anaphylactic+shock-+pathophysiology,+recognition,+and+treatment

7/26/2019 Anaphylactic+Shock-+Pathophysiology,+Recognition,+and+Treatment

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Anaphylactic Shock: Pathophysiology,Recognition, and Treatment

Roger F. Johnson, M.D.1and R. Stokes Peeles Jr., M.D.1

A!STRA"T

Anaphyla#is is a systemic, type $ hypersensiti%ity reaction that o&ten has &atal

conse'(ences. Anaphyla#is has a %ariety o& ca(ses incl(ding &oods, late#, dr(gs, and

hymenoptera %enom. )pinephrine gi%en early is the most important inter%ention. Ad*

+(ncti%e treatments incl(de &l(id therapy, 1and -histamine receptor antagonists,

corticosteroids, and ronchodilators ho/e%er these do not s(stit(te &or epinephrine.Patients /ith a history o& anaphyla#is sho(ld e ed(cated ao(t their condition,

especially /ith respect to trigger a%oidance and in the correct (se o& epinephrine

a(toin+ector kits. S(ch kits sho(ld e a%ailale to the sensiti0ed patient at all times.

)234RDS: Anaphyla#is, epinephrine, shock, allergy

4+ecti%es: A&ter reading this article, the reader sho(ld e ale to: 516 disc(ss the pathophysiology o& anaphylactic shock 5-6recogni0e anaphylactic reactions and 576 s(mmari0e the essential steps in treatment o& anaphylactic shock.

Accreditation: The 8ni%ersity o& Michigan is accredited y the Accreditation "o(ncil &or "ontin(ing Medical )d(cation to sponsorcontin(ing medical ed(cation &or physicians.

"redits: The 8ni%ersity o& Michigan designates this ed(cational acti%ity &or a ma#im(m o& 1 category 1 credit to/ard the AMAPhysician9s Recognition A/ard.

Anaphyla#is is a systemic, type $hypersensiti%ity reaction that occ(rs in sensiti0edindi%id(als res(lting in m(coc(taneo(s, cardio%asc(lar,

and respiratory mani&es*tations and can o&ten e li&ethreatening. Anaphyla#is /as &irst descried in 1;- y

Portier and Richet /hen they /ere attempting to

prod(ce tolerance in dogs to sea anemone %enom.

Richet coined the term aphylaxis 5&rom the >prophyla#is99 they hoped to achie%e. The term

aphylaxis/as replaced /ith the term anaphylaxis shortly

therea&ter. Richet /on the ?oel Pri0e in medicine or

physiology in 117 &or his pioneering /ork.1

Anaphyla#is occ(rs in persons o& all ages and

has many di%erse ca(ses, the most common o& /hich

are &oods, dr(gs, late#, hymenoptera stings, and

reactions to imm(notherapy. 4& note, a ca(se cannot e

determined in (p to one third o& cases.-=@

Anaphylactoid

reactions are identical to anaphyla#is in e%ery /ay

e#cept the &ormer are not mediated y imm(noglo(lin

) 5$g)6. "ommon ca(ses o& anaphylactoid reactionsincl(de radiocontrast media, narcotic analgesics, and

nonsteroi*dal antiin&lammatory dr(gs.

Signs and symptoms can e di%ided into &o(r

categories: m(coc(taneo(s, respiratory, cardio%as*

c(lar, and gastrointestinal. Reactions that s(rpass

Management o& Shock )ditor in "hie&, Joseph P. ynch, $$$, M.D.


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m(coc(taneo(s signs and symptoms are considered to e

se%ere, and, (n&ort(nately, m(coc(taneo(s mani&esta*tions

do not al/ays occ(r prior to more serio(s mani*&estations.

M(coc(taneo(s symptoms commonly consist o& (rticaria,

angioedema, pr(ritis, and &l(shing. "om*mon respiratory

mani&estations are dyspnea, throat tightness, stridor,

/hee0ing, rhinorrhea, hoarseness, and co(gh."ardio%asc(lar signs and symptoms incl(de hypotension,

tachycardia, and syncope.


