Regional anaesthesia and analgesia in the neonate

13 Pages·2010·0.19 MB·English

BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
ContentslistsavailableatScienceDirect
Best Practice & Research Clinical
Anaesthesiology
journal homepage: www.elsevier.com/locate/bean
2
Regional anaesthesia and analgesia in the neonate
Per-Arne Lönnqvist, MD, DEAA, FRCA, PhD, Professor of Paediatric
Anaesthesia &; Intensive Care, Senior Consultanta,b,*
aSectionofAnaesthesiology&IntensiveCare,DepartmentofPhysiology&Pharmacology,KarolinskaInstitute,
SE-17177Stockholm,Sweden
bPaediatricAnaesthesia&IntensiveCare,ALB/KarolinskaUniversityHospital,SE-17176Stockholm,Sweden
Keywords: Alargenumberofpublishedstudieshaveshownthattheuseof
regionalanaesthesia diverse regional anaesthetic techniques is associated with high-
neonatal quality pain relief following the different types of surgery and
regionalanaesthesia painful procedures that are commonly performed in neonatal
localanaesthetics patients. Apart from pain, few studies have examined other
regionalanaesthesia outcomesinthissetting.Somedatasuggestabenefitwithregional
adjuncts
anaesthesia.Inaretrospectivestudy,Bosenbergetal.foundthat
neonates
the use of epidural analgesia in neonatal patients undergoing
clonidine
ketamine tracheo-oesophagealfistularepairresultedinareducedneedfor
postoperative mechanical ventilation. Furthermore, epidural
analgesia was found to be associated with a significant and
beneficial modification of the neuroendocrine surgical stress
responseaftermajorabdominalsurgeryininfantswhencompared
topostoperativemorphineinfusions.Theuseoflocalanaesthetics
inassociationwithneonatalcircumcisionhasalsoshownabenefit
as neonates not treated with eutectic mixture of lidocaine and
prilocaine (EMLA) or a penile block had an exaggerated pain
responsetolatervaccinationsascomparedwithneonatestreated
withalocalanaesthetic technique.Finally,safety datagenerated
from large, prospective studies and audits clearly show that the
useofpaediatricregionalanaesthetictechniquesisassociatedwith
adequate safety also in neonatal patients. In conclusion, a large
varietyoflocalandregionalanaesthetictechniquescanbesafely
usedinneonatalpatients.Theuseofsuchtechniquesmustobvi-
ously be associated with sufficient knowledge about the various
* Paediatric Anaesthesia & Intensive Care, ALB/Karolinska University Hospital, SE-17176 Stockholm, Sweden. Tel.: þ46
851774705;Fax:þ46851777265.
E-mailaddress:[email protected].
1521-6896/$eseefrontmatter(cid:1)2010ElsevierLtd.Allrightsreserved.
doi:10.1016/j.bpa.2010.02.012
310 P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
techniques, as well as adherence to adequate dosage guidelines
and other safety precautions. However,if these prerequisites are
met, regional anaesthesia may offer great advantages to our
smallestandmostvulnerablepatients.
(cid:1)2010ElsevierLtd.Allrightsreserved.
Sincethe1980s,alargenumberofstudiesandscientificdatahaveshownthatbothneonatesand
prematurebabiesdopossesstheneuro-anatomicalandsynapticprerequisitestoperceivenociceptive
stimulation. Clinical studies by Anand and co-workers, focussing on the importance of providing
adequate analgesia to our smallest patients, have clearly shown that insufficient intra- and post-
operativeanalgesiadoesresultinanexaggeratedneuroendocrinestressresponse,increasedmorbidity
andevenincreasedmortalityinthecaseofneonatalcardiacsurgery.Thereisalsoevidencethatthe
foetushasasimilarresponse.Ithasalsobeenshownthat,comparedtopunctureofthenon-innervated
umbilicalcord,intrauterineexchangetransfusionsperformedthroughtheinnervatedabdominalwall
ofthefoetusresultinagreaterneuroendocrinestressresponseandsubsequentbehaviouralchanges.1,2
Notonly mayinsufficient pain relief be associated with negative short-term effects but insufficient
neonatalanalgesiaalsohaslong-termeffects.Taddioetal.haveclearlyshownthatneonatalboyswho
werecircumcisedwithoutanalgesiahaveamorepronouncedpainexperiencetolaterimmunisation
injections,comparedwithboyswhohadreceivedactiveanalgesiabymeansofEMLAcream(EMLA,
eutectic mixture of lidocaine and prilocaine).3,4 Thus, there is no doubt that both neonates and
prematurebabiesshouldreceiveadequatepainreliefforbothsurgicalinterventionsaswellaspainful
proceduresoutsidetheoperatingtheatre,forexample,intheneonatalintensivecareunit(NICU).
Oneofthebest,andmaybealsothesafest,waystoprovidehigh-qualityanalgesiaiswiththeuseof
localanaesthesia,eitheraloneorincombinationwithotherdrugs.Thesmallsizeofneonatalpatients
doesnotinanymannerprecludetheuseoflocalorregionalanaesthetictechniques.Theaimofthis
reviewistoprovideclinicallyusefulinformationonhowtouseregionalanaesthesiaandanalgesiain
asafeandeffectivewayinneonatesandprematurebabies.
