Hypersensitivity incidence after sugammadex administration in healthy subjects: a randomised controlled trial. Min et al British Journal of Anaesthesia, 121 (4): 749-757 (2018)
- A multicentre, double-blind study
- Subjects randomised 2:2:1 to Sugammadex 4mg/kg, 16mg/kg or placebo (normal saline)
- Doses were administered 5 weeks apart, to unanaesthetised healthy subjects
- Hypersensitivity signs and symptoms were assessed at 0.5, 4 and 24hrs
- Tryptase levels were assessed pre dose and at 3hrs
- IgG and IgE levels checked as an exploratory endpoint
- Hypersensitivity signs/symptoms were then adjudicated by a blinded committee
- The Sampson Criteria were used for assessing anaphylaxis
- The primary endpoint of the study was confirmed hypersensitivity
- 375 subjects recruited
- 94 subjects with 137 adverse events were sent for review by the independent adjudication committee
- Of the 94, 25 subjects were deemed to have “adjudicated” hypersensitivity, with a total of 43 events. This is a hypersensitivity rate of 6.7%.
- In the 4mg/kg cohort: 10/151 (6.6%)
- In the 16mg/kg cohort: 14/148 (9.5%)
- In the Placebo cohort: 1/76 (1.3%)
- 3 subjects from 16mg/kg required antihistamines/corticosteroids, and did not receive further doses
- 1 subject had anaphylaxis
- Hypersensitivity can occur on first exposure
- Signs and symptoms usually presented within minutes (one after 22hrs)
- There was no increase in severity with exposures ie no sensitisation. There was no significant tryptase rise. It is therefore unlikely to be mast cell mediated.
- They quoted the incidence of anaphylaxis as 1 in 199 or 3.3%
- It is unclear from this study if reactions are dose related
- They found no IgE antibodies to sugammadex
- Limited numbers to subgroup analysis of race or ethnicity
Analysis of the paper and take home thoughts:
- It is unclear who the Independent Adjudication Committee was, or how they reduced the number of hypersensitivity reactions from 94 to 25.
- The authors quoted 1 in 199 or 3.3% anaphylaxis, however they had one case in 299 subjects receiving sugammadex. I believe that this figure should therefore be 1 in 299 or 0.33%.
- This rate of anaphylaxis is far higher than the approximate 1:10,000 cases seen in NAP6, and is very worrying if sugammadex is to become more frequently used. We should definitely consider the risks and benefits prior to administration of sugammadex in our patients.
- No Asian subjects were included in the study
- Some subjects were unaccounted for in the results
- The study was funded by Merck and Co. who make Sugammadex.
Summary by Dr Leonora Bowen