Adverse reactions to neuromuscular blocking agents

  • Paul-Michel Mertes
  • Marie Claire Laxenaire
Article

Abstract

Neuromuscular blocking agents (NMBAs) play a predominant role in the incidence of severe adverse reactions occurring during anesthesia. Most hypersensitivity reactions are of immunologic origin (IgE-mediated) or are related to direct stimulation of histamine release. The incidence of IgEmediated hypersensitivity or anaphylaxis is estimated between 1 in 10,000 and 1 in 20,000 anesthesias, and NMBAs represent the most frequently involved substances, with a range of 50% to 70%. Any suspected anaphylactic reaction must be extensively investigated using combined perioperative and postoperative testing. Because of the frequent cross-reactivity observed with muscle relaxants, every available NMBA should be tested. This should help provide documented advice for future administration of anesthesia. There is no demonstrated evidence for systematic preoperative screening in the general population at this time. Other well-known adverse effects have been described, such as the succinylcholine-triggered cytotoxic effects on muscle cells, but these are responsible for characteristic clinical symptoms, which are usually easy to distinguish from anaphylactic reactions

References and Recommended Reading

  1. 1.
    Suspected Anaphylactic Reactions Associated with Anaesthesia. Revised Edition 1995. London: The Association of Anaesthetists of Great Britain and Ireland and The British Society of Allergy and Clinical Immunology; 1995.Google Scholar
  2. 2.
    Reducing the risk of anaphylaxis during anaesthesia: abbreviated text. Ann Fr Anesth Reanim 2002, 21(Suppl 1):7S–23S. The most recent French guidelines concerning management, diagnosis, identification of at-risk groups, and treatment of anaphylaxis during anesthesia are presented.Google Scholar
  3. 3.
    Laxenaire MC: Prévention du risque allergique en anesthésie: recommandations pour la pratique clinique: epidémiologie. Ann Fr Anesth Reanim 2002, 21:38–54.Google Scholar
  4. 4.
    Mertes PM, Laxenaire MC: Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol 2002, 19:240–262.CrossRefPubMedGoogle Scholar
  5. 5.
    Whittington T, Fisher MM: Anaphylactic and anaphylactoid reactions. Clinical Anaesthesiology. B Clin Anaesthesiol 1998, 12:301–323.CrossRefGoogle Scholar
  6. 6.
    Laxenaire MC: Epidémiologie des réactions anaphylactoïdes peranesthésiques. Quatrième enquête multicentrique (juillet 1994-décembre 1996). Ann Fr Anesth Reanim 1999, 18:796–809.PubMedGoogle Scholar
  7. 7.
    Currie M, Webb RK, Williamson JA, et al.: The Australian Incident Monitoring Study. Clinical anaphylaxis: an analysis of 2000 incident reports. Anaesth Intensive Care 1993, 21:621–625.PubMedGoogle Scholar
  8. 8.
    Mitsuhata H, Matsumoto S, Hasegawa J: The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan. Masui 1992, 41:1664–1669.PubMedGoogle Scholar
  9. 9.
    Mertes PM, Alla F, Laxenaire MC: Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999–2000. Anesthesiology 2003, 99:536–545. This study was the largest and most recent report on hypersensitivity reactions during anesthesia, including causative agents, clinical features, and diagnosis, with special emphasis on NMBAs.CrossRefPubMedGoogle Scholar
  10. 10.
    Fisher M, Baldo BA: Anaphylaxis during anaesthesia: current aspects of diagnosis and prevention. Eur J Anaesthesiol 1994, 11:263–284.PubMedGoogle Scholar
  11. 11.
    Laxenaire M, Mertes PM, GERAP: Anaphylaxis during anaesthesia: results of a 2-year survey in France. Br J Anaesth 2001, 21:549–558.CrossRefGoogle Scholar
  12. 12.
    Guttormsen AB: Allergic reactions during anaesthesia: increased attention to the problem in Denmark and Norway. Acta Anaesthesiol Scand 2001, 45:1189–1190.CrossRefPubMedGoogle Scholar
  13. 13.
