Severe allergic reactions induced by different muscle relaxants in the same patient in two rounds of general anaesthesia: A case report and a literature review

Severe allergic reactions induced by different muscle relaxants in the same patient in two rounds of general anaesthesia: A case report and a literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Severe allergic reactions induced by different muscle relaxants in the same patient in two rounds of general anaesthesia: A case report and a literature review Lanyun Xie, Yalei Gao, Jinwan Guo, Fei Zhou, Yongtao Sun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6199091/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Muscle relaxants (MRs) are indispensable drugs in general anaesthesia, as they are used to relax skeletal muscles for tracheal intubation and surgical operations. However, MRs are also the leading cause (accounting for 50–70%) of perioperative allergic reactions (ARs). Among the various MRs, nondepolarizing MRs are likely to cause cross-ARs due to their chemical structural similarities. Case presentation The case of a 47-year-old male patient who experienced severe ARs caused by different MRs (atracurium and cisatracurium) in two rounds of general anaesthesia is reported. Although the type of anaesthesia drugs used was changed before the second round of anaesthesia, ARs still developed, as did severe ventricular fibrillation, suggesting the occurrence of cross-ARs. Conclusion This patient experienced severe ARs during two rounds of anaesthesia. Surgery was ultimately completed successfully through genetic testing and an individualized anaesthesia regimen, suggesting the significance of detailed preoperative evaluation, allergen detection and genetic testing-guided drug selection in perioperative management. General anaesthesia Muscle relaxants Allergic reactions Cross-allergic reactions Background General anaesthesia is an indispensable part of modern surgery. Muscle relaxants (MRs), as important adjuvant drugs for general anaesthesia, are widely used for the induction of anaesthesia and intraoperative muscle relaxation. However, MRs are also one of the common drug types that cause allergic reactions (ARs) during anaesthesia, which can cause anaphylactic shock and be life-threatening to the patients in severe cases. Studies have shown that ARs caused by MRs account for 50–70% of anaesthesia-related ARs[ 1 ]. Although the incidence of MR-induced ARs is low (approximately 1/10,000 to 1/20,000)[ 2 ], the risk of fatality has attracted the attention of clinical anaesthesiologists. MR-induced ARs usually include skin flushing, rash, a sudden drop in blood pressure, a rapid heart rate, bronchospasm and other symptoms, and several of these ARs can lead to circulatory failure and respiratory failure in severe cases[ 3 ]. Due to the possible cross-ARs between different MRs, the ARs may be reinduced even if the drug types are changed[ 4 ]. Therefore, it is very critical to ask patients about their allergy history, choose drugs rationally, and make emergency preparations before surgery. Here, the case of a 47-year-old male patient who experienced severe ARs due to different MRs (atracurium and cisatracurium) during two rounds of general anaesthesia is reported. After the implementation of rescue measures such as epinephrine, glucocorticoids, and cardiopulmonary resuscitation, the patient was out of danger. Before the third round of anaesthesia, we optimized the anaesthesia regimen through genetic testing for gene polymorphisms associated with ARs to anaesthesia drugs and thereby successfully avoided AR occurrence. The diagnosis, prevention, and management strategies for MR-induced ARs are discussed, and an in-depth review of the literature on the pathological mechanisms of MR-induced ARs is provided. This report provides a reference for clinical anaesthesia safety. Case presentation A 47-year-old male experienced sudden onset of headache and dizziness with no obvious inducements more than 2 months ago. Later, slurred speech, weakness of the left limb, and blood pressure gradually developed. A cranial computed tomography (CT) scan showed intracerebral haemorrhage in the right thalamus and basal ganglia region breaking into the ventricular system. "Cranial burr hole drainage + lateral ventricle drainage" was performed, but improvement was not observed postoperatively. "Intracranial haematoma evacuation + decompressive craniectomy” was performed, and the operation went well. After surgery, the patient was treated with dehydration, neurotrophic treatment, phlegm reduction, and intracranial pressure reduction, and the patient's condition was improved. At that time, the patient was conscious and could pronounce words but could not speak complete sentences. He could not move his left limbs. He occasionally coughed and expectorated white sputum. He had no nausea or vomiting but had a right skull defect. The patient was admitted to the hospital for further treatment due to a “right temporoparietal skull defect”. The patient was fed through a nasal feeding tube, and the urinary catheter was retained. The patient had an 8-year history of hypertension and was taking “nifedipine 20 mg bid” to reduce his blood pressure, but his blood pressure was not well controlled (140–160/90–100 mmHg). Twenty years ago, his left upper extremity and left rib were fractured due to trauma, and a plate was placed in the left upper extremity (the specifics are unknown). He had a left eye injury for which he underwent surgery 3 years ago (the specifics are unknown). His father suffered from hypertension and intracerebral haemorrhage, and his brother had hypertension. The admission diagnoses were right temporoparietal skull defect, right basal ganglion haemorrhage in the recovery period, grade 3 hypertension (very high risk), left hemiparesis, motor aphasia, bilateral pneumonia, and anaemia. Cranial defect repair under general anaesthesia was planned. The patient underwent three rounds of general anaesthesia on 2021.04.28, 2021.05.11, and 2022.8.22: The first round of general anaesthesia (2021.04.28): The vital signs of the patient were normal when the patient entered the operating room. After anaesthesia was induced with 2 mg of midazolam, 14 mg of etomidate, 30 µg of sufentanil, and 50 mg of atracurium, skin flushing and systemic rash developed rapidly. The patient presented with conjunctival congestion and oedema, large face mask compression resistance, a poor chest rise, a blood pressure as low as 50/30 mmHg, and a heart rate of 118 beats/min. Anaphylactic shock was considered, and the trachea was intubated immediately. The airway pressure was 36 cm H 2 O, and the breath sounds were coarse in both lungs. The patient was given volume expansion therapy, an intravenous infusion of 0.1 mg adrenaline, an intravenous infusion of 80 mg methylprednisolone sodium succinate, intratracheal administration of salbutamol aerosol, intravenous infusion of 0.5 g diprophylline, a continuous epinephrine pump at 0.02 µg/kg/min, and a continuous norepinephrine pump at 0.02 µg/kg/min. The doses were adjusted based on the vital signs. His blood pressure gradually increased to 92/50 mmHg. Emergency arterial puncture was performed for invasive arterial blood pressure (ABP) monitoring, and emergency arterial blood gas analysis (Table 1, A) was performed. The results showed that blood K + was low, at 2.8 mmol/L, and the arterial partial pressure of carbon dioxide (PaCO 2 ) was 53.6 mmHg. The patient was given an intravenous infusion of potassium magnesium aspartate (50 mL). The haemodynamic status of the heart was monitored via transthoracic echocardiography. The systolic and diastolic functions and ventricular wall mobility were evaluated to rule out pulmonary embolism. The patient was haemodynamically stable, the breath sounds of both lungs were clear on auscultation, and the airway pressure fell to 21 cm H 2 O. After communicating with the surgeons and family members, the