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1st Paediatric Emergency Conference Kuwait October 2011
Emergency Treatment of Anaphylaxis in Infants and Children
Dr. D. Anna Jarvis
Disclaimer
I have no actual or potential conflict of interest to declare.
Photographs, images, charts and information were selected from The Hospital for Sick Children teaching file, my personal collection or downloaded from the internet.
Dr. D. A. Jarvis
Learning Objectives
On completion of this session participants will:
1.Understand the full range of paediatric anaphylaxis presentations
2.Know the high risk criteria for delayed and biphasic reactions
3.Be prepared to treat anaphylaxis in concordance with published consensus guidelines
Historical Perspective
1902 Prof Richet and Dr. Porter named ana (against) and phylaxis
(protection)
1904(approximately) Arthus described anaphylaxis in rabbits
1911 Auer ascribed lethal rabbit anaphylaxis to heart failure associated with
impaired coagulation
1960s role of mast cells and IgE described
2005-6 collaborative symposia established Epinephrine as first-line treatment and clinical definitions of anaphylaxis confirmed
Challenges – Multiple definitions
• World Health Organization (WHO)
“anaphylaxis is a severe, life-threatening generalized or systemic hypersensitivity reaction”
• National Institute of Allergy and Infection Disease (NIAID) and
Food Allergy and Anaphylaxis Network (FAAN)
“ a serious allergic reaction that is rapid in onset and may cause death” (clinical criteria defined)
Anaphylaxis – Definition 2006
Anaphylaxis is a severe, acute, potentially life-threatening medical condition caused by systemic release of mediators from mast cells and basophils, often in response to an allergen.
Note: Clinical criteria described on following slides
Second Symposium on the Definition and Management of Anaphylaxis: Summary Report
Samson J Allergy Clin Immunol 2006; 117:391-97
Clinical Definition: Anaphylaxis 2006
Anaphylaxis is likely if any of the following 3 criteria is satisfied within minutes to hours of an exposure:
1. Acute onset of illness with cutaneous and / or mucosal involvement AND at least one of the following:
a. Respiratory compromise (example: dyspnoea, bronchospasm, stridor, hypoxia)
b. Cardiovascular compromise (examples: hypotension, collapse)
Clinical Definition: Anaphylaxis 2006
2. Two or more of the following occur rapidly after exposure to a likely allergen (minutes to several hours):
a. Involvement of skin or mucosa
(examples: generalized hives, itch, flushing, swelling)
b. Respiratory compromise
c. Cardiovascular compromise
d. Persistent Gastrointestinal symptoms
(examples: crampy abdominal pain, vomiting)
Clinical Definition: Anaphylaxis 2006
3. Hypotension after exposure to known allergen for that patient (minutes to several hours):
Age-specific low blood pressure or greater than 30% decline from baseline
Hypotension in children is defined as:• less than 70mm Hg 1 month to 1 year• less than 70mm Hg + (2x age) from 1 to 10 year • less than 90 mm Hg from 11 to 17 years
American Heart Association 2010 Guidelines
Challenges - Presentations • presentations vary with age and gender• marked geographical differences in incidence and
triggers reported
• literature has multiple small series and retrospective reviews, few prospective studies
Consensus view 2011:• anaphylaxis incidence rates increasing especially
in first 2 decades of life• the majority of children with anaphylaxis continue to
be undertreated due to lack of recognition and/or failure to administer epinephrine
Anaphylaxis – Age considerations
Gender: younger ages – many more males
adolescents - males equal females
Infants: hives and vomiting more common *many had no BP documented on chart
2 - 5 years: wheezing, hoarse voice, stridor more common
Up to 5 years: generalised swelling 56%
Adolescents: trouble breathing 57%
trouble swallowing 48%
Paediatric Anaphylaxis – GermanyMehl 2005 – questionnaire paediatricians/primary care about children with anaphylaxis in previous 12 months
• 103 cases – median age 5 years – 58% boys
• Triggers: food 57% (peanut 20% tree nut 20%)
stings 13%
immunotherapy 12%
unknown 8%
• Previous anaphylaxis 27% (50% same allergen)
• Severe anaphylaxis cases 36% received adrenalin
• On discharge 17% prescribed adrenalin self injector
Paediatric Anaphylaxis – Melbourne, Australia de Silva 2008 – 5 year retrospective review of paediatric
emergency records 123 children 117 events
• Median age 2.4 years (oldest 18 years)Allergic history: 17% had previous anaphylaxis
40% eczema 32% asthma (54% on inhalers)
9% rhinitisTriggers: food 85% (peanut 18% cashew 13% cow milk 11%)
• Median time from exposure to anaphylaxis 10 minutes onset to therapy 40 minutes
• Presentations: respiratory 97% skin 97% gastrointestinal 29% cardiovascular 17%
Anaphylaxis Management
• epinephrine (adrenalin) anaphylaxis
• CAB (ABCs) PALS / ACLS
• adequate intravenous fluids shock
• H1 - antihistamines itch and hives
• H 2 - antihistamines
• β2 – adrenergic agonists bronchospasm
• glucocorticoids may prevent protracted or biphasic symptoms
NOTE: very little evidence for management exists!