Topicalapplicationandlocalinfiltration
All newborn babies should undergo metabolic screening and are therefore subjected to blood
samplingsoonafterbirth.Thisisfrequentlyaccomplishedbyheellancing,whichisassociatedwith
asignificantpainexperience.Althoughnotlicensedforuseinneonates,attemptstouseEMLAcream
priortoheellancinghavenotproducedgoodanalgesiaforthisprocedure.5Apossibleexplanationfor
thismaybethehighskinbloodflowinthisarea(thereasonforperformingsamplingatthisanatomical
point).6 By contrast, a recent Cochrane report has found the use of EMLA cream to have beneficial
effectsonpaincausedbycircumcision;beingbetterthanplacebobutlesseffectivethanapenilenerve
block.4Thus,althoughitappearsthattheefficacyofEMLAcreaminthisagegroupisdependentonthe
siteofapplication,itcanbesuccessfullyusedforanumberofdifferentproceduresinneonatesand
infants.7,8OnemustalsobecarefulwithregardtotheamountofEMLAcreamthatisappliedsoasnotto
subject the child to the risk for symptomatic methaemoglobinaemia caused by the prilocaine
componentofEMLA.Therearelimiteddatadescribingtheuseoftheotherlocalanaestheticcreams
(AmetoporRapidan)inneonatesandprematurebabies.
Inneonates,thetopicalsprayoflidocainetothelarynxandtracheacansuccessfullyminimisethe
nociception and haemodynamic stress response associated with airway manipulations. Since the
actualsprayinginthesesituationsisoftenperformedbytheear,noseandthroat(ENT)surgeon,itisof
greatimportancefortheanaesthetisttonotetheconcentrationofthelidocaineusedandlimitthedose
toreducetheriskofsystemictoxicity.InastudybyGjonajetal.,ithasbeenfoundthat8mgkg(cid:2)1of
lidocainecanbenebulisedwithoutreachingtoxicplasmaconcentrations.9
For more localised procedures, such as cut-down for silastic catheter placement, intra-osseous
needleinsertionfor vascularaccessandbonemarrowaspiration, theinjectionoflocalanaesthetics
atthesiteoftheprocedureisaneasybutoften-forgottentechnique.Aswithotherregionalanaesthetic
P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321 311
techniques,itisimportanttokeeptoasafetotaldoseoflocalanaesthetic.Oneshouldalsonotethatthe
adjunctuseofadrenalineisassociatedwithpronouncedinjectionpain/burningandshouldthusbest
beavoidedifthechildisnotundergeneralanaesthesiaalready.
Equipment
Datafromthe1996FrenchLanguageSocietyofPaediatricAnaesthesia(ADARPEF)studyshowthat
50%ofthecomplicationsofregionalanaesthesiawereduetotheuseofthewrongtypeofregional
anaesthesia equipment; most often, the use of adult-sized equipment in paediatric patients.10
Currently, age-specific regional anaesthesia equipment is commercially available. Epidural catheter
kitswithTouhyneedlesdowntothesizeof19e20-Gaswellas24-Gstylettedcaudalneedlesarenow
produced by various manufacturers. Further, recently, a specific kit to facilitate the use of the Tsui
method(seebelow)hasalsobeenmadecommerciallyavailable.Thus,thereiscurrentlynosupportor
rationalefornotusingage-adequateequipmentinchildren.
Centralnerveblocks
Spinal(intrathecal)blockade
This technique has been described in detail elsewhere in this issue. Awake spinal (intrathecal)
blockade is a well-described technique to produce surgical anaesthesia mainly for inguinal hernia
repairintheex-prematurechild.11Surprisinglylargeamountsoflocalanaestheticsarenecessaryto
produce anadequateblock (0.14mlkg(cid:2)1 ofbupivacaine 0.5%).12 A prolongation of the block canbe
achievedbytheadditionofclonidine(1mcgkg(cid:2)1).13Theuseofaspinalblocktechniquetoproduce
acompletespinalblockadeinassociationwithneonatalcardiacreconstructivesurgeryhasalsobeen
recentlydescribed(withorwithoutanintrathecalcatheterthatwillallowtheadministrationoftop-up
doses) and is reported to produce excellent conditions for this type of advanced surgery, including
beneficialmodificationoftheneuroendocrinesurgicalstressresponse.14Thismethodhassofaronly
beenusedinpatientswhoaresupportedbyextra-corporealbypass,whichprovidesadequatesafety
should excess haemodynamic reactions occur. Against this background, this technique should at
presentnotbeusedoutsidethisspecificindicationexceptaspartofanapprovedclinicaltrial.15
Caudalblockade
Thisblockisoneof themostbasic regionalanaesthetictechniquesinchildren,andisalsowell-
suitedtothesmallestpatientcategory.16Itisoneoftheeasiestblockstolearnwithonestudysug-
gesting only 32 blocks are necessary before reaching adequate success rates.17 A caudal block can,
dependingonthedoseandvolumeofthelocalanaesthetic,produceadequateanaesthesiauptothe
mid-thoracicregionand,thus,canbeusedeitheraloneasanawaketechnique,orasasupplementto
general anaesthesia for all surgical procedures from the mid-thoracic level down (Table 1). With
ultrasound,itisnowpossibletovisualisetheinjectionoflocalanaestheticsinthecaudalspaceaswell
asmonitorthecranialspread.18Theuseofultrasoundishighlyrecommendedinneonateswhoreceive
concomitantgeneralanaesthesia,butismuchmoredifficulttouseintheawakeandmobilebaby.
