| At present, the non-depolarizing muscular relaxants have been widespread applicated in tracheal intubation general anesthesia. In short-term(<lh) operations, non-depolarizing muscular relaxants usually be given a single dose by intravenous injection, which dose and pharmacodynamics has been studied clearly. For long-time procedures(>2h), muscular relaxants tend to be administrated by intermittent intravenous bolus to maintain muscle relaxant. Due to fluctuations in the plasma concentration levels and muscle tight, surgeons often complain. In the past it has been that muscle relaxants is not available for continuous intravenous infusion, but in recent years as the researchs in the delivery methods and pharmacodynamics of non-depolarizing muscular relaxants gradually mature, some scholars believe that continuous infusion is reasonable and feasible. There are suggested that keeping deep neuromuscular blockade(Post Tetanic Count, PTC=1-2) during laparoscopic surgeries can provide larger operative space, better visualization even under lower pneumoperitoneum pressure(<12mmHg). Therefore, accessing to tight spaces and immobilization are attainable. Thus, the complications due to pneumoperitoneum pressure, such as muscle image, would be reduced and the stay time in post anesthesia care unit (PACU) or intensive care unit (ICU) after surgeries would be shorten. However, the biggest concern of maintaining deep muscular blockade in long laparoscopic surgeries was whether postoperative residual neuromuscular blockade (RNMB) and related complications would be increased. Muscle weakness due to RNMB could lead to respiratory obstruction, asphyxia, hypoxemia, hypercapnia, aspiration pneumonia, atelectasis, and even death.Now is generally accepted that short-acting muscular relaxants was suitable for continuous infusion, medium-acting agents should be careful used for continuous infusion and long-acting agents should not be applied. However, using short-acting muscular relaxants to maintain deep blockade by continuous infusion in long time operations would bring out the high drugs consumption and high cost. Compared with the short-term muscular relaxants, using medium-acting agents could reduce the dosage and the cost. Currently, cisatracurium and rocuronium were commonly used in clinic, always be administrated by intermittent intravenous bolus for maintain moderate muscular blockade. The researches about continuous infusion medium-acting neuromuscular relaxants during laparoscopic procedures for depp neuromuscular blockade is less untill now. We would do comparative study on pharmacodynamics and feasibility of continuous infusion versus intermittent infusion cisatracurium during laparoscopic procedures for deep neuromuscular blockade in part one; and rocuronium would be used in part two. Aim at providing more drugs and routes of administration for selection in clinic.Part one Comparative study on pharmacodynamics and feasibility of continuous infusion versus intermittent infusion of cisatracurium during laparoscopic procedures for deep neuromuscular blockadeObjective To investigate continuous infusion and inermittent injection of cisatracurium for deep neuromuscular blockade during laparoscopic surgery, compare the feasibility and pharmacodynamics of this two ways.Methods Sixty ASA I or II patients,aged from 18 to 65,undergoing selective laparoscopic gastrointestinal surgery with general anesthesia were randomly divided into 2 groups:group A(n=30)received cisatracurium 0.15 mg/kg for intubation,and then continuous infusion of cisatracurium by micro pump of original rate 0.2 mg.kg-1.h-1 when PTC≥3; group B(n=30) was given cisatracurium 0.15 mg.kg"1 for intubation,and then intermittent infusion of cisatracurium of 0.05 mg.kg-1 when PTC ≥3. All the patients in group A or group B would be given propofol 2.5 ug/ml and remifentanl 4 ng/ml by target-controlled infusion (TCI) for induction. The propofol target plasma concentration (2.0-3.0μg/ml) and remifentanil effect-site concentration (4.0-6.0ng/ml) would be adjusted according to BIS, HR, SBP, DBP, MAP and the surgeons’ operating range, maintaining the BIS from 45 to 60 and stable hemodynamics. Using TOF-Watch SX Monitor to monitor the neuromuscular junction function. The train of four stimulation (TOF) would be used after a 50 Hz tetanic stimulation (TS) and CAL 2 calibration. When the value of T1 (the first train of four stimulations) be maintained at 100±10% after 3 min, the induction of muscular