Abstract
Aim: Residual neuromuscular blockade is a common complication after general anaesthesia. Sugammadex can reverse the action of aminosteroid neuromuscular blockers. Our study aimed to explore sugammadex safety issues in the real world and determine the spectrum of adverse reactions.
Methods: All sugammadex-related adverse events reported in VigiBase between 2010 and 2019 were classified by group queries according to the Medical Dictionary for Regulatory Activities. A disproportionality analysis of data was performed using the information component (IC); positive IC values were deemed significant.
Results: Overall, 16,219,410 adverse events were reported, and 2032 were associated with sugammadex. The most frequent reactions were recurrence of neuromuscular blockade (n = 54, IC: 6.74, IC025: 6.33), laryngospasm (n = 53, IC: 6.05, IC025: 5.64), bronchospasm (n = 119, IC: 5.63 , IC025: 5.36), and bradycardia (n = 169, IC: 5.13, IC025: 4.90). Fatal cases were more likely with cardiac disorders, especially in patients over 65 years of age. In addition, the common adverse drug reactions (ADRs) differed between different age groups (P < 0.01). The ADRs were higher between age 0–17 years than in other age groups. The onset time of common ADRs was typically within 1 day, and 68.9% occurred within half an hour after sugammadex administration.
Conclusions:Anaesthesiologists should carefully monitor the anaesthesia recovery period to correct the ADRs caused by sugammadex and recommend monitoring neuromuscular function throughout the anaesthesia process. Sugammadex should be used carefully in patients with cardiovascular diseases, and electrocardiography and hemodynamic changes should be monitored after medication.
Introduction
Muscle relaxation is a fundamental element of general anaesthesia. The neuromuscular blockers commonly used to assist general anaesthesia and promote tracheal/mechanical ventilation can provide quality surgical conditions by reducing muscle tension. However, residual neuromuscular blockade is a common complication after general anaesthesia. A Chinese study1 reported that the incidence of residual neuromuscular blockade during extubation for anaesthesia resuscitation was approximately 57.8%. Residual neuromuscular blockade may lead to a series of respiratory complications, such as hypoxemia and atelectasis, and cause subjective discomfort to the patient; death may occur in severe cases2, 3.
Sugammadex is a new type of specific neuromuscular block antagonist. It was first introduced in Europe in 20084; it was approved in the United States in 2015 and China in 2017. Sugammadex is a cyclodextrin derivative that specifically antagonizes non-depolarizing aminosteroid muscle relaxants that contain a hydrophilic outer layer and a lipophilic core. Rocuronium and vecuronium are specifically encapsulated in the lipophilic core, and sugammadex exerts antagonistic effects against them5. Compared with the traditional muscle relaxant antagonist, neostigmine, it achieved faster recovery of neuromuscular function6 (mean time to effect: 3 min) and improved patient safety7. Therefore, the muscle relaxants and anaesthesia reversal guidelines8 issued by the French Society of Anaesthesiology and Critical Care Medicine in 2020 recommend that appropriate doses of sugammadex should be administered according to body weight to antagonize the neuromuscular block during the recovery period from general anaesthesia in patients who have received rocuronium.
However, with the more frequent clinical use of sugammadex, reports of its adverse reactions have recently increased, and safety issues have become more prominent. Previous studies on the safety of sugammadex have mostly been single-centre studies or meta-analyses; this study is based on the World Health Organization (WHO) global database of individual case safety reports, namely VigiBase9, to explore the safety issues related to sugammadex in the real world. This database can provide data on rare adverse drug reactions (ADRs) and enable adverse reaction mapping of a wide spectrum of events.
Methods
2.1 Data source
We obtained the data from VigiBase, the largest pharmacovigilance worldwide database, maintained by the Uppsala Monitoring Centre (UMC), the WHO Collaborating Centre for International Drug Monitoring. The UMC receives reports of suspected ADRs from national centres in countries participating in the WHO Program for International Drug Monitoring (https://www.who-umc.org/vigibase/vigibase/). VigiBase contains more than 28 million individual case safety reports (ICSRs) from approximately 150 member states since 1968, covering approximately 99% of the world’s population. Drugs are coded according to WHODrug, and ADRs according to MedDRA references (version 20.1)10.
2.2 Study design
This observational and retrospective pharmacovigilance study explored the association between sugammadex and suspicious ADRs through a disproportionality analysis (also known as case/non-case analysis). The reference group included all ADRs in the VigiBase database. If the proportion of ADRs in patients exposed to sugammadex was greater than in patients not exposed to the drug, an association between the drug and ADRs was suspected, a potential safety signal. We analysed the detailed clinical characteristics of ADRs associated with sugammadex in Vigibase to draw a spectrum of possible adverse reactions of this drug, stratify the patients by age, and analyse the similarities and differences between patients in different age groups. The main time window for ADRs after using sugammadex was analysed according to the reaction onset time.