surgery was delayed, and the patient was returned to the ward with tracheal intubation. Second round of general anaesthesia (2021.05.11): The patient was admitted to the operation room for routine monitoring, and the invasive ABP monitoring via radial artery puncture was performed under local anaesthesia. The vital signs were normal, and arterial blood gas analysis was normal (Table 1, B). After induction of anaesthesia with 3 mg of midazolam, 100 mg of propofol, and 10 mg of cisatracurium besylate, the patient rapidly developed skin flushing and systemic maculopapular rash; his blood pressure fell to 55/36 mmHg, his heart rate was 150 beats/min, and his oxygen saturation (SpO 2 ) reached 89%. Anaphylactic shock was considered, tracheal intubation was performed immediately, and an intravenous bolus injection of 0.1 mg epinephrine was given. The effect was not satisfactory. Epinephrine was injected intravenously at a dose of 1 mg, and epinephrine was given via a continuous intravenous pump at a rate of 0.03 µg/kg/min. The doses were adjusted based on vital signs. An intravenous infusion of 80 mg of methylprednisolone sodium succinate, 1.0 g of calcium gluconate, and 100 mg of hydrocortisone was given. The patient suddenly developed ventricular fibrillation. Cardiopulmonary resuscitation was rapidly performed, and emergency electrical defibrillation (bidirectional, asynchronous, 200 J/time) was performed three times. Lidocaine (100 mg) was intravenously infused, and Cordarone (300 mg) was intravenously administered. The resuscitation was successful, and the sinus rhythm was restored. Arterial blood gas analysis was performed (Table 1, C), and the results showed a pH of 7.26 and a PaCO 2 of 60 mmHg. Hyperventilation was performed. The operation was suspended after the vital signs returned to normal. After the patient awoke, the tube was removed, and the patient was returned to the ward. The third round of general anaesthesia (2022.8. 22): In view of the ARs that occurred in the previous two rounds of anaesthesia, preoperative genetic testing for gene polymorphisms associated with anaesthetic drug sensitivity was performed. The results showed that sufentanil, remifentanil and rocuronium were recommended drugs for this patient, whereas propofol was an optional drug. After admission to the operation room, the vital signs and the bispectral index (BIS) were routinely monitored, and the patient was continuously monitored via radial artery puncture under local anaesthesia. Ultrasound-guided bilateral superior laryngeal nerve block was performed. Sufentanil (20 µg) was slowly administered intravenously in divided doses. After 8% sevoflurane inhalation, a 4# video laryngeal mask was placed. Sevoflurane and remifentanil were used to maintain anaesthesia during the surgery. Preventive use of epinephrine and norepinephrine was recommended to maintain stable vital signs. The results of two preoperative and postoperative blood gas analyses were normal (Table 1, D, E). The patient was fully awake 1 hour after surgery. No adverse reactions were reported, and the patient was safely returned to the ward. Table 1 Arterial blood gas analysis A B C D E pH 7.36 7.42 7.26 7.47 7.37 PaCO 2 (mmHg) 53.6 47.1 60.2 38.7 50.8 PaO 2 (mmHg) 102.0 73.9 120.7 71.6 92.9 BE (mmol/L) 3.2 4.5 -2.2 4.1 2.8 Glu (mmol/L) 8.6 4.9 7.8 6.5 6.3 Lac (mmol/L) 2.9 1.1 3.3 2.5 2.6 Hct (%) 47.0 40.9 49.8 37.7 35.4 Na + (mmol/L) 143.2 138.1 141.2 139.7 138.4 K + (mmol/L) 2.8 3.7 3.4 3.2 4.1 Ca 2+ (mmol/L) 1.2 1.2 1.4 1.2 1.2 Cl - (mmol/L) 108.3 105.9 107.1 103.8 104.5 tHb g/dL 15.6 13.1 15.9 13.1 12.4 SaO 2 (%) 98.1 95.5 98.6 96.7 98.5 Discussion and conclusions In this case, the patient developed severe ARs (skin flushing, hypotension, bronchospasm and ventricular fibrillation), which were in line with the characteristics of type I hypersensitivity reactions. Although midazolam was used on both occasions, on the basis of drug allergy epidemiological data, the MRs, members of quaternary ammonium group of benzylisoquinolines, were more likely to be the core allergen[5-8]. These drugs bind to IgE on the surface of mast cells, which triggers the release of histamine, resulting in vasodilation and bronchospasm[9]. Notably, the patient did not develop ARs after cisatracurium was used in the past, suggesting that immune status and genetic factors (such as HLA genotype) may affect AR susceptibility[10-13]. Atracurium and cisatracurium besylate are both benzylisoquinoline MRs with a quaternary ammonium group in their structure and may cause ARs through IgE-mediated cross-reactions[3, 14, 15]. Studies have shown that the cross-AR rate of benzylisoquinoline MRs was as high as 60–70%, whereas aminosteroids (such as rocuronium) had a low cross-AR risk due to significant differences in their chemical structures[15-17]. For the third round of anaesthesia, although genetic testing results recommended the use of rocuronium bromide, in view of the first two severe ARs, multimodal analgesia combined with a laryngeal mask for general anaesthesia was eventually used, and MRs were not used, which confirmed the reliability of the principle of “structural difference avoidance”. ARs are type I hypersensitivity reactions, and the clinical manifestations are mostly integumentary (flushing, urticaria, and angioedema), circulatory (lower blood pressure, brady or tachycardia, arrhythmias and cardiac arrest) and respiratory system (bronchospasm and increased ventilatory resistance) symptoms[18]. As the most critical AR form, anaphylactic shock is characterized by damage to multiple organs in a system, sudden onset and rapid progression, and anaphylactic shock can rapidly lead to fatal complications such as airway obstruction and circulatory collapse. In approximately 50% of patients, symptoms develop within 5 minutes of exposure to the allergen[19-21]. The core underlying mechanism is as follows: exogenous antigens activate IgE-mediated degranulation of mast cells, which release mediators such as histamine, leukotriene, and platelet-activating factors, resulting in vasodilation, increased capillary permeability, and smooth muscle contraction[22]. In clinical treatment, the suspected drug should be immediately stopped, and epinephrine should be given in a stepwise manner (initial dose 0.05–0.1 mg via intravenous infusion) to reverse the haemodynamic disorder[23-26]. Timely and effective rescue is the core for safely managing the crisis into patient stability. In this patient, when the first two ARs occurred, the anaesthesia team quickly started the standard procedure: an intravenous bolus injection of epinephrine (initial dose, 0.05–0.1 mg; titrated up to 1 mg if ineffective)[18] combined with methylprednisolone (80–120 mg) to inhibit the inflammatory cascade reactions[27]. Emergency tracheal intubation was performed to increase blood oxygen levels. Electrical defibrillation (bidirectional, 200 J) and cardiopulmonary resuscitation were performed to restore sinus rhythm[28]. The patient’s internal environment was evaluated in real time through invasive ABP monitoring and blood gas analysis, and the dose of vasoactive drugs was adjusted[4]. This case highlights the need for the anaesthesia team to regularly practice AR emergency plans and to be proficient in emergency drug dosage, airway management, and advanced life support techniques to ensure rapid identification and accurate intervention in a timely manner. Before the third round of anaesthesia, low-risk drugs (sufentanil, remifentanil, and rocuronium) were accurately screened through genetic testing, and an individualized regimen was developed based on results: ultrasound-guided superior laryngeal nerve block (0.375% ropivacaine, 4 mL/kg/min) effectively inhibited the airway reflex, reduced the number of intubation stimulations, and avoided the use of MRs[29]. Stable sedation and analgesia were achieved via inhalation of sevoflurane (maintenance concentration of 1.5–2.0%) combined with remifentanil (0.1–0.2 