RevBrasAnestesiol.2016;66(4):433---436
REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologia www.sba.com.brCLINICAL
INFORMATION
Allergic
reaction
to
patent
blue
dye
in
breast
surgery
---case
report
夽
Marcius
Vinícius
M.
Maranhão
a,∗,
Dyluzia
Kelly
Amaral
da
Nóbrega
b,
Carlos
Eduardo
Caiado
Anunciac
¸ão
a,
Barbara
de
Alcântara
Brito
Maia
a,
Paulo
Virgílio
Dantas
Mariano
aaUniversidadedePernambuco(UPE),Recife,PE,Brazil
bUniversidadeFederaldeAlagoas,Maceió,AL,Brazil
Received7December2013;accepted12February2014 Availableonline30April2016
KEYWORDS
Anesthesia; Anaphylaxis; Hypersensitivity; Patentblue
Abstract Wepresentacaseofallergicreactiontopatentblueinapatientwhounderwent excision of sentinel lymph node associated with segmental breast resection. About 20min afterthedyeinjection,thepatientdevelopedhypotension(BP=70×30mmHg)associatedwith increasedheartfrequency.Thepatientwastreatedsuccessfullywithdecreasedinspired frac-tionofinhaledanestheticandfluidreplacement.Attheendoftheprocedure,shepresented withbluishurticarial-likeplaquesonthehead,neck,upperlimbs,andtrunk;hydrocortisone wasthenused.ThepatientrecovereduneventfullyandwasdischargedfromthePACU2hafter theendofsurgerywithoutskinchanges,andwasdischargedfromhospitalonthemorningafter surgery.Theincidenceofallergicreactionswiththeuseofpatentblueisfarsuperiortothe hypersensitivityreactionsseenwithanestheticandadjuvantdrugs.Therefore,the anesthesi-ologistmustbeawareofcardiovascularinstabilityassociatedwithskinchangesduringtheuse ofpatentblue,forearlydiagnosisandappropriatetreatmentofthishypersensitivityreaction tothisdye.
© 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
PALAVRAS-CHAVE
Anestesia; Anafilaxia;
Hipersensibilidade; Azulpatente
Reac¸ãoalérgicaaocoranteazulpatenteemcirurgiademama---relatodecaso
Resumo Osautoresapresentamumcasodereac¸ãoalérgicaaoazulpatenteemumapaciente submetida à exérese de linfonodo em sentinela associada a uma ressecc¸ão segmentar de mama.Pacienteapresentouaproximadamentepós20minutosdainjec¸ãodocorantehipotensão (PA=70×30mmHg)associadaaaumentodafrequênciacardíaca.Foitratadasatisfatoriamente
夽 StudyperformedattheDepartmentofAnesthesiology,HospitalUniversitárioOswaldoCruz,UniversidadedePernambuco,Recife,PE,
Brazil.
∗Correspondingauthor.
E-mail:gabriel.n@uol.com.br(M.V.M.Maranhão).
http://dx.doi.org/10.1016/j.bjane.2014.02.018
434 M.V.M.Maranhãoetal.
comdiminuic¸ãodafrac¸ãoinspiradadoanestésicoinalatórioereposic¸ãovolêmica.Nofimdo procedimentoapresentavaplacasurticariformesazuladasemcabec¸a,pescoc¸o,membros super-ioresetroncoefoiusadahidrocortisona.Evoluiu,semintercorrências,nasaladerecuperac¸ão pós-anestésicaetevealtaduashorasapósotérminodoprocedimentocirúrgicosemapresenc¸a dasalterac¸õescutâneas.Altahospitalarnamanhãseguinteàcirurgia.Aincidênciadereac¸ões alérgicas comoempregodoazul patenteémuitosuperior àsreac¸ões dehipersensibilidade observadascomdrogasanestésicaseadjuvantes.Portanto,oanestesiologistadeveficaratento àinstabilidadecardiovascularassociadaaalterac¸õescutâneasquandodousodoazulpatente paraodiagnósticoprecoceetratamentoadequadodessareac¸ãodehipersensibilidadecomo empregodocorante.
© 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. Este é um artigo Open Access sob a licença de CC BY-NC-ND (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Introduction
Sentinellymphnodebiopsyforearlybreastcancersurgical treatmenthasbeenwidelyusedaspartofroutineprotocol and,inmost cases,it preventstotallymphadenectomy.1,2 Patent blue dye or the radioisotope technetium may be usedaloneorincombination toidentifythelymphnode.1 However, there are reports of hypersensitivity reactions mediated by IgE to blue dye, with an average incidence of1.8% (0.1%to2.8%); insome casesthesereactions can besevereandyieldserioushemodynamiceffectsrequiring vasoactivedrugs.1---4Thisfrequencyishigherthanthe hyper-sensitivityreactionsseenduringanesthesia,whichisaround 0.01%to0.02%.5
Anothereffectseenwiththeuseofpatentbluearepulse oximetrychangesbecauseitinterfereswiththewavelength readingusedtomeasuretheoxyhemoglobin.2Theobjective of thispaper is topresent acase of intraoperative aller-gicreactionaftersubdermalperiareolarinjectionofpatent bluedye.
