REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
OfficialPublicationoftheBrazilianSocietyofAnesthesiologywww.sba.com.br
REVIEW
ARTICLE
Perioperative
anaphylaxis
Marta
Inés
Berrío
Valencia
HospitalPabloTobónUribe,Medellín,Colombia
Received29August2014;accepted8September2014
Availableonline28April2015
KEYWORDS
Anaphylaxis; Hypersensitivity; Anesthesia;
Perioperativeperiod; Treatment
Abstract
Backgroundandobjective: Anaphylaxisremainsoneofthepotentialcauses ofperioperative death, beinggenerallyunanticipatedandquickly progressto alifethreatening situation. A narrativereviewofperioperativeanaphylaxisisperformed.
Content: Thediagnostictestsareprimarily toavoid furthermajorevents.The mainstaysof treatmentareadrenalineandintravenousfluids.
Conclusion:The anesthesiologistshouldbefamiliarwith theproperdiagnosis,management andmonitoringofperioperativeanaphylaxis.
©2014SociedadeBrasileiradeAnestesiologia.PublishedbyElsevier EditoraLtda.Allrights reserved.
PALAVRASCHAVE
Anafilaxia;
Hipersensibilidade; Anestesia;
Período perioperatório; Terapêutica
Anafilaxiaperioperatória
Resumo
Antecedenteseobjetivo: Aanafilaxiacontinuasendoumadascausaspotenciaisdemorte peri-operatóriapoisgeralmentenãoéprevistaeevoluirapidamenteparaumasituac¸ãoameac¸adora davida.Umarevisãodaanafilaxiaperioperatóriaérealizada.
Conteúdo: Oexamesdiagnósticossãoimportantesprincipalmenteparaevitareventos posteri-ores.Ospilaresdotratamentosãoaadrenalinaeoslíquidosintravenosos.
Conclusão:Oanestesiologistadeveestarfamiliarizadocomodiagnósticooportuno,manejoe monitoramentodaanafilaxiaperioperatória.
©2014SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Todosos direitosreservados.
E-mail:martaberrio@gmail.com(M.I.BerríoValencia).
http://dx.doi.org/10.1016/j.bjane.2014.09.002
Introduction
Theimmediatehypersensitivityreactionsoccurin1outof 5000---10,000anesthesias.1Thevariabilityoccursbecauseit
isbasedonretrospectivestudieswithacalculatedincidence accordingtovoluntaryinformationandthenumberof previ-ousanesthesiasperformed,whichmayleadtoundercounts.2
Sixtypercentofperioperativehypersensitivityreactionsare allergic, with a mortality rate of 3---9%.3 In this review
the etiology,symptomatology, diagnosis and treatment of perioperativeanaphylaxisareassessedwithsomefinal rec-ommendations.Thisreviewdoesnotfocusonlatexallergy.
Methodology
Aliterature searchwasperformed inPubMed, LILACSand Google Scholar, with no restriction of dates or types of articles; in PubMedthe following MeSH terms were used: anaphylaxis,hypersensitivity,anesthesia,perioperativeand treatment.Thesnowballmethodwasused.
