Download 3. Local Anaesthetics lecture

3. Local Anaesthetics lecture:
LA drugs
Basic structure is made up of 3 components:
Lipophilic group
Hydrophilic group
Intermediate chain to connect the two which can be either an amine or an ester
Amides:
Lignocaine
Bupivacaine
L-bupivacaine
Ropivacaine
Esters
Procaine
Chloroprocaine
Tetracaine
Cocaine
Amides are metabolized by the liver whereas esters are hydrolysed by pseudo-cholinesterase.
Chemical and physical characteristics:
1. Lipid solubility
The higher the solubility, the more potent the drug
2. pKa (the pH where 50% of the drug is non-ionized)
The higher, the slower the onset of action
3. Protein binding
The higher the binding, the longer the duration of action
4. Isomerism
L-isomers are more potent than, but less cardio toxic the R-isomers
5. Nerve anatomy
Large diameter nerves are more difficult to block
Non-myelinated nerves are easier to block than myelinated
Nerves with high impulse traffic block easier than low activity nerves
Aδ (myelinated) and C(non-myelinated) fibers are pain fibers. Pain and temp are also
transmitted via these tracts (lateral spinothalamic and post. Columns)
Note: Bupivacaine is a long acting and potent drug.
Lignocaine is shorter acting and the onset is rapid
Bupivacaine is more potent than lignocaine as it is more lipid soluble and has a higher
pKa
and protein binding value
Conversion:
1% = 1g/100ml
= 1000mg/100ml
= 10mg/ml
(Multiply by 10)
S/E of local anaesthetics?
A) Immediate complications:
 Toxic reactions
 Hypotension
 Resp. distress
 Pain on injection
B) Intermediary complications:
 Motor paralysis
 Urinary retention
C) Late complications:
 Neurological damage:
o Nerve trauma
o Anterior spinal artery syndrome
o Arachnoiditis
o Pressure on the cord
 Pneumothorax
 Headache
Clinical signs and symptoms of toxicity:
CNS
CVS
Initial phase
Circumoral parasthesias
Tinnitus
Confusion
Initial phase
HT
Tachycardia during the CNS excitation phase
Excitatory phase
Convulsions
Intermediary phase
Myocardial depression
↓ Cardiac output
Hypotension
Depressive phase
L.O.C.
Coma
Resp. arrest
Terminal phase
Peripheral vasodilation
Severe hypotension
Sinus bradycardia
Conduction defects
Ventricular dysrythmias
Maximum doses:
Lignocaine w/ adrenaline
w/out adrenaline
7mg/kg
3-4mg/kg
Bupivacaine, L-bupivacaine, Ropivacaine w/ or w/out adrenaline
2mg/kg (max 150mg)
Therefore in 60 kg man:
Lignocaine w/ adrenaline
w/out adrenaline
Bupivacaine, etc w/ or w/out adrenaline
= 420mg
= 180-240mg
= 120mg
Mx of toxicity:
1. General
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2. Specific
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Anticipate toxicity
Have resuscitation equipment available before anaesthesia is administered
Maintain respiration-give O2 and ventilate the patient
CVS should be supported. Rx hypotension with α and β-agonists. (ephedrine
10mg boluses, phenylephrine 50-100μg boluses, adrenaline 5-10µg boluses)
Convulsions: IV thiopentone 100-200mg or diazepam 5-20mg
Ventricular fibrillation: Intralipid, K+ channel openers, Bretilium tosylate
o K+ channel openers improve AV conduction, but cause myocardial
depression
o Intralipid is main solute for TPN and propofol. Extremely effective
antidote to bupivacaine induced CNS collapse.
Advantages and disadvantages of regional:
Advantages:
 patient remains conscious
 maintain his own airway
 aspiration of gastric contents unlikely
 smooth recovery requiring less skilled nursing care as compared to general
anesthesia
Disadvantages:
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patient may prefer to be asleep
practice and skill is required for the best results
some blocks require up to 30 minutes or more to be fully effective
analgesia may not always be totally effective-patient may require additional
analgesics, IV sedation, or a light general anesthetic
4. Essentials of airway mx
Mx of laryngospasm after extubation? (5)
The best mx is the avoidance thereof. If it does happen:
 Give suxamethonium
 LM or try and intubate again (RSI)
 Bag and ventilate. The positive pressure should help open the airways to allow
oxygen in.
Formula for oxygen flux? (4)
How to manage a failed intubation? (5)
 Ventilate the patient
 Try laryngoscoping and intubating the patient again. (you have 3 attempts.
Ventilate between them)
 Between each attempt, try and improve the situation. (change the position, etc)
 If cant intubate after 3 tries, place LMA.
 If cant intubate and ventilate →Cricothyroidotomy
 Consider:
o Airway patency
o Risk of aspiration
o Need for intubation
o Need for GA
o Nature of m. relaxant used
5. IV induction agents
a) Barbiturates
Sodium thiopentone
ADME:
Absorption: IV
Distribution: all well-perfused organs
It has a high lipid solubility and therefore the blood-brain [] reaches
equilibrium within 1 min (short acting)
redistributes to other tissues (muscle and fat) causes short duration of
action
Metabolism: Liver (10-15%/hr)
85% plasma protein binding to albumin.
