matt springs

8/3/2019 Matt Springs

http://slidepdf.com/reader/full/matt-springs 1/14

Local Anesthetic Toxicity:Local Anesthetic Toxicity:A Comprehensive ReviewA Comprehensive Review

InInEight MinutesEight Minutes

February 20, 2008February 20, 2008Matt Springs, MDMatt Springs, MD

Advisor: Jason Taylor, MDAdvisor: Jason Taylor, MD



Signs and Symptoms of LocalSigns and Symptoms of Local

Anesthetic Toxicity: CNSAnesthetic Toxicity: CNSEarly signs:Early signs: circumoralcircumoral numbness (earliest),numbness (earliest),

tonguetongue paresthesiaparesthesia, dizziness, dizzinessExcitatory signs such as restlessness andExcitatory signs such as restlessness and

agitation often precede CNS depression (slurredagitation often precede CNS depression (slurred

speech, drowsiness, unconsciousness)speech, drowsiness, unconsciousness)

Muscle twitching heralds the onset of tonicMuscle twitching heralds the onset of tonic--

clonicclonic

szsz

’’ss

Respiratory arrest often followsRespiratory arrest often follows

Treat withTreat with benzosbenzos, hyperventilation (, hyperventilation (↓↓CBF),CBF),

thiopental (1thiopental (1--2mg/kg), and oxygenation2mg/kg), and oxygenation




Anesthetic Toxicity: RespiratoryAnesthetic Toxicity: Respiratory

Local anesthetics depress hypoxic driveLocal anesthetics depress hypoxic drive(the(the ventilatoryventilatory response to low PaOresponse to low PaO22 ))

Apnea can result fromApnea can result from phrenicphrenic andandintercostalintercostal nerve paralysisnerve paralysis

TxTx: respiratory support as indicated: respiratory support as indicated




Anesthetic Toxicity: CVAnesthetic Toxicity: CVIn general, LAIn general, LA’’s depress myocardials depress myocardial automaticityautomaticity(spontaneous phase IV depolarization) and reduce the(spontaneous phase IV depolarization) and reduce the

refractory periodrefractory periodThis direct myocardial depression causesThis direct myocardial depression causes bradycardiabradycardia,,heart block (varying degrees), and hypotension whichheart block (varying degrees), and hypotension whichmay lead to cardiac arrestmay lead to cardiac arrest

The R(+) isomer of The R(+) isomer of bupivacainebupivacaine avidly blocks cardiacavidly blocks cardiacsodium channels and dissociates slowlysodium channels and dissociates slowly

Major CV toxicity requires about 3X the concentrationMajor CV toxicity requires about 3X the concentration

required to producerequired to produce szsz’’ssRopivacaineRopivacaine is 70% less likely to cause severe cardiacis 70% less likely to cause severe cardiacarrhythmias thanarrhythmias than bupivacainebupivacaine

Treat withTreat with vasopressorsvasopressors and ACLS protocolsand ACLS protocols

Lipid infusion....another topicLipid infusion....another topic – – www.lipidrescue.orgwww.lipidrescue.org

http://www.lipidrescue.org/





Brief History Of Local AnestheticBrief History Of Local Anesthetic

Maximum DosagesMaximum DosagesThe most conservative maximum dose for The most conservative maximum dose for lidocainelidocaine relatesrelates

back to work by T.back to work by T. GorghGorgh in the 1940in the 1940’’ss

He recommended a max dose of 300mg to the AstraHe recommended a max dose of 300mg to the Astrapharmaceutical companypharmaceutical company

However, the company decided to use 200mg instead,However, the company decided to use 200mg instead,

which remains the max dose in most of Europewhich remains the max dose in most of EuropeTypically, max doses have been determined byTypically, max doses have been determined by

extrapolating data obtained from lab animals to man,extrapolating data obtained from lab animals to man,

followed by clinical investigations in man using those dosesfollowed by clinical investigations in man using those dosesCase reports of systemic toxicity have also been used toCase reports of systemic toxicity have also been used to

derive max dosesderive max doses

No human studies of max doses causing severeNo human studies of max doses causing severetoxicitytoxicity……however however



Volunteers Needed For StudyVolunteers Needed For Study

Study aim: To determine the exactStudy aim: To determine the exact

maximum dose of maximum dose of bupivacainebupivacaine that can bethat can be

given by way of a peripheral nerve blockgiven by way of a peripheral nerve block

DoubleDouble--blinded RCTblinded RCT

End pointEnd point……severe toxicity resulting insevere toxicity resulting in szsz,,

cardiac arrhythmia, or deathcardiac arrhythmia, or death

Disclaimer: Not approved by the MUSCDisclaimer: Not approved by the MUSCEthics Committee for the general public**#Ethics Committee for the general public**#

**approval granted for anesthesia residents only**approval granted for anesthesia residents only#little to no compensation provided#little to no compensation provided



Is There Room For Comfort?Is There Room For Comfort?