Althoughthisblockcanbeusedforalmostallsurgicalinterventionsbelowtheleveloftheumbilicus
inneonatalbabies,theuseofthistechniqueinassociationwithneonatalinguinalherniarepairisbyfar
themostcommonone.
Table1
Caudalblockade.Levelsofsurgicalanaesthesiainrelationshiptoinjectedvolumeoflocalanaesthetic.Modifiedaccordingto
Armitage.72
Volumeofcaudalinjectate(mlkg(cid:2)1) Typicalsurgicalprocedures
0.5 Urogenitalþclubfootsurgery
1.0 Subumbilicalsurgery
1.25 Surgicalproceduresbelowthemid-thoraciclevel
312 P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
Theawakecaudaltechniqueisausefulalternativetogeneralanaesthesiainex-prematureinfants
who often suffer fromvariousdegreesof bronchopulmonary dysplasia. Such babies oftenhavehad
great difficulties to be weaned from mechanical ventilation and both parents and neonatologist
frequentlywanttoavoidtherisksinvolvedwithgeneralanaesthesiaandre-intubationofthetrachea.
Theuseoftheawakecaudaltechniquewillalsolimittheriskforpostoperativeapnoeainthisspecific
patientcategory.However,forthistobetrue,theblockmustbecarriedoutwithouttheuseofadjunct
sedatives(e.g.,midazolam,ketamineandlow-concentrationssevofluranebynasalprongs);otherwise
theriskforpostoperativeapnoeawillnotbereducedasexpected.Eveninthecaseofa‘pure’awake
caudaltechnique,theseneonatalpatientscannotbetransferredtoanordinarywardaftersurgerybut
must remain in an neonatal intensive care unit/high dependency unit (NICU/HDU) environment
overnight.Thisisparticularlytrueifsupplementaldrugssuchasketamineorclonidinehavebeenused
asadjunctstothelocalanaestheticsolution.19
Theuseofsupplementalsedation,however,isoftennotnecessarysincethesystemicabsorptionof
thelocalanaesthetictogetherwithlossofsensoryinputfromthelowerbodyusuallymakethechild
sleepy/sedatedapproximately15e20minfollowinginjection.20Caremustbetakennottoexceedthe
maximum dosage recommendations, particularly since these patients do not receive any sedative
drugsthatwouldusuallyincreasetheseizurethreshold.Theadministrationof3mgkg(cid:2)1ofracemic
bupivacainehasbeenshowntoproducepre-toxicEEGsignsinthispatientcategory.20Theadminis-
tration of oral sucrose can also be helpful in neonates with awake caudal anaesthesia. It not only
alleviatesthediscomfortofpreoperativestarvationbutalsohassignificantanalgesicproperties.21
Evenifthemostfrequentindicationfortheawakecaudaltechniqueinneonatesisinguinalhernia
repair,thistechniquecanalsobeveryusefulforvenouscatheterplacementinthesaphenousorfemoral
vein,andotherlowerlimbprocedures.Onespecificindication,thathasprovenusefulintheauthor’s
experience,istoprovideadequateanalgesiaandabdominalwallrelaxationwhenperforminganawake
reductionofgastroschisisaccordingtotheBianchitechnique22soonafterbirth(unpublisheddata).
Epiduralblockade
Since the popularisation of this technique for use in paediatric patients in the late 1980s, this
techniquetoproduceintra-andpostoperativepainreliefhasbecomeastandardprocedureinchildren.
Bosenbergandco-workershavebeenthepioneerswithregardtoitsuseinneonatalpatients23and
could showin an earlystudy thatepidural blockade drastically reduced the need for postoperative
ventilationinneonatesundergoingtracheo-oesophagealfistularepair.24Furthermore,Wolfetal.have
clearlyshownthattheuseofepiduralblockadeininfantsundergoingmajorabdominalsurgeryresults
insignificantlybettermodificationoftheneuroendocrinesurgicalstressresponsethanpostoperative
intravenousmorphineinfusion.25Theuseofepiduralanalgesiamayalsoshortentheperiodofpost-
operative paralytic ileus in small babies.26 Large observational studies have shown that the use of
epiduralanalgesia,eveninneonatesisassociatedwithanacceptableriskebenefitprofile.27Although
theuseofepiduralblockadeinneonatesandinfantshasbeenquestionedbysome,28thismethodfor
intra- and postoperative analgesia represents one of the cornerstones of high-quality analgesia for
neonates undergoing more extensive surgical interventions. Some technical aspects of neonatal
epiduralblockadearediscussedbelow.
