Shock Anaphylatic

8/9/2019 Shock Anaphylatic

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http://emedicine.medscape.com/article/135065-overview#showall

Practice Essentials

Anaphylais is an ac!te" potentially atal" m!ltior$an system reaction ca!sed %y the release ochemical mediators rom mast cells and %asophils.&1" '( )he classic orm involves prior sensiti*ation toan aller$en with later reepos!re" prod!cin$ symptoms via an imm!nolo$ic mechanism.

Signs and symptoms

Anaphylais most commonly aects the c!taneo!s" respiratory" cardiovasc!lar" and $astrointestinalsystems. )he s+in or m!co!s mem%ranes are almost always involved. A ma,ority o ad!lt patientshave some com%ination o !rticaria" erythema" pr!rit!s" or an$ioedema. owever" or poorly!nderstood reasons" children may present more commonly with respiratory symptoms ollowed %yc!taneo!s symptoms.&3(

nitially" patients oten descri%e a sense o impendin$ doom" accompanied %y pr!rit!s and l!shin$.ther symptoms can evolve rapidly" s!ch as the ollowin$:

• ermatolo$ic/oc!lar: l!shin$" !rticaria" an$ioedema" c!taneo!s and/or con,!nctival in,ection

or pr!rit!s" warmth" and swellin$

• 2espiratory: asal con$estion" cory*a" rhinorrhea" snee*in$" throat ti$htness" whee*in$"

shortness o %reath" co!$h" hoarseness" dyspnea

• 4ardiovasc!lar: i**iness" wea+ness" syncope" chest pain" palpitations

• astrointestinal: yspha$ia" na!sea" vomitin$" diarrhea" %loatin$" cramps

• e!rolo$ic: eadache" di**iness" %l!rred vision" and sei*!re very rare and oten associated

with hypotension7

• ther: 8etallic taste" eelin$ o impendin$ doom

9ee 4linical Presentation or more detail.

Diagnosis

Anaphylais is primarily a clinical dia$nosis. )he irst priority in the physical eamination sho!ld %e toassess the patients airway" %reathin$" circ!lation" and ade;!acy o mentation e$" alertness"orientation" coherence o tho!$ht7.

Eamination may reveal the ollowin$ indin$s:

• eneral appearance and vital si$ns:


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• )estin$ or ood aller$yies7

• )estin$ or medication aller$yies7

• )estin$ or ca!ses o $E-independent reactions

9ee or+!p or more detail.

Management

Anaphylais is a medical emer$ency that re;!ires immediate reco$nition and intervention. Patientmana$ement and disposition are dependent on the severity o the initial reaction and the treatmentresponse. 8eas!res %eyond %asic lie s!pport are not necessary or patients with p!rely localreactions. Patients with reractory or very severe anaphylais with cardiovasc!lar and/or severerespiratory symptoms7 sho!ld %e admitted or treated and o%served or a lon$er period in theemer$ency department or an o%servation area.

Nonpharmacotherapy

9!pportive care or patients with s!spected anaphylais incl!des the ollowin$:

• Airway mana$ement e$" ventilator s!pport with %a$/valve/mas+" endotracheal int!%ation7

• i$h-low oy$en

• 4ardiac monitorin$ and/or p!lse oimetry

• ntraveno!s access lar$e %ore7

• l!id res!scitation with isotonic crystalloid sol!tion

• 9!pine position or position o comort i dyspneic or vomitin$7 with le$s elevated

Pharmacotherapy

)he primary dr!$ treatments or ac!te anaphylactic reactions are epinephrine and 1 antihistamines.8edications !sed in patients with anaphylais incl!de the ollowin$:

• Adrener$ic a$onists e$" epinephrine7

• Antihistamines e$" diphenhydramine" hydroy*ine7

• ' receptor anta$onists e$" cimetidine" ranitidine" amotidine7

• Bronchodilators e$" al%!terol7• 4orticosteroids e$" methylprednisolone" prednisone7

• Positive inotropic a$ents e$" $l!ca$on7

•


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Beca!se anaphylais is primarily a clinical dia$nosis" la%oratory st!dies are not !s!ally re;!ired andare rarely help!l. owever" i the dia$nosis is !nclear" especially with a rec!rrent syndrome" or iother diseases need to %e ecl!ded" some limited la%oratory st!dies are indicated. 9+in testin$ and invitro $E tests may %e help!l. 9ee or+!p.7

Anaphylais is a medical emer$ency that re;!ires immediate reco$nition and intervention. isposition

o patients with anaphylais depends on the severity o the initial reaction and the response totreatment. ote that $!idelines or the emer$ency medical treatment o anaphylais varyinternationally.&@( 9ee )reatment and 8ana$ement.7

o to Pediatric Anaphylais and Pediatric Eercise-nd!ced Anaphylais or complete inormation onthese topics.

Pathophysiolo$y

)he traditional nomenclat!re or anaphylais reserves the term anaphylactic or reactions mediated %yimm!no$lo%!lin E $E7 and the term anaphylactoid or $E-independent events" which are clinicallyindistin$!isha%le. )he orld Aller$y r$ani*ation has recommended replacin$ this terminolo$y withimm!nolo$ic $E-mediated and nonF$E-mediated &e$" $ and imm!ne comple complementFmediated(7 and nonimm!nolo$ic anaphylais events res!ltin$ in s!dden mast cell and %asophil

de$ran!lation in the a%sence o imm!no$lo%!lins7. &5(

)he physiolo$ic responses to the release o anaphylais mediators incl!de smooth m!scle spasm inthe respiratory and $astrointestinal 7 tracts" vasodilation" increased vasc!lar permea%ility" andstim!lation o sensory nerve endin$s. ncreased m!co!s secretion and increased %ronchial smoothm!scle tone" as well as airway edema" contri%!te to the respiratory symptoms o%served inanaphylais.

