Will Sugammadex Bust Pharmacy Budgets?

DECEMBER 17, 2015
Sugammadex (Bridion) is the first selective muscle relaxant binding agent.
 
Because of its chemical structure as a modified cyclodextrin compound with a hydrophilic outer surface and a lipophilic central cavity, sugammadex encapsulates both rocuronium and vecuronium. This creates a concentration gradient by which rocuronium or vecuronium leaves the neuromuscular junction for the plasma and then subsequently binds by sugammadex [think: digoxin immune fab (DigiFab)]. 
 
The result is a dramatically shortened duration of effect for rocuronium or vecuronium. At a typical surgical reversal dose of 4 mg/kg, the median time to reach train of 4 ratio of 0.9 is 2.4 minutes for rocuronium or 3.4 minutes for vecuronium, compared with 49 minutes for neostigmine. 
 
In the emergency department, the use of a drug like sugammadex would open the possibility of freely using rocuronium for paralysis after induction of anesthesia for intubation, thus putting succinylcholine out to pasture.
 
But it’s not that simple. A recent post on The Gas Exchange blog said it best: “If sugammadex is the answer, what is the question?”
 
The post describes several different reasonable situations where sugammadex could be used. The 2 that 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 or can’t intubate/ventilate situations). I would imagine the latter would be the hot topic surrounding the drug’s use in the emergency department, given its potential to put succinylcholine out to pasture.
 
Real-world practice is going to differ from the controlled setting of an investigational study in an operating room. 
 
One study published in Anesthesiology randomized adult elective surgical patients who required induction and paralysis to either rocuronium+sugammadex or succinylcholine alone to compare the time from the start of administration of rocuronium or succinylcholine to recovery of T1 to 10% of the baseline value. Suggammadex was administered to the rocuronium group 3 minutes after the start of the rocuronium bolus.
 
In this setting, recovery from paralysis (T1 10% and T1 90%) was significantly faster with rocuronium+suggammadex than succinylcholine alone. The difference was 2.7 fewer minutes to T1 10% (mean rocuronium+suggammadex 4.4 min vs succinylcholine 7.1 min).
 
But this was 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 rapid sequence intubation attempt.

Once a complication is discovered and sugammadex is ordered, mixed (5 to 8 vials or so for a 16 mg/kg dose), and administered, that 2.7-minute difference is gone, and succinylcholine would have worn off on its own. The better question is: what is a situation where rocuronium must be reversed in a critical airway patient setting?
 
I am no expert in airway management; I am simply the pharmacist at the bedside. But if patients need an airway, and you reverse the rocuronium paralysis, they still need an airway. Supraglottic airways or cricothyroidotomy procedures may benefit from lingering paralysis.
 
So, where does sugammadex fit into clinical practice? In critical airway management, perhaps its role is not as great as we once thought.

One potential niche for emergency department folks would be in patients who require a neuromuscular exam, such as stroke or traumatic brain injury patients. In this setting, the ability to regain the exam rapidly could be a good use for sugammadex.
 
There is more to the argument. While the aforementioned study used train of 4 analysis for a marker of neuromuscular function recovery, patient-oriented outcomes (shorter vent time, mortality) have not been studied. Sugammadex may be just another expensive drug with nothing but surrogate markers to go on.
 
Since sugammadex may accumulate because it is cleared by the kidneys, this could mean an attempt at re-paralysis with rocuronium or vecuronium would not be effective or reduce efficacy in patients with a glomerular filtration rate <30. A recent Resus.ME blog post pointed out a published case where this occurred.
 
Then, there are the allergic reactions that have been reported in the literature, which formed the possible culprit for the FDA’s reluctance to approve sugammadex.
 
The problem with sugammadex is the same as Praxbind and Kcentra: it is hard to justify not having the drug on hand. The cases where it might help a patient are probably rare, but it would still be a nice drug to have for those situations.
 
Controlling widespread use of sugammadex will be a challenge. I am certain that operating room staff will request it with the same argument as intravenous (IV) acetaminophen: it will shorten post-anesthesia care unit times and get patients out faster. For IV acetaminophen, that argument hasn’t been supported, and cost has been a significant issue.
 
And so, the story of sugammadex continues to unfold.
 
I would love to hear the experiences of colleagues from other parts of the world where this drug has been available.

Craig Cocchio, PharmD
Craig Cocchio, PharmD
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com
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