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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