L07 General Anaesthetics Flashcards
What is general anaesthesia (GA) used for?
To produce unconsciousness & lack of responsiveness to all painful stimuli
- i.e. inhibition of sensory & autonomic reflexes
- i.e. involves a triad of hypnosis, amnesia & analgesia (sleep-inducing, memory loss of painful experience & elimination of pain sensation)
- Provide conditions for surgical interventions or skeletal muscle relaxation
Endpoint: Keep patients safe & alive upon GA reversal
What are some additional considerations required when a patient undergoes GA?
Control of normal physiology w/ mechanical intervention:
- Maintenance of breathing & O2 levels
- Maintenance of body temperature
- Maintenance of heart rate
Describe what the general stages of anaesthesia are.
1) Pre-assessment / Pre-medication
2) Induction of anaesthesia
3) Airway management
4) Maintenance of anaesthesia
5) Reversal of anaesthesia
6) Post-operative / Post-anaesthesia care
What constitutes an ideal GA?
1) Unconsciousness
2) Analgesia
- To inhibit subconscious reflexes to pain
- Mutually exclusive from amnesia!!
3) Muscle relaxation
4) Brief & pleasant
5) Depth of anaesthesia can be raised & lowered w/ ease
6) Minimal ADR
7) Large margin of safety
What triad of properties should be balanced for an effective GA?
Pain relief + inhibition of reflexes + unconsciousness
- To ensure that induction of GA is rapid & smooth
- AND analgesia & muscle relaxation are adequate
A single GA agent is sufficient to maintain a balanced anaesthetic effect. True or false?
False.
There is NO SINGLE AGENT that has ALL the properties of an ideal GA!
INH + IV GA are the most commonly used combination GA to effect a balanced anaesthetic effect.
Which classes of drugs are most commonly used as a combination for GA?
1) Short-acting barbiturates: induce anaesthesia
2) Neuromuscular blocking agents: muscle relaxation
3) Opioids & nitrous oxide: Analgesia
What physiochemical property of inhalant GA determines its duration of onset?
Blood solubility.
The higher the blood solubility of INH GA, the slower the onset of anaesthesia.
- GA stays in the blood & more resistant to move into CNS.
- However, faster onset DON’T mean higher GA potency; slower onset DON”T mean low GA potency!!
List some inhalant GA available for anaesthesia.
1) Volatile liquids (i.e halogenated hydrocarbons)
- HIDES: Halothane, isoflurane, desflurane, enflurane, sevoflurane
- Needs to be vaporised before inhalation
2) Gases: Nitrous oxide
- Fast onset but poor GA potency
Explain the proposed mechanism of action of inhalant GA.
1) Enhance neurotransmission at inhibitory synapses via allosterically increasing GABA receptor sensitivity to action by GABA itself.
- i.e. positive allosteric modulator; reversible in nature
AND
2) Depress neurotransmission at excitatory synapses via blocking glutamate neurotransmitters from acting on NMDA receptors thus preventing NMDA receptor activating
- i.e. negative allosteric modulator
Explain what ‘minimum alveolar concentration’ (MAC) means?
Index of inflation anaesthetic potency
- i.e. low MAC = high anaesthetic potency
Defined as the minimum concentration of drug in alveolar air that will produce immobility in 50% of patients exposed to a painful/noxious stimuli.
List all the inhalant GA in decreasing potency.
In increasing MAC: Halothane = 0.75% (potent) Isoflurane = 1.2-1.4% (potent) Enflurane = 1.7% (potent) Sevoflurane = 2-2.2% (potent) Desflurane = 6.3% Nitrous oxide = 105-110%
Concept of MAC values alter with age, condition, concomitant administration of other drugs etc.
To produce therapeutic effects, an inhalation anaesthetic need not reach a sufficient CNS concentration to suppress neuronal excitability. True or false?
False.
To produce therapeutic effects, an inhalation anaesthetic MUST reach a sufficient CNS concentration to suppress neuronal excitability.
Which host and drug properties influence the absorption rates of INH GA?
1) Concentration of anaesthetic in inspired air
- Higher conc. in inspired air = higher rate of GA uptake in blood
2) Blood solubility of GA
- Higher blood solubility of GA = higher rate of GA uptake in blood = slower onset
3) Blood flow through lungs (i.e. perfusion)
- Faster blood flow thru lungs = higher rate of GA uptake into blood
List all the inhalant GA in decreasing blood solubility.
In decreasing blood solubility: Halothane = 2.3 Enflurane = 1.8 Isoflurane = 1.4 Sevoflurane = 0.69 Nitrous oxide = 0.47 (poor)
What factors influence the distribution of INH GA?
Determined by regional blood flow:
- Highly perfused organs such as brain, lungs, liver & heart will receive GA first
- Anaesthetic levels in highly perfused organs (i.e. central compartment) equilibrate quickly after administration.
How are INH GA eliminated from the body?
