Pharmacodynamics Comparison Of Cisatracurium Besylate Administrated According To Free-fat Mass And Real Body Weight

At present, the dose of muscle relaxant is mainly calculated by body Real 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 Real Body weight are administrated according to body Real 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 Real 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 Real 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 approximately5%of heart, and blood flows throμgh isceral is accounted for73%, muscle is22%. This indicates the lean body mass is more closely related to blood volume, Would the muscle relaxant administered according to free fat mass reduce the individual differences? Firstly, establish the dose-response curve of Cisatracurium Besylate to evaluate the ED95in patients administrated according to free fat mass, then compara the clinical efficacy and individual differences of Cisatracurium Besylate administered according to body Real Body weight and lean body mass. There will be a reference for study and application in clinical.Part one The dose-effect relationship of Cisatracurium Besylate administered according to free fat massObjective To establish the dose-response curve of Cisatracurium Besylate and to evaluate the ED50,ED75,ED90,ED95of Cisatracurium Besylate in patients administrated according to lean body mass.Methods Eighty ASA Ⅰ or Ⅱ patients 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 propofol2mg/kg and fentanyl3μg/kg.The patients were randomized to receive Cisatracurium Besylate40μg/kg (group Ⅰ),50μg/kg(group Ⅱ),60μg/kg(group Ⅲ),70μg/kg (group Ⅳ). The Lean body mass of formula: Man:FFM=9.27×103×TBW/(6.68×103+216×BMI); Woman:FFM=9.27×103×TBW/(8.78×103+244×BMI); FFM is free fat mass; TBW is total body Real Body weight; BMI is body mass indexAll patients were forbidden to drink4h and to fasting8h before surgery, were not given premedication, were conventional used Agilent V24multifunctional anesthesia monitor (Hewlett-Packard Company, USA) monitoring systolic blood pressure (SBP), mean pressure (MAP), and diastolic blood pressure (DBP) on right upper arm, monitoring heart rate (HR), ECG, pulse oximetry (SpO2),Body temperature (T), end-tidal carbon dioxide partial pressure (PETCO2) into the operating room. Neuromuscular function was monitored with the transducer of force-displacement of TOF-Watch SX multifunction monitor. The patients absorb oxygen by mask after5min, Intravenous propofol2～3mg/kg. Fentanyl2～3μg/kg. When patients lost consciousness, intravenous anesthetics, and not given neuromuscular blockers, carried twitch height scaling, made the first twitch response (T1) stable at100%, and maintained5min. intravenous random dose of4group of Cisatracurium Besylate. When T1reached maximal inhibition (T1minimize repeated more than3times), Recorded the onset time of maximal inhibition. Addition the right amount Cisatracurium Besylate, to Appropriate to deepen the anesthesia and completed the intubation. The temperature of the thenar eminence surface was maintained at32～34℃and body temperature at36.0～36.9℃and room temperature at22～25℃during the induction of anesthesia.The responses of adductor pollicis muscle were defined in terms of the percentages of maximal suppression in T1of train-of-four(TOF) stimulation of ulnar nerve. Using alcohol skimmed on the surface skin of the left wrist the ulnar nerve parts, reducing the surface resistance. Distal stimulating electrodes were placed outside of the wrist pisiform, between flexor carpi and the superficial flexor, the surface of the ulnar nerve pathways within1cm, associated electrodes placed2to3cm from the stimulating electrode. Skin temperature probe fixed at thenar surface. Placed the sensor in the palm of your hand, without applying any external force cases zero. The upper limb natural outreach, palm upward fixed on the backs panel, tied to the strap wrapped around suitable location, remain relatively fixed in the monitoring process. The stimulus for the four clusters of stimulation (TOF), Stimulation parameters were as follows:Current of40mA, the duration of0.2ms, frequency2Hz gain value automatically get each TOF stimulation interval15s. Patient without any moving in the monitoring process of muscle relaxants, shedder moved the cases to be removed. According to log-probit transformation of the