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incl(ding prostaglandins, principally prostaglandin D-

5P>imm(ne de%iation99 &rom a Th- response,

/hich predominates in (tero, to a predominantly Th1

response. ack o& this >>imm(ne de%iation99 leads to

&(rther perpe*t(ation o& the Th- response to allergens.

Stim(li 5mi*croes6 that lead to a Th1 response ca(se

$*1- to e prod(ced y antigen*presenting cells. $*1-

not only perpet(ates the Th1 response (t inhiits $g)

prod(c*tion. F(rthermore, cytokines s(ch as inter&eron

gamma 5prod(ced y Th1 cells6 and $*1H 5prod(ced y

macro*phages6 s(ppress prod(ction o& $g). Th(s the

Th1 response is considered to e inhiitory to allergy.1;

The incidence o& allergic diseases is on the rise in

the 8nited States.-,1;

There are se%eral potential reasons

&or this oser%ation. Diet may play a role eca(se ne/allergens are increasingly eing introd(ced into the

American diet. For e#ample, the 8nited States is the third

largest cons(mer o& pean(ts in the /orld, @; o&

cons(mption is acco(nted &or y pean(t (tter.11

F(rthermore, the dramatic increase in the (se o& late#

prod(cts, partic(larly glo%es, in the past -; years has also

een implicated. Finally, some in%oke the >>hygiene99

hypothesis &or the increase in the pre%alence o& allergic

disease.1;

The asis o& this hypothesis is that inhaitants o&

3esterni0ed co(ntries are e#posed to &e/er 5or di&&erent6

imm(nologic challenges d(ring imm(ne

system de%elopment, /hich leads to lessstim(lation o& the Th1 path/ay.

D$A


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Tale 1 Symptoms and Signs, the ?(mer 4(t o& 177Patients /ith Anaphyla#is 3ho )#perienced Them

Patients 5? 1776

Symptom or Sign ?

"(taneo(s

8rticaria 7 BB

Angioedema @ BC

Pr(rit(s 7 BB

Fl(shing @H 7C

"on+(ncti%itis or chemosis 7; -7

Respiratory

Dyspnea B @7

Throat tightness 7 -H

3hee0ing 7@ -C

Rhinitis -- 1

aryngeal edema

oarseness

4ral and gastrointestinal

$ntraoral angioedema -; 1B

)mesis 1-

?a(sea 1-

Adominal cramps 11 H

Dysphagia B

4ral pr(rit(s B @

Diarrhea 1 1

"ardio%asc(lar

Tachycardia 7C -

Presyncope -; 1B

ypotension 1B 11

Syncope @ 7

Shock B"hest pain @ 7

!radycardia - -

4rthostasis - -

Reprod(ced /ith permission &rom 2oc(m et al.7

Tale - Some "a(ses o& Anaphylactic andAnaphylactoid Reactions

M)D$"AT$4?S

?onsteroidal antiin&lammatory dr(gs, aspirin, antiiotics, opioid

analgesics, ins(lin, protamine, general anesthetics,

streptoki*nase, lood prod(cts, progesterone, radiocontrast

media, iologic agents, imm(notherapy

F44DS

Pean(ts, tree n(ts, &ish, shell&ish, milk, eggs, is(l&ites

2M)?4PT)RA E)?4M

2ello/ +ackets, hornets, /asps, honeyees, &ire ants

M$S")A?)48S

ate#, e#ercise, gelatin, menstr(ation, seminal &l(id,

dialysis memranes

Adapted &rom R(s0nak and Peeles.@1

ne/ in&ormation regarding a ne/ method to prophyla#

against pean(t allergy and recognition that gelatin is a

signi&icant ca(se o& anaphyla#is are s(mmari0ed in the ne#t

sections. Also, late# allergy has een recogni0ed as an

important ca(se o& anaphyla#is in the past -; years, and

/e /ill re%ie/ some aspects o& late# allergy as /ell.

