LPCHStanfordchildren’sHospitalguidelinesforperi-operativemanagement

ofpatientswithcongenitallongQTsyndrome:

Authors:

M.Navaratnam,K.Motonaga,A.Nathan,J.Mendoza,G.Boltz

WhatislongQTSyndrome?

LongQTsyndrome(LQTS)isacardiacconductiondisordercharacterizedbya

prolongeddispersionofventricularrepolarization.Thisismanifestbyaprolonged

QTcintervalonsurfaceECGdefinedas>460msforfemalesand>450msformales.

Thisabnormalrepolarizationresultsinanincreasedriskofventriculararrhythmias

suchasventriculartachycardia(VT),torsadedepointes(TdP),orventricular

fibrillation(VF)thatcanpresentassyncope,seizures,orsuddencardiacdeath.

LQTScanbecongenitaloracquired.DruginducedLQTSisthemostcommoncause

ofacquiredLQTSandwillnotbediscussedhere.Therearecurrently15known

subtypesofcongenitalLQTS,althoughthisisconstantlybeingupdated.LQTStypes

I,2and3accountforapproximately90%ofthegenotypepositivepatientsand

LQTStype1.Ingeneral,sympathetic/adrenergicstimulationisthoughttobea

triggerforventriculararrhythmiasinallLQTSpatients,however,therearesome

activity/environmentaltriggersthoughttobemorespecificforeachofthe3main

typesofLQTS.Forexample,exercise,diving/swimming,andemotionalstressare

triggersmorespecificforLQTStype1.Suddenloudnoises,startling,andfearare

triggersmorespecificforLQTStype2.Lastly,pausedependentventricular

arrhythmiasduringsleepoccursmostofteninLQTStype3.

TreatmentofcongenitalLQTS:

AllpatientswhoaregenepositiveforLQTSorhavebeenclinicallydiagnosed(but

genenegative)withLQTSreceivebetablockadeasfirstlinetherapy.Approximately

25%ofpatientswithclinicalLQTShavenegativegenetictestingasallofthegenetic

mutationsthatcauseLQTSarenotyetknown.

WhilebetablockertherapyisthefirstlinetherapyforallpatientswithLQTS,there

isalsosomeevidencetosuggestothertherapiestargetedforspecificgenotypes.For

example,LQTStype1isduetoamutationintheKCNQ1gene.Studiesshowthat

betablockadeisextremelyeffectiveforreducingtheriskofventriculararrhythmias

inLQTStype1butlesseffectiveinLQTStype2.LQTStype2isduetoamutationin

KCNH2(HERG)channel.LQTStype3isduetoagainoffunctionmutationinthe

SCN5AchannelandthereforeMexiletine(asodiumchannelblocker)hasbeenused

withsomebenefit.

Inpatientswhohavehadasuddencardiacarrestorwhohavesyncopeor

ventriculararrhythmiasdespitebetablockertherapy,anInternalCardioverter

Defibrillator(ICD)isplaced.Leftcardiacsympatheticdenervation(LCSD)is

recommendedforpatientsinwhomanICDiswarrantedbutrefusedor

contraindicatedand/orbeta-blockersareeithernoteffectiveinpreventing

syncope/arrhythmias,nottolerated,notacceptedorcontraindicated.Somepatients

withLQTS3willhaveanICDplacedforprimarypreventionbecausetheyfallintoa

higher-riskgroup.

Asidefromanti-arrhythmictherapy,thetreatmentofcongenitalLQTSinvolves

lifestylemodificationssuchasavoidingcompetitivesportsandotherknown

triggers.Inaddition,patientswithLQTSshouldavoidotherdrugsthatareknownto

prolongtheQTinterval.

TheCredibleMeds®websitereviewsalltheavailableevidencehascompiledalistof

drugsinfourcategoriesbasedontheirrelativeriskofcausingTdPinapatientwith

congenitalLQTS.Thereareover200medicationsonthe“DrugstoAvoid(DTA)”list

andthislistisconstantlybeingupdatedasnewevidencearises.Tohelpphysicians

interpretevidenceforriskofTdP,theyhavedevelopedthefollowingcategories(See

Figure1)

1. KnownriskofTdP:ThesedrugsprolongtheQTintervalANDareclearly

associatedwithaknownriskofTdP,evenwhentakenasrecommended.

Thesedrugsshouldonlyrarely,ifever,begiventopatientswithcongenital

LQTSbecausetheirriskofTdPissubstantial.However,whenasafe

alternativeisnotavailable,andtheillnessissevere,somephysicianswith

expertiseinthetreatmentofarrhythmiasmayprescribethesedrugs.

2. PossibleRiskofTdP:ThesedrugscancauseQTprolongationandcould

theoreticallybedangerousinsomepatientswithcongenitalLQTS.However,

thereiscurrentlylackofevidenceforariskofTdPwhentakenas

recommendedandthereforeifadrugismedicallynecessary,itmaybe

prescribedbyamedicalspecialist.

