Anaphylaxis J Allergy Clin Immunol 2007;120:506-15 - PowerPoint Presentation

Slide1

Anaphylaxis

Slide2

J Allergy Clin Immunol 2007;120:506-15

Anaphylaxis

Slide3

Slide4

Slide5

http://www.youtube.com/watch?v=VcxdqIPLyK8&list=PL7C80B961F004CBB8

Slide6

Anaphylaxis Road Map

Definition

Pathophysiology

EpidemiologyEtiologyMorbidity and MortalityEvaluation

Treatment

Dispo

Slide7

Ana- -phylaxis

Ana- = again, up, back

-phylaxis = protection, immunity, guarding

Slide8

1902

+

Slide9

=

Slide10

1902 + a few days

+

Slide11

=

Slide12

Definition

Clinically Meaningless: acute, severe, life-threatening, potentially fatal, multi-organ, systemic reaction caused by the release of chemical mediators from mast cells and basophils

Slide13

Clinically Meaningful: When 1 of the following 3 criteria are fulfilled:

1

. Acute onset of mucocutaneous signs AND 1 of the following: respiratory

compromise (wheezing-bronchospasm, dyspnea, stridor,hypoxemia), hypotension (syncope), or hypotonia.2. Rapid onset of 2 of the following after exposure to likely allergen:

mucocutaneous signs, respiratory compromise, hypotension, or

persistent gastrointestinal symptoms.

3

. Hypotension after exposure to a known allergen.

Definition

Slide14

Pathophysiology

Slide15

Pathophysiology… for the ED doc

Slide16

Pathophysiology

Type I Hypersensitivity Phases

Slide17

Pathophysiology

Type I Hypersensitivity Phases

Step 1: Sensitization “fool me once…”

The allergen exposure 

allergen uptake by dendritic cells



broken down into antigenic peptides



peptides presented on T-lymphocytes



cytokines are secreted from the T-lymphocytes -> B lymphocytes then directly interact with the Ts



Bs produce antigen specific IgE which is packaged on the surface of mast cells (cell surfaces) and basophils (circulating)

Slide18

Pathophysiology

Type I Hypersensitivity Phases

Step 2: early-phase reaction

Allergen re-exposure  IgE on mast cell and basophil surfaces “recognizes” allergen  degranulation releases histamine, tryptase, heparin)  immediate symptoms at target organs (vasculature, skin, smooth muscle etc.)

Step 3: late-phase reaction

 about 6 hours later, allergen stimulates T-cells to produce additional inflammatory mediators (ie. leukotrienes) resulting in inflammatory cell influx etc. etc. etc.

Slide19

Slide20

Slide21

Why me?

Hypersensitivities are to substances – some people are predisposed to make IgE when exposed to these substances whereas “normals” make IgG (the activation of which would not result in hypersensitivity cascade)

Slide22

Or…

Anaphylactoid reaction is an immediate systemic reaction that mimics anaphylaxis in end-point (mast cell and basophil degranulation) but lacks IgE’s involvement. Therefore, it can happen on first exposure. Typically “dose” dependant. Clinically indistinguishable from anaphylaxis.

Slide23

Epidemiology

Very likely under-reported

1% of serious anaphylactic reactions result in death, or about 500-1000 deaths/year in the US

Foods  100 -200 fatalities / year

Beta Lactams (parenteral)  400 - 800 fatalities / year

Radiocontrast  900 fatalities / year

Insect stings  40 – 100 fatalities / year

Latex  3 fatalities / year

Desensitization injections about 3.4 fatalities / year

Allergen testing 1 fatality reported between 1990-2001

Slide24

Etiology

#1: Food

#2: Drugs – allergic reactions make up somewhere between 5-25% of all adverse drug reactions

#3: Stinging insects Hymenoptera

Apid (honeybee, bumblebee)

Vespid (yellow jacket, hornet, wasp)

Formicid (fire ant)

#4: Latex

#5: others (ie. exercise, idiopathic etc)

Slide25

Adverse Drug Reactions

WHO definition: All nontherapeutic consequences, with the exception of treatment failures, purposeful or accidental poisonings, and drug abuse.

