RevBrasAnestesiol.2017;67(2):217---220
REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologia www.sba.com.brCLINICAL
INFORMATION
Perianesthetic
refractory
anaphylactic
shock
with
cefuroxime
in
a
patient
with
history
of
penicillin
allergy
on
multiple
antihypertensive
medications
Deb
Sanjay
Nag
∗,
Devi
Prasad
Samaddar,
Shashi
Kant,
Pratap
Rudra
Mahanty
TataMainHospital,DepartmentofAnesthesiologyandCriticalCare,Jamshedpur,India
Received20June2014;accepted6August2014 Availableonline27October2014
KEYWORDS Anaphylaxis; Perianesthetic; Cefuroxime
Abstract Wereportacaseofperianestheticrefractoryanaphylacticshockwithcefuroximeina patientwithhistoryofpenicillinallergyonregulartherapywithatenolol,losartan,prazosinand nicardipine.Severeanaphylacticshockwasonlytransientlyresponsiveto10mLof(1:10,000) epinephrineandneedednorepinephrineanddopamineinfusion.Supportivetherapywith vaso-pressors and inotropes along with mechanical ventilationfor the next 24hours resulted in completerecovery.Shewassuccessfullyoperatedupon2weekslaterwiththesameanesthetic drugsbutintravenousciprofloxacinasthealternativeantibioticforperioperativeprophylaxis. ©2014SociedadeBrasileiradeAnestesiologia.Publishedby ElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).
PALAVRAS-CHAVE Anafilaxia;
Perianestésico; Cefuroxima
Choqueanafiláticorefratárioperianestésicocomcefuroximaempacientecom históriadealergiaàpenicilinarecebendováriosmedicamentosanti-hipertensivos
Resumo Relatamosumcasodechoqueanafiláticorefratárionoperíodoperianestésicocom cefuroximaempacientecomhistóriadealergiaàpenicilinaemterapiaregularcomatenolol, losartan, prazosina e nicardipine. O choque anafilático grave foi apenas transitoriamente responsivoa10mLdeepinefrina (1:10000)eprecisoudeinfusãodenorepinefrinae dopam-ina.Aterapiadeapoiocomvasopressoreseinotrópicos,juntamentecomventilac¸ãomecânica por24horasresultaramemrecuperac¸ãocompleta.Apacientefoioperadacomsucessoduas semanasmaistarde,comosmesmosagentesanestésicos,mascomciprofloxacinaintravenosa comoantibióticoalternativoparaaprofilaxiaperioperatória.
©2014SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Este ´eum artigo OpenAccess sobumalicenc¸aCCBY-NC-ND( http://creativecommons.org/licenses/by-nc-nd/4.0/).
∗Correspondingauthor.
E-mail:[email protected](D.S.Nag). http://dx.doi.org/10.1016/j.bjane.2014.08.001
218 D.S.Nagetal.
Introduction
Operatingroomisauniqueenvironmentwherethepatient
receivesexposuretomultiple drugs whichcan potentially
causeanaphylaxis.Whileantibioticsremainoneofthe
com-monestcausesofperioperativeanaphylaxis,theconcurrent
antihypertensive medications can make the anaphylactic
shock refractory toconventional therapy. Herewe report
acaseofsevererefractoryanaphylacticshockinapatient
onmultiple antihypertensivemedications.Patient consent
hasbeenobtainedforthisreport.
Case
description
A 46-year-old (70kg) lady was scheduled for an open
reductionandinternalfixation (ORIF)of fractureoflower
end of humerus. She had a history of hypertension and
hypothyroidism which was controlled on atenolol 25mg
oncedaily,losartan50mgtwicedaily,prazosin2.5mgonce
daily, nicardipine 20mg twice daily and thyroxin sodium
100microgramsoncedaily.
Shehadnohistoryofprevioussurgeryoranesthesia
expo-sure but reportedallergy topenicillin.However she gave
historyoforalintakeofamoxicillinanderythromycin
with-out any adverse reaction. Pre-anesthesia evaluation was
doneonadmissionand allherroutineinvestigationswere
withinnormallimits.ExceptforLosartan, shereceivedall
her antihypertensive medication and thyroxin sodium on
themorningof surgery. Her initialbaselinereadings were
a pulse rate of 69/min, blood pressure of 171/75mmHg
and room air saturation (SpO2) of 97%. General
anesthe-siawasinduced withfentanyl100micrograms,midazolam
1mg,propofol140mgand vecuronium6mgintravenously.
Patientwasintubatedandmaintainedonisoflurane,nitrous
oxideandoxygenthroughthecirclesystemandintermittent
positivepressureventilation.
