General Anaesthetics Flashcards
What are GA used for?
- Produce unconsciousness & a lack of responsiveness to all painful stimuli (inhibiting sensory & autonomic reflexes)
- Provide conditions for interventions (eg. surgery - skeletal muscle relaxation)
Additional considerations when using GA
Control of physiology (Need to decrease HR, while controlling body temp)
Stages of General Anaesthesia
1) Pre-assessment
2) Induction of anaesthesia
3) Airway management
4) Maintenance of anaesthesia
5) Reversal/Emergency
6) Post-operative care
What constitutes an IDEAL general anaesthetic
- Unconsciousness
- Analgesia
- Amnesia
- Muscle relaxation
- Brief & pleasant
- Depth of anaesthesia can be raised or lowered with ease
- Minimal ADE
- Large margin of safety
Balanced Anaesthesia
- Pain relief, Unconsciousness, Inhibition of Reflex
What are the 2 kinds of GA that are used in combination?
1) Inhalation
2) IV
- Used in combination to ensure that induction is smooth & rapid
- Induction usually accomplished with short-acting barbituate (eg.thiopentone) then maintain with gaseous GA
Most commonly used:
1) Short-acting barbiturates (induction of anaesthesia)
2) NM blocking agents (muscle relaxation)
3) Opioids & Nitrous oxide (analgesia)
What determines onset of Inhalant GAs
Blood solubility
- Higher b.s, slower the onset
Classification of Inhalant GAs
1) Volatile liquids (Administer using agent-specific vaporizer)
- Halothane, enflurane, desflurane, isoflurane, sevoflurane
2) Gases
- Nitrous oxide
Proposed MOA of Inhalant GAs
1) Enhance neurotransmission @ inhibitory synapses
- Allosteric binding & increasing GABA receptor sensitivity to action by GABA itself
2) Decreasing neurotransmission @ excitatory synapses
- Blocking glutamate neurotransmitter acting on NMDA receptor
Minimum Alveolar Concentration (MAC) Concept
- Lower MAC, higher anaesthetic potency
- Alters with: age, condition, concomitant administration of other drugs
PK of volatile liquids GA
- Inhalant GA must reach [CNS] sufficient to suppress neuronal excitability
Absorption:
- Increased [anaesthetic] in inspired air, increased rate of GA uptake into blood
- Increased solubility of GA, increased rate of GA uptake into blood
- Increased blood flow through lungs, increased rate of GA uptake into blood
Distribution:
- Determined by regional blood flow
- Anaesthetic levels in tissues of highly perfused organs equilibrates with those in blood quickly after administration
Elimination:
- Eliminated almost entirely in lungs
(Volatile Liquids GA) Halothane
- Volatile, non-flammable, non-irritating
- Potent (MAC 0.75%)
- Rate of onset & recovery: Medium
- Little/no analgesia until unconsciousness supervenes
Adverse Effects:
- Respiratory depression (dose-dependent)
- Bradycardia & arrhythmia (may lead to hypot/s & dysrhythmia)
- -> Decrease in BP due to depression of CO
- Halothane-associated hepatitis
- -> can recover after stopping adm
- Relaxes skeletal muscle & potentiates skeletal muscle relaxants
(Volatile Liquids GA) Isoflurane
- Pungent smell
- Potent (MAC 1.4%)
- Rate of onset & recovery: Medium
Adverse Effects: Similar to Halothane BUT less hypot/s & arrhythmia
- Decreases BP due to decrease in systemic vascular resistance
(Volatile Liquids GA) Sevoflurane
- Potent (MAC 2%)
- Rate of onset & recovery: > Rapid
Adverse Effects:
- Metabolised in the liver to release inorganic fluoride (*Nephrotoxic)
- Unstable when exposed to CO2 absorbents -> Degrades to a compound that is potentially *nephrotoxic
*NOT for those with kidney failure
(Volatile Liquids GA) Nitrous Oxide
- Non-flammable
- Lack potency (MAC 105%)
- Rate of onset & recovery: Rapid
- Analgesia & Amnesia (but not complete unconsciousness/surgical anaesthesia)
Uses (Common in dental practice):
1) Supplement analgesic effects of pri anaesthetic
2) Used alone as analgesic agent
Adverse effects:
- Postoperative N/V
Use of Intravenous GAs
1) Used alone
2) Used to supplement effects of inhalation agents
Advantages of using combination of Inhaled + IV Anaesthetics
1) Permits dosage of the inhalation agent to be reduced
2) Produce effects that cannot be achieved with an inhalation alone
Properties of Intravenous GAs
- Induction agent that induces unconsciousness fast
- But does not necessarily keep you asleep for very long
- Most agents depress respiration
(Intravenous GAs) Thiopentone (Sodium thiopental)
- EXCEPTION: Combination used in GA*
- Barbiturate with extremely high lipid solubility
- Onset of action: Rapid
- Extensively bound to plasma proteins (small amount of free drug can be excreted by glomerular filtration + reabsorption tubules)
- Slow elimination
MOA: Potentiates action of neurotransmitter GABA on the GABA^A receptor-gated Cl- channels
i) Single-dose:
- Re-distributes to less vascularized tissues
- Ultra-short duration of action
ii) Multiple doses/infusion:
- Duration of action depends on clearance
Note:
- If liver cirrhosis: Active metabolite (phenobarbital) takes longer time to get metabolised, can result in prolongation of clinical action
(Intravenous GAs) Propofol
- Induction rate is similar to thiopentone, recovery is more rapid
- Onset of action: Rapid
- Duration of action: Short
Use:
- For both induction & maintenance (continuous low-dose infusion)
- Extensively used in “day surgery”
Adverse Effects:
- Hypotension: Significant CVS effect during induction (decreases b.p & negative inotropic)
Note:
- Reduced postoperative vomiting (may be related to anti-emetic action)
- Caution use in elderly/ pts with compromised cardiac function/ hypovolemic pts
(Intravenous GAs) Ketamine
- Rapid induction, responsiveness to pain is lost
- Dissociative anaesthesia
- Can cause sedation, immobility, analgesia & amnesia
- Large Vd, rapid clearance
Use:
- Continuous infusion w/o lengthening in duration of action
Adverse Effects:
- Unpleasant psychotic reactions (hallucination, disturbing dreams, delirium) during recovery from ketamine
- -> Risk of psychologic adverse reactions may be reduced with premedication of diazepam/midazolam (work on GABA receptors)
Note:
- Only IV anaesthetic with analgesic properties
Types of Anaesthetic adjuncts/Post-Op care
1) Benzodiazepines (Anxiolytics/amnesia/sedation)
- Prior to induction of anaesthesia
2) Alpha-2 Adrenergic Agonists
- Sedation prior to and/or during procedures in non-intubated patients
3) Analgesics
- Adm with GA to reduce anaesthetic requirement
4) NM Blocking Agents
- Induction of anaesthesia to relax muscles (jaw,neck,airway) to facilitate laryngoscopy & endotracheal intubation)
(Anaesthetic adjuncts/Post-Op care) Benzodiazepine - Midazolam (I/V)
Uses:
1) Anxiolysis, amnesia & sedation
2) Sedation during procedures not requiring GA (eg, endoscopy)
- Metabolism: Liver (Slower recovery in elderly)
Side effects:
- Compounded by concurrent usage of other agents
- Minimised by slow injection (over 2min, then wait for full effects to develop before dosing again)
(Anaesthetic adjuncts/Post-Op care) Alpha-2 Adrenergic Agonists - Dexmedetomidine (I//V)
Use: Short term sedation (<24hrs)
- Sedation & analgesic effects
Side effects (Little respiratory depression):
- Nausea
- Dry mouth
- Hypotension
- Bradycardia
- Tolerable increase in BP & HR???
(Anaesthetic adjuncts/Post-Op care) Analgesics - NSAIDs
Choice: Depends on duration of action
- Minor surgical procedure: COX-2 inhibitor/paracetamol
- Perioperative peiod: Opioids (Fentanyl, morphine)
Metabolism: Liver (Remifentanil - hydrolysed in tissue & plasma esterases)
Excretion: Urine, bile
(Anaesthetic adjuncts/Post-Op care) NM Blockers
Eg.
Depolarising - Succinylcholine
Non-depolarising - Vecuronium
Use:
1) Facilitate laryngoscopy & endotracheal intubation (relaxes muscles of jaw,neck,airway)
2) Aids surgical procedures & provide additional insurance of immobility
NOTE:
- Barbituates will ppt when mixed with muscle relaxants -> Should be allowed to clear from IV line prior to injection of muscle relaxant
