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ZZ   @n?" dd@  @@`` . & ='   ' " #$%   '&!()*+,-./01_R$d!6sT^IAzb$W֖Fj 1ĘZ˗AzR$yXSa8ʚ;g4LdLd@B 0ppp@ <4ddddlpC 0_3 <4!d!dlhG 0<4BdBdlhG 00___PPT10 n___PPT9PH 2!@%&'4(P? %:> Staying Alive PQMichele Fliss, M.D. Pema Dorje, M.D. James Kim, M.D. Department of Anesthesiology.R5,4  `60 y/o male history of left thumb osteoarthritis presented for left thumb sesamoid bone excision"a`" GMeds Lisinopril HCTZ Toprol Atenolol Protonix ASA Nortriptyline Allegra2H""Ct   PSH Aortic valve replacement 01/03 Tonsillectomy and adenoidectomy Bilateral foot surgery Pre-op EKG Sinus bradycardia with HR of 47 Cardiac Cath. 11/02: EF 70% w/ no evidence of CADW  &W  &(   ;PACU Post-op Vitals BP 122/69 HR 59 RR 20 Sat. 97% T 35.5 CL((    A 22 gauge 2-inch B-bevel needle was inserted until bright red blood was aspirated from the axillary artery The needle was advanced until blood aspiration ceased   8"&6  dABC s Ventilated with Ambu bag Sat rose to mid 90 s Treatment 2 mg midazolam 150 mg propofol seizure stopped 120 mg succinylcholine Successfully Intubated MAC # 3 and 8.0 ETT. / ,* f# Patient s vitals remained stable Extubated in the PACU after 30 minutes No evidence of cardiovascular arrhythmias or hypotension Alert & Oriented x 3 Complained of chest pain and dyspnea Plan?XB6    Risks of Systemic Toxicity(<Rapid Onset Results from direct intravascular injection of local anesthetic Delayed Onset Excess absorption of local anesthetic solutions from tissue injection sites Dependent On Dose injected Vascularity at injection site Tracheal Intercostal Caudal Epidural Brachial Plexus Sciatic Inclusion of vasoconstrictors -@ -L ,@ @ L , 6UMaximum Acceptable Local Anesthetic Doses for Regional Anesthesia (non-intravascular)6VA"$ nLidocaine 5 mg/kg (7 mg/kg w/ epi) Bupivacaine 3 mg/kg (w/epi) Prilocaine 600 mg Ropivacaine 3.5 mg/kg (w/epi)        ? &FSystemic Toxicity of Local Anesthetics Manifest as CNS and CV SymptomsGG"  Seizures can be followed by CNS depression Apnea Death Seizure onset results from selective blockade of inhibitory pathways in the cerebral cortex Eventually excitatory pathways are inhibited leading to a state of CNS depressionA G 4Cardiovascular ToxicityThe CV system is more resistant to the toxic effects of local anesthetics than is the CNS High plasma concentrations produce hypotension, direct myocardial depression, and arrhythmiasMechanism of CV Toxicity Local anesthetics block cardiac sodium channels Impairing automaticity and conduction Manifests as Prolongation of the PR interval Widening of the QRS interval Positive correlation between Cardiotoxic potency of local anesthetics lipid solubility nerve blocking potency0& "  = " Q " 0& =Q  ,: w F$Bupivacaine vs. RopivacaineIs ropivacaine a  safer drug? Should ropivacaine replace bupivacaine in regional anesthesia? $` A Bupivacaine Highly lipid soluble amide local anesthetic with long duration of action Racemic mixture of levo (S -) and dextro (R+) isomers Dextrorotatory isomer responsible for systemic toxicity Narrow margin between CNS and CV toxicity Extremely potent depressant effect on the heartT9 " Z7Z>I  &!Bupivacaine ToxicityDissociates very slowly from the cardiac sodium channels Accounting for its persistent effects on the heart Accidental IV injection may result in precipitous hypotension cardiac dysrhythmias including V-tach V-fib AV block Extremely difficult resuscitation93 " &7 "  " "93&7  "2% ?Alert to Practitioners **Bupivacaine Toxicity Reactions**,@$*$George Albright, MD reported a number of cases of almost simultaneous seizures and cardiovascular collapse following unintended intravascular injection of bupivacaine Resuscitation was unsuccessful in the majority of the patients6?'"LThe Bupivacaine  Black-Boxed Warning ''(Ban on the use of 0.75% bupivacaine for obstetric anesthesia secondary to reports of cardiac arrest with difficult resuscitation or death.