Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients

We have studied dose requirements, recovery times and pharmacokinetics of rocuronium in 32 intensive care patients. After an initial dose of 50 mg, rocuronium was administered as maintenance doses of 25 mg whenever two responses to train-of-four (TOF) stimulation reappeared (bolus group; n=27) or by continuous infusion to maintain one response in the TOF (infusion group; n=5). Median requirements for rocuronium were 27.4 (range 14.5-68.3) mg h(-1) and 43.7 (30.9-50.3) mg h(-1) in patients in the bolus and infusion groups, respectively. Median total duration of rocuronium administration was 29.0 (12.4-95.5) h and 63.4 (24.0-140.3) h, respectively. Median time from administration of the last bolus dose and end of infusion to recovery of the fourth twitch in the TOF was 100 (45-300) min and 60 (15-155) min, respectively. Arterial blood samples were obtained for up to 10 h after cessation of rocuronium administration, and concentrations of the parent compound and its putative metabolites were measured using high pressure liquid chromatography (HPLC). The plasma concentration profile (n=12) was described adequately by a two-compartment model. Mean plasma clearance (CI), steady-state distribution volume (V-ss), mean residence time (MRT) and elimination half-life (T-1/2(beta)) were 3.16 (SD 1.15) ml kg(-1) min(-1), 769 (334) ml kg(-1), 262 (120) min and 337 (163) min, respectively. Recovery times, V-ss, MRT, and T-1/2(beta) differed from previously published data obtained after rocuronium infusion of moderate duration in surgical patients

Rapacuronium 2.0 or 2.5 mg kg(-1) for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg(-1)

The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg(-1) is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg(-1) during rapid-sequence induction of anaesthesia with fentanyl 1-2 mug kg(-1) and thiopental 2-7 mg kg(-1). Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg(-1) respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg(-1) was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg(-1) it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg(-1). The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P<0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg(-1) respectively (P<0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg(-1) could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction

[Sugammadex. New pharmacological concept for antagonizing rocuronium and vecuronium],[Sugammadex. New pharmacological concept for antagonizing rocuronium and vecuronium]

Contains fulltext : 79739.pdf (publisher's version ) (Closed access)Up to now only acetylcholine esterase inhibitors, such as neostigmine, were available as antagonists of residual neuromuscular blocks. Sugammadex is a modified gamma-cyclodextrin that binds rocuronium and chemically similar aminosteroidal muscle relaxants, such as vecuronium. The underlying mechanism of action is new and differs completely from that of acetylcholine esterase inhibitors. This review summarizes data published so far within the framework of the licensing procedure about the efficacy, safety and side-effects of sugammadex and presents potential new anesthesiological concepts using this compound

Sugammadex

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