μg/kg/min). Preventive pumping of epinephrine (0.01 μg/kg/min) and norepinephrine (0.05 μg/kg/min) was used to maintain haemodynamic stability[19]. This regimen successfully avoided exposure to MRs, confirming that genetic testing can be used to determine the appropriate medications for high-risk patients by revealing differences in drug metabolism and response (such as the effect of CYP2B6 on the metabolism of propofol). However, challenges are still faced in the widespread application of genetic testing in the field of anaesthesia, such as the high cost of testing and the professional knowledge required for the interpretation of test results[12]. Most existing studies have evaluated small-sample single-centre data, and large-sample multicentre studies are needed to verify the association between gene polymorphisms and drug response[19]. To prevent MR-induced ARs, a detailed allergy history (drugs, food, latex, etc.) should be obtained before surgery. Skin prick tests or serum-specific IgE tests (such as tryptase and histamine) should be performed for high-risk patients[15]. Drugs with common antigenic epitopes (such as benzylisoquinoline MRs) should be avoided, and alternative drugs with significant structural differences (such as the aminosteroid rocuronium bromide) should be used first[3]. For patients at high risk of ARs (such as those with a previous history of drug allergies), a skin prick test or serum-specific IgE tests (such as tryptase and mast cell tryptase) should be performed to clarify the sensitization risk. MRs with significantly different chemical structures (such as the aminosteroid rocuronium bromide instead of benzylisoquinoline) should be chosen first to avoid the risk of cross-ARs[3]. Moreover, during the anaesthesia process, haemodynamics (invasive ABP monitoring), airway pressure, and skin manifestations should be monitored in real time, and the suspected drugs should be stopped immediately. Rescue procedures should be started if signs of ARs (such as skin rash and a sudden drop in SpO 2 ) are detected. In the future, we will focus on the molecular mechanisms of cross-sensitivity to MRs (such as the binding characteristics of the HLA-B*57:01 genotype and quaternary ammonium group) and the development of targeted blocking antibodies or hyposensitizing drugs[30]. A gene–phenotype-medication database should be constructed and used in combination with artificial intelligence (AI) to analyse individualized medication regimens (e.g., the selection of opioid drugs based on CYP2D6 metabolizing ability)[31]. China should promote the use of rapid point-of-care testing (POCT) to obtain genetic testing results quickly (results available within 30 minutes) and reduce the cost of testing to less than 50% of that of conventional methods[32]. Conclusions In this case, the patient experienced severe ARs due to the use of different MRs during two rounds of general anaesthesia, and the patient finally underwent successful surgery with the help of genetic testing and an individualized anaesthesia regimen. This case fully demonstrates the significance of detailed preoperative evaluation, allergen detection, and genetic testing-guided drug selection in perioperative management. MR-induced ARs are severe, and there is a risk of cross-ARs. Clinicians should pay very close attention to the possibility of MR-induced ARs, and protocols for the prevention and management of MR-induced ARs should be strengthened. An in-depth study of the pathogenesis of MR-induced ARs, the optimization of genetic testing technology and clinical application of genetic testing are expected to further improve the safety of anaesthesia and provide more reliable safety for patients during medical procedures. Abbreviations MRs Muscle relaxants ARs Sallergic reactions CT Computed tomography ABP Arterry blood PaCO 2 Pressure carbon dioxide SpO 2 Pulse oximetry BIS Bispectral index POCT Point-of-Care Testing AI Artificial intelligence Declarations Author contributions Lanyun Xie and Yalei Gao contributed to performing of anesthesia and drafting of manuscript. Jinwan Guo and Fei Zhou contributed to data collection. Yongtao Sun contributed to performing of anesthesia and revising the manuscript. All authors have read and approval the final manuscript. Funding The project was supported by Clinical research Special Fund of Wu Jie-ping Medical Foundation (320.6750.2024-15-19), and Education and Teaching reform Research project of Shandong First Medical University (Shandong Academy of Medical Sciences) (XM2024091). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Data availability All data related to this case report are contained within the manuscript. Ethics approval and consent to participate None. Consent for publication Written informed consent for publication of the clinical details and clinical images was obtained from the patient. Competing interests The authors declare no competing interests. References Mertes PM, Laxenaire MC: Allergic reactions occurring during anaesthesia . Eur J Anaesthesiol 2002, 19 (4):240-262. Harper NJ, Dixon T, Dugué P, Edgar DM, Fay A, Gooi HC, Herriot R, Hopkins P, Hunter JM, Mirakian R et al : Suspected anaphylactic reactions associated with anaesthesia . Anaesthesia 2009, 64 (2):199-211. Sadleir PH, Clarke RC, Bunning DL, Platt PR: Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011 . Br J Anaesth 2013, 110 (6):981-987. Dewachter P, Mouton-Faivre C, Emala CW: Anaphylaxis and anesthesia: controversies and new insights . Anesthesiology 2009, 111 (5):1141-1150. Yasuda M, Moriwaki K, Tsutsumi YM: Concurrent positive skin tests to prophylactic antibiotics and rocuronium in two patients with life-threatening anaphylaxis after induction of anesthesia . JA Clin Rep 2021, 7 (1):37. Sun Y, Huang X: Severe anaphylaxis after general anesthesia induction . J Anesth 2021, 35 (5):771. Mertes PM, Volcheck GW: Anaphylaxis to neuromuscular-blocking drugs: all neuromuscular-blocking drugs are not the same . Anesthesiology 2015, 122 (1):5-7. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000 . Anesthesiology 2003, 99 (3):536-545. Nguyen SMT, Rupprecht CP, Haque A, Pattanaik D, Yusin J, Krishnaswamy G: Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond . Int J Mol Sci 2021, 22 (15). Moorthy SS, Laurent B, Pandya P, Fry V: Anaphylactoid reaction to etomidate: report of a case . J Clin Anesth 2001, 13 (8):582-584. Joo J, Koh HJ: Cardiac Arrest Due to Perioperative Anaphylactic Shock Induced by Re-Exposure to Propofol: A Case Report . J Clin Med 2024, 13 (18). Tang R, Lyu X, Sun J, Li H: Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases . Endocr Metab Immune Disord Drug Targets 2024, 24 (10):1215-1223. Sio YY, Shi P, Matta SA, Fok YTR, Chiang WC, Say YH, Chew FT: Functional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases . Int Arch Allergy Immunol 2023, 184 (6):609-623. Karila C, Brunet-Langot D, Labbez F, Jacqmarcq O, Ponvert C, Paupe J, Scheinmann P, de Blic J: Anaphylaxis during anesthesia: results of a 12-year survey at a French pediatric center . Allergy 2005, 60 (6):828-834. Li J, Best OG, Rose MA, Green SL, Fulton RB, Capon MJ, Krupowicz BA, Fernando SL: 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-e150. Gouel-Chéron A, Neukirch C, Chollet-Martin S, Valent A, Plaud B, Longrois D, Nicaise-Roland P, Montravers P, de Chaisemartin L: Neuromuscular blocking agent drug challenge: a literature review and protocol proposal with biological evaluation . Eur J Anaesthesiol 2024, 41 (10):722-727. Jeong J, Yun JE, Kim HJ, Jang JY, Seo JH, Lee SY, Kim WH, Seo JH, Kang HR: Neuromuscular blocking agent re-exposure in a retrospective cohort with neuromuscular blocking agent-associated anaphylaxis . Ann Allergy Asthma Immunol 2023, 131 (5):637-644.e631. Navalpakam A, Thanaputkaiporn N, Poowuttikul P: Management of Anaphylaxis . Immunol Allergy Clin North Am 2022, 42 (1):65-76. Tacquard C, Iba T, Levy JH: Perioperative Anaphylaxis . Anesthesiology 2023, 138 (1):100-110. Takazawa T, Yamaura