*=  A(# Ropivacaine Pure S(-) Enantiomer Less potential for systemic toxicity Less lipid soluble Shorter elimination half life Less protein binding Wider margin between CNS and CV toxicity Faster recovery from CNS symptoms in IV toxicity studies vs. bupivacaineb%F " r% F r  )$ Ropivacaine Less risk of cardiotoxicity Faster dissociation from cardiac Na+ channels Less depression of cardiac conductivity Less potential to induce reentrant type of ventricular arrhythmias Greater response to conventional resuscitation than patients intoxicated with bupivacaine2 *%+Equipotency of Bupivacaine and Ropivacaine?,,( ! Controversy regarding The anesthetic potency of ropivacaine The margin of safety At equal doses Ropivacaine has a wider margin of safety than bupivacaine The potential for systemic toxicity is also affected by the relative total dose required for an individual blockx; "  " ;+&+Equipotency of Bupivacaine and Ropivacaine?,,( !1999  Polley et. al. investigated the relative analgesic potencies of bupivacaine and ropivacaine by determining their MLAC values in women receiving epidural analgesia MLAC of ropivacaine was nearly 2x that of bupivacaine,'Further InvestigationsComparisons of quality of analgesia from patient controlled epidurals utilizing 0.125% ropivacaine vs. 0.125% bupivacaine No significant difference With high concentrations of local anesthetics Top of the dose  response curve Analgesic success is predictable~z " .B " z.!! & -(&Application to Peripheral Nerve Blocks''(High concentrations and large volumes of local anesthetics utilized Top of dose  response curve Analgesic success predictable In equal dosages ropivacaine has been proven to have a larger margin of safety over bupivacaineD; " O " D:$  =$ $ .)bShould Ropivacaine Replace Bupivacaine for PNB s?22(+sWise choice for blocks with higher risk of intraarterial injections: Interscalene Cervical Plexus Stellate Ganglion.E/E/]Practices to Reduce the Incidence of Local Anesthetic Toxicity During Peripheral Nerve Blocks^^$EKG, BP, and pulse oximetry monitoring before, during, and after the block. Adherence to limits of maximum dosages of local anesthetics. Use of vasoconstrictors. Administration of a test dose and monitor HR for 60s. Fractionated dosing with intermittent aspiration (5cc increments). Continuous verbal contact with the patient during and after the nerve block. Low dose sedation for block. Do not premedicate with high dosage of benzodiazepines. &'Management of Local Anesthetic Toxicity(($ABC s Anticonvulsant drugs Benzodiazepines Barbiturates Propofol Emergent intubation with succinylcholine Decreases risk of aspiration Facilitates oxygenation ACLS protocol for CV toxicity Prolonged CPR required& " )5 " 5&)5  5 New Therapy (Lipid Reversal of Bupivacaine Toxicity Weinberg et al., June 2003 issue of Regional Anesthesia and Pain Medicine demonstrated that a bolus dose of propofol can reverse an animal model of bupivacaine toxicity after standard resuscitation had failed. Mechanism? Lipid enhanced removal of local anesthetics from the cardiac receptors that produce CV depression Further investigation neededz' ' ~3  !Take Home to the Beach&(Do the block in the right place Have the available resuscitive equipment Have a index of suspicion when using Bupivacaine in large doses Always use epi with Bupivacaine Consider ropivacaine in  higher risk PNBs *Sometimes the cure is worse than the disease*7%<#7,3 88 ` MMM̙` fy3` f.f̙` jg3mof` e MMMfff` Po` yyOOw]]f` MMMr~` NfD+f3>?Zd@,x?ZZ@  @` n?" dd@   @@``PP    @ ` ` p@ @  F(    6<3 " 3 T Click to edit Master title style! !