4ardiovasc!lar eects res!lt rom decreased vasc!lar tone and capillary lea+a$e. ypotension"cardiac arrhythmias" syncope" and shoc+ can res!lt rom intravasc!lar vol!me loss" vasodilation" andmyocardial dys!nction. ncreased vasc!lar permea%ility can prod!ce a shit o 35G o vasc!larvol!me to the etravasc!lar space within 10 min!tes.

)hese physiolo$ic events lead to some or all o the classic symptoms o anaphylais:l!shin$= !rticaria/an$ioedema= pr!rit!s= %ronchospasm= laryn$eal edema= a%dominal crampin$ withna!sea" vomitin$" and diarrhea= and eelin$ o impendin$ doom. 4oncomitant si$ns and symptomscan incl!de rhinorrhea" dysphonia" metallic taste" !terine cramps" li$ht-headedness" and headache.

Additional mediators activate other pathways o inlammation: the ne!tral proteases" tryptase andchymase= proteo$lycans s!ch as heparin and chondroitin s!late= and chemo+ines and cyto+ines.)hese mediators can activate the +alli+rein-+inin contact system" the complement cascade" andcoa$!lation pathways. )he development and severity o anaphylais also depend on theresponsiveness o cells tar$eted %y these mediators.

nterle!+in >7F@ and >-13 are cyto+ines important in the initial $eneration o anti%ody andinlammatory cell responses to anaphylais. o compara%le st!dies have %een cond!cted in h!mans"%!t anaphylactic eects in mice depend on >-@2H-dependent >-@/>-13 activation o the transcription

actor" 9)A)-6 si$nal transd!cer and activator o transcription 67. &6( Eosinophils may %e inlammatoryrelease cytotoic $ran!le-associated proteins" or eample7 or anti-inlammatory meta%oli*evasoactive mediators" or eample7.

Additional mediators incl!de newly $enerated lipid-derived mediators s!ch as prosta$landin '"le!+otriene B@" and platelet-activatin$ actor PA7" as well as the cysteinyl le!+otrienes" s!ch as>)4@" >)@" and >)E@. )hese mediators !rther contri%!te to the proinlammatory cascade seen inanaphylais.

?nder ri$id eperimental conditions" histamine in!sion alone is s!icient to prod!ce most o thesymptoms o anaphylais. istamine mediates its eects thro!$h activation o histamine 1 17 andhistamine ' '7 receptors.


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chronotropy" and coronary artery vasodilation. 3 receptors in eperimental models o canineanaphylais appear to inl!ence cardiovasc!lar responses to norepinephrine. )he importance o3 receptors in h!mans is !n+nown.

Processes inducing cardiovascular changes

Anaphylais has %een associated clinically with myocardial ischemia" atrial and ventric!lar

arrhythmias" cond!ction deects" and )-wave a%normalities. hether s!ch chan$es are related todirect mediator eects on the myocardi!m" to eacer%ation o preeistin$ myocardial ins!iciency %ythe adverse hemodynamic eects o anaphylais" to epinephrine released endo$eno!sly %y theadrenals in response to stress" or to therape!tically in,ected epinephrine is !nclear.

9ince mast cells acc!m!late at sites o coronary atherosclerotic pla;!es" and imm!no$lo%!lins %o!ndto mast cells can tri$$er mast cell de$ran!lation" some investi$ators have s!$$ested that anaphylaismay promote pla;!e r!pt!re" th!s ris+in$ myocardial ischemia. 9tim!lation o the 1 histaminereceptor may also prod!ce coronary artery vasospasm. PA also delays atrioventric!lar cond!ction"decreases coronary artery %lood low" and has ne$ative inotropic eects.

4alcitonin $ene-related peptide 42P7" a sensory ne!rotransmitter that is widely distri%!ted incardiovasc!lar tiss!es" may help to co!nteract coronary artery vasoconstriction d!rin$ anaphylais.

42P relaes vasc!lar smooth m!scle and has cardioprotective eects in animal models oanaphylais.

)wo distinct physiolo$ic responses occ!r in mammals eperiencin$ hypovolemia. &I( )he initialresponse to hypovolemia is a %aroreceptor-mediated increase in overall cardiac sympathetic driveand a concomitant withdrawal o restin$ va$al drive" which to$ether prod!ce peripheralvasoconstriction and tachycardia.

hen eective %lood vol!me decreases %y '0-30G" a second phase ollows" which is characteri*ed%y withdrawal o vasoconstrictor drive" relative or a%sol!te %radycardia" increased vasopressin" !rther catecholamine release as the adrenals %ecome more active" and hypotension. ypotension in thishypovolemic settin$ is independent o the %radycardia" since it persists when the %radycardiareverses with atropine administration.

4ond!ction deects and sympatholytic medications may also prod!ce %radycardia. Ecessive veno!spoolin$ with decreased veno!s ret!rn also seen in vasodepressor reactions7 may activate tension-sensitive sensory receptors in the ineroposterior portions o the let ventricle" th!s res!ltin$ in acardio-inhi%itory Be*old-Jarisch7 rele that stim!lates the va$!s nerve and ca!ses %radycardia.

)he implications o relative or a%sol!te %radycardia in h!man anaphylais andhypovolemicshoc+ have not %een st!died.

owever" one retrospective review o approimately 11"000 tra!ma patients o!nd that mortality waslower with the 'C percent o hypotensive patients who were %radycardic when they were compared tothe $ro!p o hypotensive individ!als who were tachycardic" ater ad,!stment or other mortality actors.&K( )h!s" %radycardia may have a speciic compensatory role in these settin$s.