Definition
TheEuropeanAcademyofAllergyandClinicalImmunology definesanaphylaxisasareactionofseverelife-threatening generalized or systemic hypersensitivity.4,5 Perioperative
anaphylaxisisasystemicreactionthatoccursduring anes-thesiainductionminutesafterintravenous(IV)induction.6,7
However, the agents administered through other routes, such as chlorhexidine, latex or methylene blue may also causethereactionafter15min6duringmaintenanceof anes-thesia or during recovery due to absorption by the skin, mucosaortourniquetremoval.8
Types
The World Allergy Organization (WAO) has
pro-posed the classification of anaphylaxis in immune and non-immune.4 The immune anaphylaxis includes
immunoglobulin(Ig)E-mediated,IgG-mediatedandimmune complex/complement-mediatedreactions.4
Immunoglobulin
E-mediated
anaphylaxis
Physiopathology
This type of anaphylaxis is an immediate IgE-mediated hypersensitivity systemic reaction with release of pro-inflammatory mediators from mast cells and basophiles.9
The mediators are histamine, triptase, cytokines, medi-ators derived from phospholipids as prostaglandin D2, leukotrienes,thromboxane A2 and plateletactivating fac-torinvolved in the clinical presentation.1,10 Targetorgans
aretheskin, mucousmembranesandtherespiratory, car-diovascularandgastrointestinalsystems.1,10InIgE-mediated
druganaphylaxispriorcontactwiththeagentisnotrequired andsensibilitycanoccurthroughcross-reactivity.1
The non-immune anaphylaxis is clinically indistinguish-ablefromIgE-mediatedanaphylaxis.11
Etiology
Therisk ofanaphylaxis increaseswithfrequency,the par-enteral route of administration and the specific antigen exposuretime.9Table1presentsriskfactorsforthe
devel-opmentofanaphylaxis.3 Also,therearecomorbiditiesand
drugs that enhance the severity of the symptoms and decrease the response to treatment, such as heart dis-eases,chroniclungdisease,recentintracranialsurgery,and hyperthyroidism.4
The main etiological agents of perioperative anaphy-laxis arethe neuromuscular blocking agents, followed by latex and then the antibiotics.12---16 Anaphylaxis to
halo-genatedagentshasneverbeenreported.14Allergicreactions
to local anesthetics are very rare.17 Other substances
thatcancauseimmediateallergiesatperioperativeperiod areaprotinin,chlorhexidine,heparin,methyleneblueand anti-inflammatorysteroids.17Anaphylaxistoneuromuscular
blockerscanoccurduringthefirstexposure,17,18hasahigh
incidenceof cross-reactivityamongthevarious neuromus-cularblockers,andismorefrequentinwomen(2:1---8:1);18
themostinvolvedisthesuxamethonium.17
Clinical
features
Theclinicalpresentationofanaphylaxisischaracterizedby itsvariabilityamongpatientsandeveninthesamepatient fromoneepisode toanother.19 Clinicalanaphylaxisduring
anesthesiacan bemasked or confusedwithhypovolemia, depthofanesthesiaandextendedregionalblock.6,10,20 The
increasedvascular permeability by35% within 10min and the intrinsic compensatory response to endogenous cate-cholamines influence clinical manifestations.21 The most
commoninitialsignsarenopulse,difficultventilationand desaturation.14,22 Anothersign is the reductionof expired
carbondioxide14,23values.
There is a classification of the severity of symptoms ingrades1---5.24 Theperioperative cardiovascularcollapse
is the most common trait (88% of cases) and the worst
Table1 Factorsthatenhanceanaphylaxisrisk.
