Discussion
In our review of 241 patients undergoing liver transplantation, we found
no statistically significant difference in postoperative bleeding
outcomes in patients reversed with sugammadex vs. neostigmine. Compared
with neostigmine, the use of sugammadex had slightly prolonged aPTT at
the immediate postoperative period; however, it was associated with less
risk of postoperative red blood cell transfusion and re-operation. In
the secondary outcomes, acute organ rejection occurred slightly higher
in the sugammadex group; however, this slight increase was not
statistically significant. The sugammadex group had less PONV. Both
groups had similar LOS.
Postoperative hemorrhage is one of the broad spectra of liver
transplantation complications. Mueller et al. suggested that the most
important risk factors for early postoperative bleeding are severe
coagulopathy and thrombocytopenia.3 Everson et al.
proposed that the most significant bleeding risk is in the setting of
both severe coagulopathy and portal hypertension.7Abnormal coagulation reflected by prolongation of aPTT and PT are common
laboratory findings in these patients. Patients with cirrhosis have been
described as having a rebalanced hemostatic system due to a concurrent
reduction in pro- and anti-hemostatic. systems8, 9However, the hemostatic balance in these patients is more fragile
compared to healthy individuals. Both diffuse bleeding and thrombosis
can occur during and after liver transplantation. After liver
transplantation, it is presumed that the hemostatic system normalizes as
the liver synthetic function is restored.
Clinical trials in healthy subject and surgical patients reported that
sugammadex had transient aPTT and PTT
prolongations.4,10 Based on the information
supplemented by the Food and Drug Administration (FDA), healthy
volunteers had increased aPTT and PT/INR up to 1 hour with
administration doses up to 16mg/kg sugammadex.11Dirkmann et al. suggested the effect on coagulation may be explained by
the cyclodextrin molecule binding the phospholipid, and the
anticoagulant effects were likely an in vitro artifact observed
in commercial phospholipid-dependent assays such as the
aPTT.12 Other studies found that sugammadex does not
affect platelet or factor Xa function.13,14 However,
the sugammadex effect on postoperative bleeding is still controversial.
Tas et al. reported that sugammadex was associated with a higher amount
of postoperative bleeding than neostigmine after septoplasty in
otherwise healthy patients.15
On the contrary, Raft et al. investigated postoperative bleeding in
high-risk cancer patients, and they found sugammadex was not associated
with increased postoperative bleeding.16 Moon et
al . reported that sugammadex is not associated with increased bleeding
tendency or morbidity in healthy patients undergoing living-donor
hepatectomy.17 Our study had similar results as
sugammadex was not associated with an increased bleeding profile. In
fact, there was no instance of re-operation in the sugammadex group. To
the best of our knowledge, this is the first effort to examine the
bleeding risk of sugammadex in deceased donor liver transplantation.
In the secondary outcomes, the sugammadex group had slightly higher
acute organ rejection (0.7% patients in the neostigmine group vs. 1.9%
in the sugammadex group). However, both groups had a much lower acute
organ rejection rate than large cohort studies. (27% in the Adult to
Adult Living Donor Liver Transplantation cohort and 15.6% in the
Scientific Registry of Transplant Recipients cohort.18Sugammadex creates a steroid complex with the aminosteroid neuromuscular
blocking agents, and it has been shown to reduce other drugs’ efficacy
by encapsulating drugs with similar structures such as oral
contraceptive pills.11 Corticosteroids are a crucial
component of immunosuppression therapy in liver transplantation and are
administered during the peri-transplant period to prevent acute organ
rejection. Rezonja et al. found the concomitant administration of high
dose dexamethasone diminished the efficiency of sugammadex in the in
vitro experiment.19 However, Rezonja et al. also found
that dexamethasone does not diminish sugammadex reversal of
neuromuscular blockade in a clinical study.20Furthermore, Arslantas et al. found no difference in the risk of adverse
effects on short-term graft function in 42 patients who underwent kidney
transplantation.21
Our study also showed that the sugammadex group had less PONV, which is
consistent with previous work.3 Regarding hospital
length of stay, the two groups had small differences: 7.0 days in the
neostigmine group and 7.8 days in the sugammadex group. In a large
cohort study, patients reversed with sugammadex had earlier first postop
bowel movement compare to patients reversed with
neostigmine22, which potentially could reduce the
hospital length of stay.
There are several limitations to our study. First, the retrospective
design of the study is certainly a limiting factor. Additionally, this
data represents outcomes from a single-center, although our institution
performs roughly 150 liver transplantations a year, and there were no
significant differences in any of our demographic variables. Third,
temporal factors exist as the neostigmine group was transplanted from
2015 to 2017, versus the sugammadex group which was transplanted from
2017 to 2018. Surgical techniques and surgeon experiences may have
improved with time and could confound our results. Nevertheless, our
study is the first study to evaluate the sugammadex effect on
postoperative bleeding risk in the adult orthotopic liver
transplantation population.