| Background of study:Postoperative cognitive dysfunction(POCD) is a kind of Central Nervous System Complication happened after anesthesia and surgery, its clinical manifestation includes anxiety,memory impairment, cognitive impairment, social integration ability and verbal comprehension ability decline etc., it is often occurred in elder surgical patient, especially those above 65 year old, it may cause increasing of fatality rate, longer hospitalization time, other complication and extra medical cost etc.[1], or even development of permanent cognitive disorder[2] (alzheimer disease or aphronesia) Zeng Tao[3] et al believe that POCD is generally existed in elder operation patients and it can continue for several month.Pathogenesis of POCD is related to central nervous system, immune system and endocrine,etc,but until now it is not still clear. Studies show that cognitive impairment has relation with obvious reduction of Ach in area such as hippocampus and near temporal lobe cortex etc,reduction of cholinergic receptor before synapse,and reduction of integration ability with cholinergic receptor of Ach pivot. TANZI[4] study indicates that the morbidity of POCD and AD are all related to synapse loss and synapse dysfunction. Arriagada[5] et al believes after study that anesthesia may influence microtubulin with high phosphorylation and thus cause damage to cognitive function. Most patients have emotional response such as stress,anxiety,insomnia at night,etc.,this is one of the main risks causing cognitive obstacle of elder patients after operation.Ramsay et al[6] carried out survey and analysis on 382 cases of patients waiting for operation,in which 45% are afraid of operation,62% are afraid of anesthesia and73% have sense of fear,these emotional reaction may induce or aggravate postoperative cognitive dysfunction[7]. Relevant studies show that systemic inflammatory response caused by operative wound may be one of the important reason [8].Too high expression of inflammatory response caused by surgical stress (CRP,TNF-a,IL-6,IL-P,Glial cells etc.) may have damaging impact on brain organ and thus cause cognitive impairment[9], therefore interference in perioperative period to reduce expression of inflammatory factor has very important meaning to brain protection.It does not have unified judgment standard and diagnosis method for POCD,clinically general test method is dominated by simple MMSE, the specificity is 82%and its sensibility is 87%.[10]Meanwhile it can carry out estimation through detecting IL-10,IL-6,TNF-a and S-100β protein’s plasma level of patients. TNF-α is a kind of early damaged cell factor mainly secreted by giant salivary cell with mononuclear,it can start and trigger the cascade reaction of inflammation and promote the production of various inflammatory factors in T cell and thus promote the happening of inflammatory response,this can reflect the level of inflammation.IL-10 is a kind of negative-regulatory factor with multiple functionS,Which is mainly produced by Th2 cell, activated B cell,mononuclear cell, and macrophage.lt plays function of reducing inflammatory reaction and antagonism inflammatory medium in various diseases such as autoimmune disease,serious infectious disease. S-100β(S-100 b) is mainly existed in Schwann cell and glial cell,when the cells of central nervous system get damaged,S-100β protein enters cerebrospinal fluid (CSF) after penetrated from cytosol,it enters blood again through damaged Blood Brain Barrier,so generally it is believed that the increase of S-100β protein in CSF is that central nervous system has sensitive and special biochemical marker when get damaged,it has clinical practical value for disease and prognosis judgment,and it is related to central nervous system dysfunction[11].Treatment of POCD should be dominated by targeted prevention.Now it is claimed to carry out strict anesthetic management during perioperative period, strength preoperative preparation and improve psychotherapy during perioperative period, once mental function disorder is found, medicine intervention therapy should be carried out as early as possible.Recent study shows that a2 epinephrine receptor agonist can reduce systemic inflammatory response through inhabit central sympathetic nervous system and cause regulation function on immune system,meanwhile it can activate anti-cell-apoptosis-signal pass,and thus protect the damaged cells of various organs such as brain,heart,liver, lung,kidney,intestine,etc.Dexmedetomidine,DEX is a kind of α2 receptor agonist with relevant high selectivity, cexpress alm,analgesia and anxiety relief. Locus coeruleus of brainstem is the area with most dense α2 adrenergic receptor, it has important function in regulation of harmful neurotransmitter. The study on transgenic rat shows [12] Dexmedetomidine is to act on Locus coeruleus of brainstem,it produces anxiety, sedative-hypnotic function through activating α2 adrenergic receptor in its nucleus. Some studies [13] show that dexmedetomidine can temporarily relief nerve injury of experimental animal after overall or local cerebral ischemia, this indicates that it has protection function on nerve,but its mechanism is still not clear. Takumi Taniguchi et al[14] carried out study on impact of dexmedetomidine in mortality and inflammatory response of rat with endoxemia shock,the mortality(94%) of rat using dexmedetomidine has obvious reduction comparing to mortality(44%) of rat using no dexmedetomidine, moreover the IL-6,TNF-a and other cell factors in rat plasma using dexmedetomidine has obvious reduction. When carrying out inspection on lung tissue of rat after death, it is found that the infiltration of