Agerange Gender Pathologies Amplifiers Severity
Nursingmothers Female Asthma Fever Beta-blockeruse
Elderly Systemicmastocytosis Activeinfection ACEIuse
Pre-menstrualstate Spinalanesthesia Emotionalstate
sign.7,22 Anaphylaxiscan befatalwithinthefirst5---30min
ofitspresentation25,26withanincidenceofcardiacarrestof
10%.7,22 Myocardialischemia, acutemyocardialinfarction,
arrhythmiasand myocardial depressionmay contribute to hemodynamicdeteriorationandcardiacarrest,27 occurring
evenbeforeadministrationofadrenalin.28---31
Skinsymptoms,suchasstiffness,hivesandswelling,are recognizedin70%ofcases7,22andduringanesthesiamaybe
hiddeninthesurgicalfields.10
Tentofourteenpercentageofthereactions, especially thesevereones,affectonlyonesystem,fundamentally car-diovascularcollapseandbronchospasm,whichlead,inmany cases,tootherdiagnoses.14,32Moreover,heartfailureisthe
onlysignpresentinthereaction,in51.7%ofcases;33
there-fore,whenanyoftheprevioussignstakeplace,theprotocol forallergicreactionsshouldbeconducted.2
Other signs and symptoms are swelling of the tongue, lipsanduvula,stridor,hypoxemia,incontinence,abdominal pain,nausea,vomiting,rhinorrhea,amongothers.4Itis
nec-essarytoconsiderthatgeneral anesthesiacanmask many manifestations. In children, the skin signs and symptoms occurinmostcases,bronchospasmis themost concerning manifestation,andhypotensionandshockarenotcommon attheonsetoftheproblem.8
Diagnostic
tests
Thediagnosisofanaphylaxisismainlyclinical.4Thelackof
experience,thelackofviewofthepatient’sbody,andthe varieduseofmedicationduringanesthesiamakeitdifficult toestablishaproperdiagnosis.6Therearesometestssuch
asmeasurement oftriptase,histamineandIgElevels,but nonehasabsoluteaccuracy.8
Skintestscanidentifythecausativeagentbuttheyare performedafterthemonthinwhichanaphylaxisoccurred, whichrestrictsitsusetopreventfurthercases.10,34
Tryptase
Tryptaseisaserineproteasethathasseveralmainforms.35
Theserumtryptaseconcentrationduetomastcell degra-nulation is 300---700 times higher than that released by basophiles.2 An increase exceeding 25
gL−1 is
consid-ered an indicator of anaphylaxis.2 Tryptase levelscan be
increasedbyotherdiseasessuchassystemicmastocytosis, mastcellactivationsyndromeorhematologicaldiseases.17
Ontheotherhand,anormalleveloftryptasedoesnotrule outadiagnosisofanaphylaxis.2,4
Thehalf-lifeoftryptaseis120min8andthelevelsreturn tobaselinein 24h.35 There maybe falsepositivesdue to
severestresssuchasmajortraumaorhypoxemia.8The
sam-pleshouldbecollectedfrom15minto3hfromtheonsetof symptoms,4andafter24h.36Acoagulatedbloodsampleof
5---10mL36iscollected,alongwithclinicalhistorydata37and
samplecollectiontimeattheonsetofreaction.10
Treatment
The early treatment is essential in anaphylaxis and could avoid hypoxic-ischemic encephalopathy or death.38 The
Table2 First-linetreatment.
Withholdallpotentialcauses Stophalogenatedagents 100%oxygen
Informthesurgeon.Postponesurgery Askforhelp
Intubate
Trendelenburg,ifnotcontraindicated IVAdrenalinorIMifIVnotavailable Crystalloids
SecondIVaccess TransfertoICU/SCU Informfamily
ICU,intensivecareunit;SCU,semiintensivecareunit.
managementis basicallythe sameinall ages,considering the adjustment by weight in children.4 The mainstays of
treatmentareadrenalineandIVliquids.10
Interventions in anaphylaxis are based on recommen-dations of experts as the realization of prospective, ran-domized, double-blind, placebo-controlled studies cannot beperformedwhenthereisanunpredictablecondition.19,39
Duringanesthesia,thepatientismonitoredandhasvenous access.10 Theteamshouldbepreparedtoperformvarious
taskssimultaneously;36investigatepotentialcausessuchas
latex,chlorhexidine,bloodproducts,andmaintain anesthe-sia, if necessary, withonly halogenated agents,36 request
help, take note of the time and inform the surgeon.34,36
The advanced and fast airway management is critical to the development of laryngeal or oropharyngeal edema.27
A hundredpercent oxygen shouldbe administered;if not contraindicated,lowerlimbsshouldbeelevated,7,40andin
adults500---1000mLofcrystalloids7in10---20minshouldbe
given; in children bolus of 20mLkg−1, if theyneed more
than40mLkg−1addsupportvasopressor,41titrateto
main-tain asystolic blood pressure above90mmHg in adults,27
ideally withinvasive monitoring of blood pressure.41 WAO
recommendstheuseofnormalsaline,ratherthancolloids.38
Adrenaline is the treatment of choice in anaphylaxis5
for its alpha and beta-agonist properties, resulting in vasoconstriction,increasedperipheralvascular resistance, decreased mucosaledema,inotropism,andchronotropism and bronchodilation.28,42,43 The IV dose of adrenalin at
10---200gvariesdepending onthepatient’shemodynamic
involvementandcanberepeatedevery1---2min.17 In
chil-drenthedoseis1gkg.17,36
The intramuscular route can be used if there is no IV access.36Thebestapplicationisintheanterolateralaspect
ofthemiddlemuscleasitprovidesgreaterabsorption,each 5min, both inchildren andin adults;44 dosesof 0.5mg in
adults.17
In patients who require repeated bolus, continuous infusion of 0.05---0.1gkg−1min−1 should be started, an
titrated.10,45,46Table2showsachecklistoftheacute
man-agementofanaphylaxis.
