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
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.
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.