K, Hara T, Yorozu T, Mitsuhata H, Morimatsu H: Practical guidelines for the response to perioperative anaphylaxis . J Anesth 2021, 35 (6):778-793. McHugh K, Repanshek Z: Anaphylaxis: Emergency Department Treatment . Emerg Med Clin North Am 2022, 40 (1):19-32. Li X, Ma Q, Yin J, Zheng Y, Chen R, Chen Y, Li T, Wang Y, Yang K, Zhang H et al : A Clinical Practice Guideline for the Emergency Management of Anaphylaxis (2020) . Front Pharmacol 2022, 13 :845689. Muraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, Riggioni C, de Silva D, Angier E, Arasi S et al : EAACI guidelines: Anaphylaxis (2021 update) . Allergy 2022, 77 (2):357-377. Manian DV, Volcheck GW: Perioperative Anaphylaxis: Evaluation and Management . Clin Rev Allergy Immunol 2022, 62 (3):383-399. Bruhn I, Bauer A, Beissert S, Neumeister V, Spornraft-Ragaller P: Intraoperative anaphylaxis to atracurium . J Dtsch Dermatol Ges 2021, 19 (12):1784-1785. Wang N, Zhang Y, Hu Y, Yang Q, Su Z: Serious bronchospasm induced by cisatracurium besylate: A case report . Medicine (Baltimore) 2021, 100 (15):e25516. Mertes PM, Demoly P, Malinovsky JM: Hypersensitivity reactions in the anesthesia setting/allergic reactions to anesthetics . Curr Opin Allergy Clin Immunol 2012, 12 (4):361-368. Moitra VK, Einav S, Thies KC, Nunnally ME, Gabrielli A, Maccioli GA, Weinberg G, Banerjee A, Ruetzler K, Dobson G et al : Cardiac Arrest in the Operating Room: Resuscitation and Management for the Anesthesiologist: Part 1 . Anesth Analg 2018, 126 (3):876-888. Fowler JG, VanEenenaam DP, Jr., Johnson KN, Courtemanche CD, Strathman AJ, Reynolds JE: Single midline injection for bilateral superior laryngeal nerve block . J Clin Anesth 2020, 66 :109922. Elst J, Maurer M, Sabato V, Faber MA, Bridts CH, Mertens C, Van Houdt M, Van Gasse AL, van der Poorten MM, De Puysseleyr LP et al : Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones . Front Immunol 2021, 12 :668962. Lopes S, Rocha G, Guimarães-Pereira L: Artificial intelligence and its clinical application in Anesthesiology: a systematic review . J Clin Monit Comput 2024, 38 (2):247-259. Liu H, Li Z, Yan S, Ming S: Adverse event signal analysis of remimazolam using the FDA adverse event reporting system database . Acta Anaesthesiol Scand 2025, 69 (3):e14588. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6199091","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":453582949,"identity":"5fc247dc-71f1-47fa-b897-2026f360ccd1","order_by":0,"name":"Lanyun Xie","email":"","orcid":"","institution":"The First Affiliated Hospital of Shandong First Medical University \u0026 Shandong Provincial Qianfoshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lanyun","middleName":"","lastName":"Xie","suffix":""},{"id":453582950,"identity":"939ed9d6-7546-4f53-9527-0568b539806c","order_by":1,"name":"Yalei Gao","email":"","orcid":"","institution":"The First Affiliated Hospital of Shandong First Medical University \u0026 Shandong Provincial Qianfoshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yalei","middleName":"","lastName":"Gao","suffix":""},{"id":453582951,"identity":"cffe9e3c-6b7f-48ac-9fd8-8ace9c5de643","order_by":2,"name":"Jinwan Guo","email":"","orcid":"","institution":"The First Affiliated Hospital of Shandong First Medical University \u0026 Shandong Provincial Qianfoshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinwan","middleName":"","lastName":"Guo","suffix":""},{"id":453582952,"identity":"63606b25-f0c7-4a66-b48f-ab88c3bbb140","order_by":3,"name":"Fei Zhou","email":"","orcid":"","institution":"The First Affiliated Hospital of Shandong First Medical University \u0026 Shandong Provincial Qianfoshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Zhou","suffix":""},{"id":453582953,"identity":"5cc0f290-f812-4ebc-9a03-cfd0b0287f7c","order_by":4,"name":"Yongtao Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYFACxgYQKcfG3tj4GCzAzNxAlBZjfp7Dh40ZGAyAWhgJaYGAxJkz0tKkwVoYCGiRbz/c+LigxoZxw4Ecs+qCij/R/O1ALT8qtuHUYnAmsdl4xrE0ZoMDZ8xuzzhjkDvjMGMDY8+Z27i1SDC2SfM2HGYzONhjdpu3zSC3AaiFmbENtxb5GYztv3kb/vMYHOYxKwZpmU9IC8MNxjZm3oYDEpJtbGnMIC0bCGkB+UWa51iyAT8P82FpnjPGuRuBWg7i84t8+/GHn3lq7Orb5B82fuapkMudd/7wwQc/KvA4DCs4QKL6UTAKRsEoGAVoAACBIFfUy+GtYwAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Shandong First Medical University \u0026 Shandong Provincial Qianfoshan Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yongtao","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2025-03-11 00:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6199091/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6199091/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82320462,"identity":"0c2ec971-a332-40d5-8bc1-703b98fccf56","added_by":"auto","created_at":"2025-05-09 04:47:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1613105,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6199091/v1/8a043c88-fda0-4f9e-825b-359e9036a722.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe allergic reactions induced by different muscle relaxants in the same patient in two rounds of general anaesthesia: A case report and a literature review","fulltext":[{"header":"Background","content":"\u003cp\u003eGeneral anaesthesia is an indispensable part of modern surgery. Muscle relaxants (MRs), as important adjuvant drugs for general anaesthesia, are widely used for the induction of anaesthesia and intraoperative muscle relaxation. However, MRs are also one of the common drug types that cause allergic reactions (ARs) during anaesthesia, which can cause anaphylactic shock and be life-threatening to the patients in severe cases. Studies have shown that ARs caused by MRs account for 50\u0026ndash;70% of anaesthesia-related ARs[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although the incidence of MR-induced ARs is low (approximately 1/10,000 to 1/20,000)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], the risk of fatality has attracted the attention of clinical anaesthesiologists.\u003c/p\u003e \u003cp\u003eMR-induced ARs usually include skin flushing, rash, a sudden drop in blood pressure, a rapid heart rate, bronchospasm and other symptoms, and several of these ARs can lead to circulatory failure and respiratory failure in severe cases[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Due to the possible cross-ARs between different MRs, the ARs may be reinduced even if the drug types are changed[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, it is very critical to ask patients about their allergy history, choose drugs rationally, and make emergency preparations before surgery.\u003c/p\u003e \u003cp\u003eHere, the case of a 47-year-old male patient who experienced severe ARs due to different MRs (atracurium and cisatracurium) during two rounds of general anaesthesia is reported. After the implementation of rescue measures such as epinephrine, glucocorticoids, and cardiopulmonary resuscitation, the patient was out of danger. Before the third round of anaesthesia, we optimized the anaesthesia regimen through genetic testing for gene polymorphisms associated with ARs to anaesthesia drugs and thereby successfully avoided AR occurrence. The diagnosis, prevention, and management strategies for MR-induced ARs are discussed, and an in-depth review of the literature on the pathological mechanisms of MR-induced ARs is provided. This report provides a reference for clinical anaesthesia safety.