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Review article

Perioperative anaphylaxis caused by muscle relaxants: do we know enough?

Danica Marković1, Natalija Vuković1, Jelena Milenković2, Bojana Marković-Živković3, Ivana Budić1,4

ABSTRACT

Perioperative anaphylaxis caused by muscle relaxants represents a relatively rare, albeit a serious complication during anesthesia. It can result in serious morbidity or even mortality. This reaction usually happens before or after intubation of a patient, that is, a few minutes after muscle relaxant administration. The beginning of the reaction can be missed, even by the most experienced anesthesiologist, since its recognition depends on the severity of the symptoms. There are no guidelines specific to the therapy of muscle relaxant anaphylaxis and therefore therapy is based simply on the general guidelines. Also, in many countries, there are no registries of the incidence of anaphylaxis caused by muscle relaxants. Therefore, this is an extremely important subject for anesthesiology practice, and it requires more attention.


INTRODUCTION

Perioperative anaphylaxis represents a serious complication which occurs during anesthesia, and which requires timely recognition by the anesthesiologist and their timely reaction [1]. Anaphylactic reaction during anesthesia may occur at any moment, however, anaphylactic reaction caused by muscle relaxants most commonly occurs during the induction of anesthesia. The induction period of anesthesia is characterized by the administration of a number of medicaments, which is why it is very complicated for the anesthesiologist to determine what caused the reaction [2].

Antibiotics and muscle relaxants are amongst the most common causes of allergic reactions occurring in the perioperative period. Among the muscle relaxants, the most common triggers of allergic reactions are the following: suxamethonium, rocuronium, vecuronium, pancuronium, and atracurium [3],[4]. The incidence of perioperative anaphylaxis is unknown; however, studies indicate that frequency of occurrence ranges between one per 3,000 cases and one per 20,000 cases [5]. It particularly difficult to obtain data in less developed countries where records of these occurrences are rarely kept and the availability of postoperative testing is limited. It is interesting that data can be found in literature indicating that anaphylactic reactions in the perioperative period are exceptionally frequent in France, Great Britain, Belgium, Australia, New Zeeland, and Spain [4],[6]. Such data do not necessarily have to indicate that anaphylactic reaction to muscle relaxants is indeed characteristic of the above listed regions, rather it is more probable that in these countries there is a registry in place recording the occurrence of anaphylaxis in the perioperative period. 

Recognizing anaphylaxis in the perioperative period is not always easy, and this is yet another reason for the lack of more precise data on the incidence of anaphylactic reaction to muscle relaxants. It is most commonly recognized by manifestations on the skin and upon the development of abnormal vital signs, which are immediately apparent as they are monitored in the operating theatre. The fact is, however, that the skin of the patient is mostly covered with surgical drapes during a procedure, which is why literature advises anesthesiologists to suspect anaphylactic reaction during anesthesia whenever the patient displays unexplained hypotension, which may be refractory to inotropes and vasopressors [1]. Even when severe reactions occur, doctors are not sure which particular drug is the cause of the reaction, and, when appropriate tests are not available, these events remain unrecorded. Another aggravating factor is lack of knowledge on behalf of the doctor that anaphylactic reaction to muscle relaxants may occur even without any pervious sensitization of the patient to the particular agent [7].

ETIOLOGY

The precise mechanism of sensitization remains unknown, due to the fact that anaphylaxis occurs even in patients who had previously had no contact with muscle relaxants. Such events indicate the possibility of sensitization being caused by some external factors [6]. Data can be found in literature confirming that the occurrence of a clinically relevant allergic reaction to cross-reactive allergens is a very common occurrence. Namely, cross-reactivity is very common when muscle relaxants are concerned, and the cause of this lies in the very quaternary ammonium structure of epitopes present on the surface of the molecules of muscle relaxants and also within the structure of the molecules of other drugs and disinfection agents [3]. Cross-reactivity within a group of muscle relaxants is very common (predominantly among rocuronium, pancuronium, and vecuronium) as well as between muscle relaxants and other classes of drugs, such as: acetylcholine, morphine, choline, neostigmine, pholcodine, and others [3],[6]. Data on the activation of specific IgE antibodies, after the patient has had contact with certain foods, cosmetic products, and industrial products, can be found in literature [3],[8],[9]. Pholcodine, an opioid cough suppressant, is considered to be the most common ‘silent’ sensitizing agent [6]. 

