Effect Of Dexmedetomidine On The EC₅₀ Of Propofol TCI For Loss Of Consciousness And The Effect On The NT Index During Induction

Background and ObjectivePropofol is a rapid onset of effect of intravenous anesthetic and a short time after stopping wake up quickly and completely, no accumulation after continuous infusion, etc. are now widely used in the induction and maintenance of general anesthesia, spinal anesthesia and nerve block patients, ICU patients. Because of its linear dose-effect relationship, T1/2keo short, short half-life of the characteristics of real-time infusion to control, and rapid onset, wake up fast, used for TCI technology. As TCI continues to mature, it is easy to use and make hemodynamic stability. Using TCI in induction of general anesthesia can give stable vital signs. Meanwhile the stress response significantly reduced resulted from comparing intubation with single repeated intravenous injections.Dexmedetomidine given as an α2-adrenergic receptor agonists on behalf of the new drug, not only has sedative, analgesic characteristic and of anti-anxiety, but also can reduce the surgical stress response and so on.Recently it has been used gradually more and more by anesthesiologists application during the perioperative period, non-surgical procedures and mechanical ventilation and other fields. It is also used to aid local anesthesia, local anesthesia drugs to reduce the amount of anesthesia to improve quality and reduce adverse reactions and so on. Dexmedetomidine given as a preoperative medication, route of administration may be by intravenous injection or intramuscular injection,15min minutes of onset, is similar to the natural characteristics of calm sleep, can be awakened and quiet cooperation. A large number of clinical studies have shown that during general anesthesia combined with dexmedetomidine will be able to effectively reduce intraoperative sedative and hypnotic use of opioid dose, extubation can inhibit the stress response, stable hemodynamics, and can reduce the postoperative incidence of chills and delirium, the patient quiet, and call to be, and have minimal impact on breathing. Present studies have shown that dexmedetomidine will be able to reduce sevoflurane MAC values. However, the influence of TCI of propofol induction of anesthesia has not been reported.The aim of this study is to measure piperidine compound dexmedetomidine with propofol TCI EC50for loss of consciousness and Investigate the influence of dexmedetomidine on the EC50of TCI of propofol and the anesthesia depth of propofol-fentanyl and hemodynamic effects, provide a theoretical basis for clinical anesthesia on rational use of drugs.Methods60patients undergoing general anesthesia, ASA Ⅰ-Ⅱ, aged18to60years old, were randomly divided into two groups of30cases each. The group D was with dexmedetomidine1μg/kg and the group P was the control. Group D patients were intravenous injection10minutes of dexmedetomidine and then were undergoing propofol TCI20min later. Group P patients were intravenous injection10ml of saline in10minutes and then were undergoing propofol TCI. We evaluated the effects of dexmedetomidine and saline on SpO2, HR, SBP and DBP within10min in60patients. According to the sequential method TCI plasma target-controlled infusion turn on propofol TCI pump, the origin concentration was4.0μg/ml and the plasma target concentration was up to4.0μg/ml when if the patient does not meet the intervention conditions. When a patient lost the consciousness, the low level concentration of propofol was used in the next patient and the target concentration interval was 0.5μg/ml. Otherwise, the high level concentration of propofol was used in the next patient. If a patient’s consciousness does not disappear under the target concentration, then keep increasing the target concentration progressively until the patient lost their consciousness. Administration of intracenous fentanyl4.0μg/ml after patients lost their consciousness, intracenous rocuronium bromide0.6mg/kg2minutes later and then intubation1minute later. Eight time points of the HR, SDP, DBP, NT values were recorded at quiet in the room (TO), injection dexmedetomidine10min later (D) or injection saline lOmin later (T1), patients with loss of consciousness (T2), before intubation1min (T3), immediate intubation (T4), after intubation lmin (T5),3min (T6) and5min (T7). The criteria of loss consciousness:reflection and awareness of changes, patients with loss of eyelash reflex, no response to