Purpose   The purpose of this study was to report the incidence of anaphylaxis after sugammadex at a single center in Japan.


Background   Sugammadex is a gamma‐cyclodextrin that encapsulates the aminosteriod neuromuscular blocking agents rocuronium and vecuronium, thus reversing their effects. The estimated incidence of anaphylaxis with sugammadex is 0.0029%; however, this rate may be underestimated. Therefore, the investigators at this single center in Japan sought to report on the incidence of anaphylaxis after sugammadex.


Methodology   This was a retrospective study at the Jikei University School of Medicine, Tokyo, Japan. All surgical cases between September 2012 and August 2015 were evaluated for suspected cases of anaphylaxis based on World Allergy Organization guidelines. Data collected included patient demographics, allergy and surgical history, previous exposure to sugammadex, dose, time from injection to symptoms, symptoms, treatment, time to achieve hemodynamic stability, and any diagnostic tests.


Result   There were 6 cases of anaphylaxis out of 15,479 patients who received sugammadex for an incidence of 0.039% (95% CI 0.014%-0.084%). For comparison, there were 8 cases of intraoperative anaphylaxis unrelated to sugammadex out of 23,608 surgical cases for an incidence of 0.033%. The median time from sugammadex administration to symptoms was 1.5 minutes. Five of the six patients had hypotension to a systolic BP < 50 mm Hg; in one case the systolic decreased from 140 to 70 mm Hg. Tachycardia to a heart rate as high as 128 also occurred. Other symptoms included a decreased SpO2, elevated peak airway pressures (2 of 6 cases), trunk and upper limb uticaria (1 patient), erythema (4 of 6 patients), and cervical and facial edema (1 patient). Treatment generally consisted of small doses of epinephrine 10-100 µg, phenylephrine, fluid bolus, antihistamines, inhaled beta agonists, and hydrocortisone (200 mg). Median time from treatment to resolution of symptoms was 10.5 minutes but took as long as 40 minutes. One patient had an elevated serum tryptase level. One patient required intensive care unit admission, and the other 5 patients were admitted to the ward after the recovery room. No patients experienced major problems or a biphasic reaction.


Conclusion    This study suggests the incidence of anaphylaxis after sugammadex is similar to that of the neuromuscular blocking agents succinylcholine and rocuronium.




While anaphylaxis from anesthetic drugs is uncommon, neuromuscular blocking agents are often the causes of anaphylaxis under anesthesia. The incidence of anaphylaxis after succinylcholine and rocuronium is 0.048% and 0.04%, respectively. This study suggests that the incidence of anaphylaxis after sugammadex may be higher than previously reported, and similar to that of succinylcholine and rocuronium.


Allergic anaphylaxis can be either IgE-mediated (anaphylactic) or non-IgE-mediated (anaphylactoid). Allergic anaphylaxis is a result of degranulation of mast cells or basophils (IgE mediated) leading to the release of histamine, tryptase, carboxypeptidase A and proteoglycans; and activation and synthesis of arachidonic acid metabolites and platelet activating factor and a later release of cytokines. Histamine release leads to vasodilation and increased vascular permeability. Prostaglandins cause bronchoconstriction, pulmonary and coronary artery constriction, and peripheral vasodilatation. Leukotrienes and platelet activating factors contribute to the bronchoconstriction, myocardial depression, and increased vascular permeability. Anaphylaxis signs and symptoms include skin rash, hypotension, tachycardia, wheezing, hypoxemia, and edema.


It is critically important that anesthesia providers quickly recognize anaphylaxis, call for help, and initiate treatment. Use of cognitive aids for perioperative emergencies, such as the Stanford emergency checklists and the Stanford Perioperative Emergency Manual (http://emergencymanual.stanford.edu/) are useful. As soon as symptoms are recognized, the suspected agent should be discontinued and treatment initiated (epinephrine, antihistamines, beta-agonists, fluids, vasopressors, oxygen and airway management as appropriate). This study indicated that symptoms of anaphylaxis occur very quickly after sugammadex administration (less than 2 minutes), and patients with can be stabilized with aggressive treatment within a median of 11 minutes.