Etiolo$y$E-mediated anaphylais is the classic orm o anaphylais" where%y a sensiti*in$ anti$en elicits an$E anti%ody response in a s!scepti%le individ!al. )he anti$en-speciic $E anti%odies then %ind tomast cells and %asophils. 9!%se;!ent epos!re to the sensiti*in$ anti$en ca!ses cross-lin+in$ o cell-%o!nd $E" res!ltin$ in mast cell and/or %asophil7 de$ran!lation.

ther types o imm!nolo$ic anaphylais do not involve $E. or eample" anaphylais res!ltin$ romadministration o %lood prod!cts" incl!din$ intraveno!s imm!no$lo%!lin" or animal antiser!m is d!e" atleast in part" to complement activation. mm!ne complees ormed in vivo or in vitro can activate thecomplement cascade. 4ertain %yprod!cts o the cascadeLplasma-activated complement 3 43a7"plasma-activated complement @ 4@a7" and plasma-activated complement 5 45a7Lare calledanaphylatoins and can ca!se mast cell/%asophil de$ran!lation.

hen mast cells and %asophils de$ran!late" whether %y $E- or nonF$E-mediated mechanisms"preormed histamine and newly $enerated le!+otrienes" prosta$landins" and platelet-activatin$ actor

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PA7 are released. n the classic orm" mediator release occ!rs when the anti$en aller$en7 %inds toanti$en-speciic $E attached to previo!sly sensiti*ed %asophils and mast cells. )he mediators arereleased almost immediately when the anti$en %inds.

4ertain a$ents are tho!$ht to ca!se direct nonimm!nolo$ic release o mediators rom mast cells" aprocess not mediated %y $E. )hese incl!de opioids" detrans" protamine" and vancomycin.

8echanisms !nderlyin$ these reactions are poorly !nderstood %!t may involve speciic receptors e$"opioids7 or nonFreceptor-mediated mast cell activation e$" hyperosmolarity7.

Inciting agents

)he most common incitin$ a$ents in anaphylais are oods" ymenoptera stin$s" and intraveno!s


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reactivity with the older a$ents is d!e to $reater anti$enic similarity o the side chain not present withthe newer second- and third-$eneration a$ents.

ne report s!$$ested that the act!al incidence o anaphylais to cephalosporins in penicillin-anaphylactic patients is m!ch lower than the 10G re;!ently ;!otedLperhaps 1G" with mostreactions considered mild.&15( A retrospective st!dy eval!ated 606 hospitali*ed patients with a history o

penicillin aller$y who were $iven a cephalosporin. nly one patient 0.1IG7 had a reaction" and it wasminor .&16(

Another paper indicated that patients with a history o aller$y to penicillin seem to have a hi$her ris+%y a actor o a%o!t 37 o s!%se;!ent reaction to any dr!$ and that the ris+ o an aller$ic reaction tocephalosporins in patients with a history o penicillin aller$y may %e !p to K times as hi$h as the ris+ inthose with no history o penicillin aller$y ie" at least part o the o%served Dcross-reactivity mayrepresent a $eneral state o imm!ne hyperresponsiveness" rather than tr!e cross-reactivity7. &1I(

Pichichero reviewed the complicated literat!re and oered speciic $!idance or the !se ocephalosporins in patients who have a history o $E-mediated reactions to penicillin. &1K(

Patients with a history o positive s+in tests or penicillin aller$y are at hi$h ris+ o s!%se;!entreactions to penicillins. owever" approimately K5G o patients with a history o penicillin aller$y

have ne$ative s+in tests and a low ris+ o reactions. Patients with less well-deined reactions topenicillin have a very low ris+ 1-'G7 o developin$ anaphylais to cephalosporins. )he rate o s+in-test reactivity to imipenem in patients with a +nown penicillin aller$y is almost 50G. n contrast" no+nown in vitro or clinical cross-reactivity eists %etween penicillins and a*treonam.

hen either a penicillin or a cephalosporin is the dr!$ o choice or a patient with a lie-threatenin$emer$ency" a n!m%er o options eist. hen the history is indeinite" the dr!$ may %e administered!nder close o%servation= however" when possi%le" o%tain the patients inormed consent. mmediatetreatment meas!res or anaphylais sho!ld %e availa%le. Alternatively" when the history is moreconvincin$" an alternative a$ent sho!ld %e chosen i it provides similar eicacy or one m!st p!rs!e adesensiti*ation protocol.

8any other dr!$s have %een implicated in $E-mediated anaphylais" al%eit less re;!ently. n the

s!r$ical settin$" anaphylactic reactions are most oten d!e to m!scle relaants %!t can also %e d!e tohypnotics" anti%iotics" opioids" colloids" and other a$ents. )he prevalence o late aller$y was hi$herd!rin$ the 1CK0s d!e to the < and hepatitis B and 4 epidemics and the instit!tion o !niversalpreca!tions7" %!t the incidence has decreased si$niicantly since the widespread !se o late-reematerials. late is responsi%le or anaphylais in the perioperative settin$" reactions tend to occ!rd!rin$ maintenance anesthesia" whereas other a$ents tend to ca!se reactions d!rin$ the ind!ction oanesthesia.


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2is+ actors or severe anaphylais d!e to imm!notherapy incl!de poorly controlled asthma"conc!rrent !se o %eta-%loc+ers" hi$h aller$en dose" errors in administration" and lac+ o a s!iciento%servation period ollowin$ the in,ection.

ear-atal reactions 2s7 to s!%c!taneo!s imm!notherapy also have %een eaminedretrospectively. 6@6 aller$ist-imm!nolo$ists who responded to a s!rvey on reactions" 'I3 reported

2s. )he investi$ators deined an 2 as respiratory compromise" hypotension" or %oth" re;!irin$emer$ency epinephrine. ypotension was reported in K0G and respiratory ail!re occ!rred in 10G o2s" ecl!sively in s!%,ects with asthma. Epinephrine was delayed or not administered in 6G othese cases.

