VOLUME 31, ISSUE 2

Sugammadex is a new agent for reversal of neuromuscular blockade that was approved for use in the United States in 2015. It is a modified gamma cyclodextrin that forms a 1:1 complex with aminosteroid neuromuscular blocking (NMB) agent molecules, such as rocuronium and vecuronium. Sugammadex encapsulates the steroidal NMB agent and the complex then diffuses away from the synaptic cleft; it is renally excreted with an elimination half-life of about 100 minutes. Dosing of sugammadex is weight based and depends on the depth of residual neuromuscular blockade. The dose of 2 mg/kg should be used if the patient has 2 or more twitches. If the train-of-four only yields 1-2 post-tetanic twitches, the dose should be doubled to 4 mg/kg. The high dose of 16 mg/kg is typically only used when reversal of an intubating dose of rocuronium is required soon after administration. Sugammadex is not recommended in patients on dialysis. In the case of obese patients, actual body weight should be used to calculate the dose to prevent recurarization.1-4

The only contraindication to using sugammadex is known hypersensitivity to sugammadex or any of its components. The FDA has issued warnings regarding possible anaphylaxis or significant bradycardia after administering sugammadex. Furthermore, sugammadex can interact with other drugs. Toremifene, a selective estrogen receptor modulator used in the treatment of breast cancer, can lead to delayed recovery due to displacement of vecuronium or rocuronium from the complex with sugammadex. Hormonal contraceptives can be encapsulated by the sugammadex molecule and rendered ineffective. Therefore, women of child-bearing age should be counseled to use alternative barrier method contraception for the next 7 days.4 Cost comparisons between sugammadex and neostigmine/glycopyrrolate reversal are complex and can be influenced by price fluctuations due to drug shortages and the ability to impact institutional fixed costs by shortening the reversal and recovery process.

There are different options when neuromuscular blockade needs to be re-established after the administration of sugammadex. Recommendations exist for redosing of rocuronium (Iwasaki et al. Preparing for the unexpected: special considerations and complications after sugammadex administration. BMC Anesthesiology (2017) 17:140); however, many recommend simply converting to a nonsteroidal NMB agent such as cisatracurium.5

However, according to the Food and Drug Administration, the safety and effectiveness of sugammadex have not been established in patients less than 18 years of age. Pediatric studies have been conducted in regards to dosing and efficacy, while most of the studies regarding adverse events have been done in the adult population.

Plaud led the first study to evaluate sugammadex in pediatric patients in 2005. The primary endpoint was the recovery of the train-of-four (TOF) ratio to 0.9. Results showed a dose-response relationship with no recurrence of neuromuscular blockade, inadequate reversal, significant QT prolongation, or other abnormalities. He found that a dose of 2 mg/kg was associated with a median time of 1.1-1.2 minutes for recovery to a TOF of 0.9.3 Since then, multiple studies have been conducted comparing reversal with neostigmine versus sugammadex and found sugammadex to be superior to neostigmine in the 0.03-0.06 mg/kg dosing range.6-8 In 2017, Liu conducted an extensive search of 4 databases to evaluate the efficacy and safety of sugammadex for reversing postoperative residual neuromuscular blockade in the pediatric population. All 10 studies showed significant differences between the sugammadex and the control group. Reversal was more rapid with a lower incidence of bradycardia when sugammadex was administered.9

Anaphylactic reactions to sugammadex are uncommon but typically occur within 4 minutes after administration. Interestingly, hypersensitivity can occur without previous exposure to sugammadex due to cross-reaction from prior exposure to cyclodextrins present in food.5 There has also been a concern for sugammadex causing increases in activated partial thromboplastin time (aPTT) and prothrombin time (PT.) In 2014, Rahe-Mayer conducted a randomized, parallel-group, double-blind trial to investigate this further. The results showed that treatment with sugammadex 4 mg/kg was not associated with an increased in bleeding risk when compared to neostigmine or spontaneous reversal. There were limited mean increases in aPTT and PT, which resolved within 60 minutes.10 Lastly, Takodoro was the first to publish a study looking at the association between sugammadex and anaphylaxis in patients less than 18 years of age. Over 800,000 patients were enrolled and the study showed no significant association between sugammadex and perioperative anaphylaxis. They did, however, find a statistically significant increased incidence of anaphylaxis with increased duration of anesthesia and blood transfusion. 11

Sugammadex has significantly affected the practice of anesthesia due to the ability to reverse neuromuscular blockade at any time. It is being used successfully in the pediatric population, most notably outside of the United States. However, at this time, an in-depth cost analysis is needed to understand if the increased effectiveness of NMB agent reversal makes it prudent to use on a routine basis. Additionally, additional studies on the side effect profile of sugammadex would shed further light. At a minimum, it seems that sugammadex is safe for emergency use in pediatric patients and should be available for use when rapid reversal of aminosteroid NMB agent is required or when standard reversal regimens prove ineffective.