Loss-of-resistance(LOR)
The use of air for loss-of-resistance (LOR) has been much debated since the use of air has been
reported to cause both intravascular air embolism as well as permanent spinal cord injury.29e31
Althoughthisargumentisnotfinallysettled,ithasbeenrecommendedtouseonlysalineforLORin
paediatricpractice.32
Useoftestdosing
Duetothelimitedsizeoftheequipmentusedinsmallchildren,inadvertentintravascularplace-
mentoftheepiduralcathetercannotbereliablyidentifiedsolelyfromspontaneousbackflowinthe
catheterorfromanaspirationtest.Thereisalsocontroversyovertheutilityofusinganadrenaline
containingtestdose.TheoccurrenceofaheartrateincreaseorchangesinT-waveappearanceonthe
P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321 313
electrocardiograph(ECG)asaresultofinadvertentintravascularadministrationisinfluencedbythe
inhalationalanaestheticagentusedandifthechildhasreceivedatropinepriortotheadministrationof
thetestdose.33Sinceanegativeresultoftheuseofatestdoseisnotconclusive,manycliniciansdonot
routinelyusethissafetyprecautioninchildren.
Insertionattheappropriatedermatomallevelinrelationtothesurgicalintervention
Ofparamountimportancetoachieveawell-functioningepiduralblockisthatthetipoftheepidural
catheterissituatedatanintraspinallevelthatcorrespondstothedermatomalcentreofthesurgical
procedure.Thus,havingthetipofthecatheteratthelumbarlevelwillnotproduceadequateanalgesia
ifthepatientisundergoingathoracotomy.Themoststraightforwardapproachtogetthecathetertipat
therightintraspinallevelistoperformtheepiduralpunctureattheappropriatedermatomallevel,for
example,atTh8foramajorupperlaparotomyoratTh5foraposterolateralthoracotomy.However,to
makethistechniquereallyreliable,itisimportantnottoinsertmorethanafewcentimetresofthe
catheterintotheepiduralspace.
Despitethelowriskformajordamageassociatedwiththoracicepiduraluseinchildren10,27therisk
fortraumaticspinalcordinjurydoesstillexist,ashasbeendemonstratedbyoccasionalcasereports.34,35
Inordertoavoideventheslightestriskfortraumaticcordinjury,andtoreducetheriskofcatheter
dislodgmentmanypaediatricanaesthetists,favouralternativemethodsforepiduralcatheterinsertion.
Blindcaudalcathetertechnique
Since neonates and non-walking infants have not yet developed the adult pattern of spinal
curvatures, it is possible to access the epidural space at the caudal hiatus, and then insert a pre-
determinedlengthofthecathetertoreachthedesiredspinallevel.Ifusingthistechnique,whichwas
firstdescribedbyBosenberg,36itisimportantnottouseaTouhyneedlesinceitisverydifficulttoget
therightalignmentof theeyeof theTouhyneedlewiththespinalcanal.Toimprovethechanceof
successtheuseofaCrawfordneedleoraregularintravenouscatheterisrecommended.Averyhigh
successratehasbeenclaimedwiththisblindapproach,eventotheextentthatcertainauthorshave
suggestedthatradiographicverificationofthecathetertiplocationisunnecessary.37However,other
publicationshaveamplyshownthatcathetersthreadedfromthecaudalspacedonotatallbehavein
apredictableway,andthatradiographicverificationisclearlyindicated.38Althoughthisapproachis
appealingduetoitssimplicity,theneedforradiographicverificationincreasescomplexity.Notethatif
thetippositionissuboptimaltheadministrationofepiduralmorphinemaybeconsidered,asitseffect
isnotdependentonpreciseanatomicaladministration.
The method of threading the catheter via the caudal route may have a renaissance if it proves
possibletoeasilycheckthecathetertippositionwiththeaidofhighperformanceultrasoundimaging,
somethingthatunfortunatelyisnotsufficientlyreliableatpresent.
Nervestimulation-guidedtechnique:‘Tsui-technique’
Tsuietal.hasrecentlydescribedamethodwherebythecatheterisattachedtoanervestimulator.39
Afterinsertionofthecatheterthroughthesacralhiatusintothecaudalspace,thecurrentisincreased
to1e10mA.Thecatheteristhenslowlyadvancedinthecranialdirectioninasimilarmannertotheblind
techniquedescribedbyBosenberg.Themajoradvantagewiththistechniqueisthattheoperatorwillbe
abletofollowthemuscularresponseasthetipofthecatheteradvancesthroughthespinalcanal(this
obviouslyrequiresthatthepatientbenotparalysed!).Thetipofthecatheterisadvanceduntilmuscle
contractions are visible or palpable at the appropriate level for the planned surgical procedure. An
unexpectedmuscularresponsewillalerttheclinicianthatthecatheterisnotthreadingasexpectedand
thecatheterisslightlywithdrawnandthepatientpositionmodifiedandthecatheteradvancedagainuntil
thedesiredresponseisachieved.Tsuietal.havereportedverygoodsuccessrateswiththistechnique,and
aspecialkitforthistechniqueisnowcommerciallyavailable(althoughbeingquiteexpensive).
Ultrasound-guidedepiduraltechnique
Recently, Willschke et al. have described an ultrasound-guided approach to perform epidural
blockadeinneonatesandinfants.40,41Thismethoddoesprovidereal-timevisualisationoftheepidural
puncture as well as catheter insertion. Despite the merits of this technique, it is technically very
314 P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
demandingsinceitrequiresthehelpofawell-experiencedultrasoundassistant(‘experiencedthird
arm’),anditisalsodifficulttofindgoodworkingspaceandconditionsduringtheperformanceofthe
block.Thefuturewilltellwhetherthisnewapproachwillbecomestandardprocedureorifitwillbe
reservedforveryspecialindications.
