CHILDHOOD ANAPHYLAXIS: NEW DEVELOPMENTS IN DIAGNOSIS AND TREATMENT

CHILDHOOD_ANAPHYLAXIS_NEW_DEVELOPMENTS _IN_DIAGNOSIS_AND_TREATMENT_kapak

PERIOPERATIVE ANAPHYLAXIS

Emine Ülgen1 Handan Duman Şenol2

1Ege University, Faculty of Medicine Department of Pediatric Immunology and Allergic Diseases, İzmir, Türkiye
2Ege University, Faculty of Medicine Department of Pediatric Immunology and Allergic Diseases, İzmir, Türkiye

Ülgen E, Duman Şenol H. Perioperative Anaphylaxis. In: Harmancı K, editor. Childhood Anaphylaxis: New Developments in Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.133-145.

ABSTRACT

Perioperative anaphylaxis is a life-threatening systemic allergic reaction that occurs during anesthesia. It is rare, but the risk of morbidity or mortality is higher than other anaphylaxis. Reactions usually occur during anesthesia induction with immunoglobulin E and immunoglobulin G-mediated immune responses. Simultaneous administration of multiple drugs during surgery, use of drugs with potent effects and the presence of multiple factors in the perioperative setting that cause hypersensitivity cause difficulties in diagnosis and management. Anaphylaxis should be considered and excluded in the presence of ventilation difficulty and resistant hypotension because the patient’s skin findings cannot be observed during surgery. Management includes stabilization of the patient, differential diagnosis of the reaction, determination of the possible responsible drug, and determination of drugs that can be administered safely. The basis of acute treatment in perioperative anaphylaxis is the administration of intravenous epinephrine, fluid replacement, and stopping the infusion of other drugs being administered. It is essential for the evaluation to determine all exposures in order, including antibiotics, neuromuscular blocking agents, opioids, sedative agents, disinfectants, latex and dyes, and to select appropriate tests. Tryptase measurement is commonly used to evaluate anaphylaxis, while skin prick tests and intradermal tests are used to determine the agent causing the reaction. Allergen tests should be performed at least 4-6 weeks after anaphylaxis. Intradermal tests should not be performed if skin prick tests are positive. When skin prick tests are negative, drugs are diluted to low concentrations such as 1:1,000, 1:10,000 and intradermal tests are performed. When the agent that may cause the reaction cannot be determined, it is recommended that patients be re-evaluated after 2-3 months since the positive predictive values of the tests are 50-60%. Patients should be evaluated for mast cell diseases if skin tests are negative again. The aim is to identify the causative drug and other drugs that may cross-react, then determine alternative drugs that can be used, and ensure safe anesthesia in subsequent operations. Collaboration between the allergy, anesthesiology and surgical teams is essential for appropriately managing these patients during the reaction, post-event evaluation and preparation for subsequent operations.

Keywords: Anesthesia; Drug allergies; Perioperative anaphylaxis; Neuromuscular blocking agents; Sugammadex; Local anesthetics; Hypnotic agents

