Sugammadex Complications

Sugammadex, a modified γ-cyclodextrin, has revolutionized the reversal of neuromuscular blockade, particularly for agents such as rocuronium and vecuronium. Despite its efficacy and widespread use, sugammadex is associated with several complications and adverse effects that require clinical awareness for optimal patient management.

One significant concern is the risk of hypersensitivity reactions, including anaphylaxis. Although the overall incidence is low, such reactions can be life-threatening. Anaphylaxis associated with sugammadex typically presents with the sudden onset of symptoms like hypotension, bronchospasm, and cutaneous manifestations such as urticaria. A systematic review documented sugammadex-induced anaphylactic reactions in which patients required immediate intervention, including administration of epinephrine and airway management. Although most adverse reactions resolved without long-term complications, the review highlighted the importance of preparedness and prompt recognition of these rare but serious events (1). Given this risk, monitoring patients for signs of hypersensitivity in the immediate post-administration period is critical.

Although typically well managed, cardiovascular complications of sugammadex have been reported and warrant attention. Hypotension and bradycardia are among the most commonly observed cardiovascular effects. One notable case study described an unexpected case of hypotension occurring shortly after sugammadex administration, with blood pressure changes evident within ten minutes of dosing (2). The exact pathophysiological mechanism remains uncertain, although it is hypothesized that vascular smooth muscle relaxation or histamine release may contribute. Therefore, clinicians are advised to closely monitor hemodynamic parameters during and after administration, especially in patients with pre-existing cardiovascular compromise.

The mechanism of action of sugammadex – encapsulation and inactivation of steroidal neuromuscular blocking agents – raises concerns about potential interactions with other steroid-based medications. One of the most clinically relevant concerns involves hormonal contraceptives. Although sugammadex is not directly cytotoxic to steroid hormones, it may transiently reduce the plasma concentration of contraceptive steroids, potentially reducing contraceptive efficacy. A randomized clinical trial examining hormonal profiles after sugammadex administration found minimal long-term effects but acknowledged a transient reduction in steroid levels (3). As a result, patients should be advised to use alternative contraceptive methods for at least seven days following sugammadex administration to reduce the risk of unintended pregnancy.

Another complication that deserves attention is the phenomenon of recurarization, a condition characterized by the recurrence of neuromuscular blockade after an initial successful reversal. Although rare with appropriate dosing, recurarization can occur if sugammadex is underdosed, potentially resulting in respiratory distress if breathing support has already been removed. In-depth analyses of case reports suggest that inadequate dosing relative to the depth of blockade is a key factor contributing to this complication (4). To prevent recurrence, rigorous neuromuscular monitoring is essential to ensure complete and sustained recovery of neuromuscular function prior to extubation.

In addition, pharmacovigilance data have added to the understanding of the safety profile of sugammadex. A recent analysis of FDA adverse event reports identified a spectrum of adverse reactions ranging from mild to moderate in severity. These included common post-operative complaints such as nausea, vomiting, and transient headache, as well as isolated reports of more serious outcomes, including arrhythmias and respiratory compromise (5). The majority of these adverse events resolved without intervention, but the study highlighted the need for ongoing surveillance to refine clinical protocols and improve safety.

Although less frequently discussed, the risk of coagulation abnormalities has been highlighted in some pharmacodynamic studies. Sugammadex may theoretically alter coagulation profiles, particularly in patients on anticoagulant therapy. While the clinical significance remains uncertain, further research is warranted to establish clear guidelines. Until more definitive data are available, to reduce the risk of complications, clinicians should exercise caution when administering sugammadex to patients with existing coagulopathies or those receiving anticoagulant therapy.

References

1. Zecic F, Smart MH, Abbey TC, Pazhempallil A, Korban C. Sugammadex-induced anaphylactic reaction: A systematic review. J Anaesthesiol Clin Pharmacol. 2022;38(3):360-370. doi:10.4103/joacp.JOACP_573_20
2. Kokki M, Ali M, Turunen M, Kokki H. Suspected unexpected adverse effect of sugammadex: hypotension. Eur J Clin Pharmacol. 2012;68(5):899-900. doi:10.1007/s00228-011-1196-z
3. Lee HY, Jung KT. Advantages and pitfalls of clinical application of sugammadex [published correction appears in Anesth Pain Med (Seoul). 2022 Jul;17(3):341. doi: 10.17085/apm.19099.e1.]. Anesth Pain Med (Seoul). 2020;15(3):259-268. doi:10.17085/apm.19099
4. Iwasaki H, Renew JR, Kunisawa T, Brull SJ. Preparing for the unexpected: special considerations and complications after sugammadex administration. BMC Anesthesiol. 2017;17(1):140. Published 2017 Oct 17. doi:10.1186/s12871-017-0429-9
5. Mao X, Zhang R, Liang X, et al. A pharmacovigilance study of FDA adverse events for sugammadex. J Clin Anesth. 2024;97:111509. doi:10.1016/j.jclinane.2024.111509