3. ConditionalRiskofTdP:ThesedrugsareassociatedwithTdPBUTonly

undercertainconditionsoftheiruse(e.g.excessivedose,inapatientwith

conditionssuchashypokalemia,orwhentakenwithinteractingdrugs)OR

bycreatingconditionsthatfacilitateorinduceTdP(e.g.byinhibiting

metabolismofaQTprolongingdrugorbycausinganelectrolytedisturbance

thatinducesTdP).Thesedrugscanbeprescribedsafelyformostpatients

withcongenitalLQTSbecauseeachdrug’sriskisconfinedtocertain

conditions.Prescribingphysiciansshouldbeawareoftheseconditions

beforeprescribingthesemedications.

4. CongenitalLQTSRisk:Thesedrugshaveatheoreticalriskofcausing

arrhythmiasinsomecongenitalLQTSpatientsbecausetheyhaveadrenaline-

likeeffects.However,manyofthesemedicationsarerequiredfortreatment

ofasthma,ADHD,ornasalcongestion.Physicianswithexpertiseinthe

treatmentofarrhythmiasmayprescribethesemedicationstocarefully

selectedcongenitalLQTSpatients.

Pleaserefertothefollowingwebsiteformoreinformation:

https://www.crediblemeds.org

Figure1:CategoriesofDrugstoAvoidincongenitalLQTS

Itisimportanttorememberthatsomeofthecategorizationmaybetheresultof1or

2casereportsoradverseevents.Thereportedeventsmayhavehadconfounding

factorssuchassynergisticuseofhigherriskmedicationsortimesofincreased

sympatheticstimulationsuchasemergencefromanesthesia.Itisprudentto

minimizeexposuretocombinationsofdrugswithanydegreeofQTprolongeffect,

whereindividualeffectsonrepolarizationmaybeminorandclinicallyinsignificant

butthecombinationmayhaveadeleteriousimpact.

Anesthesia/PerioperativemedicationsandcongenitalLQTS:

MeasuringQTcprolongationisthetraditionalmethodforassessingandquantifying

adrug’simpactonelectricalrepolarization.Forexample,allvolatileagentsprolong

theQTcintervalwhereasIVpropofolhasclinicallyinsignificanteffectsontheQTcin

healthychildren(REF).SomeexpertsquestionwhetherQTcisareliablemetricfor

assessingadrug’spropensitytoinducetorsadedepointeasthedegreeofQTc

prolongationmaynotadequatelypredicttheriskforTdP.Anexaggerated

transmuraldispersionofrepolarization(TDR)isthoughttobetheelectro-

physiologicalsubstratefortorsadedepointeandsomeexpertsbelievethiscanbe

measuredonsurfaceECGastheintervalbetweenthepeakandendoftheTwave

(Tp-e).Studiesofsevofluraneandpropofolinhealthychildrenhavedemonstrated

noincreaseinTp-e,whichmaysuggestthatneitheristorsadogenic.However,since

SevofluranedoesmarkedlyprolongtheQTinterval,theclinicalimplicationsof

translatingresultsfromhealthychildrentothosewithLQTSremainsunclear.The

followingisareviewofthemostcommonlyusedanestheticsandperi-operative

medicationsused.

Volatileanesthetics:AllHalogenatedvolatileagentscanprolongtheQTinterval.

SevofluranehasthemostsignificanteffectonQTprolongationandSevoflurane

maintenancehasbeenimplicatedinafewcasereportsofventriculararrhythmias.

Sevofluranehasbeenlistedonthecrediblemeds.orgwebsiteasadrugtobeavoided

incongenitalLQTSandiscategorizedasKnownTdPRisk.Isofluranehasbeenused

safelyinpatientswithcongenitalLQTSandisnotlistedonthedrugstobeavoided

oncrediblemeds.org.

Ketamine:Hasbeenusedsafelyinthepastasapremedicationinpatientswith

undiagnosedcongenitalLQTS.Thereisatheoreticalpotentialforits

sympathomimeticpropertiestoinduceTdPbutitisNOTcurrentlylistedasadrug

tobeavoidedincongenitalLQTSontheCredibleMeds®website.

Propofol:DataonQTprolongationisconflicting.SomedatashowsthatPropofol

canrapidlyreverseQTcprolongationinducedbySevofluraneinhealthypatients.

However,theCredibleMeds®websitehaslistedPropofolasadrugtobeavoidedin

congenitalLQTSandhascategorizeditasadrugwithKnownTdPRisk.

Etomidate:Doesnotaffecttherateofventricularrepolarizationbutastudydid

showthatetomidateprolongsQTcmorethanpropofolinpatientsundergoing

electroconvulsivetherapy.ItisNOTcurrentlylistedasadrugtobeavoidedin

congenitalLQTSontheCredibleMeds®website.

