Remimazolam anaphylaxis confirmed by serum tryptase elevation and skin test

Abstract

Summary Anaphylactic reactions during the induction of general anaesthesia are rare. Anaesthetists should determine the pathogenesis of anaphylaxis in order to establish appropriate treatment and prevent recurrence. Very little clinical information has been published to date about anaphylaxis induced by the recently launched drug remimazolam. A 78‐year‐old man, scheduled for elective surgery for colon cancer, became profoundly hypotensive and hypoxic shortly following the induction of general anaesthesia with remimazolam, remifentanil and rocuronium. His physiological derangement was successfully managed with adrenaline, vasopressors and intravenous fluid resuscitation. His serum tryptase level was significantly elevated and an intradermal test with diluted remimazolam revealed a positive reaction, confirming the diagnosis of anaphylaxis. We believe this is the first case report of remimazolam‐induced anaphylactic shock diagnosed with a serum tryptase elevation and positive skin test.

Remimazolam and serious adverse events

“…131,132 Unfortunately, the use of flumazenil at the end of remimazolam anaesthesia is highly variable throughout the published trials. Unsurprisingly, resedation has only been NA ID RMZ at 0.1 and 0.01 mg ml À1 Tsurumi 104 12 mg, 6 mg kg À1 h À1 Skin MDZ, 1 month before 5.8 (4.7) ID MDZ at 0.5 mg ml À1a ID RMZ at 0.5 mg ml À1a Yamaoka 105 12 mg, 12 mg kg À1 h À1 Respiratory NA 23.8 (4.3) NA ID RMZ at 0.01 mg ml À1 Uchida 106 4 mg, bolus RMZ, 1 month before 8.3 (2.9) NA NA Uchida 106 9 mg, three boluses No previous exposure 7.8 (4.1) NA Negative (not specified) Kim 107 NA, 12 mg kg À1 h À1 NA 10.1 (4.4) Negative Negative Kim 107 NA, 12 mg kg À1 h À1 NA 14 (6.3) NA NA Kim 107 NA, 12 mg kg À1 h À1 NA 12.8 (4.2) Negative Negative Kim 107 NA, 12 mg kg À1 h À1 Skin NA 2.6 (1.5) Negative Negative Kim 107 NA, 2 mg kg À1 h À1 Skin NA 9.2 (4.2) Negative Negative ID, intradermal test; MDZ, midazolam; NA, not available; RMZ, remimazolam; SP, skin prick test. a Original case report reports a concentration of 500 mg ml À1 ; however, this a probable mistake and should have shown 500 mg ml À1 .…”

Airway collapse as the predominant clinical feature following remimazolam-induced anaphylaxis: a case report

“…Remimazolam besylate, a novel ultrashort-acting benzodiazepine, has recently been approved for clinical use as a general anesthetic. Although peri-operative anaphylaxis due to remimazolam has been gradually ascertained and reported [2][3][4][5] , the spectrum of its allergic reactions is still not well known. Here, we describe a case of anaphylaxis caused by remimazolam, which presented with complex clinical signs, including airway changes, skin symptoms, gastrointestinal manifestations and hemodynamic uctuations.…”

An update on remimazolam and anaphylaxis

“…Thus, anaphylaxis to remimazolam, which is structurally similar to midazolam, is a potential complication and should be closely monitored in the coming years owing to the development and growing use of the product. Interestingly, in the majority of cases, 9,10,13 skin tests revealed a positive reaction to remimazolam but not to midazolam. Consequently, isolated allergy to remimazolam is possible.…”

“…Remimazolam was officially approved as a novel anaesthetic agent in Japan in January 2020, and it then received marketing authorisation in Europe in March 2021 for the indication of procedural sedation 8 . Recently, anaphylactic issues have been reported with the use of remimazolam, 9–13 these 10 cases having been reported in Japan and South Korea. Clinical symptoms were frequently major cardiovascular events (hypotension, shock, and cardiac arrest), 9–13 and less frequently respiratory or cutaneous signs 13 .…”

“…8 Recently, anaphylactic issues have been reported with the use of remimazolam, 9-13 these 10 cases having been reported in Japan and South Korea. Clinical symptoms were frequently major cardiovascular events (hypotension, shock, and cardiac arrest), [9][10][11][12][13] and less frequently respiratory or cutaneous signs. 13 In all cases, the outcome was good, adequate resuscitation was provided, and epinephrine was used.…”