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 47-year-old male experienced sudden onset of headache and dizziness with no obvious inducements more than 2 months ago. Later, slurred speech, weakness of the left limb, and blood pressure gradually developed. A cranial computed\u0026nbsp;tomography (CT) scan showed intracerebral haemorrhage in the right thalamus and basal ganglia region breaking into the ventricular system. \u0026quot;Cranial burr hole drainage + lateral ventricle drainage\u0026quot; was performed, but improvement was not observed postoperatively. \u0026quot;Intracranial haematoma evacuation + decompressive craniectomy\u0026rdquo; was performed, and the operation went well. After surgery, the patient was treated with dehydration, neurotrophic\u0026nbsp;treatment, phlegm reduction, and intracranial pressure reduction, and the patient\u0026apos;s condition was improved. At that time, the patient was conscious and could pronounce words but could not speak complete sentences. He could not move his left limbs. He occasionally coughed and expectorated white sputum. He had no nausea or vomiting but had a right skull defect. The patient was admitted to the hospital for further treatment due to a \u0026ldquo;right temporoparietal skull defect\u0026rdquo;. The patient was fed through a nasal feeding tube, and the urinary catheter was retained.\u003c/p\u003e\n\u003cp\u003eThe patient had an 8-year history of hypertension and was taking \u0026ldquo;nifedipine 20 mg bid\u0026rdquo; to reduce his blood pressure, but his blood pressure was not well controlled (140\u0026ndash;160/90\u0026ndash;100 mmHg). Twenty years ago, his left upper extremity and left rib were fractured due to trauma, and a plate was placed in the left upper extremity (the specifics are unknown). He had a left eye injury for which he underwent surgery 3 years ago (the specifics are unknown). His father suffered from hypertension and intracerebral haemorrhage, and his brother had hypertension. The admission diagnoses were right temporoparietal skull defect, right basal ganglion haemorrhage in the recovery period, grade 3 hypertension (very high risk), left hemiparesis, motor aphasia, bilateral pneumonia, and anaemia. Cranial defect repair under general anaesthesia was planned.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient underwent three rounds of general anaesthesia on 2021.04.28, 2021.05.11, and 2022.8.22:\u003c/p\u003e\n\u003cp\u003eThe first round of general anaesthesia (2021.04.28): The vital signs of the patient were normal when the patient entered the operating room. After anaesthesia was induced with 2 mg of midazolam, 14 mg of etomidate, 30 \u0026micro;g of sufentanil, and 50 mg of atracurium, skin flushing and systemic rash developed rapidly. The patient presented with conjunctival congestion and oedema, large face mask compression resistance, a poor chest rise, a blood pressure as low as 50/30 mmHg, and a heart rate of 118 beats/min. Anaphylactic shock was considered, and the trachea was intubated immediately. The airway pressure was 36 cm H\u003csub\u003e2\u003c/sub\u003eO, and the breath sounds were coarse in both lungs. The patient was given volume expansion therapy, an intravenous infusion of 0.1 mg adrenaline, an intravenous infusion of 80 mg methylprednisolone sodium succinate, intratracheal administration of salbutamol aerosol, intravenous infusion of 0.5 g diprophylline, a continuous epinephrine pump at 0.02 \u0026micro;g/kg/min, and a continuous norepinephrine pump at 0.02 \u0026micro;g/kg/min. The doses were adjusted based on the vital signs. His blood pressure gradually increased to 92/50 mmHg. Emergency arterial puncture was performed for invasive arterial blood pressure (ABP) monitoring, and emergency arterial blood gas analysis (Table 1, A) was performed. The results showed that blood K\u003csup\u003e+\u003c/sup\u003e was low, at 2.8 mmol/L, and the arterial partial pressure of carbon dioxide (PaCO\u003csub\u003e2\u003c/sub\u003e) was 53.6 mmHg. The patient was given an intravenous infusion of potassium magnesium aspartate (50 mL). The haemodynamic status of the heart was monitored via transthoracic echocardiography. The systolic and diastolic functions and ventricular wall mobility were evaluated to rule out pulmonary embolism. The patient was haemodynamically stable, the breath sounds of both lungs were clear on auscultation, and the airway pressure fell to 21 cm H\u003csub\u003e2\u003c/sub\u003eO. After communicating with the surgeons and family members, the surgery was delayed, and the patient was returned to the ward with tracheal intubation.\u003c/p\u003e\n\u003cp\u003eSecond round of general anaesthesia (2021.05.11): The patient was admitted to the operation room for routine monitoring, and the invasive ABP monitoring via radial artery puncture was performed under local anaesthesia. The vital signs were normal, and arterial blood gas analysis was normal (Table 1, B). After induction of anaesthesia with 3 mg of midazolam, 100 mg of propofol, and 10 mg of cisatracurium besylate, the patient rapidly developed skin flushing and systemic maculopapular rash; his blood pressure fell to 55/36 mmHg, his heart rate was 150 beats/min, and his oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e) reached 89%. Anaphylactic shock was considered, tracheal intubation was performed immediately, and an intravenous bolus injection of 0.1 mg epinephrine was given. The effect was not satisfactory. Epinephrine was injected intravenously at a dose of 1 mg, and epinephrine was given via a continuous intravenous pump at a rate of 0.03 \u0026micro;g/kg/min. The doses were adjusted based on vital signs. An intravenous infusion of 80 mg of methylprednisolone sodium succinate, 1.0 g of calcium gluconate, and 100 mg of hydrocortisone was given. The patient suddenly developed ventricular fibrillation. Cardiopulmonary resuscitation was rapidly performed, and emergency electrical defibrillation (bidirectional, asynchronous, 200 J/time) was performed three times. Lidocaine (100 mg) was intravenously infused, and Cordarone (300 mg) was intravenously administered. The resuscitation was successful, and the sinus rhythm was restored. Arterial blood gas analysis was performed (Table 1, C), and the results showed a pH of 7.26 and a PaCO\u003csub\u003e2\u003c/sub\u003e of 60 mmHg. Hyperventilation was performed. The operation was suspended after the vital signs returned to normal. After the patient awoke, the tube was removed, and the patient was returned to the ward.\u003c/p\u003e\n\u003cp\u003eThe third round of general anaesthesia (2022.8. 22): In view of the ARs that occurred in the previous two rounds of anaesthesia, preoperative genetic testing for gene polymorphisms associated with anaesthetic drug sensitivity was performed. The results showed that sufentanil, remifentanil and rocuronium were recommended drugs for this patient, whereas propofol was an optional drug. After admission to the operation room, the vital signs and the bispectral index (BIS) were routinely monitored, and the patient was continuously monitored via radial artery puncture under local anaesthesia. Ultrasound-guided bilateral superior laryngeal nerve block was performed. Sufentanil (20 \u0026micro;g) was slowly administered intravenously in divided doses. After 8% sevoflurane inhalation, a 4# video laryngeal mask was placed. Sevoflurane and remifentanil were used to maintain anaesthesia during the surgery. Preventive use of epinephrine and norepinephrine was recommended to maintain stable vital signs. The results of two preoperative and postoperative blood gas analyses were normal (Table 1, D, E). The patient was fully awake 1 hour after surgery. No adverse reactions were reported, and the patient was safely returned to the ward.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Arterial blood gas analysis\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003epH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e7.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003ePaCO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e53.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e47.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e60.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e38.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e50.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003ePaO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e102.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e73.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e120.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e71.