CLINICAL PHARMACOLOGY OF NEUROMUSCULAR BLOCKING AGENTS

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Don't hesitate to comment below if you have any questions or additional phrases CLINICAL PHARMACOLOGY OF NEUROMUSCULAR BLOCKING AGENTS Jerrold H. Levy, MD Professor of Anesthesiology Emory University School of Medicine Division of Cardiothoracic Anesthesiology and Critical Care Emory Healthcare Atlanta, Georgia ,HISTORY OF NEUROMUSCULAR BLOCKING AGENTS AND CLINICAL DEVELOPMENT ,HISTORY 1494- Tales of travelers killed by poison darts 1551 - Ourari” or “cururu” meaning “bird killer” 1812 - Curarized cat kept alive by artificial respiration 1912 - Curare used to prevent fractures during ECT 1941 - Initial use by Griffith, Culler, and Rovenstine 1951 - Succinylcholine chloride first used in Stockholm ,INTRODUCTION OF NEW DRUGS 1494 - 1942 Curare 1947 - 1951 Succinylcholine chloride, Gallamine, Metocurine, Decamethonium 1960’sAlcuronium 1970’sPancuronium bromide, Fazadinium 1980’sVecuronium bromide, Atracurium besylate 1990Pipecuronium bromide 1991Doxacurium chloride 1992Mivacurium chloride 1994Rocuronium bromide 1999Rapacuronium bromide ,STRUCTURAL CLASSES OF NONDEPOL.ARIZING RELAXANTS Steroids: Rocuronium bromide, Vecuronium bromide, Pancuronium bromide, Pipecuronium bromide Naturally occurring benzylisoquinolines: curare, metocurine Benzylisoquinoliniums: Atracurium besylate, Mivacurium chloride, Doxacurium chloride ,THE IDEAL RELAXANT Nondepolarizing Rapid onset Dose-dependent duration No side-effects Elimination independent of organ function No active or toxic metabolites ,ONSET OF PARALYSIS IS AFFECTED BY: Dose (relative to ED95) Potency (number of molecules) Keo (chemistry/blood flow) Clearance Age ,Neuromuscular Blocking Agents and Patient Evaluation Assessing Postoperative Neuromuscular Function ,Assessing Postoperative Neuromuscular Function CLINICAL ASSESSMENT Sustained 5-second head lift Ability to appose incisors (clench teeth) Negative inspiratory force > – 40 cm H2O Ability to open eyes wide for 5 seconds Hand-grip strength Sustained arm/leg lift Quality of speaking voice Tongue protrusion Kopman AF, et al. Anesthesiology, 1997:86;765 ,Assessing Postoperative Neuromuscular Function Train-of-Four (TOF) Fade Ratio Ali HH, et al. Br J Anaesth. 1975;47:570 ,Assessing Postoperative Neuromuscular Function THE ORIGIN OF THE GOLD STANDARD TOF Ratio Vital Capacity Inspiratory Force Peak Exp. Flow Rate Control =100 100 100 100 60% 91 70 95 70%* 97 82 92 100 88 94 80% 100 91 95 90% 100 97 99 100% * Historically regarded as the Gold Standard Ali HH, et al. Br J Anaesth. 1975;47:570 ,Assessing Postoperative Neuromuscular Function NEW DATA SUGGEST THAT A TOF OF 0.90 MAY BE NEEDED TO ENSURE NORMAL FUNCTION Kopman: A TOF > 0.90 compatible with normal clinical tests (Anesthesiology. 1997;86:765) Eriksson: Pharyngeal function normal at TOF 0.90 (Anesthesiology. 1997;87:1035) ,Assessing Postoperative Neuromuscular Function ASSESSING TOF FADE RATIO Patients are often returned to the PACU with residual paralysis1 The TOF ratio of 0.70 may be inadequate for discharge of an ambulatory patient1 TOF ratios  0.40 are difficult to assess clinically2 1Viby-Mogensen J, et al. Anesthesiology. 1979;50:539 2Kopman AF, et al. Anesthesiology. 1994;81:1394 ,Assessing Postoperative Neuromuscular Function TOF FADE RATIO: CONCLUSION Recovery is inadequate if fade is detected1,2 Clinical trials are needed to demonstrate measurement techniques for TOF ratios of 0.902 1Eriksson, LI, et al. Anesthesiology. 1997;87:1035 2Bevan, DR, et al. Anesthesiology. 1988;69:272 ,Neuromuscular Blockers:Chemical Structure & Key Characteristics Aminosteroids Vagolytic Partially block cardiac muscarinic receptors involved in heart rate slowing, resulting in increased heart rate: rapacuronium > pancuronium > rocuronium > vecuronium Generally do not promote histamine release Exception: rapacuronium Organ-dependent elimination Kidneys and liver Savage DS, et al. Br J Anaesth. 1980;52 Suppl 1:3S Durant NN, et al. J Pharm Pharmacol. 1979:31(12):831 Marshall IG,