All allergic reactions are ADRs, but not all ADRs (nausea, diarrhea, malaise) are allergic reactions, so clarify with your patient what their “allergy” really is.

Slide26

Adverse Drug Reactions

Immediate hypersensitivity (IgE)

Nonimmediate allergic reactions (not IgE, typically)

SJS TENNonimmunological reactions

Anaphylactoid

Nonspecific histamine release (morphine itch, vanco red man)

Bradykinin accumulation (ACE-I angioedema)

Complement activation (radiocontrast)

Leukotrienes (NSAIDs)

Slide27

DDx

Anaphylaxis / Anaphylactoid

Neurocardiac reaction (fancy pants for Vasovagal)

Other Shock classes (cardiogenic, hemorrhagic, septic)“Flush” syndromes (carcinoid, medullary thyroid carcinoma)

“Restaurant” syndromes (Scrombroid, MSG)

Excess endogenous histamine production (things with big names)

Nonorganic (nuts, the psych kind)

Other (ACE-I, C1 esterase difficiency, pheos)

Slide28

Symptoms

Slide29

Clinically Meaningful: When 1 of the following 3 criteria are fulfilled:

1

. Acute onset of mucocutaneous signs AND 1 of the following: respiratory

compromise (wheezing-bronchospasm, dyspnea, stridor,hypoxemia), hypotension (syncope), or hypotonia.2. Rapid onset of 2 of the following after exposure to likely allergen:

mucocutaneous signs, respiratory compromise, hypotension, or

persistent gastrointestinal symptoms.

3

. Hypotension after exposure to a known allergen.

Definition

J Allergy Clin Immunol 2006 ;117 : 391-7

Slide30

Criteria 1 :

skin lesions and/or mucosa lesions (urticaria, itching or erythema, lip edema or tongue-uvula edema). With one or more or following signs :

Respiratory troubles (dyspnea, bronchospasm, stridor, decreased of peak flow, hypoxia)

Systolic BP<90 mmHg) or organ dysfunction (hypotonia, syncope, incontinence)

Slide31

Criteria 2

 :

2 or more signs after exposition to a

probable allergen

:

skin lesions and/or mucosa lesions (urticaria, itching or erythema, lips edema or tongue-uvula edema). With one or more of the following signs :

Respiratory troubles (dyspnea, bronchospasm, stridor, decreased of peak flow, hypoxia)

Systolic BP<90 mmHg) or organ dysfunction (hypotonia, syncope, incontinence)

Persistent gastrointestinal troubles (abdominal pain, vomiting)

Slide32

Criteria 3

: hypotension, know exposure

Decrease of SBP< 90mmHg or more than 30% compared to basal in adults* after exposition to

known allergen

.

*In child decrease of SBP is defined as: SBP < 70 mmHg from 1 month to 1 year, below (70 mmHg + [2 x age]) from 1 to 10 years, <90mmHg from 11 to 17 years.

Slide33

Symptoms

Up to 35% of circulating volume can be displaced extravascularly within just 10 MINUTES of symptom onset

Most cases have cutaneous findings

A few cases do notCutaneous 90%

Respiratory 50% +/- 10%

Cardiovascular (dizzy, syncope, low BP) 33%

GI 25-30%

Other Sxs (HA, chest pain, Sz) <8%

Slide34

Diagnostic Tests

Yeaaaaah…

For the inpatient team, you could send serum tryptase levels (which obviously peak between 60-90 minutes)

Slide35

Treatment

Which of the following are first line agents for the treatment of anaphylaxis (select all that apply)?

a. IV Corticosteroids

b. PO Corticosteroids c. Parenteral Epinephrine d. Nebulized Beta agonists e. Oral Antihistamines

f. IV Antihistamines

Slide36

Treatment

Slide37

Treatment

Slide38

Treatment

AIRWAY

Control it early (waaaaay easier to explain to an alive patient why they maybe didn’t need it then to explain to the family why the deceased, in retrospect, did)

