Transcript Anaphylaxis

Anaphylaxis
Jesse Sturm, MD
PEM Fellow
October 3, 2007
This is a Test
It is ONLY a Test
2
A 16 y/o girl just passed out after receiving her penicillin
shot for strep throat (“doesn’t swallow pills”). Which of
the following will be most useful to know in treating her:
A
B
C
D
3
Her Blood Pressure
Her Glucose level
Her Heart Rate
Your Heart Rate
Which of the following is the safest and most
efficient route to administer epinephrine in an
allergy emergency:
A
B
C
D
4
IV
Sub Q
IM
PR
When advising parents/patients on how to
administer an “epi-pen” you should tell them
to:
A. hold it against the triceps and squeeze the trigger
B. “stab” it into the anterior thigh
C. hold it against the lateral thigh and push
5
Which is NOT a clinical presentation of
anaphylaxis:
A.
B.
C.
D.
6
Vomiting and Diarrhea
Syncope
Altered Mental Status
Itchy Tongue
In counseling a 50kg 15 year old after a severe episode of
anaphylaxis to a bee sting your best advice is that if they
get stung again they first should take
A.
B.
C.
D.
7
(2) 25mg diphenhydramine capsules PO
(5) tsp diphenhydramine elixir PO
.5mg epinephrine SQ
60mg prednisone PO
Which of the following treatments has been shown to
decrease the incidence of biphasic reactions:
A. Corticosteroids
B. Epinephrine
C. Diphenhydramine
D. Ranitidine
8
Objectives
 Definition of anaphylaxis
 Epidemiology
 Presenting signs and symptoms
 What is the management algorithm
• Supporting evidence for medication usage
• Biphasic reactions
9
History
 First recorded case in
Egyptian hieroglyphics 2641
B.C. – Pharaoh Menes died
after wasp sting
 Modern times – named by
French scientists
investigating anemone
stings on dogs
• “aphylaxis”
 a – contrary
 phylaxis – protection
• Changed to anaphylaxis
because sounded better
10
Definition
 Anaphylactic: allergic, IgE-mediated, immediate
hypersensitivity reactions to protein substances
• Requires previous exposure to antigen to form IgE
 Anaphylactoid: clinically indistinguishable, NOT IgEmediated i.e. contrast media
• Does not require previous antigen exposure
• Unknown mechanism
 Anaphylaxis: clinical syndrome, regardless of
mechanism
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Mechanism
 IgE antibodies form upon initial Ag exposure
• IgE binds to high-affinity Fc receptor on mast cell
• Re-exposure, Ag bridges IgE → mast cell
degranulation → release of preformed mediators
(histamine, prostaglandin D2, leukotrienes)
 Direct complement cascade activation by Ag
resulting in anaphylatoxins C3a and C5a
• Directly degranulate mast cells
 Non-IgE and non-complement mechanism
• Direct activity on mast cells
• Hyperosmolar solutions (mannitol, radiocontrast)
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Epidemiology
 Incidence varies – lack of consensus definition
• ~ 10.5 per 100,000 person-years
 1% of all ED visits in both children and adults
 Fatality rate: ~ 1%
 1500 deaths per year in all ages
• 1300 drug induced
• 100 food and sting induced
 Children with atopy and asthma at higher risk
 One study – males < 15yo, OR 1.9 for anaphylaxis
compared to girls
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Clinical Criteria
Anaphylaxis is highly likely when any one of the following 3 criteria are met.
1.
Acute onset of an illness with involvement of skin, mucosal tissue, or both
and at least one of the following:
a. Respiratory compromise
b. Reduced BP or end-organ
dysfunction.
2.
Two or more of the following that occur rapidly after exposure to a likely
allergen for that patient:
a. Involvement of the skin mucosal tissue
b. Respiratory compromise
c. Reduced BP or associated symptoms
d. Persistent GI symptoms
3.
Reduced BP after exposure to known allergen for that patient.
Sampson et al Annals of Emerg Med Apr 2006
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Anaphylaxis Triggers
Reaction to previously known antigen: 21.1%
1.
FOOD: 56%
-Peanut, egg, dairy, seafood, food additives/dyes
2.
3.
DRUGS: 5%
-Penicillins, cephalosporins, NSAIDs, other
INSECTS: 5%
-Bees, wasps, ants
4.