Thepatientwasmaintainingstablehemodynamicsover
thenext15min whenshe waspositionedandpart
prepa-ration of the surgical site was done. Within minutes of
initiating the intravenous injection of cefuroxime (1.5g
dilutedin 20mLof sterile water) the heart rate dropped
to36min,peakairwaypressuresincreasedtoabove40cm
of H20 and blood pressure became unrecordable. By this
timeonly750mg cefuroximehadbeen administered.
Fur-theradministrationofcefuroximewasimmediatelystopped.
Acallforhelpwasgivenandallanestheticgaseswereturned
off.The patientwas switched tomanual ventilation with
100%oxygen.Higherresistancetoventilationwas
appreci-atedwhilesqueezingthebagoftheanesthesiaworkstation.
The bradycardia was initially non-responsive to 0.6mg of
intravenousatropine,butrespondedtoaseconddosewith
heartraterisingto112/min.Thepatientdeveloped
maculo-papular rash all over her body with evident angioedema
causingrapidswellingofeyelids,lipsandface.
Anaphylaxis was diagnosed and immediately 1mL of
(1:10,000) Epinephrine was administered intravenously
along withrapid transfusion of 1000mL of normal saline,
200mg of intravenous hydrocortisone and 25mg of
intra-muscular promethazine hydrochloride. Her lower limbs
were elevated. Simultaneously 10 puffs of salbutamol
were deliveredinto the endotracheal tube. On observing
noresponse,incremental dosesof 10mL (1:10,000)
intra-venous Epinephrine was administered over 10min. This
resulted in an appreciable peripheral pulse and a blood
pressure of 81/30mmHg on the non-invasive blood
pres-sure monitor. Bronchospasm started gettingrelieved with
mild chest expansion and faint breath sounds were
audible on auscultation. Saturation (SpO2) increased to
85---90% over the next 5min the blood pressure again
started dropping with very feeble central pulses and
became unrecordable very soon. Central venous access
wasimmediatelysecuredthroughthesubclavianrouteand
dopamineinfusionwasstartedat 5microgram/kg/minand
increased to 10microgram/kg/min, resulting in a blood
pressure of 80/39mmHg over the next 15min.
Suspec-tingrefractoryanaphylacticshock,norepinephrineinfusion
was also started at 2microgram/min and increased to
5microgram/minresultinginbloodpressureof92/43mmHg
withheartrateof146/min.Shebecameconscious,started
breathingspontaneouslyandrespondedbyeyemovements
inthenext15min.Thedecisionwasmadetopostponethe
surgeryandthepatientwasshiftedtotheCriticalCareUnit
(CCU).
In the CCU, she was put on mechanical
ventila-tion and the initial Arterial Blood Gas (ABG) showed
mixed metabolic and respiratory acidosis. She was
advised intravenous hydrocortisone 50mg/6 hourly and
ranitidine 50mg/12 hourly. She needed inotropic
sup-port withdopamine10microgram/kg/min,norepinephrine
5microgram/minandepinephrine2microgram/minwithan
aim to maintain blood pressure above 70% of pre-shock
levels.Norepinephrinewasgraduallytapered andstopped
overthenext2h.Bloodpressuregraduallyimprovedfrom
99/54mmHg to 140/90mmHg with heart rate range of
98---113min by next morning, 24h after the event. All
vasoactiveagentsweregraduallytaperedandstopped.She
wasconsciousandresponsivetocommands.AfteraT-Piece
trial, shewasextubated. Postextubation shewasableto
speakandmaintainhervitalparameterswithoxygen
supple-mentationbymask.Hydrocortisonewasstoppedonthethird
dayaftertheeventandthepatientwasshiftedtohercabin.
Facialswellinggraduallyreducedandsherecoveredbackto
normalcy without any residual effect of the anaphylactic
reaction.
Herantihypertensivedrugswererestarted3dayslater.
She was operated upon after two weeks with
periopera-tive antibiotic coverage of intravenous ciprofloxacin and
general anesthesia with propofol, fentanyl and
vecuro-niumforinductionandendotrachealintubation,isoflurane,
nitrous oxideandvecuronium were usedfor maintenance
of anesthesia. After the surgery, reversal of
neuromuscu-larblockadewasdonewithneostigmineandglycopyrrolate.
Following an uneventful intraoperative and postoperative
course, she was discharged from the hospital two weeks
afterhersurgery.