Immunologic reactions to aspirin, NSAIDs, and ACE inhibitors

2eactions to aspirin and nonsteroidal anti-inlammatory dr!$s 9As7 in the past have %eenclassiied as $E-independent %eca!se they were tho!$ht to occ!r rom a%errant meta%olism oarachidonic acid.

solated c!taneo!s reactions to aspirin/9As and %ronchospasm in aspirin-sensitive asthmaticsoten in association with nasal polyposis7 are indeed mediated thro!$h $E-independentmechanisms. Bloc+ade o cyclooy$enase %y these dr!$s ca!ses the prostanoid pathway to sh!t

down" res!ltin$ in an overprod!ction o le!+otrienes via the 5-lipoy$enase pathway. )hese patientshave mar+ed cross-reactivity %etween aspirin and most 9As.

Anaphylais ater ta+in$ these dr!$s" however" apparently occ!rs via a dierent mechanism that ismore consistent with $E-mediated anaphylais. ith tr!e anaphylais" the dierent cyclooy$enaseinhi%itors do not appear to cross-react. Anaphylais occ!rs only ater ' or more epos!res to theimplicated dr!$" s!$$estin$ a need or prior sensiti*ation. inally" patients with tr!e anaphylais do not!s!ally have !nderlyin$ asthma" nasal polyposis" or !rticaria.

n one st!dy o nearly 5'"000 people ta+in$ 9As" 35 developed anaphylactic shoc+.

An$iotensin-convertin$ en*yme A4E7 inhi%itors" widely !sed in the treatment o hypertension" areassociated with an$ioedema in 0.5-1.0G o patients who ta+e them. 9ystemic anaphylais is rarelyassociated with these a$ents.

Immunologic IgE-independent reactions

Anaphylais may res!lt rom administration o %lood prod!cts" incl!din$ < imm!no$lo%!lin" or animalantiser!m" at least partly as a conse;!ence o activation o the complement cascade. 4ertain%yprod!cts o the cascade are capa%le o ca!sin$ mast cell/%asophil de$ran!lation. 9eePathophysiolo$y.7

Eercise-ind!ced anaphylais is a rare syndrome that can ta+e 1 o ' orms. )he irst orm is ooddependent" re;!irin$ eercise and the recent in$estion o partic!lar oods e$" wheat" celery7 ormedications e$" 9As7 to ca!se an episode o anaphylais. n these patients" eercise alone doesnot prod!ce an episode" and" similarly" in$estin$ the c!lprit ood or medication alone does not ca!sean episode.

)he second orm is characteri*ed %y intermittent episodes o anaphylais d!rin$ eercise"independent o any ood in$estion. Anaphylais does not necessarily occ!r d!rin$ every episode ophysical eertion.

Anaphylais can %e a maniestation o systemic mastocytosis" a disease characteri*ed %y ecessivemast cell %!rden in m!ltiple or$ans. 9!ch patients appear to %e at increased ris+ or ood and venomreactions. Alcohol" vancomycin" opioids" radiocontrast media" and other %iolo$ic a$ents that candirectly de$ran!late mast cells are $enerally disco!ra$ed in these patients.

Nonimmunologic reactions

4ertain a$ents" incl!din$ opioids" detrans" protamine" and vancomycin" are tho!$ht to ca!se direct"nonimm!nolo$ic release o mediators rom mast cells. Evidence also eists that detrans and

protamine can activate several inlammatory pathways" incl!din$ complement" coa$!lation" andvasoactive +alli+rein-+inin7 systems.


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ntraveno!sly administered radiocontrast media ca!se an anaphylactoid reaction that is clinicallysimilar to tr!e anaphylais and is treated in the same way. )he reaction is not related to priorepos!re. Approimately 1-3G o patients who receive hyperosmolar < contrast eperience areaction. 2eactions to radiocontrast media !s!ally are mild most commonly !rticarial7" with only rareatalities reported. 2is+ o a atal reaction has %een estimated at 0.C cases per 100"000 epos!res.

Pretreatment with antihistamines or corticosteroids and !se o low-molec!lar-wei$ht >87 contrasta$ents lead to lower rates o anaphylactoid reactions to < radiocontrast media approimately 0.5G7.4onsider these meas!res or patients who have prior history o reaction" since rate o rec!rrence isestimated at 1I-60G. 9ome instit!tions !se only >8 a$ents. Personnel" medications" ande;!ipment needed or treatment o aller$ic reactions always sho!ld %e availa%le when these a$entsare administered. %tain consent %eore administration.

Patients who are atopic and/or asthmatic also are at increased ris+ o reaction. n addition" aller$icreaction is more diic!lt to treat in those ta+in$ %eta-%loc+ers.

9hellish or iodine aller$y is not a contraindication to !se o < contrast and does not mandate apretreatment re$imen. As with any aller$ic patient" $ive consideration to !se o >8 contrast a$ents.n act" the term iodine allergy is a misnomer. odine is an essential trace element present thro!$ho!tthe %ody. o one is aller$ic to iodine. Patients who report iodine aller$y !s!ally have had either a prior

contrast reaction" a shellish aller$y" or a contact reaction to povidone-iodine Betadine7.

8!cosal epos!re e$" " $enito!rinary &?(7 to radiocontrast a$ents has not %een reported to ca!seanaphylais= thereore" a history o prior reaction is not a contraindication to or ? !se o thesea$ents.

