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Wednesday, December 16, 2015

Sugammadex, revisited

Sugammadex (I call it Suggs) is a selective muscle relaxant-binding agent. As a result of its chemical structure, modified cyclodextrin compound with a hydrophilic outer surface and a lipophilic central cavity, sugammadex encapsulates both rocuronium and vecuronium.  This encapsulation creates a concentration gradient by which rocuronium or vecuronium leaves the neuromuscular junction for the plasma and then subsequently bound by sugammadex (think DigiFab).  The result is a dramatically shortened duration of effect of rocuronium or vecuronium.  At a typical surgical reversal dose of 4 mg/kg the median time to reach train of four ratio of 0.9 is 2.4 minutes after rocuronium or 3.4 minutes for vecuronium compared to 49 minutes using neostigmine. 

In the emergency department, the use of a drug like this would open up the possibility of freely using rocuronium for paralysis after induction of anesthesia for intubation, putting succinylcholine out to pasture. But it’s not that simple. The Gas Exchange blog said it best: “If sugammadex is the answer what is the question?”

In this awesome post, Dr. Jolley describes several different reasonable situations where suggs could be used. The two I think best apply to emergency medicine are pre-planned reversal of rocuronium (patients with neuromuscular disorders; and patients with severe pulmonary disease with limited reserve) and unplanned rocuronium reversal (unexpected difficult airway / can’t intubate, can’t ventilate situations).  The latter, I would imagine, would be the hot topic surrounding its use in the ED given the potential to put succinylcholine out to pasture.

Real world practice is going to be different compared to the controlled setting of an investigational study in an OR. A study of elective surgical adult patients who required induction and paralysis were randomized to rocuronium+suggs or succinylcholine alone to compare the time from start of administration of rocuronium or succinylcholine to recovery of T1 to 10% of the baseline value. Suggs was administered to the rocuronium group 3 minutes after the start of the rocuronium bolus. In this OR setting, rocuronium+suggs compared to succinylcholine alone recovery from paralysis (T1 10%, and T1 90%) was significantly faster with rocuronium+suggs.  This difference was 2.7 (mean rocuronium+suggs 4.4 min vs succinylcholine 7.1 min) minutes faster to T1 10%.  But (as pointed out in the Gas Exchange blog as well) this is a controlled setting. If there is a situation where rocuronium needs to be reversed, that decision is made when the prevailing issue is discovered. In other words, not before a RSI attempt. Therefore, once a complication is discovered, suggs ordered, mixed (5-8 vials or so for a 16 mg/kg dose) and administered, that difference of 2.7 minutes is gone and succinylcholine would have worn off on its own. The better question is what is that situation where rocuronium must be emergently reversed in a critical airway patient setting? I am no expert in airway management, I am simply the pharmacist at the bedside, however if a patient needs to be intubated / needs an airway, if you revers the rocuronium paralysis… they STILL need an airway. Supraglottic airways or cric procedures may benefit from lingering paralysis.

So where does sugammadex fit into clinical practice? In critical airway management, perhaps the role is not as great as once thought.

There is more to the argument, of course. 1) While the above study used train of four analysis for a marker of neuromuscular function recovery, patient oriented outcomes (shorter vent time, LOS, mortality) have not been studied. Another expensive drug with nothing but surrogate markers to go on. 2) Cost. Probably a lot. Probably not worth it. 3) Patients with GFR < 30. The drug may accumulate since it is cleared by the kidneys. This could mean an attempt at re-paralysis with roc/vec would not be effective or reduced efficacy. The RESUS ME blog pointed out a published case where this occurred. 4) Allergic reactions. Reported in the literature and the possible culprit for the FDA reluctance to approve.

The problem is the same as with Praxbind or Kcentra. It is hard to justify not having it on hand. The case where it might help a patient is probably a rare one, but it would be a nice drug to have on hand for those n=1 situations.

Controlling widespread use will be a challenge. I’m certain OR staff will request it with the same argument as IV acetaminophen – it will shorten PACU times, and get patients out faster. Just like with IV APAP, that argument hasn’t been supported, and the cost has been a significant issue.

The story of suggs continues to unfold.

I would love to hear the experience from our colleagues from the rest of the world where this has been available.

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