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 ObjectivesOn 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 Perspective1902 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 ReportSamson 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 femalesInfants: hives and vomiting more common

*many had no BP documented on chart2 - 5 years: wheezing, hoarse voice, stridor more

commonUp 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 symptomsNOTE: very little evidence for management exists!

Consensus that epinephrine is medication of choiceSimons 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 glucosebeta – 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 Immunol379 patients with hymenoptera stings11.6% had tryptase levels over 11.4 ng/l

70.5% of these had systemic anaphylaxis34 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 reactionTreatment required Biphasic

reactionUniphasic 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 reactionanaphylactic 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 13.0Time 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 anaphylaxis27% 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 27Shelf Life (months)

12 – 18 12 – 18 21 – 24

Description (with case)Weight (g) 75.5 45.4 28.8Length (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 / observation25% injured area warmed 9% nitroglycerine paste22% injection lidocaine and / or

phentolamine20% other treatments12% 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

ReferencesAnaphylaxis 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 reviewde Silva IL, Mehr SS, Tey D, Tang MLKAllergy 2008; 63: 1071-76

Paediatric allergic reactions in the emergency department: a reviewMelville N, Beattie TEmerg Med J 2008; 655-58

Management of Anaphylaxis in ChildrenLiberman DB, Teach SJPediatric Emergency Care 2008; 24: 861-69

Prevention and treatment of anaphylaxisTang MLK, Kang LWPaediatrics and Child Health Journal (UK) 2008; 18(7); 309-16

ReferencesIncidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patientsEllis AK, Day JHAnn Allergy, Asthma & Immunol 2007; 98:64-69

Self-injectable Epinephrine for First-Aid Management of AnaphylaxisSicherer SS, Simons FER, and the Section on Allergy and ImmunologyPediatrics 2007; 119: 638-46

Paediatric emergency department anaphylaxis different patterns from adultsBraganza SC, Acworth JP, McKinnon DRL, Peake JE, Brown AFTArch Dis Child 2006; 91: 159-63

Anaphylactic reactions children – a questionnaire-based survey in GermanyMehl A, Wahn U, Niggeman BAllergy 2005; 1440-44