Clinical Research Of The Priming Technique's Effects On The Onset Time Of Cisatracurium

General anesthesia has four elements, including calmative, analgesia, muscle relaxation and reflex inhibition.The ideal muscle relaxants should be non-depolarization, has strong effects, fast inducement, quickly recovering, no accumulation, without histamine releasing, and little influence to the cardiovascular system.The induction phase of general anesthesia is a danger phase, during which the protection reflex of the respiratory tract is suppressed due to the using of anesthesia drugs, so patient can develop complications, such as respiratory depression, hypoxia, countercurrent mistake inhalation, etc. The risks is even higher for the patients of emergency trauma, waiting for delivery, with full stomach, digestion tract obstruction. When the satisfied tracheal intubation has been achieved, the induction time should be made as short as possible, and then the tracheal can be controlled safely as soon as possible. The inducing time depends on the effects speed and the administering way of the muscle relaxants, so choosing the proper muscle relaxants and the way of using it is critical in promoting the safety of anesthesia.As a new type of non-depolarization muscle relaxants of intermediate time-effect, cisatracurium is a cis optical isomerism of atracurium, the metabolic product of which has no muscle relaxing effects. It exerts the muscle relaxing effect by competing with acetylcholine for binding its receptors. It has advantages of rapid onset, fast recovery, no accumulation effect, no histamine releasing, little influence on the cardiovascular system, and its metabolism doesn't depend on the function of liver and kidney. Also, the cisatracurium has little difference in pharmacokinetics among individuals; only a slight changes in the onset time, and has no influence on the recovering phase of muscle relax. So cisatracurium was widely used in clinical practice recent years. It can be used on old patients, children (2 to 12 years old), patients with impaired liver and kidney function, severe cardiovascular disease, and in ICU. It's an ideal muscle relaxants, and has an excellent application prospect. The ED95 value of cis-atracurium is 0.05mg/kg. The usual intravenous dose is 0.10mg/kg-0.15mg/kg (2ED95-3ED95) for intubation, with a long onset time, about 4 minutes. So, how to reduce the onset time is an urgent problem needed to resolve.Many researchers has made some useful explorations on the subject of reducing the onset time of muscle relaxants. The main techniques to accelerate the effect speed of muscle relaxants include large dose technique, priming technique, time limiting technique, combined drug using technique, and explore new drugs, etc. Until now, initial successes have been achieved on shortening the onset time of nondepolarization drugs by priming technique. The consensus is that, priming technique is to give a small dose (priming dose) first, usually 10% of the dose for intubation (2ED95-3ED95), i.e.20%-30% ED95, when performing tracheal intubation using non-depolarization muscle relaxants, then to give the remained dose (usually 3ED95 in clinic practice) after a certain time interval. Although the new type nondepolarization muscle relaxants, cisatracurium, has many advantages, such as high effect-dose rate (3.2-3.5 times of atracurium), little influence on cardiovascular function, its onset time is long than the atracurium of equal effect-dose rate, which is 0.5-2 minutes longer at the dose of 2ED95 for intubation. Recently, the researches on the subject of cisatracurium's onset time affected by priming technique, combining the qualitative study on healthy volunteers and quantitative study in clinical trials, is rare. Although some researchers have concluded that priming technique can accelerate the onset speed of cisatracurium, these conclusions are not all perfect, restricted by design and conditions of the clinic trial. Our research contains two sections:to validate whether the priming technique can reduce the onset time of cisatracurium, using the isolated forearm test, and to measure the effects of 3 kinds of priming doses of cisatracurium and 4 kinds of priming time interval on the onset time and intubation condition. Through this research, we hope to find the best priming technique for clinic application, gain further evidences to direct the clinic practice of accelerating the onset time of cisatracurium.PartⅠthe tests of health volunteersObjective:to assess the effects of priming intravenous injection of cisatracurium, using isolated forearm mode.Methods:the tests were performed on the forearm of 10 adult health volunteers. Tourniquets were applied on both of the volunteers' forearm, and 20 gage indwelling needles were fixed to the both hand's dorsal veins. The nerve-muscle excitation transmission function was monitored using the TOF-Guard accelerograph. Exterior electrodes were placed at the ulnar nerve area of