Pharmacodynamics Comparative Of Cis-atracurium According To Real Body Weight And Fat-free Mass

The dose of neuromuscular blocking agents is mainly calculated on actual body weight and the ED95, but large differences were found in the actual effect between different individual, especially between male and female, thin and obese patients, adults and children. The incidence of postoperative residual block is higher in elderly and obese patients when neuromuscular blocking agents is administered at a dose calculated according to actual body weight. Comparing with normal patients, the onset time of the obese patients is shorter and the effect of muscle relaxant is stronger when neuromuscular blocking agents is administrated according to real body weight. The reason may be over does. Some scholars hypothesized that neuromuscular blocking agents should be administered according to standard body real body weight. Usually the pharmacological effects of the drug effectiveness depends on the drug in a target cell concentration and drug effect is proportional to its plasma concentration. the lean body mass is more closely related to blood volume.Many formulas measure lean body mass.Janmahasatian equations for estimating LBW are more accurate in estimating LBW for obesity patients. The aim of part one of the present study was to compare the individual differences and clinical efficacy of cis-atracurium intermittent bolus injected according to fat-free mass and real body weight; The aim of the part two of the present study was To compare the individual differences and clinical efficacy of cis-atracurium continuous injected according to fat-free mass and real body weight.Part one Effect of body mass index on neuromuscular blockage induced by cisatracuriumObjective To observe the effect of body mass index on neuromuscular blockage induced by cisatracurium.Methods Forty ASA Ⅰ～Ⅱ patients undergoing elective surgery under total intravenous anesthesia were enrolled in this study. All patients were divided into4groups: group Ⅰ (a low BMI) with BMI<18.5kg/m2; group Ⅱ (normal BMI) with BMI18.5～24.9kg/m2; group Ⅲ(high BMI) with BMI25～29.9kg/m2;group IV(obesity) with BMI≥30.0kg/m2. Four group received cisatracurium0.15mg/kg according to real body weight. The responses of adductor pollicis to train of four(TOF) stimulation of ulnar nerve were monitored by TOF-Watch SX Multifunction monitor. General anaesthesia was induced and maintained with target-controlled infusion. Intubation was attempted when Ti reached maximal inhibition (T1minimize repeated more than3times). The onset time (time from end of bolus injection to100%twitch depression), intubation conditions, clinical duration (time from the end of bolus injection to recovery of twitch tension to25%of control), pharmacological duration (time from the end of bolus injection to recovery of twitch tension to90%of control) and recovery index (the time lapse from25%to75%of recovery of T1) were recorded. The relationship between duration of action of cisatracurium and BMI was analyzed using linear regression analysis. The onset time、recovery index、clinical duration and pharmacological duration in these four groups was compared using one-way analysis of variance (ANOVA) and Tukey’s post-hoc test. A P value<0.05 was considered statistically significant.Results A significant correlation between clinical duration and BMI (R2=0.628,n=40,P<0.01) was found by linear regression analysis. A significant correlation was also found between pharmacological duration and BMI(R2=0.601, n=40,P<0.01). A significant difference was found between groups by one-way ANOVA;clinical duration and pharmacological duration was found to be significantly longer in the obesity group compared with the low BMI、normal BMI and high BMI groups by Tukey’s post-hoc analysis[(57.9±9.9)min,(38.2±5.3)min,(42.3±5.6)min,(47.6±7.2)min];[(77.1±11.68)min,(51.46±6.07)min,(58.41±7.54)min,(66.9±9.87) min; P<0.05]. A difference in recovery index and the onset time was not found between the four groups(P<0.05).Conclusion In adult patients, the clinical duration and pharmacological duration of cisatracurium increases with BMI when the drug is administered according to actual body weight.Part two Pharmacodynamics comparative of cis-atracurium intermittent bolus injected according to real body weight and fat-free mass during long time abdominal surgeryObjective To compare the individual differences and clinical