Detecting The ED₉₅ Values Of Cis-atracurium And Vecuronium And Evaluating Pharmacodynamic Of Cis-atracurium In Epileptics

There are more than 6 million epileptics in China, of which 25% patients are refractory epileptics. Epilepsy has been the second most common neurological disease.Epileptic surgery is an effective way for the treatment of refractory epilepsy. Epilepsy due to its pathophysiological changes and long-term use of antiepileptic drugs causes lower block effects of muscle relaxants.The sensitivity of neuromuscular blockade was decreased in epileptic surgery.This phenomenon was confirmed in non-depolarizing muscle relaxants such as pancuronium, vecuronium, rocuronium and so on. It is necessary to confirm whether there is a similar pharmacodynamic in cis-atracurium.The dose of muscle relaxant should be increased in induction and maintenance of anesthesia in order to meet the needs of surgical muscle relaxation. Without the appropriate guidance with the reported data, it could easily make application of intraoperative muscle relaxants deficiency and excess, resulting in lack of muscle relaxation in surgery and residual muscle relaxation in anesthesia recovery period and increasing the risk of epileptics. For epileptics, establishing the appropriate dose-response curve of muscle relaxants may make the application of muscle relaxants more reasonable. So it is necessary to establish a objective dose of non-depolarizingmuscle relaxants in order to apply them rationally in epileptic surgery.At present,the application of non-depolarizing muscle relaxants in epileptic surgery is less studied.The test of cisatracurium dose-response curve for epileptics is currently no reported.It can determine dose-response curves of cis-atracurium (CIS) and vecuronium (VEC) by taking a single dose.Determining the ED95 values and the clinical efficacy of CIS and VEC in epileptics can provide a reference in the clinical application of muscle relaxants.Part one Pharmacodynamics comparative of cis-atracurium between epileptics and non-epileptic patientsObjective To compare the clinical efficacy of CIS between epileptics and non-epileptic patients.Methods Forty ASA gradeⅠorⅡepileptics were enrolled in this study,of which 20 patients for epileptic surgery,20 patients for non-epileptic brain surgery divided into group NE and group E. The responses of adductor pollicis to train of four(TOF) stimulation of ulnar nerve were monitored by HXD-Ⅰmultifunction. Anesthesia was induced by TCI(target-controlled infusion) with propofol 4μg/ml, remifentanil 4ug/ml, CIS 0.15mg/kg,and maintained with propofol given by TCI with the effect-site concentration set at 3～4ug/ml and remifentanil given by TCI with the effect-site concentration set at 4～6ug/ml 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, the onset time between the two groups (P> 0.05). There were significant differences in the clinical role of time, recovery index,TOFr 70% recovery time, TOFr 90% recovery time between two groups(P< 0.05).Conclusion Application dose of CIS in epileptics should be increased.Part two The measurement of dose-response curve of cis-atracurium in epileptics Objective To determine the dose-response curve of cis-atracurium and to evaluate the ED95 of cis-atracurium in epileptics.Methods Forty ASA grade I or II epileptics were enrolled in this study.All patient were divided into four groups and were determined with the method of single dose injection under midazolam-fentanyl intravenous anesthesia.Each of four groups of patients received intravenous bolus of 20,30,40,50μg/kg of Cisatracurium respectively.The neuromuscular block was measured by neuromuscular transmission monitor, the responses were defined in terms of the percentages of maximum suppression in T1 of TOF of the adductor pollicis muscle. According to log-probit transformation of the data of dose and response, the dose-response curve of cis-atracurium was established through linear regression. The onset time of cis-atracurium was also observed.Results The ED50, ED75, ED9o and ED95 of cis-atracurium in epileptics were 36.3μg/kg,46.1μg/kg,57.4μg/kg,65.4μg/kg.No significant change in onset time among 4 groups.Conclusion The ED95 of cis-atracurium in epileptics was 65.4μg/kg, increasing of 30.8% than the ED95 50μg/kg of normal human.Part there Determining the ED95 value of vecuronium in epilepticsObjective To determine the ED95 value of vecuronium in epileptics.Methods Fifty ASA gradeⅠ～Ⅱepileptics were enrolled in this study.All patient were divided into five groups and were determined with the method of single dose injection under intravenous anesthesia.Each of five groups of patients received intravenous bolus of 20,30,40,50 or 60μg/kg of vecuronium respectively.The neuromuscular block was measured by neuromuscular transmission monitor, the responses were defined in terms of the percentages of maximum suppression in T1 of TOF of the adductor pollicis muscle. According to log-probit transformation of the data of dose and response, the dose-response curve of vecuronium was established through linear regression. The onset time of vecuronium was also observed.Results The ED95 value of vecuronium in epileptics was 57.2μg/kg.No significant change in onset time among five groups.Conclusion The ED95 value of vecuronium in epileptic patients is 57.2μg/kg.