2. Objectives To emphasize the importance of not missing the diagnosis and not under-reporting the events To remind our department about the available anaphylaxis investigation protocol and help implement it in sites that don’t currently have it available To step back and analyze the efficiency of our protocol. How can we improve it?

3. Structure 2 Clinical cases Considerations in anesthesia Definition, clinical signs, epidemiology and common causative agents Diagnostic tests New information on specific drugs ANAPHYLAXIS INVESTIGATION - how others do it and where we can improve

4. Clinical case 1 38 year old male Elective laparoscopic cholecystectomy GERD, mild asthma, obese No previous GA No known allergies

5. Clinical Case 1 Midazolam, Fentanyl, Propofol, Lidocaine, Rocuronium, Ancef 5 min: profound hypotension No rash, no wheeze Good response to Epinephrine

6. Clinical Case 1 INVESTIGATIONS AND FOLLOW UP  Tryptase (19mcg/L) Allergy consult 6/52 later ? False positive intradermal test for Rocuronium

7. Clinical Case 2 25 year old male Pinning of fractured metacarpal Healthy No known allergies IV started Monitors attached

8. Clinical Case 2 Sudden onset tachycardia  LOC Pruritis Empty bag of Cefazolin Rash Severe hypotension Good response to epinephrine and IV fluid

9. Clinical Case 2 FOLLOW UP Blood work according to protocol Referral for allergy consult RESULTS  Tryptase (46mcg/L) No consult note on netcare

10. Anaphylaxis in Anesthesia - usually not a “open-and-shut case” multiple drugs common cardiovascular responses to anesthesia are also manifestations of anaphylaxis position changes insufflation underlying systemic disease might mask the presence of anaphylaxis no rash/patient covered delayed reactions

11. Anesthesia and Anaphylaxis anesthetic drugs antibiotics blood products heparin polypeptides (latex, protamine) IV volume expanders antiseptics (chlorhexidine and betadine)

12. Anaphylaxis - Definition Classic: Pathophysiological definition Now: Clinical Any severe systemic hypersensitivity reaction of rapid onset, which may cause death or other adverse outcomes “Anaphylactoid” - outdated

13. Clinical manifestations of Anaphylaxis in Anesthesia

14. Epidemiology 1 in 10 000 - 20 000 anesthetic procedures France: 1 in 13 000, 1 in 6 500 with NMBA Mortality: 3.4% Edmonton: 31 cases over 7 years 20 000 anesthetics/year 1 in 5 000

15. Common causative agents Antibiotics NMBA’s Latex Geographical variation

16. Common causative agents - NMBA’s Reaction without previous exposure Quaternary ammonium ions Commonly used chemicals might sensitize patients Pholcodine in France and Norway Cross-reactivity 60 - 70%

17. How to diagnose perioperative anaphylaxis

18. SECOND EVIDENCE (Biological) PRIMARY investigations - histamine - tryptase (initial and baseline) SECONDARY investigations - IgE assays

19. How to diagnose perioperative anaphylaxis IgE assay specific for succinylcholine The other NMBA: markers with similar epitopes are used PAPPC vs Allergen c261 Pholcodine

20. How to Diagnose Anaphylaxis THE GOLD STANDARD THIRD EVIDENCE: SKIN TESTS Detects IgE mediated reactions Important tool to identify and avoid culprit substance 6 weeks before testing ALL drugs and substances Positive and negative controls

22. Propofol and egg allergy

23. Retrospective chart review 42 patients with egg allergy received Propofol 1 allergic reaction in a boy with history of anaphylaxis to eggs

24. Antibiotics and cross-reactivity “Penicillin allergy” is common Cephalosporin antibiotics are popular with surgeons How likely is cross-reactivity? Clinical practice based on old case reports More recent publications

25. Antibiotics and Cross-reactivity What if my patient really needs a ß-lactam antibiotic? 85% of “penicillin allergic patients” have negative skin tests. Caution: history of anaphylaxis Graded dose escalation

26. Opioids True allergy is rare Side effect v.s. Pseudo-allergy v.s. Real allergy Cross reactivity amongst different structural classes Thorough allergy history before analgesic plan