When hypersensitivity to rocuronium is concerned, cross-reactivity with other muscle relaxants is very common. In a study by Brereton et al., cross-reactions were recorded in as many as 65% of the cases, of which 29% were caused by succinylcholine [10].

Most allergic reactions to muscle relaxants are IgE mediated and include basophiles and mastocytes in their mechanisms. The above-mentioned quaternary ammonium structure is responsible for this mechanism of the reaction development [10]. Other mechanisms of anaphylaxis reaction development have been observed – immunological mechanisms (IgG mediated) and non-immunological (direct activation of mastocytes by MRGPRX2 receptors) [6].

SYMPTOMS

For the anesthesiologist, the first potential warning sign for the possibility of anaphylaxis reaction in the perioperative period is data obtained during an examination/consultation with the patient or during preoperative rounds, indicating an allergy to other agents, the so-called atopic disposition. It is rarely that data on previous allergic reactions during anesthesia are obtained from the patient [6]. For all of the above-stated reasons, it is particularly important to ask the patient, during preoperative preparation, to describe how the allergic reaction had previously manifested.

Recognizing the signs and symptoms of anaphylaxis is of the utmost importance for successful treatment and a positive outcome. The advantage that the anesthesiologist has is intraoperative monitoring, which is mandatory in each operating theatre, as well as availability of the venous catheter, which is placed before the patient is taken into the operating room [1].

Depending on the severity of the hypersensitivity reaction, four types of clinical manifestations have been described [1]: grade 1 severity (skin reactions), grade 2 severity (skin reactions together with evident, but non-life-threatening symptoms, such as hypotension, tachycardia, coughing, and other), grade 3 severity (life-threatening symptoms: collapse, tachycardia, bradycardia, arrythmia, bronchospasm), grade 4 severity (cardiac or respiratory arrest). In case of intraoperative anaphylaxis caused by muscle relaxants, symptoms usually occur immediately after anesthesia is induced in a patient, and they include skin, respiratory and cardiovascular symptoms [6].

Skin reactions usually occur first, in the form of erythema, urticaria, and angioedema, and they have the highest incidence (80 – 90%). However, the fact remains that, if these symptoms are absent at the beginning of the procedure, there is often a delay in diagnosing anaphylaxis. Skin manifestations may be absent in patients who were given corticosteroids during their preoperative preparation. Often, skin manifestations occur later and are discovered only after the surgical drapes are removed [1]. Cardiovascular symptoms, in the form of tachycardia, bradycardia, arrythmia, hypotension, cardiovascular collapse, and, in the most severe cases, cardiac arrest, are usually the first symptoms to be observed after skin manifestations are noted. These symptoms are the ones most easily spotted in the environment of the surgical suite, i.e., in the presence of predominantly non-invasive patient monitoring, during every procedure. Also, cold and wet hands and feet and a thready pulse can be noted. Respiratory symptoms, in the form of bronchospasm, usually become evident after tracheal intubation and manifest as failure of the balloon to deflate, while if the respiratory symptoms occur earlier, they manifest as labored breathing through the mask, which is when intubation should be performed, and appropriate therapy should be administered as soon as possible [1]. Sometimes, intubation of such patients is really difficult and challenging [11]. Respiratory symptoms are present in 70% of the cases. Symptoms of the central nervous system are very often not evident in the perioperative period, since the patient is sedated or anesthetized [1].

