Rev. Bras. Anestesiol. vol.67 número4

REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

SCIENTIFIC

ARTICLE

Fetoscopic

tracheal

occlusion

for

severe

congenital

diaphragmatic

hernia:

retrospective

study

夽

Angélica

de

Fátima

de

Assunc

¸ão

Braga

,

Franklin

Sarmento

da

Silva

Braga

,

Solange

Patricia

Nascimento

_,

_Bruno

_Verri

_,

_Fabio

_C.

_Peralta

_,

_João

_Bennini

_Junior

_,

Karina

Jorge

a_{UniversidadeEstadualdeCampinas(UNICAMP),FaculdadedeCiênciasMédicas,DepartamentodeAnestesiologia,Campinas,SP,}

Brazil

b_{HospitaldeBaseDr.AryPinheiro,PortoVelho,RO,Brazil} c_{HospitalVivalle,SãoJosédosCampos,SP,Brazil}

d_{UniversidadeEstadualdeCampinas(UNICAMP),FaculdadedeCiênciasMédicas,DepartamentodeTocoginecologia,Campinas,}

SP,Brazil

Received22October2015;accepted29December2015 Availableonline25November2016

KEYWORDS

Congenital diaphragmatic hernia;

Prenataldiagnosis; Trachealocclusion; Fetoscopy;

Fetalsurgery; Anesthesia

Abstract

Backgroundandobjectives: The temporary fetal trachealocclusion performedby fetoscopy accelerates lung development andreduces neonatal mortality. The aimof thispaper is to presentananestheticexperienceinpregnantwomen,whosefetuseshavediaphragmatichernia, undergoingfetoscopictrachealocclusion(FETO).

Method: Retrospective,descriptivestudy,approvedbytheInstitutionalEthicsCommittee.Data wereobtainedfrommedicalandanestheticrecords.

Results:FETO was performed in 28 pregnant women. Demographic characteristics: age 29.8±6.5; weight 68.64±12.26; ASA I and II. Obstetric: IG 26.1±1.10 weeks (in FETO); 32.86±1.58 (reversal of occlusion); 34.96±2.78 (delivery). Delivery: cesarean section, vaginal delivery. Fetal data: Weight (g) in the occlusion and delivery times, respectively (1045.82±222.2 and 2294±553); RPC in FETO and reversal of occlusion: 0.7±0.15 and 1.32±0.34,respectively.Preoperativematernalanesthesiaincludedranitidineand metoclo-pramide,nifedipine(VO)andindomethacin(rectal).Preanestheticmedicationwithmidazolam IV.Anesthetictechniques: combinationof0.5%hyperbaricbupivacaine(5---10mg)and sufen-tanil; continuous epidural predominantlywith 0.5%bupivacaine associated with sufentanil, fentanyl,ormorphine;general.In8cases,therewasneedtocomplementviacatheter,with5 submittedtoPCand3toBC.Thirteenpatientsrequiredintraoperativesedation;ephedrinewas usedin15patients.Fetalanesthesia:fentanyl10---20mg.kg−1_{andpancuronium0.1---0.2mg.kg}−1 (IM).Neonatalsurvivalratewas60.7%.

夽 _{ThisworkrealizedattheDepartamentodeAnestesiologiadaFaculdadedeCiênciasMédicasdaUniversidadeEstadualdeCampinas}

(UNICAMP),Campinas,SP,Brasil.

∗_{Correspondingauthor.}

E-mail:franklinbraga@terra.com.br(A.F.Braga).

http://dx.doi.org/10.1016/j.bjane.2015.12.001

Conclusion:FETOisaminimallyinvasivetechniqueforseverecongenitaldiaphragmatic her-niarepair.Combinedblockadeassociatedwithsedationandfetalanesthesiaprovedsafeand effectivefortrachealocclusion.

©2016SociedadeBrasileiradeAnestesiologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).

