Local Anaesthetics 4th year MBChB tutorial

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!

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

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

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)

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

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!

Physiology

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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