As of 1991, in their case reports, clinicians started reporting acute coronary syndrome caused by coronary vasospasm and mainly described it as allergic angina or Kounis syndrome [12],[13]. It occurred mostly in men aged between 40 and 80 years and was observed around an hour after the administration of the causative agent. Clinical signs observed during these episodes were as follows: ST elevation (predominantly on lead II of the ECG printout), severe hypotension, drop in the level of ETCO2, tachycardia with ventricular extrasystoles [12].

It is a fact that the lethal outcome, as the consequence of perioperative anaphylactic reaction, is not that rare. With respect to anaphylaxis caused by muscle relaxants, mortality is estimated to be as high as 4%, despite the timely execution of resuscitation measures [6]. Also, statistical data indicated that anaphylactic reaction resulted in significant morbidity, while 2% of the patients developed long-term neurological sequelae [5].

There is no established rule that would prepare an anesthesiologist for the appropriate reaction, since experience has shown that initial symptoms may be mild, in the form of hypotension, while in a different patient a cardiovascular symptom may initially present as a severe form of bradycardia progressing to cardiac arrest [14]. Although the symptoms of anaphylaxis are easily recognizable in a patient who is awake, they may be disguised during anesthesia and may remain unnoticed even by an experienced anesthesiologist. The most commonly occurring symptoms may easily be attributed to the overdosing of drugs used in the induction of anesthesia, as well as to histamine release. Tachycardia and respiratory symptoms may be interpreted by inexperienced anesthesiologists as the consequence of shallow anesthesia or malignant hyperthermia. It is important to remember that the absence of skin reactions does not necessarily exclude the diagnosis of anaphylaxis [14].

TREATMENT

According to the recommendations for the treatment of perioperative anaphylaxis, it is necessary to first discontinue the administering of the drug causing the anaphylaxis, if there is reasonable suspicion as to which drug is the cause of the particular reaction. It is of the utmost importance to secure the airway and to begin with the administration of oxygen. The drug of choice is adrenalin 1%, 0.15 – 0.6 mg, administered intramuscularly, and in more severe cases, administered in a bolus, at the dose of 1 mcg/kg of body weight, intravenously. The dose may be readministered every 10 to 15 minutes, or even every five minutes, if the reaction is of a greater severity. Adrenalin acts on alpha and beta receptors, and therefore, as a consequence, its action results in vasoconstriction, vascular permeability reduction, bronchodilatation, edema reduction, and inotropic action on the myocardium. Regardless of whether it is administered intramuscularly or intravenously, adrenalin is the fastest acting of all drugs that can be used in anaphylaxis. Adrenalin can also be administered through inhalation, in case of laryngeal edema and in case of bronchospasm. In bronchospasm it is recommended that a beta agonist, for example salbutamol, is added to the adrenalin inhalation. Other drugs that may also be used in the treatment of anaphylaxis are the following: dopamine, noradrenalin, vasopressin. If a venous catheter is not already in place, it is necessary to provide for one, before the possible occurrence of vascular collapse. The venous catheter needs to be preserved through constant fluid application. During fluid administration, it is important to understand that dextrans and hydroxyethyl starch (HES) are absolutely contraindicated in the treatment of anaphylaxis. After the administration of adrenalin, aminophylline may be applied, at a dose of 6 mg/kg of body mass, intravenously. Also, it is advised to administer an antihistamine. Glucocorticoids are not useful in the acute phase of anaphylactic reaction [15],[16],[17].

It is important to remember that adrenalin is the therapy of choice in anaphylaxis, combined with plenty of fluids – the so called “filling of the circulatory system”. It is also important to bear in mind that therapy must be introduced immediately after anaphylaxis is suspected [6]. The use of adrenalin is limited by the individual assessment of the clinician regarding the risk of the development of severe arrythmia in the individual patient. Arrythmia mainly occurs as a complication of adrenalin administration, when it is applied in a dose exceeding the one necessary for the situation at hand, which stems from the fact that existing recommendations are not in agreement regarding the initial dose and the route of administration. Also, it has been proven that the risk of the development of harmful effects to the cardiovascular system is reduced when adrenalin is administered intramuscularly. It is of note that the treatment of anaphylactic reaction must be adjusted to the clinical presentation, the patient’s medical history, and the level of response to the applied therapy [1].