Referanslar

  1. Manian DV, Volcheck GW. Perioperative Anaphylaxis: Evaluation and Management. Clin Rev Allergy Immunol [Internet]. 2022;62(3):383-99. [Crossref]  [PubMed]
  2. Khaleva E, Franz A, Garvey LH, Jay N, Ylescupidez A, Bahnson HT, et al. Perioperative anaphylaxis in children: Etiology, time sequence, and patterns of clinical reactivity. Pediatr Allergy Immunol. 2020;31(1):85-94. [Crossref]  [PubMed]
  3. Laguna JJ, Archilla J, Doña I, Corominas M, Gastaminza G, Mayorga C, et al. Practical guidelines for perioperative hypersensitivity reactions. J Investig Allergol Clin Immunol. 2018;28(4):216-32. [Crossref]  [PubMed]
  4. Pumphrey RSH. Lessons for management of anaphy laxis from a study of fatal reactions. Clin Exp Allergy. 2000;30(8):1144-50. [Crossref]  [PubMed]
  5. Volcheck GW, Hepner DL. Identification and Management of Perioperative Anaphylaxis. J Allergy Clin Immunol Pract [Internet]. 2019;7(7):2134-42. [Crossref]  [PubMed]
  6. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. [Crossref]  [PubMed]
  7. Pouessel G, Tacquard C, Tanno LK, Mertes PM, Lezmi G. Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps. Clin Exp Allergy. 2024;54(1):11-20. [Crossref]  [PubMed]
  8. Wakimoto M, Miller R, Kim SS, Uffman JC, NafiuS OO, Tobias JD, et al. Perioperative anaphylaxis in children: A report from the Wake-Up Safe collaborative. Paediatr Anaesth. 2021;31(2):205-12. [Crossref]  [PubMed]
  9. Habre W, Disma N, Virag K, Becke K, Hansen TG, Jöhr M, et al. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe. Lancet Respir Med [Internet]. 2017;5(5):412-25. [Crossref]  [PubMed]
  10. Orhan F, Canitez Y, Bakirtas A, Yilmaz O, Boz AB, Can D, et al. Anaphylaxis in Turkish children: A multi-centre, retrospective, case study. Clin Exp Allergy. 2011;41(12):1767-76. [Crossref]  [PubMed]
  11. Karaatmaca B, Sahiner UM, Sekerel BE, Soyer O. Perioperative hypersensitivity reactions during childhood and outcomes of subsequent anesthesia. Paediatr Anaesth. 2021;31(4):436-43. [Crossref]  [PubMed]
  12. Mertes PM, Volcheck GW, Garvey LH, Takazawa T, Platt PR, Guttormsen AB, et al. Epidemiology of perioperative anaphylaxis. Presse Med. 2016;45(9):758-67. [Crossref]  [PubMed]
  13. Garvey LH, Ebo DG, Mertes PM, Dewachter P, Garcez T, Kopac P, et al. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions. Allergy Eur J Allergy Clin Immunol. 2019;74(10):1872-84. [Crossref]  [PubMed]
  14. McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature [Internet]. 2015;519(7542):237-41. [Crossref]  [PubMed]  [PMC]
  15. Mertes PM, Alla F, Tréchot P, Auroy Y, Jougla E, Cottineau C, et al. Anaphylaxis during anesthesia in France: An 8-year national survey. J Allergy Clin Immunol. 2011 Aug 1;128(2):366-73. [Crossref]  [PubMed]
  16. Ewan PW, Dugué P, Mirakian R, Dixon TA, Harper JN, Nasser SM. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin Exp Allergy. 2010;40(1):15-31. [Crossref]  [PubMed]
  17. Qi Z, Cheng Y, Su Y, Qiao Y, Zhang J, Yang J jun, et al. Clinical variables and genetic variants associated with perioperative anaphylaxis in Chinese Han population: A pilot study. World Allergy Organ J [Internet]. 2024;17(1):100854. [Crossref]  [PubMed]  [PMC]
  18. Mori F, Saretta F, Riscassi S, Caimmi S, Bottau P, Liotti L, et al. Risk factors for drug hypersensitivity reactions in children. Ital J Pediatr [Internet]. 2024;50(1):1-10. [Crossref]  [PubMed]  [PMC]
