Suxamethonium
Summary
Less than 10% of all adverse reactions to drugs have immunological background, and only a part of those are IgE-mediated.
Epidemiology
In many countries, NMBAs represent a significant cause of anesthesia-related anaphylaxis. For example, in Australia anaphylaxis to NMBAs remains the leading cause of perioperative anaphylaxis.
A survey showed that the mortality rate from an immediate hypersensitivity reaction to NMBAs administration was relatively high (4.1%) in France over the period 2000–2012.
Also, the French data revealed that Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.
Allergy to neuromuscular blocking agents (NMBA) constitutes a major cause of potentially life-threatening perioperative anaphylaxis. In a study with 344 patients, NMBA accounted for 40% of all patients with an IgE-mediated perioperative allergy. However other studies showed even higher values (up to 60%).
Risk Factors
Several clinical features are reported as risk factors of anaphylactic reactions induced by anesthetic agents including NMBAs: older age, asthma, hypertension and antihypertensive drugs.
Route Of Exposure
NMBAs are mainly administered intravenously but may also be given intramuscularly.
Clinical Relevance
Anaphylaxis during general anesthesia is rare but it can be severe, as it is often complicated by significant morbidity. Identification of the cause of anaphylaxis may pose a significant dilemma to the allergist and anesthetist. Results from a study in the UK showed that when the drug culprit of anaphylaxis was detected NMBAs represented 38.1% of the cases.
Following diagnosis of anaphylaxis to a NMBA, identifying safe alternatives for subsequent anesthesia is critical because a patient with anaphylaxis to one NMBA can also have an allergic reaction to other NMBAs (cross-reactivity).
Cross-Reactivity
Cross-reactivity between different NMBA is common since they all share the quaternary ammonium ion allergenic epitope. However, the extent of cross-reactivity varies considerably between patients and it is unusual for an individual to be allergic to all NMBAs. The explanation for this is that IgE antibody paratopes may not only recognize the quaternary ammonium ion, indeed sometimes the molecular environment around the ammonium ion is also part of the allergenic epitope. The possibility of multiple allergies to NMBAs should therefore be considered.
References
- Perry J, Lee J, Wells G. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2003(1):CD002788.
- Lee C. Goodbye suxamethonium! Anaesthesia. 2009;64 Suppl 1:73-81.
- Ebo DG, Faber M, Elst J, Van Gasse AL, Bridts CH, Mertens C, et al. In Vitro Diagnosis of Immediate Drug Hypersensitivity During Anesthesia: A Review of the Literature. The Journal of Allergy and Clinical Immunology: In Practice. 2018;6(4):1176-84.
- Meng J, Rotiroti G, Burdett E, Lukawska JJ. Anaphylaxis during general anaesthesia: experience from a drug allergy centre in the UK. Acta Anaesthesiol Scand. 2017;61(3):281-9.
- Mertes PM, Laxenaire MC, Alla F, Groupe d'Etudes des Reactions Anaphylactoides P. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology. 2003;99(3):536-45.
- Eberlein B, Wigand S, Lewald H, Kochs E, Ring J, Biedermann T, et al. Utility of basophil activation testing to assess perioperative anaphylactic reactions in real-world practice. Immun Inflamm Dis. 2017;5(4):416-20.
- Decuyper, II, Mangodt EA, Van Gasse AL, Claesen K, Uyttebroek A, Faber M, et al. In Vitro Diagnosis of Immediate Drug Hypersensitivity Anno 2017: Potentials and Limitations. Drugs R D. 2017;17(2):265-78.
- Li J, Best OG, Rose MA, Green SL, Fulton RB, Capon MJ, et al. Assessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis. Br J Anaesth. 2019;123(1):e144-e50.
- Reitter M, Petitpain N, Latarche C, Cottin J, Massy N, Demoly P, et al. Fatal anaphylaxis with neuromuscular blocking agents: a risk factor and management analysis. Allergy. 2014;69(7):954-9.
- Petitpain N, Argoullon L, Masmoudi K, Fedrizzi S, Cottin J, Latarche C, et al. Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012. Allergy. 2018;73(11):2224-33.
- Leysen J, Uyttebroek A, Sabato V, Bridts CH, De Clerck LS, Ebo DG. Predictive value of allergy tests for neuromuscular blocking agents: tackling an unmet need. Clin Exp Allergy. 2014;44(8):1069-75.
- Armentia A, Ruiz-Munoz P, Quesada JM, Postigo I, Herrero M, Martin-Gil FJ, et al. Clinical value of morphine, pholcodine and poppy seed IgE assays in drug-abusers and allergic people. Allergol Immunopathol (Madr). 2013;41(1):37-44.
- Mirone C, Preziosi D, Mascheri A, Micarelli G, Farioli L, Balossi LG, et al. Identification of risk factors of severe hypersensitivity reactions in general anaesthesia. Clin Mol Allergy. 2015;13(1):11.
- Florvaag E, Johansson SG. The Pholcodine Case. Cough Medicines, IgE-Sensitization, and Anaphylaxis: A Devious Connection. World Allergy Organ J. 2012;5(7):73-8.
- 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(2):167-70.
- Ebo DG, Fisher MM, Hagendorens MM, Bridts CH, Stevens WJ. Anaphylaxis during anaesthesia: diagnostic approach. Allergy. 2007;62(5):471-87.
- Florvaag E, Johansson SG, Oman H, Venemalm L, Degerbeck F, Dybendal T, et al. Prevalence of IgE antibodies to morphine. Relation to the high and low incidences of NMBA anaphylaxis in Norway and Sweden, respectively. Acta Anaesthesiol Scand. 2005;49(4):437-44.