Hashimoto et al. described two case reports wherein all the symptoms developing upon the administration of the muscle relaxant disappeared after the administration of sugammadex. Such an event was described by Kim et al., as well [2],[14]. Definitely, sugammadex is not the drug of first choice, as it is of the utmost importance to preserve hemodynamics whilst treating anaphylaxis [2]. What must be pointed out is the fact that there are conflicting opinions on the therapeutic potential of sugammadex in treating anaphylaxis. Namely, some studies describe that sugammadex is, in fact, one of the triggers of anaphylactic reaction, which most commonly presents postoperatively, during the patient’s recovery from anesthesia. The reactions may be such as to require the patient to be intubated again, after he/she has left the operating theatre [1],[8],[19]. The theory of using sugammadex as a therapeutic agent during an anaphylactic reaction to certain muscle relaxants is based on the fact that sugammadex encapsulates the muscle relaxant molecule, however, it is believed that this is not enough to prevent further interaction of ammonium groups with IgE antibodies. Also, the encapsulation of the muscle relaxant is not enough to prevent further mediator release by the already activated mastocytes and basophils [1]. If the anesthesiologist is not certain as to the cause of the reaction, it is better to treat the symptoms.

The decision placed before the anesthesiologist is particularly difficult – should the surgical procedure be continued despite the evident clinical presentation that matches anaphylactic reaction? The answer to this question would be the following: if the reaction is mild and responds to the administered therapy, it is only reasonable to continue with the surgery, especially if the surgical procedure is of great importance to the patient and their health or if the surgery in question is an emergency procedure [20].

POSTOPERATIVE PROCEDURE

The postoperative procedure which follows a reasonable suspicion of allergic reaction caused by muscle relaxants begins with informing the patient of this event and writing a report which the patient will be carrying with them until the suspected hypersensitivity is either confirmed or disproved. The second step is referring the patient for testing, wherein the concentration of histamine/tryptase is measured. Ideally, the measurements are performed immediately after the event (within 15 to 60 minutes), and again after a certain amount of time has elapsed [1]. In Serbia, in smaller centers, testing immediately after anaphylaxis is not possible. Also, it is recommended that a skin test is performed as well, and it represents the third method of confirming the existence of an allergic reaction to muscle relaxants. In case the results are inconclusive, the specific IgE test and the flow cytometry-assisted basophil activation test (BAT) can determine the diagnosis more precisely [6]. The advantage of these tests is that they cannot cause an anaphylactic reaction, as they do not put the patient in contact with the allergen [1]. Another advantage of these tests is their precision, since the BAT test has shown a sensitivity and specificity for anaphylaxis caused by rocuronium of 91.7% and 100%, respectively [21]. With respect to other muscle relaxants, BAT has shown a high specificity with a lower sensitivity. Such a flaw is overcome by combining several tests [1]. 

It is of the utmost importance to decide on the future types of anesthesia in patients with a known history of anaphylactic reaction to muscle relaxants, in cooperation with the surgeon and the patient themselves. If the surgical procedure permits it, the best option is to revert to regional anesthesia. However, if the patient does not consent to this type of anesthesia, it is best to test the sensitivity of the patient to other muscle relaxants and then safely anesthetize the patient [22],[23].

If the recorded anaphylactic reaction was caused by succinylcholine, it is reasonable to revert to the use of rocuronium, as an appropriate substitute for rapid sequence induction, if it is necessary. Such a practice is in place, especially in countries where sugammadex is available, as an efficient reversal of muscle relaxation caused by rocuronium [7],[24],[25]. Extensive epidemiological studies have shown that the incidence of anaphylactic reaction to vecuronium is lower than it is for rocuronium. The reaction to atracurium is ten times less frequent than the reaction to rocuronium and succinylcholine, while the lowest incidence of anaphylactic reaction is for cisatracurium, which is why it can be considered as the drug of choice for future procedures [7],[8]. These data can be a guide in choosing drugs for the induction of anesthesia, in patients with suspected or confirmed allergy to muscle relaxants.