Patients using beta blockers may require high doses of adrenaline when they have a poor response; in these cases norepinephrine should be added at a dose of 0.1gkg−1min−1.17IVglucagon101---2mgIVcanbeusedeach
5min,34 followedby5---15
Table3 Noresponsetoadrenalin.
Norepinephrine Vasopressin2---10UIV
GlucagonIV1---2mgIVeach5min Reports:methyleneblue
Reports:sugammadex16mgkg−1IVinanaphylaxisto rocuronium
according to responsedose6 as shown in Table 3. In
chil-drenvasopressin17 isnotrecommended.Therearereports
of cases of useof methylene blue in severe unresponsive anaphylacticshock.18,47Inthecaseofanaphylaxisto
rocuro-nium, the successful use of sugammadex 16mgkg−1 IV is
described, at a dose according tothe situation of cannot intubate,cannotventilate.18
The beta2-adrenergic agentsrelievebronchospasm,but not upper airway obstruction and shock.48 The patient
shouldremainunderobservationduring24hasthebiphasic reactions4 cannot bepredicted. In case ofcardiac arrest,
the basic managementand advanced pattern isfollowed, consideringthatitispreferabletocontinuetheinfusionof adrenalineduringandaftercardiacarrest.27
In the second line of anaphylaxis treatment line are glucocorticoids,thedosesofwhichextrapolateasthma man-agementanditsonsetofactiontakesseveralhours,38 and
thereisnoevidenceofitsuseintheacutemanagement.5,49
Adose of200mgIVof hydrocortisoneis recommendedin over12yearsofageand100mgIVtothoseof6---12yearsof age.36
Antihistaminesarealsonotrecommendedfortheinitial management; theyare indicated totreat hives, pruritus5
andrhinorrheia,26consideringthatsomecancause
hypoten-sionanddrowsiness.26Diphenhydramine1---2mgkg−1IVcan
beused,maximum50mgandcanbeassociatedwith raniti-dine50mgforadultsor1mgkg−1.50
Referral
to
allergologist
Theanesthesiologistresponsibleforthepatientshouldmake a referral to the allergologist if during general anesthe-siathereisanunexplainedreactionofseverehypotension, bronchospasmor edemaat recuperation.14 This referralis
performed inordertoconfirm thenatureofthe reaction, the offender drug, the possibility of cross-reactivity and recommendationsfor furtherstudies.1 The referral report
should include a medicalhistory of allergic reaction, the patientdemographics,allergicandatopichistory,the medi-calhistoryandthemedicationstheytake,theadministered drugsandthechronologicalsequenceofadministration,the detaileddescriptionofthereaction,thesuspectdrug,route ofadministration,theclinicalfeatures,thedegreeof sever-ity,thetreatmentgiven,theevolutionandthedurationof reaction.2Inaddition,includeinformationaboutexposure
tolatex,infusionsandexposuretime,interventionssuchas centrallineorurinarycatheterandfoodallergies.51Also,all
substanceexposuresshouldbenotedintheanesthesiaand referralrecord,includingthoseusedbythesurgeon,even iftheyarenotIV,suchaslocalanesthetics,fluidirrigation, latex,disinfectants,methyleneblue,amongothers.10
To
consider
Thereshouldbeaccesstoprotocolsforthemanagementof anaphylaxis.37,38
Thereshouldbeahabitofreportingtheadversereaction todrugs52anddiscussingthecaseforeducationalpurposes.
