Flashcards in General Anaesthetics Deck (62):
who was the first to make nitrous oxide ?
he suggested in 1800 that it could be used to relieve pain
- it was originally thought to be very toxic
it become the common fairground attraction and it produced euphoria, analgesia and loss of consciousness= laughing gas
when was nitrous oxide first used ?
horace wells, a dentist had a tooth extracted using it
what did william morton do ?
in 1846 he convinced the chief surgeon at mass gen hospital to allow him to administer ether to induce anaesthesia and it was very successful
what are modern anaesthetics described as ?
controlled and reversible loss of sensation and consciousness - has to be under controlled conditions
who used anaesthetics prior to 1800s?
the ancient greeks
what are the characteristics of a general anaesthetic ?
amnesia- dont want to remember what happened
loss of consciousness
relaxation of skeletal muscles for surgery and setting bones
suppression of somatic, autonmic and endocrine reflexes- avoid increased blood flow and release of adrenaline
haemodynamic stability- stability of cardiovascular system
what some key factors when administering an anaesthetic ?
it needs o be quick and pleasant
it needs to be maintained smoothly and the patient wants to recover from it rapidly
what are the 4 stages of anaesthesia ?
3- surgical anaesthesia
4- medullary depression
what is stage 1 of general anaesthesia ?
- it is analgesia without amnesia, patient is conscious but drowsy - blunting of pain sensation
- the levels of analgesia vary with different agents - nitrous oxide causes pronounced analgesia
what is stage 2 of general anaesthesia ?
- loss of conciousness
- patients no longer respond to non-painful stimuli but respond to painful stimuli in reflex fashion
- patient may move and talk incoherently
- respiration rapid and irregular due to stimulation of this system
- dangerous stage and modern anaesthetic procedures are designed to eliminate or minimise this stage
- want to get through this stage as quickly as possible
What is stage 3 of general anaesthesia ?
- loss of consciousness - 4 planes of increasing depth
- plane 1= decrease in eye movements
- plane 2= loss of corneal reflex
- planes 3 and 4= loss of pharnygeal reflex, decrease in muscle tone and respiratory depression
what is stage 4 general anaesthesia ?
- loss of spontaneous respiration
- depression of cardiovascular reflexes
- regarded as an overdose requiring respiratory and circulatory support
this is a highly dangerous stage and you want to keep the patient out of this
patient will be given support for breathing and also receive adrenaline
what are the properties for an ideal GA for the patient ?
pleasant induction- simple injection
tasteless- if an inhalation drug
no side effects
rapid recovery - no lethargy and headaches
what are the ideal properties for an GA for the surgeon ?
no increased bleeding - no anticoagulant effects
long duration possible
what are the ideal properties of a GA for the anaesthesist ?
controllable - to help maintain patient in stage 3
no long term effects
easy mixing- if its a gas it must be easily mixed with air to maintain normal blood-oxygen levels
what are the ideal properties of a GA for the manufacturer?
easy to make
what are 2 very important factors necessary for a GA ?
what are the 2 theories for the mechanisms of action of GA?
what was the meyer-overton hypothesis ?
close correlation between anaesthetic potency and lipid solubility- many different theories noticed that the potency of an anaesthetic is closely related to lipid solubility
what happens to the potency of an anaesthetic as the lipid solubility increases ?
as lipid solubility increases the potency of the anaesthetic increases
what is plotted in the lipid theory ?
plot of minimum alveolar concentration (MAC) against lipid solubility expressed as oil:gas partition coefficient
what is the oil:gas partition coefficient ?
it is a measure of the amount of anaesthetic that has partitioned in the lipid
e.g. if it is 1 then the anaesthetic will be equally distributed in lipid as what remains as gas
what is the oil:gas partition coefficient of methoxyflurane?
this means that 1000 more is in lipid compared to in gas
what is MAC ?
minimum alveolar concentration
it is the concentration that prevents 50% of patients responding to a painful stimulus and is an index of anaesthetic potency- bit like LD50 or EC50
what did the lipid theory suggest ?
suggested anaesthesia was due to alteration of membrane function
what were to the 2 mechanisms proposed in the lipid theory ?
volume expansion of membrane - this changes functioning of transporters and proteins in the membrane
altered membrane fluidity
what are some exceptions to the lipid theory ?
enantiomers of some GAs have different anaesthetic properties but identical physical properties
e.g. isoflurane and etomidate
because one doesnt have anaesthetic properties this indicates that it is not physico-chemical properties that are just involved
what is the protein theory ?