NO cause identified: 18%
Braganza et al. Arch Dis Child 2006 N=57
Others: Blood products, Immunotherapy, Latex,
Vaccines, Radiocontrast media
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Causes of Anaphylaxis: All Ages
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Retrospective review
601 patients with anaphylaxis
Excluded hymenoptera stings
Causes:
Idiopathic: 59%
Food:
22%
Meds:
11%
Exercise:
5% – rare in children
Latex:
1%
Webb M. Ann Allergy Asthma Immunol. 2006
Foods
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Peanut and Tree nuts: 1% Americans (3 million) allergic
Legumes: 25-35% also allergic to tree nuts
Shellfish
Fish
Milk
Eggs
Food additives: sulfites
Foods That May Contain Peanut Oil
 Arachis oil (peanut oil)
 Baked Goods and
mixes
 Biscuits, cookies,
pastries
 Candy
 Cereals
 Chocolate
 Emulsifiers, flavorings
 Ethnic foods: African,
Chinese, Mexican,
Thai, Vietnamese
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Ice Cream
Margarine
Milk formula
Satay Sauce (thai
sauce)
Soft drinks
Soups
Sunflower seeds
Vegetable fats and oils
Medication Triggers: All Ages
 69 anaphylactic events
 Causes:
Aspirin:
35%
NSAID:
22%
B-Lactam: 20%
Insulin:
10%
Protamine: 3%
 PCN and cephalosporins cross react in 4-10%
 Penicillin and NSAIDs most common in children
• PCN IgE mediated 1:40,000 in children
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Venoms/Antivenins
 5 major stinging insects in the US:
• honeybees
• wasps
• yellow jackets
• hornets
• fire ants
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Latex
 Incidence low, except for risk groups:
• Medically complex, multiple procedures
 >1000 episodes and 15 deaths attributed
 Surgical and dental procedures highest risk
 RAST testing available
22
Vaccinations
 Rare event < 1.5 events per million
 Most common MMR and Influenza
• Both chick-derived cellular vaccines
 MMR safe to give in egg allergy
 Influenza contraindicated in egg allergy
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Anaphylaxis: Signs and Symptoms
 Cutaneous
90%
Urticaria and angioedema
90%
Flushing
50%
Pruritus without rash
5%
 Respiratory
60%
Throat pruritis/tingling
50%
Dyspnea, wheeze
50%
Upper airway angioedema
60%
Rhinitis
20%
 Dizziness, syncope, hypotension 35%
 Abdominal
30%
Nausea, vomiting, diarrhea, cramping pain
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Lieberman et al. American Academy of Allergy, Asthma and Immunology 2005
Other Symptoms to Look For
 Sense of impending doom
 Uterine cramps
 Visual disturbances
 Metallic taste
 Increased lacrimation
 Seizure
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Anaphylaxis Boy
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Timing and Route of Exposure
 Most symptoms occur within 5-30 minutes
 Parentally injected medication and hymenoptera
envenomation –more rapid
 Oral ingestion – may be rapid or delayed
 Food ingestions more often associated with GI
symptoms
27
Differential Diagnosis
 Vasovagal reaction
 Hereditary angioedema
 Panic Attack
 Urticarial disorders
 Seizure
 Vocal cord dysfunction
 Systemic mastocytosis
 Status asthmaticus, croup, tracheitis
 Upper airway obstruction, foreign body
28
Management of Anaphylaxis
 Medications:
• Epinephrine
• H1 and H2 antagonists
• Vasopressors
• Glucagon
• Corticosteroids
• Albuterol
29
 Supportive measures:
• Oxygen
• Positioning
• Fluid Resuscitation
 Observation period
 Outpatient follow-up
Immediate Assessment
 CR Monitor, pulseox
 Supine positioning with Trendelenberg if shock
 Assessment of ABC’s
 Oxygen by NRB, wean as tolerated
 Early elective intubation for significant hoarseness
and/or lingual or oropharyngeal edema
• Consider sedated intubation without paralysis
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Epinephrine
 α1: promote vasoconstriction and decrease edema
 β1: increase inotropy and chronotropy
 Β2: bronchodilation and decreased mast cell
degranulation
 Dose: 0.01mg/kg: 0.1-0.5mg (0.5mL) of Epi 1:1000
 IM anterolateral thigh superior to SQ
 Repeat dose at 5-10min intervals as needed
 Persistent hypotension may reflect volume
depletion and not failure of Epinephrine
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IM vs. SQ
2 studies by Simons et al
Patients NOT experiencing anaphylaxis