P)A?8T A)R


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hypersensiti%ity to eggs. $n the minds o& Dr. elso and

his colleag(es, this made little sense eca(se many

children /ith egg hypersensiti%ities /ere (ne%ent&(lly

administered MMR %accines /hereas only t/o o& -H

reports o& anaphylactic reactions to %accines occ(rred in

egg*allergic children.-1

The ast(te oser%ations o& these

in%estigators, co(pled /ith serendipity 5their patient

reported that the reaction to the %accine /as >>kind o&like /hat happens /hen $ eat Jell*4996

-1 led these

in%estigators to a paradigm*shi&ting disco%ery.

Follo/ing the lead o& elso et al, in%estigators in

Japan characteri0ed anaphylactic reactions to %accines

as also mediated y anti*gelatin $g).--

$n addition, they

(nco%ered a link to hypersensiti%ity reactions to orally

ingested gelatin, /hich, interestingly, de%eloped a&ter

the %accine*related reaction in &i%e o& se%en children.

The same in%estigators also traced gelatin as the ca(se

o& anaphyla#is in erythropoietin administered

intra%eno(sly to hemodialysis patients.-7


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Downloadedby:UniversityofWisconsin-Madison.Copyrightedm

aterial.

Fig(re 1 Ac(te management o& anaphyla#is. Reprod(ced /ith permission &rom Joint Task Force on Practice Parameters.B

TR)ATM)?T

4nce the diagnosis o& anaphyla#is is elie%ed likely,

immediate administration o& epinephrine sho(ld occ(r. A

management algorithm is sho/n in Fig. 1 and an

e#planation o& the medications (sed in the treatment o&

anaphyla#is is sho/n in Tale @. Diphenhydramine and

corticosteroids as /ell as -lockers are also ad%ocated

as ad+(ncti%e treatments in the management o& anaphy*

la#is ho/e%er, they are no s(stit(te &or prompt admin*

istration o& epinephrine.B$t sho(ld e noted that patients

can progress &rom eing relati%ely stale to a state o&

e#tremis in a %ery short time. !iphasic or late phase

reactions, in /hich patients ha%e a recr(descence o&

anaphylactic signs and symptoms se%eral ho(rs a&ter

the anaphylactic episode, ha%e een descried in (p to

-; o& cases.B,11,1-

Patients sho(ld there&ore e oser%ed

&or at least @ ho(rs eca(se ; o& iphasic reactions

occ(r /ithin this time period.11Observation for as

long


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Tale @ Treatment o& Anaphyla#is

Therapy $ndication Dosage


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care pro%iders do not recogni0e the di&&erence et/een

epinephrine gi%en &or treatment o& anaphyla#is and

epinephrine gi%en &or res(scitation /ith respect to dose,

ro(te, and rapidity o& in&(sion.17

$t has also een

reported that some proportion o& patients die regardless

o& treatment /ith epinephrine.11,17

Recent data ha%e come to light regarding thepre&erred method o& administering epinephrine. Simons

et al per&ormed a st(dy in children in /hich they

reported that $M in+ection o& epinephrine is s(perior to

s(c(taneo(s administration.7B

This concl(sion /as

ased in delayed epinephrine asorption /ith s(c(ta*

neo(s compared /ith $M administration. The di&&erence

/as hypothesi0ed to e d(e to the c(taneo(s %asocon*

stricti%e properties o& epinephrine. They e#tended their

&indings to ad(lts and &(rther de&ined that $M in+ection

into the thigh 5%ast(s lateralis6 is pre&erred to $M

in+ection into the deltoid.7C

This concl(sion is ased on

the s(perior ser(m le%els o& epinephrine achie%ed ythis method in comparison to s(c(taneo(s in+ection as

