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LOCAL ANAESTHETICS
Nernst Equation
To calculate equilibrium for individual ions
Membrane potential = RT ln[X]out
FZ [X]in
R = Universal gas constant (8.31 J/K/mol)
T = Absolute temp
F = Faraday constant (coulombs per mole of charge)
Z = Valence
[61.5]
Na/K ATPase
Membrane relatively permeable to K+/impermeable to
Na+
Membrane Potential
IN
OUT
POTENTIAL
(mV)
Na
5
140
+60
K
150
5
-90
Cl
10
125
-70
Membrane Potential
• Resting Potential
– -70mV
• Gradients
– Electrical
– Chemical
Ion
Electrical
Chemical
Cl
Out
In
K
In
Out
Na
In
In
Goldman Constant Field Equation
• Includes membrane permeabilities for
each ion
Membrane potential
• Nernst values
• Small difference in K+
concentration, large effect on
membrane
[K]
Potential
2
-115
Stabilised
4.5
-90
Normal
8
-78
Excitable
[Na]
Potential
110
+53
140
+60
165
+64
Local Anaesthetics
• Binds open Na channels from the inside
LA - Structure
• Amides: lignocaine, bupivacaine, prilocaine
• Esters: cocaine, procaine, amethocaine
• Lipid-soluble hydrophobic aromatic group
• charged hydrophilic amide group
• bond between these two groups determines the class of the drug
Structure
• Lignocaine
• Bupivacaine
LA - Differences between esters and amides
• Ester linkage is more easily broken than the amide
• Ester less stable in solution, cannot be stored as long as amides
• Metabolism of esters results in the production of paraaminobenzoate (PABA)
• PABA associated with allergic reaction
• For these reasons amides are now more commonly used than
esters.
Physicochemical properties
Weak bases
• Speed of onset
- pKa
• Duration
- protein binding
• Potency
- lipid solubility
pKa
Definition
Negative logarithm to the base 10 of the dissociation constant
Law of Mass Action
Henderson-Hasselbach equation
At pKa 50% ionised/unionised
At pH 7.4 all LAs are more ionised than unionised (as pKa greater
than 7.4)
Unionised drug enters cell through the lipid cell membrane
Drug which is more unionised at physiological pH reaches target site
faster
Lignocaine has a faster onset of action than bupivacaine
pKa
Importance:
• lower pKa -> better absorption into nerve tissue
• higher pKa -> more effective blockade within nerve
Inflamed/infected tissue
• acidic environment
• reduced unionised fraction
• Increased blood supply – so faster washout
Physicochemical properties
Lignocaine
Bupivacaine
Relative Potency
1
4
Lipid solubility
150
1000
pKa
7.9
8.1
% unionised at pH7.4
25
15
% Protein bound
70
95
Lipid solubility
• Potency
• Highly lipid soluble drugs readily cross membranes
• Lipid partition coefficient
– Prilocaine 0.9
– Lignocaine 2.9
– Bupivicaine 28
Duration of action
• Determined mainly by protein binding
• Fraction available for metabolism
Metabolism and excretion
Esters (except cocaine)
•
•
•
•
rapid metabolism by plasma esterases
short half life
cocaine hydrolysed in the liver
ester metabolite excretion is renal
Amides
• metabolised hepatically by amidases
• slower, hence half-life longer
• can accumulate
Metabolism and excretion
Prilocaine
• metabolised most rapidly of amides– hepatic/renal
• O-toluidine
• high doses – methaemoglobinaemia
» Methylene blue
Levobupivacaine
• enantiomer of bupivacaine
• similar onset / duration to bupivicaine
• less cardio/cns toxicity
• expressed as mg of base (not mg of hydrochloride salt)
• so 13% more activity per given dose
EMLA
• 5% (2.5% lignocaine / 2.5% prilocaine)
• 2 compounds mixed to form substance with single set of
characteristics
• oil:water emulsion instead of crystalline
• not on mucus membranes
Types of Neurone
• C
Pain & temperature
Post ganglionic autonomic
• B
Pre ganglionic autonomic - warm limb
• A delta
Pain & temperature
Loss of pain sensation
• A-gamma
Motor to muscle spindles - proprioception loss
• A-beta
Touch and pressure loss
• A-alpha
Motor paralysis
Neurones
size (μm)
myelin
Conduction
speed (m/s)
A alpha
1-20
Y
70-120
A beta
1-20
Y
50-70
A delta
1-20
Y
30-50
A gamma
1-20
Y
<30
B
1-3
Y
<15
C
<1
N
<2
LA Toxicity
