For decades suxamethonium has retained it’s position as top dog when it comes to the choice of neuromuscular blocking agents for RSI. The strange thing though, is how it has remained a mainstay of RSI in spite of a host of adverse side effects and the widespread availability of the arguably superior drug, rocuronium. So I am wondering what is it still doing in our fridge and how come it hasn’t it been relegated to the history books?
Suxamethonium came into use in the early 1950’s at which point it was unrivalled in terms of it’s properties. Curiously, it’s paralysing effects had been completely missed for over forty years prior to this during which time it’s cardiovascular properties had been investigated on curarised animals, thereby entirely masking what was to become it’s USP. Once recognised, it’s rapid onset of paralysis in about 45 seconds, followed by spontaneous return of muscular activity were unique amongst clinically available drugs, and in an era when tracheal intubation was rare, a short period of paralysis to facilitate surgical interventions followed by spontaneous ventilation was desirable. The concept that breathing could resume automatically in the face of a difficult intubation scenario, or more worryingly, a CICO situation (not that it was called that at that point), was an advantage that emerged in terms of it’s importance as surgery became more complex and tracheal intubation more common.
Since then the emergency airway landscape has changed dramatically. Difficult airways were presumably no more or less common but the equipment available to manage them was very different, so running into unmanageable difficulties will have been significantly more common. The development of the laryngeal mask provided alternative ventilation options, and fibre-optic and digital technologies have enabled the development of flexible endoscopic laryngoscopy and in turn video-laryngoscopy, which between them have revolutionised the management of the difficult airway. Meanwhile drugs such as remifentanil and dexmedetomidine have made awake procedures significantly easier and safer to undertake, not to mention more acceptable to the patient.
Conversely our expectations of what we can and should treat have continued to rise. We find ourselves in the ED and critical care environments embarking on aggressive management of progressively sicker patients who tolerate the rapid sequence procedure much less well and for whom the underlying pathology means that spontaneous or drug mediated reversal of muscle relaxation is not a realistic option. In these patients the ability to reverse neuromuscular blockade is largely irrelevant, and the ability to employ the available equipment is in the most part made more difficult by the partial resumption of muscular activity. This often makes it harder to adequately oxygenate the patient who is now at a higher risk of vomiting and aspiration and resisting our efforts to maintain, let alone secure their airway.
It’s easy to see the attraction of suxamethonium when all you’ve got to work with is a strong left arm and a gum-elastic bougie, and your patient group is mainly having a RSI because of a full stomach or acid-reflux risk (so can be woken up if you can’t intubate), but with a patient group who for whom waking up is not an option and with far more physical and pharmacological technologies to hand, the longer duration of action of rocuronium is appealing and suxamethonium has become a much less attractive option.
Rocuronium has been commonly available since 1994, during which time a number of things have happened to promote it from an atracurium alternative that can survive outside the fridge to vying for supremacy in emergency airway management and arguably the only muscle relaxant you need in the cupboard. The body of evidence has developed over the years which has helped define it’s role in RSI, such as, for example, the best dose with which to match the onset of suxamethonium (1.2 mg/kg).
Arguably the most important development, however, may be the development and widespread availability of sugammadex, which by chelating and therefore reversing the activity of rocuronium overcomes what is probably the most common objection to rocuronium use in RSI; the inability to resume spontaneous ventilation in the event of failure to ventilate/oxygenate. In fact, the only reason a 2015 Cochrane Review continued to recommend suxamethonium over Rocuronium (at a dose of 1.2 mg/kg) was for it’s shorter duration of action.
Arguably this last point, the ability to just allow the patient to start breathing again, is largely academic since as we have discussed many of these patients are being intubated because their spontaneous ventilation is inadequate to sustain life, and many have such bad respiratory pathology that rapid desaturation is commonplace and a return of spontaneous ventilation several minutes later is several minutes too late. There is little doubt, however, that the reassurance that the muscle relaxant could be reversed is significant, albeit probably of greater value to the psychology of the intubator than physiology of the patient.
So that still leaves the question of why suxamethonium remains in common use, and in many respects this is baffling. It’s list of contra-indications is considerable, with relevant patient details often not being available at the time of emergency intubation, and the list of side effects is equally long. Although not that common, many of these, such as malignant hyperthermia, hyperkalaemic cardiac arrest and suxamethonium apnoea, carry high morbidity or mortality rates. By contrast rocuronium has barely any contra-indications and hardly any side effects, allergy aside, other than a slightly higher pharmacy bill (particularly if sugammadex use is taken into account). Even the risk of allergy has been downgraded significantly in the light of evidence produced from NAP6.
I can only think of one remaining advantage of suxamethonium after cost; that being the risk of awareness. Suxamethonium has the practical advantage that the patient for whom ongoing sedation has inadvertently not yet been started has probably also not been given a secondary longer acting muscle relaxant and when they start coughing or fighting the ventilator there is an obvious prompt to address both these problems before awareness develops. With the marked physiological derangements of critical illness obscuring physiological evidence of emergence from sedation, and rocuronium preventing physical movement, there is potentially one less barrier to awareness. This is, however, nothing that the use of a good RSI checklist can’t address, but that’s another story…
If the sequence of introduction of rocuronium and suxamethonium had been the other way around, would suxamethonium have subsequently gained traction as a drug of choice in RSI? I struggle to think of a single reason that it might. Some might argue for it’s continued use in ECT, or for other elective situations where a very short acting muscle relaxant is useful, but certainly in the emergency RSI situation, it’s role has become less obvious. Inertia within the medical system explains a great deal of why we do things the way we do, and it often requires consistent effort to bring change to bear. This is particularly true in relation to high stress or high-risk scenarios where there is a strong urge to stick with what we know. Familiarity has a lot going for it, but isn’t it now time to ask why we still have Suxamethonium in the fridge?
Andrew Burtenshaw
References:
Goodbye Suxamethonium! Lee, C. Anaesthesia, 2009, 64 (Suppl. 1), pages 73-81.
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