Sugammadex is a newer neuromuscular blockade reversal agent which was approved for use in the United States in 2015.¹ Neostigmine, another reversal agent, exerts its neuromuscular blockade reversing effects against non-depolarizing neuromuscular blocking agents through reversible inhibition of acetylcholinesterase, thereby increasing the concentration of presynaptic acetylcholine to facilitate skeletal muscle contraction.² In contrast, Sugammadex directly binds the non-depolarizing neuromuscular blocking agents rocuronium and vecuronium. Sugammadex binds to rocuronium and vecuronium in a dose-dependent fashion and renders them ineffective, facilitating rapid clearance of these neuromuscular blocking agents and reversal of neuromuscular blockage.³ However, like any medication, there are restrictions and limitations on the use of Sugammadex.

There are few absolute contraindications to the use of Sugammadex, though there are populations for which the use of Sugammadex should be judicious, with pros and cons weighed prior to its administration. The two absolute contraindications are a documented hypersensitivity reaction to the medication and a creatinine clearance less than 30 mL/min.¹ A 2018 study found a dose-dependent hypersensitivity or anaphylaxis reaction to Sugammadex when administered without prior neuromuscular blocking agent (0.0%; 0.7%; 4.7% for placebo, Sugammadex 4 mg/kg, and Sugammadex 16 mg/kg, respectively).⁴ Sugammadex is renally cleared and was demonstrated to have significantly impaired renal clearance in patients with end-stage kidney disease (ESKD) (5.5 mL/min vs 95.2 mL/min in patients with ESKD versus those without ESKD, p < 0.05).⁵

There are certain populations for which the clinical indications for use of Sugammadex should be weighed against known complications or lapses in knowledge, with restrictions and limitations decided by the clinical team. For patients taking hormonal birth control, it is recommended that a back-up method of contraception (e.g., male/female condom, spermicides) are used for the next seven days following administration of Sugammadex. This is due to in vitro studies which suggest Sugammadex may bind to progestogen, with a response equivalent to missing a dose of an oral contraceptive containing an estrogen or progestogen.¹ In patients who breastfeed, the National Institute of Child Health and Human Development’s Drugs and Lactation Database recognize that there is little information on the effects of Sugammadex during breastfeeding but, due to its chemical properties, consider absorption in milk and oral absorption of the drug by the infant to be unlikely.⁶

Sugammadex doses up to 16 mg/kg have been associated with increases in the activated partial thromboplastin time as well as prothrombin time/international normalized ratio.¹ Thus, for patients with known coagulopathy or at increased risk for coagulopathy, adjudication of the use of Sugammadex should be made carefully, weighing the risk of worsened or acute coagulopathy against clinical benefit. Finally, Sugammadex is more expensive than neostigmine, limiting its use, especially early in its introduction. One study demonstrated that despite a decreased time to extubation and lower incidence of bradycardia in the Sugammadex treated group compared to the neostigmine treated group, the total costs were significantly higher in the Sugammadex group than in the neostigmine group ($212.0 ± 49.5 vs $50.6 ± 21.4, respectively).⁷

In conclusion, Sugammadex is a newer neuromuscular blockade reversal agent for non-depolarizing neuromuscular agents (i.e., rocuronium and vecuronium). It has a favorable pharmacodynamic profile to facilitate rapid reversal of neuromuscular blockade. There are few absolute contraindications to the clinical use of Sugammadex, but restrictions remain and require careful adjudication of its clinical utility.

References

1. United States Food and Drug Administration. BRIDION® (sugammadex) Injection US Prescribing Information. U S Food Drug Adm. Published online December 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022225lbl.pdf
2. Neely GA, Sabir S, Kohli A. Neostigmine. In: StatPearls. StatPearls Publishing; 2024. Accessed September 9, 2024. http://www.ncbi.nlm.nih.gov/books/NBK470596/
3. Epemolu O, Bom A, Hope F, Mason R. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology. 2003;99(3):632-637; discussion 6A. doi:10.1097/00000542-200309000-00018
4. De Kam PJ, Nolte H, Good S, et al. Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers. Br J Anaesth. 2018;121(4):758-767. doi:10.1016/j.bja.2018.05.057
5. Staals LM, Snoeck MMJ, Driessen JJ, et al. Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study. Br J Anaesth. 2010;104(1):31-39. doi:10.1093/bja/aep340
6. National Institute of Child Health and Human Development. Sugammadex. Drugs Lact Database Lact. Published online April 15, 2023. https://www.ncbi.nlm.nih.gov/books/NBK500924/pdf/Bookshelf_NBK500924.pdf
7. Lan W, Tam KW, Chen JT, et al. Cost-Effectiveness of Sugammadex Versus Neostigmine to Reverse Neuromuscular Blockade in a University Hospital in Taiwan: A Propensity Score-Matched Analysis. Healthc Basel Switz. 2023;11(2):240. doi:10.3390/healthcare11020240