الفهرس 
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Abstract
Background: Rocuronium bromide is mainly excreted by the liver and its duration might be prolonged in patients with hepatic dysfunction. Sugammadex, a modified γ-cyclodextrin, forms a tight complex with rocuronium which undergoes renal elimination. The use of sugammadex in patients with liver dysfunction might change the hepatic elimination of rocuronium to a renal pathway. The comparative evaluation of neostigmine and sugammadex to antagonize rocuronium-induced neuromuscular block in patients with liver cirrhosis has not been investigated.
Methods: This randomized controlled study included 30 patients with liver cirrhosis categorized as Child class ―A‖. Additional 30 patients with normal liver functions served as controls. All patients were undergoing liver resection. Anesthesia was induced with fentanyl and propofol and maintained with enotropy-guided titrated end-tidal sevoflurane concentration. Endotracheal intubation was facilitated with the use rocuronium 0.6mg/kg. Top-up doses of 0.15mg/kg were given to maintain a single twitch response to train-of-four (TOF) ulnar nerve stimulation. Adductor pollicis contractions were monitored using kinemyography. At the end of surgery and after recovery of two twitches of the TOF responses (T2), patients with liver cirrhosis and controls were divided randomly to two equal subgroups (n=15, each) according to the type of antagonist: sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 20 μg/kg. The primary efficacy variable was the time from antagonist administration to a TOF ratio 0.9. The durations of the intubating and top-up doses of rocuronium and the total intraoperative requirements were recorded. Safety variables included clinical evidence of reoccurrence of neuromuscular block after antagonism.
Results: Fifty-five patients completed the study. The mean (SD) ages in patients with liver cirrhosis and controls were 60.1 (5.4) and 33.7 (12.5) years, respectively (p<0001). The durations of anesthesia and surgery were comparable in the four study groups. The duration of intubating doses of rocuronium was significantly prolonged in patients with liver cirrhosis compared to controls [42.8 (4.5) versus 36.0 (5.9)] min, respectively (p=0.009). Furthermore, the duration of action of successive maintenance top-up doses was progressively prolonged in patients with liver cirrhosis and in controls. The total rocuronium requirements were lower in patients with liver cirrhosis [133.0 (33.0) versus 179.3 (26.8)] mg, respectively (p=0.003). The times to achieve a TOF ratio of 0.9 after sugammadex administration in liver cirrhosis patients were comparable to controls [3.1 (1.0) and 2.6 (1.0) min], respectively (p=1.0). The times to a TOF ratio of 0.9 after neostigmine administration were much longer than sugammadex and were comparable in liver cirrhosis and control patients [14.5 (3.6) and 15.7 (3.6)] min, respectively (p=1.0). Recurrence of neuromuscular block was not observed in any patient in the four study groups.
Conclusions. Sugammadex administered at reappearance of T2 rapidly and effectively reverses residual rocuronium-induced neuromuscular block in patients with Child class ―A‖ liver cirrhosis undergoing liver resection. The duration of adequate neuromuscular recovery after sugammadex antagonism is comparable in patients with liver cirrhosis and controls. Sugammadex antagonism is associated with almost 80% reduction in the time to adequate neuromuscular recovery compared to neostigmine. Further studies are required to categorize the pharmacokinetic profile of sugammadex-rocuronium complex in patients with liver dysfunction.