| OBJECTCongenital heart disease(CHD)is a common disease of cardiovascular system,the incidence of more concentrated in the infants and teenagers(1),the incidence of is closely related to genetic factors,drugs,intrauterine infection and contact poison physical and chemical.With the development of modern medical technology progress and social economy and culture,the detection rate of CHD rising.Congenital heart disease in only a minority can be natural recovery,most of as the growth of the age,complications will be gradually increased,the condition will be aggravated gradually.In open heart operation under extracorporeal circulation is the main method of correction of congenital heart disease.Since 1953,the first cases of open heart surgery under cardiopulmonary bypass declared a success,the development of extracorporeal circulation technology rapidly,improving the nervous system monitoring technology,the sensitivity and specificity of higher biochemical monitoring index,cardiopulmonary bypass equipment more in generation,perfusion methods continue to improve to make surgery more and more high,a large sample of recent study shows that[1],despite the complexity of congenital heart disease surgery has improved,but the postoperative in-hospital mortality rate lower than 3%.The contradiction lies in the central nervous system complications after CPB is rising day by day,study shows that postoperative dysfunction of central nervous system occurred in 2%?3%,its long-term performance are the learning and memory disorders,abnormal behavior,distractibility and hyperactivity,seriously affect the quality of life of patients and bring heavy burden to the family.[3]Study of neuropsychiatric symptoms in open heart surgery has become a new hotspot.Brain tissue has a high metabolism,but low energy reserves,and characteristics of ischemia and hypoxia tolerance ability,in the process of extracorporeal circulation micro thrombosis,inflammatory cytokines and oxygen free radicals may lead to hypoxia ischemia brain damage.At present,cerebral protection drugs are common in:Edaravone Injection,nimodipine,magnesium sulfate,glucocorticoid,the cerebral protective mechanism for the removal of the body and brain tissue oxygen free radicals,reduce the cell lipid per oxidation,inhibit cell calcium influx,inhibit the activity of excitatory amino acids,but between the combined application of drug delivery method and the drug dose effect relationship and so on is still difficult for scientific research.Effects of ulinastatin and dexmedetomidine is a commonly used adjuvant drug in open heart operation under cardiopulmonary bypass in,both in the chemical structure and pharmacological characteristics are not the same,the combined use of both werther produce cerebral protective effect in different ways by inhibiting extracorporeal circulation ischemia reperfusion injury and inflammatory injury better,is the key point of the project.Ulinastatin is a kind of trypsin inhibitor extracted from fresh human urine can inhibit a variety of proteolytic activity,has inhibitory effect on trypsin,neutrophil elastase and other serine proteases,hyaluronic acid enzyme,cathepsin G,and it can inhibit the inflammatory cascade,scavenging oxygen free radicals,immune regulation function and so on,have a protective effect on multiple organ.Cao Lijun[26]research shows that,the effect of ulinastatin on the hippocampus,dentate gyrus neurons play a role in the regulation of the density and enhanced expression of synaptophysin and effectively alleviate cerebral ischemia reperfusion injury.Dexmedetomidine is a new highly selective alpha 2-adrenergic receptor agonist,at present already in the ICU sedation and procedural sedation achieved extensive application,rsearch shows that by reducing brain ischemia and hypoxia zone catecholamine levels,inhibition of cell calcium influx,reducing the release and activity of the excitatory neurotransmitter glutamate etc.,play a protective effect on the nervous system.Effects of ulinastatin and dexmedetomidine alone during CPB for open heart operation has obtain great attention.But the application of the combination of synergistic or whether the strengthening effect,whether to further reduce the inflammatory response during cardiopulmonary bypass,the level of oxygen free radical and lipid peroxidation and plays a role in protecting brain better rarely reported.Through the experiments of single and combined use of ulinastatin and dexmedetomidine,with extracorporeal circulation in open heart operation were as the research object,discusses whether the two have a synergistic effect or strengthening effect of brain protection,in order to provide new ideas for improving the postoperative neurological dysfunction.Method1 average data chooses 36 patients undergoing open heart operation under extracorporeal circulation as the object of study,children with ASA ???,age 2?12 months,weight 3?10 kg.Randomly divided into control group(group C),ulinastatin group(group U),dexmedetomidinegroup(group D),ulinastatin + dexmedetomidine group(B group),9 cases in each group.Four groups in gender,age,weight and other general preoperative data were compared,no significant difference(P>0.05),preoperative electrocardiogram,blood coagulation function,blood routine,biochemical routine,liver and kidney function were within the normal range,within 3 weeks of upper respiratory infection symptoms.2 anesthesia methods all of the patients were using intravenous inhalation anesthesia,before entering the operation room are not using premedication.Children before routine monitoring of ECG,Sp02.anesthesia induction:intravenous injection of 0.2?0.4mg/kg of midazolam,fentanyi citrate 10 g/kg,rocuronium bromide 0.6 mg/kg after tracheal intubation anesthesia machine,connected with mechanical ventilation,respiratory parameters setting:tidal volume,respiratory frequency 8?10ml/kg 25?30 time/min,breath ratio of 1:1.5,the inspired oxygen concentration 50%?60%.Maintenance of anesthesia:inhalation of sevenhalothane 1%?2%,When the incision and sternotomy,before the start of cardiopulmonary bypass,after