anaphylaxis
DESCRIPTION
Anaphylaxis. Anaphylaxis. J Allergy Clin Immunol 2007;120:506-15. http://www.youtube.com/watch?v=VcxdqIPLyK8&list=PL7C80B961F004CBB8. Anaphylaxis Road Map. Definition Pathophysiology Epidemiology Etiology Morbidity and Mortality Evaluation Treatment Dispo. Ana- - p hylaxis. - PowerPoint PPT PresentationTRANSCRIPT
Anaphylaxis
J Allergy Clin Immunol 2007;120:506-15
Anaphylaxis
http://www.youtube.com/watch?v=VcxdqIPLyK8&list=PL7C80B961F004CBB8
Anaphylaxis Road Map
DefinitionPathophysiologyEpidemiologyEtiologyMorbidity and Mortality
EvaluationTreatmentDispo
Ana- -phylaxisAna- = again, up, back-phylaxis = protection, immunity, guarding
1902
+
=
1902 + a few days
+
=
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
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
Pathophysiology
Pathophysiology… for the ED doc
PathophysiologyType I Hypersensitivity Phases
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)
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.
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)
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.
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
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)
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.
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)
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)
Symptoms
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
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)
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)
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.
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%
Diagnostic Tests
Yeaaaaah…
For the inpatient team, you could send serum tryptase levels (which obviously peak between 60-90 minutes)
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
Treatment
Treatment
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)
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….”
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
Treatment - Epinephrine
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)
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
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
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
Take away the beta…
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)
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”
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
Other
Nebs
Terbutaline
Vasopressin – evidence supports
Other vasopressors
Disposition
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
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
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
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)
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)
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)
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%
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