Pharmacodynamics Comparson Of Rocuronium Adninistrated Accordin To Lean Body Mass And Weight

At present, the dose of muscle relaxant is mainly calculated by body weight and the ED95,we found that there were laege differences in the actual effect between different individual, especially between obese and thin patients, male and female, children and adults. The incidence of postoperative residual block is higher in elderly and obese patients.When both obese patients and normal body weight are administrated according to body weight, in the obese patients onset time is faster and the effect of muscle relaxant is stronger, particularly in longer aging. The reason may be that the dose calculated by body weight is too much.Obesity influences the efficacy of muscle relaxants have been reported. Some scholars proposed that muscle relaxants should be applied according to standard body weight. Usually the pharmacological effects of the drμg effectiveness depends on the drμg in a target cell concentratio,Drμg effect is proportional to its plasma concentration, Compared with normal body mass of people, obese patient musculature and adipose tissue is increasing, but adipose tissue increased more than muscle tissue. Obese patients per kg of body quality have less muscle tissue and more adipose tissue. Usually flows throμgh the blood flow less fat, accounting for approximately 5% of heart, and blood flows throμgh isceral is accounted for 73%, muscle is 22%. This indicates the lean body mass is more closely related to blood volume, Would the muscle relaxant administered according to lean body mass reduce the individual differences? Firstly, establish the dose-response curve of rocuronium to evaluate the ED95 in patients administrated according to lean body mass,then compara the clinical efficacy and individual differences of rocuronium administered according to body weight and lean body mass.There will be a reference for study and application in clinical.Part one The dose-effect relationship of rocuronium administered according to lean body massObjective To establish the dose-response curve of rocuronium and to evaluate the ED50,ED75,ED9o,ED95 of rocuronium in patients administrated according to lean body mass.Methods Eighty ASAⅠorⅡpatients undergoing elective surgery under general anesthesia were enrolled in this study.Patients with neuromuscular disease were excluded and no patient was taking any drμg that might influence the effect of muscle relaxant.General anesthesia was induced with propofol 2 mg/kg and fentanyl 3μg/kg.The patients were randomized to receive rocuronium 0.15mg/kg (group Rl),0.2mg/kg (group R2),0.3 mg/kg (group R3),0.4mg/kg (group R4).Neuromuscular function was monitored with the transducer of force-displacement of HXD-Ⅰmultifunction monitor. The temperature of the thenar eminence surface was maintained at 32～34℃and body temperature at 36.0～36.9℃and room temperature at 22～25℃during the induction of anesthesia.The responses of adductor pollicis muscle were defined in terms of the percentages of maximal suppression in T1 of train-of-four(TOF) stimulation of ulnar nerve.According to log-probit transformation of the data of dose and response,the dose-response curve of rocuronium was established throμgh linear regression.The onset time of rocuronium was also observed.Results No significant difference in sex,age,body weight,height,body mass index and lean body mass among four groups (P>0.05).The percentages of maximal suppression of T1 rised when increasing the dose of rocuronium (P< 0.05). There was no a significant change in onset time among four groups(P>0.05),the onset time of 0.2mg/kg,0.3mg/kg and 0.4mg/kg rocuronium was not significantly shorter than that of 0.15mg/kg rocuronium.The ED50,ED75,ED90,ED95 of rocuronium were 0.19,0.27,0.36 and 0.43 mg/kg respectively. Conclusion The ED50,ED75,ED90,ED95 of rocuronium are 0.19,0.27,0.36 and 0.43 mg/kg respectively. The onset time of ROC was not significantly shorter while increasing dosage when the drμg is less than ED95.Part two Pharmacodynamics comparison of rocuronium administrated according to lean body mass and weightObjective To compara the clinical efficacy and individual differences of ROC administered according to lean body mass and body weight.Methods Eighty ASAⅠorⅡpatients without any neuromuscular disease undergoing elective surgery under general anesthesia were randomly divided into two groups(group W and group L) according to the different administration method of calculating the amount,40 patients in each group. The responses of adductor pollicis to train of four(TOF) stimulation of ulnar nerve were monitored by HXD-Ⅰmultifunction.Anesthesia was induced with propofol 2mg/kg, fentanyl 3μg/kg, ROC0.6mg/kg (group W) or 0.86mg/kg (group L),and maintained with propofol given by TCI(target-controlled infusion) with the effect-site concentration set at 3～4μg/ml and increments fentanyl 1μg/kg as required. Before and after anesthesia induction, record systolic blood pressure(SBP), mean pressure (MAP) and diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), bispectral index (BIS) and temperature (T); record intubating conditions, onset time, T1 maximum inhibition, the clinical role of time, recovery index, pharmacological effects of time. SPSS 13.0 were used to analyze the data. All data are reported as the mean±standard deviation.Comparisons between groups were made by student t-test. Differences were considered significant at P<0.05.Results No significant differences were found in general, hemodynamic changes, BIS, T, endotracheal intubation conditions and muscle relaxant effects except the amount of medicine between the two groups. Group W was significantly less than the group L in the amount of medicine.There were no significant differences in the variability of T1 maximal inhibition, the onset time, recovery index, dosage,between the two groups.Compare with the group W, the differences of clinical role of time and the pharmacological effects of time between different