General Anaesthetics Flashcards
What is GA used for?
- Produce unconsciousness and lack of responsiveness to all painful stimuli
- Balanced anesthesia:
~ Triad of hypnosis/unconsciousness, amnesia and analgesia/pain relief
~ Inhalation + IV used together
What are the stages of GA?
1) Pre-assessment
2) Induction of amnesia
3) Airway management
4) Maintenance of analgesia
5) Reversal/emergency
6) Post-op
What are the most common drug types for each point of balanced anaesthesia?
Induction:
- Short acting barbiturates
Muscle relaxation:
- Neuromuscular blocking agents
Analgesics:
- Opioids and nitrous oxide
What is the tissue distribution for gaseous anaesthesia?
Gas -> Lung -> Blood -> Brain and other tissues
Higher the solubility in blood = slower onset
- If it is not very soluble in blood, it accumulates in the brain quicker
~ Nitrous oxide has low solubility
~ Halothane has high solubility
~ NO < Sevo < Iso < Enflurane < Halothane
What are the classification of gaseous anaesthesia?
Gases:
- NITROUS OXIDE
Volatile liquids (need to be vaporised)
- HALOTHANE
- Enflurane
- Desflurane
- ISOFLURANE
- SEVOFLURANE
What is the MOA of GA?
1) Increases GABA receptor sensitivity to action
- Enhances neurotransmission at inhibitory synapses
- Positive allosteric modulator
2) Blocks glutamate neurotransmitter acting on NMDA receptor
- Depresses neurotransmission at excitatory synapses
- Prevents NMDA receptor activation
- Negative allosteric modulator
What is minimum alveolar potency?
- Anesthetic potency
~ Low MAC = high potency
~ Min. conc. of a drug in the alveolar air that will produce immobility in 50% of px exposed to a painful stimulus - Nitrous oxide has the lowest potency
~ Des < Sevo < Isoflurane (highest potency)
What are the pharmacokinetics of gaseous anesthetics?
- Must reach CNS conc. sufficient to suppress neuronal excitability
Absorption:
- Conc. of anesthetic in inspired air
- Solubility of GA
- Blood flow through lungs
Distribution:
- Determined by regional blood flow
- In highly perfused organs, tissue anesthetic levels quickly equilibrate with blood leveks after administration
~ Brain, liver, lungs, heart
Elimination:
- Almost entirely by lungs/exhalation
- Minimal hepatic metabolism
- Factors that determine uptake also determine elimination
Metabolism:
- Isoflurane and enflurane fluorides are nephrotoxic
- Halothane is hepatotoxic
What are the traits of halothane?
- Potent
- Medium rate of onset and recovery
- Analgesia
~ Little to no UNTIL unconsciousness occurs - Relaxant
~ Relaxes skeletal muscle and potentiates relaxants - Not compatible with epinephrine
Adverse effects
- Causes respiratory depression dose-dependently
- Decreases BP due to depression of CO
- Bradycardia or arrhythmia
~ Leads to hypotension and dysrhythmia
- May lead to halothane-associated hepatitis
What are the traits of isoflurane and sevoflurane?
Isoflurane:
- Pungent
- Potent
- Medium rate of onset and recovery
- Similar to halothane with less hypotension and arrhythmia
- Decreases BP mainly due to dec in systemic vascular resistance
Sevoflurane:
- Potent
- More rapid rate of onset and recovery
- Metabolized in the liver
~ Nephrotoxic
- Unstable
~ When exposed to CO2 absorbents in anesthesia machines
~ Degrades into a nephrotoxic compound
What are the traits of nitrous oxide?
- Odorless
- Rapid-onset and recovery
- Lacks potency
- Gives analgesia and amnesia
- Does not give complete unconsciousness or surgical anesthesia
~ Supplements the analgesic effects of primary anesthetic instead (eg NO + halothane)
~ If used alone, only as an analgesic agent in situations where px does not need to be unconscious (eg dentistry) - Not much effects on BP and respiration
Side effects:
- Major postop N/V
What are IV GA used for?
- Mostly as an induction agent to induce unconsciousness
~ But does not necessarily keep asleep for long - Depresses respiration
~ Manual respiration needed - May be used alone or to supplement gaseous agents
- THIOPENTONE
- PROPOFOL
- KETAMINE
- Etomidate
- Midazolam
What are the advantages of using gaseous + IV anesthetics together?
- Permits dosage of gaseous agent to be reduced
- Produces effects that cannot be achieved with inhalation alone
What are the traits of thiopentone/sodium thiopental?
