Give Me Some Sugammadex

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Should you reach for this agent the next time you can’t intubate and can’t ventilate?

Airway management is perhaps the most important skill of the emergency physician, and the decision to intubate is not taken lightly. Once RSI is undertaken and a paralytic is administered, the patient is at considerable risk if the airway cannot be secured. Thus emergency physicians devote significant attention to managing airways safely, including being prepared for a surgical airway if other efforts to secure the airway fail. Any developments that make airway management safer or easier are always welcome.

While succinylcholine has traditionally been the favorite neuromuscular blocker of emergency physicians, rocuronium is gaining in popularity. In fact, some providers reach for rocuronium first since it does not have succinylcholine’s theoretical issue of hyperkalemia, and the contraindication in neuromuscular disease. In addition, many favor the prolonged intubating conditions created by rocuronium, provided the patient can be adequately ventilated while airway attempts are made.

The FDA recently approved the first selective reversal agent for rocuronium, known as sugammadex. Already in use in Europe since 2008, sugammadex’s approval in the U.S. was delayed due to concerns about hypersensitivity. Once U.S.-based trials showed the risk of anaphylaxis was low (0.3%), the drug was approved in 2015. Here we will review basics of this novel drug and discuss ways it may impact emergency airway management.

Marketed under the brand name Bridion, sugammadex is currently approved for use in patients undergoing surgery. It is given to reverse neuromuscular blockade from rocuronium or vecuronium in patients whose surgical case ends earlier than anticipated. It can also be used in extubated patients with poor respiratory effort from residual neuromuscular blockade. Most importantly for us, however, it is also approved for emergent reversal of neuromuscular blockade in a “can’t intubate, can’t oxygenate” scenario in the OR. Although the package insert does not specifically address ED use, ED providers may also face a failed airway situation. Sugammadex reverses neuromuscular blockade from rocuronium in approximately three minutes, faster than spontaneous recovery from succinylcholine, raising the question of whether a rocuronium plus sugammadex strategy would be appropriate to improve safety of intubation, should a “can’t intubate, can’t oxygenate” scenario arise [1].

While sugammadex sounds like it would be a great reversal agent for a failed airway, there seems to be consensus among experts that sugammadex should not be relied on as a panacea in a “can’t intubate, can’t oxygenate” scenario [1-3]. There are multiple reasons for this. First, unless sugammadex were readily available in the ED, the time to get the drug from pharmacy would be prohibitive. Secondly, even if the drug were already at the bedside, the three minutes required to fully reverse neuromuscular blockade, plus the time of the failed airway, is still too long a duration of hypoxia. Furthermore, an airway that has been manipulated with a laryngoscope blade can swell, and simple reversal of NM blockade does not ensure that the airway will still be patent. Several published case reports of sugammadex in a “can’t intubate, can’t oxygenate” scenario in the OR describe that even when neuromuscular blockade was successfully reversed as measured by train-of-four peripheral nerve monitor, the patient remained difficult to ventilate and ultimately required a surgical airway, presumably due to laryngeal edema from airway manipulation. Finally, the underlying pathology that caused the patient to require intubation, and the physical challenges that made it impossible to ventilate and intubate will still be present. Therefore, emergency providers should prepare for the difficult airway and have backup plans including video laryngoscopy, supraglottic airways, and ultimately cricothyrotomy, rather than relying on sugammadex [1-3].

A more promising role for sugammadex in the ED is for evaluation of the patient with neurologic injury. For example, take the case of patient who had a large MCA stroke a week prior, who comes in with status epilepticus, presumably due to the infarct acting as a seizure focus. The patient requires intubation for airway protection, but succinylcholine is contraindicated due to recent stroke. In this case, rocuronium could be used, and reversal of NM blockade with sugammadex would be very helpful to monitor ongoing seizure activity. Similarly, in the case of a head-injured patient intubated with rocuronium, the neurosurgeon would not have to wait up to 45 minutes for rocuronium to wear off to get a detailed neurologic exam if sugammadex were used for reversal.

How It Works
Sugammadex rapidly binds to rocuronium, with full reversal of NM blockade occurring in approximately three minutes,. This is quicker than spontaneous recovery of NM blockade after succinycholine, and also 3-8 times faster than reversal with neostigmine [4]. It is also more effective than reversal with neostigmine, with lower rates of residual neuromuscular blockade [5].

Sugammadex is named for its component parts, su- for the sugar molecules comprising it, and -gammadex for its basic structure as a Gamma-cyclodextron. It is a ring-shaped molecule of 8 sugar groups whose 3-D shape resembles a hollow cone, the interior of which is hydrophobic (see image above) [6]. Sugammadex’s hydrophobic core binds at very high affinity with a 1:1 ratio to rocuronium, effectively trapping rocuronium in its hollow structure, and preventing rocuronium’s binding to the acetylcholine receptor [7]. Meanwhile, the hydrophilic exterior of sugammadex means that the sugammadex-rocuronium complex is water soluble and gets excreted in the urine. Sugammadex encapsulates 25 million times as much rocuronium as it releases during a given time period, and is extremely pH- and temperature stable [6].  Sugammadex also inactivates rocuronium’s cousin vecuronium, although with a lower affinity than for rocuronium.