  19. Dhopeshwarkar N, Sheikh A, Doan R, Topaz M, Bates DW, Blumenthal KG, et al. Drug-Induced Anaphylaxis Documented in Electronic Health Records. J Allergy Clin Immunol Pract. 2019;7(1):103-11. [Crossref]  [PubMed]  [PMC]
  20. Kroigaard M, Garvey LH, Gillberg L, Johansson SGO, Mosbech H, Florvaag E, et al. Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia. Acta Anaesthesiol Scand. 2007;51(6):655-70. [Crossref]  [PubMed]
  21. Mertes PM, Malinovsky JM, Jouffroy L, Aberer W, Terreehorst I, Brockow K, et al. Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice. J Investig Allergol Clin Immunol. 2011;21(6):442-53.
  22. Harboe T, Guttormsen AB, Irgens A, Dybendal T, Florvaag E. Anaphylaxis during Anesthesia in Norway. Anesthesiology. 2005;102(5):897-903. [Crossref]  [PubMed]
  23. Tacquard C, Collange O, Gomis P, Malinovsky JM, Petitpain N, Demoly P, et al. Anaesthetic hypersensitivity reactions in France between 2011 and 2012: the 10th GERAP epidemiologic survey. Acta Anaesthesiol Scand [Internet]. 2017;61(3):290-9. [Crossref]  [PubMed]
  24. Ebo DG, Van Gasse AL, Decuyper II, Uyttebroek A, Sermeus LA, Elst J, et al. Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018. J Allergy Clin Immunol Pract. 2019;7(7):2194-2204.e7. [Crossref]  [PubMed]
  25. Kuhlen JL, Camargo CA, Balekian DS, Blumenthal KG, Guyer A, Morris T, et al. Antibiotics Are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions. 2016 [cited 2025 Feb 16]. [Crossref]  [PubMed]  [PMC]
  26. Baldo BA, Fisher MM, Pham NH. On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: An immunochemical perspective. Clin Exp Allergy. 2009;39(3):325-44. [Crossref]  [PubMed]
  27. Harboe T, Johansson SGO, Florvaag E, Öman H. Pholcodine exposure raises serum IgE in patients with previous anaphylaxis to neuromuscular blocking agents. Allergy Eur J Allergy Clin Immunol. 2007;62(12):1445-50. [Crossref]  [PubMed]
  28. Leynadier F, Dry J. Anaphylaxis to muscle-relaxant drugs: Study of cross-reactivity by skin tests. Int Arch Allergy Immunol. 1991;94(1-4):349-53. [Crossref]  [PubMed]
  29. Pitlick MM, Volcheck GW. Perioperative Anaphylaxis. Immunol Allergy Clin North Am [Internet]. 2022;42(1):145-59. [Crossref]  [PubMed]
  30. Sadleir PHM, Clarke RC, Bunning DL, Platt PR, Harboe T, Ülgen, Duman Şenol Perioperative Anaphylaxis Guttormsen AB, et al. Anaphylaxis to Neuromuscular-blocking Drugs. Anesthesiology. 2015;110(6):981-7. [Crossref]  [PubMed]
  31. Mertes PM, Volcheck GW. Anaphylaxis to Neuromuscular-blocking Drugs. Anesthesiology. 2015;122(1):5-7. Mertes PM, Volcheck GW. Anaphylaxis to Neuromuscular-blocking Drugs. Anesthesiology. 2015;122(1):5-7. [Crossref]  [PubMed]
  32. Harper NJN, Cook TM, Garcez T, Farmer L, Floss K, Marinho S, et al. Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6). Br J Anaesth [Internet]. 2018;121(1):159-71. [Crossref]  [PubMed]
  33. Lobera T, Audicana MT, Pozo MD, Blasco A, Fernández E, Cañada P, et al. Study of hypersensitivity reactions and anaphylaxis during anesthesia in Spain (Journal of Investigational Allegology and Clinical Immunology (2008) 18, 5, (350356)). J Investig Allergol Clin Immunol. 2008;18(6):495.
  34. Gonzalez-Estrada A, Pien LC, Zell K, Wang XF, Lang DM. Antibiotics are an important identifiable cause of perioperative anaphylaxis in the United States. J Allergy Clin Immunol Pract [Internet]. 2015;3(1):101-105.e1. [Crossref]  [PubMed]
