Does sugammadex have multiple mechanisms for causing anaphylaxis?

Orihara, Masaki; Nagumo, Kazuhiro; Takazawa, Tomonori

doi:10.1016/j.jaip.2020.04.049

Cited by 6 publications

(4 citation statements)

References 4 publications

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“…Hotta et al previously suggested by skin test that γ-cyclodextrin might be an epitope of sugammadex [4]. In contrast, we recently performed skin tests with γ-cyclodextrin on a patient with anaphylaxis caused by sugammadex but did not observe a positive reaction [6]. Because the results of the current case again suggested that γ-cyclodextrin is not necessarily an epitope, further studies are needed to clarify this issue.…”

Section: Discussioncontrasting

confidence: 61%

“…Recently, an increasing number of patients with positive skin tests for sugammadex-rocuronium complex but negative for sugammadex has been reported [5,8]. There have been many cases in which sugammadex alone showed positive results in skin tests, as in this case; thus, multiple mechanisms of sugammadex-induced anaphylaxis are considered [6].…”

Section: Discussionmentioning

confidence: 84%

“…Not surprisingly, researchers are interested in the mechanisms underlying sugammadex-induced anaphylaxis. Although various hypotheses have been put forward, they have not been clarified thus far [4][5][6]. Here, we report a case of sugammadex-induced anaphylaxis in which we utilized the basophil activation test (BAT) to investigate the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Possible immunoglobulin-E-dependent sugammadex-induced anaphylaxis caused by an epitope other than γ-cyclodextrin: a case report

et al. 2021

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Background Sugammadex is a synthetic γ-cyclodextrin derivative designed to selectively bind to steroidal neuromuscular blocking agents and reverse their effects. Although many cases of sugammadex-induced anaphylaxis have been reported, few studies have investigated the underlying mechanism. Case presentation A 55-year-old Japanese man underwent a laryngectomy under general anesthesia. One month before laryngectomy, he had undergone laryngoscopy under general anesthesia and received sugammadex administration without causing hypersensitivity. He had no history of allergies. The operation was finished without complications. Shortly after sugammadex administration, his blood pressure dropped to approximately 70 mmHg, and his heart rate increased to 110 beats/minute with systemic erythema. Suspecting anaphylaxis, he was treated with the intravenous injection of phenylephrine, d-chlorpheniramine, and hydrocortisone. After these treatments, his cardiovascular condition stabilized. Eight months after the event, skin prick tests and intradermal tests with all agents used during general anesthesia were performed. Intradermal tests showed positive results only for sugammadex. Subsequently, basophil activation tests with CD203c were performed using sugammadex, γ-cyclodextrin, and positive controls (anti-immunoglobulin-E and formyl-methionyl-leucyl-phenylalanine). In addition to both controls, sugammadex, but not γ-cyclodextrin, induced significant upregulation of CD203c expression. We performed additional basophil activation tests with wortmannin, an inhibitor of phosphoinositide 3-kinase, to investigate the mechanism underlying sugammadex-induced basophil activation. The inhibitory effect of wortmannin on basophil activation due to sugammadex was similar to that of anti-immunoglobulin-E, suggesting an immunoglobulin-E-dependent mechanism. Although the patient showed no hypersensitivity after the first exposure of sugammadex, anaphylaxis appeared after the second administration. Because most cases of sugammadex-induced anaphylaxis reportedly appeared after first administration, this seems to be a rare case. Conclusions In the present case, sugammadex-induced anaphylaxis might have occurred through an immunoglobulin-E-dependent mechanism and not involve γ-cyclodextrin as an epitope. Physicians should pay attention to the occurrence of sugammadex-induced anaphylaxis even when the patient has a history of safe administration of sugammadex.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Possible immunoglobulin-E-dependent sugammadex-induced anaphylaxis caused by an epitope other than γ-cyclodextrin: a case report

et al. 2021

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“…No cases of anaphylaxis with sugammadex were present in the study population. Although it has been described, 14 it is very rare. Maybe some of these side-effects will be controlled by the use of new alternatives to sugammadex 15 .…”

Section: Discussionmentioning

confidence: 99%

Earlier and lower dose administration of sugammadex

Duranteau¹,

Fernandez²,

Tuna³

et al. 2021

European Journal of Anaesthesiology

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BACKGROUND Sugammadex allows for rapid reversal of muscle relaxation after the use of rocuronium or vecuronium. The lowest recommended dose is 2 mg kg−1 intravenously when there are two twitches during the train-of-four stimulation. OBJECTIVE To study the efficacy and risks of a lower dose of sugammadex administered earlier. DESIGN Monocentric randomised controlled double-blind study. SETTING Academic hospital. PATIENTS Eighty patients were enrolled and randomised in 8 groups of 10 patients, 56 were finally evaluated. INTERVENTIONS Patients were distributed in two clusters constituting four groups each. In the first cluster, injections were administered after the return of one twitch with the train-of-four (TOF1). In the second cluster, injections were delivered after the return of two twitches with the TOF (TOF2). We created four groups in each cluster for different dosages: placebo, 0.5, 1 or 2 mg kg−1. MAIN OUTCOME MEASURES Time between the injection of sugammadex and full recovery (TOF ratio > 0.9) that is expressed in minutes. RESULTS Fifty-six successive patients were assessed between February and August 2018. The difference to TOF greater than 0.9 was not statistically significant between groups with the same dose administered at different times (F value = 0.001, P value = 0.975). There was a significant difference between groups with a different dosage administered at the same time (F ratio = 28.34; P value <0.0001). Concerning the time to TOF greater than 0.9 from the time point of TOF1, the timing of the dosages were statistically significant using log rank test (P < 0.0001). No patient presented a reparalysis. CONCLUSION No difference between injecting sugammadex at TOF1 or TOF2 was found regarding time to full recovery. Difference regarding sugammadex quantity was found and compatible with other studies. TRIAL REGISTRATION clinicaltrials.gov: ‘BRIDION_ERASME’, EudraCT: 2017-005074-19.

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Anaphylactic Responses to Neuromuscular Blockade Drugs and Reversal Drugs

Quayle,

Cook

2023

Curr Anesthesiol Rep

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Does sugammadex have multiple mechanisms for causing anaphylaxis?

Cited by 6 publications

References 4 publications

Possible immunoglobulin-E-dependent sugammadex-induced anaphylaxis caused by an epitope other than γ-cyclodextrin: a case report

Possible immunoglobulin-E-dependent sugammadex-induced anaphylaxis caused by an epitope other than γ-cyclodextrin: a case report

Earlier and lower dose administration of sugammadex

Anaphylactic Responses to Neuromuscular Blockade Drugs and Reversal Drugs

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