Idiopathic anaphylais

diopathic anaphylais is a syndrome o rec!rrent anaphylais or which no consistent tri$$ers can %edetermined despite an eha!stive search.&'@( )his rec!rrent syndrome sho!ld %e distin$!ished rom asin$le episode o anaphylais or which the etiolo$y may %e !nclear.

diopathic anaphylais can %e cate$ori*ed as inre;!ent N 6 episodes per year7 or re;!ent O6episodes per year or ' or more episodes within the last ' months7. &'@(ne approach is epectanttreatment with epinephrine" antihistamines" and prednisone or individ!als who have inre;!entepisodes and a prolon$ed taper o prednisone or those with re;!ent episodes.

8ost o these patients are emale" and atopy appears to %e an !nderlyin$ ris+ actor. )wo thirds opatients have 5 or ewer episodes per year" while one third have more than 5 episodes per year.

A s!%pop!lation o women develops anaphylais in relationship to their menstr!al cycle= thisphenomenon is +nown as catamenial anaphylaxis.&'5" '6( n severe cases" these patients re;!iremanip!lation o their hormonal levels %y medical pit!itary s!ppression and even oophorectomy. 8osto these patients react to shits in pro$esterone levels" and the dia$nosis can %e conirmed %yprovo+in$ an anaphylactic event thro!$h administration o low doses o pro$esterone.

!iphasic and persistent anaphylais

)he reported incidence o %iphasic rec!rrent7 anaphylais varies rom less than 1G to a maim!m o'3G. Additionally" the reported time o onset o the late phase may vary rom 1 to I' ho!rs mostocc!r within K-10 h7. Potential ris+ actors incl!de severity o the initial phase" delayed or s!%optimaldoses o epinephrine d!rin$ initial treatment" laryn$eal edema or hypotension d!rin$ the initial phase"delayed onset o symptoms ater epos!re to the c!lprit anti$en oten a ood or insect stin$7" or priorhistory o %iphasic anaphylais.&'I(

Persistent anaphylais" anaphylais that may last rom 5-3' ho!rs" occ!rred in I o '5 s!%,ects 'KG7in the 9tar+ and 9!llivan report" with ' atalities. &'K( 13 s!%,ects analy*ed in a report on atal or near-atal anaphylais to oods" 3 '3G7 similarly eperienced persistent anaphylais. &'C( 2etrospective datarom other investi$ators" however" s!$$est that persistent anaphylais is !ncommon.

either %iphasic nor persistent anaphylais can %e predicted rom the severity o the initial phase o

an anaphylactic reaction. 9ince lie-threatenin$ maniestations o anaphylais may rec!r" it may %e


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necessary to monitor patients '@ ho!rs or more ater apparent recovery rom the initial phase. &'I( henprescri%in$ epinephrine" all patients sho!ld %e instr!cted to have ' in,ectors on hand at all times.

"is# $actors

As mentioned a%ove" atopy is a ris+ actor or anaphylais. n the 2ochester Epidemiolo$y Pro,ect"53G o the patients with anaphylais had a history o atopic diseases e$" aller$ic

rhinitis" asthma" atopic dermatitis7.&1'( )he 8emphis st!dy detected atopy in 3IG o the patients.&30( ther st!dies have shown atopy to %e a ris+ actor or anaphylais rom oods" eercise-ind!cedanaphylais" idiopathic anaphylais" radiocontrast reactions" and late reactions. ?nderlyin$ atopydoes not appear to %e a ris+ actor or reactions to penicillin or insect stin$s.

2o!te and timin$ o administration aect anaphylactic potential. )he oral ro!te o administration isless li+ely to ca!se a reaction" and s!ch reactions are !s!ally less severe" altho!$h atal reactionsocc!r ollowin$ in$estions o oods %y someone who is aller$ic. )he lon$er the interval %etweenepos!res" the less li+ely that an $E-mediated reaction will rec!r. )his is tho!$ht to %e d!e tocata%olism and decreased synthesis o aller$en-speciic $E over time. )his does not appear to %e thecase or $E-independent reactions.

A retrospective emer$ency department st!dy o 30' patients presentin$ with anaphylais" KI 'CG7 o

whom were ta+in$ at least 1 antihypertensive medication" o!nd that antihypertensivepharmacotherapy increased the ris+ o or$an system involvement and hospitali*ation. &31" 3'( )here was amore than '-old increased ris+ o involvement in 3 or more or$an systems when A4E inhi%itors" %eta%loc+ers" di!retics" or any antihypertensive medications were !sed. 8ost o these a$ents were alsoassociated with an increased ris+ or inpatient admission.&31" 3'(

Epidemiolo$y

)he tr!e incidence o anaphylais is !n+nown. 9ome clinicians reserve the term or the !ll-%lownsyndrome" whereas others !se it to descri%e milder cases. )he re;!ency o anaphylais isincreasin$" and this has %een attri%!ted to the increased n!m%er o potential aller$ens to whichpeople are eposed.

A review concl!ded that the lietime prevalence o anaphylais is 1-'G o the pop!lation as a whole.&33(

%nited States statistics

e!$!t et al estimated that 1-15G o the ?9 pop!lation is at ris+ o eperiencin$ an anaphylactic oranaphylactoid reaction.&3@( )hey estimated that the rate o act!al anaphylais to ood was 0.000@G"0.I-10G or penicillin" 0.''-1G or radiocontrast media 2487" and 0.5-5G ater insect stin$s.