 Single blind study in children, n=17
 MMEC= mean max epi concentration
 Location of injections not described
SQ: n=9. MMEC=1802pg/ml, @ 34min
IM: n=8. MMEC=2136pg/ml, @ 8min
Simons F. J Allergy Clin Immunol 1998
Simons F. J Allergy Clin Immunol 2001
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Serum Levels: Adults
33
IM vs SQ: Adults
 Adults:6 way crossover study, n=13
SQ deltoid:
IM deltoid:
Epipen thigh:
IM thigh:
Saline IM:
Saline SQ:
34
2,877 pg/ml
1,821 pg/ml
12,222 pg/ml
9,722 pg/ml
1458 pg/ml
1495 pg/ml
Epipen
35
IV Epinephrine
 Indicated for persistent hypotension after IM Epi,
IVF, and positioning OR shock
• IV/IO: Epi 1:10,000 at 0.01mg/kg (0.1mL/kg), max 1mg
• Continuous infusion may be needed: 0.1-1μg/kg/min
 Evidence based on a few adult studies
 Can cause lethal arrhythmias
• Requires careful continuous monitoring,
especially in the elderly
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Epinephrine: Other Routes
 Sublingual epinephrine vs. IM
• Current study in rabbit model shows SL may be
similar in efficacy
• Not definitive
 Inhaled Epi from MDI-type system shown to be
ineffective
37
Vasopressors
 First line: intravenous epinephrine
 Second line: Vasopressin
2 adult case reports of anaphylaxis with shock
-42y/o s/p hornet sting, no improvement with 1mg
Epi IV, improved with vasopressin (10 IU)
-47y/o s/p wasp sting improved with vasopressin (40 IU)
 Other vasopressors: dopamine or norepinephrine
 Glucagon in persistently hypotensive pt taking betablockers
Kill C, Int Arch Allergy Immunol, 2004.
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Glucagon
 Theoretical utility and case reports of efficacy:
• Activates adenylate cyclase independent of
Beta receptor
• May reverse refractory hypotension and
bronchospasm
• Particularly helpful if taking beta-blocker
 Adults: 1-5 mg IV
 Children 20-30 mcg/kg (max 1mg)
 Followed by infusion 5-15mcg/min
 Significant SE of emesis
Javeed N. Cath & Card Diag, 1996.
39
Anti-histamines
For symptomatic treatment of urticaria-angioedema and pruritus
 H1 antagonists (Diphenhydramine):
• 25-50mg for adults
• 1mg/kg for children (max 50mg)
• IV route preferred for significant reactions
 With H2 antagonists (Ranitidine, Cimetidine):
-Double blind controlled trial demonstrated efficacy
 Claritin and other second generation antihistamines
may have more efficacy than diphenhydramine but
lack IV formulation
Lin R, Ann Emerg Med 2000.
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Primary Outcomes at 2 hours
Anaphylaxis symptoms at 2 hours with and without Zantac
N = 91
adults
Diphenhydramine+
Ranitidine
Urticaria
4
11
Erythema
13
20
Angioedema
11
14
Lin R, Ann Emerg Med 2000.
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Diphenydramine +
Placebo
Corticosteroids
 No placebo-controlled trials supporting efficacy
 Theoretical utility
• May reduce late phase reaction based on results
with asthma
• Some studies have found them to be ineffective
 Dosage:
• methylprednisolone 1-2mg/kg IV Q6 up to 125mg
• prednisone 1-2mg/kg (max=50mg)
• No data on dexamethasone
 Duration for 72hrs for latent reactions
Biphasic reactions will be discussed in a few slides….
42
Supportive Measures
 Supplemental oxygen
 Inhaled β2 agonists for wheezing
• No data on inhaled Atrovent in anaphylaxis
 Positioning in recumbent position
 Fluid resuscitation
• Vasodilatation and extravasation cause
distributive shock
• Circulating volume can drop 35% within 10min
• May require multiple boluses of crystalloid and/or
colloid (up to 60-80 mL/kg)
Pumphrey R. J Allergy Clin Immunol 2003
Boulain T. Chest 2002
43
Biphasic Reactions
 Delayed reactions – up to 72 hours
• Largest review in children - 6% incidence
• Asymptomatic intervals 1.3 hrs to 28.4 hrs
 Failure to administer prompt adequate doses of Epi
increases risk of biphasic reaction
 Route, quantity, and type of antigen NOT correlated
with latent reaction
 Symptoms and severity during initial reaction NOT
predictive of latent reaction
44
Observation Period
Can we predict biphasic reactions?
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Study
Number
Frequency
Time (hr)
Brazil
6/34
18%
4.5-29.5
Douglas
6/103
6%
1-72
Lee
6/105
5%
5-47.6
Stark
5/25
20%
1-8
Brady
2/67
3%
24-28
Smit
15/282
5%
1-23
Ellis
20/103
19.4%
2-38
Predictors of biphasic reactions?