In 2003, McCartney et al investigated theIn 2003, McCartney et al investigated the

intravenous dose of intravenous dose of ropivacaineropivacaine whichwhichwould cause mild CNS symptomswould cause mild CNS symptoms

All patients toleratedAll patients tolerated ropivacaineropivacaine 60mg60mg i.vi.v..The peak blood level was found to beThe peak blood level was found to be

4.48ng/mL at the time of mild symptoms4.48ng/mL at the time of mild symptoms

Also determined that up to 0.03mg/kgAlso determined that up to 0.03mg/kg

versedversed i.vi.v. did not mask symptoms. did not mask symptoms



Is There Room For Comfort?Is There Room For Comfort?How does 4.48ng/mL relate to us?How does 4.48ng/mL relate to us?

In 2006,In 2006, VanterpoolVanterpool et al from Duke investigatedet al from Duke investigated

plasma levels of plasma levels of ropivacaineropivacaine after lumbar plexusafter lumbar plexusblock (35cc of 0.5% cblock (35cc of 0.5% c epiepi) versus combined) versus combinedLP/sciatic (60cc of 0.5% cLP/sciatic (60cc of 0.5% c epiepi))

In the twenty patients, there was no evidence of In the twenty patients, there was no evidence of systemic effectsystemic effect

The averageThe average CCmaxmax for the LPSN group wasfor the LPSN group was

1560ng/mL, with the highest being 2345ng/mL1560ng/mL, with the highest being 2345ng/mLThis is essentially half of the plasma concentrationThis is essentially half of the plasma concentrationshown in McCartneyshown in McCartney’’s study to illicit mild CNSs study to illicit mild CNS

symptomssymptoms



Patient Related Factors to Consider DuringPatient Related Factors to Consider During

Large VolumeLarge Volume PNBPNB’’ss

AGE:AGE:

Newborns have about half the adult concentration of Newborns have about half the adult concentration of αα11--acid glycoprotein (AAG) which binds free LAacid glycoprotein (AAG) which binds free LA’’ss -- reduce byreduce by

15%15%Persons over 70 showPersons over 70 show sensitivity to LAsensitivity to LA’’s and decreaseds and decreasedclearanceclearance – – reduce by 10reduce by 10--20%20%

RenalRenal DysfxnDysfxn::

There is may or may not be a change in clearance of LA inThere is may or may not be a change in clearance of LA innonuremicnonuremic andand uremicuremic ptspts

More importantly,More importantly, uremicuremic pts show a rapid rise in [LA]pts show a rapid rise in [LA]

probably secondary to aprobably secondary to a hyperdynamichyperdynamic circulation (circulation ( circ =circ = uptake)uptake)

The good newsThe good news – – uremicuremic pts havepts have AAGAAG

Recommendation: reduce LA bolus by 10Recommendation: reduce LA bolus by 10--20% in20% in uremicuremic

pts and reducepts and reduce continuouscontinuous regional anesthetic techniquesregional anesthetic techniquesby 10by 10--20%20%




Large VolumeLarge Volume PNBPNB’’ssHepaticHepatic DysfxnDysfxn::

Clearance of LA can be dramaticallyClearance of LA can be dramatically ↓↓ but plasmabut plasmaconcentrations remain close to normal secondary toconcentrations remain close to normal secondary to

VVdd

These patients also can have renal and cardiacThese patients also can have renal and cardiacdysfxndysfxn

RecRec: Initial bolus can be in the normal dose range: Initial bolus can be in the normal dose range

but continuous infusions should be reduced 10but continuous infusions should be reduced 10

--50%50%

Heart Failure:Heart Failure:

↓↓ blood flow to the liver and kidneys can cause ablood flow to the liver and kidneys can cause a ↓↓

in clearancein clearanceRepeat or continuous dosing of LARepeat or continuous dosing of LA’’s should bes should bereduced b 10reduced b 10--20%20%




Large VolumeLarge Volume PNBPNB’’ss

Pregnancy:Pregnancy:

Progesterone mayProgesterone may sensitivity of nerve axonssensitivity of nerve axons

There seems also to be an enhanced risk of There seems also to be an enhanced risk of cardiotoxicitycardiotoxicity bybybupivacainebupivacaine andand ropivacaineropivacaine in pregnancy induced byin pregnancy induced byprogesteroneprogesterone

in CO causesin CO causes uptakeuptake

RecRec: avoid large volume: avoid large volume PNBPNB’’ss in 1in 1

stst

trimester trimester Reduce doses in epidural and spinal anesthesia in pregnancyReduce doses in epidural and spinal anesthesia in pregnancy

Drug interaction:Drug interaction:

Amides are cleared by the liver Amides are cleared by the liver cytochromecytochrome P450 enzymesP450 enzymes

PropanololPropanolol,, cimetidinecimetidine andand itraconazoleitraconazole cancan ↓↓bupivacainebupivacaineclearance by 30clearance by 30--35%35%

CiproCipro andand fluvoxaminefluvoxamine decreased the clearance of decreased the clearance of ropivacaineropivacaine

RecRec: single shots are of little concern but continuous infusions: single shots are of little concern but continuous infusionsshould be altered (10should be altered (10--20% decrease)20% decrease)



ConclusionsConclusions

Severe local anesthetic toxicity is a rare butSevere local anesthetic toxicity is a rare butdevastating side effect of LAdevastating side effect of LA’’s administration occurrings administration occurring

in 7.5 to 20 adults per 10K blocksin 7.5 to 20 adults per 10K blocksKnow the signs and symptoms and be prepared toKnow the signs and symptoms and be prepared totreat immediatelytreat immediately

Inadvertent intravascular injection is the #1 cause of Inadvertent intravascular injection is the #1 cause of toxicity at the time injectiontoxicity at the time injection

Use epinephrine when at all possibleUse epinephrine when at all possible

AvoidAvoid bupivacainebupivacaine if possibleif possible

In healthy pts, standard maximum doses are likely aIn healthy pts, standard maximum doses are likely avery safe estimate and can probably be increasedvery safe estimate and can probably be increased

However, special consideration should be given toHowever, special consideration should be given tocertain pt populationscertain pt populations



ReferencesReferences

McCartney, Colin J.L. et al. IntravenousMcCartney, Colin J.L. et al. Intravenous ropivacaineropivacaine bolusbolusis a reliable marker of intravascular injection inis a reliable marker of intravascular injection in

premedicatedpremedicated healthy volunteers.healthy volunteers. Can J Can J Anesth Anesth 2003;2003;50:79550:795--800800

Morgan, G. Edward, Jr. Chapter 14, Local Anesthetics.Morgan, G. Edward, Jr. Chapter 14, Local Anesthetics.20062006

RenehanRenehan, Elizabeth M. et al. Scavenging, Elizabeth M. et al. Scavenging NanoparticlesNanoparticles: An: AnEmerging Treatment for Local Anesthetic Toxicity.Emerging Treatment for Local Anesthetic Toxicity. Regional Regional Anesthesia and Pain Medicine Anesthesia and Pain Medicine 2005; 30:3802005; 30:380--8484

Rosenberg, H. MD PhD et al. Maximum RecommendedRosenberg, H. MD PhD et al. Maximum Recommended

Doses of Local Anesthetics: ADoses of Local Anesthetics: A MultifactorialMultifactorial Concept.Concept.Regional Anesthesia and Pain Medicine Regional Anesthesia and Pain Medicine 2004; 29:5642004; 29:564--575575

VanterpoolVanterpool, Stephanie et al. Combined Lumbar , Stephanie et al. Combined Lumbar --Plexus andPlexus andSciaticSciatic--Nerve Blocks: An Analysis of PlasmaNerve Blocks: An Analysis of Plasma RopivacaineRopivacaine

Concentrations.Concentrations. Regional Anesthesia and Pain Medicine Regional Anesthesia and Pain Medicine 2006; 31:4172006; 31:417--421421

matt springs

Documents