PALAVRAS-CHAVE

Hérniadiafragmática congênita;

Diagnóstico pré-natal; Oclusãotraqueal; Fetoscopia; Cirurgiafetal; Anestesia

Oclusãotraquealporfetoscopiaemhérniadiafragmáticacongênitagrave:estudo retrospectivo

Resumo

Justificativaeobjetivos: A oclusão traqueal fetal temporária feita por meio da fetoscopia aceleraodesenvolvimentopulmonarereduz amortalidade neonatal.Oobjetivodeste tra-balhoéapresentarexperiênciaanestésicaemgestantescujosfetoseramportadoresdehérnia diafragmáticaeforamsubmetidosàoclusãotraquealporfetoscopia(FETO).

Método: Estudoretrospectivo, descritivo, aprovado peloComitêdeÉtica daInstituic¸ão.Os dadosforamobtidosdasfichasanestésicasedosprontuários.

Resultados: AFETOfoifeitaem28gestantes.Característicasdemográficos:idade29,8±6,5; peso68,64±12,26;ASAIeII.Obstétricas:IG26,1±1,10semana(naFETO);32,86±1,58 (des-oclusão); 34,96±2,78(parto). Viade parto: cesárea, partovaginal. Dados fetais: peso(g) nos momentos da oclusão e nascimento, respectivamente (1.045,82±222,2 e 2294±553); RPC na FETO e desoclusão: 0,7±0,15 e 1,32±0,34, respectivamente. Anestesia materna: pré-operatório incluiuranitidina emetoclopramida; nifedipina (VO) eindometacina (retal). Medicac¸ãopré-anestésicacommidazolamEV.Técnicasanestésicas:bloqueiocombinadocom bupivacaína0,5%hiperbárica5-10mgassociadaaosufentanil;periduralcontínua predominan-tementecombupivacaína0,5%associadaasufentanil,fentaniloumorfina;geral.Emoitocasos houvenecessidadedecomplementac¸ãopelocateter,cinconassubmetidasaPCetrêsaBC. Nointraoperatório13pacientesnecessitaramdesedac¸ão;efedrinafoiusadaem15pacientes. Anestesiafetal:fentanil10a20mg.kg−1_{epancurônio0,1-0,2mg.kg}−1_{(IM).Ataxadesobrevida} neonatalfoide60,7%.

Conclusão:A FETOconstitui técnicaminimamenteinvasivaparacorrec¸ãodehérnia diafrag-máticacongênitagrave.Obloqueiocombinadoassociadoàsedac¸ãoeanestesiafetalsemostrou seguroeeficazparaaoclusãotraqueal.

©2016SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Este ´eum artigoOpen Accesssobumalicenc¸aCCBY-NC-ND( http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Advances in prenatal diagnostic tools, such as high-resolution ultrasound and biochemical and cytogenetic analysis of fetal amniotic fluid and blood, more often have enabled the diagnosis and early correction of birth defects,delayeditsevolutionandpreventeditfrom becom-ingirreversible.1---4

Numerous studies have shown that the main causes of death in fetuses with diaphragmatic hernia are pul-monaryhypoplasia andpulmonary hypertension, but they canbenefitsignificantlywithintrauterinetherapy.However, problemsofopensurgery,suchaspretermlaborand prema-tureruptureofmembranes,areobstaclestothesuccessof thisprocedureandresultedinthedevelopmentofminimally invasivetechniquesperformedbyfetoscopy.5---9

The aim of this paper is to present the initial experi-enceandviability offetoscopic tracheal occlusion(FETO) andanestheticexperienceinpregnantwomenwhosefetuses hadseverediaphragmatichernia.

Method

withprolongedpostnatalsurvival,detectedbyconventional karyotypeanalysis.