Standard of care is NOT to call ENT to look at larynx. You either look at the larynx yourself or you make a call based on symptoms (Voice change, respiratory distress, etc. One day, ultrasound)

Many difficult airway devices will not work

LMA – nope

Combitube – eh eh

Things to have:

Bougie

Tubes many sizes smaller than you typically use

Fiberoptics (but Bougie + Glidescope pretty good too)

½ dose Etomidate without paralytic for “awake” intubation

Crich tray or kit (seldinger)

ENT, Anesthesiology (time permitting, don’t be proud, be smart)

Slide39

Treatment

CIRCULATION (and A and B)

Be vigilant for tachycardia (brady and other dysrhythmias can sometimes also happen), hypotension, etc.

IV fluids – lots of them Epinephrine – Dr. House says, “Don’t be a….”

Slide40

Treatment - Epinephrine

Study #1: 13 fatal or near-fatal cases of anaphylaxis

of 6 who died, only 2 received epi within 1 hour of sx onset

of 7 who survived, 6 received epi within 30 minutesStudy #2: there were others, but I lost them, so here we are….

Delay in epi administration also associated with higher rate of biphasic reactions

No placebo controlled allowed, so keep all your snooty journal club whining to yourselves

Slide41

Treatment - Epinephrine

Slide42

Treatment - Epinephrine

BEST ROUTE = IM to the anterolateral middle third of the thigh with a needle long enough to reach MUSCLE

SubQ

 unreliable absorptionIV  unless you need it, that sh$&% will kill you (virtually ALL adverse outcomes resulted from IV administration)

Slide43

Epi Dosing

Adults

IM 0.2 – 0.5mg

Literature suggests that you go big (0.5 -1mg) or go homePedsIM 0.01mg / kg up to a max of 0.3mg

IM solution is the 1:1000 one (which means

1gm /1000mL

1000mg / 1000mL

1mg in 1mL

0.5mg = 0.5mL

Do this once. In five minutes, if necessary, do it again.

Then draw up a third and mix up the IV epi for when the third fails.

IV dosing is not well established

Slide44

Want to hear something scary?

Multicenter study found:

fewer than 25% of “serious reactions” received epi

fewer than 16% discharged with Rx for epi-pens but.. 72% received antihistamines 48% systemic steroids

33% Nebs

Another study:

only 5% of housestaff new appropriate route and dosage

Slide45

Who SHOULDN’T get Epi?

ABSOLUTELY NO ABSOLUTE CONTRAINDICATIONS!

It IS safe (IM, anyway)….

A study of epi used in asthma exacerbations demonstrated safety in patients ages 15-96 years

HOWEVER…

… in patients using beta blocker, may get unopposed alpha, so some advise half-dose epi

Slide46

Take away the beta…

Slide47

Antihistamines

H1 Blockers

SECOND LINE, NEVER THE SOLE TX OF ANAPHYLAXIS

SLOW ONSET (effects take 30 – 45 min to start)WORK TO PROHIBIT FURTHER DEGRANULATIONS, NOT TREAT THAT WHICH HAS ALREADY OCCURRED!H2 Blockers

SECOND LINE

Sound data to support use (randomized, double blind, placebo controlled)

Slide48

Corticosteroids

SECOND LINE

JOINT TASK FORCE IN ALLERGY blah blah and blah says, “systemic corticosteroids have no role in the acute management of anaphylaxis because they might have no effect for 4 to 6 hours, even when administered intravenously.”

