59
Anaphylaxis

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

Embed Size (px)

Citation preview

Page 1: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Anaphylaxis

Page 2: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

J Allergy Clin Immunol 2007;120:506-15

Anaphylaxis

Page 3: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis
Page 4: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis
Page 5: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

Page 6: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Anaphylaxis Road Map

DefinitionPathophysiologyEpidemiologyEtiologyMorbidity and Mortality

EvaluationTreatmentDispo

Page 7: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Ana- -phylaxisAna- = again, up, back-phylaxis = protection, immunity, guarding

Page 8: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

1902

+

Page 9: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

=

Page 10: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

1902 + a few days

+

Page 11: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

=

Page 12: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

Page 13: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

1. Acute onset of mucocutaneous signs AND 1 of the following: respiratorycompromise (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, orpersistent gastrointestinal symptoms.

3. Hypotension after exposure to a known allergen.

Definition

Page 14: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Pathophysiology

Page 15: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Pathophysiology… for the ED doc

Page 16: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

PathophysiologyType I Hypersensitivity Phases

Page 17: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

PathophysiologyType 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)

Page 18: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

PathophysiologyType 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.

Page 19: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis
Page 20: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis
Page 21: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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)

Page 22: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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.

Page 23: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

EpidemiologyVery likely under-reported

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

Foods 100 -200 fatalities / yearBeta Lactams (parenteral) 400 - 800 fatalities / yearRadiocontrast 900 fatalities / yearInsect stings 40 – 100 fatalities / yearLatex 3 fatalities / yearDesensitization injections about 3.4 fatalities / yearAllergen testing 1 fatality reported between 1990-2001

Page 24: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Etiology#1: Food

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

#3: Stinging insectsHymenoptera

Apid (honeybee, bumblebee)Vespid (yellow jacket, hornet, wasp)Formicid (fire ant)

#4: Latex

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

Page 25: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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.

Page 26: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Adverse Drug Reactions

Immediate hypersensitivity (IgE)

Nonimmediate allergic reactions (not IgE, typically)SJSTEN

Nonimmunological reactionsAnaphylactoidNonspecific histamine release (morphine itch, vanco red man)Bradykinin accumulation (ACE-I angioedema)Complement activation (radiocontrast)Leukotrienes (NSAIDs)

Page 27: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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)

Page 28: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Symptoms

Page 29: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

1. Acute onset of mucocutaneous signs AND 1 of the following: respiratorycompromise (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, orpersistent gastrointestinal symptoms.

3. Hypotension after exposure to a known allergen.

DefinitionJ Allergy Clin Immunol 2006 ;117 : 391-7

Page 30: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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)

Page 31: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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)

Page 32: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Criteria 3: hypotension, know exposureDecrease 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.

Page 33: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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 not

Cutaneous 90% Respiratory 50% +/- 10%Cardiovascular (dizzy, syncope, low BP) 33%GI 25-30%Other Sxs (HA, chest pain, Sz) <8%

Page 34: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Diagnostic Tests

Yeaaaaah…

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

Page 35: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment

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

a. IV Corticosteroidsb. PO Corticosteroidsc. Parenteral Epinephrined. Nebulized Beta agonistse. Oral Antihistaminesf. IV Antihistamines

Page 36: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment

Page 37: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment

Page 38: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

TreatmentAIRWAYControl 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 workLMA – nopeCombitube – eh eh

Things to have: BougieTubes many sizes smaller than you typically useFiberoptics (but Bougie + Glidescope pretty good

too)½ dose Etomidate without paralytic for “awake”

intubationCrich tray or kit (seldinger)

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

Page 39: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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….”

Page 40: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment - Epinephrine

Study #1: 13 fatal or near-fatal cases of anaphylaxisof 6 who died, only 2 received epi within 1 hour of sx onsetof 7 who survived, 6 received epi within 30 minutes

Study #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

Page 41: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment - Epinephrine

Page 42: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Treatment - Epinephrine

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

SubQ unreliable absorption

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

Page 43: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Epi DosingAdultsIM 0.2 – 0.5mg

Literature suggests that you go big (0.5 -1mg) or go home

PedsIM 0.01mg / kg up to a max of 0.3mg

IM solution is the 1:1000 one (which means 1gm /1000mL1000mg / 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

Page 44: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Want to hear something scary?

Multicenter study found:fewer than 25% of “serious reactions” received epifewer than 16% discharged with Rx for epi-pensbut..72% received antihistamines48% systemic steroids33% Nebs

Another study: only 5% of housestaff new appropriate route and dosage

Page 45: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

Page 46: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Take away the beta…

Page 47: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Antihistamines

H1 BlockersSECOND LINE, NEVER THE SOLE TX OF ANAPHYLAXISSLOW ONSET (effects take 30 – 45 min to start)WORK TO PROHIBIT FURTHER DEGRANULATIONS, NOT TREAT THAT WHICH HAS ALREADY OCCURRED!

H2 BlockersSECOND LINESound data to support use (randomized, double blind, placebo controlled)

Page 48: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Corticosteroids

SECOND LINEJOINT 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”

Page 49: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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

Page 50: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Other

Nebs

Terbutaline

Vasopressin – evidence supports

Other vasopressors

Page 51: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Disposition

Page 52: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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 hours

Retrospective study of 164 cases of fatal anaphylaxis showed that vast majority of deaths occurred within 4 hours, all within 6

Page 53: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Dispo

Extend observation and consider admission for: Asthmatic component of reactionHistory of biphasic reactionsContinuing absorption of allergenPoor access to emergency careOvernight or alone at homeSevere reactions with slow onsetUnable to use epi-pen

AdmitAnyone not cardiorespitorily perfect after 8 hours

Page 54: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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 immediately

Instructions 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

Page 55: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

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 vasodilatorUsually localized to head, neck Lacks cutaneous features of true allergyAnaphylaxis Tx never proven effective (epi, roids, H1&2s), but airway control hasFFP replenishes ACE levels (class II)Icatibant (not likely available) specific bradykinin B2 receptor inhibitor (Class II, off-label use)

Page 56: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

ACE-Inhibitor Angioedema

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

Nearly half warranted ICU admissionOne-third required definitive airway

So, they recommended outpt or obs for sxs limited to face, lips, soft palateInpt for lingual edema, ICU for posterior lingual or laryngeal

edema (whether visualized or based on sxs of stridor, dyspnea, voice change)

Page 57: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

C1 Esterase Inhibitor Deficiency2 Forms

Autosomal dominantAcquired (often associated with lymphoproliferative and autoimmune

dzs)also De Novo mutations

C1EI 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)

Page 58: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Penicillin and CephsShared 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 2nd gen and 3rd 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 2nd or 3rd 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%

Page 59: Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15 Anaphylaxis

Radiographic Contrast MaterialsANAPHYLACTOID (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