Anaesthetics, hypnotics and sleep management Flashcards
Define: anaesthesia. (20:41)
- Provision of insensibility to pain during surgical, obstetric (childbirth), therapeutic and diagnostic procedures
- Involves monitoring and restoration of homeostasis during postoperative period
How do local anaesthetics work? Examples?
- Blocks generation and conduction (propagation) of nerve impulses at local contact site
- Consciousness is maintained (e.g. dental work)
Examples: lignocaine, bupivacaine, ropivacaine(___caine suffix; cocaine was discovered as OG anaesthetic)
What are some clinical examples of local anaesthetic use?
Topical
- Nasal mucosa and wound margins
Infiltration
- Vicinity of peripheral nerve endings and major nerve trunks in dental practice
Regional
- IV injection leading to numbing of larger area of body in labour/childbirth (e.g. caesarean section)
What is the mechanism of action of local anaesthetics?
- Affects depolarisation
- Charged and uncharged LAs at equilibrium in the ECF
- Uncharged LAs pass through lipid bilayer, becoming charged in the ICF and bind to NaV ion channel on the inside
- Charged thus ‘trapped’ in the ICF (like base trapping), Na+ channels closed thus no influx = no depolarisation
How do general anaesthetics?
- Alters central neural processing
- Readily reversible loss of consciousness, with decreased response to painful stimuli and muscle tone
- Two types: inhalation and IV aneasthetics
What historical techniques for general anaesthetics were performed?
- ‘Knock-out’ blows
- Carotid artery compression (in the neck)
- Ingestion of ethanol and herbal mixtures
What are the three main stages of anaesthesia, and what do they entail?
A; Induction
- Inhalation or IV agents used
B; Maintenance
- Mainly w/volatile agents (good for even distribution of anaesthesia)
C; Recovery
- Monitoring to assure recovery (vitals in order)
What are the four main stages of analgesia WRT the depth of analgesia given?
I - Analgesic stage (onset)
II - Excitement stage (erratic)
III - Surgical anaesthesia stage (ideal)
IV - Medullary paralysis stage (danger)
Describe the Analgesic stage WRT the depth of anaesthesia.
• First stage WRT depth of anaesthesia; induction
- Less higher cortical function
- Consciousness not lost; but thoughts blurred (people tripping out before unconsciousness)
- Reflexes present
- Small and PAIN lost at this stage
Describe the Excitement stage WRT the depth of anaesthesia.
• II stage; more complex, unpredictable
- Cortical inhibitory centres depressed
- Increased muscle tone
- Potential vomiting; anti-emetic given before
- Temperature control lost; suppressing hypothalamus; give blanket
- A-rhythm of EEG desynchronised (brain activity)
- Respiration increased/irregular (suppressed respiratory centres in the brain)
Describe the Surgical anaesthesia stage WRT the depth of anaesthesia.
• III stage; predictable/ideal stage
- Slow synchronised EEG rhythms (brain)
- Regular slow breathing
- Medullary centres depressed; patient attached to artificial ventilator for respiration
- Reflexes lost
- Pupils dilated
Described the medullary paralysis stage WRT the depth of anaesthesia.
• IV stage; DANGER
- Loss of respiration (medullary centre v. depressed)
- EEG waves; small; lost
- Death
Describe the signs of the Analgesic (induction) stage WRT the depth of anaesthesia.
- Pupils; normal size, responsive to light (constrict)
- Respiration; regular
- Pulse; irregular
- BP; normal
Describe the signs of the Excitement stage WRT the depth of anaesthesia.
- Pupils; normal size, responsive to light (constrict)
- Respiration; slightly increased/irregular
- Pulse; irregular and fast
- BP; high (erratic)
Describe the signs of the Surgical anaesthesia stage WRT the depth of anaesthesia
- Pupils; normal size; UNRESPONSIVE to light (reflexes lost)
- Respiration; slow and regular
- Pulse; steady and slow
- BP; normal
Describe the signs of the Medullary paralysis stage WRT the depth of anaesthesia
- Pupils; dilated (medullary centre depressed?); remain dilated w/light
- Respiration; loss of
- Pulse; weak & thready
- BP; low
»> DANGER OF DEATH
What are the types of inhaled general anaesthetics? Give examples.
