Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a cont...Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a continuous Rb administration method based on effect-site concentrations calculated by a pharmacokinetic/pharmacodynamics model during propofol, sevoflurane, and desflurane anesthesia. Methods: The 36 enrolled patients were equally divided into three groups (P;propofol, S;sevoflurane, and D;desflurane groups). After induction and administration of Rb 0.6 mg/kg, we calculated the simulated effect-site concentration at the point which the first twitch (%T1) recovered to > 0% and defined this as the Rb recovery concentration (Rbr.c.) level appropriate for continuous rocuronium administration. The continuous administration doses of Rb were adjusted to maintain Rbr.c. during surgery. The Rbr.c. and the recovery time at %T1 > 25% were recorded for each type of anesthesia. Results: Rbr.c. (μg/mL) for the P, S, and D groups were 1.54 ± 0.2, 1.24 ± 0.2, and 1.09 ± 0.2, respectively. Continuous administration doses (μg/kg/min) in the P, S, and D group were 6.7 ± 0.9, 5.2 ± 1.0, and 4.5 ± 0.8, respectively. Rbr.c. and continuous doses in the S and D groups were lower than the P group. Neuromuscular relaxations during surgery in the S and D groups were more strongly maintained than for the P group. There was also a significantly prolonged recovery duration for the %T1 > 25% in the D versus the other two groups (P < 0.05). Conclusion: Results showed that our continuous administration method was effective for maintaining sufficient muscle relaxation without excessively prolonged recovery effects for both sevoflurane and desflurane as well as propofol anesthesia.展开更多
Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose...Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose, and amino acid metabolism, as well as whether L-carnitine may improve suppression of free fatty acid metabolism. Methods: Male Sprague-Dawley rats, fasted for 16 hours, were allocated to the following two groups: (Group P;continuous intravenous administration of 10 mg/kg/h propofol;n = 8) and (Group P + C;intravenous administration of 50 mg/kg and then 50 mg/kg/h L-carnitine continuously;n = 8). Concentrations of glucose, free fatty acid (FFA), amino acids, in-sulin, and β-hydroxybutyric acid were measured at the start and then one, two, and three hours after propofol administration. Intrahepatic triglyceride levels were measured at the end of experiments. In vitro experiments comprised measurement of oxygen consumption in human hepatocytes (Hepg2) and investigating dependency on palmitic acid, glucose, and glutamine as fuel during propofol administration, with or without L-carnitine. Results: FFA increased in Group P and gradually decreased in Group P + C. There were significant differences between the two groups (Group P;331.2 ± 64.5 μM vs. Group P + C;199 ± 73.6 μM). Glucose decreased in both groups (Group P;53.8 ±16.6 mg/dL vs. Group P + C;88 ± 11.3 mg/dL). Amino acid concentrations were higher in Group P + C after experiments;alanine and glutamine increased significantly. β-hydroxybutyric acid increased significantly in Group P + C, and intrahepatic triglyceride decreased in Group P + C. Dependency on fatty acid metabolism significantly decreased with propofol only;addition of L-carnitine prevented these effects. Conclusions: Propofol impaired mitochondrial fatty acid metabolism, which was compensated mainly by a switch to glucose metabolism and partially by amino acid metabolism. Addition of L-carnitine may improve this imbalance of energy metabolism.展开更多
文摘Purpose: Although rocuronium bromide (Rb) is suitable for continuous administration use, determination of optimal continuous doses is difficult due to individual differences. This study examines the efficacy of a continuous Rb administration method based on effect-site concentrations calculated by a pharmacokinetic/pharmacodynamics model during propofol, sevoflurane, and desflurane anesthesia. Methods: The 36 enrolled patients were equally divided into three groups (P;propofol, S;sevoflurane, and D;desflurane groups). After induction and administration of Rb 0.6 mg/kg, we calculated the simulated effect-site concentration at the point which the first twitch (%T1) recovered to > 0% and defined this as the Rb recovery concentration (Rbr.c.) level appropriate for continuous rocuronium administration. The continuous administration doses of Rb were adjusted to maintain Rbr.c. during surgery. The Rbr.c. and the recovery time at %T1 > 25% were recorded for each type of anesthesia. Results: Rbr.c. (μg/mL) for the P, S, and D groups were 1.54 ± 0.2, 1.24 ± 0.2, and 1.09 ± 0.2, respectively. Continuous administration doses (μg/kg/min) in the P, S, and D group were 6.7 ± 0.9, 5.2 ± 1.0, and 4.5 ± 0.8, respectively. Rbr.c. and continuous doses in the S and D groups were lower than the P group. Neuromuscular relaxations during surgery in the S and D groups were more strongly maintained than for the P group. There was also a significantly prolonged recovery duration for the %T1 > 25% in the D versus the other two groups (P < 0.05). Conclusion: Results showed that our continuous administration method was effective for maintaining sufficient muscle relaxation without excessively prolonged recovery effects for both sevoflurane and desflurane as well as propofol anesthesia.
文摘Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose, and amino acid metabolism, as well as whether L-carnitine may improve suppression of free fatty acid metabolism. Methods: Male Sprague-Dawley rats, fasted for 16 hours, were allocated to the following two groups: (Group P;continuous intravenous administration of 10 mg/kg/h propofol;n = 8) and (Group P + C;intravenous administration of 50 mg/kg and then 50 mg/kg/h L-carnitine continuously;n = 8). Concentrations of glucose, free fatty acid (FFA), amino acids, in-sulin, and β-hydroxybutyric acid were measured at the start and then one, two, and three hours after propofol administration. Intrahepatic triglyceride levels were measured at the end of experiments. In vitro experiments comprised measurement of oxygen consumption in human hepatocytes (Hepg2) and investigating dependency on palmitic acid, glucose, and glutamine as fuel during propofol administration, with or without L-carnitine. Results: FFA increased in Group P and gradually decreased in Group P + C. There were significant differences between the two groups (Group P;331.2 ± 64.5 μM vs. Group P + C;199 ± 73.6 μM). Glucose decreased in both groups (Group P;53.8 ±16.6 mg/dL vs. Group P + C;88 ± 11.3 mg/dL). Amino acid concentrations were higher in Group P + C after experiments;alanine and glutamine increased significantly. β-hydroxybutyric acid increased significantly in Group P + C, and intrahepatic triglyceride decreased in Group P + C. Dependency on fatty acid metabolism significantly decreased with propofol only;addition of L-carnitine prevented these effects. Conclusions: Propofol impaired mitochondrial fatty acid metabolism, which was compensated mainly by a switch to glucose metabolism and partially by amino acid metabolism. Addition of L-carnitine may improve this imbalance of energy metabolism.