relaxants would be given. Then intubation done when T1 reach the maximum inhibition (T1=0). The TOF would be used during the whole operation and PTC would be proceeded every 6 min. The infusion rate in group A would be adjusted according to PTC in 30 min after pumping begin. All patients in these two groups would be keep deep neuromuscular blockade (PTC<2)during operation.40min expected before the end of surgery to stop using muscle relaxants, wait for the natural recovery.General conditions of patients (sex, age, height, weight), ASA classification, surgical region, MAP, HR, blood-gas analysis results, duration of neuromuscular blocking agent used (group A:from induction to the end of infusion; group B:from induction to the last infusion), cisatracurium consumption, times of adjusting infusion rate (group A) or relaxants addition(group B), the time from neuromuscular blockade induction to T1=0, PTC≥3, the time from relaxants withdrawal to T1 recover, T2 recover, the time of T1 recovered to 25%,75%,TOFr recovered to 0.7,0.9, PTC proceeding times and results, satisfaction of neuromuscular blockade (grade 0-10) of the surgeons at the begin/lh/2h/end of the operation, the TOFr when extubation, whether can perform sustained tongue depressor test when TOFr=0.9, the incidence rate of hyoxemia after extubation, pneumonia,atelectasis were recorded.Using SPSS 20.0 statistical software for analysis. Measurement data were expressed as mean±standard deviation (x±s), the normal line of test and homogeneity of variance test would be done. When the distribution is satisfied and homogeneity of variance between groups has no significant difference, two independent samples t-test would be used. And t-test Cochran & Cox approximate variances would be done when conditions are not satisfied. Count data between the two groups were compared using χ2 test. Ratings data using nonparametric rank sum test. Repeated measurements using repeated measures analysis of variance. P values below 0.05 were considered statistically significant.Results Compare to group B, the cisatracurium consumption in group A was significantly more (P<0.05), and the satisfaction of the surgeons were significantly higher at the start、1h、2h of the operation (P<0.05).The satisfaction of the surgeons respectively showing no significant differences between groups at the end of the operation. Recovery index (T1 from 25% to 75%), time of TOFr recovery to 0.7,0.9in group A is increased,but not respectively (P>0.05).Two patients in group A is hyoxemia after extubation while 1 in group B,the incidence rate was not significantly (P>0.05); 3 patients in group A was inability to perform sustained tongue depressor test while 4 in group B,the incidence rate was not significantly (P>0.05); all of the patients were not suffered pneumonia,atelectasis.Conclusion Continuous infusion cisatracurium during laparoscopic procedures for deep neuromuscular blockade is effective and safe. The cisatracurium consumption may be more and the satisfaction of the surgeons would be higher compare to intermittent infusion.Continuous infusion may effect on the time of muscle relaxant,but have on influence on the residual effect of muscle relaxant.Part two Comparative study on pharmacodynamics and feasibility of continuous infusion versus intermittent infusion of rocuronium during laparoscopic procedures for deep neuromuscular blockadeObjective To investigate continuous infusion and inermittent injection of rocuronium for deep neuromuscular blockade during laparoscopic surgery, compare the feasibility and pharmacodynamics of this two ways.Methods Eighty ASA I or II patients,aged from 18 to 65,undergoing selective laparoscopic gastrointestinal surgery with general anesthesia were randomly divided into 4 groups:group A1(n=20)received rocuronium 0.9 mg/kg for intubation,and then continuous infusion of rocuronium by micro pump of original rate 0.9 mg.kg-1.h-1 when PTC≥3; group A2(n=20) received rocuronium 0.9 mg/kg for intubation, then continuous infusion of rocuronium by micro pump of original rate 0.9 mg·kg-1.h-1 when PTC≥3, and intravenous injected neostigmine 0.04mg/kg+atropine 0.02mg/kg after surgery; group B1(n=20)was given rocuronium 0.9 mg.kg-1 for intubation,and then intermittent infusion of rocuronium 0.3 mg.kg-1 when PTC≥3; group B2(n=20) was given rocuronium 0.9 mg.kg-1 for intubation, then intermittent infusion of rocuronium 0.3 mg.kg-1 when PTC≥3, and intravenous injected neostigmine 0.04mg/kg+atropine 0.02mg/kg after