&  0Ԟ3 "  3 TClick to edit Master text styles - Second level Third level Fourth level Fifth level!    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MMM̙y___PPT10Y+D=' = @B +  `0^(  0r 0 S y4P  4  0 0 {4 y Y` LRECHO 4/03 Bioprosthetic aortic valve w/ no evidence of aortic insufficiency PE Ht: 69 in. Wt: 117 kg Airway 3 cm mouth opening H - M 6 cm Mallampati III Thick neckG<G  < H 0 0޽h ? MMM̙y___PPT10Y+D=' = @B +  ;34(  4 4 04 ,$ 0 xPre-op Vitals Bp 134/77 HR 70 RR 16 Sat. 98% T 36.6 C Anesthetic Plan General LMA Patient deferred regional technique0 ZZ+0 ZfZ0 ZZ00 ZZ* $u 4 04 ,$ 0 Pre-med 2mg Mdz Induction 150mcg fentanyl 200mg propofol # 5 LMA placed Intraop Bradycardic to HR of 39 Resolved with 0.4mg atropine Z Z 0 ZZ/0 ZfZ0 ZZ50 ZZ -5, ]H 4 0޽h ? MMM̙y___PPT10Y+D=' = @B +    <(  < < S 4  4 , h$  < 0D4   8After 15 Minutes Patient reports 9/10 pain of left thumbP(' h  < 0,4  ,E >OPTIONS ? Infraclavicular block attempted - unsuccessful in eliciting nerve stimulation Patient prepped for axillary brachial plexus blockx  .3  . hH < 0޽h ? MMM̙y___PPT10Y+D=' = @B +  p7(  r  S T4  4   c bA*3110_axillary_block-2Figure 1:]ek  04# KNot an actual patient 2@  <4 ?"6@ NNN?NWZYD<4___PPT9 JPatient was positioned supine with his arm abducted to 90 and elbow flexed. The axillary artery was palpated as high in the axilla as possible. Skin was localized with 1% lidocaine.^0ZZ2LC&B8XH  0޽h ? MMM̙y___PPT10Y+D=' = @B +_  ~@(  @ @ S D3 r 4 *`~ @ C VA*110_axillary_block-3Figure 2: // : @ HH 3 ?"6@ NNN?N  Transarterial Approach*0ZZ  ~ @ H8 3 ?"6@ NNN?N  NLocal Anesthetic 40 cc 0.5% bupivacaine 1:200,000 epinephrine 50 mcg clonidineP0ZZ>0ZZ>H @ 0޽h ? MMM̙y___PPT10Y+D=' = @B +  p D{(  Dr D S 83 3  D <3 ?"6@ NNN?NNTLD___PPT9& 5 cc increments of the bupivacaine solution was injected with intermittent aspiration 33 cc of injected anesthetic solution seizure onsetn~0ZZ0ZZ~<d8X D <,3 ?"6@ NNN?N~  @Vitals Sinus rhythm with HR in 60 s BP 132/74 Oxygen saturation began declining to a low of 83%P0ZZY0ZZ$Y8!!ii D Hl53 ?"6@ NNN?N 2< P ! ACTION !* 0ZZ 0  D <63 ?"6@ NNN?Np O Continued* 0ZZ2 H D 0޽h ? MMM̙___PPT10e.+D=' = @B +  `H(  Hr H S $L3Pp 3 H H 0޽h ? MMM̙y___PPT10Y+D=' = @B + ( (    S t^3\   3 H  0޽h ? MMM̙y___PPT10Y+D=' = @B +   L(  Lr L S (f3  3  L 0i34,$ 0 ASTAT EKG Sinus bradycardia STAT Chest X-ray Normal Patient Admitted overnight for observation serial cardiac enzymes Cardiac Index Profile negative x 3 Patient Discharged Home The following day in stable condition> 0Z0ZZ0ZZ0ZZ0ZZT0ZZ0ZZ&0ZZU' %%H L 0޽h ? MMM̙y___PPT10Y+D=' = @B +m  P\$(  \r \ S q3  3 r \ S q3` 3 H \ 0޽h ? MMM̙y___PPT10Y+D=' = @B +}  0`$(  `r ` S $3Jj  3 r ` S 䕻30p 3 H ` 0޽h ? MMM̙___PPT10i. pn+D=' = @B +  0dp(  dr d S %3  3 b d <3 ?"6@`NNN?N@  BRestlessness Vertigo Tinnitus Slurred speech Tonic-clonic seizures&C0ZZC3  AAT d < 3 ?"6@`NNN?N442 TIncreasing plasma concentrations of local anesthetics are associated initially with:*U0ZZUAAH d 0޽h ? MMM̙___PPT10i..+D=' = @B +  @h(  hr h S 3 3 H h 0޽h ? MMM̙___PPT10i.@A5+D=' = @B +}  l$(  lr l S 3`  3 r l S 3@0  3 H l 0޽h ? MMM̙___PPT10i.+D=' = @B +}  @p$(  pr p S ,4P`  4 r p S 4P2 4 H p 0޽h ? MMM̙___PPT10i.