Dosing and Adjustments
When used in the OR, the dose is either 2 mg/kg or 4 mg/kg, depending on the depth of neuromuscular blockade as measured by train of fours. The dose for emergency reversal of neuromuscular blockade, in a “can’t intubate, can’t oxygenate situation,” is 16 mg/kg. Dosing of sugammadex is based on ideal body weight. No adjustments are necessary for mild to moderate renal failure. However, it is not recommended for CrCl < 30 [8].

Cautions
Sugammadex may decrease the efficacy of hormonal contraceptives. Patients on hormonal contraceptives should use a non-hormonal method of contraception for seven days following treatment with sugammadex. Intravenous lines in which zofran, ranitidine, or verapamil were infused should be flushed with saline prior to administration of sugammadex since the sugammadex-drug complex could precipitate in the line [9].

Adverse Effects
The most common adverse effects of sugammadex are minor and include nausea and vomiting (15%). More serious side effects include bradycardia (1-5%) QT prolongation (6%) recurrence of neuromuscular blockade (1%), and anaphylaxis (0.3%) [8,9].

Pregnancy
There is no data on sugammadex in pregnant women. Adverse effects have been observed in animal reproductive studies, and use in pregnancy is not recommended by the manufacturer. It is unknown if sugammadex is excreted in breast milk [9].

Cost

  • Solution 200 mg/2 mL (2 mL) : $114 8
  • Solution 500 mg/5 mL (5 mL): $208.80
  • Price for a 16 mg/kg emergent reversal dose for a 70 kg individual: $468

REFERENCES

  1. Curtis R, Lomax S, Patel B. Use of sugammadex in a ‘can’t intubate, can’t ventilate’ situation. Br J Anaesth. 2012;108(4):612-614. doi: 10.1093/bja/aer494 [doi].
  2. Dada A, Dunsire F. Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’scenario? Anaesthesia. 2011;66(2):141-142.
  3. Kyle B, Gaylard D, Riley R. A persistant’can’t intubate, can’t oxygenate’crisis despite rocuronium reversal with sugammadex. Anaesth Intensive Care. 2012;40(2):344.
  4. Ledowski T. Sugammadex: What do we know and what do we still need to know? A review of the recent (2013 to 2014) literature. Anaesth Intensive Care. 2015;43(1):14-22. doi: 20140551 [pii].
  5. Carron M, Zarantonello F, Tellaroli P, Ori C. Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: A meta-analysis of randomized controlled trials. J Clin Anesth. 2016;35:1-12. doi: S0952-8180(16)30293-8 [pii].
  6. Karalapillai D, Kaufman M, Weinberg L. Sugammadex. Crit Care Resusc. 2013;15(1):57-62.
  7. Yang LP, Keam SJ. Sugammadex. Drugs. 2009;69(7):919-942.
  8. Lexicomp. sugammadex: Drug information. www.uptodate.com. Updated 2017. Accessed April 21, 2017., .
  9. Bridion (sugammadex): Annotated prescribing information. Merck Sharp & Dohme B V. 2017.

ABOUT THE AUTHORS

Karen Serrano, MD is an assistant professor in the department of emergency medicine at the University of North Carolina.

Dr. Shenvi is an assistant professor in the department of emergency medicine at the University of North Carolina. She authors RX Pad each month in EPM.

2 Comments

  1. Oh no… not in the ED! This drug is by anesthesiologist for anesthesiologist, and maybe neurosurgeons. We are talking about a very different patient population. In my opinion, paralyzing a patient in your attempt to place an airway is like jumping from an airplane… there is no way back and the ground is approaching fast! You will follow your airway algorithm all the way to cric if needed, just like you would use your parachutes in your way down at gravity speed. If you expect that reversing paralysis will save your patient (and you) is like hoping from gravity to send you back up to the airplane. Nonsense! Moreover, the reason you wanted to intubate the patient in the first place hasn’t resolved, so you will end up with the same sick patient PLUS more hypoxia, hypercapnia and acidosis. So, thank you, but no thank you.

  2. Brad Garmon, BS, NRP, FP-C on

    While the tone of this article suggests a new tool in difficult airway management has just reached US hospitals, the most important comments lie in the paragraph describing the clinical limitations. The idea of a paralytic reversal agent in the hands of prehospital clinicians emergently intubating patients is very concerning. We operate in an environment outside of hemodynamically stable, well-fasted outpatient surgery clients. Our decision to intubate a spontaneously breathing patient by way of RSI should be made on the clinical presentation of either an oxygenation or ventilation failure or impending failure. To say a solution to our inability to secure the airway is to reverse the paralytics would only leave our patients in the same impending failure that they were in moments before; only now they suffer from the spasms, swelling, bleeding and aspirations that routinely accompany failed airway attempts. The later of these complications is also a significant side effect of Bridion.

    It is in the benefit of our patients to not reach for a paralytic reversal agent but. instead to push forward with the intubation, utilizing frequent practice of technique and a mastery of the anatomy. Prepare and master back up devices, procedures and maneuvers. It will happen: Difficult airways are what you plan for, failed airways are something you experience.

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