  35. Azamgarhi T, Shah A, Warren S. Teicoplanin anaphylaxis associated with surgical prophylaxis. Br J Clin Pharmacol. 2018;84(5):1038-44. [Crossref]  [PubMed]  [PMC]
  36. Kayode OS, Rutkowski K, Haque R, Till SJ, Siew LQC. Teicoplanin hypersensitivity in perioperative anaphylaxis. J Allergy Clin Immunol Pract [Internet]. 2020;8(6):2110-3. [Crossref]  [PubMed]
  37. Parisi CAS, Kelly KJ, Ansotegui IJ, Gonzalez-Díaz SN, Bilò MB, Cardona V, et al. Update on latex allergy: New insights into an old problem. World Allergy Organ J [Internet]. 2021;14(8):100569. [Crossref]  [PubMed]  [PMC]
  38. Arasi S, Barni S, Caminiti L, Castagnoli R, Giovannini M, Liotti L, et al. Latex Allergy in Children. J Clin Med. 2024;13(1):1-22. [Crossref]  [PubMed]  [PMC]
  39. Parisi CAS, Petriz NA, Busaniche JN. Prevalence of latex allergy in a population of patients diagnosed with myelomeningocele. Arch Argent Pediatr. 2016;114(1):30-5. [Crossref]
  40. Blaabjerg MSB, Andersen KE, Bindslev-Jensen C, Mortz CG. Decrease in the rate of sensitization and clinical allergy to natural rubber latex. Contact Dermatitis. 2015;73(1):21-8. [Crossref]  [PubMed]
  41. Komenaka IK, Bauer VP, Schnabel FR, Horowitz E, Joseph KA, Ditkoff BA, et al. Allergic reactions to isosulfan blue in sentinel lymph node mapping. Breast J. 2005;11(1):70-2. [Crossref]  [PubMed]
  42. Sajan A, Griepp DW, Hakmi H, Sohail AH, Hunt J, Wolf M, et al. Isosulfan Blue and Anaphylaxis. Ochsner J. 2021;21(4):419-24. [Crossref]  [PubMed]  [PMC]
  43. Savic L, Savic S, Hopkins PM. Anaphylaxis to sugammadex: should we be concerned by the Japanese experience? Br J Anaesth [Internet]. 2020;124(4):370-2. [Crossref]  [PubMed]
  44. Suzuki Y, Liu S, Yamashita N, Yamaguchi N, Takasaki Y, Yorozuya T, et al. Perioperative Anaphylaxis in Japanese Secondary Care Institutions: Incidence, Causes, and the Imperative for Improved Diagnostic Practices. Cureus. 2024;16(4). [Crossref]
  45. Stepanovic B, Sommerfield D, Lucas M, von Ungern-Sternberg BS. An update on allergy and anaphylaxis in pediatric anesthesia. Paediatr Anaesth. 2019;29(9):892-900. [Crossref]  [PubMed]
  46. Molina-Infante J, Arias A, Vara-Brenes D, Prados-Manzano R, Gonzalez-Cervera J, Alvarado-Arenas M, et al. Propofol administration is safe in adult eosinophilic esophagitis patients sensitized to egg, soy, or peanut. Allergy Eur J Allergy Clin Immunol. 2014;69(3):388-94. [Crossref]  [PubMed]
  47. Harper NJN, Dixon T, Dugué, Edgar DM, Fay A, Gooi HC, et al. Guidelines suspected anaphylactic reactions associated with anaesthesia [Internet]. Anaesthesia. 2009:64;199-211. [Crossref]  [PubMed]  [PMC]
  48. Mertes PM, Laxenaire MC, Alla F. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology. 2003;99(3):536-45. [Crossref]  [PubMed]
  49. Levy JH, Adkinson NF. Anaphylaxis during cardiac surgery: Implications for clinicians. Anesth Analg. 2008;106(2):392-403. [Crossref]  [PubMed]
  50. Beierlein W, Scheule AM, Dietrich W, Ziemer G. Forty years of clinical aprotinin use: A review of 124 hypersensitivity reactions. Ann Thorac Surg. 2005;79(2):741-8. [Crossref]  [PubMed]
  51. Mertes PM, Ebo DG, Garcez T, Rose M, Sabato V, Takazawa T, et al. Comparative epidemiology of suspected perioperative hypersensitivity reactions. Br J Anaesth. 2019;123(1):e16-28. [Crossref]  [PubMed]