Determinationofliverherniationintothechestwas per-formedbyidentifyingtheliverparenchymaandvesselsinto the chest with ultrasound guidance (color Doppler). The lung-to-headratio(LHR)wasinitiallyachievedwithan ultra-soundtransversecross-sectionofthefetalchestatthelevel of the cardiacfour-chamber. In thisimage, the lung area contralateraltotheCDH wasdrawnmanually(dottedline method)and expressedin mm2_{.This area wasdividedby} measuring the head circumference (expressed in mm) in cross-sectionofthefetalhead.10,11

Demographic (age,weight,physicalstatus)and obstet-rical (gestational age at the time of tracheal occlusion, balloonwithdrawalanddelivery)characteristicsofpregnant women were recorded, as well as fetal data (weight at thetimeof trachealocclusionand birth,LHR at thetime of tracheal occlusion and removalof the balloon, mater-nalandfetalanesthesia,procedureduration,andneonatal outcomes).

Results

Duringthestudyperiod,28pregnantwomen,ASAphysical status1---2,meanageof29.89±6.57(16---38)years,whose fetuses dad severe diaphragmatic hernia, and eligiblefor prenatal endoscopictherapy were selected.Tracheal bal-loon insertion was successful in 22 patients (78.5%) with mean gestational age of 26.1±1.10 (26---30) weeks, and proceduredurationwas53.39±26.38(20---120)min. There wasfailureinsixcases:trachealocclusionwasnotpossible and patients did not accept new intervention. Mean val-uesandstandarddeviationofLHRandfetalweightat the timeoftrachealocclusionwere0.70±0.15(0.33---0.94)and 1045.8±222.2(644---1464)g,respectively.

All procedures were performed in the operating room under the same recommended antisepsis conditions for laparoscopicsurgeries.

At admission, the patients underwent to the follow-ingpreparation beforetheprocedure: fasting for atleast 8h;oralnifedipine(20mg);rectalindomethacin(50mg)8h beforesurgery;intravenous cefazolin(1g);oral nifedipine (20mg);ranitidine(50mg);andmetoclopramide(10mg)1h beforeintervention.

Seventeen patients (60.7%) receivedintravenous mida-zolam (1---3mg) as premedication. Most procedures were performedwithspinalblock:continuousepidural(10cases) and combined block (17 cases); in one case, the patient had von Willebrand’s disease and general anesthesia was indicated. In this case, the anesthesia was induced with fentanyl, propofol and rocuronium and maintained with sevoflurane in 100% oxygen. In the continuous epidu-ral technique, 0.25% bupivacaine was used in two cases (43.75±8.83mg) and 0.5% bupivacaine in eight cases (80±8.86mg).Inallcases,thelocalanestheticwas associ-atedwithanadjuvant:morphine(2mg)orfentanyl(100␮g) or sufentanil (20␮g). Combined blockade was performed using 0.5% hyperbaric bupivacaine (5---7.5mg) associated withsufentanil (5---7.5␮g).In 50% of patients (five cases) who received continuous epidural, there was need for supplementation with2% lidocaine(100mg) or 0.5%

bupi-vacaine (35---40mg) via catheter. Of the 17 patients who underwentthe combinedblockade, supplementation with localanestheticviacatheterwasnecessaryinonecase(0.5% bupivacaine---50mg).Therewasaneedforsedationduring surgeryin13cases,achievedwithmidazolamalone(3.1mg) orcombinedmidazolam(1---3mg)andfentanyl(25---75␮g), intravenously.Ofthe13patientswhorequired intraopera-tivesedation,11alsoreceivedmidazolamaspreanesthetic medication.Inallcases,fetalanesthesiawasachievedwith fentanyl (15---20␮g.kg−1_{), pancuronium (0.1---0.2mg.kg}−1_), intramuscularlywith20G or 22G needle,guided by ultra-sound,atatotaldosebasedonestimatedfetalweight.

Therewerenohemodynamicandrespiratorychangesor maternalcomplicationsrelatedtotheanesthesia.Regarding the surgical procedure, the most common complications werelossofamnioticfluidintothematernalperitoneal cav-ity(onecase)andprematureruptureofmembranes(three cases)towithdrawtheballoon.

In all cases, the patients were hydrated with Ringer’s lactatesolution(10mL.kg−1_.h−1_).

