Sugammadex Versus Neostigmine in Patients With Liver Cirrhosis Undergoing Liver Resection
Information source: Cairo University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cirrhosis and Chronic Liver Disease
Intervention: Sugammadex (Drug); Neostigmine (Drug); Rocuronium (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Cairo University Official(s) and/or principal investigator(s): Mohamed Abdulatif Mohamed, M.D., Principal Investigator, Affiliation: Cairo University
Overall contact: Mohamed Abdulatif Mohamed, M.D., Phone: +201002550237, Email: abdulatif@hotmail.com
Summary
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.
Clinical Details
Official title: Sugammadex Versus Neostigmine for Antagonism of Rocuronium-induced Neuromuscular Blockade in Patients With Liver Cirrhosis Undergoing Liver Resection: A Controlled Randomized Study
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The time from reversal to Train-of-four (TOF) ratio of 0.9
Secondary outcome: The time from reversal to Train-of-four (TOF) ratio of 1Length of stay in the post-anesthesia care unit (PACU) Time from last Rocuronium dose to Train-of-four (TOF) ratio of 0.9 Duration of action of the initial intubating dose of Rocuronium Incidence of postoperative re-curarization Total dose of Rocuronium Duration of anesthesia
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- American Society of Anesthesiologists physical status (ASA) class I for patients with
preoperative normal liver function test (two groups) and I-III for patients with
liver cirrhosis (two groups).
- For the two "Liver Cirrhosis" groups: Patients with liver Cirrhosis with Child
classification "A" and a Model for End-Stage Liver Disease (MELD) score <10
undergoing Liver resection surgeries.
- For the two "Normal Liver" groups: Patients with normal preoperative liver functions
undergoing Liver resection surgeries.
Exclusion Criteria:
- Co-existing neuromuscular disease.
- Body mass index more than 35 kg/m-2.
- Renal impairment.
- Medications known to affect neuromuscular transmission (e. g. Aminoglycoside
antibiotics or Magnesium Sulphate).
- Bleeding tendency.
- Intra-operative adverse events (e. g. massive bleeding or hypothermia).
Locations and Contacts
Mohamed Abdulatif Mohamed, M.D., Phone: +201002550237, Email: abdulatif@hotmail.com
National Liver institute, Garden City, Cairo 11562, Egypt; Recruiting Khaled Ahmed Yassen, M.D., Phone: +201063080170, Email: khaledyaseen61@hotmail.com
Additional Information
Related publications: Schaller SJ, Fink H. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid. 2013;8:57-67. doi: 10.2147/CE.S35675. Epub 2013 Sep 25. Review. Edginton AN, Willmann S. Physiology-based simulations of a pathological condition: prediction of pharmacokinetics in patients with liver cirrhosis. Clin Pharmacokinet. 2008;47(11):743-52. Kopman AF, Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia. 2009 Mar;64 Suppl 1:22-30. doi: 10.1111/j.1365-2044.2008.05867.x. Review. Caldwell JE. Clinical limitations of acetylcholinesterase antagonists. J Crit Care. 2009 Mar;24(1):21-8. doi: 10.1016/j.jcrc.2008.08.003. Epub 2009 Jan 17. Review. Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. 2007 Mar;104(3):575-81. Review. Nonaka T, Fujimoto M, Nishi M, Yamamoto T. [The effect of rocuronium and sugammadex in hepatic tumor patients without preoperative hepatic impairment]. Masui. 2013 Mar;62(3):304-8. Japanese. Batistaki C, Matsota P, Kalimeris K, Brountzos E, Kostopanagiotou G. Sugammadex antagonising rocuronium in three patients with liver dysfunction undergoing transjugular intrahepatic portosystemic shunt. Anaesth Intensive Care. 2012 May;40(3):556-7. Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7. Illman HL, Laurila P, Antila H, Meretoja OA, Alahuhta S, Olkkola KT. The duration of residual neuromuscular block after administration of neostigmine or sugammadex at two visible twitches during train-of-four monitoring. Anesth Analg. 2011 Jan;112(1):63-8. doi: 10.1213/ANE.0b013e3181fdf889. Epub 2010 Oct 26.
Starting date: December 2014
Last updated: April 8, 2015
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