Peripheralnerveblocks
Peripheralnerveblocksrepresentaveryelegantwayofproducinganalgesiaforsurgeryorpainful
procedures. However, the indications for peripheral nerve blocks in neonates are limited. One very
usefulindicationisinfraorbitalnerveblocksforneonatalcleftlipsurgery.42Ultrasound-guidedilioin-
guinal/iliohypogastricnerveblocksrepresentarelevantalternativetocaudalblocksforinguinalhernia
repair,43e45butcanonlybeusedasasupplementtogeneralanaesthesiaandnotasan‘awake’technique.
Othertypesofperipheralnerveblocksmay,ofcoure,beusedinspecificinstances,forexample,axillary
plexusblockforupperlimbischaemiafollowingarterialcannulationinprematurebabies46ortransverse
abdominal plane (TAP) blocks for major neonatal abdominal surgery.47 Indications for continuous
peripheralcathetertechniquesarerareintheneonatalpopulationbutcontinuousthoracicparavertebral
nerveblockscanprovideanalternativetoepiduralanalgesiaandmaybeusedforunilateralsurgical
procedureonthetrunk,forexample,posterolateralthoracotomyorrenalsurgery.48,49
Wound-infiltrationtechniques
Localinfiltrationandwoundinstillationwithlocalanaesthetichavebeendescribedinassociationwith
inguinalherniarepairbutonlyproduceabriefeffect.Inadultpractice,theuseofcathetersinthesurgical
woundhasrecentlybecomequitepopularforavarietyofsurgicalinterventions,andrecently,Tirottaetal.
describedthesuccessfuluseofwoundcathetersafterpaediatriccardiacsurgerybymediansternotomy,
withbetterpainrelief,lessopioidconsumptionandlessneedforsedativesupplementationcomparedto
a placebo wound infusion.50 The study adhered to the recognised dosage guidelines, and plasma
concentrationsoflevo-bupivacainewerefoundtobewithinsafelimits.However,onlyinfantsandchil-
drenolderthan3monthsand/orweightmorethan5kgwereincludedinthestudy.Successfuluseof
continuouswoundinfiltrationforiliacbonegraftinginolderchildrenhasalsorecentlybeendescribed.51
Thetechniqueofcontinuouswoundcathetersrepresentsanattractiveavenuetoachieveadequate
postoperativepainreliefinneonatesandsmallinfantsasthecathetercanbeplacedunderdirectvision
bythesurgeon,andtherefore,theriskforcomplicationsisminimised.Nopublisheddatasofarexistin
thispatientcategorybut,attheKarolinskaUniversityHospital,wearecurrentlyconductingstudies
bothintermneonatesaswellasinprematurebabiesundergoingductusligationusingthistechnique.
Preliminaryresultsfromtheductusligationstudyshowthattheuseofindwellingwoundcatheters
reducesthedurationofthesupplementalmorphineinfusionfrom4.5to2postoperativedaysaswellas
lowersthetotalpostoperativemorphinerequirementsbymorethan50%(Fig.1).However,moredata
areneededtoclarifyifwoundcathetertechniquescanchallengeotheralternativestoproducegood-
qualitypostoperativepainreliefinneonatalpatients.
Riskofcomplicationsandsafetyissues
Duringtheearlydaysofthemorewidespreaduseofregionalanaesthetictechniquesininfantsand
children,therewereanumberofcasereportsandcaseseriesofseriouscomplications,includingboth
systemic toxicity (seizuresand ventriculararrhythmias), traumatic injuryof the spinal cord and air
embolism. These reports prompted both an Anesthesia Patient Safety Foundation (APSF) study
resulting in the generation of dosage guidelines (see below) as well as a prospective study on the
complicationsassociatedwiththeuseofregionaltechniquesinchildren.10Thislaterstudyperformed
by ADARPEF included more than 24000 paediatric regional blocks and found the incidence of
complicationstobeapproximately1/1000;ofwhichnoneresultedinanylong-termsequalaeorlegal
action.Of further interest,peripheral nerve blockswere notfound tobeassociated withany major
complications at all. Use of caudal blocks in the age groupterme6 months of agewas found tobe
associatedwiththehighestincidenceofcomplications(0.37%).Averyrecentfollow-upstudybythe
P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321 315
Morphine infusion (microg/kg) tot
800
700
600
500
400
300
200
100
0
without local anaesthesia with local anaesthesia
group A group B
Fig.1. Effectof woundcatheterinfiltrationwith levobupivacainefollowingductus ligationinprematurebabies.The need for
morphineinfusionwassignificantlyshorter(1,8vs.4,5days)andthetotalmorphineconsumptionwassignificantlylowerinthe
grouptreatedwithwoundcatheterinfiltrationwithlevobupivacaine(274vs641mg/kg).74
same organisation has corroborated their earlier results, reporting an overall complication rate of
approximately 1/1000 blocks. An interesting trend in this new study was the use of many more
peripheralnerveblocks,includingcontinuouscathetertechniquescomparedwithcentralnerveblocks
(EcoffeyC,ADARPEF,personalcommunication).