Consensus that epinephrine is medication of choice
Simons 2009, 2010 Samson 2006
Epinephrine (Adrenalin) pharmacology
adreneric receptors
benefits adverse effects
alpha – 1 vasoconstriction ↑ BP↑ peripheral vascular resistance
pallor headache
alpha – 2 ↓ insulin release ↑ blood glucose
beta – 1 ↑ heart rate + force of cardiac contractions
palpitations↑ coronary blood flow
beta – 2 bronchodilation vasodilation↓ mediators(histamine / tryptase)
tremor vasodilation (musles)↑ mediators(very low doses)
central CNS anxiety
Epinepherine Intrinsic Limitations
• rapidly metabolized (parental administration)
• if swallowed rapidly metabolized by:
catechol - o - methyltransferase - GI tract wall
monoamine oxidase - GI tract wall + liver
• narrow therapeutic / toxic dose range
• break down in solution (12 - 18 months?)
NOTE:
danger of injuries during administration
“missed dose” hazard with incorrect administration technique
Risk factors for sting anaphylaxis
• angiotension converting enzyme inhibitors • pre-existing vespid allergy• male sex• serum mast cell tryptase levels above 5ng/l
Bonadonna 2009 J Allergy Clin Immunol
379 patients with hymenoptera stings
11.6% had tryptase levels over 11.4 ng/l
70.5% of these had systemic anaphylaxis
34 patients with elevated levels underwent bone marrow biopsy 61.7% had systemic mastocytosis
Do large local reactions increase risk of future anaphylaxis?
5-10% patients with large local reactions have anaphylaxis
17% patients with anaphylaxis to stings have no history of prior exposure
Golden 2009 reported 41 patients with large local reactions after controlled sting challenge, randomly assigned to venom immunotherapy then re-challenged after 7-11 weeks:
42% treated patients had smaller reactions 18% untreated patients had smaller reactions
Anaphylaxis: risks of biphasic reaction
Treatment required Biphasic reaction
Uniphasic reaction
P
more than 1 dose epinephrine
58% 22% 0.01
and / or fluid bolus 42% 8% 0.01
median age (years) 9.6 2.4 (1 patient 18.8 years)
Mehr 2009 Clinical and Experimental Allergy 39: 1390-965 year retrospect study Australia• 109 episodes in 104 children• 95 (87%) uniphasic, 12 (11%) biphasic and 2 (2%)
protracted reactions
Anaphylaxis – biphasic reactions 12 children
Type of biphasic reaction
anaphylactic non-anaphylactic
Children involved (no.) 42% (5) 58% (7)
> 1 dose epinephrine and / or fluid bolus during first episode
5 of 5 6 of 7
Median age (years) 2.0 13.0
Time to rebound (hours)
1.5 16
Mehr 2009compared to first anaphylaxis episode – biphasic reaction: milder 58% similar 33% more severe 9%
Which patients require follow up and / or further evaluation?