A pop!lation-%ased st!dy rom 2ochester" 8innesota" o!nd an avera$e ann!al incidence oanaphylais o 5K.C cases per 100"000 person-years" which had increased rom @6.C cases per100"000 in 1CC0.&1'( identiied ca!ses" in$estion o a speciic ood was responsi%le or 33G" insectstin$s or 1K.5G" and medications or 13.IG. )wenty-ive percent o cases were consideredidiopathic. Episodes o anaphylais occ!rred more re;!ently rom J!ly thro!$h 9eptem%er" adierence that is attri%!ta%le to insect stin$s.

n a st!dy o patients reerred to a !niversity-ailiated aller$y-imm!nolo$y practice in 8emphis")ennessee" ood was the ca!se o anaphylais in 3@G o patients" medications in '0G" and eercisein IG anaphylais d!e to insect stin$s or 94) was ecl!ded rom the st!dy7. &30( )he ca!se co!ld not%e determined in 5CG ie" they were dia$nosed with idiopathic anaphylais7. A separate st!dyestimated that there are '0"000-@I"000 cases o idiopathic anaphylais in the ?nited 9tates per yearapproimately K-1C episodes per 100"000 person-years7.

2eactions to insects and other venomo!s plants and animals are more prevalent in tropical areas%eca!se o the $reater %iodiversity in these areas. Epos!re and thereore reactions to medicationsare more common in ind!striali*ed areas.

International statistics

)he incidence o anaphylais does not appear to vary si$niicantly %etween co!ntries. )wo E!ropeanst!dies detected a lower avera$e ann!al incidence than o!nd in the 2ochester st!dy 3.' cases oanaphylactic shoc+ per 100"000 person-years in enmar+= C.K cases o o!t-o-hospital anaphylais

http://emedicine.medscape.com/article/134825-overviewhttp://emedicine.medscape.com/article/134825-overviewhttp://emedicine.medscape.com/article/296301-overviewhttp://emedicine.medscape.com/article/296301-overviewhttp://emedicine.medscape.com/article/296301-overviewhttp://emedicine.medscape.com/article/1049085-overviewhttp://emedicine.medscape.com/article/134825-overviewhttp://emedicine.medscape.com/article/134825-overviewhttp://emedicine.medscape.com/article/296301-overviewhttp://emedicine.medscape.com/article/1049085-overview


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per 100"000 person-years in 8!nich" ermany&35( 7. 2ates in E!rope ran$e rom 1-3 cases per 10"000.&36" 35( owever" the incidence o anaphylais may %e increasin$. &3I(

9imons and collea$!es eamined the rate o epinephrine prescriptions or a pop!lation o 1.15 millionpatients in 8anito%a" 4anada" and o!nd that 0.C5G o this pop!lation was prescri%ed epinephrine" anindicator o perceived ris+ that !t!re anaphylais may occ!r. &3K( 8oneret-


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Another analysis o '3 !nselected cases o atal anaphylais determined that 16 o '0 Dimmediatedeaths death occ!rrin$ within one ho!r o symptom onset7 and 16 o the '3 cases that !nderwenta!topsy were d!e to !pper airway edema.

eath can occ!r rapidly. An analysis o anaphylais atalities occ!rrin$ in the ?nited in$dom rom1CC' to '001 revealed the interval %etween initial onset o ood anaphylais symptoms and atal

cardiop!lmonary arrest avera$ed '5-35 min!tes" which was lon$er than or dr!$s mean" 10-'0min!tes pre-hospital= 5 min!tes in-hospital7 or or insect stin$s 10-15 min!tes7.

Asthma is a ris+ actor or atal anaphylais. elayed administration o epinephrine is also a ris+ actor or atal o!tcomes.&C(

Post!re also inl!ences anaphylais o!tcomes. n a retrospective review o prehospital anaphylacticatalities in the ?nited in$dom" the post!ral history was +nown or 10 individ!als. &@5( o!r o the 10atalities were associated with the ass!mption o an !pri$ht or sittin$ post!re d!rin$ anaphylais.Postmortem indin$s were consistent with p!lseless electrical activity and an Dempty heart attri%!tedto red!ced veno!s ret!rn rom vasodilation and redistri%!tion o intravasc!lar vol!me rom the centralto the peripheral compartment.

Patients may eperience m!ltiple anaphylactic episodes. )he 2ochester st!dy detected a total o 15@

anaphylactic episodes involvin$ 133 people in a 5-year period. &1'( 8ost patients 1167 had only 1episode in those 5 years. )hirteen people had ' episodes" and @ people had 3 episodes.

n contrast" in the 8emphis st!dy" @KG o patients had 3 or more anaphylactic episodes. &30( the 11'patients who responded to s!rvey" however" 3K patients 3@G7 reported a rec!rrence o symptomsand the remainin$ I@ patients 66G7 reported remission o symptoms. verall" K5G o patients eitherwere in remission or reported diminished symptom severity in a s!%se;!ent episode or episodes. )he8emphis st!dy eval!ated a reerral pop!lation and also deli%erately ecl!ded patients withanaphylais d!e to insect stin$s or 94).&30(

Patient Ed!cation

Avoidance ed!cation is cr!cial" especially in yo!n$er patients with ood anaphylais. mportant iss!esincl!de cross-contamination and inade;!ate la%elin$ o oods. )he ood Aller$y Q Anaphylaisetwor+ is an ecellent reso!rce or amilies" as well as physicians. A st!dy o children with oodaller$y visitin$ a s!%specialty aller$y clinic o!nd 5CG had an epinephrine a!toin,ector with them"altho!$h I1G o parents reported +eepin$ the a!toin,ector availa%le at all times. )he only varia%lepositively associated with havin$ an a!toin,ector availa%le was epinephrine a!toin,ector instr!ction. &@6(

Patients with sensitivity to m!ltiple anti%iotics sho!ld %e provided a list o alternative anti%iotics. )heycan present this list to their primary care physicians when anti%iotic therapy is re;!ired.

