1. Local Anaesthetics
4th year MBChB tutorial

2. Introduction
Most of your clinical rotation in anaesthesia will expose you to the patient undergoing a general anaesthetic
Local anaesthesia is a very important and invaluable part of anaesthesia
Regional anaesthetic techniques have hopefully made a strong impression on you already!

3. Definitions Regional anaesthesia Local anaesthetic drugs
Loss of sensation in a circumscribed area of the body
Local anaesthetic drugs
Produce a reversible blockade of neural transmission in autonomic, sensory and motor nerve fibres, depending on the concentration of drug applied

4. History
Rendering body parts numb by physical means is an ancient practice
Cold to reduce pain sensation
“Refrigeration anaesthesia” ICE
Ethyl chloride spray
Ischaemia

5. Before regional anaesthesia as we know it could be practised, 3 things were needed:
Understanding of the physiology of nervous system
Development of reversible local anaesthetic drugs
Method of delivering the drug to the required area (needles and syringes invented in 1850s)

6. What does this have to do with local anaesthesia???
1884 – cocaine synthesised from cocoa leaves

7. Historical figures in Local Anaesthesia
1898 – August Bier, German surgeon, administered cocaine into the CSF on himself and his medical students!
The very first spinal described
Also the very first spinal headache!
From this point on, regional anaesthesia developed in leaps and bounds
General anaesthesia was already
40 years old!

8. Physiology

11. Classification of nerve fibres
Fibre type
Myelin
Diameter (um)
Conduction velocity (m.sec)
Function Aα
+++
15-20
70-120
Motor Aβ ++
5-12
30-70
Touch & pressure Aφ
5-10
Proprioception Aδ +
2-5
12-30
Pain & temperature B
1-4
3-15
Preganglionic autonomic C -
0.5-1
0.5-2
Postganglionic autonomic

12. Applied Physiology Sequence of nerve blockade from first to last:
Peripheral vasodilatation and increased skin temperature
Loss of pain and temperature sensation
Loss of proprioception
Loss of touch and pressure sensation
Motor paralysis

13. Pharmacology – chemical structure
Weak bases
Lipophilic ring
Hydrophilic amine
Intermediate chain:
ester or amide linkage

14. Esters or Amides Esters Amides Amethocaine Cocaine Lignocaine
Bupivacaine
Ropivacaine
Levobupivacaine
Prilocaine

15. Preparations of Local Anaesthetics
All local anaesthetics are weak bases
They are stored as salts of hydrochloric acid
The acidity enhances chemical stability and prolongs shelf life
Multi-dose vials also contain preservatives

16. Mechanism of Action – reversible sodium channel blockade
Unionised lipid-soluble
drug passes across
membrane
Active drug blocks Na channel from
within cell, and stops nerve conduction
Ionised again inside the axoplasm
due to the lower pH in cell

17. Physiochemical properties
Lipid solubility
The more lipophillic, the more potent, and therefore longer duration of action
Intermediate chain length
Increased chain length increases potency
Protein binding
The greater the protein binding the longer the duration of action
pKa
The pH at which 50% 0f drug is ionised and 50% is unionised

18. Only unionised drug can enter the nerve membrane
pKa
The pKa determines which percentage of drug exists in each form (ionised or unionised)
Local anaesthetic: HA (unionised form)
Dissociation: HA → H+ + A- (ionised form)
When the drug is injected into the body at pH of 7.4, a certain percentage of the drug will become ionised
Only unionised drug can enter the nerve membrane
Therefore pKa determines the rate of onset of local anaesthetic effect

19. Factors influencing the activity of LA
Vasoconstrictors: ADRENALINE
Decreases rate of systemic absorption of LA, making more available for nerve uptake
Improved analgesic quality
Prolongs duration of action
Decreases surgical bleeding
Decreases toxic side-effects
Concept of a “test-dose”
Carbonated
Alkalinisation
Temperature

20. Pharmacodynamics
Pharmacodynamics describe the effect of the drug on the body
Sodium channels are found everywhere in the body
This is why local anaesthetics have the potential to cause toxicity in the CNS and CVS

21. CNS Toxicity Symptoms and signs (in increasing order of severity)
Numbness of mouth and tongue
Dizziness and lightheadedness
Visual disturbances (stars or spots)
Tinnitus (ringing in the ears)
Irrational behaviour and speech
Convulsions
Unconsciousness and coma
Apnoea

22. Treatment of CNS Toxicity
Emergency situation: A B C’s
Airway – is the airway patent
Breathing – is the patient still conscious and breathing, if so, they can hyperventilate
LA toxicity is worse with a high CO2
Intubate if not breathing
Terminate the seizure
Thiopentone: 2 mg/kg (it is also an anticonvulsant)
Benzodiazepines

23. CVS Toxicity Cardiac sodium channel blockade →
slows myocardial conduction
myocardial depression
peripheral vasodilatation
Hypotension
Bradycardia
Tachyarrhythmias
Cardiac arrest
2 - 4 x the CNS toxic plasma levels
Bupivacaine toxicity occurs at low plasma levels → resistant VF

24. Treatment of CVS Toxicity
Hypertension & tachycardia
Hypotension
Fluids
Vasopressors: ephedrine or phenylephrine
Inotropes: adrenaline
Arrhythmias
Difficult to treat
Wait until the sodium channel blockade has worn off
May need prolonged treatment or resuscitation
VF from bupivacaine
Often resistant to defibrillation
Intralipid infusion
Try hyperventilation, magnesium

25. Intralipid® Lipid emulsion of soya oil, glycerol and egg phospholipids
Acts as a circulating lipid sink
Draws bupivacaine out of plasma and removes free fraction that was able to bind at Na channels

26. Prevention of toxicity
Use maximum safe dose
Aspirate regularly during injection
Adrenaline if appropriate
Test doses

27. Anaphylaxis Rare Linked more to the Esters
Metabolite: PABA from hydrolysis with plasma cholinesterase

28. Esters Cocaine Amethocaine Dose: 3mg/kg Surface anaesthesia in ENT
Potent vasoconstrictor
CVS stimulant
Addictive
Amethocaine
Dose: 1mg/kg
Topical eye drops
LA cream: AMETOP
Useful for venepunture

29. Amides Lignocaine Bupivacaine Dose: Used in many ways Versatile
3mg/kg
7mg/kg (with adrenaline)
Used in many ways
Versatile
Rapid onset
Moderate duration of action
Anti-arrhythmic
Bupivacaine
Dose: 2mg/kg
More potent than lignocaine
Long duration of action
Very cardiotoxic

30. Next up: Regional Anaesthesia
How to use the Local Anaesthetics…