`#+D=' = @B +{ 2(  r  S 3G' 3   S |ɻ30  3 H  0޽h ? MMM̙y___PPT10Y+D=' = @B +}  Pt$(  tr t S ѻ3  3 r t S ѻ3N 3 H t 0޽h ? MMM̙___PPT10i.Z+D=' = @B +}  $(  r  S "3P  3 r  S ߻3` 3 H  0޽h ? MMM̙___PPT10i.A'y8+D=' = @B +}  $(  r  S p3   3 r  S D3  3 H  0޽h ? MMM̙___PPT10i.1`)+D=' = @B +}  $(  r  S 3  3 r  S 3 `  3 H  0޽h ? MMM̙___PPT10i.G, +D=' = @B +}  $(  r  S @4P`  4 r  S 4 ~` 4 H  0޽h ? MMM̙___PPT10i.H0+D=' = @B +}  $(  r  S  4 0  4 r  S  40 4 H  0޽h ? MMM̙___PPT10i.I0(+D=' = @B +$  $(  r  S 4   4 r  S 4@ 4 H  0޽h ? MMM̙80___PPT10.J@/$  $(  r  S  4  4 r  S !4p  4 H  0޽h ? MMM̙80___PPT10.L` 3$  $(  r  S (34`  4 r  S 34 4 H  0޽h ? MMM̙80___PPT10.MtW}  $(  r  S A4 P  4 r  S |B4~p 4 H  0޽h ? MMM̙___PPT10i.Os+D=' = @B +}  $(  r  S PM4  4 r  S $N4p`  4 H  0޽h ? MMM̙___PPT10i.P@(,+D=' = @B +  |:(  |r | S  S4P  4  | S t;4  4 "p`PpH | 0޽h ? MMM̙y___PPT10Y+D=' = @B +  :(  r  S da4  4   S j4   4 "p`PpH  0޽h ? MMM̙y___PPT10Y+D=' = @B +m  $(  r  S ~4   4 r  S h4  4 H  0޽h ? MMM̙y___PPT10Y+D=' = @B +  (    64 ` <Insulin Treatment for Bupivacaine Induced Cardiac Depression<=Z$0'$"  <Ќ4 ?"6@ NNN?N @ xBupivacaine administered at 0.5mg/kg/min IV until MAP decreased to 40mmHg Insulin-glucose-potassium (IGK) group IV bolus of regular insulin 2U/kg was given Followed by a glucose infusion 2cc/kg of 50% dextrose in water for 30 min. and a potassium infusion (1-2mmol/kg/hr) Control group was administered a glucose infusion MAP, HR, CO, MVO2 and end tidal CO2 recovered toward baseline in the IGK group All IGK dogs survivedp0ZZ0ZZ20ZZe0ZZp2e8ddH  < 4 ?"6@ NNN?N  ,[Kim et al., Anesthesia & Analgesia 2004,  The Effect of Insulin on the Resuscitation of Bupivacaine Induced Severe Cardiovascular Toxicity in Dogs ]H0ZZmH  0޽h ? MMM̙y___PPT10Y+D=' = @B +[  z(    B428[ B Mechanism?  (  <4 ?"6@ NNN?N- tBupivacaine Blocks transient outward K+ currents Repolarization of ventricular myocytes Alters Ca2+ release from the cardiac sarcoplasmic reticulum Insulin Enhances the transient outward K+ current Repolarization Increases Ca2+ transport activity of the sarcoplasmic reticulum Increases cytoplasmic glucose concentration and pyruvate availability to mitochondria, thereby improving myocardial energetics and performanceh |0 ZZ}0 ZZ  ,F< 8BBH  0޽h ? MMM̙y___PPT10Y+D=' = @B +}  $(  r  S 4 0  4 r  S p4 4 H  0޽h ? MMM̙___PPT10i.D+D=' = @B +r@'QgXL`[psx:k;~p˟@Ť&.@eeb(p8BǿLxUeJ.3Oh+'0T hp   Axillary University of MichiganCloudsiCAS91Microsoft PowerPointn@@M,@PuSGSg  )'    """)))UUUMMMBBB999|PP3f333f3333f3ffffff3f̙3ff333f333333333f33333333f33f3ff3f3f3f3333f33̙33333f333333f3333f3ffffff3f33ff3f3f3f3fff3ffffffffff3ffff̙fff3fffff3fff333f3f3ff3ff33f̙̙3̙ff̙̙̙3f̙3f333f3333f3ffffff3f̙3f3f3f333f3333f3ffffff3f̙3f3ffffffffff!___www4'A x(xKʦ 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  ( 0 On-screen Show&University of Michigan Medical CenterTaJY($ )Arial WingdingsHigh Tower TextSymbolCloudsStaying AliveSlide 2Slide 3Slide 4Slide 5Slide 6 Slide 8Slide 9 Slide 10 Slide 11 Slide 12Risks of Systemic ToxicityVMaximum Acceptable Local Anesthetic Doses for Regional Anesthesia (non-intravascular)GSystemic Toxicity of Local Anesthetics Manifest as CNS and CV Symptoms Slide 16Cardiovascular ToxicityMechanism of CV ToxicityBupivacaine vs. Ropivacaine BupivacaineBupivacaine Toxicity@Alert to Practitioners **Bupivacaine Toxicity Reactions**'The Bupivacaine Black-Boxed Warning Ropivacaine Ropivacaine,Equipotency of Bupivacaine and Ropivacaine?,Equipotency of Bupivacaine and Ropivacaine?Further Investigations'Application to Peripheral Nerve Blocks2Should Ropivacaine Replace Bupivacaine for PNBs?^Practices to Reduce the Incidence of Local Anesthetic Toxicity During Peripheral Nerve Blocks(Management of Local Anesthetic Toxicity New Therapy Slide 34 Slide 35Take Home to the Beach  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