Avoidance ed!cation is also important or persons who are hypersensitive to insect stin$s. 4a!tionpatients to avoid !se o per!mes or hy$iene prod!cts that incl!de per!mes" partic!larly loral scents"as these attract lyin$ ymenoptera. Bri$htly colored clothin$ attracts %ees and other pollinatin$insects. Avoid locations o +nown hives or nests" and avoid !sin$ e;!ipment that dist!r%s the hive.

Persons who are sensitive to ymenoptera and who m!st %e o!tdoors sho!ld carry an epinephrinea!toin,ector see %elow7. norm patients who react to ymenoptera venom o the availa%ility odesensiti*ation therapy. n dischar$e" warn patients o the possi%ility o rec!rrent symptoms" andinstr!ct them to see+ !rther care i this occ!rs.

n '011" the Joint )as+ orce on Practice Parameters" representin$ the American Academy o Aller$y" Asthma Q mm!nolo$y" the American 4olle$e o Aller$y" Asthma Q mm!nolo$y" and the Joint 4o!ncilo Aller$y" Asthma and mm!nolo$y" iss!ed an !pdated practice parameter on insect stin$hypersensitivity. )he practice parameter states that patients with a possi%le systemic reaction sho!ld%e reerred to an aller$ist or imm!nolo$ist" where they sho!ld %e ed!cated a%o!t their ris+ o anotherreaction" their options or preventative treatment" and the %eneits o wearin$ a medical identiicationnec+lace or %racelet. Avoidin$ insect stin$s and dealin$ with an emer$ency sho!ld %e disc!ssed.&@I( )he '010 Joint )as+ orce !pdated anaphylais parameter and the '011 orld Aller$y r$ani*ation

$!idelines are $enerally in accordance with these recommendations.&@K" @C(

http://emedicine.medscape.com/article/296301-overviewhttp://www.foodallergy.org/http://www.foodallergy.org/http://www.foodallergy.org/http://emedicine.medscape.com/article/296301-overviewhttp://www.foodallergy.org/http://www.foodallergy.org/


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or patient ed!cation inormation" see e8edicineealths Aller$ies 4enter . Also" seee8edicineealthRs patient ed!cation articles 9evere Aller$ic 2eaction Anaphylactic 9hoc+7" ood Aller$y" and r!$ Aller$y.

Epinephrine autoin&ector instruction

ood evidence s!$$ests that physicians !nderprescri%e epinephrine and that patients or their

parents7 ail to !se epinephrine as ;!ic+ly as possi%le.&50" 51" 5'( Accordin$ly" at dischar$e" all patientssho!ld %e provided an epinephrine a!toin,ector and sho!ld receive proper instr!ction on how to sel-administer it in case o a s!%se;!ent episode. &51(

Patients sho!ld %e instr!cted to +eep an epinephrine a!toin,ector with them at all times= they sho!ldalso carry diphenhydramine and ta+e this in con,!nction with !se o the epinephrine a!toin,ector. )heysho!ld %e instr!cted to +eep the device rom etremes o temperat!re. Epinephrine is sensitive to%oth li$ht and temperat!re and thereore sho!ld not %e stored" or eample" in a reri$erator or in amotor vehicle $love compartment. )hey also sho!ld %e instr!cted to replace any epinephrinea!toin,ector %eore its epiration date.

Patients sho!ld %e instr!cted to have ready and prompt access to emer$ency medical services ortransportation to the closest E or treatment. )hey sho!ld also %e instr!cted to o%tain emer$ency

medical care immediately ater in,ectin$ the epinephrine %eca!se the eect is short lived N 15 min7and %iphasic reactions can occ!r.

An EpiPen ey Pharma" apa" 4ali7 a!toin,ector or ad!lts is availa%le with a sin$le 0.3-m$ 1:1"000v/v7 dose. 9imilarly" an EpiPen Jr." with a 0.15-m$ 1:'"000 v/v7 dose" is availa%le or children whowei$h less than 30 +$. )he Adrenaclic+ 9chiono$i ?9A" nc." lorham Par+" J7 is also availa%le as asin$le-dose a!toin,ector o either 0.15 m$ or 0.3 m$. )he )win,ect 9chiono$i ?9A" nc." lorhamPar+" J7 is a pen-si*ed device containin$ ' doses o epinephrine availa%le either as a 0.15- or 0.3-m$ orm!lation. n %oth cases" the irst o the ' doses is delivered %y a!toin,ector" and the second isin,ected man!ally.

Place%o syrin$es are recommended as ed!cational tools. >ive demonstrations o in,ections mi$ht %econsidered on a case-%y-case %asis when the patient or parent epresses a ear o in,ection. &51(

http://www.emedicinehealth.com/Collections/CO1661.asphttp://www.emedicinehealth.com/Articles/8479-1.asphttp://www.emedicinehealth.com/Articles/8479-1.asphttp://www.emedicinehealth.com/Articles/8479-1.asphttp://www.emedicinehealth.com/articles/8567-1.asphttp://www.emedicinehealth.com/articles/8567-1.asphttp://www.emedicinehealth.com/Articles/8523-1.asphttp://www.emedicinehealth.com/Articles/8523-1.asphttp://www.emedicinehealth.com/Collections/CO1661.asphttp://www.emedicinehealth.com/Articles/8479-1.asphttp://www.emedicinehealth.com/articles/8567-1.asphttp://www.emedicinehealth.com/articles/8567-1.asphttp://www.emedicinehealth.com/Articles/8523-1.asp


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http://emedicine.medscape.com/article/135065-clinical#showall

istory

Anaphylais is an ac!te m!ltior$an system reaction. )he most common or$an systems involvedincl!de the c!taneo!s" respiratory" cardiovasc!lar" and $astrointestinal 7 systems. n most st!dies"the re;!ency o si$ns and symptoms o anaphylais is $ro!ped %y or$an system.