CONCLUSION

Anaphylactic reactions during anesthesia are a relatively rare occurrence, which is why literature is still mainly based on review papers, case reports, and recommendations of individual work groups. These events can definitely be fatal, and it is necessary to carry out more comprehensive research in the near future, as well as to introduce official recommendations on the procedure following the occurrence of an anaphylactic reaction during anesthesia.

  • Conflict of interest:
    None declared.

Informations

Volume 3 No 4

Volume 3 No 4

December 2022

Pages 462-470
  • Keywords:
    anesthesia, anaphylactic reaction, muscle relaxants
  • Received:
    24 October 2022
  • Revised:
    02 November 2022
  • Accepted:
    04 November 2022
  • Online first:
    25 December 2022
  • DOI:
Corresponding author

Danica Marković
Clinic for Anesthesiology and Reanimatology, University Clinical Center in Niš
48 Dr Zoran Đinđić Boulevard, 18000 Niš, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


  • 1. Takazawa T, Yamaura K, Hara T, Yorozu T, Mitsuhata H, Morimatsu H; Working Group for the Preparation of Practical Guidelines for the Response to Anaphylaxis, Safety Committee of the Japanese Society of Anesthesiologists. Practical guidelines for the response to perioperative anaphylaxis. J Anesth. 2021 Dec;35(6):778-93. doi: 10.1007/s00540-021-03005-8. [CROSSREF]

    2. Hashimoto M, Sato Boku A, Tachi N, Okumura Y, Kadoi K, Harada J, Okuda M. Two Cases of Rocuronium-Induced Anaphylaxis/Anaphylactic Shock Successfully Treated with Sugammadex. Anesth Prog. 2019 Fall;66(3):151-5. doi: 10.2344/anpr-66-01-07. [CROSSREF]

    3. Di Leo E, Delle Donne P, Calogiuri GF, Macchia L, Nettis E. Focus on the agents most frequently responsible for perioperative anaphylaxis. Clin Mol Allergy. 2018 Jul 9;16:16. doi: 10.1186/s12948-018-0094-7. [CROSSREF]

    4. Reddy JI, Cooke PJ, van Schalkwyk JM, Hannam JA, Fitzharris P, Mitchell SJ. Anaphylaxis is more common with rocuronium and succinylcholine than with atracurium. Anesthesiology. 2015 Jan;122(1):39-45. doi: 10.1097/ALN.0000000000000512. [CROSSREF]

    5. Miller J, Clough SB, Pollard RC, Misbah SA. Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis. Br J Anaesth. 2018 Jun;120(6):1195-201. doi: 10.1016/j.bja.2018.02.033. [CROSSREF]

    6. Mertes PM, Tacquard C. Muscle Relaxants. In: Bircher AJ, Maibach HI, Brockow K, Barbaud A. Cutaneous Drug Hypersensitivity. Cham:Springer; 2022  pp 215–22. [CROSSREF]

    7. Mertes PM, Volcheck GW. Anaphylaxis to Neuromuscular-blocking Drugs: All Neuromuscular-blocking Drugs Are Not the Same. Anesthesiology 2015; 122: 5–7. [CROSSREF]

    8. 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 Jul;123(1):e144-e150. doi: 10.1016/j.bja.2019.03.001. [CROSSREF]

    9. 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 Jun;110(6):981-7. doi: 10.1093/bja/aes506. [CROSSREF]

    10. Brereton A, Russell WJ. Anaphylaxis to muscle relaxants: an audit of ten years of allergy testing at the Royal Adelaide Hospital. Anaesth Intensive Care. 2012 Sep;40(5):861-6. doi: 10.1177/0310057X1204000515. [CROSSREF]

    11. Janković R, Marković D. Airway trauma and management. Anaesthesia 2015; 1(1): 2-7.

    12. Gurunathan U, M Dai B, Dm Cavaye J, R Judd M, A Beuth J, Iswariah H. Coronary vasospasm in the setting of perioperative anaphylaxis: A case report. Anaesth Intensive Care. 2022 Nov;50(6):491-4. doi: 10.1177/0310057X221088602. [CROSSREF]

    13. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract. 1991 Summer;45(2):121-8.