1) INH GA are excreted almost entirely through the lungs via expiration.
- Minimal hepatic metabolism; however, some metabolites can be toxic!
2) Factors that determine uptake also determine rate of elimination
- If blood flow to brain is high, INH GA levels will also drop rapidly when administration is stopped.
Nephrotoxic: Inorganic fluorides of isoflurane, enflurane & sevoflurane
Hepatotoxic: Halothane
What are the clinical indications relating to the use of nitrous oxide?
1) Analgesia for dentistry & during delivery (due to high analgesic properties when used alone)
2) GA (possibly as an adjunct to other volatile liquid INH GA due to low potency / high MAC)
- Supplement analgesic effects of primary anaesthetic
What are some important clinically significant properties of halothane?
- Volatile liquid, non-flammable & non-irritating
- Potent (MAC 0.75%)
- Medium onset & recovery due to highest blood solubility of 2.3
- However, little or no analgesia until subconsciousness supervenes
- Relaxes skeletal muscle & potentiates skeletal muscle relaxants
What are some possible side effects of halothane?
1) Dose-dependent respiratory depression
2) Depression of cardiac output:
- Resulting in bradycardia, arrhythmia, hypotension & dysrhythmia
3) Halothane-associated hepatitis
Which drug is contraindicated when a patient is administered with halothane as INH GA?
Epinephrine / Adrenaline
What are some important clinically significant properties of isoflurane?
Similar to halothane
- Volatile liquid, non-flammable & non-irritating
- Potent (MAC 1.4%)
- Medium onset & recovery due to relatively high blood solubility of 1.4
- Pungent smell
What are some possible side effects of isoflurane?
1) Depression of systemic vascular resistance:
- Resulting in bradycardia, arrhythmia, hypotension & dysrhythmia
2) Nephrotoxicity (due to inorganic fluoride metabolite)
What are some important clinically significant properties of sevoflurane?
- Volatile liquid, non-flammable & non-irritating
- Potent (MAC 2%)
- More rapid onset & recovery due to very low blood solubility of 0.69, amongst volatile halogenated hydrocarbons
What are some possible side effects of sevoflurane?
1) Depression of systemic vascular resistance:
- Resulting in bradycardia, arrhythmia, hypotension & dysrhythmia
2) Nephrotoxicity:
- Due to inorganic fluoride metabolite via hepatic metabolism
- When exposed to CO2 adsorbents in anaesthetic machines, sevoflurane becomes unstable & degrade in to potentially nephrotoxic metabolites.
Which drug is contraindicated when a patient is administered with sevoflurane as INH GA?
CO2 adsorbents
What are some important clinically significant properties of nitrous oxide?
- Non-flammable, odourless gas
- Rapid onset & recovery (due to poor blood solubility of 0.47)
- Lack potency (due to MAC 105-110%)
- Gives analgesia & amnesia, BUT NOT complete unconsciousness or surgical anaesthesia (i.e. subconscious pain reflexes may still be active!
- No muscle relaxant effects
What are some possible side effects of nitrous oxide?
Postoperative nausea & vomiting
Which type of GA induces unconsciousness?
IV GA
Intravenous general anaesthetics can keep a patient asleep for long periods of time. True or false?
False.
IV GA only induces unconsciousness, BUT unable to keep one asleep for long.
What is one important consideration with regards to the use of IV GA in patients?
Need to ensure mechanical ventilation are in place!
- Most IV GA depresses respiration!
What are the advantages of using a combination of INH GA & IV GA?
1) Permit reduced dosage of INH GA
2) Produces effects that cannot be achieved by IV GA alone
- IV GA to induce; INH GA to maintain
List all examples of IV GA available.
KEMPT: Ketamine 1.5 mg/kg Etomidate 0.2-0.3mg/kg Midazolam 0.02mg/kg (for anxiolysis as well) Propofol 2-4mg/kg Thiopentone / Thiopental 4-7mg/kg
Describe the pharmacokinetic profile of thiopental.
Barbiturate with extremely high lipid solubility
A:
- Enters brain easily & rapidly w/ rapid onset of action (unconsciousness w/in 10-20s after IV)
- Ultra-short acting barbiturate w/in 10-20min when injected alone / w/o INH agents
- Duration of action depends on its clearance
D:
- Redistributes to less vascularised tissues
- Large Vd due to high lipophilicity
- Extensively bound to plasma protein as well
M:
- Slow hepatic metabolism into active metabolite (pentobarbital)
- Accumulation of pentobarbital results in prolongation of clinical action, leading to liver cirrhosis if unchecked
E:
- Less than 1% excreted unchanged
- Small amt of free drug can be excreted by glomerular filtration
- Potentially reabsorbed in tubules
Describe the mechanism of action of thiopental.
Potentiates GABA-A-mediated Cl- currents by binding allosterically at the barbiturate site of GABA-A receptors, leading to CNS depression via enhancing neurotransmitters at inhibitory synapses.
