The Clinical Pharmacodynamics Study Of Rocuronium In Infants Operation

Muscle relaxants are very important for anesthesia induction and maintaining. Even some results about the application of muscle relaxants in the adults have been conducted, but this kind of studies in infants'anesthesia is rare because of the incomplete development of infant organs and the different distribution and metabolism of muscle relaxants in the infants when comparing to the adults. Muscle relaxants can be divided into two groups:depolarizing muscle relaxants and non-depolarizing muscle relaxants. Succinylcholine, the most popular depolarizing muscle relaxants, can cause bradycardia, muscle fiber bundle contraction and even induce malignant hyperthermia, hyperkalemia and some other side effects. Unfortunately, almost all of the non-depolarizing muscle relaxants can induce slow onset, hemodynamic changes, histamine release and some other defects. But rocuronium, a new non-depolarizing muscle relaxants, shows many advantages when used in infants'anesthesia, such as rapid onset, rare histamine release, no autonomic festival block, little effect on hemodynamics and etc. At present, few researches about the application of rocuronium in infants' anesthesia have been reported, so it has a significant clinical meaning studying the pharmacodynamics of rocuronium in infants'anesthesia. ObjectiveIn this study, single dose technique was used to determine the curves of efficacy-dose response of rocuronium in Chinese infants, and then the paramaters including half effective dose(ED50),90% effective dose (ED90) and 95% effective dose (ED95) were calculated. The intubating conditions, muscle relaxant effect and side effects were also recorded when single ED95,1.5 ED95,2 ED95,3 ED95 rocuronium were used in infants. From the above parameters, the optical dosage of rocuronium which is suitable for used in quick tracheal intubation in the infants was determined.Methods80 infants, undergoing elective orthopaedic surgery under general anesthesia, were included in this trial. The following criterions were met:aged 1～12 months, ASA physical statusⅠ～Ⅱ, normal function of heart, lungs, liver and kidney, normal biochemistry parameters, no neuromuscular disorders and no second-hand smoke exposure. Antibiotics and so other drugs that can disturbance neuromuscular transmission function should not be used in the included infants. According to the aims of this study, the trail was divided into two parts:1.Determining the effect-dose relationship of rocuronium.40 of the 80 included infants were randomly divided into 4 groups (I group:160μg·kg-1,Ⅱgroup:180μg.kg-1,Ⅲgroup:200μg.kg-1 andⅣgroup:220μg.kg-1),10 infants per group. After the ordinal intravenous injection of penehychdine hydrochloride(0.25～0.3mg), midazolam(0.1mg.kg-1), sufentanil(0.6μg.kg-1) and propofol(2mg.kg-1), rocuronium was injected when eyelid reflection disappeared and muscles loose detector was corrected. After injection of rocuronium, minimum value of the first muscular trill(T1) was recorded after every stimulation and then the curve of effect-dose relationship was established in order to calculate ED5o,ED90 and ED95 of rocuronium.2.Observing and determining the muscle relaxation time-effect of rocuronium. Expect for the 40 infants included in step 1, the other 40 infants were divided into 4 groups (Ⅴgroup:ED95,Ⅵgroup:1.5 ED95,Ⅶgroup:2 ED95 andⅧgroup:3 ED95). After the ordinal intravenous injection of penehychdine hydrochloride(0.25-0.3mg), midazolam(0.1mg.kg-1), sufentanil(0.6μg.kg-1) and propofol(2mg.kg-1), rocuronium was injected. After the infants entered into operating room, blood pressure, pulse, pulse oximeter saturation and electrocardiogram were recorded conventionally, then mean artery pressure and heart rate were monitored before induction of general anesthesia, before and after rocuronium injection, immediate and 5 minutes later after intubation. During the operation, endtidal carbon dioxide gas tension and temperature were continuously recorded, and simultaneously lowest T1 value, the effect-acting period, recovery time, recovery index, intubation conditions and adverse reactions were recorded.Results1 No significant differences in gender, age, weight between each group(P> 0.05).2.The dose-response formulae of rocuronium in infants is:Probit=—25.112 +13.423X.3.ED50, ED90 and ED95 of rocuronium in infants respectively is:175,218 and 232μg.kg-1.4.Clinical pharmacodynamics:the effect-acting period of rocuronium in each group isⅤgroup:(107.40±8.03) s,Ⅵgroup:(95.40±7.78) s,Ⅶgroup: (85.70±9.98) s andⅧgroup:(63.70±6.38) s, significant differences occur between groups (P<0.05). Comparing withⅤgroup andⅥgroup, muscle twitching recovery time inⅦgroup,Ⅷgroup was obviously extended. Recovery index inⅦgroup andⅧgroup was also obviously extended thanⅤgroup andⅥgroup(P<0.05), the volue isⅦgroup:(15.50±2.01) min,Ⅷgroup:(21.50±2.55) min,Ⅴgroup:(9.00±1.95) min andⅥgroup:(10.10±2.13) min. There was no difference betweenⅤgroup andⅥgroup.5.In accordance to the Cooper rating criteria, the scores of tracheal intubation conditions inⅥ,ⅦandⅧgroups were between 7 and 9 points, no significant differences between each group. The scores of tracheal intubation conditions in V groop was poorer.Conclusion1. ED95 of infants rocuronium is 232 u g. kg-1, Age is an important factor for influencing the effect-dose relationship of rocuronium, and the optimum drug effect can be achieved when rocuronium is used clinically with the minimal effective dosage according to ED95 in infants, and at the same time, the postoperative residual muscle loose can also be reduced.2.0.35mg.kg-1 of rocuronium, also 1.5 ED95, can provide good tracheal intubation conditions and is suitable to short-time and tracheal intubation operation. Higher dosage can shorten the effect-acting period and prolong the recovery time.