Toxicity depends on amount of free drug in plasma
• 1. Dose given
• 2. Rate of injection
• 3. Site of injection
– the greater the blood supply, the greater the systemic absorption
• interpleural > intercostal > pudendal > caudal > epidural > brachial
plexus > infiltration
• absorption from injection site
• direct intravascular injection
LA Toxicity
• CNS
– unintended epidural injection during posterior lumbar plexus
block
– LAs relatively small molecules
– readily cross the blood-brain barrier
• Lignocaine
3mg/kg ( +adr 7mgkg)
• Bupivacaine
2mg/kg
• Prilocaine
6mg/kg ( +adr 9mg/kg)
Cardiac SEs
• Class Ib, shorten AP
• direct depressant effect on myocytes in dose-dependent fashion
• myocardial contractility diminished at equivalent dose to achieve
sodium channel block
• example of frequency-dependent blockade
• blockade of conducting system increases activity in re-entrant
pathways
– VT/VF resistant to treatment
• highly lipid-soluble agents (bupivicaine) demonstrate different
receptor binding patterns, so-called 'fast in, slow out'
Treatment
• ABC, amiodarone
• Prolonged resuscitation may be required
• Consider cardiopulmonary bypass
• Intralipid®
– brand name nutritional supplement
– emulsion of fats
• Propofol/etomidate supplied in an emulsion of intralipid
•
•
•
•
•
20% Intralipid
1.5 mL/kg as an initial bolus, followed by
0.25 mL/kg/min for 30-60 minutes
Bolus could be repeated 1-2 times for persistent asystole
Infusion rate could be increased if the BP declines
CNS SEs
• CNS excitation
– light-headedness, dizziness
– circumoral paraesthesia
– acute anxiety, disorientation
• CNS Depression
– drowsiness
– siezures
– loss of consciousness
– respiratory hypoventilation / arrest
Treatment
ABC, oxygen
• seizures increase oxygen demand from 200 ml/min to 800 ml/min
• increased CO2 produces respiratory acidosis
• exacerbates CNS toxicity
• midazolam 1 - 2 mg iv bolus
• thiopentone 50mg
Prevention
• Intravascular marker: epinephrine 1:200 000 or 1:400 000
• Incremental injection: careful aspiration after 5ml of LA
• Monitoring: maintain verbal contact
Cardiac/CNS Ratio
• ratio of blood level producing irreversible cardiovascular collapse to
that level required to produce convulsions
• bupivicaine 4
• lignocaine 7
• the lower the ratio, the more potentially hazardous
• NO bupivicaine for ivra
Regional Anaesthesia of
Lower Limbs
Basic Setup
• Patient position
• Monitoring
– ECG
– Pulse oximeter (audible tone)
– NIBP (5 min cycle)
• Oxygen
• IV access and fluid
• Resuscitation Equipment
• Airway kit
• Assistant to operate nerve stimulator / inject LA
Basic Setup
• Skin disinfectant
• Skin LA
• Sterile gloves (scrub for LPB)
• Landmarks
• Sedation
– Midazolam 0.5 - 2mg IV bolus
– Fentanyl 25 - 50mcg IV bolus
Nerve Stimulator
• Peripheral nerve stimulator
– Positive to patient (ECG electrode)
– Negative to needle
• Attach syringe to tubing extension
• Set initial current to 2 mA, 2Hz
• Endpoint
– good twitch amplitude at < 0.5 mA
– reduction of twitch response > 0.25 mA
• N.A.P.T.A. (negative aspiration, positive twitch abolition) when 1ml
injected
Landmarks
• Anterior
– Anterior superior iliac spine
– Pubic tubercle
– Inguinal ligament (ASIS - PT)
– Posterior superior iliac spine
– Greater trochanter
– Femoral crease
Posterior
– Iliac crest / intercristal line
– Posterior superior iliac spine (PSIS)
– Greater trochanter (GT)
– Sacral hiatus (SH)
– Ischial tuberosity (IT)
Landmarks
Distal
• Femoral condyles
• Groove between biceps femoris (BF) and vastus lateralis (VL)
• Tibial tuberosity
• Fibular head
• Ankle malleoli
Anatomy
Anatomy
• A myotome is the group of muscles supplied by a nerve
• An osteotome is that part of the bone
whose periosteum is supplied by a
nerve root
•
•
•
•
•
•
•
•
•
•
•
1. Subcostal n.
2. ILIH
3. Genitofemoral
4. LFCN
5. Femoral n.
6. Obturator n.
7. Accessory Obturator
8. Inguinal ligament
9. ASIS
10. PT
11. Sympathetic chain
• 1. Sympathetic chain
• 2. ILIH
• 3. Genitofemoral
• 4. LFCN
• 5. Iliac crest
• 6. Sciatic n.
• 7. Sciatic notch
• 8. Femoral n.
