Hypothermia prolongs the time-course of action of non-depolarizing neuromuscular blocking agents. The mechanism, however, is unknown. We studied the influence of hypothermia (by surface cooling, nasopharyngeal temperature < or = 31 degrees C) on the time-course of action and on the pharmacokinetics of rocuronium in humans. Nineteen neurosurgical patients were divided into hypothermic and normothermic groups. Hypothermia (30.4 +/- 0.8 degrees C (mean +/- SD)) increased the duration of action, temperature dependently, and delayed the recovery. Hypothermia reduced the plasma clearance significantly (2.17 +/- 0.62 vs. 4.26 +/- 0.50 mL kg-1 min-1, P = 0.004), did not change the volume of distribution (224 +/- 64 vs. 232 +/- 60 mL kg-1 min-1, P = 1.0), and prolonged the mean residence time (108 +/- 39 vs. 56 +/- 19 mL kg-1 min-1, P = 0.01). We conclude that hypothermia prolongs the duration of action of rocuronium and delays spontaneous recovery and that altered pharmacokinetics, such as a decreased clearance, play an important role in this.
Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated.Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied.The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively.In male subjects, sugammadex safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium in a dose-dependent manner. Sugammadex enhanced the renal excretion of rocuronium, and its clearance is approximately one third that of rocuronium.