Theresultsofalargeprospectivesafetystudyconcerningtheuseofpaediatricepiduralanalgesia,
including more than 10000 epidural blocks, has recently been published by the Association of
PaediatricAnaesthetistsofGreatBritainandIreland.27Theincidenceofpermanentcomplicationsthat
couldbeattributedtotheuseoftheepiduralblockwasapproximately1/10000blocks,whereasthe
incidenceoflessseverecomplicationswerefoundtorangebetween1/1000and1/2000.Theneonatal
subgroup, comprising 529 neonatal epidural blocks, had a 1.13% overall incidence of complications,
whichwassignificantlyhigherthaninotheragegroups.However,mostcomplicationsweredueto
drugerrorsorsystemictoxicityandnocomplicationsrelatedtocatheterinsertionwerereported.The
overall conclusion drawn from this large prospective audit was that the use of paediatric epidural
analgesia,regardlessofagegroup,isassociatedwithanacceptableriskebenefitprofile.
Althoughtheriskforsystemictoxicityhasbeensubstantiallyreducedfollowingthepublicationofthe
Berdedosagerecommendations,systemictoxicitycanstilloccurafterinadvertentintravascularinjec-
tion.Themorepreciseinjectionoflocalanaestheticsthatfollowstheuseofultrasoundguidancemay,in
fact,increasesystemicabsorptionofthelocalanaestheticsiftheamountisnotappropriatelyreduced.45
Sinceitispossibletoreducethevolumeoflocalanaestheticsusedbyatleast50%whenusingultrasound
guidance,52volumereductionisstronglyrecommendedwhenusingthisnewtechnique.
Theinfusionofalipidemulsiontotreatsystemictoxicityoflocalanaestheticshasrecentlybeen
described, and has been found surprisingly effective both in animal studies and in case reports.
Excellent web-based guidelines for dose are currently available.53,54 If regular measures to treat
systemiclocalanaestheticarenotimmediatelysuccessful,thenlipidshouldbeused(bolusof20%lipid
emulsion: 1.5mlkg(cid:2)1 followed by infusion of 0.25mlkg(cid:2)1 min(cid:2)1; if not successful, two additional
bolus injections can be given 5min apart). Successful use of this new treatment modality has also
recentlybeenreportedinaninfant.55
Currentdiscussionpointsregardinglipidforlocalanaesthetictoxicityincludewhetherthisnovel
treatmentshouldbestartedearlierinthetherapeuticsequencethanwhatiscurrentlyrecommended,
andifthedoseofadrenalineusedshouldbelimitedtoabolusinjectionof(cid:3)10mcgkg(cid:2)1.Thelatterissue
isbasedonananimalstudyshowingthathigherdosesofadrenalineareassociatedwithlessfavourable
outcome.56Interestingly,arecentstudyhassuggestedthatlipidisonlyeffectiveifbupivacainehasbeen
administeredandnotifthelesslipidsolublelocalanaestheticsropivacaineormepivacaineareused.57
Consideringcaudalblockade,therehasbeenanongoingdiscussionifnormalsharpbevelneedles
canbeusedorifitismandatorytouseastylettedneedledesign.Thereasonforthisdiscussionisthat
certain experts, for example, Dalens, claim that the use of non-styletted needles carries the risk of
introducinglivingskincellsintothecaudalspace,therebycausingtheriskforepidermoidgrowthin
the caudal space. This view has been questioned by others because centres that have performed
thousandsofcaudalblockshaveneverexperiencedthiscomplicationaswellasduetothelackofwell-
described case reports in the literature. Recently, new data have shown that only dead stratum
316 P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
Table2
Clinicallyrelevantkeypointsconcerningcomplicationstoregionalanaesthesiainneonatesandinfants.
1.Alwaysusepaediatricequipmentofcorrectsize.
2.Onlyusesalineforloss-of-resistance.
3.Rememberthatanegativetestdosedoesnotprovide100%securityagainst
inadvertentintravascularinjection.
4.Donotexceedthemaximumdosagerecommendationsforlocalanaesthetics.
5.HaveIntralipid20%immediatelyavailableincaseofsystemictoxicity.
6.Rememberthatepiduralabscessesmaypresentweeksandevenmonthsaftertheremovaloftheepiduralcatheter.
7.Re-evaluatetheneedforcontinuousepiduralanalgesia,especiallyinneonatesand/orifthe
caudalinsertionapproachhasbeenused,after48hinordertominimisetheriskforsystemictoxicityandinfection.
Continueonlyiftherisk-benefitanalysisshowsthattheuseofcontinuousepiduralanalgesiaisclearlyinthebest
interestofthepatient.
corneumcellsmaybecarriedduringtheuseofanormalsharpbevelneedle.58Thisdoesinferthatthe
riskofepidermoidgrowthisnegligibleifusinganon-stylettedneedle.Despitethisrecentreassuring
report,itisstillrecommendedtousethecommerciallyavailablestylettedcaudalneedleswhenper-
formingcaudalblocksinneonates.
SomerelevantclinicalkeypointsregardingpotentialcomplicationsarelistedinTable2.