Additionally,theimportanceofreferraltoanallergologist shouldbeemphasizedtothepatient.38 Incase ofknowing
theoffenderdrug,itshouldbeputontheelectronic medi-calrecord,andamedicalidentification,suchasabracelet shouldbeputon.38
Incaseofreactiontocodeineormorphine,noneofthe twoistobeadministered,butthereisnocontraindication tootheropioids.17
If allergic to seafood, iodinated media is not contraindicated.17 There is one case of anaphylaxis to
protamine in a patient with allergy to fish, but the literaturedoesnotwarrantitsprohibition.17
Ifthereisany allergytoeggorsoybean, propofolmay beadministered.Thereis asinglecase ofhypersensitivity topropofolinapatientallergictoegg.17
Recommendations
Whenthepatientissubmittedtoanaphylaxisstudywitha positivetestandrequiresanesthesia,oneshouldavoidthe identifiedagentandhistamine-liberatingsubstances,inject thedrugsslowly,fractionedandseparated,ifpossible,and bepreparedtotreatananaphylacticreaction.45
Whenapatientwhohasahistoryofcardiovascular col-lapseinaprevious anesthesiapresentsfor urgentsurgery, withno study of anaphylaxis, care shouldbe provided in a latex-free environment, with the use of halogenated agents; in case of having previous record of anesthesia, avoid all medications used prior to collapse, except for halogenated agents, and avoid all neuromuscular block-ingagents in the eventof one beingpreviously used.18 If
thereis norecordofanesthesia, allneuromuscular block-ersshouldbeavoidedaccordingtotherisk-benefitbalance, andregionalorlocalanesthesiashouldbefavored,avoiding chlorhexidine(allergytoiodineislesscommon)andavoid histamine-releasingdrugs.18 Thereisnoevidencethat
pro-phylaxis,eitherwithantihistaminesorsteroids,preventor reducetheseverityofreaction.18,53
Duetothepotentiallyfatalfeatureofanaphylaxis, clin-icalsuspicionand the knowledge of the management are fundamental tothe impact of morbidity and mortality. It would alsobe perfect that a national network for repor-tingofcasesandnotificationofallergiesbeprovidedamong differenthealthinstitutions.
Conflict
of
interest
Theauthordeclaresnoconflictsofinterest.
References
2.Escolano Villén F.Reacciones alérgicas durantela anestesia. Situaciónactualyperspectivasdefuturo.RevEspAnestesiol Reanim.2005;52:67---70.
3.Simons FE, ArdussoLR, BilòMB, et al.,World Allergy Orga-nization.2012Update:WorldAllergyOrganizationGuidelines fortheassessmentandmanagementofanaphylaxis.CurrOpin AllergyClinImmunol.2012;12:389---99.
4.Girotra V, Lalkhen A. Anaphylaxis. Anaesth Intensive Care. 2014;15:15---9.
5.DhamiS,PanesarSS,RobertsG,etal.,EAACIFoodAllergyand AnaphylaxisGuidelinesGroup.Managementofanaphylaxis:a systematicreview.Allergy.2014;69:168---75.
6.Rocha JF. Cómo hacer frente a una reacciónalérgica en el perioperatorio: del rash a la anafilaxia. Rev Med Aeronaut. 2013;36:S288---90.
