Knowledge
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Sugammadex is pharmacologically great. A modified γ-cyclodextrin Selective Relaxant Binding Agent that reverses rocuronium muscle relaxation 10-times faster than neostigmine (see: Is sugammadex as good as we think?).
At launch, its biggest obvious disadvantage was simply the new drug's high cost. Now as sugammadex has become more widely used, sugammadex-anaphylaxis has risen as a new, prominent concern.
In Japan, where there was a uniquely rapid take-up of sugammadex, it became one of the commonest causes of anaphylaxis. Oriharia (2020) demonstrated an incidence of sugammadex anaphylaxis in Japan of 1 in 5,000 – a risk that most medically communities would consider too high for routine use of a drug with acceptable alternatives.
Given that in some regions (notably Australia & New Zeleand) rocuronium itself has a high-risk of anaphylaxis, the combination of rocuronium-sugammadex may present a greater risk than even old-school drugs such as suxamethonium.
In other countries, such as the United Kingdom, there has not been quite the same incidence of sugammadex-anaphylaxis. Is this simply because of the lower initial use than in Japan, or are there environmental and phenotypical differences as have been implicated for rocuronium anaphylaxis?
Worryingly, if the Japanese experience is representative, then for some locations the combination of rocuronium-sugammadex may in fact have a higher risk of anaphylaxis than using suxamethonium alone.
The true risk of sugammadex-anaphylaxis is still unclear for many populations. However with the looming expiry of the sugammadex patent in 2023, we will see a rapid increase in its use and subsequently reveal any latent anaphylaxis risk.
summary
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Calabadions are heterocyclics molecule that offers rapid and complete reversal of both aminosteroids, such as rocuronium and vecuronium, and benzylisoquinoline NMBDS, such as atracurium and cisatracurium.
Notably, calabadion 2 binds rocuronium 89 times stronger than sugammadex. Additionally it also binds etomidate and ketamine.
Calabadions are still undergoing pre-human animal testing, and so are some time away from entering clinical practice.
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Possibly... but with some important caveats.
“Sugammadex is likely the most exciting drug in clinical neuromuscular pharmacology since the introduction of atracurium and vecuronium in the middle 1980s.” – RD Miller (2007).
Sugammadex (Bridion®) is a remarkable drug – and the anaesthesia community has moved very quickly to embrace the potential of this first ‘selective relaxant binding agent’ (SRBA), despite it’s considerable cost.
Sugammadex offers a new and improved way of reversing aminosteroid muscle relaxation, in particular from rocuronium. The speed at which it reverses even profound neuromuscular blockade is incredible and potentially life saving. Sugammadex’s onset is 10 times faster than neostigmine and three times faster than edrophonium.
Though beyond the parlour-trick of speedy action, or the possibility of rescuing a cannot-intubate-cannot-ventilate crisis – the biggest benefit of sugammadex for our patients may be in the dramatic reduction of post-operative residual paralysis. A common problem with serious consequences that the anaesthetic community has ignored for far too long.
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