Midazolam:DoesnotmodifyQTcorthetransmuraldispersionrateandis

consideredasafemedicationforpatientswithcongenitalLQTS.Recommendedfor

pre-operativeanxiolysis.

Opioids:Remifentanil,Alfentanil,Fentanylandmorphineareconsideredsafein

patientswithcongenitalLQTS.AlfentanilhasbeenshowntoreverseQT

prolongationseenwithSuxamethoniumduringtrachealintubation.

MuscleRelaxation:Suxamethoniumshouldbeusedwithcautionsinceitmay

prolongQTintervalinpatientswithcongenitalLQTSorinduceavagalresponse,

whichmayresultinpausedependentTdP.SuxamethoniumisNOTcurrentlylisted

ontheCredibleMeds®website.Vecuronium,AtracuriumandCisatracuriumdonot

prolongQTcandcanbesafelyused.Pancuroniumshouldbeavoidedbecauseofits

vagolyticpropertiesanditscausalassociationwithVFinacasereport,althoughitis

currentlyNOTlistedontheCredibleMeds®website.Rocuroniumcanalso

sometimescausetachycardiaandshouldbeavoidedifpossible,althoughitis

currentlyNOTlistedontheCredibleMeds®website.

Dexmedetomidine:CurrentevidenceforDexmedetomidineandQTprolongation

islimitedandconflicting.However,theCredibleMeds®websitehaslisted

DexmedetomidineasadrugtobeavoidedincongenitalLQTSandhascategorizedit

asadrugwithPossibleriskofTdP.

Anticholinesterase:Administeringanticholinergicagentssuchasatropineand

Glycopyrrolateandtheresultingtachycardiaduetounbalancedsympathetic

stimulationmayincreasetheriskforventriculararrhythmias.However,noneofthe

muscarinicanticholinergicagentsoranticholinesterasesarelistedasdrugstobe

avoidedincongenitalLQTS.

Sympathomimetics:Dopamine,Epinephrine,PhenylephrineandEphedrineare

knowntocauseTdPandarelistedontheCredibleMeds®websiteasdrugstobe

avoidedincongenitalLQTS.TheyarecategorizedasKnownTdPRisk.Vasopressin

isoneoftheonlyperipheralvasoconstrictormedicationsthatisconsideredsafein

congenitalLQTSandisNOTlistedontheCredibleMeds®website.

Anti-emetics:OndansetronanddroperidolareknownprolongtheQTcandare

knowntocauseTdP.Theyshoulddefinitelybeavoidedinpatientswithcongenital

LQTs.TheyarelistedontheCredibleMeds®websiteasdrugstobeavoidedin

congenitalLQTSandarecategorizedasKnownTdPRisk.

LPCHPERI-OPERATIVEMANAGEMENTGUIDELINES:

Therearenopublishedguidelinesforoptimalperi-operativemanagementof

patientswithcongenitalLQTS.Aswithmanypediatricdiseases,thereremainsa

lackofarobustevidencetosupportoneparticularpracticeguideline.Currentdata

ontheeffectsofanestheticandperi-operativemedicationsinpatientswith

congenitalLQTSconsistsofcasereports,smallcaseseriesandretrospectivereviews

withdifferingoutcomes.Althoughthetrueriskofperi-operativearrhythmiasis

hardtoquantify,significantmorbidityandmortalityhasbeenreportedunder

generalanesthesiaespeciallyinthosewithundiagnosedoruntreatedcongenital

LQTS.Afterreviewingthecurrentliterature,wehavewrittenthisdocumentto

serveasaguidetoperi-operativemanagementofpatientswithcongenitallongQT

syndromeatLucilePackardChildren’sHospitalatStanford(LPCH).

Pre-operativeassessment:

Historyandphysicalexamination:

Inadditiontostandardpre-operativehistoryandphysicalexam,anypatientwith

congenitalLQTSshouldbeaskedspecificallyaboutsymptomcontrolwithcurrent

medicationregimen(palpitations,dizziness,syncope),compliancewithmedication

andanyconcerningnewsymptomssuchasfatigue,poorexercisetolerance,

nightmares,seizures,pre-syncopeorsyncope.Anyidentifiednewsymptoms

warrantapre-operativediscussionwiththepatient’scardiologistorLPCH

Electrophysiologist.

Investigations:

1. Lookfornotesfrommostrecentcardiologyclinicvisit.Iftheyhavenotbeen

seenbytheirprimarycardiologistorelectrophysiologistwithinthelastyear,

theyshouldhaveaclinicalevaluationbytheirprimarycardiologistor

electrophysiologistbeforeanyelectiveprocedure.Iftheyarehavingan

urgent/emergentprocedurethatshouldnotbedelayed,consultationby

phonewiththeirprimarycardiologistorelectrophysiologistiswarranted.