- Barbiturate with high lipid solubility
~ Enters brain easily and rapidly
~ Within 10-20 sec after IV - Potentiates action of GABA on GABA ion channels
~ Causes CNS depression (due to hyperpolarization of cell) - Single dose
~ Re-distributes to less vascularized tissues (ultra-short duration) - Multiple doses
~ Duration of action depends on clearance - Slow elimination
- Large volume of distribution
~ Easily goes to peripheral organs (especially fatty ones) - Active metabolite (pentobarbital)
~ Complicates liver cirrhosis - Extensively bound to plasma protein
~ Small amount of free drug can be excreted by kidneys
What are the traits of propofol?
- No need to reconstitute
- Induction rate similar to thiopentone, but more rapid recovery rate
- Used both for induction and maintenance
- Short duration of action
~ Due to rapid redistribution from brain to other tissues
~ Needs continuous, low-dose infusion for extended effects - Has reduced postop vomiting
Side effects:
- Decreased BP, hypotension during induction
~ To be used w caution in elderly px, cardiac dysfunction px and hypovolemic px
What are the traits of ketamine?
- Causes dissociative anaesthesia
~ Consciousness is intact but feels dissociated from the environment - Rapid induction
- Can cause sedation, immobility, analgesia and amnesia
- Only IV anesthetic with analgesic property
- Metabolized in the liver, excreted in urine and bile
- Large volume of distribution rapid clearance
~ Suitable for continuous infusion without lengthening the duration of action
Side effects:
- Hallucinations, disturbing dreams, delirium during recovery
- Risk of adverse reactions may be reduced with diazepam or midazolam
What are anesthetic adjuncts?
BZP
- Anxiolytics, amnesia and sedation prior to induction
alpha2 adrenergic agonists
- Sedation prior to and during procedures in non-intubated px
Analgesics
Neuromuscular blocking agents
- Induction of anesthesia to relax muscles to facilitate laryngoscopy and ETT
What are the traits of midazolam?
- Used for anxiolysis, amnesia and sedation during induction
- Rapid onset of unconsciousness
- High therapeutic index
~ Lesser CVS and respiratory depressing effects compared to other IV anesthetics - Metabolized in the liver
~ Elderly tend to be more sensitive and have a slower recovery - Side effects are compounded by concurrent use of other agents
- Adverse effects can be minimized by slow injection of midazolam (> 2 mins)
What are the traits of alpha2 adrenergics?
DEXMEDETOMIDINE
- Highly selective
- Short-term sedation
- Sedation and analgesic effects
~ but not reliable GA even at maximal doses - Little respiratory depression
- Tolerable decrease in blood pressure and heart rate
Side effects:
- Nausea
- Dry mouth
- Hypotension
- Bradycardia
When are NSAIDs used as analgesics?
- Minor surgical procedures
- Opioids (morphine, fentanyl)
Duration of actions:
- Remifentanil (ultra short 10 mins)
- Sufentanil (15 mins)
- Alfentanil (20 mins)
- Fentanyl (30 mins)
Metabolized in the liver
- Except remifentanil (esterases)
Excreted in urine and bile
What are the traits of neuromuscular blockers?
- Administered during induction of anesthesia to relax muscles of the jaw, neck and airway
~ to facilitate ETT
Will precipitate barbiturates if mixed together so need to clear line first
Traits summary
Sedation
- Midazolam (BZP IV)
- Dexmedetomidine (a2 adrenergic IV)
Analgesic
- Dexmedetomidine (a2 adrenergic IV)
- NSAIDS (opioids iv)
- Halothane (slight, gaseous)
- Nitrous oxide (gaseous)
Anxiolysis
- Midazolam (BZP IV)
Amnesia
- Midazolam (BZP IV)
- Nitrous oxide (gaseous)
Muscle relaxant:
- Succinylcholine, vecuronium (neuromuscular blockers IV)
- Halothane (slight, gaseous)
- Isoflurane, sevoflurane
summary slide
- GA produce unconsciousness and insensitivity to painful stimuli
- Balance anaesthesia
- MAC : dec MAC → ^ potency
- Mechanism of action by
inhalation anaesthetics - Inhalation anaesthetics
eliminated through expired air - Principal adverse effects of GA:
depression of respiratory & cardiac performance - Nitrous oxide differs from other
Gas in: (1) very high MAC, cannot
be used alone to produce GA & (2)
high analgesic potency, tf
frequently combined with other
gas to supplement their analgesic
effects - Induction of anaesthesia usually
accomplished with a short-acting
barbiturate (eg. thiopentone) - IV Ketamine– dissociative anaesthesia
Ability of an adequate GA includes the ability to suppress ‘recall’ / awareness