Dosagerecommendations
When paediatric regional anaesthesia, and especially continuous epidural techniques, became
popular during the late 1980s, no consensus existed regarding dosage guidelines. This resulted in
anumberofcasereportsofsystemictoxicity,especiallyinthecontextofcontinuousinfusiontech-
niques.Asaresultofthis,anAPSFsponsoredstudywasperformedintheUS.Inthisstudy,allchildren
whohadsystemictoxicityhadinfusionratesinexcessof0.5mgkg(cid:2)1h(cid:2)1ofracemicbupivacaine.59
Basedontheresultsofthisstudy,guidelineswereissuedforthesafedosageofracemicbupivacaine
(Table3).59Followingtheintroductionoftheseguidelines,theincidenceofsystemictoxicityoflocal
anaestheticsismoreunusual,althoughtoxicityduetoinadvertentintravascularinjectionstilloccurs.
However,itshouldbepointedoutthatusingthemaximumrecommendeddosageofracemicbupi-
vacaineforcontinuousepiduralinfusionsinneonatesmayresultinborderlinetoxicplasmalevelsof
bupivacaine,andinfusionsinexcessof48hshouldonlybeusedininfantswhoarejudgedtohave
considerablebenefitoftheircontinuousregionalanaestheticblock.60
Sincetheintroductionoftheguidelinesforracemicbupivacaine,newlong-actinglocalanaesthetics
(e.g.,ropivacaineandlevo-bupivacaine)havebeenintroducedandsomepharmacokineticdataarenow
availableforthesenewagentsinneonatalpatients.Boththesedrugsareassociatedwithalargersafety
margin regarding systemic toxicity and are also associated with less motor blockade, both distinct
advantages compared to racemic bupivacaine. With regard to the choice of ropivacaine or levo-
bupivacaine,nodecisivedifferencesexistforpaediatricuseandthechoiceisuptopersonalprefer-
enceormarketavailability.
InstudiesbyBosenbergetal.,ithasbeenshownthatacaudalbolusinjectionof3mgkg(cid:2)1ofropi-
cavaine or a continuous epidural infusion of 0.2e0.4mgkg(cid:2)1h(cid:2)1 of the same drug was clinically
effective and did not result in excessive plasma levels of the drug.61,62 Relevant pharmacokinetic
informationwithregardtotheuseoflevo-bupivacaineinneonatesandsmallinfantshasalsobeen
Table3
Maximumdosesofracemicbupivacaine,modifiedaccordingtoBerde.59Althoughitmaybepossibletouseslightlyhigherdoses
of levo-bupivacaine or ropivacaine the author still recommends not exceeding the maximum doses outlined for racemic
bupivacaine.
Bolusinjection
Neonates 1.5e2.0mgkg(cid:2)1
Children 2.5mgkg(cid:2)1
Continuousinfusion
Neonates 0.2mgkg(cid:2)1h(cid:2)1
Children 0.4mgkg(cid:2)1h(cid:2)1
P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321 317
published.63However,evenifthesenewdrugsappeartohavealowerpotentialforsystemictoxicity,itis
stillrecommendednottoexceedthemaximumdosagelimitsasoutlinedbyBerde.59
Localanaestheticsandadjunctdrugs
Theuseofadjunctdrugstoprolongandenhancepostoperativeanalgesiaiscommoninpaediatric
regionalanaesthesia.64,65Inarelativelyrecentsurvey,Saundersreportthatapproximately60%ofUK
paediatricanaesthetistsroutinelyuseadjunctdrugsincombinationwithlocalanaestheticsforcaudal
blocks withketamineandclonidinebeingthemostcommonly used.64 Thecommonuseofadjunct
drugsoutsidetheUKhasalsorecentlybeenconfirmedbydatafromEichandStrauss.65Inpatients
outside the neonatal age group, the use of a caudal block with a combination of S-ketamine and
clonidine in saline (no local anaesthetics used) has been reported to produce good quality of post-
operativeanalgesiaduringthefirst24hfollowinginguinalherniarepair.66
Whileclonidineandketaminerepresentthemostcommonlyusedadjunctdrugstoenhancethe
effectofcaudalblockade(Table4),theuseofotherdrugshasalsobeendescribed.Unfortunately,theuse
ofopioidshasaquestionableefficacy(withtheonlyexceptionbeingpreservative-freemorphine)and
opioidsarealsoassociatedwithahighincidenceofsideeffects(e.g.,PONV,pruritusandparalyticileus),
makingtheirroutineusehighlydebatable.67Likeallnewdrugs,ornewmodesofdrugdelivery,theuseof
adjunctdrugsshouldonlybeusedroutinelyoncethereisgoodevidenceforefficacyandsafety.
In ex-premature babies scheduled for inguinal hernia repair, an awake regional technique (i.e.,
spinalorcaudalblockade)isoftenusedandadvocatedtoavoidgeneralanaesthesiaandendotracheal
intubation.Inthissetting,clonidinehasbeenusedtoextendthedurationoftheblockaswellasto
enhance postoperative analgesia.13,19 However, the use of an awake regional technique in ex-
premature babies does not rule out the risk of postoperative apnoea.19 Thus, such patients must
postoperativelybecaredforinanenvironmentthatallowsclosesupervisionandmonitoringduringat
leastthefirstpostoperativenightevenifonlyplainlocalanaestheticsareused.Therearenodataon
howtheuseofclonidineinfluencestheriskofapnoea.