Aftersurgery,pregnantwomenstayedinthehospitalfor atleast24h,atrelativerest,takenoralnifedipine(20mg; every8h) andanalgesics,asneeded. Afterdischarge,the patientreturnedtothehospitalforweeklyorbiweekly pre-natalvisitsandultrasoundexaminations.

Theballoonwithdrawalwasperformedusingafine nee-dleaspirationguidedbyultrasound;gestationalageatthat time was 32.8±1.58 (28---34) weeks, and fetal LHR was 1.32±0.34(0.5---1.8),withanincreaseofabout100% com-paredtothatobservedattrachealocclusion.

Meangestationalage atbirth was34.96±2.78(27---39) weeksandtheaverageweightofnewbornswas2294±553 (920---3495)g.

Inthesixcasesinwhichtrachealocclusionwasnot possi-ble,therewasonecaseofintrauterinedeath,threecasesof deathafterbirthwhodidnotundergoCDHsurgicalrepair, andtwonewborns survivedaftersurgery (primaryclosure andpatchplacement dueto extensivedefect). Of the22 casesoftrachealocclusion,15newborns(68%)survivedafter surgery (primary closure or patch) and seven died----four casesaftersurgeryand,inthreecases,thesurgicalrepair wasnotpossible.Ofthe28casesofsevereCDHselectedin thestudyperiod,17newborns(60.71%)survived,10(35.7%) died after birth, and there was one case of intrauterine death.

Discussion

About half of fetuses with congenital diaphragmatic her-nia survive after postnatal surgery. The other half dies of pulmonary hypoplasia. Due to the high postnatal mor-tality (>90%) associated with hypoplasia and pulmonary hypertension present in fetuses with severe congenital diaphragmatic hernia, early intrauterine treatment tech-niques have been described to promote prenatal lung developmentandgreaterchanceofsurvivalafterbirth.12

trachealocclusioninordertominimizeorreversepulmonary hypoplasia.12---15

Fetal surgery in humans was preceded by extensive animal studies and demonstrated that tracheal occlusion promoteslunggrowthanddevelopmentthroughaneffective andsustainedobstructionthatcanbedoneendoscopically withadetachableballoonwithouttrachealinjury,andthe subsequentintrauterinereversalofthisobstruction allows inuteropulmonaryrecoveryoftypeIIpneumocyteand pro-ductionofsurfactant.16---20

Animalstudiesinwhich CDHwasexperimentally devel-oped demonstrated that intrauterine tracheal occlusion allows the retention of pulmonary secretions----the likely mechanism of action responsible for lung development and growth, pulmonary hypoplasia reversal, and LHR normalization.15,20,21

This study performed at a university center in Brazil showsthepreliminaryresultsoftheanesthetictechniques usedin fetoscopyandreversibletrachealocclusionwitha balloonandthefeasibilityofaminimallyinvasivetechnique (FETO)infetuseswithsevereCDH,intrathoracicliver her-niation,andLHR<1.

Ifweconsidermortalitygreaterthan90%infetuseswith severe CDH, our results were satisfactory in relation to maternal safetyand the possibilityof fetal lung develop-ment,withasurvivalrateof60.7% forfetusesthatwould haveapoorprognosisinthepresenceofsevereCDH.In2004, Deprestetal.22 _{reportedsurvivalandhospitaldischargein}

48%ofthe20casessubmittedtoFETO.InaEuropean multi-centrestudy,whichincluded210cases,Janietal.23_reported

resultsof38%and49%survivalinrightandleftCDH, respec-tively.Manriqueetal.24 _{performedFETOinninecaseswith}

CDH, with a survival rate of 45.5% compared with 0% in controlgroup who underwentwatchfulwaiting. In Brazil, astudy by Peraltaetal.25 _{showedsurvival of 46.2%in 13}

casesevaluated.

In this study, the inclusion criteriafor liver herniation intothechestandLHR<1arewidelyacceptedaslife treat-ingindicatorsinCDH.26 _Janietal.26_{observedthattheLHR}

is directly proportional to the survival rate. The authors investigatedthecorrelationbetweenLHRandsurvivaland found survivalof 17%, 62%, and78% in cases withLHR of 0.4---0.5,0.6---0.7,and0.8---0.9,respectively,undergoing tra-chealocclusion.Itwassignificantlyhigherthaninthosewho underwentwatchfulwaiting,withasurvivalrateof0%,0%, and16%,respectively.