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    16. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S444-64. doi: 10.1161/CIR.0000000000000261. [CROSSREF]

    17. Ring J, Beyer K, Biedermann T, Bircher A, Fischer M, Fuchs T, et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE). Allergo J Int. 2021;30(1):1-25. doi: 10.1007/s40629-020-00158-y. [CROSSREF]

    18. Kim SM, Oh SH, Ryu SA. Treatment of rocuronium-induced anaphylaxis using sugammadex - A case report. Anesth Pain Med (Seoul). 2021 Jan;16(1):56-9. doi: 10.17085/apm.20074. [CROSSREF]

    19. Ho G, Clarke RC, Sadleir PH, Platt PR. The First Case Report of Anaphylaxis Caused by the Inclusion Complex of Rocuronium and Sugammadex. A A Case Rep. 2016 Nov 1;7(9):190-2. doi: 10.1213/XAA.0000000000000382. [CROSSREF]

    20. Schulberg EM, Webb AR, Kolawole H. Early skin and challenge testing after rocuronium anaphylaxis. Anaesth Intensive Care. 2016 May;44(3):425-7. doi: 10.1177/0310057X1604400306.  [CROSSREF]

    21. Ebo DG, Bridts CH, Hagendorens MM, Mertens CH, De Clerck LS, Stevens WJ. Flow-assisted diagnostic management of anaphylaxis from rocuronium bromide. Allergy. 2006 Aug;61(8):935-9. doi: 10.1111/j.1398-9995.2006.01094.x. [CROSSREF]

    22. Agrawal N, Gogia AR, Dayal M. Dilemmas in Anesthetic Management of a Patient with History of Anaphylaxis to Vecuronium. Anesth Essays Res. 2017 Apr-Jun;11(2):525-527. doi: 10.4103/0259-1162.186597. [CROSSREF]

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    24. Janković R, Dinić V, Stojanović M, Savić N, Marković D. Rapid sekvens indukcija- da li je vreme za promene? SJAIT 2015; 37(7-8): 315-8.

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REFERENCES

1. Takazawa T, Yamaura K, Hara T, Yorozu T, Mitsuhata H, Morimatsu H; Working Group for the Preparation of Practical Guidelines for the Response to Anaphylaxis, Safety Committee of the Japanese Society of Anesthesiologists. Practical guidelines for the response to perioperative anaphylaxis. J Anesth. 2021 Dec;35(6):778-93. doi: 10.1007/s00540-021-03005-8. [CROSSREF]

2. Hashimoto M, Sato Boku A, Tachi N, Okumura Y, Kadoi K, Harada J, Okuda M. Two Cases of Rocuronium-Induced Anaphylaxis/Anaphylactic Shock Successfully Treated with Sugammadex. Anesth Prog. 2019 Fall;66(3):151-5. doi: 10.2344/anpr-66-01-07. [CROSSREF]

3. Di Leo E, Delle Donne P, Calogiuri GF, Macchia L, Nettis E. Focus on the agents most frequently responsible for perioperative anaphylaxis. Clin Mol Allergy. 2018 Jul 9;16:16. doi: 10.1186/s12948-018-0094-7. [CROSSREF]

4. Reddy JI, Cooke PJ, van Schalkwyk JM, Hannam JA, Fitzharris P, Mitchell SJ. Anaphylaxis is more common with rocuronium and succinylcholine than with atracurium. Anesthesiology. 2015 Jan;122(1):39-45. doi: 10.1097/ALN.0000000000000512. [CROSSREF]

5. Miller J, Clough SB, Pollard RC, Misbah SA. Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis. Br J Anaesth. 2018 Jun;120(6):1195-201. doi: 10.1016/j.bja.2018.02.033. [CROSSREF]