surgery. All the patients would be given propofol 2.5 ug/ml and remifentanl 4 ng/ml by target-controlled infusion (TCI) for induction. The propofol target plasma concentration (2.0-3.0μg/ml) and remifentanil effect-site concentration (4.0-6.0ng/ml) would be adjusted according to BIS, HR, SBP, DBP, MAP and the surgeons’ operating range, maintaining the BIS from 45 to 60 and stable hemodynamics. Using TOF-Watch SX Monitor to monitor the neuromuscular junction function. The train of four stimulation (TOF) would be used after a 50 Hz tetanic stimulation (TS) and CAL 2 calibration. When the value of T1 (the first train of four stimulations) be maintained at 100±10% after 3 min, the induction of muscular relaxants would be given. Then intubation done when T1 reach the maximum inhibition (T1=0). The TOF would be used during the whole operation and PTC would be proceeded every 6 min. The infusion rate in group A1 and A2 would be adjusted according to PTC in 30 min after pumping begin. All patients in these two groups would be keep deep neuromuscular blockade (PTC≤2)during operation.40min expected before the end of surgery to stop using muscle relaxants. The patients in group A1 or B1 would wait for the natural recovery and those in group A2 or B2 would be given neostigmine 0.04mg/kg+atropine 0.02mg/kg when T2 recovered.General conditions of patients (sex, age, height, weight), ASA classification, surgical region, MAP, HR, blood-gas analysis results, duration of neuromuscular blocking agent used (group A:from induction to the end of infusion; group B:from induction to the last infusion), rocuronium consumption, times of adjusting infusion rate (group A) or relaxants addition(group B), the time from neuromuscular blockade induction to T1=0, PTC≥3, the time from relaxants withdrawal to T1 recover, T2 recover, the time of T1 recovered to 25%,75%,TOFr recovered to 0.7,0.9, PTC proceeding times and results, satisfaction of neuromuscular blockade (grade 0-10) of the surgeons at the begin/lh/2h/end of the operation, the TOFr when extubation, whether can perform sustained tongue depressor test when TOFr=0.9, the incidence rate of hyoxemia after extubation, pneumonia,atelectasis were recorded. The dosage of neostigmine in group A2 and B2 need to be recorded as well.Using SPSS 20.0 statistical software for analysis. Measurement data were expressed as mean ± standard deviation (x±s), the normal line of test and homogeneity of variance test would be done. When the distribution is satisfied and homogeneity of variance between groups has no significant difference, the one-way classification analysis (one-way classification ANOVA) would be done and the Kruskal case of missing variance-Wills H test would be done when conditions are not satisfied. Count data were compared with a plurality of sample rate comparisons R× C table data χ2 test. Ratings data using Kruskal-Wills H test. Repeated measurements using repeated measures analysis of variance. P values below 0.05 were considered statistically significant.Results Compare to group B1,the average rocuronium consumption in group A1 and group A2 were significantly more (P<0.05). Compare to group A1,group B1 or group B2, the times of T1 and T2 return are increased respectively (P<0.05) Compare to group A2 or group B2, the recovery index (T1 from 25% to 75%) of group A1 and group B1 is increased significantly(P<0.05). The time of TOFr recovery to 0.7,0.9in group B2 was longer than group A1, group A2 or group B1, respectively (P<0.05). Compare to group A2 and group B2, the satisfaction of the surgeons were significantly higher at 1h of the operation in group A1 and group B1 (P<0.05). Compare to group A2 and group B2, the satisfaction of the surgeons were significantly higher at 2h of the operation in group A1 (P<0.05).The incidence rate of hyoxemia after extubation, inability to perform sustained tongue depressor test was not significantly among groups. All of the patients were not suffered pneumonia,atelectasis.Conclusion Rocuronium is suitable for continuous infusion in laparoscopic surgery for deep neuromuscular blockade. The rocuronium consumption of continuous would be more and the satisfaction of the surgeons would be higher compare to intermittent infusion. Rocuronium would cumulate for a few time after long-time intravenous injection, intermittent infusion or continuous infusion. It’s necessary to use antagonism after long time application of rocuronium. |
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