Sugammadex Versus Neostigmine in Patients With Liver Cirrhosis Undergoing Liver Resection
Condition: Cirrhosis and Chronic Liver Disease
MeSH terms: Liver Diseases; Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Sugammadex; Neostigmine; Rocuronium
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of sugammadex 2mg/kg.; Rocuronium-induced neuromuscular blockade will be reversed at the end of the operation when two responses to train-of-four ulnar nerve stimulation are detected (T2) by injection of neostigmine 50 micro-gram/kg combined with atropine 20 micro-gram/kg.; An intubating dose of Rocuronium (0.6 mg/kg) will be given with induction of anesthesia and the degree of muscle relaxation will be evaluated through out the operation by recording the response of the hand muscles to train-of-four ulnar nerve stimulator (Mechanosensor Neuromuscular Transmission Module of General Electric AISYS Anaesthesia machine USA) according to the Good Clinical Research Practice (GCRP) guidelines for pharmacodynamic neuromuscular studies. Muscle relaxation will be maintained by additional top-up doses of Rocuronium (0.15mg/kg) which will be administered after detection of the first response to TOF stimulation (T1).
Other intervention name(s): Bridion; Prostigmine; Esmeron
Intervention MeSH terms: Rocuronium; Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sugammadex; Neostigmine; Rocuronium; Cirrhosis; Liver resection; Neuromuscular