stimulation of language and no changed when shake shoulders could judge to be with loss of consciousness.Calculation of EC50:1gEC50=∑nLgX/∑n, standard error (Sm)=d∑p(1-p)/n-1, d is the number of difference doses of two adjacent,95%confidence interval of EC50was calculates by the formula lg-1(1gEC50±1.96Sm).SPSS13.0was used for statistical analysis. Using mean±standard deviation (x±s) in normal distribution of measurement data and using t test to compare a group with another group and using repeated measurements analysis of variance with comparison in a group, a=0.05as the test standard to count data compared.Results:1. The factors of the age, weight and height and so on were no statistical significance (P>0.05) between the two groups.2. The calculation of the propofol’s EC50and the95%confidence interval of the two groups.For group P the TCI patients’consciousness disappear EC50value of the propofol was3.053μg/ml and the95%confidence interval was2.048μg/ml～4.46961μg/ml. For group D the TCI patients’consciousness disappear EC50value of the propofol was1.493μg/ml and the95%confidence interval was0.0515μg/ml～0.1399μg/ml. The TCI patients’consciousness disappear EC50value of propofol in group D was lower than in group P. 3. Comparison of the anesthesia depth index at each time point between the two groups Comparison of NT values in two patients groups of each time point T1～T7, group D was significantly lower than the group P and showed the statistical difference in two groups (P<0.05).4.The comparison of the hemodynamic parameters between the two groups4.1Intra-group comparisonFor SBP and DBP, an one-way ANOVA in group P was investigated, the results shows that there was no statistical significance (P>0.05) between T1and T0.The value of T2, T3, Ts, T6and T7was lower than preoperative basic value To and there was significant difference (P<0.05). The SBP and DBP of T4was significantly increased compared with T2, T3, T5, T6and T7and there was significant difference (P<0.05. Further intra-group comparison of the values among different times using LSD between each two time point of T2, T3, T5, T6and T7were investigated and there were no significant difference (P>0.05). For SBP and DBP, an one-way ANOVA in group D was investigated, the results shows that the value of T from T1to T7was lower than preoperative basic value To and there was significant difference (P<0.05). Further intra-group comparison of the values among different times using LSD between the other each two time point were investigated and there were no statistical differences (P>0.05)For HR, an one-way ANOVA was investigated, as a result, in group P the values of all the HR time point but T1was lower than preoperative basic value To and there was statistical differences (P<0.05). Further intra-group comparison of the values among different times using LSD between the other each two time point were investigated and there were statistical differences. The value of T4was significantly increased compared with T2, T3, T5, T6and T7and there was statistical differences (P<0.05). In group P, the values of all the HR time point but T1was lower than preoperative basic value To and there was statistical differences (P<0.05). Further intra-group comparison of the values among different times using LSD between each two time point in T1to T7were investigated and there were no statistical differences (P>0.05) 4.2Inter-group comparisonThere were no statistical differences of SBP and DBP in time of T0、T2、T3、T5、 T6、T7(P>0.05) and was statistical differences of SBP in times of T1and T4(P<0.05) between group P and group D. There were statistical differences of HR in time of T1and T4(P>0.05). There were statistical differences of HR in time of T1, T2and T4(P <0.05) and were no statistical differences of HR in time of T0, T3, T5, T6and T7(P>0.05) between group P and group D.Conclusions1. Administration intravenous1μg/kg dexmedetomidine could be able to significantly reduce the EC50of propofol TCI patient’s loss of consciousness. It also could be able to reduce the stress response of propofol induced result from intubation and the hemodynamics is more stable.2. Administration of combining dexmedetomidine and propofol can significantly enhance the depth of anesthesia. Two drugs in the sedative and hypnotic aspect has a synergistic effect.3. Application of combined propofol TCI with dexmedetomidine should be reduced target-controlled plasma concentration of propofol TCI and strengthen the monitoring of vital signs.