Classification - Chemical Properties
Esters
- Procaine
- Chlorprocaine
- Cocaine
- Benzocaine
- Tetracaine
Amides
- Lignocaine
- Bupivacaine
- Ropivacaine
- Prilocaine
- Mepivacaine
- Etidocaine
Classification - Duration of Action and Potency
Short DOA, low potency
- Procaine
- Chlorprocaine
Intermediate DOA and potency
- Lignocaine
- Mepivicaine
- Prilocaine
- Cocaine
Long DOA, high potency
- Bupivacaine
- Tetracaine
- Etidocaine
Factors affecting onset of action
- pKa
- pH
- Concentration
- Lipid solubility
- CT surrounding nerve
- Temperature
- Vasoconstrictors
Shortening onset of action
- Warm local anaesthetic
- Add sodium bicarbonate 1ml/ 10ml LA
- Add adrenaline separately
Factors affecting duration of action
- Lipid solubility
- Protein binding
- Dose
- Site of Injection
- Additives
Additives prolonging duration of action
- Alpha-adrenergic agonists (e.g. adrenaline, clonidine or dexmetetomidine)
- Opioids (neuraxial blocks)
- NaHCO3 (epidural blocks)
- Hyluronidase (ophthalmic blocks)
- Ketamine (caudal and epidural blocks)
- Magnesium (peripheral nerve - controversial)
- Dextrose (increase baricity for intrathecal injection)
Factors affecting absorption
- Site of injection (IVI > tracheal > intercostal > caudal > paracervical > epidural > brachial plexus > subcutaneous)
- Vasoconstrictors
- Protein bindings
Mechanism of action
Primarily: block conduction via Na+ channels by binding to the α subunit
Secondarily: block K+ and Ca2+ channels, and NMDA glutamate receptors
Metabolism and Excretion
Esters: plasma pseudocholinesterase (butyrylcholinesterase) breaks LA down to PABA (may trigger allergic reaction) - excreted unchanged in urine
Cocaine: partially metabolised by the liver, partially excreted unchanged by the kidney
Amides: microsomal P450 system (lignocaine > ropivacaine > bupivacaine)
Potency
Bupivacaine > levobupivacaine > ropivacaine > lignocaine > procaine
Toxicity - CNS
Initial Phase
- Circumoral paraesthesia
- Tinnitus
- Confusion
Excitatory Phase
- Convulsions
Depressive Phase
- Loss of consciousness
- Coma
- Respiratory depression
Management
- Stop injection
- Apply oxygen
- Secure airway
- Avoid hypoventilation and acidosis
- Treat seizures
- Midazolam 0.05-0.1mg/kg
- Propofol 0.5-1mg/kg
- Thiopentone 1-2mg/kg
Toxicity - CVS
Initial phase
- Hypertension
- Tachycardia
Intermediary phase
- Myocardial depression
- Decreased CO
- Hypotension
Terminal phase
- Peripheral vasodilation
- Severe hypotension
- Sinus bradycardia
- Conduction defects
- Dysrhythmias
Management
- Resuscitate according to ACLS
- Intravenous fluids, vasopressors
- Amiodarone and vasopressors instead of lignocaine and adrenaline
- Intralipid infusion
- CPR
- Insulin, 50% glucose, and potassium infusion (2IU/kg/hr, 2ml/kg/hr, 2mmol/kg/hr respectively)
Intralipid (Dosage)
- 20% solution
- 1.5ml/kg bolus IVI over 1 minute
- Followed by 0.25ml/kg/min infusion
- Bolus can be repeated twice at 5 minute intervals
- Infusion can be increased to 0.5ml/kg/min
Side Effects
- Direct neuronal toxicity
- Cauda equina syndrome (persistent neurological injury)
- Transient neurological syndrome (marked dysaesthesia)
- Allergy
- PABA from ester metabolism
- Methylparaben preservative in amide formulations
- Myotoxicity (hyper contraction, vacuole formation, edema, and necrosis)
- Hematological
- Reduced coagulation, enhanced fibrinolysis (lignocaine)
- Prilocaine (metabolised to orthotoline which oxidises Hb to metHb - treated with methylene blue 1-2mg/kg IVI over 5 minutes)
Contraindications to adrenaline
- CVS
- Unstable angine
- Arrhythmia
- Uncontrolled hypertension
- Uteroplacental insufficiency
- Drugs
- MAOI
- TCA
- Poor collateral flow (digits, penis)
- IV regional anesthesia
Maximum Dosages
- Bupivacaine, ropivacaine, tetracaine, and cocaine - 3mg/kg
- Procaine - 12mg/kg
- Lignocaine - 4.5/7mg/kg
1% means 1ml = 10mg
Duration of block
- Procaine and cocaine - 0.5-1 hour
- Lignocaine - 0.75-2 hours
- Tetracaine - 1.5-6 hours
- Bupivacaine and ropivacaine - 1.5-8 hours
Cocaine
- MOA: inhibit adrenaline and NA reuptake
- Use: topical anesthesia in ENT surgery and bronchoscopy
- Onset: 2-5 min
- Duration: 30-40 min
- Dose: 3mg/kg
Lignocaine - Uses
- Regional anesthesia (spinal -controversial, epidural, plexus and peripheral nerve blocks)
- Local infiltration
- Topical (4%)
- Intravenous regional
- Blunt hemodynamic response to intubation
- Antiarrhymic
- Acute postoperative pain
- Chronic neuropathic pain
- Neuro- and cardioprotective
Lignocaine - Dosing
Maximum dose
- Neonates - 3mg/kg (5mg/kg with adrenaline)
- Adults - 4.5mg/kg (7mg/lg with adrenaline)
Onset of action: rapid (5-10 min)
Duration of action: 30-60 min (120 min with adrenaline; half life 1.5-2 hours)
Bupivacaine - Uses
- Infiltration
- Topical mucous membrane anesthesia
- Spinal
- Epidural and caudal
Bupivacaine - Dosing
Maximum dose: 2-3mg/kg
Onset of action: 10-15 min
Duration of action: 180-300 min (120-480 with adrenaline) (half life 2.7 hours (8 in neonates))
EMLA
- Eutectic mixture of LA
- 2.5% lignocaine + 2.5% prilocaine in oil-water emulsion
- 3-5mm penetrating
- Applied 1-2 hours prior procedure; duration 1-2 hours
- Use: IV line insertion, suturing minor wounds, split thickness skin grafts, circumcision
- Dose:
- Paeds: 1g/10cm skin
- Adult: 1-2g/10cm skin
- Side effects: blanching, erythema, edema, metHb
- Alternative: Amethocaine (tetracaine 4%)
EMLA - Maximum Dosage
