RevBrasAnestesiol.2015;65(5):407---410
REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
OfficialPublicationoftheBrazilianSocietyofAnesthesiologywww.sba.com.br
CLINICAL
INFORMATION
Treatment
of
status
migrainosus
by
general
anesthesia:
a
case
report
Artur
Udelsmann
a,∗,
Priscila
Saccomani
b,
Elisabeth
Dreyer
c,
Alberto
Luiz
Cunha
da
Costa
daDepartamentodeAnestesiologia,FaculdadedeCiênciasMédicas,UniversidadeEstadualdeCampinas,Campinas,SP,Brazil
bServic¸odeAnestesia,HospitaldasClínicas,UniversidadeEstadualdeCampinas,Campinas,SP,Brazil
cHospitaldasClínicas,UniversidadeEstadualdeCampinas,Campinas,SP,Brazil
dAmbulatóriodeCefaleia,HospitaldasClínicas,UniversidadeEstadualdeCampinas,Campinas,SP,Brazil
Received31July2013;accepted9September2013 Availableonline13February2014
KEYWORDS
Migrainedisorder; Combinedtherapy; Generalanesthesia
Abstract
Backgroundandobjectives: Thestatusmigrainosusisacomplicationofmigrainecharacterized bysevereheadacheformorethan72hthatdidnotrespondtotreatment,withriskofstroke andsuicide. Researchesontreatmentaredirectedtodrugs thatstimulateGABAreceptors; propofolandisofluraneactonsub-GABAareceptorsandtheoreticallycouldbeinteresting.The firsthasbeenthesubjectofresearchinseveremigraine.Opioidsareemployedinpain,andits useinchronicheadacheisdebatable,buttheseagentsareemployedinacutecases.Thegoal istopresentacaseofrefractorystatusmigrainosusinthatwedecidedtobreakthepaincycle bygeneralanesthesia.
Casereport: Femalepatient,aged50years,withstatusmigrainosus,inthelastfivedayswith visitstotheemergencydepartment,medicatedparenterallywithvariousagentswithoutresult. Withoutcomorbidities,dehydrated,describedherpainas‘‘wellover10’’inVisualNumeric Scale (VNS).After consulting the literature, andgiven the apparent severity ofthe condi-tion, weoptedfor ageneralanesthesia:inductionwith fentanyl,propofol,andvecuronium andmaintenancewithisofluraneandpropofolfortwohours.Followingthetreatment,inthe postanestheticrecuperation(PAR),thepatient relatedherpainasVNS3, andwasreleased afterfivehourswithVNS2.Subsequently,herpreventivetreatmentwasresumed.
Conclusion: Statusmigrainosusisararedisablingcomplicationandanestheticshavebeenthe subjectofresearchinitstreatment;theoptionforgeneralanesthesiawithagentsthatstimulate GABAreceptors,propofol andisoflurane,inassociationwith fentanyl,provedeffective and shouldencouragenewresearch.
© 2013SociedadeBrasileirade Anestesiologia.Publishedby ElsevierEditoraLtda.Allrights reserved.
∗Correspondingauthor.
E-mail:au1849@gmail.com(A.Udelsmann).
408 A.Udelsmannetal.
PALAVRAS-CHAVE
Transtornode enxaqueca; Terapiacombinada; Anestesiageral
Tratamentodoestadodemal-enxaquecosopelaanestesiageral:relatodecaso
Resumo
Justificativaeobjetivos: Oestadodemal-enxaquecosoécomplicac¸ãodamigrânea caracteri-zadaporcefaleiaseverapormaisde72horasnãoresponsivaàterapêuticacomriscodeAVC esuicídio.PesquisasnotratamentosedirecionamàsdrogasqueestimulamreceptoresGABA; propofoleisofluranoatuamnossub-receptoresGABAa eteoricamentepoderiamser interes-santes.Oprimeirojáfoiobjetodepesquisasnamigrâneasevera.Opioidessãoempregadosem dor,seuusocrôniconascefaleiasédiscutível,massãoempregadosnoscasosagudos.Oobjetivo éapresentarcasodeestadodemal-enxaquecosorefratárioemqueseoptouparaquebraro cicloálgicoporumaanestesiageral.