Binding decreased in pts with acidosis or hypoalbuminaemia. NB as the
unbound fraction of thiopentone is the active part, therefore if less bound,
more active… So one must decrease the dose.
Excretion: small percentage excreted unchanged in the kidneys.
Pharmacodynamics:
 CNS
o Sedation, hypnosis, anticonvulsant effects
o Protection in focal but not global ischaemia
o Beneficial for neurological compromised as:
 ↓ICP
 CMRO2 (cerebral oxygen consumption) ↓
 Resp
o Depression is dependant on:
 Dose
 Rate of administration
 Admin of other CNS ↓
o Sensitivity to CO2 is ↓
o Depression is self-limiting
 Larynx and bronchi
o May sensitize to reflex activity
o May more readily cause laryngospasm and bronchospasm in
susceptible pts
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CVS
o ↓CO due to peripheral vasodilation and depression of myocardial
contractility
o HYPOTENSION
 May be life-threatening in pt with fixed cardiac output as they
cant compensate by ↑stroke volume e.g. Constrictive
pericarditis, tight mitral or aortic valves, complete heart block,
etc.
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Extravenous injection
o Ulceration and damage to surrounding tissue
o Rx: inject 1% lignocaine to dilute and anaesthetize area
Intra-arterial injection
o Early
 White hand, intense burning pain
 Skin discolouration
 Delayed induction
o Late
 Oedema
 Blisters and ulceration
 Gangrene → loss of limb
S/E:
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C/I:
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Absolute
o Porphyria variegate
o Airway obstruction
o Fixed CO
o Shock
o Adrenal insufficiency
Relative
o Status asthmaticus
o Hypovolaemia
o Severe anaemia
o Severe liver disease dystrophica myotonia
b) Non-barbiturates
Propofol
Physio-chemistry:
 Highly soluble
 1% propofol dissolved in Intralipid(soybean oil, glycerol and egg phosphate)
 Easily colonized with bact
 Milky white
 20ml ampoule, with 10mg/ml
ADME:
Absorption: IV
Distribution: large volume of distribution
Half life 2-8 min
Elimination half-life 1-3 hours
Protein binding=98%
Metabolism: liver and probably the lungs
Conjugated to inactive glucuronides and sulphates
Excretion: kidneys, faeces and lungs
Renal disease does not influence kinetics
Pharmacodynamics:
 CNS
o Hypnotic. Lower doses can cause induction but onset is delayed
o Subhypnotic doses→sedation and amnesia
o ↓ICP by 30% (not as much as thiopentone)
o CMRO2 ↓ 36%
o Cerebral perfusion ↓10%
o ↓intra ocular pressure 30-40%
 Resp
o Apnoea (good for putting in LMA)
o ↓resp rate for at least 2 min
o ↓minute volume for at least 4min
 CVS
o 25-40% ↓ in SBP during induction (X use in Hypovolaemia)
Other non-hypnotic uses of propofol:
Antiemesis
Antipruritic
Sedation
Etomidate
The 4-5 B’s
Brand
Beweging
 Associated with grand mal epilepsy
 High incidence of myoclonic movements
Braking
 Nausea and vomiting in 30-40%
Bynier
 Inhibits the synthesis of adrenal gland hormones
Baie stabiel
 Minimal ↓ of CVS
 Less than 10% change in Mean arterial pressure
 10% increase in heart rate (minimal)
Benzodiazepines
2 commonly used: Diazepam 5mg/ml in 2ml ampoule
Poorly soluble in H2O, dissolved in 40% propylene glycol
IM painful and poorly absorbed
Midazolam 1or 5mg/ml in ampoule
Water soluble
Low incidence of pain after IM/IV
Closed ring structure with phys pH of 7.4 may enhance
lipid
solubility
Most lipid soluble as well as most potent benzo available
ADME:
Absortion: IM/IV
Distribution:
Metabolism: Liver (microsomal or glucuronides conjugation)
Diazepam: 2 active metabolites (desmethyldiazepam, oxazepam)
Therefore prolonged effects and half-life of 96hours
Midazolam: rapid oxidation of ring, no active metabolites. Short action
Elimination: significant differences
Termination due to redistribution from GABA receptor to less fat rich
tissue.
