More than 1500 laparoscopic abdominal gynaecological surgeries are performed at our Hospital
every year and hence there is a need to provide excellent analgesia and minimize side effects
from medications to improve patient satisfaction and outcomes. Postoperative nausea and
vomiting (PONV) may occur in 30% of women undergoing gynaecological surgery. In a patient
population with multiple risk factors (e.g. female gender, duration of surgery > 2 hours,
non-smoker, history of PONV or a history of motion sickness), the incidence is up to 80%.
PONV has a significant negative effect on patient satisfaction after anesthesia and is one of
the most common causes for unexpected hospital admissions in day-surgery.
The primary aim of our study is to determine whether Sugammadex would reduce the incidence of
self-reported postoperative nausea after surgery in high-risk women 24-hours after undergoing
laparoscopic gynaecological surgery, when compared to Neostigmine. The secondary aims are to
investigate the effects of Sugammadex on the severity of self-reported PONV at 6-hour; the
quality of recovery score at 24-hours; total number of patients with PONV, pain intensity and
overall satisfaction score with anaesthesia following laparoscopic gynaecological surgery in
high-risk women. This study is intended as a double-blinded, randomised, single-center trial
at KK Women's and Children's Hospital.
Sugammadex is a selective relaxant-binding agent that provides rapid reversal from
neuromuscular blockade induced during general anaesthesia to facilitate surgical procedures.
The main advantage of sugammadex is that its action is not dependent on inhibition of
acetylcholinesterase when compared to traditional reversal agents such as Neostigmine.
Therefore, sugammadex is not associated with the cholinergic side effects like nausea,
vomiting and bradycardia. This present study intends to provide a new, effective anaesthetic
regimen producing a reduction in side effects from surgery and anaesthesia, with higher
patient satisfaction.
Sugammadex was identified as the first selective relaxant-binding agent providing rapid
reversal from neuromuscular blockade induced during general anaesthesia when used to
facilitate surgical procedures (Welliver 2006). The mechanism of Sugammadex differs from that
of other commonly used reversal agents, such as neostigmine and edrophonium, which are
reversible acetylcholinesterase inhibitors.
Neostigmine relies on inhibition of acetylcholinesterase, causing autonomic instability and
side effect like headache, blurred vision, slowing of the heart rate (bradycardia), and
gastrointestial symptoms including anorexia, nausea, vomiting, abdominal cramps and diarrhea.
Hence, an anticholinergic drug such as atropine has to be administered concurrently to
prevent excessive muscarinic effects such as bradycardia (Gilman 1980). A previous study
(Lovstad et al 2001) showed that neostigmine increases the incidence of postoperative nausea
and vomiting after gynaecological surgery compared to a placebo. However, in the current
practice of providing neuromuscular blockade for laparoscopic surgery, maintenance of
neuromuscular blockade is required to facilitate surgery, thereby making reversal agents
necessary to prevent postoperative residual neuromuscular blockade.
Knowledge Gap:
Without preventative treatment, about 30% of patients undergoing general anaesthesia are
likely to suffer postoperative nausea and vomiting (PONV) (Cohen et al, 1994; Apfel et al,
1999). In a patient population with multiple risk factors (e.g. female gender, duration of
surgery > 2 hours, non-smoker, history of PONV or history of motion sickness), the incidence
is up to 80%. PONV has a significant negative effect on patient satisfaction after
anaesthesia and is one of the most common causes for unexpected hospital admissions after
day-surgery.
Since at our Hospital more than 1500 laparoscopic gynaecological surgeries are performed
every year, this a significant clinical problem. Unplanned hospital admissions due to
postoperative nausea and vomiting after a low-risk, day-surgical, gynaecological procedure at
our hospital accounted for 29 cases out of a total of 163 cases last year (18%). In fact, the
Ministry of Health tracks unplanned hospital admission as a performance indicator.
Sugammadex is more expensive when compared to neostigmine, and therefore its use should be
limited to the high-risk PONV group, in order to maximize its cost-benefit potential.
Sugammadex was first approved for use in the European Union in 2008 and is also approved in
Australia, Iceland, New Zealand and Norway. A recently published Cochrane systematic review
on Sugammadex (Abrishami et al 2012) examined the efficacy and safety of Sugammadex and the
authors concluded that Sugammadex was shown to be more effective than placebo (no medication)
or neostigmine in reversing muscle relaxation caused by neuromuscular blockade during surgery
and is relatively safe. Inadequate reversal of neuromuscular blockade may lead to breathing
problems or hypoxia due to an inability to breathe adequately, potentially leading to
prolonged hospitalisation, thereby causing increased healthcare costs.
Train-of-four (TOF) monitoring enables the anaesthetist to assess if neuromuscular blockade
could be safely reversed. The expert recommendation is to reverse neuromuscular blockade when
TOF is at least 2 (0 to 4, 0= dense neuromuscular blockade, 4= minimal neuromuscular
blockade). Sugammadex may potentially lead to greater patient safety in anaesthesia and at
the same time offer greater patient satisfaction in terms of reducing the side effects of
neostigmine like nausea and vomiting. However, there is little evidence about the clinical
outcomes after administration of Sugammadex, such as the incidence and severity of PONV after
surgery and the quality of recovery and pain intensity in high-risk women following
laparoscopic gynaecological surgery.
Our current proposal will compare Sugammadex with neostigmine in women at high-risk of PONV
after laparoscopic gynaecological surgery. As this study is the first clinical trial
targeting the population at high-risk of developing PONV and may change routine clinical
practice. If our hypothesis is true, Sugammadex will provide a new anaesthetic regime with
better patient safety and efficacy such as reduction in unplanned hospital admissions;
reduction in anaesthetic complications such as nausea, vomiting and inadequate reversal of
neuromuscular blockade routinely produced during anaesthesia.