the wrist, acceleration transducers were affixed to the anterior aspects of the thumb, by which the contraction process of the thumb adductor could be monitored. The automatic current is 60 mA when the machine is starting. When the T1 is stable at 100% by adjusting the tranducer gain, the results were monitored using the train-of-four stimuli, and all parameters were recorded continually. The blood circulation of both forearms were isolated from the system circulation, by blocking the blood stream in and out of the forearm, as the tourniquets of both forearms were set at 40 kPa simultaneously.0.05mg/10ml cisatracurium was firstly injected through presetted cannula at the observation side.4 minutes later,0.5mg/20ml cisatracurium was simultaneously injected within 60 seconds through indwelling tube (the given cisatracurium dose was 80% or larger of the dose that could produce neuromuscular block, and the priming injection dose was 10% of this dose). Th, TOF of the observation side and the most inhibition of T1 time and 25% inhibition of Th time of both sides were recorded.Results:At the observation side, the time when the Th achieved 25% inhibition (Th1/Th0=25%) was 205.0±4.137 seconds, the time when T1 achieved the most inhibition (T4/T1=0) was 176.3±3.401 seconds. At the contralateral side, the time when the Th achieved 25% inhibition (Th1/Th0=25%) was 253.4±3.806 seconds. the time when T4/T1=0 was 221.4±3.978 seconds. There is a statistical difference between two groups. Th1/Th0, t=-27.923, P=0.000; T4/T1, t=-26.489, P=0.000. This implied that the priming technique can accelerate the onset speed of cisatracurium.Conclusions:priming injection of cisatracurium can significantly shorten its onset time.PartⅡthe tests of patientsObjective:To observe the best priming dose and time interval for cisatracurium injection.Methods:192 Patients of stage ASAⅠwere enrolled in a randomized double-blinded study and divided into four groups. GroupⅠwas the contrast group, in which all patients were administered with 15ml normal saline. GroupⅠwas further divided into 4 subgroups from I1 to I4, and the remained dose,0.15mg/kg of cisatracurium, were administered to the patients in each subgroup, at a time interval of 3,4,5, and 6minutes after the priming injection respectively. GroupⅡwas further divided into 4 subgroups fromⅡ1 toⅡ4, all of which the cisatracurium priming dose was 0.005mg/kg, and the remained dose,0.145mg/kg were administered at a time interval of 3,4,5, and 6 minutes respectively. Similarly, the cisatracurium priming dose of groupⅢwas O.Olmg/kg, and the remained dose,0.14mg/kg were administered at a time interval of 3,4,5, and 6 minutes for its 4 subgroups respectively. The cisatracurium priming dose of groupⅣwas 0.015mg/kg, and the remained dose,0.135mg/kg were administered at a time interval of 3,4,5, and 6 minutes for its 4 subgroups respectively. The total amount of cisatracurium dose was 0.15mg/kg (3/ED95) for each group. The end stage TOFR values of priming period of each group were recorded by the muscle relaxation monitor, as well as the ranks of intubation conditions, and the onset times of muscle relaxation effect.Results:1.The differences of age, body mass index, and nasopharyngeal temperature between groups were not statistical significant (P>0.05).2.The difference of end stage TOFR values of priming period between groups was statistical significant (F=420.979, P<0.001). Through multiple comparison, the difference between groupⅠ,Ⅱ, andⅢwas not statistical significant (P>0.05), the difference between group IV and the other 3 groups was statistical significant (P<0.01).In groupⅢ, F=22.693, P<0.001 between each time interval, via multiple comparison, the onset time differences between the time intervals of 3 and 4minutes were not statistical significant (P>0.05), but the differences between time intervals of 3 and 4minutes and time intervals of 5 and 6 minutes were statistical significant (P<0.05). In group IV, F=22.932, P<0.001 between each time interval, the differences between time interval of 3 minutes and 4,5,6 minutes were statistical significant (P<0.005), but the differences between group 3,4, and 5 were not statistical significant (P>0.05). Meanwhile, the differences between 4 groups were statistical significant (F=103.6999, P<0.001). Since the TOFR value of group 4 apparently changed, which implied that a certain muscle relaxation effects had been produced. From the angle of safe use in clinic, the onset time between groupⅠ,Ⅱ, andⅢwas compared, the subgroupⅢ1 can be considered as the best, according to the comparison between time intervals and the average.3.In all the groups, the intubation conditions were good and excellent, and no complications happened during the induction phase, such as respiratory depression, nausea and vomiting, countercurrent mistake inhalation, etc.Conclusions:Sub groupⅢ1, in which the priming dose was 0.01mg/kg, and the priming time interval was 3 minutes, ought to be a better choice.