Relatodecaso:Pacientedosexofemininocom50anosemestadodemal-enxaquecosohavia cincodiascompassagensanterioresporservic¸odeurgências,medicadaporviaparenteralcom váriosagentessemresultado.Semcomorbidades,desidratada,descreviasuadorcomo‘‘muito superiora10’’naENV.Apósconsultaàliteratura,faceàgravidadeaparentedo quadro,optou-se pela feitura de uma anestesia geral; a induc¸ão foi com fentanil, propofol, vecurônioe manutenc¸ãocomisofluranoepropofol porduashoras.Nofim,naRPA, noprimeirocontato classificousuadorcomENV3,tevealtaapóscincohorascomENV2.Ulteriormenteretomou seutratamentopreventivo.
Conclusão:Omal-enxaquecosoéumacomplicac¸ãoraraincapacitanteeanestésicostêmsido objetodepesquisasnotratamento;aopc¸ãoporumaanestesiageralcomagentesque estim-ulamosreceptoresGABA,propofoleisoflurano,aliadosaofentanil,mostrou-seeficazedeve incentivarpesquisas.
©2013SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Todosos direitosreservados.
Introduction
The state migrainosus is, according to the International Headache Society, a severe complication of migraine characterizedbydisablingpaincrises,lastsforlongerthan 72handispresentedinacontinuousmannerwithout remis-sion and unresponsive to usual treatments.1 It is a rare condition, but always an emergency and a challenge to primary care physicians. The risk of stroke and suicide attempts are part of the complications described in the literature2,3andthatshouldbeconsidered.The pathophysi-ologyresponsibleforthistypeofevolutionisstillsubjectto muchcontroversy4,5andduetothecommonfailureofthe usualtreatmentinsuchcircumstances,variousapproaches inboutsofseveremigrainewithanestheticdrugshavebeen made, from local endovenous anesthetics6 to opioids,7,8 and alsowith hypnotics as propofol.9---11 This latter strat-egyhas come tovery interesting results, and hisalleged action would be the interaction with the central GABA receptors,9withanmechanismsimilartootheranesthetic agents,includinginhaledisoflurane,9,12,13notnecessarilyin the same receptor subtypes. Therefore, other drugs with similarmechanism of action in these receptors also have beena targetofresearchfor thetreatment ofmigraine.9 Someofthedosesofpropofolproposedintheliterature10,11 were superior to those used in general anesthesia and, although intermittent,conducted toloss of consciousness and respiratory depression, reaching11 a bispectral index (BIS)of40. Giventheseassumptions inthe literature,we reportacaseinwhichageneralanestheticwassuccessful inanattempttoabortacrisisofseverestatusmigrainosus whichwaspresentinthelastfivedays,afterthefailureof severalattemptswiththefirst-linetherapy.
Case
report
Treatmentofstatusmigrainosusbygeneralanesthesia 409
attempttostopthepainstatus.Aftercarefulexplanation tothepatient,andverifyingherfastingstatus,weobtained her informed consent, proceeding with a clinical exam: blood pressure was150×90mmHg, heart rate=104bpm,
withnoothernoteworthy findings.The patientwastaken to the operating room, withECG monitoring with similar DII,pulseoximetryandnoninvasivebloodpressure determi-nationandinductedwithfentanyl200g,propofol150mg and vecuronium 7mg after ventilation by mask with O2
100%.Thepatientwasintubatedandunderwentcontrolled mechanicalventilationkeepingsaturationalwaysabove98% and capnometry with values between 34 and 36mmHg. Maintenance of anesthesia wasperformed with isoflurane 0.5% in oxygen 40% and continuous infusion of propofol 1mgkg−1h for two hours.The patient remained hemody-namically stable throughout this period. After that, the patientwasdecurarized, awakened, extubated and taken tothepostanesthesiarecoveryroom.Oncethefirstcontact waspossible, thepatientquantifiedanddescribed consid-erable improvement her headache,having rated her pain as VAS=3. After five hours, the patient was discharged. Before that, the patient drank water, remained without nausea and rated her pain as VNS=2. A week after her discharge,thepatientreportedthatherheadachehad stabi-lized,withapatternalikethecircumstancesprecedingthe statusmigrainosuscrisis,whichallowedthereintroduction oftheusualpreventivemedicationbyherattendingdoctor.