Case
report
Femalepatient,45yearsold,72kg,ASAP2,referredfrom the Oncology Center (CEON) of the Oswaldo Cruz Uni-versity Hospital, University of Pernambuco (UPE), Recife, scheduled for segmentalresectionof the leftbreast with sentinellymphnode resection.Duringpreanesthetic eval-uation, the patient reported history of hypertension and use of enalapril, without other comorbidities; she denied smokingand allergiestomedicines, foods,and latex,and reported being a social drinker, using tranquilizers (bro-mazepam),andhavingundergonepreviousanesthesia with-outcomplications.Preoperativetests,suchascardiac exam-ination,bloodcount,coagulation,biochemistry(urea, glu-cose,creatinine,AST,ALT),andurinalysiswerenormal.The patientwasnotpremedicated.Attheoperatingroom, ven-oclysiswasperformedattheleftupperlimbwith20GTeflon catheter.Basicmonitoringwithcardioscope,pulseoximeter, andnoninvasivebloodpressureshowednormalsinusrhythm, heartrate(HR)of90bpm,oxygensaturation(SpO2)of98%,
andbloodpressureof130×70mmHg.Afterpreoxygenation
with100%O2viafacemaskandadministrationofcefazolin
(2g), induction of anesthesia wasachieved with fentanyl (250g), propofol (150mg) and rocuronium (50mg).
Tra-cheal intubation was performed with a 7.5mm cuffed tube and basic monitoring complemented with capnogra-phy; controlled mechanical ventilation with 570mL tidal volume and 12ipm respiratory rate. At that point, car-diorespiratoryparametersevidenced normalsinus rhythm, HR85bpm,SpO2 100%, ETCO2 30, andPA110×65mmHg.
Maintenance of anesthesia wasachievedwith sevoflurane (2---2.5%)andO2/N2O(50/50%).Immediatelybeforethe
inci-sion,asubdermalperiareolarinjectionof2.5%patentblue (2mL) was performed. About 20min after the blue dye injection, hypotension (70×30mmHg) and increased HR
(100bpm)occurredwithoutchangesinheartrhythm,SpO2,
and capnography. Ringer’s lactate (400mL) was adminis-tered and end-tidal sevoflurane concentration decreased to 1.5%. About 10min after volume replacement and a decreaseinthefractionofinspiredhalogenated,blood pres-surewas100×60mmHgandHR90bpm,withoutchangesin
the remaining parameters.The anesthetic-surgical proce-durewentthroughwithoutcomplications.Dipyrone(2g)was used for postoperativeanalgesia. The duration of surgery was50min. Atthe end of theprocedure, atropine (1mg) andneostigmine(2mg)wereusedforneuromuscular block-adereversal.Aftersurgicalfieldremoval,thepresence of numerousurticaria-likeplates(bluish)wasobservedmainly intheface,neck,upperlimbs,andthorax(Figs.1and2). Hydrocortisone (500mg) was administered. The patient quickly awakened from anesthesia and was extubated in the operating room. She was conscious, complained of mild pruritus, free of pain, and with cardiovascular and respiratory stability (blood pressure: 150×90mmHg, HR:
95bpm, and SpO2:98%). The patientpresented with
nau-sea, received ondansetron (8mg), and was taken to the post-anesthesiacareunit(PACU).After60min,thepatient hadnoskinchangesandwasdischargedfromPACU120min aftersurgery.Thepatientwasdischargedfromhospitalthe morningaftersurgerywithoutcomplications.
Discussion
Allergicreactiontopatentblueinbreastsurgery 435
Figure1 Presenceofnumerousurticaria-likeplaquesonthe face,neck,upperlimbsandchest.
Figure2 Presenceofnumerousurticaria-likeplaques.