• systemic reactions especially “idiopathic” episodes
• anaphylaxis
• education about avoidance of allergens, epinephrine self injection or treatment required
• candidate for skin testing, specific IgE measurement or immunotherapy
• coexisting medical condition(s) which might predispose to repeated episodes
Epinephrine therapy: Learning from survivors
Simons et al J Allergy Clin Immunul 2009; 124: 301-6
1885 patients with clinical anaphylaxis
27% self administered epinephrine
Reasons given for not administering epinephrine: 38% used antihistamine instead
28% not prescribed epinephrine
Epinephrine (Adrenalin) autoinjectorsEpi Pen Twinjet/Adrenaclick Anapen
Dose 1:1000 epinephrine (mg)
0.15, 0.3 0.15, 0.3 0.15, 0.3, 0.5
Exposed needle length (cm)
1.3 / 1.48 1.29 / 1.32 1.3
Needle gauge (G) 22 25 27
Shelf Life (months)
12 – 18 12 – 18 21 – 24
Description (with case)
Weight (g) 75.5 45.4 28.8
Length (cm) 15.6 16 16.9
Autoinjectors – unintentional injectionsSimons 2009 Ann Allergy Asthma Immunol
• Systematic review, English Language 1966 – 2008• 1998-2008 26 reports 69 cases (58% female)• No deaths / severe morbidity – What of “lost doses”?• Home 42% finger or thumb injury 91%• 65% assessed in emergency department:
13% no treatment / observation
25% injured area warmed
9% nitroglycerine paste
22% injection lidocaine and / or phentolamine
20% other treatments
12% no details available
Note: Additional 10231 cases 1994-2005 reported
ReferencesAnaphylaxis: past, present and futureBen-Shoshan M, Clarke AEAllergy 2011; 66: 1-14
Emergency treatment of anaphylaxis in infants and childrenCheng A, Canadian Paediatric Society, Acute Care CommitteePaediatr Child Health 2011; 16: 35-40
Epinephrine and its use in anaphylaxis: current issuesSimons KJ, Simons FERCurr Opin Allergy Clin Immunology 2010; 10: 354-61
Multicenter Study of Repeat Epinephrine Treatments for Food-Related AnaphylaxisRudders SA, Banerji A, Corel B, et alPediatrics 2010; 125: e711-18
References
Anaphylaxis and insect allergyDemain JG, Minaei AA, Tracy JMCurr Opinion in Allergy and Clinical Immunology 2010; 10: 318-22
Voluntarily reported unintentional injections from epinephrine auto-injectorsSimons FER, Edwards ES, Read EJ Jr et alJ Allergy Clin Immunology 2010; 125: 419-23
Clinical predictors for biphasic reactions in children presenting with anaphylaxisMehr S, Liew WK, Tey D, Tang MLKClinical Et Experimental Allergy 2009; 39: 1390-96
Anaphylaxis: Recent advances in assessment and treatment Simons FEJ All Clin Imm 2009; 124: 625-36
ReferencesPredictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase – a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom HypersensitivityRueff F, Przbyilla B, Bilo MB et alJ Allergy Clin Immunology 2009; 124: 1047-54
Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levelsBonadonna P, Perbellini O, Passalacqua G et alJ Allergy Clin Immunology 2009; 123: 680-86
Anaphylaxis in the community: Learning from the survivorsSimons FER, Clark S, Camargo CAJ Allergy Clin Immunology 2009; 124: 301-6
Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy OrganizationKemp SF, Lockey RF, Simons FER on behalf of the World Allergy Organization ad hoc Committee on Epinephrine in AnaphylaxisAllergy 2008; 63: 1061-70
References
Paediatric anaphylaxis: a 5 year retrospective review
de Silva IL, Mehr SS, Tey D, Tang MLK
Allergy 2008; 63: 1071-76
Paediatric allergic reactions in the emergency department: a review
Melville N, Beattie T
Emerg Med J 2008; 655-58
Management of Anaphylaxis in Children
Liberman DB, Teach SJ
Pediatric Emergency Care 2008; 24: 861-69
Prevention and treatment of anaphylaxis
Tang MLK, Kang LW
Paediatrics and Child Health Journal (UK) 2008; 18(7); 309-16
References
Incidence and characteristics of biphasic anaphylaxis: a prospective
evaluation of 103 patients
Ellis AK, Day JH
Ann Allergy, Asthma & Immunol 2007; 98:64-69
Self-injectable Epinephrine for First-Aid Management of Anaphylaxis
Sicherer SS, Simons FER, and the Section on Allergy and Immunology
Pediatrics 2007; 119: 638-46
Paediatric emergency department anaphylaxis different patterns from adults
Braganza SC, Acworth JP, McKinnon DRL, Peake JE, Brown AFT
Arch Dis Child 2006; 91: 159-63
Anaphylactic reactions children – a questionnaire-based survey in Germany
Mehl A, Wahn U, Niggeman B
Allergy 2005; 1440-44