Incidence of Perioperative and Anesthesia Allergies

Perioperative allergic reactions are rare but potentially lethal responses to drugs administered before, during, or after a surgical procedure. The incidence of hypersensitivity reactions due to anesthetic agents is difficult to determine because they occur in a context in which a multitude of drugs are administered in a short period of time; furthermore, a patient, as well as their clinicians, may be unaware that the patient is having a reaction while under general anesthesia. Skin reactions, one of the most common symptoms of hypersensitivity, may be concealed by surgical drapes. Cardiac symptoms may be falsely interpreted as pharmacological side effects, and respiratory issues can be misattributed to insufficient sedation. As such, a wide range of estimates regarding the incidence of perioperative and anesthesia allergies have been reported worldwide.¹

A recent epidemiological review of perioperative and anesthesia allergies from global surveillance studies concluded that there is clear evidence that variability in incidence does exist between countries, likely as a result of differences in clinical practice, the evaluation and reporting of allergic reactions, and even gene-environment interactions. Estimates of perioperative allergic reactions of all severity grades range from one in 353 procedures to one in 18,600.²

Anaphylaxis, a type of allergic reaction, may occur at an incidence of between one in 10,000 and 20,000 anesthetic procedures.³ One review notes incidences between one in 4,500 procedures (according to a study in France), and one in 25,000 cases (according to a study in Australia).⁴ The United Kingdom’s 6th National Audit Project (NAP6), “Anaesthesia, Surgery and Life-Threatening Allergic Reactions,” estimated that an anesthetic will trigger Grade III-V (severe to deadly) anaphylaxis in 1 in 10,000 cases, but noted that true incidence could be up to 70 percent higher. All National Health Service hospitals participated in the large, prospective study, which collected reports of 266 life-threatening anaphylaxis reactions out of three million anesthetics given during one reporting year.⁵ High-powered studies from France and the United States have found similar incidences of immunoglobulin E-mediated (allergic) reactions.²^{, 6}

While determining the incidence of perioperative allergic reactions is challenging, it has encouraged large surveillance efforts and increased international discourse in order to expand collective knowledge about anesthesia allergies and develop prevention and response strategies.² Numerous studies have reported neuromuscular blocking agents (NMBAs) to be the most common cause of allergic reactions. France’s GERAP Network (Groupe d’étude Des réactions Anaphylactiques périopératoires) longitudinally monitors perioperative allergic reactions and has repeatedly found that NMBAs trigger most allergic reactions (60.6 percent in a 2017 report, which synthesized data from 2011-2012). Rocuronium accounted for the greatest share of NMBA reactions, followed by suxamethonium.⁷

Across studies, NMBAs are generally highlighted as the most common cause of anesthesia allergic reactions, in 50 to 70 percent of cases. While suxamethonium and rocuronium are associated with a high frequency of allergic reactions, vecuronium and pancuronium have a moderate frequency and atracurium, mivacurium, and cisatracurium a low one.⁸ A safe, alternative NMBA should be identified when a patient demonstrates an allergy. Published guidelines on responding to NMBA allergies exist but are not always closely adhered to; in addition, there remains uncertainty about the harms versus benefits of administering sugammadex (which reverses certain NMBAs), as well as other reversal agents, during resuscitation of perioperative anaphylaxis, necessitating further clinical trials.⁷

Allergic reactions to antibiotics administered perioperatively are being reported with increased frequency. Antibiotics accounted for 18.2 percent of reactions in the 2011-2012 GERAP study⁷ and approximately 15 percent in a 2018 review.¹ However, the UK’s NAP6 survey found that they were the main cause of life-threatening, perioperative anaphylaxis in their dataset, accounting for 46 percent of cases. Anaphylaxis onset was rapid in these cases (within five to ten minutes in nearly all cases) and therefore administration of antibiotics several minutes before induction of anesthesia could help improve detection, simplify treatment, allow for subsequent investigation.⁵

Whereas hypnotic agents in the past accounted for a substantial number of allergic reactions, they now account for as few as 2.2 percent of cases (according to a GERAP study), likely as a result of the discontinuation of certain agents (Cremophor EL) and declining use of others (thiopental).² Some experts have previously worried that propofol may not be suitable for those with egg and soy allergies because of ingredients in its formulation. However, the American Academy of Allergy Asthma and Immunology has produced guidelines stating that those with egg and soy allergies can safely receive propofol.^9,10The UK’s NAP6 survey found only a single case of propofol anaphylaxis, even though approximately 2 million patients are administered propofol in the UK each year.⁵

Practical recommendations for responding to perioperative and anesthesia allergies have been produced globally. Where diagnostic tests cannot be used prior to an operation — such as with certain inhalants and NMBAs — clinicians must have appropriate preparation to monitor and respond with emergency treatments, protocols that involve maintaining airways and administering epinephrine.¹ Taking careful patient histories is critical, as the primary risk factor for an allergic reaction is a previous uninvestigated one. This underscores the importance of thorough follow-up and ongoing surveillance efforts.¹⁰

References

Pfützner W, Brockow K. Perioperative drug reactions – practical recommendations for allergy testing and patient management. Allergo J Int. 2018;27(4):126-129. doi:10.1007/s40629-018-0071-1

Mertes PM, Ebo DG, Garcez T, et al. Comparative epidemiology of suspected perioperative hypersensitivity reactions. Br J Anaesth. 2019;123(1):e16-e28. doi:10.1016/j.bja.2019.01.027

Dewachter P, Mouton-Faivre C, Emala CW. Anaphylaxis and anesthesia: controversies and new insights. Anesthesiology. 2009;111(5):1141-1150. doi:10.1097/ALN.0b013e3181bbd443

Nicklas RA. Anaphylaxis during general anesthesia, the intraoperative period, and the postoperative period. J Allergy Clin Immunol. 1998;101(6):S512-S516. doi:10.1016/s0091-6749(18)30584-0

Harper NJN, Cook TM, Garcez T, 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. 2018;121(1):159-171. doi:10.1016/j.bja.2018.04.014

Saager L, Turan A, Egan C, et al. Incidence of intraoperative hypersensitivity reactions: A registry analysis: A registry analysis A registry analysis. Anesthesiology. 2015;122(3):551-559. doi:10.1097/aln.0000000000000529

Tacquard C, Collange O, Gomis P, et al. Anaesthetic hypersensitivity reactions in France between 2011 and 2012: the 10th GERAP epidemiologic survey. Acta Anaesthesiol Scand. 2017;61(3):290-299. doi:10.1111/aas.12855

Gonzalez A, Maria G, Franco A, Jesus M, Carnero Pinto B, Castedo M. Perioperative allergic reactions: A case of intraoperative anaphylactic shock. World Allergy Organ J. 2007;NA;S319-S320. doi:10.1097/01.wox.0000301513.06300.53

American Academy of Allergy Asthma and Immunology. Soy-allergic and egg-allergic patients can safely receive anesthesia. https://www.aaaai.org/conditions-and-treatments/library/allergy-library/soy-egg-anesthesia

Dewachter P, Kopac P, Laguna JJ, et al. Anaesthetic management of patients with pre-existing allergic conditions: a narrative review. Br J Anaesth. 2019;123(1):e65-e81. doi:10.1016/j.bja.2019.01.020

Incidence of Perioperative and Anesthesia Allergies

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