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e92.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eBE (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e-2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eGlu (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eLac (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eHct (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e40.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e49.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e37.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e35.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eNa\u003csup\u003e+\u003c/sup\u003e (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e143.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e138.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e141.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e139.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e138.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eK\u003csup\u003e+\u003c/sup\u003e (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eCa\u003csup\u003e2+\u003c/sup\u003e (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eCl\u003csup\u003e-\u0026nbsp;\u003c/sup\u003e(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e108.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e105.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e107.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e103.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e104.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003etHb g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e15.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eSaO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e98.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e95.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e98.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e96.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 74px;\"\u003e\n \u003cp\u003e98.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eIn this case, the patient developed severe ARs (skin flushing, hypotension, bronchospasm and ventricular fibrillation), which were in line with the characteristics of type I hypersensitivity reactions. Although midazolam was used on both occasions, on the basis of drug allergy epidemiological data, the MRs, members of quaternary ammonium group of benzylisoquinolines, were more likely to be the core allergen[5-8].\u0026nbsp;These drugs bind to IgE on the surface of mast cells, which triggers the release of histamine, resulting in vasodilation and bronchospasm[9].\u0026nbsp;Notably, the patient did not develop ARs after cisatracurium was used in the past, suggesting that immune status and genetic factors (such as HLA genotype) may affect AR susceptibility[10-13].\u003c/p\u003e\n\u003cp\u003eAtracurium and cisatracurium besylate are both benzylisoquinoline MRs with a quaternary ammonium group in their structure and may cause ARs through IgE-mediated cross-reactions[3, 14, 15].\u0026nbsp;Studies have shown that the cross-AR rate of benzylisoquinoline MRs was as high as 60\u0026ndash;70%, whereas aminosteroids (such as rocuronium) had a low cross-AR risk due to significant differences in their chemical structures[15-17].\u0026nbsp;For the third round of anaesthesia, although genetic testing results recommended the use of rocuronium bromide, in view of the first two severe ARs, multimodal analgesia combined with a laryngeal mask for general anaesthesia was eventually used, and MRs were not used, which confirmed the reliability of the principle of \u0026ldquo;structural difference avoidance\u0026rdquo;.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eARs are type I hypersensitivity reactions, and the clinical manifestations are mostly integumentary (flushing, urticaria, and angioedema), circulatory (lower blood pressure, brady or tachycardia, arrhythmias and cardiac arrest) and respiratory system (bronchospasm and increased ventilatory resistance) symptoms[18]. As the most critical AR form, anaphylactic shock is characterized by damage to multiple organs in a system, sudden onset and rapid progression, and anaphylactic shock can rapidly lead to fatal complications such as airway obstruction and circulatory collapse. In approximately 50% of patients, symptoms develop within 5 minutes of exposure to the allergen[19-21]. The core underlying mechanism is as follows: exogenous antigens activate IgE-mediated degranulation of mast cells, which release mediators such as histamine, leukotriene, and platelet-activating factors, resulting in vasodilation, increased capillary permeability, and smooth muscle contraction[22]. In clinical treatment, the suspected drug should be immediately stopped, and epinephrine should be given in a stepwise manner (initial dose 0.05\u0026ndash;0.1 mg via intravenous infusion) to reverse the haemodynamic disorder[23-26].\u003c/p\u003e\n\u003cp\u003eTimely and effective rescue is the core for safely managing the crisis into patient stability. In this patient, when the first two ARs occurred, the anaesthesia team quickly started the standard procedure: an intravenous bolus injection of epinephrine (initial dose, 0.05\u0026ndash;0.1 mg; titrated up to 1 mg if ineffective)[18]\u0026nbsp;combined with methylprednisolone (80\u0026ndash;120 mg) to inhibit the inflammatory cascade reactions[27]. Emergency tracheal intubation was performed to increase blood oxygen levels. Electrical defibrillation (bidirectional, 200 J) and cardiopulmonary resuscitation were performed to restore sinus rhythm[28].\u0026nbsp;The patient\u0026rsquo;s internal environment was evaluated in real time through invasive ABP monitoring and blood gas analysis, and the dose of vasoactive drugs was adjusted[4].\u0026nbsp;This case highlights the need for the anaesthesia team to regularly practice AR emergency plans and to be proficient in emergency drug dosage, airway management, and advanced life support techniques to ensure rapid identification and accurate intervention in a timely manner.\u003c/p\u003e\n\u003cp\u003eBefore the third round of anaesthesia, low-risk drugs (sufentanil, remifentanil, and rocuronium) were accurately screened through genetic testing, and an individualized regimen was developed based on results: ultrasound-guided superior laryngeal nerve block (0.375% ropivacaine, 4 mL/kg/min) effectively inhibited the airway reflex, reduced the number of intubation stimulations, and avoided the use of MRs[29]. Stable sedation and analgesia were achieved via inhalation of sevoflurane (maintenance concentration of 1.5\u0026ndash;2.0%) combined with remifentanil (0.1\u0026ndash;0.2 \u0026mu;g/kg/min). Preventive pumping of epinephrine (0.01 \u0026mu;g/kg/min) and norepinephrine (0.05 \u0026mu;g/kg/min) was used to maintain haemodynamic stability[19]. This regimen successfully avoided exposure to MRs, confirming that genetic testing can be used to determine the appropriate medications for high-risk patients by revealing differences in drug metabolism and response (such as the effect of CYP2B6 on the metabolism of propofol).\u003c/p\u003e\n\u003cp\u003eHowever, challenges are still faced in the widespread application of genetic testing in the field of anaesthesia, such as the high cost of testing and the professional knowledge required for the interpretation of test results[12]. Most existing studies have evaluated small-sample single-centre data, and large-sample multicentre studies are needed to verify the association between gene polymorphisms and drug response[19]. To prevent MR-induced ARs, a detailed allergy history (drugs, food, latex, etc.) should be obtained before surgery. Skin prick tests or serum-specific IgE tests (such as tryptase and histamine) should be performed for high-risk patients[15]. Drugs with common antigenic epitopes (such as benzylisoquinoline MRs) should be avoided, and alternative drugs with significant structural differences (such as the aminosteroid rocuronium bromide) should be used first[3].