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General anaesthetics, Ketamine:, Xenon:, Four main features of balanced…
General anaesthetics
Anaesthesia is the reversible loss of response to noxious stimuli.
It may be general anaesthesia if associated with loss of consciousness
or local anaesthesia where consciousness is maintained.
Ketamine:
it is a phencyclidine(hallucinogenic) derivative that is administered in a dose of 2mg/kg.
its onset of action is 30-60 sec whereas action terminates in 15-20 min due to redistribution.
It acts by blocking NMDA receptors of glutamate.
Ketamine is a very strong analgesic but lacks muscle relaxant property.
It is used for producing dissociative anaesthesia
which is a state of profound analgesia, amnesia with slight sleep, immobility, feeling of dissociation from one’s own body and the surroundings.
Ketamine doesn’t depress pharyngeal and laryngeal reflexes.
Therefore is the agent of choice for emergency anaesthesia with full stomach
(because vomiting will prevent aspiration).
Ketamine increases all pressures(blood pressure, intracranial tension, intraocular pressure) in the body.
It is therefore intravenous anaesthetic of choice for shock increases blood pressure.
Further it is contraindicated in glaucoma(increases IOP) and head injuries(increases ICT).
It is a powerful bronchodilator agent and is therefore intravenous anaesthetic of choice in bronchial asthma.
Halothane is the inhalational anaesthetic agent of choice for bronchial asthma.
It is the intravenous anaesthetic agent of choice for induction in children.
Sevoflurane is the inhalational agent of choice in children.
On discontinuation of ketamine anaesthesia, several adverse effects may be seen known as emergence reaction.
Hallucinations are the most common side effect.
Other effects include vivid dreams, illusions and excitement.
Xenon:
it is Greek for stranger.
It was discovered in 1898 and found to be the only noble gas to be anaesthetic under normobaric conditions.
Xenon is extremely scarce with an average room containing only 4ml.
It is very close to the ideal agent.
It is a colourless and odourless gas with no irritation to the respiratory tract.
Well tolerated with gas induction.
It has lowest blood/gas partition coefficient(0.115)
allowing rapid induction and reversal of anaesthesia.
It produces unconsciousness with analgesia and a degree of muscle relaxation.
It has a MAC of 60-70% that allows a reasonable inspired oxygen concentration.
It doesn’t cause respiratory depression, to the point of apnea.
It has no effect on cardiovascular function.
It is not metabolised in the body and is eliminated rapidly and completely via the lungs.
It is non toxic and is not associated with allergic reactions.
It is stable in storage, has no interaction with anaesthesia circuits or sodalime.
However it shouldn’t be used with rubber anaesthesia circuits
as there is high loss through the rubber.
Xenon is non-inflammable.
Major problem with xenon is that is highly expensive
and routine usage will only be possible with a closed circuit delivery system that recycles xenon.
Four main features of balanced anaesthesia:
Unconsciousness
Analgesia
Muscle relaxation
Abolition of compensatory reflex responses
Important features of halothane
It can cause hepatitis on repeated use.
It can also result in malignant hyperthermia, which can be treated with dantrolene.
It can result in post-anaesthetic chills and shivering. Pethidine is used for the treatment of this condition.
Halothane relaxes the uterus.
Due to this property, it is the agent of choice in internal version and manual removal of placenta.
As version can be accomplished easily in relaxed uterus.
However due to its uterine relaxing property, it is contraindicated in labour,
because if post-partum haemorrhage results, it will be difficult to control(contraction of uterus stops bleeding after labour).
It sensitizes the heart to the arrythmogenic action of catecholamines.
It is therefore contra-indicated in patients with pheochromocytoma.
It is also a cardiodepressant drug that causes hypotension, bradycardia and arrythmias.
Halothane is the inhalational agents of choice in bronchial asthma due to its bronchodilator action.
It is an excellent agent for induction in children.
A.Thiopentone:
it is an ultrashort acting barbiturate and is the most commonly used intravenous inducing agent.
It is used as 2.5 % solution. Sulphur is added to pentobarbitone to increase the lipid solubility.
Due to high lipid solubility, it is the very fast acting drug.
Action of this drug terminates very quickly due to redistribution although half life is longer.
It also possesses anticonvulsant action.
Another barbiturate methohexitone increases the risk of convulsions, therefore used for electroconvulsive therapy.