efficacy of cis-atracurium intermittent bolus injected according to fat-free mass and real body weight during long time abdominal surgery.Methods Forty patients (ASAI-II) who had no neuromuscular disease and underwent selective abdominal surgery under general anesthesia were randomly divided into group FFM (n=20) and group RBW(n=20) according to the different administration method. The responses of adductor pollicis to train-of-four (TOF) stimulation were monitored. Anesthesia was induced with propofol and remifentanyl given by target-controlled infusion, cis-atracurium129.6μg/kg (group FFM) or100μg/kg (group RBW), and maintained with propofol and remifentanyl given by target-controlled infusion. Intubation was attempted when T1reached maximal inhibition. When the TOF stimulus T1recovery to5%, both group additional cis-atracurium64.8μg/kg (group FFM) or50μg/kg (group RBW). The onset time, nonresponsive time, clinical duration, recovery index, pharmacological duration, cis-atracurium consumption, interval and frequency were recorded. Measurement data were expressed as mean±standard deviation (x±s), t-test or ANOVA was applied in comparison between groups. P values below0.05were considered statistically significant.Results1, General status in both groups:No significant differences were found in age, body height and weight, operation duration between the two groups (P>0.05); In the40patients, no clinical manifestations of histamine release suchas tachycardia, flushing and bronchospasm occurred.2, The response of neuromuscular blockade in both groups:There were no significant differences in interval, frequency, onset time, clinical duration, nonresponsive time, recovery index, pharmacological duration between the two groups (P>0.05).3, The consumption of cisatracurium:There were significant differences in the cisatracurium consumption between two groups (P<0.05);4, The CV of the response and dosage of Cisa:Compare with the group RBW, the differences of pharmacological duration and nonresponsive time between different individuals in group FFM were smaller (P<0.05)Conclusion It can reduce the individual differences of muscle relaxant effect to apply cis-atracurium and cis-atracurium consumption according to fat-free mass. Part three Clinical application of cis-atracurium continued injected according to fat-free mass during long time abdominal surgeryObjective To compare the individual differences and clinical efficacy of cis-atracurium continuous injected according to fat-free mass and real body weight during long time abdominal surgery.Methods Forty patients (ASAI-II) who had no neuromuscular disease and underwent selective abdominal surgery under general anesthesia were randomly divided into group FFM (n=20) and group RBW(n=20) according to the different administration method. The responses of adductor pollicis to train-of-four (TOF) stimulation were monitored. Anesthesia was induced with propofol and remifentanyl given by target-controlled infusion, cis-atracurium129.6μg/kg (group FFM) or100μg/kg (group RBW), and maintained with propofol and remifentanyl given by target-controlled infusion. Intubation was attempted when T1reached maximal inhibition. When the TOF stimulus T1recovery to3, both group infuse rate was set at129.6μg· kg-1·h-1(group FFM) or100μg·kg-1·h"1(group RBW).The onset time, PTC, recovery index, T25, cis-atracurium consumption were recorded. Measurement data were expressed as mean±standard deviation (x±s), t-test or ANOVA was applied in comparison between groups. P values below0.05were considered statistically significant.Results1, General status in both groups:No significant differences were found in age, body height and weight, operation duration between the two groups (P>0.05). In the40patients, no clinical manifestations of histamine release suchas tachycardia, flushing and bronchospasm occurred.2, The response of neuromuscular blockade in both groups:There were no significant differences in onset time, PTC, T25, recovery index between the two groups (P>0.05). 3, The consumption of cisatracurium:cisatracurium consumption was less in group FFM than in the group RBW (8.8±2.8mg versus11.9±4.2mg)(P<0.05).4, The CV of the response:The differences of T25was less in group FFM than in the group RBW(0.18versus0.30)(P<0.05).Conclusion It can reduce the individual differences of muscle relaxant effect to apply cis-atracurium and cis-atracurium consumption according to fat-free mass.