Femoral Nerve Block
3 in 1 Block
Landmark:
Mid-inguinal point = Fem art
• 1cm below inguinal ligament
• 1cm lateral to artery
Stimulation
• patella twitch
• sartorius too superficial/lateral
• Distal pressure to get obturator (3 in 1)
LCNT
• Landmark
– ASIS
– 2 cm inferior, 2 cm medial
– Blunted needle
•
•
•
•
•
Perpendicular
Advance needle through skin
Discern a 'pop' or click as fascia penetrated
Fanwise distribution
10mls
Fascia Iliaca Block
• Landmarks
– ASIS
– Pubic tubercle
– Connect & divide into thirds
– Mark junction of lateral 1/3rd & medial 2/3rd
– Insert blunt needle 1 cm inferior to mark
• Perpendicular
• Advance needle through skin
• Discern 2 'pops' or clicks as fascia penetrated
– fascia lata, fascia iliacus
• 30mls
Sciatic Nerve Block
-Labat technique
Position
• Lateral position (Sim's) with operative side uppermost
Landmarks
• GT, PSIS
• Connect & mark midpoint
• From midpoint, draw perpendicular in caudad direction
• Join this to line from GT, sacral hiatus
Sciatic - Labat
Stimulation
• Initially direct stimulation of gluteus maximus
• Accept stimulation of tibial (plantar flexion)
• Hamstrings
– too medial
• Electric shocks down half of penis / vagina
– stimulation of pudendal nerve, toomedial
• Common peroneal (dorsiflexion + eversion)
– too lateral
Sciatic Nerve Block
-Raj technique
Landmarks
• Greater trochanter
• Ischial tuberosity
• Intermuscular groove
• Insert needle midpoint between GT / IT
• 1 - 2 cm along longitudinal groove
• Perpendicular in all planes
• 6 - 8 cm
Stimulation
• Stimulation of tibial (plantar flexion + inversion)
• Contraction of the hamstrings: may be direct stimulation
• If no motor response re-insert needle 1cm caudal along PSIS/IT line
Lumbar Plexus Block
Landmarks
• Lateral position with operative side uppermost
• Intercristal line (IC) / Tuffiers line = L4
• PSIS, line parallel to horizontal
• Aim to hit TP L4 and walk off above/below
• 8-12cm depth
• Mainly injecting into psoas – watch dose
Stimulation
• Patella twitch
Perpendicular in all planes
Location of TP and Nerve
Posterior View
Lumbar Plexus Block
• Too medial = paravertebral = epidural injection
• Hamstrings contraction
– L4 component of lumbosacral trunk nerve
– re-direct needle supero-laterally to initial pass
• Iliopsoas contraction upper part of thigh
– needle in psoas muscle
– further advancement risks penetration through anterior surface of
psoas & into adjacent structures
Ankle Block
• This block is often described as the blockade of 5 nerves
• 4 needle insertions, one of which will block 2 nerves
Anterior to medial malleolus: Saphenous nerve
• 1cm anterior to malleolus, 1cm proximal to inter-malleolus line (skin
crease)
• 5ml LA
Posterior to medial malleolus: Tibial nerve
• Posterior to posterior tibial artery
• Contact bone and withdraw needle by 1mm
• 5ml LA
Ankle Block
Anterior to lateral malleolus:
Deep Peroneal
– Insert needle between EHL and DP pulse; advance 1cm
– 5ml LA to block Deep peroneal nerve
Superficial Peroneal
– Withdraw needle to skin, re-direct towards lat malleolus
– Subcutaneous deposit 5ml LA along line to block Superficial
peroneal nerve
Posterior to lateral malleolus: Sural nerve
– Insert needle along line between lat malleolus & Achilles' tendon
– Subcutaneous deposit 5ml LA along line
PROCEDURE
SUGGESTED PNB
LP
Fem 3-in-1
TKA
Sciatic (Mansour / Labat)
ACL
Knee
LP
Fem 3-in-1
Sciatic (Mansour / Labat / Raj)
AKA
LP
Fem 3-in-1
Sciatic (Mansour / Labat / Raj)
BKA
LP
Fem 3-in-1
Sciatic (Mansour / Labat / Raj)
IM Nail
LP
Fem 3-in-1
Sciatic (Mansour / Labat / Raj)
PROCEDURE
SUGGESTED PNB
THA
LP
Fem 3-in-1
Hip
Fracture NOF
LP
Fem 3-in-1
Fascia iliaca
LP
Fem 3-in-1
IM Nail
Sciatic (Mansour / Labat /
Anterior)
Plan B
• GA
• Total LA amount-rescue infiltration
Dr Wakelings Rule of Regional
Anaesthesia
• It doesn’t work
TIME TO COOK
• “Failed” block often ends up with excellent post op analgesia
Technique
Blockade
Mean (mins)
Range
Sensory
9
3 - 20
Motor
16
3 - 75
Sensory
8
1 - 25
Motor
14
10 - 50
Labat
Subgluteus
Contraindication to RA
• Absolute contra-indications:
– Patient refusal
– Infection at proposed block site
– Overt septicemia
– Significant coagulopathy
– LA allergy
Complications
Prospective survey > 100 000 cases of regional anesthesia. Overall
neurological complication rate 0.03%
Estimated risk of complication
Per 100 000 cases
PNB
Spinal
Neuropathy
1.9
5.9
Death
0.5
1.5
THE END