Anaphylactic reactions almost always involve the s+in or m!co!s mem%ranes. reater than C0G opatients have some com%ination o !rticaria" erythema" pr!rit!s" or an$ioedema. n the 8emphisst!dy" or eample" KIG o patients had !rticaria and/or an$ioedema. &30( ther retrospective st!dieshave reported similar rates o m!coc!taneo!s involvement.

4hildren" however" may %e dierent. An A!stralian st!dy eval!ated 5I children !nder a$e 16 yearswho presented to a pediatric emer$ency department E7 over a three-year period. 4!taneo!seat!res were noted in K'.5G" whereas C5G had respiratory symptoms. )he reasons why a lac+ odermal indin$s wo!ld %e more common in children than in ad!lts are not well !nderstood.

)he !pper respiratory tract commonly is involved" with complaints o nasal con$estion" snee*in$" orcory*a. 4o!$h" hoarseness" or a sensation o ti$htness in the throat may presa$e si$niicant airway

o%str!ction. Eyes may itch and tearin$ may %e noted. 4on,!nctival in,ection may occ!r.yspnea is present when patients have %ronchospasm or !pper airway edema. ypoia andhypotension may ca!se wea+ness" di**iness" or syncope. 4hest pain may occ!r d!e to%ronchospasm or myocardial ischemia secondary to hypotension and hypoia7. symptoms ocrampli+e a%dominal pain with na!sea" vomitin$" or diarrhea also occ!r %!t are less common" eceptin the case o ood aller$y.

)he 8emphis st!dy reported dyspnea in 5CG" syncope or li$htheadedness in 33G" and diarrhea ora%dominal cramps in 'CG.&30( ther st!dies have reported similar indin$s.

nitially" patients oten descri%e a sense o impendin$ doom" accompanied %y pr!rit!s and l!shin$.)his can evolve rapidly into the ollowin$ symptoms" %ro+en down %y or$an system:

•4!taneo!s/oc!lar - l!shin$" !rticaria" an$ioedema" c!taneo!s and/or con,!nctival pr!rit!s"

warmth" and swellin$

• 2espiratory - asal con$estion" rhinorrhea" throat ti$htness" whee*in$" shortness o %reath"

co!$h" hoarseness

• 4ardiovasc!lar - i**iness" wea+ness" syncope" chest pain" palpitations

• astrointestinal - yspha$ia" na!sea" vomitin$" diarrhea" %loatin$" cramps

• e!rolo$ic - eadache" di**iness" %l!rred vision" and sei*!re very rare and oten associated

with hypotension7

• ther - 8etallic taste" eelin$ o impendin$ doom

9ymptoms !s!ally %e$in within 5-30 min!tes rom the time the c!lprit anti$en is in,ected %!t can occ!r within seconds. the anti$en is in$ested" symptoms !s!ally occ!r within min!tes to ' ho!rs. n rarecases" symptoms can %e delayed in onset or several ho!rs. Parenteral administration o monoclonal

anti%odies and oral in$estion o mammalian meat e$" %ee" por+" lam%7 have recently %een reportedto %e potential ca!ses or anaphylais characteri*ed %y delayed onset. &53" 5@" 55" 56" 5I( t m!st %eremem%ered that anaphylais can %e$in with relatively minor c!taneo!s symptoms and rapidlypro$ress to lie-threatenin$ respiratory or cardiovasc!lar maniestations. n $eneral" the more rapidlyanaphylais develops ater epos!re to an oendin$ stim!l!s" the more li+ely the reaction is to %esevere.

A thoro!$h history remains the %est test to determine a ca!sative a$ent. or rec!rrent idiopathicepisodes" a patient diary may %e help!l to implicate speciic oods or medications" incl!din$ over-the-co!nter )47 prod!cts.

Physical Eamination

)he irst priority in the physical eamination sho!ld %e to assess the patients airway" %reathin$"

circ!lation" and ade;!acy o mentation e$" alertness" orientation" coherence o tho!$ht7.


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eneral appearance and vital si$ns vary accordin$ to the severity o the anaphylactic episode and theor$an systems7 aected. esion%orders are !s!ally irre$!lar and si*es vary mar+edly. nly a ew small or lar$e lesions may %ecome

conl!ent" ormin$ $iant !rticaria. At times" the entire dermis is involved with di!se erythema andedema.

n a local reaction" lesions occ!r near the site o a c!taneo!s epos!re e$" insect %ite7. )he involvedarea is erythemato!s" edemato!s" and pr!ritic. only a local s+in reaction as opposed to $enerali*ed!rticaria7 is present" systemic maniestations e$" respiratory distress7 are less li+ely. >ocal reactions"even i severe" are not predictive o systemic anaphylais on reepos!re.

An$ioedema sot-tiss!e swellin$7 is also commonly o%served. )hese lesions involve the deeperdermal layers o s+in. t is !s!ally nonpr!ritic and nonpittin$. 4ommon areas o involvement are thelaryn" lips" eyelids" hands" eet" and $enitalia.

enerali*ed whole-%ody7 erythema or l!shin$7 witho!t !rticaria or an$ioedema is also occasionallyo%served.

4!taneo!s indin$s may %e delayed or a%sent in rapidly pro$ressive anaphylais.


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'astrointestinal $indings

Shock Anaphylatic

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