Gas:
- Nitrous oxide (NO; laughing gas)
Volatile liquids: - Halothane - Enflurane - Isoflurane - Sevoflurane - Desflurane (\_\_\_ane suffix; vaporised through anaesthetic gas machine through face mask)
What are the types of IV general anaesthetics?
Inducing agents (first stage of anaesthesia):
- Thiopental
- Methohexitone/methohexital
- Propofol
- Etomidate
Benzodiazepines (multiple function; muscle relaxant + calm/sedates patient):
- Diazepam
- Lorazepam
- Midazolam
Dissociative anaesthesia:
- Ketamine
What are the characteristics of an ‘ideal’ inhalation anaesthetic?
- Stable over range of temperatures
- Not degraded by light (storage)
- Odourless (don’t want it to be an irritant)
- Analgesic, anti-emetic, muscle relaxant properties
- Minimal respiratory depression
- Minimal CV effects
- Excreted completely by respiratory system
- Not metabolised/no active metabolites; don’t want clearance by kidney/liver (aid recovery stage)
How is the potency of inhaled analgesics measured?
- Defined as minimum alveolar concentration (MAC)
- Inhaled dose that prevents movement to a standard surgical stimulus (skin incision) in 50% of patients
- < MAC no. = more potent (less required)
- > MAC no. = less potent
What are the most/least potent inhalation anaesthetics according to MAC?
- Halothane = 0.75 (% in 100% O2; most potent)
- Isoflurane, Enflurane, Sevoflurane = 1.15 - 2.05%
- Nitrous Oxide (N2O) = 104% (least potent; can’t work on its own)
What characteristics of inhaled anaesthetics allow it to pass through the BBB? What variables need considering?
- Lipid soluble (target is brain)
Lungs > Blood > Brain - Partial pressure gradient; driving anaesthetic from respiratory pathway to the brain
- Steady state; for maintenance of anaesthesia; dependent on partial pressures of alveoli, blood and brain
What are the different phases that an inhalation anesthetic goes through from Lungs to Brain?
- Phase I; anaesthetic ‘wash-in’
- Phase II; uptake and distribution (blood-gas partition coefficient, cardiac output, alveolar-to-venous partial pressure gradient)
- Phase III; uptake and distribution to the brain
- Phase IV; elimination/recovery
What does Phase I of the inhalation anaesthetic journey (anaesthetic wash-in) entail?
Equilibrium between gas present in functional residual capacity (air lefts in lungs already) and anaesthetic achieved
What does a high blood-gas partition coefficient mean re. Phase II of an inhaled anaesthetic’s journey? Give an example
- Greater amount of anaesthetic must be dissolved in arterial blood in order to equilibrate with the alveoli
»> Slower rate of induction and recovery (need more)
E.g. halothane
What does a low blood-gas partition coefficient mean re. Phase II of an inhaled anaesthetic’s journey? Give an example
- Minimal amount of anaesthetic must be dissolved in arterial blood in order to equilibrate w/alveoli
»> Quick induction; blood is not target site, brain is»_space;> inducing anaesthetic faster means better recovery
E.g. nitrous oxide
What relevance is the blood-gas partition coefficient with inhaled anaesthetics?
- Relevant in Phase II of its journey
- Influences speed of anaesthetic induction e.g. nitrous oxide quickly saturates blood
What does a high cardiac output mean for inhaled anaesthetics?
- Phase II of its journey (uptake and distribution)
- High cardiac output means faster removal of the anaesthetic from alveoli to the peripheral tissues
- Slower to gain access to the brain
»> Peripheral tissue is NOT target
What does a low cardiac output mean for inhaled anaesthetics?
- Phase II of its journey (uptake and distribution)
- Low cardiac output results in slower removal of anaesthetic from alveoli to peripheral tissues
- Thus faster to gain access to the brain
What is the relevance of the rate of cardiac out WRT inhaled analgesics?
Influences speed of anaesthetic induction (low cardiac output good; faster gaining access to the brain)
What relevance is the alveolar-to-venous partial pressure gradient of anaesthetic?
- Anaesthetic transferred to peripheral tissues from arterial blood due to pressure gradient
- Venous circulation depleted of anaesthetic returns to lungs with more gas moving into the blood due to a partial pressure gradient
»> Anaesthetic concentration difference between alveolar (arterial) blood and venous; the higher the uptake, the slower the induction (BAD) - Will take longer to get to the brain
What does Phase III of inhaled anaesthetic intake entail?