    Rose M, Fisher M: Rocuronium: high risk for anaphylaxis? Br J Anaesth 2001, 86:678–682.CrossRefPubMedGoogle Scholar
  14. 14.
    Watkins J: Incidence of UK reactions involving rocuronium may simply reflect market use. Br J Anaesth 2001, 87:522.PubMedGoogle Scholar
  15. 15.
    Leynadier F, Dry J: Anaphylaxis to muscle-relaxant drugs: study of cross-reactivity by skin tests. Int Arch Allergy Appl Immunol 1991, 94:349–353.PubMedGoogle Scholar
  16. 16.
    Laxenaire MC, Gastin I, Moneret-Vautrin DA, et al.: Crossreactivity of rocuronium with other neuromuscular blocking agents. Eur J Anaesthesiol Suppl 1995, 11:55–64.PubMedGoogle Scholar
  17. 17.
    Porri F, Lemiere C, Birnbaum J, et al.: Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening. Clin Exp Allergy 1999, 29:72–75.CrossRefPubMedGoogle Scholar
  18. 18.
    Moneret-Vautrin DA, Renaudin JM, Kanny G, et al.: Prospective study of the latent sensitization to muscle relaxants. In Progress in Allergy and Clinical Immunology, vol 4. Edited by Dehling AK, Huerat-Lopez JG. Cancun: Hogrefe and Huber; 1997:361–376.Google Scholar
  19. 19.
    Pichler WJ: T cells in drug allergy. Curr Allergy Asthma Rep 2002, 2:9–15.CrossRefPubMedGoogle Scholar
  20. 20.
    Aubert N, Janaszak M, Laxenaire M, et al.: Dendritic cells present neuromuscular blocking agent related epitopes to T cells from allergic patients [abstract]. Eur J Anaesthesiol 2003, 20:125.Google Scholar
  21. 21.
    Baldo BA, Fisher MM: Substituted ammonium ions as allergenic determinants in drug allergy. Nature 1983, 306:262–264.CrossRefPubMedGoogle Scholar
  22. 22.
    Birnbaum J, Vervloet D: Allergy to muscle relaxants. Clin Rev Allergy 1991, 9:281–293.PubMedGoogle Scholar
  23. 23.
    Baldo BA, Harle DG: Drug allergenic determinants. In Molecular Approaches to the Study of Allergens: Monographs in Allergy, vol 28. Edited by Baldo BA. Basel: Karger; 1990:11–51.Google Scholar
  24. 24.
    Moneret-Vautrin DA, Laxenaire MC: The risk of allergy related to general anaesthesia. Clin Exp Allergy 1993, 23:629–633.CrossRefPubMedGoogle Scholar
  25. 25.
    McManus MC: Neuromuscular blockers in surgery and intensive care, Part 1. Am J Health Syst Pharm 2001, 58:2287–2299.PubMedGoogle Scholar
  26. 26.
    Koppert W, Blunk JA, Petersen LJ, et al.: Different patterns of mast cell activation by muscle relaxants in human skin. Anesthesiology 2001, 95:659–667.CrossRefPubMedGoogle Scholar
  27. 27.
    Hunter JM: New neuromuscular blocking drugs. N Engl J Med 1995, 332:1691–1699.CrossRefPubMedGoogle Scholar
  28. 28.
    Jooste E, Klafter F, Hirshman CA, Emala CW: A mechanism for rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism. Anesthesiology 2003, 98:906–911.CrossRefPubMedGoogle Scholar
  29. 29.
    Stellato C, de Paulis A, Cirillo R, et al.: Heterogeneity of human mast cells and basophils in response to muscle relaxants. Anesthesiology 1991, 74:1078–1086.CrossRefPubMedGoogle Scholar
  30. 30.
    Mertes PM, Laxenaire M: Anaphylaxis during general anaesthesia: Prevention and management. CNS Drugs 2000, 14:115–133.CrossRefGoogle Scholar
  31. 31.