andpatentblue (commonly usedin Braziland theUnited States) and less frequently methylene blue.1,6 Both the isossulfanblueandpatentbluebelongtothegroupof tri-arylmethanedyes.Patent blue has an additionalhydroxyl group.1 Numerous immediate hypersensitivity reactions have been attributed to dyes and theremay be a cross-sensitivitybetweenthetwodrugs.1,6Incontrast,methylene bluehasbeen consideredsaferthanpatentblueandisan effectiveoption toittoidentifythesentinellymphnode, afact,however,contestedbysomeauthors.1Thereis evi-dencethatabout 2.7%ofthepopulationwouldbeallergic toblue dye,which maybedue tosensitizationcaused by repeatedexposuretosomeproducts,suchastextiles, cos-metics,paper, leather, and drugs containing these dyes.1 Aftertheintradermalorintraparenchymalinjection,patent blueistakenupbythelymphaticvesselsfromdrainingarea, bindstoalbumin, andtwothirdsareabsorbedinthefirst hourwhilethetotalityin24h.Itisexcretedintheurineand bile,andthepatienturinemayturnblueforupto24h.1,3
There are three degrees of severity associated with the hypersensitivity reactions to patent blue:3,4 grade I (69---87%), characterized by bluish color urticaria, pruri-tus, and general rasch; grade II (3.2---8%), characterized by hypotension (systolic blood pressure <70mmHg) with-outtheneedforvasopressor,andabsenceofbronchospasm andlaryngospasm;gradeIII(1.1%),characterizedbysevere cardiovascular collapse that require vasopressor, suspen-sion of the surgical procedure, and patient’s transfer to the intensive care unit. The early signs of allergic reac-tionare hypotensionand skin rash without bronchospasm orairwayedema.Althoughaninitialmanifestation,theskin changesare not always immediately seen because of the drapes.5Thelateonsetofhypersensitivityoccursbetween 10and45minafterthedyeinjection(mean=17min),unlike theusualhypersensitivityreactionsseenduringanesthesia thatoccurs earlier, which often slows down the differen-tialdiagnosisofallergicreaction.3,5Skinreactionsdisappear from1to 20h.3 Treatment varies accordingto the sever-ity of the allergic symptoms. In patients with grade I or II, drug treatment is based on corticosteroids (hydrocor-tisone,dexamethasone),antihistamines(diphenhydramine, promethazine),and volume replacement withcrystalloid. Inpatients classifiedasgradeIII,thereisaneed for vaso-pressor (epinephrine, metaraminol, etilefrine, ephedrine, noradrenaline).Vasopressorresponsemaybeobtainedwith astartingdose ofthedrugormayrequireprolongeddrug infusion.1---4 Cardiovascularsystem depression maybe pro-longedandrequirecardiovascularsupportandadmissionto theintensive care unit.Cardiac arrestis infrequent, with satisfactory resuscitation.6 We found nocase of death in theliteratureduetoallergicreactiontopatentblue. Note-worthytoanesthesiologistsisthattheallergicreactionsto patentbluemaybebiphasicwiththeoccurrenceofa sub-sequentepisodeof hypotensionbetweensix and8h after theinitialevent.PatientsshouldbemonitoredinthePACU orICUduringthisperiod,evenifhemodynamicallystable.5 Positiveskintestforallergiestopatentblueandincreased serumhistamine levels (normal value ≤10nmoLL−1), IgE,
and tryptase (due to mast cell degranulation; normal value=13.5gL−1)areusuallypresentinthesepatients.5---8
436 M.V.M.Maranhãoetal.
isrecommended. Serumtryptasehas apeakplasma level withinan hour and remains high for 6h.5 Twosamples of tryptase with 60 and 120min are recommended. Normal tryptaselevelsdonotexcludeahypersensitivityreaction, assome allergic reactions aremediated by basophils and complementactivation,whichdoesnotincreasetheserum levelsof tryptase.6 The hypersensitivity test by injecting asmallamount of thedrugand waitinga fewminutes to checkfortheseallergicreactions hasbeen recommended. However,theuseoftestdoseiscontroversialandthereisno evidenceofreducedanaphylaxis.9Theskintest(skinprick or,mainly,intradermal)inwhichamuchsmallervolumethan thetestdose isusedseemstobetheidealtestwithhigh sensitivityand specificity toidentify patients with hyper-sensitivitytopatentblue.9Allergicpatientsandthoseusing angiotensinconverting enzymeinhibitors or angiotensin II receptorinhibitorareat risktodevelop allergicreactions withtheuseofpatentblue.5
Another effect seen with the use of patent blue is interference in pulse oximeter readings, which causes an apparentdecreaseinoxygensaturation.Thisinterferenceis duetotheabsorptionpeakofthepatentbluelight(638mm) beveryclosetothat of deoxyhemoglobin(660mm).5 The increasedlightabsorptioninthisregionmaybeinterpreted bythepulseoximeterasthepresenceofdeoxyhemoglobin andfalselydecreaseoxygensaturation.5Latencyand dura-tionofoxygensaturationfalldependonthesiteofinjection of patent blue. Intravascular injection causes an imme-diate and severe drop in oxygen saturation that persists forafewminutes.5 Whenadministeredintothemammary parenchyma, a reduction of 11% (5% on average) occurs 15---30minafterinjection.5
Hypersensitivityreactionstopatentbluearemuchmore frequent than those usually seen during anesthesia and may range from skin changes to severe and prolonged cardiovascular depression and require admission to the intensivecareunitandcardiovascularsupport.Ourpatient
hadahypersensitivityreactiongradeIIduetosubcutaneous injectionofpatentblue,whichevolvedsatisfactorily with-outsequelae.Therefore,anesthesiologistsshouldbeaware ofallergytopatentblueincaseofcardiovascular instabil-ityandlookfor thepresenceofskinchangesthatconfirm theclinicaldiagnosisofhypersensitivityreaction,whichmay besupplemented bymeasurement ofserumtryptase, his-tamineandIgE,aswellasskintests.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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