Nodatawithregardtoadjunctuseofdrugsforcontinuousepiduralanalgesiaorperipheralnerve
blocksarecurrentlyavailableintheneonatalsurgicalpopulation,butdatafromolderchildrenshow
that the adjunct use of clonidine for epidural analgesia is beneficial68,69 as is the adjunct use of
clonidineinperipheralnerveblocks.70
Theevidencebaseforneonatalregionalanaesthesia
A large number of published studies have shown that the use of diverse regional anaesthetic
techniques is associated with high-quality pain relief following the different types of surgery and
Table4
Adjunctdrugsusedtoenhancetheeffectsoflocalanaestheticsinchildren;fromMazoit&Lönnqvist.73
Dose
Morphine
Caudal/epiduralbolus 33e50mcg/kg
Fentanyl
Caudal/epiduralbolus 1.0e1.5mcg/kg
Epiduralinfusion 5mcgkg(cid:2)124h(cid:2)1
Sufentanil
Epiduralbolus 0.6mcg/kg
Epiduralinfusion 2mcgkg(cid:2)124h(cid:2)1
Clonidine
Caudal/epiduralbolus 1e2mcg/kg
Epiduralinfusion (cid:4)0.1mcgkg(cid:2)1h(cid:2)1
Ketamine
Caudalbolus,racemicketamine 0.25e0.5mg/kg
Caudalbolus,S(þ)ketamine 0.5e1.0mg/kg
318 P.-A.Lönnqvist/BestPractice&ResearchClinicalAnaesthesiology24(2010)309e321
painfulproceduresthatarecommonlyperformedinneonatalpatients.Apartfrompain,fewstudies
haveexaminedotheroutcomesinthissetting.Somedatasuggestabenefitwithregionalanaesthesia.
Inaretrospectivestudy,Bosenbergetal.foundthattheuseofepiduralanalgesiainneonatalpatients
undergoingtracheo-oesophagealfistularepairresultedinareducedneedforpostoperativemechanical
ventilation.24 Furthermore, epidural analgesia was found to be associated with a significant and
beneficialmodificationoftheneuroendocrinesurgicalstressresponseaftermajorabdominalsurgery
ininfantswhencomparedwithpostoperativemorphineinfusions.25Theuseoflocalanaestheticsin
associationwithneonatalcircumcisionhasalsoshownabenefitasneonatesnottreatedwithEMLAor
a penile block had an exaggerated pain response to later vaccinations as compared with neonates
treated with a local anaesthetic technique.3,71 Finally, safety data generated fromlarge, prospective
studies and audits10,27 clearly show that the use of paediatric regional anaesthetic techniques is
associatedwithadequatesafetyalsoinneonatalpatients.
In conclusion, a large variety of local and regional anaesthetic techniques can be safely used in
neonatalpatients.Theuseofsuchtechniquesmustobviouslybeassociatedwithsufficientknowledge
about the various techniques, as well as adherence to adequate dosage guidelines and other safety
precautions.However,iftheseprerequisitesaremet,regionalanaesthesiamayoffergreatadvantages
tooursmallestandmostvulnerablepatients.
Practicepoints
(cid:5) Regionalanaesthetictechniquescanbeusedinallpaediatricagegroupsincludingneonates
andprematurebabies.
(cid:5) Bothcentralandperipheralnerve-blockingtechniquesareassociatedwithadequatesafetyif
performedaccordingtoestablishedpractice.
(cid:5) As in adult regional anaesthesia practice, the current trend in paediatrics is to more
frequentlyuseperipheralnerveblockingtechniquesascomparedwithcentralapproaches,
includingtheuseofcontinuouscathetertechniques.
(cid:5) Theuseofultrasoundguidanceoffersclearadvantageswhenusedinassociationwithmost
peripheralnerve-blockingtechniques.Theadvantages,whenusedinassociationwithcentral
nerveblocks,arelessclearatpresent.
(cid:5) Clonidinecanbeusedasanadjunctbothtocentralandperipheralnerveblocks.
(cid:5) An emerging trend in paediatric regional anaesthesia is the use of wound catheter
techniques.
Researchagenda
(cid:5) Regionalanaesthetictechniquesshouldbecomparedwithgeneralanaesthesiainpremature
babiesandneonatestoinvestigateifregionaltechniquesmayprovebeneficialwithregardto
thecurrentlymuch-discussedissueofapoptosis.
(cid:5) Regional anaesthetic techniques should be compared to other methods of postoperative
analgesia in neonatal surgerywith regard to clinicallysignificantdifferences in morbidity,
mortalityandlengthofhospitalstay.
(cid:5) Furtherstudiescomparingcentralversusperipheralnerve-blockingtechniquesconcerning
qualityofanalgesia,incidenceofsideeffectsandriskofpotentialcomplicationsareclearly
indicated.
(cid:5) Furtheradjunctstolocalanaestheticsshouldbeinvestigatedforuseinchildrenandneonates
followingadequatesafetyandefficacytrialsperformedinanimalsandadults.