individuals in group L were smaller.Conclusion It can reduce the individual differences of muscle relaxant effect to apply ROC according to lean body mass. and decrease the dose of muscle relaxants.Part three The detection of the ED95 of rocuronium in male and female patients administrated according to lean body massObjective Separately to establish the dose-response curve of rocuronium and to evaluate the ED5o,ED75,ED9o,ED95 of rocuronium in male and female patients administrated according to lean body mass.Methods Eighty ASAⅠorⅡpatients, male forty female forty undergoing elective surgery under general anesthesia were enrolled in this study.Patients with neuromuscular disease were excluded and no patient was taking any drμg that might influence the effect of muscle relaxant.General anesthesia was induced with propofol 2 mg/kg and fentanyl 3μg/kg.The patients were randomized to receive rocuronium 0.15mg/kg (group R1),0.2mg/kg (group R2),0.3 mg/kg (group R3),0.4mg/kg (group R4).Neuromuscular function was monitored with the transducer of force-displacement of HXD-Ⅰmultifunction monitor. The temperature of the thenar eminence surface was maintained at 32～34℃and body temperature at 36.0-36.9℃and room temperature at 22～25℃during the induction of anesthesia.The responses of adductor pollicis muscle were defined in terms of the percentages of maximal suppression in T1 of train-of-four(TOF) stimulation of ulnar nerve.According to log-probit transformation of the data of dose and response,the dose-response curve of rocuronium was established throμgh linear regression.The onset time of rocuronium was also observed.Results No significant difference in age,body weight,height,body mass index and lean body mass among in four male and female's patient groups (P>0.05).The percentages of maximal suppression of T1 rised when increasing the dose of rocuronium (P< 0.05). There was not a significant change in onset time among four male and female's patient groups (P>0.05),the onset time of 0.2mg/kg,0.3mg/kg and 0.4mg/kg rocuronium was not significantly shorter than that of 0.15mg/kg rocuronium.The male's ED50,ED75,ED90,ED95 of rocuronium were 0.18,0.27,0.38 and 0.46 mg/kg respectively. The female's ED50,ED75,ED90,ED95 of rocuronium were 0.20,0.26,0.35 and 0.40 mg/kg respectively.Conclusion The male's ED50,ED75,ED90,ED95 of rocuronium are 0.18,0.27,0.38 and 0.46 mg/kg respectively. The onset time of ROC shortens while increasing dosage. The female's ED50,ED75,ED90,ED95 of rocuronium are 0.20,0.26,0.35 and 0.40 mg/kg respectively. The onset time of ROC was not significantly shorter while increasing dosage when the drμg is less than ED95.Part four Pharmacodynamics comparison of rocuronium in male patients administrated according to lean body mass and weightObjective To compara the clinical efficacy and individual differences of ROC administered according to body weight and lean body mass in male patients.Methods Forty ASAⅠorⅡpatients, without any neuromuscular disease undergoing elective surgery under general anesthesia were randomly divided into two groups(group MW,group ML) according to the different administration method of calculating the amount,20 patients in each group. The responses of adductor pollicis to train of four(TOF) stimulation of ulnar nerve were monitored by HXD-Ⅰmultifunction.Anesthesia was induced with propofol 2mg/kg, fentanyl 3μg/kg, ROC 0.6mg/kg (group MW),0.92mg/kg (group ML)and maintained with propofol given by TCI(target-controlled infusion) with the effect-site concentration set at 3～4μg/ml and increments fentanyl 1μg/kg as required. Before and after anesthesia induction, record systolic blood pressure(SBP), mean pressure (MAP) and diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), bispectral index (BIS) and temperature (T); record intubating conditions, onset time, T1 maximum inhibition, the clinical role of time, recovery index, pharmacological effects of time. SPSS 13.0 were used to analyze the data. All data are reported as the mean±standard deviation.Comparisons between groups were made by student t-test. Differences were considered significant at P<0.05. Results No significant differences were found in hemodynamic changes, BIS, T, endotracheal intubation conditions and muscle relaxant effects in the male patient groups. There were no significant differences in the variability of T1 maximal inhibition, the onset time and recovery index among the four groups.In the male patients' group, group MW was less than the group ML in the amount of medicine. Compare with the group MW, the differences of clinical role of time and the pharmacological effects of time among different individuals in group ML were smaller.Conclusion It can reduce the individual differences of muscle relaxant effect to apply ROC according to lean body mass in male patients' groups. In the male patients' group, the dose of muscle relaxants decrease according to lean body mass.Part five Pharmacodynamics comparison of rocuronium in female patients administrated according to lean body mass and weightObjective To compara the clinical efficacy and individual differences of ROC administered according to body weight and lean body mass in female patients.Methods As same as Part fourResults No significant differences were found in hemodynamic changes, BIS, T, endotracheal intubation conditions and muscle relaxant effects in female's patient groups. There were no significant differences in the variability of T1 maximal inhibition, the onset time and recovery index among groups In the female patients' group, There were no significant differences in the amount of medicine. Compare with the group FW, the differences of clinical role of time and the pharmacological effects of time among different individuals in group FL were smaller.Conclusion It can reduce the individual differences of muscle relaxant effect to apply ROC according to lean body mass in the female patients' groups. In the female patients' group, There were no significant differences in the amount of medicine.