Theseresultsaresimilartothoseofother authorswho reported a lifespan shorter than 10% in watchful waiting casesand50%inprenatalinterventioncases.22

The right timefor intervention and occlusionduration isessential toensurethequalityof pulmonary vesseland airwayresponses.Thebestresultsareseeninsurgery per-formed as early aspossible, with increased survival even in FETO performed between the 25th and 29th week of pregnancy.7,22,27,28

Unpluggingshouldpreferablybedonebetweenthe32nd and34thweeksofgestation,asstudieshaveshownthat pro-longedtrachealocclusionleadstodecreasedalveolartypeII pneumocyteanddecreasedlungsurfactant,whichcanlead tothedevelopmentofhyalinemembraneafterbirth.19,29

The fetal surgery anesthesia involves two patients, motherandfetus, and therefore care toensure maternal

andfetalsafetyshouldbeconsidered.Amongthematernal care,inadditiontothoserelatedtothespecificchangesof pregnancy,thereare:preventionofprematurelaborusing pre-, intra-,and postoperative tocolytic agents and post-operativeanalgesia.Regardingfetalcare,attentionshould bepaidtoanesthesia, immobility,and preventionoffetal asphyxia.1,2

Preterm labor is the result of stimulation and uterine contraction caused by manipulation and uterine incision. This manipulation may cause placental detachment with decreased placental blood flow and fetal anoxia. Preven-tion and treatment of preterm labor areessential to the success of the surgeryand includethe use of pre-, intra-, and postoperative tocolytic drugs.30 _{However, its use}

hasbeen associated withmaternalcomplications, suchas hypotension, cardiac arrhythmias, pulmonary edema and metabolicchanges;thechoicewilldependentonthe mater-nalsideeffects.Prostaglandin-synthetaseinhibitors(suchas indomethacin),beta-adrenergicdrugs(suchasterbutaline), andcalciumchannelblockers(suchasnifedipine)areamong themostcommonlyusedagents.Fetalsideeffectshavealso beendescribedafterusingtheseagents.Thelong-termuse ofindomethacinmaybeassociatedwithrenaldysfunction, necrotizing enterocolitis, intracranial hemorrhage, espe-ciallyinpreterminfants(<30weeks).Regardingnifedipine, therearenoreportsofadverseeffectsinhumans,although reductioninuterinebloodflowandfetalacidosishavebeen demonstratedinanimals.1,2

Regarding anesthetic technique, the physiological respiratory disorders of pregnancy contribute to the increased risk of hypoxia, which can be minimized by O2 administration.1,2 _{Hyperventilation may be aggravated by}

anxiety and stress, with consequent hypocapnia, oxyhe-moglobincurveshifttotheleft,anddecreasedavailability ofoxygentothefetus.Additionally,thereisadecreasein venousreturn,maternalcardiacoutput,anduterineblood flow,themaindeterminantofplacentalflow.1,31 _Thus,itis

important toprevent anxiety andpre- and intraoperative stress, maintaining the respiratory rate to avoid PETCO2 valuesbelow30mmHg.1,2

Gastrointestinal changes increase the risk of gastric contentaspiration,andpreventivemeasuressuchas intra-venous metoclopramide (10mg) and ranitidine (50mg) and rapid sequence induction and intubation should be considered.1,2,30---32

Regarding cardiovascular stability, hypotension and hypertension and noradrenergic activity with myometrial vasoconstrictionshouldbeavoided,astheycausedecreased uterinebloodflowwithlossoffetalwell-being.Thelower vena cava compressionby thegraviduterus duringsupine positioncauses a decreasein venous returnandmaternal hypotension; it is mandatorytodeviate theuterus tothe lefttopreventfetalasphyxia.31---33