It is the agent of choice for cerebral protection as it decreases cerebral oxygen consumption,
decreases intracranial tension
and decreases cerebral metabolic rate.
It causes peripheral vasodilation
and also depresses cardiovascular system therefore can cause hypotension.
Instead of producing analgesic effect, it can produce hyperalgesia at subanaesthetic doses.
Respiratory depression and transient apnea are other problems seen with this agent.
Propofol:
it is a milky white powder that is preservative free.
Therefore it must be used within 6 hours.
It is an oil based preparation.
Therefore injection is painful.
Its onset of action is within 15 seconds and last for 5-10 minutes due to redistribution
It possesses very strong antiemetic action and antipruritic action.
It decreases blood pressure and impairs baroreceptor reflexes.
It produces more severe and prolonged respiratory depression than thiopentone.
It has no muscle relaxant activity.
It has cerebroprotective activity but doesn’t possess anticonvlsant activity.
Rather myoclonic jerking and muscle twitching can be seen with the use of propofol.
It is the intravenous anaesthetic of choice for day care surgery.
Propofol is also the intravenous anaesthetic of choice for sedation in ICU.
Propofol is the intravenous anaesthetic of choice in paatients with malignant hyperthermia.
This agent is intravenous anaesthetic of choice and is used with alfentanil for total intravenous anaesthesia TIVA.
Blood gas partition coefficient:
it is determined by solubility of an agent in the blood.
It determines the speed of onset and recovery of an anaesthetic drug.
Greater is blood gas partition coefficient, lesser is the speed of onset and recovery and vice versa.
MAC is inversely related to potency
whereas blood gas partition cooefficient is inversely related to speed of onset
and recovery of an inhalational agent.
Desflurane is the fastest acting agent as it has minimum blood gas partition coefficient 0.42. Xenon 0.115
methoxyflurane is the slowest acting agent(maximum blood gas partition coefficient).15.
Ether:
it is a pungent smelling and irritant liquid can result in excessive secretions.
It is highly inflammable and explosive agent.
Cautery should not be used with ether anaesthesia.
It is very good analgesic agent and muscle relaxant.
It is very slow in induction of anaesthesia.
Guedel’s four stages of anaesthesia are based on ether.
It doesn’t affect the ciliary action and is also a good bronchodilator.
Therefore it is safe in asthmatic patients.
It is very economical and can be used as a sole agent for anaesthesia.
It is the safest agent in unskilled hands.
It can result in hyperglycemia, therefore contraindicated in diabetic patients.
B. Opioids:
Fentanyl, alfentanil, sufentanil and remifentanil are the opioids used in anaesthesia.
These are 100 times more potent than morphine.
Sufentanil is the most potent opioid.
These drugs possess very strong analgesic activity.
Fentanyl is used along with droperidol for neurolept analgesia.
If nitrous oxide is added, the combination can be used as neurolept anaesthesia N2O + fentanyl + droperidol.
These agents can lead to post operative muscle rigidity(SCh causes post operative muscle pain and fasciculations).
Alfentanil is used for day care surgery and for total intravenous anaesthesia.
Remifentanil is the shortest acting opioid due to its metabolism by esterase.
classification
Intravenous agents:
Inducing agents: thiopentone, methohexitone, propofol, etomidate and ketamine.
Slower acting drugs:
Benzodiazepines: diazepam, lorazepam and midazolam.
opioids: fentanyl, remifentanil, alfentail and sufentanil.
Neuroleptic agent: droperidol.
Inhalational agents:
Gases: nitrous oxide, Entonox and xenon.
Liquids: chloroform, trilene, cyclopropane, ether, halothane, enflurane, isoflurane, desflurane, sevoflurane and methoxyflurane.
Minimum alveolar concentration(MAC):
it is the minimum concentration of an inhalation agent required in the alveoli
to produce unresponsiveness to the skin incision in 50% of the patients.
It is the measure of potency of an agent. Greater is the MAC, lesser is potency.
Nitrous oxide is a gas with maximum MAC and thus least potency. Its MAC is 104%.
i.e even with pure 100% nitric oxide alone, we cant get complete anaesthesia.
This is thus not a complete anaesthetic agent.
Methoxyflurane is the most potent agent having least MAC(0.16%).
Nitrous oxide:
It is poor muscle relaxant. It shows fast induction and recovery of anaesthesia(low blood gas partition coefficient.).
It is used in concentration of 50-65% with 33% oxygen.