Describe the mechanism of action of propofol.
Potentiates GABA-A-mediated Cl- currents by binding allosterically to GABA-A receptors, leading to CNS depression via enhancing neurotransmitters at inhibitory synapses.
Which IV GA is extensively used in day surgeries?
Propofol
- Most common IV
Why is propofol extensively used as IV GA in day surgeries?
1) Ready-made in injectable form, no need to reconstitute
- Most common IV anaesthetic used in Singapore
2) Induction rate similar to thiopentone, recovery is more rapid
- Used for both induction and maintenance
3) Rapid onset of action: unconsciousness within 60 seconds
- Short duration of action: 3 – 5mins following single injection
- Rapid redistribution from brain to other tissues
- However, need continuous, low-dose infusion for extended effects.
What are some possible side effects of propofol?
1) Reduced postoperative vomiting
- May be related to antiemetic action
2) Significant CVS effect during induction:
- Hypotension (decreased BP) & negative inotropic (i.e. force) cardiac effect
What are some possible side effects of thiopental?
1) Greater tolerance & dependency than BZDs
2) More severe withdrawal effects than BZDs
- i.e. disturbed sleep, rebound anxiety, tremors & convulsions
3) Medullary depression & coma
- Impt. autonomic responses are heavily depressed at very high doses
- Absent in increasing dose of BZD due to plateau of dose-response curve, unlike positive correlation for barbiturates
Which selected populations should propofol be used with caution when administering as IV GA?
Elderly
Compromised cardiac function
Hypovolemia
Describe the mechanism of action of ketamine.
Depress neurotransmission at excitatory synapses via blocking glutamate neurotransmitters from acting on NMDA receptors thus preventing NMDA receptor activating.
What state is ketamine known to produce as part of its intended effect as an IV GA?
Dissociative anaesthesia
- Pt feel dissociated from environment, but still has awareness
- Altered state of consciousness
What are some possible side effects of ketamine?
CNS: Hallucination, disturbing dreams, delirium during recovery
- Reduced w/ premedication of diazepam or midazolam
Explain why ketamine is very popular in its use as IV GA in developing countries?
Only IV anaesthetic w/ analgesic property w/o need of INH GA
- Causes sedation, immobility, analgesia & amnesia as one drug
- Available as IM, PO & rectal formulations as well
- Suitable for continuous infusion w/o lengthening duration of action due to large Vd & rapid clearance
Which stereoisomer of ketamine is more potent as an INH GA?
S- > R+
- However, only available as a racemic mixture
What is the main intention behind the use of anaesthetic adjuncts?
List all available drug classes used as anaesthetic adjuncts.
Allow lower dose of GA.
1) BZDs
- Anxiolytics, amnesia, sedation prior to induction of anaesthesia
2) Alpha-2 adrenergic agonists (i.e. dexmedetomidine)
- Sedation prior to and/or during procedures in non-intubated patients
3) Analgesics (i.e. NSAIDs & opioids)
- Typically administered w/ GA to reduce anaesthetic requirements
4) Neuromuscular blocking agents (NMBA)
- Induction of anaesthesia to relax muscles (jaw, neck, airway) to facilitate laryngoscopy & endotracheal intubation
- Aids many surgical procedures & provide additional insurance of immobility
- Depolarising: Succinylcholine
- Non-depolarising: Vecuronium
What are the clinical indications of using midazolam IV as an anaesthetic adjunct?
1) Anxiolysis, amnesia and sedation prior to induction (perioperative period)
OR
2) Sedation during procedures NOT requiring GA (e.g. endoscopy)
How are the side effects of midazolam IV minimised?
Low-dose midazolam IV results in less CVS & respiratory depressing effect.
- Minimised by avoiding concurrent usage of other anaesthetic agents
- Inject midazolam slowly (over 2 or more min) & waiting another 2 or more min for full effects to develop before dosing again.
What are some important clinically significant properties of dexmedetomidine as an anaesthetic adjunct?
Highly selective alpha-2 adrenergic agonist
- Short term sedation (< 24h)
- ONLY produces sedation & analgesic effects; unreliable GA even at max dose
- Little respiratory depression
- Tolerable decrease in BP & heart rate
What are some possible side effects of dexmedetomidine?
Little respiratory depression
Tolerable decrease in BP & heart rate
Antiadrenergic SE: Hypotension, nausea, dry mouth, bradycardia
- Alpha-2 agonism results in antiadrenergic SE
Which drug class is contraindicated when a patient is administered with either succinylcholine or vecuronium as an anaesthetic adjunct?
Barbiturates (i.e. thiopental)
- Precipitates when mixed w/ NMBA
- Should be allowed to clear for IV line prior to injection of NMBA
Which opioid, when used as an anaesthetic adjunct, is not eliminated via hepatic metabolism?
Remifentanil
How is remifentanil eliminated from the body?
Hydrolysed by tissue & plasma esterases
Subsequently excreted by urine or as bile.
