Lecture 64 Local Anesthetics Richard D Minshall PhD Tobias Piegeler MD Departments of Anesthesiology and Pharmacology February 28th 2012 Outline A Pharmacologic aspects Basic structural characteristics Mechanism of nerve conduction Mechanisms of local anesthetic action Characteristics of local anesthetic action Metabolism Why are vasoconstrictors often added to the local anesthetic preparations B Clinical Aspects Problem based learning with clinical vignettes Chemical structure O Procaine C2H5 H2N C O CH2 CH2 N C2H5 Ester linked O Tetracaine CH3 HN C O CH2 CH2 N C4H9 O CH3 Bupivacaine NH C N CH3 CH3 Lidocaine NH CH3 O C CH2 C4H9 C2H5 N C2H5 Amide linked CH3 Lipophilic group Linker Hydrophilic group Definition Local anesthetics are drugs used to prevent or relieve pain in specific regions of the body without loss of consciousness reversibly block pain sensation by blocking nerve conduction Neural transmission Resting potential Action potential Mechanism of action Local anesthetics reversibly bind to the voltagegated Na channel VGSC block Na influx and thus block action potential and nerve conduction Local anesthetics Propagation failure VGSC 1 I II III IV LA Catterall WA Neuron 2000 26 1 13 25 VGSC 2 Pink Local anesthetic binding site in the inner cavity of the pore In Segment 6 of Domain IV IVS6 Helix Green Binding site for Tetrodrotoxin Catterall WA Neuron 2000 26 1 13 25 Influence of fiber type Local anesthetics Propagation failure Local anesthetics more effectively block small nerve fibers Different nerve fiber types Use dependent block Nerves with higher firing frequency and more positive membrane potential are more sensitive to local anesthetic block Influence of pH Low pH High pH Normal pH Reason for pH influence BH B H Na extracellular B BH H B BH intracellular closed open inactivated Metabolism 1 Most ester linked local anesthetics are quickly hydrolyzed by plasma cholinesterase exception cocaine 2 Amide linked local anesthetics undergo oxidative dealkylation oxygenation by monooxygenases and hydroxylation by carboxylesterase in the liver 3 Water soluble metabolites are excreted in the urine Vasoconstrictor addition 1 Local anesthetics are removed from depot site mainly by absorption into blood 2 Addition of vasoconstrictor drugs e g epinephrine reduces absorption of local anesthetics thus prolonging anesthetic effect and reducing systemic toxicity NOTE Do not use vasoconstrictors in areas with functional end arteries possible development of necrosis due to prolonged hypoperfusion What s the problem Too much local anesthetic History Corning JL Spinal anaesthesia and local medication of the cord New York State Med J 42 483 1885 Bier A Versuche ber Cocainisirung des R ckenmarkes Deutsche Zeitschrift f r Chirurgie 1899 51 361 Today Examples of local anesthetic use Infiltration Topical anesthesia Spinal anesthesia Epidural nerve block Nerve block Field block Intravenous regional block Case 1 67 y o male with a histologically proven malignancy in the right sidewall of his bladder presenting for a TUR B PMH COPD w 90 py and counting FEV1 65 VC HTN no known CAD or CVD Meds Tiotropium bromide inhaler ACE I Previous surgeries anesthesias Cystoscopy 01 2012 under GA PONV Vitals HR 78 min BP 135 78 RR 14 min Pulse regular SpO2 91 at room air Auscultation S1 S2 no murmurs rhythmic lungs with discrete basal expansion crackling rales on both sides Proposed anesthesia Case 1 Spinal Anesthesia Hyperbaric Bupivacaine opioid SPA testing the effect Try to establish the area where the patient will recognize a cool pack as a warm sensation or won t recognize it at all Spinal segments correlate with dermatomes T10 is sufficient for cystoscopy NOTE 1 Hypotension due to loss of sympathetic tone C fibers T5 L1 2 High spinal above T4 block of the Nn accelerantes sympathetic cardiac accelerators Is that enough Obturator nerve Obturator nerve block General technique for a block with a nerve stimulator 1 2 3 4 Stimulation started at e g 2 mA for 0 1 ms at 1 Hz Advance the needle at the correct location until desired muscle twitching is visible Current is gradually decreased to 0 2 mA to confirm proximity to the nerve After confirmation of needle position LA is injected Case 2 You are on call It s 3 am in the morning You receive a call from the OB resident requesting your service for a 27 y o female gravida 1 para 0 in the labor room otherwise healthy She just needs a little pain relief the resident tells you When you enter the room you find a profusely sweating young woman in serious distress and pain who is yelling at an exhausted young male who seems to be her husband as well as at the mid wife who tries to calm her down Now she starts screaming at you Procedure Case 2 Epidural Anesthesia Epidural Anesthesia 1 Disinfection and prepping Skin and subcutaneous infiltration Needle insertion Epidural Anesthesia 2 Then 1 Test dose of LA with epinephrine Tachycardia 2 Start of LA e g ropivacaine 0 1 walking epidural low dose sufentanil Needle advancement with loss of resistance technique Catheter insertion Case 2 Unforeseen The epidural works fine the mother stopped yelling and swears to name her baby after you for taking her pain away and you get back to bed 4 am The OB resident tells you now that they have to do a non emergent C section on your patient due to unforeseen positioning of the baby And now General anesthesia with a high risk of aspiration and airway problems Solution Change the ropivacaine from 0 1 to 0 33 and give a bolus Check the effect dermatomes and repeat and or raise continuous infusion until effective analgesia is reached Case 3 A 37 y o male with a fracture of the distal radius after an accident with his bicycle is scheduled for ambulant surgical repair of the fracture PMH healthy Meds None Past surgeries None Vitals excellent You decide to cover the patients needs with a axillary plexus block plus a musculocutaneous nerve block Oh no After an easy approach you inject the local anesthetic bupivacaine remove the needle and are proud of yourself Seconds later the patient tells you that his tongue and lips are getting a little numb and you notice that he gets more and more aggitated and anxious Right after that the patient suffers from a generalized seizure looses consciousness and stops breathing Your patient is dying unless YOU help him What would you do Let s save a life Working hypothesis Local Anesthetic Systemic Toxicity LAST 1 Get help 2 Initial Focus a Airway management
View Full Document
Unlocking...