- Uptake and distribution to the brain
- Partial pressure of alveolar blood is in equilibrium to the arterial blood and that in turn is in equilibrium with brain partial pressure
»> Desired (steady state); inhalation favourable as a result
Cerebral blood flow:
- Brian is highly perfused; rapidly achieves steady with partial pressure of anaesthetic in the blood
What does Phase IV of inhaled anesthetic intake entail?
- Similar to uptake and distribution w/nitrous oxide, exiting the body faster than halothane
(with low blood/gas coefficient)
How does the oil-gas partition coefficient influence inhaled anaesthetic uptake?
- The greater the lipid solubility, the better the drug gain entry to the brain via the BBB
E.g. N2O (nitrous oxide) has a low blood-gas coefficient, but has a high oil-gas partition coefficient; difficult to access the brain (halothane converse)
What is the typical journey like through the body for an intravenous anaesthetic?
- Once in bloodstream, some of the drug binds to plasma proteins (e.g. albumin); rest remains unbound and ‘free’
- Drug is transported through venous blood then systemic circulation, eventually gaining access to cerebral circulation
- Partial pressure gradient permits entry of the anaesthetic to the brain, where it takes effect
What are the preferred qualities of an intravenous anaesthetic?
- Unbound
- Lipid soluble
- Unionised
»> Cross the BBB the quickest
What IV anaesthetics are availible?
- Propofol
- Thiopental
- Etomidate
- Ketamine
Describe Propofol’s efficacy as an IV anaesthetic.
Which stage is it used in?
• Induction
- Short acting w/onset of 30 seconds, rapid recovery
- Decreases BP and intracranial pressure
- Does NOT provide analgesia (thus analgesic required)
- Accompanied by excitatory phenomena; muscle twitching, yawning, hiccups etc.
- Some antiemetic effects post-recovering
Describe Thiopental’s efficacy as an IV anaesthetic.
What is it similar to?
- Similar to propofol; fast acting within 1 minute (induction good)
- S/Es; may cause apnoea (cessation of breathing), coughing, chest wall spasm, laryngospasm
- Not commonly used; better agents availible
Describe Etomidate’s efficacy as an IV anaesthetic.
When is it used?
- Hypnotic agent; induces anaesthesia BUT lacks analgesia
- Benefit; little to no effects on CV system (favoured for CVD surgery)
- Used in sufferers of cardiac dysfunction
Describe Ketamine’s efficacy as an IV anaesthetic.
When is it used?
- Patient unconscious but appears awake; induces amnesia, hence dissociative anaesthesia (person has no recollection)
- Increases blood pressure and cardiac output (resulting in faster removal of drug from alveolar to periphery; bad)
- Potent bronchodilator; useful for asthmatics
»> Favoured in children or elderly - NOT favoured in young adults due to induction of hallucinations
What is the proposed mechanism of action of general anaesthetics?
- Increases GABAa/strychnine-sensitive glycine levels, resulting in increased Cl- influx (hyperpolarisation) and thus leading to greater INHIBITORY processes (most anaesthetics)
- Also; role in decreasing EXCITATORY transmission (inhibiting receptor subtypes?) e.g. lesser 5-HT3, neuronal nicotinic, Glu at NMDA/AMPA (ketamine, NOS)
What occurs when uncharged anaesthetic molecules concentrate in lipid membranes?
- Membrane expansion; conformational change
- Induces anaesthesia
What is the target site for general anaesthetics?
Reticular activating system:
- Arousal, sleep, wakefulness
> Results in transmission (radiation across cerebral cortex e.g. increased GABAa/strychnine-sensitive glycine) = CNS suppression/depression
Effects on:
- Visual impulses
- Reticular formation
- Ascending general sensory tracts; touch, pain, temperature
- Descending motor projections to spinal cord
- Auditory impulses
What is the typical practical anaesthesia regime for general anaesthetic goal, given no single agent is ideal?
• Premedication:
- Atropine; decrease secretions (muscarinic blocker)
- Benzodiazepine; sedation (if anxious)
• Fast induction:
- Thiopental (IV; within a minute)
• Maintenance:
- Isoflurane (inhaled)
• Muscle relaxation:
- Neuromuscular blocking drug e.g. BDZ dual effect
• Reduce pain:
- Analgesic (opiate; also used post-operatively)