27. The chemical classes of Opioids PHENYLPIPERIDINES: miperidine, fentanyl, sufentanil, remifentanil DIPHENYLHEPTANES: methadone, propoxyphene MORPHINE GROUP: morphine, codeine, hydrocodone, oxycodone, oxymorphone, hydromorphone, nalbuphine, butorphanol, levophanol, pentazocine

28. Latex and food allergy

29. NMBA’s - cross reactivity IgE antibodies to quatarnary ammonium ions Succinylcholine > Benzylisoquinolinium compounds > Aminosteroids 60 - 70% cross-sensitivity

30. Local- and Inhaled Anesthetics Local anesthetics: esters > amides Type IV reactions Inhaled anesthetics: no reports of anaphylaxis

31. Anaphylaxis Investigation Australia, France and England have country wide guidelines Edmonton: 1 of 2 centers in Canada with a formal protocol No need to reinvent the wheel CAS for country wide guidelines

34. The French Guidelines 2005 French Society for Anesthesia and Intensive care

35. French Guidelines RESPONSIBILITIES OF THE ANESTHETIST: Initiate investigation Inform patient Report the event

36. French Guidelines: follow-up Written report from allergist Conclusion, recommendations Document to patient Bracelet, medic-alert warning

37. Levels of anaphylaxis follow-up 1) Anesthesia Referral for allergy consultation - complete history is important Informing patient “Allergy letter” to patient and family doc Who should be responsible for follow-up?

38. Levels of anaphylaxis follow-up 1) Anesthesia STATISTICS: 31 cases 10 allergy consultations 6 confirmed allergies - 3 to latex - 2 to Ancef - 1 to Bacitracin

39. Levels of anaphylaxis follow-up 2) Allergologist Faxed consult, no closed-loop communication Contacting patients Availability of report Closer collaboration needed

40. Levels of Anaphylaxis follow-up 3) The Laboratory Various laboratories involved Results hard to find

41. Conclusions It is important to diagnose and follow-up on peri-operative allergic events Revision of current protocol and possible nationwide guidelines would might be a realistic aim for the future Better collaboration between Anesthesia and Allergology is needed Patients need to leave the hospital with a letter and information about their potential allergy, which should be updated as information becomes available

42. THANK YOU & QUESTIONS Dr J Lujic Dr E Bishop

43. References Levy JH, Adkinson NF. Anaphylaxis During Cardiac Surgery: Implications for Clinicians. Anesthesia Analgesia 2008;106:392- 403 Hepner DL, Castells MC. Anaphylaxis During the Perioperative Period. Anesthesia Analgesia 2003;97:1381-95 Murphy A, Campbell E, Baines D, Mehr S. Allergic Reactions to Propofol in Egg-Allergic Children. Society for Pediatric Anesthesia, Anesthesia Analgesia 2011;113:140-4 Gurrieri C, Weingarten TB, Martin DP et.al. Allergic Reactions During Anesthesia at a Large United States Referral Center. Anesthesia Analg 2011;113:1202-12 AAGBI Safety Guideline - Suspected Anaphylactic Reactions Associated with Anaesthesia. The Association of Anaesthetists of Great Britain and Ireland. July 2009

44. References Mertes PM, Laxenaire MC, Lienhart A. Reducing the risk of anaphylaxis during anaesthesia: guidelines for clinical practice. J Invest Allergol Clin Immonol 2005; Vol. 15(2): 91-101 Dewachter P, Mouton-Faivre C, Emala CW. Anaphylaxis and Anesthesia, controversies and New Insights. Anesthesiology 2009; 111:1141-50 Analgesic Options for Patients with Allergic-Type Opioid Reactions. Pharmacist’s Letter. February 2006 - volume 22 - Number 220201 ImmunoCAP Allergen c261 Pholcodine. www.immunocapinvitrosight.com. April 2009 www.immunocapinvitrosight.com Fisher MM, Jones K, Rose M. Follow-up after anaesthetic anaphylaxis. Acta Anaesthsiol Scand 2011;55: 99-103