The Effects Of Dexmedetomidine And Ulinastatin On The Patients With Supratentorial Tumor Resection Perioperation In Cerebral Oxygen Balance,Brain Energy Metabolism And The Concentration Of Serum SOD,MDA,S100βProtein And

ObjectiveBrain tissue is sensitive to hypoxic-ischemic at normal temperature for the characteristic of hypermetabolism and the low reserve. Quite a number of patients with intracranial tumors had suffered from intracranial pressure and cerebral pre-operation.Which may be caused or worsen by the use of electrocoagulation and brain spatula intraoperation, hypotension and body-fluid imbalances cause by hemorrhage.And then bring brain tissue into the imbalance between supply and demand of oxygen and the metabolic disorder of energy.So it’s very important to monitor the oxygen balance of the brain tissue and the brain energy metabolism in the perioperative period, maintain the normal function of the nerve cells,insure the success of neurosurgical anesthesia and surgery.Ulinastatin separated and purified from the human urine is one of the trypsin inhibitor, with a variety of hydrolytic enzymes which can inhibit activity of trypsin, chymotrypsin and hyaluronidase, elastase, cathepsin G etc.Also can inhibit inflammatory reaction, scavenge free radicals,regulate immunologic function,protect visceral organ.For the patient with craniocerebral trauma or extracorporeal circulation,Ulinastatin can reduce the produce and release of inflammatory mediators,improve brain circulation,block Phospholipase activation pathway by calcium overload in ischemia re-perfusion,inhibit the produce and release of plasma endothelin,reduce oxygen free radicals,improve oxygen balance of encephalon,reduce cell apoptosis.Then can reduce the brain edema predictable caused by craniocerebral surgery,protect the brain cells and improve patients1prognosis.Dexmedetomidine is a new type which with high selectivity and specificity of a2adrenergic agonists.Numerous animal experiments have demonstrated the Dexmedetomidine would have neuroprotection,can alleviate the nerve cell damage by ischemia hypoxiaD But the exact mechanism has not been been really clear.lt may be connected with the functions of Dexmedetomidine,such as the reduction of the level of catecholamine in brain tissue cause by hypoxic-ischemic,the balance of apoptosis and resisting apoptosis protein,reduction of the release of excitatory neurotransmitters, especially glutamate,reduction of cellular damage cause by neuronal cell membrane depolarization and calcium influx.There were few reports that there was any obviously affect on the Cerebral oxygen balance,cerebral energy metabolism and cerebral protection in the combined use of Ulinastatin and Dexmedetomidine on the patients with supratentorial tumor resection.It’s the same that there was any synergistic effect.In this study:jugular bulb venous oxygen saturation (SjvO2),arteriovenous oxygen content difference (Ca-jVO2),cerebral oxygen extraction rate (CERO2) lactic acid generation rate (LacPR) and lactic acid oxygen index (LOI) would be analysed in order to research the effect of the combined use on balance of cerebral oxygen supply and energy metabolism.The concentration of superoxide dismutase (SOD),malondialdehyde (MDA),S100β protein (S100β) and neuron specific enolase (NSE) in internal jugular bulb venous would be quantitative detected for further Exploring whether there was any cerebral protection,effectively combat operations, or any association with the lower level of oxygen free radicals or the lower level of lipid peroxidation on cerebral protective mechanism.Method:1General InformationChoose48cases with supratentorial tumor resection which have normal preoperative electrocardiogram, hematological, biochemical and hepatic and renal function and other checks, no coagulopathy, and Glasgow scoring15are points, aged from18to60years, ASA I or II degree. Hemoglobin(Hb) shouldn’t less than100g/L, hematocrit(Hct) not less than30%. The patients with hypertension, diabetes, previous cerebrovascular accident history and long-term medication were exclude. The patients were divided into four groups by random number table:a control group (group A) and ulinastatin groups (group U), dexmedetomidine group (group D) group, ulinastatin and dexmedetomidine(group UD), Each group is12cases.2AnesthesiaAnesthesia was induced by TCI with a target of propofol3-3.5μg·ml-1and remifentanil2-4ng·ml-1and cisatracuronium0.15mg·kg-1. Anesthesia maintenance was achieved by TCI with a target of propofol2.5-3.5μg·ml-1and remifentanil2- 4ng·ml-1and cisatracuronium2ug-kg·lmin-1. PETCO2was maintained from30to33mmHg. Narcotrend was maintained EO-E1. Muscle relaxant maintenance was the four clusters stimulate (TOF) T1inhibited more than95%. Ulinastatin(2ku/kg) were injected at beginning of operation, and then were pumped injection on the rate of1ku-kg-1·h-1to the end at group U. And Dexmedetomidine(lug/kg) were injected at beginning during15minutes, pumped injection on the rate of lu-kg-1·h-1to the end at group D.While the same use of Ulinastatin and Dexmedetomidine at group UD, equivalent0.9%saline solution only at group C.3Specimen collectionBlood were took from internal jugular bulb venous and dorsalis pedis synchronous for blood gas analysis at the time before the induction of general anesthesia (T1), before cutting the skin(T2)，,1h after cutting the dura mater (T3), seaming dura mater (T4), End of the surgery (T5),24h after surgery (T6). And5ml jugular bulb venous blood were took into a test tube for centrifuging.4Testing indexTesting indexes includearterial oxygen content(CaO2), jugular bulb venous oxygen saturation(SjvO2), internal jugular venous oxygen content(CjvO2), arteriovenous oxygen content difference(Ca-jvO2), cerebral oxygen extraction rate(CERO2), rates of glucose uptake(GluER), lactic acid generation rate(LacPR) and lactic acid oxygen index(LOI), the concentration of superoxide dismutase(SOD), malondialdehyde (MDA), S100β protein (S100β) and neuron specific enolase (NSE)in internal jugular bulb venous.5Statistical analysisUse SPSS13. O-statistical analysis software.signify data with mean and standard deviation, variance analysis for repeated measurement measurement data, LSD for multiple comparisons, two independent samples t-test or single-factor analysis of variance for the compared of same point-time at different group, one-way ANOVA for Group of patients basic information. There was significant difference when P<0.05.Consequence1General conditions of four groupsThere was no significant difference in the age, weight, total anesthesia time and infusion volume(P=0.583,0.881,0.517,0.438,respectively). Amount of propofol and remifentanil of group D and group UD decline more than that in group A and group U.2Index of cerebral oxygen balance2.1CaO2There was no significant difference in different time in the same group (F=48.270, P<0.01). there was more dramatic decline at time T2、T3、T4、T5and T6than T1of each group (P<0.001)There was no significant difference in different group.2.2CjvO2There was significant difference in different time in he same group (F=29.151, P<0.01).there was more dramatic decline at time T2、T3、T4、T5and T6than T1of each group (P<.001)There was no significant difference in different group.2.3SjvO2There was significant difference in different time in the same group (F=8.288, P<0.001). There was more dramatic raise at timeT3、T4and T5than T1at group D and group UD(P<0.001). There was no significant difference in different time of group A and group U(P=0.699,0.969).There was more dramatic decline at timeT3、T4and T5of group D than the same time of group C and group U (P<0.05),the same as group UD. There was no significant difference at the same time of group A and group U (P>0.05)。2.4Ca-jvO2There was significant difference in different time in the same group (F=42.535, P<0.001). There was more dramatic decline at time T3、T4、T5and T6than T1of group D and group UD (P<0.001)There was significant difference in the same time of different group (F=8.416, P<0.001). There was more dramatic decline at time T3、T4、T5and T6of group D than the same time of group A and group U (P<0.05), the same as group UD (P<0.05). While there was no significant difference of the other time.2.5CERO2There was significant difference in different time of the same group (F=9.193， P<0.001). There was more dramatic decline at time T4and T5than T1of group D and group UD (P<0.001).There was more dramatic decline at time T3、T4and T5of group D than the same time of group A and group U(P<0.05), the same as group UD(P<0.05). While there was no significant difference at the other time.3Brain Energy Metabolism3.1GluERThere was no significant difference in either different time of the same group nor the same time of different group (F=0.026,P=0.994; F=0.008, P=0.999)3.2jv-aLacThere was significant difference in different time of the same group (F=40.301, P<0.001).There was more dramatic decline at timeT3、T4、T5and T6than T1of each group (P<0.010)There was no significant difference in different group at the same time.(F=0.302, P=0.824) 3.3LacPRThere was significant difference in different time of the same group (F=31.104, P<0.001).There was more dramatic decline at time T2-T6than T1of each group (P<0.001)。There was no significant difference in different group at the same time.