\u003c/p\u003e\n\u003cp\u003eFor patients at high risk of ARs (such as those with a previous history of drug allergies), a skin prick test or serum-specific IgE tests (such as tryptase and mast cell tryptase) should be performed to clarify the sensitization risk. MRs with significantly different chemical structures (such as the aminosteroid rocuronium bromide instead of benzylisoquinoline) should be chosen first to avoid the risk of cross-ARs[3]. Moreover, during the anaesthesia process, haemodynamics (invasive ABP monitoring), airway pressure, and skin manifestations should be monitored in real time, and the suspected drugs should be stopped immediately. Rescue procedures should be started if signs of ARs (such as skin rash and a sudden drop in SpO\u003csub\u003e2\u003c/sub\u003e) are detected.\u003c/p\u003e\n\u003cp\u003eIn the future, we will focus on the molecular mechanisms of cross-sensitivity to MRs (such as the binding characteristics of the HLA-B*57:01 genotype and quaternary ammonium group) and the development of targeted blocking antibodies or hyposensitizing drugs[30]. A gene\u0026ndash;phenotype-medication database should be constructed and used in combination with artificial intelligence (AI) to analyse individualized medication regimens (e.g., the selection of opioid drugs based on CYP2D6 metabolizing ability)[31]. China should promote the use of rapid point-of-care testing (POCT) to obtain genetic testing results quickly (results available within 30 minutes) and reduce the cost of testing to less than 50% of that of conventional methods[32].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this case, the patient experienced severe ARs due to the use of different MRs during two rounds of general anaesthesia, and the patient finally underwent successful surgery with the help of genetic testing and an individualized anaesthesia regimen. This case fully demonstrates the significance of detailed preoperative evaluation, allergen detection, and genetic testing-guided drug selection in perioperative management. MR-induced ARs are severe, and there is a risk of cross-ARs. Clinicians should pay very close attention to the possibility of MR-induced ARs, and protocols for the prevention and management of MR-induced ARs should be strengthened. An in-depth study of the pathogenesis of MR-induced ARs, the optimization of genetic testing technology and clinical application of genetic testing are expected to further improve the safety of anaesthesia and provide more reliable safety for patients during medical procedures.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMRs Muscle relaxants \u003c/p\u003e\n\u003cp\u003eARs Sallergic reactions \u003c/p\u003e\n\u003cp\u003eCT Computed tomography \u003c/p\u003e\n\u003cp\u003eABP Arterry blood \u003c/p\u003e\n\u003cp\u003ePaCO\u003csub\u003e2\u003c/sub\u003e\u003csub\u003e \u003c/sub\u003ePressure carbon dioxide \u003c/p\u003e\n\u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e\u003csub\u003e \u003c/sub\u003ePulse oximetry \u003c/p\u003e\n\u003cp\u003eBIS Bispectral index\u003c/p\u003e\n\u003cp\u003ePOCT Point-of-Care Testing\u003c/p\u003e\n\u003cp\u003eAI Artificial intelligence \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLanyun Xie and Yalei Gao contributed to performing of anesthesia and drafting of manuscript. Jinwan Guo and Fei Zhou contributed to data collection. Yongtao Sun contributed to performing of anesthesia and revising the manuscript. All authors have read and approval the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe project was supported by Clinical research Special Fund of Wu Jie-ping Medical Foundation (320.6750.2024-15-19), and Education and Teaching reform Research project of Shandong First Medical University (Shandong Academy of Medical Sciences) (XM2024091). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data related to this case report are contained within the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the clinical details and clinical images was obtained from the patient.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMertes PM, Laxenaire MC: \u003cstrong\u003eAllergic reactions occurring during anaesthesia\u003c/strong\u003e. \u003cem\u003eEur J Anaesthesiol \u003c/em\u003e2002, \u003cstrong\u003e19\u003c/strong\u003e(4):240-262.\u003c/li\u003e\n\u003cli\u003eHarper NJ, Dixon T, Dugu\u0026eacute; P, Edgar DM, Fay A, Gooi HC, Herriot R, Hopkins P, Hunter JM, Mirakian R\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSuspected anaphylactic reactions associated with anaesthesia\u003c/strong\u003e. \u003cem\u003eAnaesthesia \u003c/em\u003e2009, \u003cstrong\u003e64\u003c/strong\u003e(2):199-211.\u003c/li\u003e\n\u003cli\u003eSadleir PH, Clarke RC, Bunning DL, Platt PR: \u003cstrong\u003eAnaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011\u003c/strong\u003e. \u003cem\u003eBr J Anaesth \u003c/em\u003e2013, \u003cstrong\u003e110\u003c/strong\u003e(6):981-987.\u003c/li\u003e\n\u003cli\u003eDewachter P, Mouton-Faivre C, Emala CW: \u003cstrong\u003eAnaphylaxis and anesthesia: controversies and new insights\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2009, \u003cstrong\u003e111\u003c/strong\u003e(5):1141-1150.\u003c/li\u003e\n\u003cli\u003eYasuda M, Moriwaki K, Tsutsumi YM: \u003cstrong\u003eConcurrent positive skin tests to prophylactic antibiotics and rocuronium in two patients with life-threatening anaphylaxis after induction of anesthesia\u003c/strong\u003e. \u003cem\u003eJA Clin Rep \u003c/em\u003e2021, \u003cstrong\u003e7\u003c/strong\u003e(1):37.\u003c/li\u003e\n\u003cli\u003eSun Y, Huang X: \u003cstrong\u003eSevere anaphylaxis after general anesthesia induction\u003c/strong\u003e. \u003cem\u003eJ Anesth \u003c/em\u003e2021, \u003cstrong\u003e35\u003c/strong\u003e(5):771.\u003c/li\u003e\n\u003cli\u003eMertes PM, Volcheck GW: \u003cstrong\u003eAnaphylaxis to neuromuscular-blocking drugs: all neuromuscular-blocking drugs are not the same\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2015, \u003cstrong\u003e122\u003c/strong\u003e(1):5-7.\u003c/li\u003e\n\u003cli\u003eMertes PM, Laxenaire MC, Alla F: \u003cstrong\u003eAnaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2003, \u003cstrong\u003e99\u003c/strong\u003e(3):536-545.\u003c/li\u003e\n\u003cli\u003eNguyen SMT, Rupprecht CP, Haque A, Pattanaik D, Yusin J, Krishnaswamy G: \u003cstrong\u003eMechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond\u003c/strong\u003e. \u003cem\u003eInt J Mol Sci \u003c/em\u003e2021, \u003cstrong\u003e22\u003c/strong\u003e(15).\u003c/li\u003e\n\u003cli\u003eMoorthy SS, Laurent B, Pandya P, Fry V: \u003cstrong\u003eAnaphylactoid reaction to etomidate: report of a case\u003c/strong\u003e. \u003cem\u003eJ Clin Anesth \u003c/em\u003e2001, \u003cstrong\u003e13\u003c/strong\u003e(8):582-584.\u003c/li\u003e\n\u003cli\u003eJoo J, Koh HJ: \u003cstrong\u003eCardiac Arrest Due to Perioperative Anaphylactic Shock Induced by Re-Exposure to Propofol: A Case Report\u003c/strong\u003e. \u003cem\u003eJ Clin Med \u003c/em\u003e2024, \u003cstrong\u003e13\u003c/strong\u003e(18).\u003c/li\u003e\n\u003cli\u003eTang R, Lyu X, Sun J, Li H: \u003cstrong\u003eGenetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases\u003c/strong\u003e. \u003cem\u003eEndocr Metab Immune Disord Drug Targets \u003c/em\u003e2024, \u003cstrong\u003e24\u003c/strong\u003e(10):1215-1223.\u003c/li\u003e\n\u003cli\u003eSio YY, Shi P, Matta SA, Fok YTR, Chiang WC, Say YH, Chew FT: \u003cstrong\u003eFunctional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases\u003c/strong\u003e. \u003cem\u003eInt Arch Allergy Immunol \u003c/em\u003e2023, \u003cstrong\u003e184\u003c/strong\u003e(6):609-623.\u003c/li\u003e\n\u003cli\u003eKarila C, Brunet-Langot D, Labbez F, Jacqmarcq O, Ponvert C, Paupe J, Scheinmann P, de Blic J: \u003cstrong\u003eAnaphylaxis during anesthesia: results of a 12-year survey at a French pediatric center\u003c/strong\u003e. \u003cem\u003eAllergy \u003c/em\u003e2005, \u003cstrong\u003e60\u003c/strong\u003e(6):828-834.