Discussion
It is estimated that migraine has a prevalence of 15% in the general population14; of this percentage, 1.4---2.2% is present in the formof chronic migraine,15 that, in adult-hood, affects women twice, as compared with men.16 The treatment of migraine is targeted at relieving the symptomsbyadministrationofanalgesics,nonsteroid anti-inflammatory drugs, ergot alkaloids,triptans, antiemetics andopioids.Preventivetherapymakesfrequentuseof beta-blockers, antidepressants and antiepileptic drugs, but a numberofpatientsdemonstraterefractoriness,andthatis amajorchallenge.Duringcrises,theabsorptionoftheoral medication becomesaffected,11 and the parenteral via is preferred.Statusmigrainosusisacomplicationofits evolu-tion and,although considered rare,a prospective study17 of 2006 showed that at some point of their lives about 20%ofpatientswithchronicmigraineexperiencedpainfor longerthan72h.Modifications ofneurotransmission occur in migraine and studies have shown that these patients have analteration inthe metabolismof serotonin(5-HT). Potentagonistsof5-HTreceptorswithantimigraineactivity havetheireffectsexplainedbythereductionofvasogenic inflammation andpartly bythe vasoconstrictoreffects on meninges, upon stimulation of 5-HT receptors.11 By 1985 it wasdemonstratedthat GABAwould exertan inhibitory control over serotonergic neurons18 and that drugs effec-tive in fighting migraine have their effects mediated by theagonism of GABAareceptors,increase of GABAin the brainand decreaseinthe frequencyof stimulationof the dorsalrapheserotonergiccells.19Since1996,withthework ofCutrerandMoskowitz,20itisknownthattheprospectof newdrugsformigrainetreatmentwasinthestudyofagents
withhighaffinityforGABAareceptorandtheirmodulation sites.Given the difficulty of overcomethe painin severe conditions,perhapsthefirstideaofusinganestheticsarose in1999withtheworkofPonnuduraietal.,21whoobserved aprotectiveeffectofpropofol(anhypnoticagent)against postoperativeheadache in aparticular group of patients. Sincethen,severalinvestigationswiththeuseofanesthetic agentshavebeen conducted.Propofol isahypnoticagent foruseinanestheticprocedures,haveantiemeticproperties anditsefficacyhasbeen demonstratedincasesof severe migraine. This agent would act through its agonist activ-ityat theGABAareceptorsubunits1,activatingchloride channelsandinhibitingsynaptictransmission.11Opioidsare agentsthatproviderelieffrompain,andarewidelyusedin anesthesiaandofteningreatnumberofpainfulconditions. Then,theiruseinrefractorymigraineisnotsurprising.Their continueduse is,however, amatter of controversy.Some authorsfoundnosignificantimprovementinthelongterm in74%of cases,22 while othersemphasize theirbenefit,7,8 andmethadoneis themost widelyuseddruginthese cir-cumstances.TheGABAasubreceptorisanimportanttarget of inhalational anesthetics,12 and these drugs, aswell as intravenousagents,stimulatethereceptor23,24ina mecha-nismsimilartothatofthe drugscurrentlystudied forthe treatmentof migraine,which justifies thismentioninthe literature9 andthe interestin thiscase.General anesthe-siawithpropofol,fentanylandisofluranewasan extreme optioninanextremecaseunsolvedforaseveraldays,and itsuse had its foundations withthe knowledge of litera-ture,andshouldbeinvestigatedfurtherformoredefinitive conclusions.Forthispurpose, aprotocolwassubsequently presentedtotheEthicsResearchCommitteeandapproval wasobtained.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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