6. Mertes PM, Tacquard C. Muscle Relaxants. In: Bircher AJ, Maibach HI, Brockow K, Barbaud A. Cutaneous Drug Hypersensitivity. Cham:Springer; 2022  pp 215–22. [CROSSREF]

7. Mertes PM, Volcheck GW. Anaphylaxis to Neuromuscular-blocking Drugs: All Neuromuscular-blocking Drugs Are Not the Same. Anesthesiology 2015; 122: 5–7. [CROSSREF]

8. 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 Jul;123(1):e144-e150. doi: 10.1016/j.bja.2019.03.001. [CROSSREF]

9. 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 Jun;110(6):981-7. doi: 10.1093/bja/aes506. [CROSSREF]

10. Brereton A, Russell WJ. Anaphylaxis to muscle relaxants: an audit of ten years of allergy testing at the Royal Adelaide Hospital. Anaesth Intensive Care. 2012 Sep;40(5):861-6. doi: 10.1177/0310057X1204000515. [CROSSREF]

11. Janković R, Marković D. Airway trauma and management. Anaesthesia 2015; 1(1): 2-7.

12. Gurunathan U, M Dai B, Dm Cavaye J, R Judd M, A Beuth J, Iswariah H. Coronary vasospasm in the setting of perioperative anaphylaxis: A case report. Anaesth Intensive Care. 2022 Nov;50(6):491-4. doi: 10.1177/0310057X221088602. [CROSSREF]

13. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract. 1991 Summer;45(2):121-8.

14. Dardeer A, Shallik N. Perioperative anaphylaxis: A new visit to an old topic. Trends in Anaesthesia and Critical Care. 2019; 26-7: 1-10.  [CROSSREF]

15. Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, et al.; EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014 Aug;69(8):1026-45. doi: 10.1111/all.12437. [CROSSREF]

16. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S444-64. doi: 10.1161/CIR.0000000000000261. [CROSSREF]

17. Ring J, Beyer K, Biedermann T, Bircher A, Fischer M, Fuchs T, et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE). Allergo J Int. 2021;30(1):1-25. doi: 10.1007/s40629-020-00158-y. [CROSSREF]

18. Kim SM, Oh SH, Ryu SA. Treatment of rocuronium-induced anaphylaxis using sugammadex - A case report. Anesth Pain Med (Seoul). 2021 Jan;16(1):56-9. doi: 10.17085/apm.20074. [CROSSREF]

19. Ho G, Clarke RC, Sadleir PH, Platt PR. The First Case Report of Anaphylaxis Caused by the Inclusion Complex of Rocuronium and Sugammadex. A A Case Rep. 2016 Nov 1;7(9):190-2. doi: 10.1213/XAA.0000000000000382. [CROSSREF]

20. Schulberg EM, Webb AR, Kolawole H. Early skin and challenge testing after rocuronium anaphylaxis. Anaesth Intensive Care. 2016 May;44(3):425-7. doi: 10.1177/0310057X1604400306.  [CROSSREF]

21. Ebo DG, Bridts CH, Hagendorens MM, Mertens CH, De Clerck LS, Stevens WJ. Flow-assisted diagnostic management of anaphylaxis from rocuronium bromide. Allergy. 2006 Aug;61(8):935-9. doi: 10.1111/j.1398-9995.2006.01094.x. [CROSSREF]

22. Agrawal N, Gogia AR, Dayal M. Dilemmas in Anesthetic Management of a Patient with History of Anaphylaxis to Vecuronium. Anesth Essays Res. 2017 Apr-Jun;11(2):525-527. doi: 10.4103/0259-1162.186597. [CROSSREF]

23. Naruse S, Iwata H, Suzuki K, Uraoka M, Katoh T, Sato S. [A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test]. Masui. 2016 Jun;65(6):646-8. Japanese.

24. Janković R, Dinić V, Stojanović M, Savić N, Marković D. Rapid sekvens indukcija- da li je vreme za promene? SJAIT 2015; 37(7-8): 315-8.

