Sugammadex, rocuronium and mast cell numbers in the rat liver


We were interested to read about the effects of rocuronium and sugammadex on rat livers by Tomak et al. [1], but are concerned that they misrepresented the findings of the study by Clarke et al. [2] who used an in-vivo human model of IgE-mediated anaphylaxis that demonstrated that patients were anergic to sugammadex-bound rocuronium. However, there was no attenuation in the wheal-and-flare response when sugammadex was administered after the reaction had commenced. Tomak et al. incorrectly quoted the paper as stating that sugammadex was effective when it was not.

We also have some questions regarding their paper. Firstly, rats in their study were not sensitised to rocuronium and there was no evidence of anaphylaxis to rocuronium in any rat. How then can they make any statement regarding the effects of sugammadex in rocuronium-induced anaphylaxis? Secondly, the groups of rats were not treated comparably. Group R (rocuronium-only) were given an ether anaesthetic, positive-pressure ventilation and a tracheostomy, whereas the control group received none of these. How were the authors able to exclude these interventions as being the cause of the observed differences in mast cell numbers? Thirdly, it would appear from the body of the article that the authors are using the number of tryptase-staining mast cells to indicate the magnitude of mast cell degranulation. We are unclear how this can be construed as a surrogate marker of degranulation. It was interesting that the proportion of tryptase-positive mast cells compared with total mast cells was actually lower in the rocuronium group than the sugammadex followed by rocuronium groups. However, we do not believe that these methods can accurately quantify the degree of mast cell activation that has occurred. In addition, our understanding is that mast cell numbers in tissues are relatively fixed but can increase after migration of precursors from the bone marrow. This process takes days, not hours. The finding of increased numbers after only 24 h is therefore surprising, and the authors have not discussed possible alternative explanations such as inherent errors in the choice of staining techniques and their methodology.

We welcome the continued investigation of the effects of sugammadex on rocuronium-induced anaphylaxis. However, we do not believe that Tomak et al. have demonstrated that sugammadex attenuates the activation of mast cells as stated in their final conclusion.