    Laroche D, Lefrancois C, Gerard JL, et al.: Early diagnosis of anaphylactic reactions to neuromuscular blocking drugs. Br J Anaesth 1992, 69:611–614.CrossRefPubMedGoogle Scholar
  32. 32.
    Laroche D, Dubois F, Gérard J, et al.: Radioimmunoassy for plasma histamine: a study of false positive and false negative values. Br J Anaesth 1995, 74:430–437.CrossRefPubMedGoogle Scholar
  33. 33.
    Assem ES: Anaphylactic anaesthetic reactions: the value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone. Anaesthesia 1990, 45:1032–1038.CrossRefPubMedGoogle Scholar
  34. 34.
    Gueant JL, Mata E, Monin B, et al.: Evaluation of a new reactive solid phase for radioimmunoassay of serum specific IgE against muscle relaxant drugs. Allergy 1991, 46:452–458.PubMedGoogle Scholar
  35. 35.
    Guilloux L, Ricard-Blum S, Ville G, Motin J: A new radioimmunoassay using a commercially available solid support for the detection of IgE antibodies against muscle relaxants. J Allergy Clin Immunol 1992, 90:153–159.CrossRefPubMedGoogle Scholar
  36. 36.
    Fisher MM, Baldo BA: Immunoassays in the diagnosis of anaphylaxis to neuromuscular blocking drugs: the value of morphine for the detection of IgE antibodies in allergic subjects. Anaesth Intensive Care 2000, 28:167–170.PubMedGoogle Scholar
  37. 37.
    Fisher MM, Bowey CJ: Intradermal compared with prick testing in the diagnosis of anaesthetic allergy. Br J Anaesth 1997, 79:59–63.PubMedGoogle Scholar
  38. 38.
    Levy JH, Gottge M, Szlam F, et al.: Wheal and flare responses to intradermal rocuronium and cisatracurium in humans. Br J Anaesth 2000, 85:844–849.CrossRefPubMedGoogle Scholar
  39. 39.
    Berg CM, Heier T, Wilhelmsen V, Florvaag E: Rocuronium and cisatracurium-positive skin tests in non-allergic volunteers: determination of drug concentration thresholds using a dilution titration technique. Acta Anaesthesiol Scand 2003, 47:576–582.CrossRefPubMedGoogle Scholar
  40. 40.
    Moneret-Vautrin DA, Gueant JL, Kamel L, et al.: Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases. J Allergy Clin Immunol 1988, 82:745–752.CrossRefPubMedGoogle Scholar
  41. 41.
    Laxenaire MC, Moneret-Vautrin DA: Allergy and anaesthesia. Current Opin Anaesth 1992, 5:436–441.Google Scholar
  42. 42.
    Leynadier F, Sansarricq M, Didier JM, Dry J: Prick tests in the diagnosis of anaphylaxis to general anaesthetics. Br J Anaesth 1987, 59:683–689.CrossRefPubMedGoogle Scholar
  43. 43.
    McKinnon RP, Wildsmith JA: Histaminoid reactions in anaesthesia. Br J Anaesth 1995, 74:217–228.CrossRefPubMedGoogle Scholar
  44. 44.
    Mata E, Gueant JL, Moneret-Vautrin DA, et al.: Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs. Allergy 1992, 47:471–476.CrossRefPubMedGoogle Scholar
  45. 45.
    Gueant JL, Masson C, Laxenaire MC: Biological tests for diagnosing the IgE-mediate allergy to anaesthetic drugs. In Monographs in Allergy. Edited by Assem K. Basel: Karger; 1992:94–107.Google Scholar
  46. 46.
    Sainte-Laudy J, Vallon C, Guerin JC: Analysis of membrane expression of the CD63 human basophil activation marker. Applications to allergologic diagnosis. Allerg Immunol (Paris) 1994, 26:211–214.Google Scholar
  47. 47.
    Abuaf N, Rajoely B, Ghazouani E, et al.: Validation of a flow cytometric assay detecting in vitro basophil activation for the diagnosis of muscle relaxant allergy. J Allergy Clin Immunol 1999, 104:411–418.CrossRefPubMedGoogle Scholar
  48. 48.