Entonox is a mixture of 50% N2O + 50% O2.
It is also called as “laughing gas”.
It is colourless, non-irritating and non-inflammable.
Colour of N2O cylinder is blue.
It is very good analgesic agent but weak anaesthetic agent which has highest MAC.
Isoflurane
It is an isomer of enflurane.
It is not a good analgesic agent.
Cardiac output is maintained with isoflurane.
Therefore it is the inhalational agent of choice for cardiac surgery.
It produces maximum decrease in blood pressure, therefore is the inhalational agent of choice for producing controlled hypotension.
It produces least increase in intracranial tension, therefore is the agent of choice for neurosurgery.
Isoflurane can be used in day care surgery.
It is safe in pheochromocytoma(doesn’t sensitize the heart to catecholamines.
It can cause coronary steal phenomenon.
Desflurane:
it has minimum blood gas partition coefficient and therefore is the fastest inducing agent.
It has very high vapour pressure. Its boiling point is 23 degree Celsius.
Therefore it boils at room temperature. It requires special vaporizers due to this property.
It produces cardiovascular effects similar to isoflurane except coronary steal phenomenon.
Induction with desflurane is unpleasant as it can lead to coughing, breath holding and laryngospasm.
It can also be used in day care surgery.
Methoxyflurane:
It is the most potent inhalation agent(least MAC).
It has the slowest induction and recovery.
Highest blood gas partition coefficient.
It can lead to high output renal failure.
Highest amount of fluoride content.
It should not be used in closed circuit(reacts with rubber tubing of the closed circuit).
Desflurane has the lowest boiling temperature 24 degree Celsius
whereas methoxyflurane has the highest boiling point 104 degree Celsius.
other important features
Trilene has maximum analgesic activity.
Ether has maximum muscle relaxant activity.
All inhalational agents increase cerebral blood flow(maximum with halothane)
as well as intracranial tension(maximum with halothane and ether).
Halothane, chloroform and methoxyflurane are hepatotoxic
whereas methoxyflurane and sevoflurane are nephrotoxic.
accidental injection of thiopentone in the arteries
it can lead to thrombosis and vasoconstriction that may progress to ischemia and gangrene.
It is accompanied by very severe pain.
This condition is treated by leaving the needle in situ(needle should not be withdrawn),
dilution of injected thiopentone with saline,
immediate heparinization and papaverine injection to relieve spasm.
Vasodilators, steroids, lignocaine and urokinase can also be employed.
Brachial plexus and stellate ganglion block should be performed.
Barbiturates are absolutely contraindicated in acute intermittent porphyria.
Etomidate:
it doesn’t interfere with cardiovascular functions.
Therefore is the agent of choice for aneurysms surgeries and cardiac disease.
It causes minimal respiratory depression.
Maximum incidence of nausea and vomiting is seen with the use of this agent.
It can produce myoclonus.
Injection of etomidate is painful and may result in thrombophlebitis.
It can lead to adrenocortical suppression.
Vitamin C deficiency can also develop with the use of etomidate.
A. benzodiazepines:
important benzodiazepines are diazepam, lorazepam and midazolam.
These are not analgesic agents.
However these possess muscle relaxing and anticonvulsant property.
Lorazepam is the most commonly used benzodiazepine in pre-anaesthetic medication.
Midazolam is used for day care surgery.
These agents may cause sedation and anterograde amnesia.
Inhalational agents:
These agents are stored in the cylinders and are delivered to the patient through Boyle’s machine.
Colour coding of the cylinders for identification and the pin index system is present for the safety
so that only the required cylinder can fit in the machine at that site.
Colour coding of cylinders
N2O – blue.
Cyclopropane – orange.
Air – grey body with white shoulders.
O2 – black body with white shoulders.
CO2 – grey.
Helium – brown.
Entonox – blue body with white shoulders.
Pin index system
Air – 1,5.
O2 – 2,5.
N2O – 3,5.
CO2 - >7.5% - 1,6.
CO2- <7.5% - 2,6.
Cyclopropane – 3,6.
Entonox – 7.
Two important properties of an inhalational agent
is its minimum alveolar concentration(MAC) and blood gas partition coefficient.
Ether
Ether also has a very high value of this coefficient 12.
Therefore it is also a slow acting agent.
Due to its slow onset of action, we can differentiate the four stages of general anaesthesia
whereas with modern anaesthetics like desflurane, these stages are hardly discernible.