GAs bind to hydrophobic domains in receptor/ion channel proteins as well as partitioning in the membrane
- anaesthetic sensitivity differs in mutant receptors suggesting specific binding domains
what was demonstrated about GAs with the GABAa receptor ?
site directed mutagenesis of glycine and GABAa receptor affects anaesthetic sensitivity
- with normal subunits GABAa activity is increased with GAs
- GABA subunit roe is insensitive to GAs
- therefore it proved that there was a specific region on the GABAa receptor inducing the effects of GAs
what was the consensus about the protein theory ?
anaesthetics concentrate at the lipid protein interface in the membrane and so can affect protein function but also potency is related to oil/gas partition coefficient
what is the mechanism of action of GAs?
inhibit synaptic transmission
minimal effects on axonal conduction
reduce release of excitatory transmitters
response of post-synaptic receptors inhibited
GABA mediated inhibitory transmission is enhanced by some GAs - enhancement of inhibitory transmission - enflurane and isoflurane
depression of CNS activity
what can nitrous oxide and ketamine do at the concentrations reached during anaesthesia ?
inhibit the function of excitatory ionotropic NMDA receptors and/or activate 2 pore domain potassium channels TREK
TREK channels are important for maintaining resting membrane potential - they are the leak channels
what sites in the CNS can GAs produce specific components of the anaesthetic state ?
thalamus, cortex and hippocampus- particularly sensory nuclei in the thalamus and sensory areas of the cortex
what are the most sensitive areas to GA ?
thalamic sensory relay nuclei
deep layer of cortex to which these nuclei project - route taken by sensory impulses reaching cortex
what is the main factor to determine the rate of induction and recovery of inhalation GAs?
blood:gas parition coefficient
if an inhalation GA has a low solubility in the blood what does this mean ?
the faster the process of equilibration because less has to be dissolved in blood to increase the partial pressure
- when a gas is dissolved in blood/tissue its partial pressure is inversely proportional to its solubility in the tissue
-therefore a GA with a low solubility in blood has a fast onset of action because it reaches equilibrium quickly
- same priniciple for wash out because if it has a low solubility recovery will be faster
what does the recovery phase include?
a rapid phase being followed by a hangover effect
when is the hangover effect of a GA enhanced ?
when the GA is highly fat soluble because it has been maintained for a long time- takes longer time for the anaesthetic to come out of the fat
what happens to a GA with a high oil:gas partition coefficient ?
it accumulatess in the body fat and is released slowly post operation
can cause pronounced hangover effect
what anaesthetics have a fast induction/recovery and why ?
- low blood:gas coefficient - 0.5m low oil:gas coefficient- 1.4
- low blood:gas coefficient- 0.4 low oil:gas coefficient - 23
- low blood:gas coefficient-0.6 low oil:gas coefficient- 53
what anaesthetics have a medium induction/recovery and why ?
isoflurane- slightly higher blood:gas coefficient- 1.4 and higher oil:gas coefficient - 91
halothene- higher blood:gas coefficient - 2.4 and very high oil:gas coefficient- 220
what does a higher oil:gas partition coefficient cause ?
the higher the anaesthetic potency and so MAC is lower
GAs cause depression of the force of contraction of the heart and relax vasuclar smooth muscle what can this lead to ?
hypotension and reduce organ perfusion
exception= nitrous oxide because it increases sympathetic tone and therefore increases HR and BP
what can halogenated GAs cause ?