/ell as $M in+ection into the deltoid. S(periority o& lood

&lo/ to the %ast(s lateralis is hypothesi0ed to acco(nt &or

this di&&erence.7C

$t has een s(ggested that patients taking eta

lockers may e at increased risk &or se%ere reactions

d(ring anaphyla#is.@,B

!eta lockers administered orally

and e%en topically may inter&ere /ith epinephrine treat*

ment y antagoni0ing its e&&ects at the eta adrenergic

receptor.@,1-

$n e#perimental models, an H;*&old increase in

dose o& isoproterenol /as re'(ired to o%ercome the e&&ects

o& eta lockade.@,1-

Similarly, angiotensin con*%erting

en0yme 5A")6 inhiitors may also e prole*matic d(ring

anaphyla#is.1-,7

D(ring anaphyla#is, &l(id shi&ts occ(r s(ch

that (p to B; o& the plasma %ol(me may e lost &rom the

circ(lation in as little as 1; min(tes.@,7

To compensate &or

this, angiotensin, a potent %asoconstrictor, is released y

the action o& the renin=angiotensin=aldosterone system.

!lockade o&

A") pre%ents this compensatory response &rom taking

place.@,1-,7An important aspect o& treatment is pre%ention o&

&(rther e%ents. This incl(des, o& co(rse, a%oidance o&

the allergen and ed(cation o& the patient regarding

strategies &or allergen a%oidance. $t is also important &orpatients to e a/are o& potential cross*reacting

allergens, partic(*larly dr(gs and n(ts.17

)d(cation o&

teachers and sta&& at schools and other child care

%en(es is also important.CPatients prone to anaphyla#is

sho(ld also e ad%ised to /ear MedicAlert1racelets.

$n addition, patients prone to anaphyla#is sho(ld

e pro%ided /ith one or more a(toin+ector kits 5)pi*Pen1

or )piPen Jr16 and sho(ld e instr(cted on their (se.

This sho(ld take place /ith an )piPen1demon*strator in

the physician9s o&&ice. $t has een reported thatphysicians are de&icient in teaching patients to (se

a(toin+ectors, and in some cases, the physicians them*

sel%es are (ns(re o& ho/ to properly (se the de%ice.7H,7

Patients /ith a history o& anaphyla#is sho(ld e ad%ised to

carry the a(toin+ector kit on their person at all times.

Patients sho(ld e instr(cted to seek medical attention,

especially i& they ha%e had a reaction serio(s eno(gh to

re'(ire (se o& an epinephrine a(toin+ector. $deally, )piPen1

or )piPen Jr1sho(ld e (sed e&ore its e#piration date, andthis is recommended eca(se epi*nephrine &rom o(tdated

a(toin+ectors has consideraly red(ced ioa%ailaility.@;

$&,

ho/e%er, a patient is s(d*denly in need o& epinephrine, it

has een sho/n that o(tdated epinephrine a(toin+ectors

ha%e a percent o& laeled epinephrine content in%ersely

proportional to months past e#piration date. The a(thors o&

this st(dy concl(ded that o(tdated )piPen1and )piPen Jr

1

can e (sed i& no discoloration or precipitate is present. The

asis o& their concl(sion is that i& a li&e*threatening

anaphylactic episode occ(rs, the potential ene&its o& (sing

o(tdated a(toin+ectors o(t/eigh potential risks.@;

$n

patients /ho are taking eta*lockers and /ho s(&&eranaphyla#is, some case reports s(ggest gl(cagen may e

e&&ecti%e in those patients /ho &ail to respond to other

therapies listed in Tale @.@1

"4?"8S$4?

Anaphyla#is is a systemic, type $ allergic reaction that o&ten

has &atal conse'(ences. Anaphyla#is has a %ariety o&

ca(ses incl(ding &oods, late#, dr(gs, and hymenoptera

%enom. )pinephrine gi%en early is the most important

inter%ention in the treatment o& anaphyla#is. 4ther

ad+(ncti%e treatments incl(de 1 and - receptor an*

tagonists, corticosteroids, and ronchodilators ho/e%er

these do not s(stit(te &or epinephrine. Patients /ith a

history o& anaphyla#is sho(ld e ed(cated ao(t their

condition, especially /ith respect to trigger a%oidance.

These patients sho(ld also e instr(cted on the correct (se

o& epinephrine a(toin+ector kits and e co(nseled to keep

these kits on their person at all times.

F8?D$?

anaphylactic+shock-+pathophysiology,+recognition,+and+treatment

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