Sugammadex Versus Neostigmine for Antagonism of Rocuronium-induced Neuromuscular Blockade in Patients With Liver Cirrhosis Undergoing Liver Resection: A Controlled Randomized Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The time from reversal to Train-of-four (TOF) ratio of 0.9
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Co-existing neuromuscular disease.
- •Body mass index more than 35 kg/m-
- •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).
研究组 & 干预措施
Sugammadex/ Normal liver
Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection.
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.
干预措施: Sugammadex (Drug)
Sugammadex/ Normal liver
Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection.
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.
干预措施: Rocuronium (Drug)
Neostigmine / Normal liver
Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection.
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.
干预措施: Neostigmine (Drug)
Neostigmine / Normal liver
Patients with American Society of Anesthesiologists physical status (ASA) class I with normal preoperative liver functions undergoing liver resection.
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.
干预措施: Rocuronium (Drug)
Sugammadex / Liver cirrhosis
Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score <10 undergoing liver resection.
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.
干预措施: Sugammadex (Drug)
Sugammadex / Liver cirrhosis
Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score <10 undergoing liver resection.
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.
干预措施: Rocuronium (Drug)
Neostigmine / Liver cirrhosis
Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score <10 undergoing liver resection.
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.
干预措施: Neostigmine (Drug)
Neostigmine / Liver cirrhosis
Patients with liver cirrhosis, Child classification "A" with a Model for End-Stage Liver Disease (MELD) score <10 undergoing liver resection.
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.
干预措施: Rocuronium (Drug)
结局指标
主要结局
The time from reversal to Train-of-four (TOF) ratio of 0.9
时间窗: 15 min
The time from the administration of Sugammadex or Neostigmine till recovery of the TOF ratio to 0.9
次要结局
- The time from reversal to Train-of-four (TOF) ratio of 1(30 min)
- Length of stay in the post-anesthesia care unit (PACU)(4 hours)
- Time from last Rocuronium dose to Train-of-four (TOF) ratio of 0.9(1 hour)
- Duration of action of the initial intubating dose of Rocuronium(45 min)
- Incidence of postoperative re-curarization(4 hours)
- Total dose of Rocuronium(24 hours)
- Duration of anesthesia(24 hours)
研究者
Professor Mohamed Abdulatif Mohamed
Prof. Mohamed Abdulatif Mohamed, MD
Cairo University