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Guidelines for the management of anaphylaxis

Speaker: F Estelle R Simons

29 September 2012


GUIDELINES FOR THE MANAGEMENT OF ANAPHYLAXIS

F. Estelle R. Simons MD, FRCPC, FAAP, FACAAI, FAAAAI Professor Department of Pediatrics & Child Health Department of Immunology The University of Manitoba


DISCLOSURE F. Estelle R. Simons MD, FRCPC, FAAP, FACAAI, FAAAAI

NIH/NIAID Food Allergy Expert Panel

Food Allergy and Anaphylaxis Network Medical Advisory Board ALK-Abello, Mylan, and Sanofi Medical Advisory Boards Contributing Editor, The Medical Letter Anaphylaxis Section Editor, UpToDate


OBJECTIVES …to review the World Allergy Organization (WAO) Anaphylaxis Guidelines (2011) and the WAO Anaphylaxis Guidelines Update (2012)…

…to focus on management of anaphylaxis in healthcare settings and self-management in the community…


ACKNOWLEDGMENTS WAO ANAPHYLAXIS SPECIAL COMMITTEE 2009-2013 F E R Simons MD, Chair

M Sanchez-Borges MD, Co-Chair

LRF Ardusso MD

R F Lockey MD

M B Bilo MD

J Ring MD PhD

V Dimov MD

G E Senna MD

M Ebisawa MD

A Sheikh MD

Y M El-Gamal MD PhD

B Y- H Thong MD

D K Ledford MD

M Worm MD

ALL CONTRIBUTORS IN THE WAO MEMBER SOCIETIES G W Canonica MD J Schaffer


WAO GUIDELINES: 2011 FOR ASSESSMENT AND MANAGEMENT OF ANAPHYLAXIS • developed by allergists in WAO member societies - no corporate funding • for use in the 64% of WAO member countries without guidelines • for use as a resource in the 36% of WAO countries with guidelines • goal: to  awareness of current concepts of anaphylaxis

- “serious allergic reaction, rapid in onset, may be fatal”

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


WAO ANAPHYLAXIS GUIDELINES: 2011 UNIQUE ASPECTS • preceded by global assessment of availability of essentials • provide a perspective on risk factors, mechanisms, triggers • emphasize prompt clinical diagnosis and prompt initial treatment • written concisely (22 pages, 150 references) • contain illustrations that highlight key concepts in the text

• propose a global agenda for anaphylaxis research • describe plans for updates and for global dissemination

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


PATIENTS AT ↑ RISK OF FATAL ANAPHYLAXIS

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


MECHANISMS AND ETIOLOGY

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


VALIDATED CLINICAL CRITERIA: DIAGNOSIS

Simons FER et al for WAO, J Allergy Clin Immunol 2011;127:587-593e22 Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7 Campbell RL et al. J Allergy Clin Immunol 2012;128:748-52 Harduar-Morano L et al. J Allergy Clin Immunol 2010;126:98-104


PROMPT INITIAL TREATMENT

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


PROMPT INITIAL TREATMENT

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


“HAVE AN ANAPHYLAXIS PROTOCOL” • a protocol was implemented in a pediatric emergency department • anaphylaxis outcomes were compared “before” versus “after” • implementation of the protocol led to: -  epinephrine injection (in 27% vs 57.6%) (p = 0.012) -  admissions to the observation unit (p = 0.003) -  length of stay in the observation unit (p = 0.005)

Arrobarren I et al. Pediatr Allergy Immunol 2011;22:708-14


PROMPT INJECTION OF EPINEPHRINE • life-saving effects are time and concentration dependent • given promptly, in an optimal dose, epinephrine:

-  release of mediators of inflammation - α-1 agonist-induced vasoconstriction predominates • given late, or in a low dose, it has paradoxical effects: -  release of mediators of inflammation - β-2 agonist-induced vasodilation predominates

• “precious minutes lost early on cannot be regained”

Simons FER et al for WAO, J Allergy Clin Immunol 2011;127:587-593e22


EPINEPHRINE DECREASES MEDIATOR RELEASE “BRIEF WINDOW OF TIME” • PAF is a potent mediator of human anaphylaxis •  serum PAF levels correlate with  anaphylaxis severity • in human vascular smooth muscle cells, PAF  PGE2 release - this effect was time and concentration dependent • to  PGE2 release, early addition of epinephrine was essential

• epinephrine was less effective when added late PAF, platelet-activating factor; PGE2, prostaglandin E2

Vadas P, Perelman B. J Allergy Clin Immunol 2012;129:1329-33


EPINEPHRINE DECREASES MEDIATOR RELEASE “BRIEF WINDOW OF TIME”

Vadas P, Perelman B. J Allergy Clin Immunol 2012;129:1329-33


EPINEPHRINE: 1st-LINE MEDICATION • epinephrine is the recommended treatment for anaphylaxis • there can be uncertainties in making this clinical diagnosis • epinephrine injection can consequently be delayed