(F=1.515, P=0.224)3.4LOIThere was significant difference in different time of the same group (F=5.379, P<0.001).There was more dramatic decline at timeT2-T6than T1of each group (P<0.010)There was no significant difference in different group at the same time.(F=0.058, P=0.981)4Activity of serum SOD in internal jugular vein bulbThere was significant difference at different time of the same group (F=208.721, P<0.001).There was more dramatic decline at timeT3-T6than T1of each group (P0.001)There was significant difference at the same time of different group in the Activity of serum SOD (F=19.517, P<0.001). The Activity of serum SOD of group U and UD were higher than group A at time T3-T6(P<0.001), while group D was higher than group A at time T4-T6(P<0.001), group UD was higher than group U and D at time T3-T5(P<0.001). There was not significant difference between group U and group D (P=0.197)5Content of serum MDA in internal jugular vein bulbThere was significant difference at different time of the same group in the content of serum MDA(F=164.780,P<0.001). There was more dramatic rise at time T3-T6than Ti of each group (P<0.001) There was significant difference at the same time of different group in the content of serum MDA (F=40.351, P<0.001). There was more dramatic decline at time T3-T6of group UD than group A (P=0.002-P<0.001), the same as group U and D. While there was more dramatic decline at time T3-T5of group UD than group U and D (P<0.001). There was no significant difference between group U and group D (P=0.787)。6Concentration of serum S100βprotein in internal jugular vein bulbThere was significant difference at different time of the same group in the concentration of serum S100βprotein (F=217.314, P<0.001). There was more dramatic rise at timeT3-T6than T1of group A,U and D (P<0.001).There was more dramatic rise at timeT3-T5than T1of group UD (P<0.001)There was significant difference at the same time of different group in the concentration of serum S100β protein (F=46.233, P<0.001). There was more dramatic decline at time T3-T5of group U and D than group A (P<0.001), While there was more dramatic decline at time T3-T6of group UD than group A (P <0.001). There was more dramatic decline at time T3-T6of group UD than group U and D (P<0.001). There was no significant difference between group U and group D (P=0.666)。7Concentration of serum NSE in internal jugular vein bulbThere was significant difference at different time of the same group in the concentration of NSE (F=373.180, P<0.001). There was more dramatic rise at timeT3-T6than T1of each group (P<0.001)。There was significant difference at the same time of different group in the concentration of NSE (F=40.351, P<0.001). There was more dramatic decline at timeT3-T5of group U and D than group A (P<0.001), While there was more dramatic decline at time T3-T6of group UD than group A (P<0.001). There was more dramatic decline at timeT3-T6of group UD than group U and D (P<0.001) There was no significant difference between group U and group D (P=0.632)conclusion1. There were changes in cerebral oxygen balance and cerebral energy metabolism in the patients with supratentorial tumor resection perioperation by total intravenous anesthesia with propofol. But it’s still normal. Surgical trauma could reduce the ability of scavenging free radicals, increase oxygen free radicals and damage Nerve cell til24hour postoperation.2. Ulinastatin could not benefit to the patients with supratentorial tumor resection in cerebral oxygen balance and cerebral energy metabolism perioperation by total intravenous anesthesia with propofol in such Medication method. But it can improve the activity of serum SOD intraoperation and after24hour postoperative, decrease the concentration of serum MDA, S100β protein and NSE at the same time. Ulinastatin took protective effect on cerebral protection.3. Dexmedetomidine could improve partly cerebral oxygen balance in the patients with supratentorial tumor resection perioperation by total intravenous anesthesia with propofol, nor cerebral energy metabolism. But could improve the activity of serum SOD intraoperation and after24hour postoperative, decrease the concentration of serum MDA, S100β protein and NSE at the same time. Dexmedetomidine took protective effect on cerebral protection.4. Just the same as using Dexmedetomidine only, the combined useing of Dexmedetomidine and Ulinastatin could improve partly cerebral oxygen balance in the patients with supratentorial tumor resection perioperation by total intravenous anesthesia with propofol nor cerebral energy metabolism.lt could improve the activity of serum SOD intraoperation and after24hour postoperative, decrease the concentration of serum MDA, S100β protein and NSE more pronounced at the same time. The combined useing is superior to useing one drug only on cerebral protection.