7.Soetens FM. Anaphylaxis during anaesthesia: diagnosis and treatment.ActaAnaesthesiolBelg.2004;55:229---37.
8.Ebo DG, Fisher MM, Hagendorens MM, et al. Anaphylaxis during anaesthesia: diagnostic approach. Allergy. 2007;62: 471---87.
9.Cardona R,MontoyaF,Orrego JC, etal. Anafilaxia.IATREIA. 2000;13:16---31.
10.KroigaardM,GarveyLH,GillbergL,etal.ScandinavianClinical PracticeGuidelinesonthediagnosis,managementand follow-upofanaphylaxisduringanaesthesia.ActaAnaesthesiolScand. 2007;51:655---70.
11.PhillipL.Anaphylaxis.MedClinNorthAm.2006;90:77---95. 12.PepysJ,PepysEO,BaldoBA,etal.Anaphylactic/anaphylactoid
reactions to anaesthetic and associated agents. Skin prick tests in aetiological diagnosis. Anaesthesia. 1994;49: 470---5.
13.Moneret-Vautrin DA,MorissetM,FlabbeeJ, etal. Epidemiol-ogyoflife-threateningandlethalanaphylaxis:areview.Allergy. 2005;60:443---51.
14.MertesPM,LaxenaireMC.Allergyandanaphylaxisin anaesthe-sia.MinervaAnestesiol.2004;70:285---91.
15.Mertes PM, Laxenaire MC, Alla F. Anaphylactic and anaphy-lactoid reactions occurring during anesthesia in France in 1999---2000.Anesthesiology.2003;99:536---45.
16.Thong BY, Yeow C. Anaphylaxis during surgical and inter-ventionalprocedures.AnnAllergyAsthmaImmunol.2004;92: 619---28.
17.MertesPM,MalinovskyJM,JouffroyL,etal.Reducingtherisk ofanaphylaxisduringanesthesia:2011updatedguidelinesfor Clinical Practice. J Investig Allergol Clin Immunol. 2011;21: 442---53.
18.BustamanteR.Anafilaxiaalosbloqueadoresneuromusculares. RevChilAnest.2011;40:316---34.
19.SimonsFE,SheikhA.Evidence-basedmanagementof anaphy-laxis.Allergy.2007;62:827---9.
20.Echeverría Zudaire LA, del Olmo de la Lama MR, Santana Rodríguez C. Anafilaxia en pediatría. Protoc Diagn Pediatr. 2013;1:63---80.
21.KempSF,LockeyRF,SimonsFE,WorldAllergyOrganizationad hocCommitteeonEpinephrineinAnaphylaxis.Epinephrine:the drugofchoiceforanaphylaxis.AstatementoftheWorldAllergy Organization.Allergy.2008;63:1061---70.
22.WhittingtonT,FisherMM.Anaphylacticandanaphylactoid reac-tions.BailliereClinAnesthesiol.1998;12:301---23.
23.Kotur PF. Hypersensitive reactions during anaesthesia...can
we diagnose and treat them? Indian J Anaesth. 2006;50: 86---8.
24.Bustamante R, Luxoro C. Anafilaxia perioperatoria: cuadro clínicoydiagnóstico.RevChilAnest.2010;39:36---52.
25.Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30: 1144---50.
26.SheikhA,TenBroekV,BrownSG,etal.H1-antihistaminesforthe treatmentofanaphylaxis:cochranesystematicreview.Allergy. 2007;62:830---7.
27.VandenHoekTL,MorrisonLJ,ShusterM,etal.Part12:Cardiac ArrestinSpecialSituations:2010AmericanHeartAssociation. Guidelinesfor CardiopulmonaryResuscitationandEmergency CardiovascularCare.Circulation.2010;122:S829---61.
28.Sheikh A, Shehata YA, Brown SG, et al. Adrenaline for the treatmentofanaphylaxis:cochranesystematicreview.Allergy. 2009;64:204---12.