 Delayed administration of epinephrine
 Suspected but not proven
• Patient requiring high doses of epinephrine
• Lower doses of corticosteroids given
• Ingested antigen
There are NO reliable clinical predictors of
biphasic reactions
 Observation period individualized, but at least 6
hours
46
Laryngoscopy?
 Consider early elective intubation in severe cases
 Endotracheal intubation for all children with orofacial
bee stings AND any airway compromise
• Not all facial swelling requires intubation
Ditto A. Ann of All, Asthma and Immunol, 1995.
Tome R. Am J of Otolaryng, 2005.
47
48
Laboratory tests
 Useful in uncertain cases
• Prick skin tests: best screening test
 high false positives; very few false negatives
 may require food challenge
• RAST: measures specific IgE
 less sensitive than skin prick
• Plasma Histamine: increases in 5-10 min, elevated for
only 30-60min – not clinically useful
• Serum Tryptase: peak 1-1.5 hrs, inc for up to 5hrs
 Alpha: secreted constitutively
 Beta: released during degranulation, ratio helpful
• C1 inhibitor assay in hereditary angioedema
• These tests have only limited utility in setting of
LaRoche D. Anethesiology 1991.
acute severe anaphylaxis
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Disposition
(after appropriate observation period)
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Severe reactions require observation for minimum 6-24hrs
Observation time based on: severity of initial reaction,
home supervision, reliability of parent, access to care
High risk patients:
•
History of biphasic reaction, asthma, possibility of
continued Ag absorption
Prescriptions for steroids and antihistamines for 72 hours
Three key components of disposition:
1. Self-injectable epi-pen
2. Education about avoidance of triggers and return of
symptoms
3. Follow-up evaluation with allergist
50
Physician compliance
Study of patients with food related anaphylaxis from ED:
• 35% patients given instructions for return symptoms
• 22% given prescription for epi-pen
• 13% referred to allergy specialist
Only 2% received all three!
Clark S. J Clin Immunol 2004
Clark S. J Clin Immunol 2005
51
Epipen dosing
 2 fixed doses available (1:1000)
• Epipen JR: 0.15mg (10kg-25kg)
• Epipen: 0.3mg (>25kg)
• <10kg – can be given Epi ampule and syringe
needle
 Parents studied took several minutes to draw
up doses, were inaccurate, and uncomfortable
drawing up medication
 Weigh risk and benefit with parents
Simons FE, J All and Clin Imm. 2002
52
Epipen
 2 doses available at all times
• Second injections necessary in 36% of patients
 Childcare facilities and other caregivers must be
familiar with indications for use and technique
 Epi degrades over time and heat/cold will hasten
degradation
• Refill prescriptions at least annually
53
Summary
 Give Epi IM in the thigh, dose early in course
 IV Epi reserved for persistently hypotensive patients
 Observation periods must be tailored to the
individual since biphasic reactions are unpredictable
• Minimum of 6 hrs
 Disposition requires:
• Return precautions and trigger avoidance
• Epipen prescriptions
• Verbal referral to allergist
 Ongoing multicenter studies:
• Predictors of biphasic reactions
54
A 16 y/o girl just passed out after receiving her penicillin
shot for strep throat (“doesn’t swallow pills”). Which of
the following will be most useful to know in treating her:
A
B
C
D
55
Her Blood Pressure
Her Glucose level
Her Heart Rate
Your Heart Rate
Which of the following is the safest and most
efficient route to administer epinephrine in an
allergy emergency:
A
B
C
D
56
IV
Sub Q
IM
PR
When advising parents/patients on how to
administer an “epi-pen” you should tell them
to:
A. hold it against the triceps and squeeze the trigger
B. “stab” it into the anterior thigh
C. hold it against the lateral thigh and push
57
Which is NOT a clinical presentation of
anaphylaxis:
A.
B.
C.
D.
58
Vomiting and Diarrhea
Syncope
Altered Mental Status
Itchy Tongue
In counseling a 50kg 15 year old after a severe episode of
anaphylaxis to a bee sting your best advice is that if they
get stung again they first should take
A.
B.
C.
D.
59
(2) 25mg diphenhydramine capsules PO
(5) tsp diphenhydramine elixer PO
.5mg epinephrine SQ
60mg prednisone PO
Which of the following treatments has been shown to
decrease the incidence of biphasic reactions:
A. Corticosteroids
B. Epinephrine
C. Diphenhydramine
D. Ranitidine
60
QUESTIONS?
61
END OF SHOW
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