Theseproceduresusuallydonotrequiregeneral anesthe-sia,whichisassociatedwithahigherincidenceofmaternal morbidity and mortality; regional anesthesia is used in mostcenters.However,regionalanesthesiatechniquesmay present some difficulties due to maternal anxiety, and doesnotprovidefetalimmobility,withendoscope displace-ment,bleeding,fetaltrauma,cordcompression,andfetal death.1---3,31,32 _{Alternatively, local infiltration of the skin}

maternal sedation, canbe used.Some authorsperformed these procedures with combined blockade and maternal sedationandfoundthatremifentanilincontinuousinfusion providedmaternalsedationandfetalimmobilizationequal toorhigherthanthatobtainedwithdiazepam.34

Deprestetal.,14_{inastudyperformedin2011,recognized}

thespinaltechniqueasmoreadvantageouscomparedwith generalanesthesia,asitisaneasytohandleandshort sur-gicalprocedure. Leoetal.35 _{found thatlowdosesof 0.5%}

hyperbaricbupivacaine(7mg)providedarapidblockadeand effectiveanesthesiaforcesareansectionwithreduced inci-denceofhypotensioncomparedwithdosesof8 and9mg. However, due to its short duration, the use of an epidu-ral catheterwould notbefeasible for apossibleneed for supplementation.

As described in previous studies,22,25 _{the anesthetic}

technique most used in this work was the spinal block, particularlythecombinedblockade.Lowdosesoflocal anes-thetics andadjuvants wereused,which waseffective for theprocedurewithoutmaternalhemodynamicchangesand withlessneedforcathetersupplementationcomparedwith epiduralblock.

Although in 53.6% of patients undergoing spinal block ephedrinehasbeen usedin lowdoses,theanalysisof the anestheticrecordsshowedhemodynamicstability through-out the surgical procedure. This can be justified by the criterion adopted, considering ‘‘zero tolerance’’ for reducedbloodpressureandassumingtheuseofvasopressors foranydecreaseinsystolicbloodpressurebelowthe base-line pressure levels (pre-anesthetic). The crystalloid and colloidadministrationtotreathypotensioninthesepatients shouldbecontrolled,astheroutineuseoftocolyticagents mayincreasetheriskofacutepulmonaryedema.Regarding theuseofpressoramines,ephedrine,althoughitcancause fetalacidosis,itisstillthemostusedvasopressordotoits beta-adrenergiceffectandminimalactiononuterineblood flow.1,30,36

There is evidence that the fetus can experience pain, andthesurgicalmanipulationofanunanesthetizedfetuses resultsin theautonomic nervoussystem stimulation,with effects onheartrate, increasedhormonelevels andfetal motoractivity,changesthatcanbeeliminatedwithproper fetal anesthesia.1,31,37 _{Among the opioids, the option for}

fentanyl (5---20␮g.kg−1_{) due to the efficacy and safety} observedinprematureinfantsundergoinganesthesia.1,30,37

Fetalmovementshavebeensafelymanagedwith pancuro-nium (0.2---0.3mg.kg−1_{) or pipecuronium (0.2mg.kg}−1_{) or} vecuronium(0.2mg.kg−1_).1,8,30,37,38_{The choiceof}

pancuro-nium in this study was due to its vagolytic activity, with increased heart rate, desirable to maintain fetal cardiac output.31 _{Fetalheart ratemonitoringwasperformedusing}

ultrasound,theuseofatropinewasnotneeded.

Adequate postoperative analgesia has been achieved withlocalanestheticsandmorphineadministeredthrough acatheterintheepiduralspacethatextremelyimportant for the fetal surgery success due to its role in preterm laborprevention.1 _{Thestudyresults allowconcludingthat}

FETOisaminimallyinvasivetechniqueforseverecongenital diaphragmaticherniarepairandprovideslungdevelopment andpostnatalsurvival.Thisanesthetictechniqueselection should beconsidered for asuccessful procedure, and the

combinedblockadeassociatedwithsedationandfetal anes-thesiaprovedtobesafeandeffectivefortrachealocclusion.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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