神经肌肉阻断剂

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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,1960sAlcuronium,1970sPancuronium bromide,Fazadinium,1980sVecuronium 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 ED,95,),Potency(number of molecules),K,eo,(chemistry/blood flow),Clearance,Age,Neuromuscular Blocking Agents and Patient Evaluation,Assessing Postoperative Neuromuscular Function,Sustained 5-second head lift,Ability to appose incisors(clench teeth),Negative,inspiratory,force,40 cm H,2,O,Ability to open eyes wide for 5 seconds,Hand-grip strength,Sustained arm/leg lift,Quality of speaking voice,Tongue protrusion,Assessing Postoperative Neuromuscular Function,CLINICAL ASSESSMENT,Kopman AF,et al.,Anesthesiology,1997:86;765,Ali HH,et al.,Br J Anaesth,.1975;47:570,Assessing Postoperative Neuromuscular Function,Train-of-Four(TOF)Fade Ratio,99,97,100,100%,95,91,100,90%,94,88,100,80%,92,82,97,70%*,95,70,91,60%,100,100,100,Control=100,Peak Exp.Flow Rate,Inspiratory Force,Vital Capacity,TOF Ratio,Assessing Postoperative Neuromuscular Function,Ali HH,et al.,Br J Anaesth,.1975;47:570,THE ORIGIN OF THE GOLD STANDARD,*Historically regarded as the Gold Standard,NEW DATA SUGGEST THAT A TOF OF 0.90 MAY BE NEEDED TO ENSURE NORMAL FUNCTION,Assessing Postoperative Neuromuscular 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,Patients are often returned to the PACU with residual paralysis,1,The TOF ratio of 0.70 may be inadequate for discharge of an ambulatory patient,1,TOF ratios,0.40 are difficult to assess clinically,2,ASSESSING TOF FADE RATIO,1,Viby-Mogensen J,et al.,Anesthesiology,.1979;50:539,2,Kopman AF,et al.,Anesthesiology,.1994;81:1394,Assessing Postoperative Neuromuscular Function,Recovery is inadequate if fade is detected,1,2,Clinical trials are needed to demonstrate measurement techniques for TOF ratios of 0.90,2,1,Eriksson,LI,et al.,Anesthesiology.,1997;87:1035,2,Bevan,DR,et al.,Anesthesiology,.1988;69:272,TOF FADE RATIO:CONCLUSION,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,Neuromuscular Blockers:Chemical Structure&Key Characteristics,Aminosteroids,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,et al.,Br J Anaesth,.1980;52 Suppl 1:11S,Absence of,vagolytic,effect,these drugs do not block cardiac-,vagal,(,muscarinic,)receptors,Histamine release,dTc,atracurium,mivacurium,cisatracurium,can cause rare,bronchospasm,decreased blood pressure,increase of heart rate,Generally organ-independent elimination,1,esp,:,atracurium,cisatracurium,mivacurium,Noncumulative,2,Neuromuscular Blockers:Chemical Structure&Key Characteristics,Benzylisoquinolines,1,Stenlake JB,et al.,Br J Anaesth.,1983;55;3S,2,Ali HH,et al.,Br J Anaesth.,1983;55:107S,Ultra-Short,Short,Clinical duration,(injection to T,25,),6-8,12-20,30-45,60,30,succinyl-choline,mivacurium,cisatracurium,doxacurium,Assumes bolus dose=2x ED,95,1,Anectine,(succinylcholine chloride)Package Insert,2,Mivacron,(mivacurium chloride)Package Insert,3,Nimbex,(cisatracurium besylate)Package Insert,4,Nuromax,(doxacurium chloride)Package Insert,1,2,3,4,DURATION OF ACTION OF NEUROMUSCULAR BLOCKING AGENTS,Ultra-Short:Succinylcholine chloride,Short:,Mivacurium,chloride,Intermediate:Rocuronium bromide,Vecuronium bro