ANAPHYLAXIS:
Epidemiology
• Incidence- likely under-reported because no set definition
Pathophysiology 
• Sensitization-exposure leads to Ig-E antibodies on mast
cells and basophils
• Re-exposure-cross-linking of antibodies causes release of
active mediators
⇒ Histamine, cytokines, leukotrienes…
Classification
• Gell-Coombs classification
⇒ See Chart (Am Fam Physician 2003;68:1781-90)
• Anaphylactoid reaction
⇒ Immediate systemic reaction that mimics anaphylaxis but→ no Ig-E antibodies
⇒ Can occur on first exposure
⇒ Reactions dependent on systemic exposure
⇒ Example: radiographic contrast
⇒ Acute treatment similar to true anaphylaxis
Clinical Symptoms (4 organ sx)
• Respiratory-upper or lower
• Cardiovascular-entire spectrum
• Gastrointestinal- N/V/D, wide variety sx
• Skin-we associate with anaphylaxis but skin findings absent 10%
Definition
• No good definition→we know it when we see it
• Spectrum
⇒ Urticaria, Angioedema
√ versus non-specific rash?
⇒ Anaphylaxis (at least 1 out of 2: )
√ Respiratory difficulty→throat, posterior pharynx, larynx
√ Hemodynamic instability
Etiology
• Foods→most common
⇒ Early life: allergens that are outgrown (eggs, milk, soy)
⇒ Later life: peanuts, treenuts, fish, shellfish
√ If these occur in early life→ tend to not outgrow
• Medications→antimicrobials, NSAIDS, ASA, any
• Exercise induced→ ½ are food induced
• Idiopathic→20%
• Other→Hymenoptera, latex, blood components, beer, others
Differential diagnoses
• Scombroid poisoning: 30 min after spoiled fish (tuna, mackerel, mahi-mahi), N/V/D, urticaria
⇒ Treatment→antihistamines
• Angioedema:
⇒ Hereditary→C1 esterase inhibitor replacement, FFP; (not associated with urticaria)
⇒ ACE-inhibitor induced→ manage airway + usual treatment
• Severe Asthma
• Panic disorders
Treatment Recommendations (J Allerg Clin Immunol 2005;115:S483-523)
• Oxygen
• IV Fluids
• Epinephrine (1st line agent)
⇒ Route
√ IV→ virtually all adverse outcomes in literature are from IV use
i ↑adverse effects when given too rapidly, too concentrated, or too high of a dose
ii Reserve for sickest patients (true shock, not responsive to IM)
√ IM vs SQ→ more rapid peak plasma concentrations with IM use in children and adults
i Adults-J Allergy Clin Immunol. 2001;108:871– 873; Children: J Allerg Clin Immunol 1998;101:33
ii SQ absorption decreased in shock states
iii Epinephrine is vasoconstrictor→ decreases its own absorption
iv Limitations of recommendations→need study with both injections in thigh, studies done with
patient not in anaphylaxis
√ Recommendations: IM is better than SQ, regardless of age
⇒ Dose
√ IM Dose
i Adults IM: 0.3-0.5 mg IM of 1:1000 repeat q 5-15 min
ii Pediatrics IM: 0.01 mg/kg to max 0.3 mg 1:1000 IM repeat q 5-15 min
√ IV Dose: 0.1mg IV = 100 mcg IV = 1ml of 1:10,000 (need to dilute to 10 or
100ml→see below!)
i Dilution options: go to http://emrap.tv/
(a) Option #1: add 1ml of 1:10,000 solution to 9ml NS →10 ml of
1:100,000 dilution (10mcg/ml) over 5-10 min →10-20mcg/min
(b) Option #2: add 1ml of 1:10,000 (crash cart epi) to 100ml NS and run
over 5-10min→ (1mcg/ml) = 10mcg/min
(c) Compare to epinephrine gtt→1-4 mcg/min
(d) Pediatrics: 0.1mcg/kg/min (diluted to 1:100,000 solution) and titrate to
response
√ Epinephrine gtt: same dilution as option #2→(1mcg/ml), to run at 1-4
ml/min (1-4 mcg/min)
⇒ Safety?