25. Marković D, Janković R. Wide awake under anesthesia: Scoline apnoea update. SJAIT 2016; 38(3-4): 95-100. [CROSSREF]

1. Takazawa T, Yamaura K, Hara T, Yorozu T, Mitsuhata H, Morimatsu H; Working Group for the Preparation of Practical Guidelines for the Response to Anaphylaxis, Safety Committee of the Japanese Society of Anesthesiologists. Practical guidelines for the response to perioperative anaphylaxis. J Anesth. 2021 Dec;35(6):778-93. doi: 10.1007/s00540-021-03005-8. [CROSSREF]

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6. Mertes PM, Tacquard C. Muscle Relaxants. In: Bircher AJ, Maibach HI, Brockow K, Barbaud A. Cutaneous Drug Hypersensitivity. Cham:Springer; 2022  pp 215–22. [CROSSREF]

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12. Gurunathan U, M Dai B, Dm Cavaye J, R Judd M, A Beuth J, Iswariah H. Coronary vasospasm in the setting of perioperative anaphylaxis: A case report. Anaesth Intensive Care. 2022 Nov;50(6):491-4. doi: 10.1177/0310057X221088602. [CROSSREF]

13. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract. 1991 Summer;45(2):121-8.

14. Dardeer A, Shallik N. Perioperative anaphylaxis: A new visit to an old topic. Trends in Anaesthesia and Critical Care. 2019; 26-7: 1-10.  [CROSSREF]

15. Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, et al.; EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014 Aug;69(8):1026-45. doi: 10.1111/all.12437. [CROSSREF]

16. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S444-64. doi: 10.1161/CIR.0000000000000261. [CROSSREF]

17. Ring J, Beyer K, Biedermann T, Bircher A, Fischer M, Fuchs T, et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE). Allergo J Int. 2021;30(1):1-25. doi: 10.1007/s40629-020-00158-y. [CROSSREF]

18. Kim SM, Oh SH, Ryu SA. Treatment of rocuronium-induced anaphylaxis using sugammadex - A case report. Anesth Pain Med (Seoul). 2021 Jan;16(1):56-9. doi: 10.17085/apm.20074. [CROSSREF]

19. Ho G, Clarke RC, Sadleir PH, Platt PR. The First Case Report of Anaphylaxis Caused by the Inclusion Complex of Rocuronium and Sugammadex. A A Case Rep. 2016 Nov 1;7(9):190-2. doi: 10.1213/XAA.0000000000000382. [CROSSREF]

20. Schulberg EM, Webb AR, Kolawole H. Early skin and challenge testing after rocuronium anaphylaxis. Anaesth Intensive Care. 2016 May;44(3):425-7. doi: 10.1177/0310057X1604400306.  [CROSSREF]

21. Ebo DG, Bridts CH, Hagendorens MM, Mertens CH, De Clerck LS, Stevens WJ. Flow-assisted diagnostic management of anaphylaxis from rocuronium bromide. Allergy. 2006 Aug;61(8):935-9. doi: 10.1111/j.1398-9995.2006.01094.x. [CROSSREF]

22. Agrawal N, Gogia AR, Dayal M. Dilemmas in Anesthetic Management of a Patient with History of Anaphylaxis to Vecuronium. Anesth Essays Res. 2017 Apr-Jun;11(2):525-527. doi: 10.4103/0259-1162.186597. [CROSSREF]

23. Naruse S, Iwata H, Suzuki K, Uraoka M, Katoh T, Sato S. [A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test]. Masui. 2016 Jun;65(6):646-8. Japanese.

24. Janković R, Dinić V, Stojanović M, Savić N, Marković D. Rapid sekvens indukcija- da li je vreme za promene? SJAIT 2015; 37(7-8): 315-8.

25. Marković D, Janković R. Wide awake under anesthesia: Scoline apnoea update. SJAIT 2016; 38(3-4): 95-100. [CROSSREF]


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