Never validated in placebo controlled trials, nor have standard dose, route, or type been proven superior

But, duh

European recs: 200 mg hydrocortisone IM or IV “following the initial resuscitation of the patient”

Slide49

Glucagon

For either refractory or Beta-blocked patients

Stimulate cAMP production (like Epi does) but via a different non-beta-blocked receptor

1 – 5 mg IV over 5 minutes (peds = 20-30 microg / kg, max 1mg), then IV infusion of 5 – 15 microg / min titrated to response

Slide50

Other

Nebs

Terbutaline

Vasopressin – evidence supportsOther vasopressors

Slide51

Disposition

Slide52

DISPO

Observe for at least 6 hours (8 appears better) from the time of symptom IMPROVEMENT, not onset

Biphasic reactions occur in 5 – 20% of cases

Latency period highly variable but nearly always within 72 hoursRetrospective study of 164 cases of fatal anaphylaxis showed that vast majority of deaths occurred within 4 hours, all within 6

Slide53

Dispo

Extend observation and consider admission for:

Asthmatic component of reaction

History of biphasic reactions Continuing absorption of allergen Poor access to emergency care Overnight or alone at home

Severe reactions with slow onset

Unable to use epi-pen

Admit

Anyone not cardiorespitorily perfect after 8 hours

Slide54

BEFORE DISCHARGE, ALWAYS

Clear instructions to return PRN and what constitutes PRN

Rx for 3 days (72 hours for a reason) of antihistamine and steroids

EPI-PEN x2 (either in their hand or RX able to be filled immediatelyInstructions how to use the epi-pen

Follow up appointment / plan

Among MDs who commonly rx epi-pens, only 25% correctly demonstrated the proper technique for use, only 24% knew it was available in 2 dosage forms

Slide55

ACE-Inhibitor Angioedema

0.1%- 0.5% of users (more so in A-As, ACE-I cough more so in Asians)

Likely inhibition of ACE breakdown of bradykinin, a potent vasodilator

Usually localized to head, neck Lacks cutaneous features of true allergyAnaphylaxis Tx never proven effective (epi, roids, H1&2s), but airway control has

FFP replenishes ACE levels (class II)

Icatibant (not likely available) specific bradykinin B2 receptor inhibitor (Class II, off-label use)

Slide56

ACE-Inhibitor Angioedema

In one retrospective study of angioedema, ACE-I were responsible for 1/3 of events. Of those:

Nearly half warranted ICU admission

One-third required definitive airway So, they recommended

outpt or obs for sxs limited to face, lips, soft palate

Inpt for lingual edema, ICU for posterior lingual or laryngeal edema (whether visualized or based on sxs of stridor, dyspnea, voice change)

Slide57

C1 Esterase Inhibitor Deficiency

2 Forms

Autosomal dominant

Acquired (often associated with lymphoproliferative and autoimmune dzs) also De Novo mutationsC1EI modulates complement activation, but it also helps regulate bradykinin formation

Lack of Inhibitor means more bradykinin

(ACE-I = inability to breakdown brady)

(C1EI def = inability to slow creation)

Recurrent episodes of well-circumscribed, nonpruritic angioedema

May involve Gi and respiratory tracts (unexplained, recurrent abd pain)

FFP, C1EI concentrate (both Class II)

Slide58

Penicillin and Cephs

Shared beta-

lactam

structure“10% cross-reactivity” = from 1970s, 1st gen

cephs

which later were found to have trace amounts of PCN in them! (derived from same mold)

New data suggest side chains may be more important than beta-

lactam

ring

AAP recently endorsed use of 2

nd

gen and 3

rd

gen

Cephs

for

otitis

in PCN allergic

peds

as long as prior reaction was not hypersensitivity type 1 (fewer than 10% of those claiming PCN allergy have Type 1)

All in all, risks of serious reaction to 2

nd

or 3

rd

Ceph

in a pt with a self-reported / non-skin tested PCN allergy are low (perhaps <1% but realistically type 1 reaction to any given

abx

is 1-3%

Slide59

Radiographic Contrast Materials

ANAPHYLACTOID (and therefore dose dependent, no IgE)

Maybe some IgE cases

Related to the osmolarity of the solution, now everyone uses safer “low osmolarity

” (3.1% adverse

rx

, 0.04% severe) some using even safer “

iso-osmolar

”

No absolute contraindication

History of Iodine-containing food allergy is NOT predictive (another 1970s study gone awry)

RFs

=

hx

of one,

atopy

/ asthma, Beta blockade, CAD

Tx

Sxs

like any other allergic / anaphylactic reaction

Pretreatment appears to reduce event likelihood by 10-fold