√ IV→ virtually all adverse outcomes in literature are from IV use
√ IM/SQ→not too bad
√ Caution: elderly, hypertensive, CAD
⇒ Contraindications?
√ No absolute contraindications
√ β –blockers:
i Anaphylaxis may be worse
(a) relative state of hypoadrenergic;
(b) β –receptors are blocked (Epi won’t work on β receptors→unopposed α blockade)
ii Recommendations:
(a) ½ dose of epinephrine→ evaluate for response
(b) Glucagon (bypass β receptor altogether→ still stimulates cAMP)
(i) Dose: Glucagon 1-2 mg IV q 5-10min
(ii) Adverse effects: Nausea/Vomiting
√ Epinephrine allergy
i Not true allergy, likely preservative allergy→ MBS, sulfite
ii Recommendation: Sulfite-free epinephrine?
• Antihistamines (2nd line agent)
⇒ H1 blockers
√ Diphenhydramine→works well, can give IV
√ Non-sedating H1 blockers?→not available for IV use
⇒ H2 blockers
√ Benefit over H1 blockers alone
√ Low adverse effects (except possibly cimetidine→CYP450)
• Corticosteroids
⇒ Delayed effect of corticosteroids?
⇒ May prevent recurrent anaphylaxis
⇒ No role in acute management?? (J Allerg Clin Immunol 2005;115:S483-523)
⇒ Effects never been validated in placebo controlled studies, effects extrapolated from asthma
• Inhaled β2 agonist (albuterol)→if bronchospasm
• Remove source: venom sac! Stop antibiotics
• Vasopressin?
• AHA Summary of treatment recommendations (Circulation 2005;112;IV-143-IV-145)
⇒ Click on this: http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-143
• Special Case: Cardiac Arrest
⇒ Aggressive fluid resuscitation (4-8L)
⇒ High dose epinephrine IV: 1mg→3mg→5mg then start infusion at 4-10mcg/min
⇒ Antihistamine IV
⇒ Steroids IV
⇒ Prolonged CPR→effective CPR may maintain O2 delivery until catastrophic effects of anaphylaxis resolve
• Airway management
⇒ RSI normal way vs
⇒ Supraglottic device (LMA, Combitube)→less increasing edema without endotracheal tube in?
⇒ Angioedema ?→ consider nasotracheal intubation (prepare for cric)
Disposition
• Mild Urticaria (no respiratory compromise/hemodynamic instability)→Home
• Severe anaphylaxis (intubated, epinephrine gtt)→ICU
• Anaphylaxis that improves?
⇒ Recurrent anaphylaxis?
√ Biphasic or multiphasic form of anaphylaxis
√ Reappearance of allergic phenomenon after resolution of original symptoms
√ As high as 20% and as long as 72 hours after initial event! (see chart below)
√ Hong Kong study (Journal of Emergency Medicine, Vol. 28, No. 4, pp. 381–388, 2005)
i Biphasic symptoms in 5% of 282 patients
ii 3 patients with stable VS on presentation→ developed hypotension or severe dyspnea on
recurrence
√ Corticosteroids do not prevent this phase from recurring
⇒ Observation?→ no firm established criteria
√ Mild sx→ several hours, 4hours
√ Severe sx → observe x 24hours or admit
⇒ High risk features for fatal anaphylaxis
√ Specific allergens: peanuts, treenuts
√ H/O Asthma
• Discharge planning
√ Reliable caretaker?
√ Access to 911?
√ H1/H2 blocker
√ Corticosteroids x 3-5 days
√ Self-injectable epinephrine
i Underprescribed→ should be given to all true anaphylaxis,
maybe multiple
ii EpiPen and EpiPen Jr
iii Twinject→can administer 2 doses
iv Education: YouTube?
Adverse Drug Reactions
• Define: All non-therapeutic consequences of drug, excluding treatment failure, poisonings or drug abuse.
• Allergic ADRs: 5-25% of ADRs
⇒ Type 1 Hypersensitivity→ small fraction of allergic ADRs
⇒ Is patient having a true ADR?
• Non-allergic ADRs: N/V/D, weakness, non-specific rash (urticaria vs routine maculopapular eruption)???