rewarming,extracorporeal circulation stop after intravenous injection of an additional midazolam of 0.1?0.2 mg/kg,rocuronium bromide0.3 mg/kg,fentanyl citrate 10 g/kg.Group U after induction of anesthesia administered Ulinastatin 10 000u/kg after rewarming and after shutdown were given Ulinastatin 5000 U/Kg.D group after induction of anesthesia administered dexmedetomidine 1 mu g/kg,and then to 0.5?g/kg/h rate is maintained until the end of operation.B group after induction of anesthesiaadministered Ulinastatin 10000 U/kg and dexmedetomidine 1 u g/kg,after dexmedetomidineto 0.5u g/kg/h rate is maintained until the end of operation,rewarming and after CPB again intravenous Ulinastatin 5000 U/Kg.The control group with the same point with the equal volume normal saline instead of.3 samples collecte every 30 min after induction of anesthesia in children,respectively(T1),30 min(T2)after rewarming,30 min(T3)after the shutdown,4 h(T4)after the shutdown,24 h after the shutdown(T5)vein drawn within five time points after carotid 3 ml of blood,the blood after centrifugation 2500 r/min centrifugation 10 min,the upper layer of sterile injecting serum silicified plastic tube,seal placed at-80 ? cryopreservation equipment seized.4 observation and routine monitoring intraoperative detection index invasive arterial blood pressure,ECG,central venous pressure,sp02,and record blood loss,urine,blood transfusion,operative time,cardiopulmonary bypass time.S100? plasma protein,brain-derived neurotrophic factor(BDNF),interleukin-6(IL-6)and tumor necrosis factor ?(TNF?)concentrations were measured by enzyme-linked immunosorbent assay(ELISA).5 Statistical processing applications SPSS 17.0 statistical software for statistical analysis,measurement data from the mean ± standard deviation(± s),said the group were compared using ANOVA,using LSD Comparison between each group at different time points differences.Duplicate data between the two groups were compared using two-factor analysis of variance were compared between groups at different time points using the Bonferroni method.With P<0.05 as significant difference was statistically significant.Results1 four groups of children generally compareFour groups of children in sex,age,weight,cardiac function,brain development status and other general There was no significant difference(P>0.05)materials.Four groups of children in the type of surgery,cardiopulmonary bypass time,operation time after extubation time relatively well,there was no significant difference(P>0.05).2 serum TNF? concentrationCompared with group C,U group,D group slightly lower serum TNF?concentration in T1,but no significant difference(P>0.05),while in T2,T3,T4,T5 serum TNF? concentrations were significantly lower and there is significant difference(P<0.05);compared with group C,group B serum TNF? concentrations at each time point were significantly lower(P<0.05);U group and D group,plasma TNF? concentrations did not change significantly at all time points(P>0.05);with the U group,D group,group B plasma TNF? concentrations at each time point were significantly lower(P<0.05).3 serum concentrations of IL6Compared with group C,U group,D group decreased slightly in T1IL6 serum concentrations,but no statistically significant difference(P>0.05),while in T2,T3,T4,T5 were significantly lower and there is significant difference(P<0.05);compared with group C,group B serum IL6 concentrations at each time point were significantly lower(P<0.05);U group and D group,plasma IL6 concentrations did not change significantly(P at each time point>0.05);and U group,D group,group B plasma concentrations of IL6 slightly lower at all time points,but no significant difference(P>0.05).4 serum concentrations S100?Compared with group C,U group,D group B plasma S100? concentrations at each time point were significantly lower(P<0.05);D group and U group,plasma S100? concentrations did not change significantly(P at each time point>0.05);and the U group,D group,group B S100? plasma concentrations at each time point were significantly lower(P<0.05).5 serum BDNF concentrationCompared with group C,U BDNF serum concentrations did not change significantly(P>0.05)at all time points,D,group B serum BDNF concentrations in T1 slightly higher but not statistically significant(P>0.05),in T2,T3,T4,T5 and other time points were significantly higher and has a statistically significant difference(P<0.05);U group and group B serum BDNF concentrations at each time point were significantly increased(P<0.05).Conclusion1 after beginning CPB To stop after four hours,within each group of plasma IL-6,TNF?and increased compared with preoperative T1 increments form,indicating cardiopulmonary bypass heart surgery during the activation of the inflammatory response.2 after beginning CPB To stop after four hours,within each group group plasma S100?,BDNF compared with preoperative T1 increased,indicating cardiopulmonary bypass heart surgery on the brain to produce some damage.3 alone ulinastatin group and the control group,the plasma at each time point IL-6,TNFa,S100p concentrations were significantly lower(P<0.05),but Ulinastatin no significant difference in plasma BDNF concentration(P>0.05),said ulinastatin surgery can suppress the inflammatory response during cardiopulmonary bypass while reducing S100? concentrations reach neuroprotective effect.4 alone right dexmedetomidine group and the control group,plasma IL-6,TNFa,S100? concentrations were significantly lower outside except T1(P<0.05)and plasma BDNF concentrations were significantly increased(P<0.05),described right dexmedetomidine both to inhibit inflammation and can reduce ischemic brain injury.5 alone right dexmedetomidine group or ulinastatin group with combined Ulinastatin given dexmedetomidine group,the plasma IL-6,TNFa,S100?concentrations were significantly lower(P<0.05)and plasma BDNF concentrations were significantly increased(P<0.05),shows that both can be used in combination to further suppress inflammation and reduce ischemic brain damage,reduce the incidence of postoperative neurological dysfunction. |
PDF Full Text Request