    Monneret G, Benoit Y, Gutowski M, Bienvenu J: Detection of basophil activation by flow cytométrie in patients with allergy to muscle-relaxant drugs. Anesthesiology 2000, 92:275–277.CrossRefPubMedGoogle Scholar
  49. 49.
    Bermejo N, Guéant J, Mata E, et al.: Platelet serotonin is a mediator potentially involved in anaphylactic reaction to neuromuscular blocking drugs. Br J Anaesth 1993, 70:322–325.CrossRefPubMedGoogle Scholar
  50. 50.
    Assem E: Release of eosinophil cationic protein (ECP) in anaphylactoid anaesthetic reactions in vivo and in vitro. Agents Actions 1994, 41:C11-C13.CrossRefPubMedGoogle Scholar
  51. 51.
    Assem E: Leukotriene C4 release from blood cells in vitro in patients with anaphylactoid reactions to neuromuscular blockers. Agents Actions 1993, 38:C242-C244.CrossRefGoogle Scholar
  52. 52.
    Hosking MP, Lennon RL, Gronert GA: Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation. Anesth Analg 1988, 67:1089–1092.PubMedCrossRefGoogle Scholar
  53. 53.
    Doenicke A, Moss J, Lorenz W, et al.: Effect of oral antihistamine premedication on mivacurium-induced histamine release and side effects. Br J Anaesth 1996, 77:421–423.PubMedGoogle Scholar
  54. 54.
    McKinnon RP: Allergic reactions during anaesthesia. Curr Opin Anaesth 1996, 9:267–270.CrossRefGoogle Scholar
  55. 55.
    Vervloet D, Arnaud A, Senft M, et al.: Anaphylactic reactions to suxamethonium: prevention of mediator release by choline. J Allergy Clin Immunol 1985:222–225.Google Scholar
  56. 56.
    Thomas H, Eledjam JJ, Macheboeuf M, et al.: Rapid pre-operative immunotherapy in a patient allergic to muscle relaxants. Eur J Anaesthesiol 1988, 5:385–389.PubMedGoogle Scholar
  57. 57.
    Moneret-Vautrin DA, Kanny G, Gueant JL, et al.: Prevention by monovalent haptens of IgE-dependent leucocyte histamine release to muscle relaxants. Int Arch Allergy Immunol 1995, 107:172–175.PubMedCrossRefGoogle Scholar
  58. 58.
    Ben Abraham R, Cahana A, Krivosic-Horber RM, Perel A: Malignant hyperthermia susceptibility: anaesthetic implications and risk stratification. QJM 1997, 90:13–18.PubMedGoogle Scholar
  59. 59.
    Naguib M, Magboul MM: Adverse effects of neuromuscular blockers and their antagonists. Drug Saf 1998, 18:99–116.CrossRefPubMedGoogle Scholar
  60. 60.
    Kampe S, Krombach JW, Diefenbach C: Muscle relaxants. Best Pract Res Clin Anaesthesiol 2003, 17:137–146. In this article, the various side-effects of NMBAs are presented under the broad heading of toxicity.CrossRefPubMedGoogle Scholar
  61. 61.
    Iaizzo PA, Lehmann-Horn F: Anesthetic complications in muscle disorders. Anesthesiology 1995, 82:1093–1096.CrossRefPubMedGoogle Scholar
  62. 62.
    Book WJ, Abel M, Eisenkraft JB: Adverse effects of depolarising neuromuscular blocking agents: incidence, prevention and management. Drug Saf 1994, 10:331–349.PubMedGoogle Scholar
  63. 63.
    Blunk JA, Seifert F, Schmelz M, et al.: Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings. Eur J Anaesthesiol 2003, 20:245–253.CrossRefPubMedGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Paul-Michel Mertes
    • 1
  • Marie Claire Laxenaire
    • 1
  1. 1.Département d’Anesthésie-réanimationCHU de Nancy, Hôpital CentralNancy CedexFrance

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