• of 270 patients with anaphylaxis during anesthesia - only 46% received epinephrine - this increased to 83% in those with shock or cardiac arrest

Garvey LH, Belhage B, Kroigaard M, et al. Anesthesiology 2011;115:111-6


CARDIAC MAST CELLS:THE ENEMY WITHIN ACUTE CORONARY SYNDROME AND ANAPHYLAXIS • play a role in ischemic heart disease and in anaphylaxis • mediators (histamine, PAF, LTC4) lead to coronary artery spasm • ACS occurs in anaphylaxis even if no epinephrine is given • ACS occurs in children with anaphylaxis and no heart disease • ACS occurs when anaphylaxis unmasks subclinical CAD

• ACS occurs after epinephrine overdose (especially IV) ACS, acute coronary syndromes; CAD, coronary artery disease

Yaegashi T, Nakamura Y, Sakagami S, et al. Intern Med 2011;50:451-4 Valla M, Moulin F, Angioi M, et al. Int J Cardiol 2011;148:e63-65 Scheiba N, Viedt-Suelmann C, Schakel K. Acta Derm Venereol 2011;91:593-4 Winogradow J, Geppert G, Reinhard W, et al. Int J Cardiol 2011;147:309-11


SELF-TREATMENT IN COMMUNITY SETTINGS

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22


FAILURE TO PRESCRIBE EPINEPHRINE FOR THOSE AT RISK OF ANAPHYLAXIS IN THE COMMUNITY • “alarming” under-prescription of EAI in infants, children, teens • also an issue in patients older than 50 yrs discharged from ED • implementing an anaphylaxis protocol  EAI prescribing - rate 6.7% before implementation vs 54.5% after (p = 0.005)

EAI, epinephrine autoinjector; ED, emergency department

Flokstra-de Blok BM et al. Pediatr Allergy Immunol 2011;22:374-7 Campbell RL et al. Ann Allergy Asthma Immunol 2011;106:401-6 Arrobarren I et al. Pediatr Allergy Immunol 2011;22:708-14


FAILURE TO INJECT EPINEPHRINE FOR ANAPHYLAXIS IN COMMUNITY SETTINGS • in a study of 969 children and teens, EAIs were seldom used - despite respiratory symptoms or loss of consciousness • in a qualitative study, most teens carried EAIs, but few used it • in another study, children and teens actually self-injected - using the EAI did not increase their anxiety

EAI, epinephrine autoinjector

Noimark L, Wales J, Du Toit G, et al. Clin Exp Allergy 2012;42:284-92 Gallagher M, Worth S, et al. Clin Exp Allergy 2011;41:869-77 Hellstrom A, Erikkson K, Efraimsson EO, et al. Acta Paediatr 2011;100:e34-5.


NOVEL EPINEPHRINE AUTOINJECTORS • autoinjectors with improved design are now available - needle protection after injection • another new autoinjector has been approved by the FDA

- human factors engineering and intuitive design - electronic voice prompt system - needle protection before and after injection • failure to recognize anaphylaxis remains a barrier to EAI use

Edwards ES et al. J Allergy Clin Immunol 2012;129:AB179


WAO ANAPHYLAXIS GUIDELINES: 2011 GLOBAL AGENDA FOR ANAPHYLAXIS RESEARCH •√ develop instruments to quantify patient risk factors for fatality •√ validate the clinical criteria for diagnosis • develop rapid in vitro tests to confirm the clinical diagnosis •√ develop in vitro tests to identify clinical risk of recurrences •√ accelerate research to prevent recurrences in those at risk

•√ accelerate epinephrine research (epidemiology, pharmacology) •√ perform randomized controlled trials of 2nd-line interventions √ good or excellent progress in these areas of research in 2011-2012

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22 Simons FER et al for the WAO, Curr Opinion Allergy Clin Immunol 2012;12:389-99


WAO ANAPHYLAXIS GUIDELINES: 2011-12 GLOBAL DISSEMINATION • Journal of Allergy and Clinical Immunology (open access paper) • WAO Journal publication: member society website downloads • summary posters and pocket cards translated into 10 languages • presented at meetings and congresses; med school courses • used in other specialties (eg sports medicine/2012 Olympic Games)

• 2012 update is published; 2013 update is being prepared • smart phone apps will be developed in the future

Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22 Simons FER et al for the WAO, Curr Opinion Allergy Clin Immunol 2012;12:389-99


Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22 Simons FER et al for the WAO, Curr Opinion Allergy Clin Immunol 2012;12:389-99


Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22 Simons FER et al for the WAO, Curr Opinion Allergy Clin Immunol 2012;12:389-99


Simons FER et al for the WAO, J Allergy Clin Immunol 2011;127:587-593e22 Simons FER et al for the WAO, Curr Opinion Allergy Clin Immunol 2012;12:389-99


THANK YOU FOR YOUR ATTENTION…

F Estelle R Simons