TheirevaluationstypicallyincludeanECG,ambulatoryheartrhythm

monitor,andpossiblyanexercisestresstestdependingontheirage.

2. RecentECG(within3monthsofprocedureifwellcontrolled)-lookfor

restingHRandQTcinterval.

3. Recentelectrolytes:KandMgshouldbenormalized.

Medications:

Itisessentialtocontinueanti-arrhythmicdrugtherapyincludingonthedayof

surgery.PatientsonB–Blockertherapymaybeatincreasedriskofhypoglycemia

andshouldhavebloodsugarmonitoredduringtheperi-operativeperiod.

Avoidperi-operativephysiologicalandmetabolicstressorsofmyocardial

repolarizationreservesuchaspain,fear,dehydration,hypothermiaandelectrolyte

disturbance.

HIGHRiskCongenitalLongQTPatients:

PatientswhosatisfyANYofthefollowingcriteria:

1. Anyonepresentingwithnewsymptoms(syncope,palpitations)thathavenot

yetbeenadequatelyevaluatedortreated

2. QTinterval>500ms

3. AnypatientwithLongQTandanICD

4. Timothysyndrome(LQT8)

Adedicatedpediatriccardiacanesthesiologistorananesthesiologistwhohas

completedadvancedtraininginpediatriccardiacanesthesiashouldcareforpatients

whohavebeenidentifiedasfallingintoahigh-riskgroup.Ageneralpediatric

anesthesiologistcancareforallothercongenitalLongQTpatients.

Inductionofanesthesia:

AlthoughIVinductionispreferable,theanesthesiologistshouldconsider

minimizingpre-operativestressandanxiety.

1. Midazolampremedicationissafeandeffective.

2. ECGmonitoring-recommendtrendingQTcpreoperatively,throughout

procedureandpost-operative

3. Ifplacementofpre-opIVisthoughttobeproblematicandmaycauseundue

stresstothepatientbriefperiodsofsevofluraneinductionhasbeenreported

intheliteratureasbeingsafelyusedwithoutadverseeffectuntilanIVcan

beplaced.

4. Bothintubationandextubationmaytriggerventriculararrhythmias.

Considertopicalanesthesiawithlidocaineforintubationsupplementedwith

anopioidtominimizeadrenergicsurges.IntravenousBBlockermayalsobe

consideredpriortointubationorextubation.Itisprudenttoavoidhigh

inspiratorypressurepeaksandwideinspiratory/expiratoryratiossincethe

ValsalvamaneuvermayalsoprolongtheQTc.

5. Adefibrillatorandstafftrainedinits’useshouldbereadilyavailableduring

theperi-operativeperiod.

Maintenanceofanesthesia:

1. Ifusingavolatileagent,isofluraneisthepreferredagent.

2. Opioidsmaybeusedsafely.

3. Cautionwithpropofol(CredibleMeds®websitehaslistedPropofolasadrug

tobeavoidedincongenitalLQTSandhascategorizeditasadrugwith

KnownTdPRisk)anddexmedetomidine(CredibleMeds®websitehaslisted

DexmedetomidineasadrugtobeavoidedincongenitalLQTSandhas

categorizeditasadrugwithPossibleriskofTdP).

4. Cis-atracuriumorVecuroniumisthepreferredNMBagent.Cautionwith

reversalagents.Considerdeepextubationifappropriate.

5. Monitorbloodsugar.

EMERGENCYMEDICATIONS

Arrhythmias:

1. Esmolol250-500mcg/kgIVbolus,25mcg/kg/mininfusiontitrateevery10-

15minupto250mcg

2. Magnesium25-50mg/kgslowIVbolus

3. Lidocaine1mg/kgIVbolus,then25mcg/kg/mininfusion

DoNOTuseamiodaroneforarrhythmiasincongenitalLongQTsyndromeas

thiswillfurtherprolongtheQTinterval.

ForVentricularFibrillationArrest–CPRandDefibrillationassoonaspossible.

Esmolol,Lidocaine,andMagnesiumpreferredanti-arrhythmicagentsas

amiodaroneandepinephrinewillfurtherprolongQTcandworsenarrhythmias

Hypotension:

1. IVfluidbolus

2. Vasopressinissafeandthepreferredvasoconstrictormedication

Drugsthatarecontraindicatedforroutinehypotension-phenylephrine,

ephedrine,epinephrineandDopamine.

Regionalanesthesia:

Localanestheticswithoutepinephrine

Post-operativecare:Post-operativedispositionwilldependonthepatient’sconditionandtheprocedure

performed.Werecommendpost-operativehospitaladmissionwithtelemetric

monitoringinanintensivecareunitforpatientswithhighriskcongenitallongQT.