Cirrhosis and Chronic Liver Disease Clinical Trial
Official title:
Sugammadex Versus Neostigmine for Antagonism of Rocuronium-induced Neuromuscular Blockade in Patients With Liver Cirrhosis Undergoing Liver Resection: A Controlled Randomized Study
Liver cirrhosis is a progressive disease characterized by loss of functional hepatocytes
that substantially affects drug pharmacokinetics. Rocuronium onset time is longer and
recovery time from it is prolonged in cirrhotic patients than in those with normal liver
function.
This randomized controlled study is designed to compare the pharmacodynamic profiles of
sugammadex and neostigmine when used for the antagonism of moderate degree of
rocuronium-induced neuromuscular block in cirrhotic patients undergoing liver resection and
in patients with preoperative normal liver functions undergoing liver resection.
Liver resection is a lengthy operation that has major effects on patient hemodynamics and
perioperative liver functions. These effects are more obvious in patients with liver
cirrhosis. Liver cirrhosis is a progressive disease characterized by loss of functional
hepatocytes that substantially affects drug pharmacokinetics.
Rocuronium is an intermediate acting steroidal non-depolarizing neuromuscular blocker that
is mostly metabolized by the liver. Its onset time is longer in cirrhotic patients than in
those with normal liver function. This can be explained by an increase in the volume in
which it initially distributes. Although elimination kinetics are unchanged in patients with
cirrhosis, Rocuronium recovery time is prolonged in cirrhotic patients.
To speed up the process of antagonism of residual neuromuscular blockade, inhibitors of
acetyl cholinesterases such as Neostigmine are usually administered only when there is
evidence of spontaneous recovery of neuromuscular function. Too early administration of
Neostigmine is not effective and may produce serious side-effects from accumulation of
Acetylcholine in other organs, especially the brain and heart.
Sugammadex, a modified γ-cyclodextrin, is the first selective relaxant binding agent. It
forms very tight, stable complexes in a 1:1 ratio with Rocuronium. The inactive
Sugammadex-Rocuronium complex undergoes renal elimination. Sugammadex has no effect on
acetyl cholinesterases or on any receptor system in the body, eliminating the need for
anticholinergic drugs. Sugammadex can antagonize any level of neuromuscular blockade,
including the profound blockade induced by Rocuronium.
The use of Sugammadex in different patient populations including end-stage renal failure is
associated with consistent, complete and rapid recovery of neuromuscular functions. It is of
clinical relevance to note that in the presence of Sugammadex, the hepatic biotransformation
and final clearance of Rocuronium via biliary excretion is changed to a completely different
(liver-independent) renal pathway. A recent report described the successful use of
Sugammadex to antagonize prolonged deep rocuronium-induced neuromuscular block in patients
with normal liver functions undergoing liver resection. Furthermore, the successful use of
Sugammadex to antagonize Rocuronium neuromuscular block was also reported in a case series
of three patients with liver dysfunction.
To the best of our knowledge, there are no controlled randomized studies evaluating the use
of Sugammadex to antagonize residual Rocuronium-induced neuromuscular blockade in patients
with liver cirrhosis undergoing open surgical liver resection. This randomized controlled
study is designed to compare the pharmacodynamic profiles of Sugammadex and Neostigmine when
used for the antagonism of moderate degree of Rocuronium-induced neuromuscular block in
cirrhotic patients undergoing liver resection and in patients with preoperative normal liver
functions undergoing liver resection.
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Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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