cause malignant hyperpyrexia
e.g malignant hyperthermia induced by halothane
- quite common
- happens in some patients indicated by increased by body temperature and contraction of skeletal muscle
describe nitrous oxide :
- excellent analgesic properties
- low potency MAC >80% because it has a low oil:gas coefficient- so it has a rapid onset
- often combined with other inhalational agents during maintenance of anaesthesia
- low blood:gas partition coefficient
- depresses methionine synthase leading to bone marrow depression so there is a risk of anaemia in long term use (>6hours)
- been linked to increased risk of abortion/foetal abnormality in operating theatre staff
- easily controlled by anaesthetist
describe halothane :
not used in developed countries anymore
- potent- MAC= 0.8% due to high oil:gas partition coefficient - leads to hangover effects
- medium blood:gas partition coefficient so medium onset and recovery kinetics
- biotransformed (15-30%) to trifluoracetic acid which can covalent bond to liver enzymes and trigger hepatotoxicity
- cardiac dysrhythmias
replaced by isoflurane
- similar potency to halothane so little is used due to hangover effect
- relatively high blood:gas partition coefficient medium onset and recovery
- <1% biotransformed but can cause malignantt hyperthermia - serious side effect
- cause seizures during recovery and induction
- similar potency to halothane- therefore hangover effects
- <0.2% biotransformed
- more expensive than halothane
- may precipitate myocardial ischaemia in patients with coronary artery disease
- more commonly used
- <0.1% biotransformed
- rapid induction and recovery because blood:gas coefficient is low
- useful for day case surgery
- MAC 6%, respiratory tract irritation at levels used for induction
- similar to desflurane
- 3% biotransformed
- intermediate potency MAC 2% between isoflurane and desflurane - less respiratory irritation compared to desflurane
- fast induction and recovery
what are examples of inhalation agents ?
what are some examples of obsolete inhalation agents and why ?
- chloroform- hepatotoxicity and cardiac dysrhythmia
- diethyl ether- explosive and respiratory tract irritant
- cyclopropane- explosive, marked respiratory depressant and hypotension
- methoxyflurane- slow recovery due to high oil:gas coefficient and causes renal toxicity due to 50% biotransformed releasing fluoride and oxalate
- halothane- hepatoxicity and malignant hyperthermia
- enflurane- malignant hyperthermia and seizures
what acts more quickly intravenous agents or inhalation agents ?
intravenous agents- unconscious in seconds to minutes
20s, normally used for induction
what is the anaesthetic duration for intravenous agents ?
- due to redistribution, first to tissues with a large blood flow then to muscles then to fats
- subsequent metabolism is much slower
for long operations an inhalation agent is used to maintain the anaesthesia
no analgesic effect but unconscious in 20s
blood concentration drops rapidly due to redistribution
marked respiratory and cardiovascular depression even at doses that fail to abolish reflex effects to painful stimuli
high lipid solubility so hangover effects
used for induction
better than thiopentone
- less respiratory depression at clinically relevant doses
- more rapidly metabolised than thiopentone
- can cause involuntary movements during induction
- can cause post-operative nausea and vomitting
very fast onset and recovery
rapidly metabolised so no hangover
continuous infusion used to maintain surgical anaesthesia so used in majority (75%) of day case surgery
main side effect= ccardiovascular and respiratory depression
slow onset- 2-5 min
produces dissociative anaesthesia- may remain conscious though amnesic effects induced and insensitive to pain
BP and HR usually increase but respiration is unaffected
hallucinations and irrational behaviour during recovery
used in surgery for adults and childrens with respiratory problems
- anxiolytic, sedative, muscle relaxant, anticonvulsant, amnesia
- slow onset
- little respiratory or cardiovascular depression
- used as a pre-op or for procedures such as endoscopy
what are examples of intravenous agents ?
how are general anaesthetics usually used ?
normally used in combination, rarely achieved with a single agent