  52. Mertes PM, Bazin A, Alla F, Bienvenu J, Caldani C, Lamy B, Ülgen, Duman Şenol Perioperative Anaphylaxis et al. Hypersensitivity reactions to blood components: Document issued by the allergy committee of the French medicines and healthcare products regulatory agency. J Investig Allergol Clin Immunol. 2011;21(3):171-8.
  53. Jiang S, Tang M. Allergy to Local Anesthetics is a Rarity: Review of Diagnostics and Strategies for Clinical Management. Clin Rev Allergy Immunol [Internet]. 2023;64(2):193-205. [Crossref]  [PubMed]
  54. Calderon AL, Diot N, Benatir F, Christin F, Hautin É, Truc C, et al. Immediate allergic cross-reactivity to levobupivacaine and ropivacaine. Anaesthesia. 2013;68(2):203-5. [Crossref]  [PubMed]
  55. Platzgummer S, Bizzaro N, Bilò MB, Pravettoni V, Cecchi L, Sargentini V, et al. Recommendations for the use of tryptase in the diagnosis of anaphylaxis and clonal mastcell disorders. Eur Ann Allergy Clin Immunol. 2020;52(2):51-61. [Crossref]  [PubMed]
  56. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-25. [Crossref]  [PubMed]  [PMC]
  57. Schwartz LB, Irani AMA. Serum tryptase and the laboratory diagnosis of systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14(3):641-57. [Crossref]  [PubMed]
  58. Berroa F, Lafuente A, Javaloyes G, Ferrer M, Moncada R, Goikoetxea MJ, et al. The usefulness of plasma histamine and different tryptase cut-off points in the diagnosis of peranaesthetic hypersensitivity reactions. Clin Exp Allergy. 2014;44(2):270-7. [Crossref]  [PubMed]
  59. Ebo DG, Bridts CH, Mertens CH, Hagendorens MM, Stevens WJ, De Clerck LS. Analyzing histamine release by flow cytometry (HistaFlow): A novel instrument to study the degranulation patterns of basophils. J Immunol Methods [Internet]. 2012;375(1-2):30-8. [Crossref]  [PubMed]
  60. Fisher MM, Jones K, Rose M. Follow-up after anaesthetic anaphylaxis. Acta Anaesthesiol Scand. 2011;55(1):99-103. [Crossref]  [PubMed]
  61. Volcheck GW, Mertes PM. Local and general anesthetics immediate hypersensitivity reactions. Immunol Allergy Clin North Am. 2014;34(3):525-46. [Crossref]  [PubMed]
  62. Brockow K. Dilemmas of allergy diagnosis in perioperative anaphylaxis. Allergy Eur J Allergy Clin Immunol. 2014;69(10):1265-6. [Crossref]  [PubMed]
  63. Garvey LH, Dewachter P, Hepner DL, Mertes PM, Voltolini S, Clarke R, et al. Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations. Br J Anaesth. 2019;123(1):e50-64. [Crossref]  [PubMed]
  64. Heytman M, Rainbird A. Use of alpha-agonists for management of anaphylaxis occurring under anaesthesia: Case studies and review. Anaesthesia. 2004;59(12):1210-5. [Crossref]  [PubMed]
  65. Dewachter P, Savic L. Perioperative anaphylaxis: pathophysiology, clinical presentation and management. BJA Educ [Internet]. 2019;19(10):313-20. [Crossref]  [PubMed]  [PMC]
  66. Guyer AC, Saff RR, Conroy M, Blumenthal KG, Camargo CA, Long AA, et al. Comprehensive allergy evaluation is useful in the subsequent care of patients with drug hypersensitivity reactions during anesthesia. J Allergy Clin Immunol Pract [Internet]. 2015;3(1):94-100. [Crossref]  [PubMed]
  67. Kroigaard M, Garvey LH, Gillberg L, Johansson SGO, Mosbech H, Florvaag E, et al. Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia. Acta Anaesthesiol Scand [Internet]. 2007;51(6):655-70. [Crossref]  [PubMed]