data of dose and response, the dose-response curve of Cisatracurium Besylate was established through linear regression. The onset time of Cisatracurium Besylate was also observed.the the implanted peripheral venous catheter on the left elbow middle of vein puncture to establish the route of administration. Used for anesthesia induction and maintenance of medication.Recorded onset time and T1maximal inhibition values, collect Data.Results No significant difference in sex, age, body Real Body weight, height, body mass index and lean body mass among four groups (P>0.05).The percentages of maximal suppression of T1rised when increasing the dose of Cisatracurium Besylate (P<0.05). There was no a significant change in onset time among four groups(P>0.05),the onset time of45.4μg/kg、52.5μg/kg、59.9μg/kg、64.8μg/kg Cisatracurium Besylate was not significantly shorter than that of0.15mg/kg Cisatracurium Besylate. The ED50,ED75,ED90,ED95of Cisatracurium Besylate were45.4μg/kg、52.5μg/kg、59.9μg/kg、64.8μg/k grespectively.Conclusion The ED5o,ED75,ED9o,ED95of Cisatracurium Besylate are45.4μg/kg、52.5μg/kg、59.9μg/k、64.8μg/kg respectively. onset time of Cisatracurium Besylate was not significantly shorter while increasing dosage when the drμg is less than ED95.Part two Pharmacodynamics comparison of Cisatracurium Besylate administrated according to Free Fat mass and Real Body weightObjective To compara the clinical efficacy and individual differences of Cisatracurium Besylate administered according to free fat mass and body Real Body weight.Methods Eighty ASA I or II patients 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,20patients in each group. All patients were forbidden to drink4h and to fasting8h before surgery, were not given premedication, were conventional used Agilent V24multifunctional anesthesia monitor (Hewlett-Packard Company, USA) monitoring systolic blood pressure (SBP), mean pressure (MAP), and diastolic blood pressure (DBP) on right upper arm, monitoring heart rate (HR), ECG, pulse oximetry (SpO2), Body temperature (T), end-tidal carbon dioxide partial pressure (PETCO2) into the operating room.The responses of adductor pollicis to train of four(TOF) stimulation of ulnar nerve were monitored by TOF-Watch SX multifunction monitor. The responses of adductor pollicis muscle were defined in terms of the percentages of maximal suppression in T1of train-of-four(TOF) stimulation of ulnar nerve. Using alcohol skimmed on the surface skin of the left wrist the ulnar nerve parts, reducing the surface resistance. Distal stimulating electrodes were placed outside of the wrist pisiform, between flexor carpi and the superficial flexor, the surface of the ulnar nerve pathways within1cm, associated electrodes placed2to3cm from the stimulating electrode. Skin temperature probe fixed at thenar surface. Placed the sensor in the palm of your hand, without applying any external force cases zero. The upper limb natural outreach, palm upward fixed on the backs panel, tied to the strap wrapped around suitable location, remain relatively fixed in the monitoring process. The stimulus for the four clusters of stimulation (TOF), Stimulation parameters were as follows:Current of40mA, the duration of0.2ms, frequency2Hz gain value automatically get each TOF stimulation interval15s. Patient without any moving in the monitoring process of muscle relaxants, shedder moved the cases to be removed. Anesthesia was induced with propofol2mg/kg, fentanyl3μg/kg, Cisatracurium Besylate150μg/kg (group W) or195μg/kg (group L),and maintained with propofol given by TCI(target-controlled infusion) with the effect-site concentration set at3～4μg/ml and increments fentanyl1μg/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, recorded onset time (the end of administration to T1to a minimum value and repeated for3consecutive times unchanged) and Tl maximal inhibition values, the clinical effects of time(T1to recovery to25%from the end of administration),the recovery index(T1to recover from25%to75%), pharmacological effects of time(T1to recovery to90%from the end of administration), give Cisatracurium Besylate regulator T1stable as a base value of100%.SPSS13.0were 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 T1maximal 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 Cisatracurium Besylate according to free fat mass. and decrease the dose of muscle relaxants.