\u003c/li\u003e\n\u003cli\u003eLi J, Best OG, Rose MA, Green SL, Fulton RB, Capon MJ, Krupowicz BA, Fernando SL: \u003cstrong\u003eAssessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis\u003c/strong\u003e. \u003cem\u003eBr J Anaesth \u003c/em\u003e2019, \u003cstrong\u003e123\u003c/strong\u003e(1):e144-e150.\u003c/li\u003e\n\u003cli\u003eGouel-Ch\u0026eacute;ron A, Neukirch C, Chollet-Martin S, Valent A, Plaud B, Longrois D, Nicaise-Roland P, Montravers P, de Chaisemartin L: \u003cstrong\u003eNeuromuscular blocking agent drug challenge: a literature review and protocol proposal with biological evaluation\u003c/strong\u003e. \u003cem\u003eEur J Anaesthesiol \u003c/em\u003e2024, \u003cstrong\u003e41\u003c/strong\u003e(10):722-727.\u003c/li\u003e\n\u003cli\u003eJeong J, Yun JE, Kim HJ, Jang JY, Seo JH, Lee SY, Kim WH, Seo JH, Kang HR: \u003cstrong\u003eNeuromuscular blocking agent re-exposure in a retrospective cohort with neuromuscular blocking agent-associated anaphylaxis\u003c/strong\u003e. \u003cem\u003eAnn Allergy Asthma Immunol \u003c/em\u003e2023, \u003cstrong\u003e131\u003c/strong\u003e(5):637-644.e631.\u003c/li\u003e\n\u003cli\u003eNavalpakam A, Thanaputkaiporn N, Poowuttikul P: \u003cstrong\u003eManagement of Anaphylaxis\u003c/strong\u003e. \u003cem\u003eImmunol Allergy Clin North Am \u003c/em\u003e2022, \u003cstrong\u003e42\u003c/strong\u003e(1):65-76.\u003c/li\u003e\n\u003cli\u003eTacquard C, Iba T, Levy JH: \u003cstrong\u003ePerioperative Anaphylaxis\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2023, \u003cstrong\u003e138\u003c/strong\u003e(1):100-110.\u003c/li\u003e\n\u003cli\u003eTakazawa T, Yamaura K, Hara T, Yorozu T, Mitsuhata H, Morimatsu H: \u003cstrong\u003ePractical guidelines for the response to perioperative anaphylaxis\u003c/strong\u003e. \u003cem\u003eJ Anesth \u003c/em\u003e2021, \u003cstrong\u003e35\u003c/strong\u003e(6):778-793.\u003c/li\u003e\n\u003cli\u003eMcHugh K, Repanshek Z: \u003cstrong\u003eAnaphylaxis: Emergency Department Treatment\u003c/strong\u003e. \u003cem\u003eEmerg Med Clin North Am \u003c/em\u003e2022, \u003cstrong\u003e40\u003c/strong\u003e(1):19-32.\u003c/li\u003e\n\u003cli\u003eLi X, Ma Q, Yin J, Zheng Y, Chen R, Chen Y, Li T, Wang Y, Yang K, Zhang H\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eA Clinical Practice Guideline for the Emergency Management of Anaphylaxis (2020)\u003c/strong\u003e. \u003cem\u003eFront Pharmacol \u003c/em\u003e2022, \u003cstrong\u003e13\u003c/strong\u003e:845689.\u003c/li\u003e\n\u003cli\u003eMuraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, Riggioni C, de Silva D, Angier E, Arasi S\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eEAACI guidelines: Anaphylaxis (2021 update)\u003c/strong\u003e. \u003cem\u003eAllergy \u003c/em\u003e2022, \u003cstrong\u003e77\u003c/strong\u003e(2):357-377.\u003c/li\u003e\n\u003cli\u003eManian DV, Volcheck GW: \u003cstrong\u003ePerioperative Anaphylaxis: Evaluation and Management\u003c/strong\u003e. \u003cem\u003eClin Rev Allergy Immunol \u003c/em\u003e2022, \u003cstrong\u003e62\u003c/strong\u003e(3):383-399.\u003c/li\u003e\n\u003cli\u003eBruhn I, Bauer A, Beissert S, Neumeister V, Spornraft-Ragaller P: \u003cstrong\u003eIntraoperative anaphylaxis to atracurium\u003c/strong\u003e. \u003cem\u003eJ Dtsch Dermatol Ges \u003c/em\u003e2021, \u003cstrong\u003e19\u003c/strong\u003e(12):1784-1785.\u003c/li\u003e\n\u003cli\u003eWang N, Zhang Y, Hu Y, Yang Q, Su Z: \u003cstrong\u003eSerious bronchospasm induced by cisatracurium besylate: A case report\u003c/strong\u003e. \u003cem\u003eMedicine (Baltimore) \u003c/em\u003e2021, \u003cstrong\u003e100\u003c/strong\u003e(15):e25516.\u003c/li\u003e\n\u003cli\u003eMertes PM, Demoly P, Malinovsky JM: \u003cstrong\u003eHypersensitivity reactions in the anesthesia setting/allergic reactions to anesthetics\u003c/strong\u003e. \u003cem\u003eCurr Opin Allergy Clin Immunol \u003c/em\u003e2012, \u003cstrong\u003e12\u003c/strong\u003e(4):361-368.\u003c/li\u003e\n\u003cli\u003eMoitra VK, Einav S, Thies KC, Nunnally ME, Gabrielli A, Maccioli GA, Weinberg G, Banerjee A, Ruetzler K, Dobson G\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eCardiac Arrest in the Operating Room: Resuscitation and Management for the Anesthesiologist: Part 1\u003c/strong\u003e. \u003cem\u003eAnesth Analg \u003c/em\u003e2018, \u003cstrong\u003e126\u003c/strong\u003e(3):876-888.\u003c/li\u003e\n\u003cli\u003eFowler JG, VanEenenaam DP, Jr., Johnson KN, Courtemanche CD, Strathman AJ, Reynolds JE: \u003cstrong\u003eSingle midline injection for bilateral superior laryngeal nerve block\u003c/strong\u003e. \u003cem\u003eJ Clin Anesth \u003c/em\u003e2020, \u003cstrong\u003e66\u003c/strong\u003e:109922.\u003c/li\u003e\n\u003cli\u003eElst J, Maurer M, Sabato V, Faber MA, Bridts CH, Mertens C, Van Houdt M, Van Gasse AL, van der Poorten MM, De Puysseleyr LP\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eNovel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones\u003c/strong\u003e. \u003cem\u003eFront Immunol \u003c/em\u003e2021, \u003cstrong\u003e12\u003c/strong\u003e:668962.\u003c/li\u003e\n\u003cli\u003eLopes S, Rocha G, Guimar\u0026atilde;es-Pereira L: \u003cstrong\u003eArtificial intelligence and its clinical application in Anesthesiology: a systematic review\u003c/strong\u003e. \u003cem\u003eJ Clin Monit Comput \u003c/em\u003e2024, \u003cstrong\u003e38\u003c/strong\u003e(2):247-259.\u003c/li\u003e\n\u003cli\u003eLiu H, Li Z, Yan S, Ming S: \u003cstrong\u003eAdverse event signal analysis of remimazolam using the FDA adverse event reporting system database\u003c/strong\u003e. \u003cem\u003eActa Anaesthesiol Scand \u003c/em\u003e2025, \u003cstrong\u003e69\u003c/strong\u003e(3):e14588.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"General anaesthesia, Muscle relaxants, Allergic reactions, Cross-allergic reactions","lastPublishedDoi":"10.21203/rs.3.rs-6199091/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6199091/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMuscle relaxants (MRs) are indispensable drugs in general anaesthesia, as they are used to relax skeletal muscles for tracheal intubation and surgical operations. However, MRs are also the leading cause (accounting for 50\u0026ndash;70%) of perioperative allergic reactions (ARs). Among the various MRs, nondepolarizing MRs are likely to cause cross-ARs due to their chemical structural similarities.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eThe case of a 47-year-old male patient who experienced severe ARs caused by different MRs (atracurium and cisatracurium) in two rounds of general anaesthesia is reported. Although the type of anaesthesia drugs used was changed before the second round of anaesthesia, ARs still developed, as did severe ventricular fibrillation, suggesting the occurrence of cross-ARs.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis patient experienced severe ARs during two rounds of anaesthesia. Surgery was ultimately completed successfully through genetic testing and an individualized anaesthesia regimen, suggesting the significance of detailed preoperative evaluation, allergen detection and genetic testing-guided drug selection in perioperative management.\u003c/p\u003e","manuscriptTitle":"Severe allergic reactions induced by different muscle relaxants in the same patient in two rounds of general anaesthesia: A case report and a literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 04:31:36","doi":"10.21203/rs.3.rs-6199091/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a19cc647-b72d-4064-b4d3-630782b90d37","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-09T04:31:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 04:31:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6199091","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6199091","identity":"rs-6199091","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}