Discussion
Whiletheincidenceofperioperativeanaphylaxishasbeen
reportedtobebetween1in10,000---20,000anesthesia
pro-cedures, it is responsible for 3---10% of the perioperative
Perianestheticrefractoryanaphylacticshockwithcefuroximeinapatient 219
anesthesiologistswhoadministermultipledrugswith
poten-tialtocausefatalhypersensitivitytoanydrug.2Anaphylaxis
has been defined as‘‘a serious, life-threatening
general-ized or systemic hypersensitivity reaction’’ or ‘‘a serious
allergic reaction that is rapid in onset and might cause
death.’’3Allergicreactionstoanestheticdrugsusuallyoccur
within10min of the drug exposure but can alsooccur as
lateas30min toseveralhourslater.4However,morethan
90%ofreactionsevokedbyintravenousdrugsoccurwithin
3min of its administration.5 In this case the patient was
maintaininggoodhemodynamicparameterstillcefuroxime
injectionwasstarted.Thereforeitappearsthatcefuroxime
wasthecauseofthisanaphylacticreaction.Thesubsequent
uneventfuladministrationofgeneralanesthesiatwoweeks
laterusingthesamedrugs(exceptcefuroxime)before
inci-sionreaffirmed ourbeliefthat it wascefuroximeinduced
anaphylaxis.
Thereisadequateliteratureevidenceaboutthesafetyof
cephalosporins(includingcefuroxime)inpatientsreporting
allergytopenicillin.6,7Althoughskintestingcouldhavebeen
done prior to administration of cefuroxime, novalidated
diagnostictest (includingskintesting) is ofsufficient
sen-sitivityforevaluatingofIgE-mediatedallergytoantibiotics
otherthanpenicillin.8Eveninpatientswhoaretruly
aller-gictopenicillin,theriskofareactionfromacephalosporin
withsidechainsdifferent frompenicillin/amoxicillinis so
lowthatitsuseis‘‘justifiedandmedico-legallydefensible
bythecurrentlyavailableevidence’’.9
Inourpatient,anaphylaxiswasdiagnosedbythe‘‘clinical
criteriafordiagnosinganaphylaxis’’assuggestedby
Samp-sonetal.10Bradycardiaisanuncommonpresentationduring
anaphylaxis.Inourpatient,premedicationwithbetablocker
and severe hypoxia couldbethe probable reason for this
uncommonpresentation.11
Therearenumerouscasesofsevereanaphylacticshock
refractory to catecholamines.12 ACE inhibitors have been
reported to be associated with increased risk for more
severereactionfromvenomimmunotherapyorfieldsting.13
Thereareisolatedcasereportsofresistancetoepinephrine
in patients on alpha adrenergic blockers.14 Resistance to
exogenous catecholaminesin patients onbeta-blockers is
notonlyduetodesensitizationofadrenergicreceptors,it
alsoinvolvesnitric oxidewhichplaysapivotal rolein the
pathophysiologyofanaphylaxis.Increasednitricoxide
syn-thesishasbeenfoundtoberesponsibleforthevasodilatory
shock resistant tovasopressors.15 Greaterrisk of
anaphy-laxis exists in patients on ACE inhibitors and angiotensin
receptor blockers as they ‘‘inhibit the metabolism of
angiotensin, bradykinin, and substance P’’ and derange
the compensatory activation of the rennin-angiotensin
system.13 ACEinhibitorsalsocauseimpairedbreakdownof
bradykinin (a vasoactive mediator causing hypotensionin
severeanaphylaxis).13Possibly,thesynergisticeffectofall
theconcurrentantihypertensive drugs(atenolol, losartan,
prazosin, nicardipine) contributed to the refractory
ana-phylactic shock with only transient response to 10mL of
(1:10,000)epinephrineinourpatient.
In refractory anaphylactic shock, norepinephrine,
metaraminol, methylene blue or glucagon has been
recommended.1,15 Although an infusion of dopamine and
norepinephrine was started in our patient, ‘‘no clear
superiority of dopamine, dobutamine, norepinephrine,
phenylephrine,orvasopressin(eitheraddedtoepinephrine
alone,or compared withone another), has been
demon-stratedinclinicaltrials’’.16Basedontheclinicalresponse,
epinephrine infusion was added in the CCU and
norepi-nephrine was subsequently tapered off. In suspected
anaphylaxis, blood samples for estimation of tryptase
shouldbesentbetween 15and 180min andforhistamine
between15 and 60min fromthe onsetof symptoms. The
specificityof thesetests hasbeen questioned andnormal
valuesdonotruleoutanaphylaxis.16Ithasbeensuggested
thatskintesting shouldbeperformed4---6weeksafterthe
reactiontoidentifythespecificallergy.17Thereisevidence
that in cases of conclusive clinical history and strong
temporalassociation with the implicated drug, skin tests
orinvitro specificIgE,and/orchallengetestsmaynotbe
warranted.12 Facilities forthesetestswereunavailable at
oursetup,thereforenotconsideredforfurtherevaluation.
Epinephrine remains the only first line medication in
anaphylaxis and refractory anaphylactic shock should be
considered in patients on multiple antihypertensive
med-ications.As peri-anestheticanaphylaxis is becomingmore
common,18vigilanceandearlyrecognitionofanaphylaxisis
ofparamountimportancetoreduceitsadverseoutcome.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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