Uses:
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Anxiolysis
Sedation
Induction and maintenance of anaesthesia
Decrease MAC of halothane by 30%
Anterograde amnesia
Increase threshold for convulsions of LA
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Interindividual variation with midozalam biggest prob
Thrombophlebitis
Prolonged effects if combined with opiate
Synergism with induction agents, opioids, sedatives in comb with benzo’s to
give severe resp depression and drop in arterial BP
S/E:
Ketamine:
ADME:
A: IM/IV/PO/PR
D: very fat soluble
M: liver (microsomal)
E:kidney
Pharmacodynamics:
 CNS
o 1-2mg/kg
o Induces cataleptic state
o Onset of action 30sec-1min and in signified by nystagmus
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Resp
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CVS
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Protective reflexes (corneal, cough, swallowing)retained to an extent
↑lacrimation, salivation, skeletal m. tone
Good bronchodilator
Unwanted S/E: hypersalivation (give anticholinergic)
CVS stimulation(releases Nor-adrenaline and inhibits uptake of
catecholamines)
o Can block this with barbiturates or benzo
o The ↑NA causes HT, tachycardia and ↑CO
7. Muscle relaxants
Contra-indications for the use of scoline? (5)
Absolute:
Spinal cord injuries
Burns patients from 24hrs→20-60days
Relative:
Severe trauma
Severe intra-abdominal sepsis
Prolonged immobilsation (as more extra-junctional receptors have formed)
Disuse atrophy
CNS injury/infection from 10 days→60days after insult
S/E of scoline:
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Scoline apnoea
Massive release of potassium
Myalgia
Malignant hyperpyrexia
Masseter muscle spasm (in children)
Hypersensitivity
Signs of inadequate muscle relaxation?
Difference cisatracurium and atracurium:
Isomer number
breakdown
Duration of action
Renal failure
Atracurium
10
Hoffmann elimination and
ester hydrolysis
Shorter than
Drug of choice
Cisatracurium
1
Only Hoffmann elimination
Longer than
Not drug of choice
Breakdown of atracurium:
 Hoffmann elimination
o Spontaneous breakdown at N body temp and pH
o Breakdown product is called laudanosine
o Excreted by the kidneys
 Ester hydrolysis
According to the notes, the ED95 is:
 Dose required to decrease the amplitude of a single twitch (with a nerve
stimulator) with 95% 
 Indicates the potency of a muscle relaxant
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8.
Opioids
10. Fluids
Calcium:
Potassium:
18. Obstetrics
Aorta caval compression syndrome:
Dx: pt in supine position has a 30-56% ↓ in CO
Improves with left lateral tilt and when the baby is out of the uterus
When will present? Last trimester
What will present with?
o Paleness
o Hypotension
o Sweating
o Reflex bradycardia
Rx:
o Left lateral tilt (tilted 15 degrees to the left)
o Get the baby out
o Do not do CPR unless in left lateral tilt position
Pre-eclampsia
Triad:
 HT
 Proteinuria
 Generalized oedema
Very ill
Hypovolaemia
Hypersensitive to exogenous and endogenous vasopressors
May develop cerebral haemorrhage and pulm. Oedema
May have received magnesium sulphate therapy. (be careful. Non-depolarisers will lengthen
magnesium sulphate action)
Rx:
1.
2.
3.
4.
Fluids
Left lateral tilt
Pulse rate. If slow give ephedrine or adrenaline, not phenylephrine
Oxygen
19. Paeds
Fluid management for 23kg toddler undergoing inguinal hernia repair?
Show calculations. (4)
Maintenance: 1ml/kg/hr= 23mls per hour
Deficits: depends on how many hours NPO
Replacement: replace fluids lost per ml.
Then in 1st hour: maintenance + 50% deficits + replacement
In 2nd hour: maintenance + 25% deficits + replacement
In 3rd hour: maintenance + 25% deficits + replacement
Or use 50th percentile weight (kg) = (age x 2) + 9 (???)
Difference between adult and paediatric airway?
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Faster resp rate
Lower lung compliance
Greater chest wall compliance (chest wall collapse with inspiration & low
RV)
Hypoxic and hypercapnic ventilator drives not fully developed→ depressed
ventilation
Large head and tongue
Narrow nasal passages
Anterior and cephalic larynx
Long epiglottis
Narrowest part of airway at cricoids (if under 5 years)
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Short trachea and neck
Prominent adenoids and tonsils
Weak intercostals and diaphragmatic muscles
High resistance to airflow (paucity of small airways and alveoli)
Horizontal ribs
Blood volume of neonate (premature / fullterm); infant ; adult (F & M)?
Adult F:
Adult M:
27. CPR
The dose of adrenaline depends on the condition:
Hypotension: 10-20μg/as per response (wait to see what happens)
Anaphylaxis: 5-10µg/kg IV
Cardiac arrest: 10-20μg/kg IV
Can give adrenaline every 4min(the halflife of adrenaline)
Dose of joules for “defibrillation”
Adults:
Monophasic manual defibrillator= 360J
Biphasic manual defibrillator= 150-200J
Children:
4J/kg in both debfibrillator types (for first and subsequent shocks)
Why we ventilate with 100% oxygen:
The FRC of the lung includes the ERV and RV. This is +/- 35ml/kg
Lets now say that a person has 2500ml left in his lungs. This translates to 500ml of oxygen as
room air has only 20% oxygen.
The baseline oxygen consumption is 3.5ml/kg/min or 1 MET. (more in babies, can be up to 78MET)
So if this person is about 70kg, that would make his oxygen consumption per min 240ml.
Therefore if he had to go into cardiac arrest at the end of expiration, he would only have about 2
min of oxygen to spare before things became critical.
If we were to give him 100% oxygen, this would give him 10min (5x 2min).
Contributing causes that we must treat: (the H’s and T’s)