by?
carboxylic acid
85% by urine
15% in bile
Etomidate has ________ emergence from anaesthesia
rapid
What are side effect of etomidate?
emesis (vomiting)
pain
involuntary myoclonic movements
inhibition of adrenal steroid synthesis
Ketamine is chemically and pharmacologically related to _____.
PCP -phencyclidine which was originally developed as an anaesthetic
What is the MOA of ketamine ?
it inhibits NMDA receptors (glutamate receptors)
enhance EPSP
Ketamine can be used as …
analgesic (interacts with opioid receptors)
dissociative anaesthesia
What are the physical characteristic of dissociative anaesthesia observed in ketamine?
cataleptic appearance (loss of consciousness but rigid)
eyes open
reflexes in tact
purposeless but coordinated movements
Ketamine stimulates the ____________ nervous system
sympathetic
Ketamine indirectly stimulates the _________ system
cardiovascular
direct myocardial depressant
What is the effect of ketamine on the CNS?
increases cerebral metabolism and intracranial pressure
State the threshold for seizures with ketamine
low threshold
What are the psychomimetic (emergence reactions) of ketamine ?
vivid dreaming extracorporeal (floating- out-of-body) experience misperceptions, misinterpretations, illusions
may be associated with euphoria, excitement, confusion and fear
Ketamine is often used in ____________ surgery
ketamine
Why was diazepam replaced by midazolam?
Diazepam requires a non-aqueous vesicle (not soluble) and thus there is pain on injection. Midazolam is water soluble and thus can delivered pain free
Briefly describe metabolism of benzodiazepines?
they are rapidly distributed and slowly metabolised
Benzodiazepines can be used as sole anaesthesia for what kind of procedures and why?
non painful procedures such as endoscopies, cardiac catheterization
This is because they are not analgesic so do not bind to opioid receptors or affect eicosanoids which have an effect on Adelta and C pain fibres
Benzodiazepines are commonly used for …
preoperative sedation and anxiolysis
induction of anaesthesia
cannot produce GA on its own
Benzodiazepines are safe (minimal respiratory and CV depression) when used alone. Why does the safety level decrease if used with other anaesthesia?
can potentiate effects of other anaesthesia
e.g. opioids
Rapid administration of benzodiazepines can cause…
transient apnea
Opioids are usually delivered in combination with…
benzodiazepines or inhalant
Give examples of opioids used as IV GA
fentanyl and analogues - sufentanil, alfentanil, remifentanyl
Morphine
Side effects of opioid anaesthetics include
Nausea and vomiting
delayed recovery
respiratory depression
What is the effect of opioid GA on the CVS?
little CV depression
provide more stable hemodynamics
What is the benefit of opioid analgesics?
Smooth emergence except nausea and vomiting
intraoperative analgesia
decrease post-operative pain
What is balanced anaesthesia?
using specific drugs for each components; sensory, cognitive, motor and autonomic
Give examples of drugs used for sensory analgesia
nitrous oxide
opioids
ketamine- NMDA antagonist; prevents excitation of pain receptors
What is the function of drugs that affect cognition in amnesia?
Anterograde amnesia (can’t form new memories)
unconsciousness
What drugs can affect conginitive abilities in GA
Nitrous oxide, 0.25-0.5 MAC of an inhaled agent
or IV hypnotic such as midazolam, diazepam, thipental (benzodiazepines) and propofol
(the lower the MAC the more potent the anaesthetic; less is required to prevent stimulus in patient)
What is the most common combination of amnesia?
Morphine- 10mg iv 3-5 minutes prior to induction; additional 5mg 45 minutes before the end of procedure, if it lasts longer than 2 hours
Propofol 2-3mg/kg on induction
Nitrous oxide 70%; second gas effect
Sevoflurane/isoflurane 0.3-0.6%
relaxant of choice
Give another example of combination GA drugs
Fentanyl (75-150 on indution, 25-50 mg now and then during the case)
Propofol 2-3mg/kg on induction
N2O-70&
Sevoflurane/isoflurane - 0.3-0.6%
Relaxant of choice
Neuromuscular blocking drugs block…
synaptic transmission at NM junction
Neuromuscular blocking drugs affect…
transmission only at skeletal muscle
does not affect nerve transmission, action potential generation
Neuromuscular blocking drugs act at …
nicotinic acetylcholine receptor Nii
What is the effect of acetylcholine of nicotinic cholinergic receptors on muscle membrane?
they cause a wave of depolarisation
sodium gated ion channels
What is the MOA of suxamethonium a neuromuscular blocking drug?
It is a short acting depolarising neuromuscular blocking drug
binds to nicotinic cholinergic receptors and mimic ACh
they are hydrolyse much slower than ACh (by plasma cholinesterase) which means depolarisation is prolonged causing neuromuscular blockade
What are the side effects of suxamethonium?
bradycardia
muscle pain
hyperkalaemia (beware in patients with burns or renal failure)
raised intraocular pressue
Give examples of non depolarising neuromuscular blocking drugs
vecuronium
rocuronium
What is the MOA of non depolarising muscle relaxants ?
competitive antagonism
competes with ACh to binding to nicotinic cholinergic receptor
What is the purpose of neuromuscular blocking drugs in GA?
to facilitate endotracheal intubation to aid surgical relaxation
improve access to mouth
How can neuromuscular blocked be reversed when using non-depolarising muscle relaxants ?
administration of anticholinesterase
These are drugs that prolong the existence of acetylcholine by preventing their metabolism by cholinesterase enzymes
