Research On Clinical Pharmacodynamics Of Rocuronium In Different Age Of Children

Objectives Accumulative administration was used to determining thecurves of efficacy-dose response of rocuronium in children ranged indifferent ages, such as, neonate, infant, young children and children, andcalculating values of half effective dose (ED₅₀), 90ï¼…(ED₉₀) and 95ï¼…(EDge)effect-dose. To observe the on-set time, acting time after the rocuroniumgiven by 2 times of ED₉₅ and recovery index, and, changes of the circulatoryparameters after the administration, among different groups, offering thetheoretical gists for clinical medications.Methods 160 pediatric patients undergoing elective surgical proceduresunder total intravenous anesthesia (TIVA), ASA physical statusâ… -â…¡, wereincluded in the study, and randomly divided into four groups accordingto ages: neonate(0-28days)group, infant(1 month＜age≤12 months)group,young children(1 year＜age≤3 years)group and children(3 year＜age≤10years)group, 40 in each. The study was separated to two different partsby the purpose. (1) determination for effect-dose relationship ofrocuronium and antagonism of its muscle relaxation: establishing, ofthe curve of effect-dose relationship using four times cumulativeadministrative techniques at first, then, calculating the halfeffect-dose(ED₅₀), 90ï¼…and 95ï¼…effect-dose (ED₉₀&ED₉₅) from 20 patientsselected out from each group. After that, eligible dose of rocuronium wasadded to the patients whose train-of-four(TOF) response to stimulationswere not zeroed, until the response showed zero. Neostigmine, 0.03mg/kg,was injected intravenously as TOF response gradually recovered to 15ï¼…ofcontrol value of the first muscular trill(T1). Observing and recordingthe periods of T1 to 25ï¼…, 75ï¼…and TR=0.7 after administration. (2)observations of time-effect of muscle relaxation after rocuroniuminjected: the rest 20 cases in each group were given reciprocal 2 ED₉₅ doseof rocuronium respectively to observe and record both effective andrecovery periods of muscle relaxation after administration and changes in patients' heart rate(HR) and mean arterial blood pressure(MAP) pre-and post- injection.Results The dose-response formulae in each group was as follows:neonate, Probit=-11.21+5.68X; infant: Probit=-11.49+5.68X; youngchildren: Probit=-12.28+5.68X and children: Probit=-13,31+5.68X. Theresult of Pearson Goodness-of-Fit test for all groups wasperfect(x²=37.83, P=1.00). Result of Parallelism test indicated thatregress lines among groups were parallel(x²=0.00, P=1.00). ED₅₀, ED₉₀,and ED₉₅ of rocuronium, in neonate, 94, 158 and 183μg/kg; ininfant, 105, 178 and 206μg/kg; in young children, 145, 244 and 282μg/kgand in children, 220, 371 and 429μg/kg, respectivelly, there was anincremental tendency in dose given of rocuronium as age increase. The moreolder age, the more rocuronium required. There was no statisticalsignificances in time-effects of muscle relaxition among infant, youngchildren and children's groups after 2ED₉₅ of rocuronium given. (theaverage value of p is more than 0.05, p＞0.05) The on-set time,clinically acting periods, acting periods in the body and the recoveryindex were remarkably higher than that of other groups except for the edgevalue (the average value of p is less than 0.01, p＜0.01) in neonate group.There was no statistical significances in HR and MAP Pre-and post-10minutes intravenous administration of rocuronium among groups (theaverage value of p is more than 0.05, p＞0.05) There is remarkablyantagonistic effect for neostigmine on muscle relaxation caused byrocuronium in all groups, which can accelerate the recovery period ofmuscle relaxation nearly 50ï¼…, but the recovery period of muscle relaxationin neonatal group is still longer than that of in other groups(the averagevalue of p is less than 0.01, p＜0.01).Conclusions The sensitivity among Children in different ages such asneonate, infant, young children and children to rocuronium varied fromwide ranges. ED₅₀, ED₉₀, and ED₉₅ of rocuronium were neonate＜infant＜young children＜children respectivelly, there was an incremental tendency indose given of rocuronium as age increase. The influence to the relationshipof effect-dose between children's age and dose of rocuronium given shouldbe reconstructed clinically. The best drug effect can be achieved by giventhe most minimal effective dosage by ED₉₅ among different ages so as todecrease untoward reactions. A similar effects of muscle relaxation canbe seen after 2ED₉₅ of rocuronium injected among infantile, youngchildren's and children's groups. There is still some differences withother groups found in neonatal group at iso-effect dosage, so, monitoringof muscle relaxation effect should be taken as rocuronium is given toneonates during the operations. There is no remarkable effects on both HRand MAP among children ranged from different ages after the administrationof rocuronium. Neostigmine has similar antagonistic effects of musclerelaxation caused by rocuronium among children ranged from different ages,but the recovery period is relatively prolonged in the neonates than thatis found in other groups after neostigmine is administrated...