29.BrownSG.Cardiovascularaspectsofanaphylaxis:implications fortreatmentanddiagnosis.CurrOpinAllergyClinImmunol. 2005;5:359---64.
30.Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol. 2006;110:7---14.
31.MaroneG,BovaM,DetorakiA,etal.Thehumanheartasashock organinanaphylaxis.NovartFoundSymp.2004;257:133---49. 32.HepnerDL,CastellsMC.Anaphylaxisduringtheperioperative
period.AnesthAnalg.2003;97:1381---95.
33.Mertes PM,Laxenaire MC. Épidémiologie des réactions ana-phylactiqueset anaphylactoïdesperanesthésiquesenFrance. Septième enquête multicentrique (Janvier 2001-Décembre 2002).AnnFrAnesthReanim.2004;23:1133---43.
34.EscolanoF,SánchezS.Anafilaxiaenanestesia.RevEsp Aneste-siolReanim.2013;60Suppl.1:55---64.
35.Michalska-Krzanowska G. Tryptase in diagnosing adverse suspected anaphylactic reaction. Adv Clin Exp Med. 2012;21:403---8.
36.Harper NJ, Dixon T, Dugué P, et al. Suspected anaphy-lactic reactions associated with anaesthesia. Anaesthesia. 2009;64:199---211.
37.CurrieM,KerridgeRK,BaconAK,etal.Crisismanagement dur-inganaesthesia:anaphylaxisandallergy.QualSafHealthCare. 2005;14:e19.
38.SimonsFE, ArdussoLR, DimovV, etal.,World Allergy Orga-nization. World Allergy Organization Anaphylaxis Guidelines: 2013updateoftheevidencebase.IntArchAllergyImmunol. 2013;162:193---204.
39.NelL,ErenE.Peri-operativeanaphylaxis.BrJClinPharmacol. 2011;71:647---58.
40.Brown A. Manejo actual de la anafilaxia. Emergencias. 2009;21:213---23.
41.MuraroA,RobertsG,ClarkA,etal.Themanagementof anaphy-laxisinchildhood:positionpaperoftheEuropeanacademyof allergologyandclinicalimmunology.Allergy.2007;62:857---71. 42.SimonsFE.Anaphylaxis,killerallergy:long-termmanagement
inthecommunity.JAllergyClinImmunol.2006;117:367---77. 43.SichererSH,SimonsFE.Quandariesinprescribinganemergency
actionplanandself-injectableepinephrineforfirstaid manage-mentofanaphylaxisinthecommunity.JAllergyClinImmunol. 2005;115:575---83.
44.EgeaEE,EgeaEA,GaravitodeEgeaG.Anafilaxis,estadodel arte.SaludUninorte.2004;18:30---40.
45.LuxoroC,BustamanteR.Anafilaxiaperioperatoria:tratamiento ymanejoalergoanestésico.RevChilAnest.2010;39:53---68. 46.Brown SG, Blackman KE, Stenlake V, et al. Insect sting
anaphylaxis;prospective evaluationof treatmentwith intra-venous adrenaline and volume resuscitation. Emerg Med J. 2004;21:149---54.
47.Ben-Shoshan M, Clarke AE. Anaphylaxis: past, present and future.Allergy.2011;66:1---14.
48.Pérez J. Anafilaxia: conceptos actuales. Rev Alerg Mex. 2009;56:181---4.
50.Mendoza M, Rosas MA, Guillén JE, et al. Anafi-laxia y choque anafiláctico. Rev Alerg Mex. 2007;54: 34---40.
51.MillsA,SiceP,FordS.Anaesthesia-relatedanaphylaxis: inves-tigationand follow-up. Contin EducAnaesth CritCare Pain. 2013;14:57---62.
52.RuizM,LópezCA,HernándezIA,etal.Reporteespontáneoy oportunodereaccionesadversasmedicamentosas:unacultura necesaria.MedicinaUPB.2010;29:56---61.