Breathing circuits:
Open: ether, chloroform and ethyl chloride may be used.
Semi-closed(Mapelson circuit):
Type B: not used
Type C(water’s): not used
Type D(bain’s): most commonly used circuit and circuit of choice for controlled ventilation(FGF=1.6 X RMV)
Type A(magill): circuit of choice for spontaneous ventilation. Fresh gas flow(FGF = respiratory minute volume(RMV).
Type E(ayre’s T piece): pediatric circuit.
Type F(Jackson Rees): most commonly used pediatric circuit.
Closed
Closed: sodalime or barylime are used to absorb CO2.
barylime donot contain silica and is less efficient than sodalime.
It is preferred in conditions with high production of CO2(e.g. malignant hyperthermia).
Trilene, sevoflurane and methoxyflurane should not be used in closed circuit.
Concentration effect
is seen with agents like N2O, which are administered in high concentrations.
Due to high concentration, when diffusion occurs from alveoli to blood,
there is generation of negative pressure in the alveoli
that leads to more removal of anaesthetic gas from the cylinder.
Second gas effect
is seen when another inhalational agent like halothane is administered along with N2O.
Due to generation of negative pressure,
second gas is also taken in from the cylinder.
Diffusion hypoxia
occurs when supply of N2O is stopped while recovery from anaesthesia.
It can be prevented by 100% oxygen inhalation for a few minutes before discontinuing N2O.
Other side effects due to N2O
Methemoglobinemia and laryngospasm may occur due to the presence of impurities like nitric oxide NO and nitrogen dioxide(NO2).
Bone marrow depression and megaloblastic anemia due to vitamin B12 deficiency may also occur.
Latter can result in subacute combined degeneration of spinal cord.
N2O use is contraindicated in pneumothorax and volvulus
because it may lead to development of high pressure in the closed cavities in the body like gut, pneumothorax and pneumoperitoneum.
It is used as a supplement to anaesthesia because it is not a complete anaesthetic. It is also used as a carrier gas for inhalational agents like halothane.
Halothane:
It is a colourless, volatile liquid.
It is a non-irritant, non explosive and pleasant smelling agent.
It is stored in amber coloured bottles and contains thymol(0.01%) as preservative.
It is good anaesthetic but very poor analgesic agents.
Enflurane:
It is a halogenated ether.
It is inflammable at high concentrations >5%.
It is contraindicated in epilepsy as it can raise intracranial tension and produce tonic clonic seizures.
Like other new agents, it is also not a good analgesic.
Sevoflurane:
it is the inhalational agent of choice for induction in children.
It is a very good muscle relaxant but poor analgesic agent.
It should not be used in closed circuit because it can produce a nephrotoxic metabolite, compound A.
Tricholoroethylene:
trilene is the most potent analgesic agent.
It should not be used in closed circuit because reaction with soda lime can result in
the production of phosgene gas responsible for acute respiratory distress syndrome
and dichloroacetylene(neurotoxic to 5th and 7th cranial nerves).
It can be used in analgesia for labour.
Cyclopropane:
it is highly inflammable and explosive agent.
Colour of its cylinder is orange.
It is the inhalational agent of choice in hemorrhagic shock(increases BP by increasing sympathetic tone).
It should be stopped slowly because sudden discontinuation may result in hypotension(cyclopropane shock).
Chloroform:
it is a cardiotoxic agent and can result in ventricular fibrillation.
It is also hepatotoxic.
It can cause profound hyperglycemia.
Carbondioxide:
5% concentration is used for creating pneumoperitoneum in laparoscopy.
Colour of its cylinder is grey.
Helium:
it is lighter than air.
Mixture of 80 % helium and 20% oxygen is used in cases of tracheal obstruction.
Intravenous agents:
these may be fast acting used for induction or may be slow acting.
Methohexitone:
it is also an ultra short acting barbiturate.
It is 3 times more potent than thiopentone.
It induces seizures, therefore it is the agent of choice for electroconvulsive therapy.
Neuroleptic agent:
droperidol is a D2 blocker.
It is used along with fentanyl to produce neurolept analgesia and neurolept anaesthesia.
It can produce extrapyramidal symptoms.
Drugs useful for day care surgery:
Desflurane
Midazolam
Sevoflurane
isoflurane
Alfentanil
Propofol
Mivacurium(muscle relaxant)
Individual drugs
Inducing agents:
slow acting agents: