HNS20 General Anaesthetics Flashcards
Modern general anaesthetics
Only IV / Inhalation
—> NO oral preparation
Anaesthesia vs Analgesia
Anaesthesia: Absence of ALL sensations
—> general anaesthesia (GA): ALL sensations including consciousness
—> regional anaesthesia (RA) (e.g. nerve block): consciousness preserved
Analgesia: Absence of pain
Multiple ways of stopping pain
- Local anaesthetic
- block pain signal transduction (block Na channel) - Opioid
- modify pain signals - General anaesthetic
- shut off brain
- even though pain signals generated, conducted, but NOT interpreted
Modern balanced anaesthesia
3 targets:
- Unconsciousness (by GA)
- Analgesic (by opioid / LA)
- Muscle relaxation (by neuromuscular blocker)
Action of inhaled anaesthetics
MOA still not fully understood
—> till today NO antidote to GA
—> patient only wake up after body metabolise and excrete GA
Only thing known (part of mechanism):
- bind to GABA receptor (ligand-gated Cl channel) —> Cl channel open —> hyperpolarisation
Pharmacokinetics of GA
Narrow therapeutic window
- ED95 = LD05
- ED50 close to LD50
Potential danger of unconsciousness
- Airway obstruction (tongue fall back to touch posterior pharyngeal wall)
- Aspiration (due to vomit go into lung + loss of protective airway reflexes) —> aspiration pneumonitis
Intravenous GA
Must have following properties:
- ***Lipid-soluble (diffuse BBB to gain access to brain)
- ***Less context-sensitive (i.e. not accumulate)
- Thiopentone (thiopental)
- not commonly used now - Propofol
- Ketamine
- Etomidate
Pharmacokinetics of Thiopentone
- Ampule form (also contain NaHCO3 powder)
—> reconstitute with water —> alkaline solution —> thiopentone in ionised state
—> injected into body (pH 7.4) —> becomes unionised —> rapid conversion to highly lipid-soluble form
—> readily crosses BBB - Terminal t1/2: 12 hrs (i.e. takes 36 hours to leave body, does NOT mean patient wakes up after 36 hours, ∵ redistribution of thiopentone)
- Redistribution of thiopentone in body: from CNS (site of action) to other parts (muscles, fat) —> ∴ patient wake up before terminal t1/2
- Significance of redistribution: accumulation of drug in body (muscles / fat) —> longer context-sensitive half-time —> ∴ thiopentone not used repeatedly / continuous infusion (only used at initial stage: Anaesthetic induction), use other substance subsequently (如果唔係有排都唔醒)
Pharmacodynamics of Thiopentone
- ↓ vascular resistance (vasodilatation)
- ↓ cardiac contractility
- ***↓ arterial pressure
—> reflex ↑ HR - ***↓↓ respiration
Pharmacokinetics of Propofol
- very lipid soluble
- cannot be dissolved in water
- Terminal t1/2: 4.8 hrs
- accumulate much less extent —> much ***less context-sensitive —> good for IV infusion (no need to replace with something else after induction)
Target Controlled Infusion (TCI)
Input target plasma concentration to computer
—> computer calculate dosing rate accounting for accumulation, patient factors, pharmacokinetic variations etc.
—> can achieve precise level of sleep in patient (sedation / drowsiness / sleep / anaesthesia)
Pharmacodynamics of Propofol
- ***↓↓ vascular resistance (vasodilatation)
- ↓ cardiac contractility
- ***↓↓ arterial pressure —> Not desirable in patients with active bleeding (low BP)
- ***↓↓ respiration
Pharmacokinetics of Ketamine
Fairly similar to other IV GA
Pharmacodynamics of Ketamine
**No CVS depression, BUT cause **hallucination, nightmares
- ***↑ vascular resistance (vasoconstriction)
- ↑ cardiac contractility
- ***↑ arterial pressure —> good for patients with active bleeding, but undesirable for patients with IHD, hypertension
- ↓ respiration
Pharmacokinetics of Etomidate
Fairly similar to other IV GA
Pharmacodynamics of Etomidate
CVS stable, BUT causes **CNS excitation, a lot of **N+V
- NO change vascular resistance (vasoconstriction)
- NO change HR
- NO change cardiac contractility
- NO change arterial pressure —> good for ***cardiac anaesthesia patients who cannot tolerate hypertension / hypotension
- ↓ respiration
Inhaled GA
Volatile liquids (NOT gas) —> Vaporisers —> deliver a known concentration of GA vapour through intubation (endotracheal tube)
- 1st ever inhaled GA: Ether
6 drug:
- Isoflurane
- Desflurane
- Sevoflurane
- Enflurane (NOT used anymore)
- Halothane (NOT used anymore)
- Nitrous oxides (rarely used)
Vaporisers
Carrier gas (oxygen-air mixture) —> vaporising chamber OR bypass channel (controllable by dial) —> one exit
Minimum alveolar concentration (MAC)
Alveolar concentration of inhaled agent which prevents movement in response to a standard painful stimulation in 50% of subjects
—> Potency measure
—> NOT a fixed number
—> depends on patients’ age (children have ***higher MAC value —> harder to anaesthetised)
General number:
- Isoflurane: 1.15 vol%
- Desflurane: 7 vol%
- Sevoflurane: 2.05 vol%
How to measure alveolar conc of inhaled GA:
- Use concentration in mouth
MAC and Oil:gas partition coefficient
Measure of ***lipid solubility
Higher oil:gas partition coefficient —> more lipid soluble —> Lower MAC
Meyer-Overton correlation (log MAC vs log O:G) —> Negative linear relationship
Blood:gas partition coefficient
Predict ***pharmacokinetic properties of inhaled GA
—> Determine speed of Wash-in effect (how quickly Fa approaches Fi)
—> higher blood:gas partition coefficient —> slower wash-in
Fa: alveolar concentration
Fi: inhaled concentration
Wash-in effect: Fa / Fi
Fa: alveolar conc
Fi: inhaled conc
Faster to reach 1 —> goes into alveoli more quickly / build up of GA in alveoli —> faster onset
Affected by:
- Drug itself (Blood:gas partition coefficient: higher —> slower wash-in) (∵ carried away quickly, take longer time to build up in alveoli —> slower onset)
- Ventilation rate (higher rate —> faster wash-in)
- Cardiac output (higher CO —> slower wash-in) (∵ carried away quickly, take longer time to build up in alveoli —> slower onset)
Metabolism %
Inhaled GA metabolised to very little extent (a few %)
—> Not really metabolised
—> patient awake not by breaking down GA
—> excreted through ***elimination
1. Lungs (via concentration gradient with blood: Blood has higher concentration after vaporiser switched off)
2. Kidney unchanged
Pharmacodynamics of Inhaled GA
Similar to Thiopentone and Propofol
- ↓ CO
- ↓ Vascular resistance
- ↓ Arterial pressure
—> reflex ↑ HR
Factor important when considering GA in clinical perspective
Co-morbidities (e.g. heart disease)
Summary of choice of IV GA
- Thiopentone
- longer context-sensitive half-time
—> ∴ thiopentone not used repeatedly / continuous infusion (only used at initial stage: Anaesthetic induction), use other substance subsequently - Propofol
- much ***less context-sensitive —> good for IV infusion
- ↓↓ arterial pressure —> Not desirable in patients with active bleeding (low BP) - Ketamine
- No CVS depression, BUT cause ***hallucination, nightmares
- ↑ arterial pressure —> good for patients with active bleeding, but undesirable for patients with IHD, hypertension - Etomidate
- CNS excitation, a lot of N+V
- for cardiac anaesthesia patients who cannot tolerate hypertension / hypotension