inflammatory cells (neutrophils) in airway and pulmonary vascular wall. Their dosage effect and time effect on Dexmedetomidine in inflammatory response are proved in following experiments1151, it is proposed that in endoxemia rat model,the bigger the Dexmedetomidine dosage is,the lower the mortality of rate will be,the lower expression of inflammatory factor will be also,and more early using of Dexmedetomidine is,the lower expression of mortality and inflammatory factor shall be also.Currently,the etiology and pathogenesis of POCD for lack of definitive trestment,study of dexmedetomidine given cognitive function only on the animal experiments showed some advantages, less relevant clinical research, prevention and treatment effect is not exact,Along with the increasing of elder surgical patient,the occurrence rate and various impact of POCD shall be more serious,therefore more and deeper understanding and concern should be carried out in POCD prevention.ObjectiveDiscuss its impact on postoperative cognitive function of elder hip replacement surgical patients after general intravenous anesthesia through pre-infusion of Dexmedetomidine in elder hip replacement surgical patients, detection of plasma level in IL-10,TNF-a and S-100β protein and carrying out MMSE evaluation, in order to provide reference for clinical anesthesia.MethodRandomly divide 90 elder hip replacement surgical patients (65-80years) selecting proper time into contrast grou (group C),Dexmedetomidine group(groupDi)and Dexmedetomid-ine group (group D2),30 cases respectively.Group C is given of normal saline with e-qual volume, group D1 is given of intravenous infusion of Dexmedetomidine 0.5 μg/-kg, before anesthesia, group D2 is given of intravenous infusion of Dexmedetom-idine(1 μg/kg) before anesthesia, the infusion time are all lOmin. The 3 groups of patients all adopt general anesthesia under laryngeal mask united by lower limb ne-rve block.Patients did not use any drugs before operation,Group D1 and D2 were respectiv-ely given of 0.5μg/kg Dexmedetomidine and 1μg/kg Dexmedetomidine(all diluteed to 4μg/ml by normal saline, infusion is completed within in 10m) 20min before anesthe-sia,contrast group (group C) is given of normal saline in equal volume 20 min before anesthesia. Lately connect the nerve stimulator (PAJUNK BF) to nerve block punc-ture needle (PAJUNK 100mm) to carry out lower limbs never block(lumbar plexus and sciatic nerve united puncture) puncture under the guidance and positioning of po-rtable color doppler ultrasound,lumbar plexus and sciatic nerve are respectively infu-sed of 20ml 0.3% ropivacaine after successful puncture.Observe 15m,start general anesthesia induction after confirming block effect: et-omidate 0.1-0.3mg/kg, Cisatracurium 0.15mg/kg,Fentanyl 1～2μg/kg, place prop-er laryngeal mask after mature muscle relax condition. Connect anaesthesia machine to carry out controlling breath after successful placing of laryngeal mask, VT 8-10 ml/kg, RR 10-12 time/min, and timely carry out regulation,and maintain PetCO2 within the range of 35-40mmHg.Anesthesia maintenance:target-controlled infusion of Propofol and Fentanyl,set plasma concentration as 2μg/ml and 3.5ng/ml respecti-vely, carry out regulation according to EEG depth of anesthesia, blood pressure,heart rate and surgical stimul-ation of patient,maintain EEG depth of anesthesia(sedation index LOCl:40-60;injury pain index LOC2:30-50), blood pressure and heart rate fluctuation at ±20% before op-eration.After the end of operation,conduct sputum suction and get off laryngeal mask when patient’s consciousness,cough,swallowing reflex and autonomous respiration are recovered to good condition.Conduct continuous block analgesia by lumbar plexus catheter (Patient-controlled nerve block analgesia,PCNA) after operation,formula:40ml 1% ropivacaine hydrochloride is diluted to 200ml by adding saline, the concentration is 0.2%, background dose is infused by 5 ml/h,additional quantity is 2.5 ml/time,pressing interval is 30min.Record general situation of 3 groups of patients,including gender,ASA grade,weight, height,education year,operation time,bleeding volume etc.;During oper-ation,regularly monitor non-invasive blood pressure (SBP,DBP,MAP),heart rate (HR),electrocardiogram(ECG),arterial oxygen saturation(SpO1),end-tidal carbon dioxide (PetCO2) and EEG depth of anesthesia(sedation index LOC1:40-60;injury pain index LOC2:30-50).Extract 5m venous blood of no infusion side at various time points:24h (To) before operation,1 h (T1),8h (T2),24h (T3),48h (T4) after operation, centrifuge 10 min at 4000r/min, separate serum and place into-80 ℃ refrigerator for safekeeping, stay and detect content of S-100β protein,IL-10 and TNF-a level.Use mini-mental state examination (MMSE) to carry out neuropsychological test and record scoring at time points such as 24h (To) before operation,8h (T2),24h (T3),48h (T4) after operation, and calculate out POCD occurrence case number in 3 groups of patients.Record the 2 groups of patients’general anesthesia maintaining time,autonomous respiration recovery time,eye opening time by calling, extubation time, total amount of propofol and fentanyl, as well as bradycardia, tachycardia, hypotension, respiratory depression, delayed recovery and other anesthetic complications.The preoperative assessment of all patients are classified as 1-2 grade according to ASA,average weight is (55±8.5) kg,all patients use no drugs before operation,there are also no alcoholism history, hypertension,diabetes,cerebrovascular disease,neuropsychic disease, history of using corresponding drugs, serious internal environment disorder.All measurement data are expressed by mean ± standard deviation (x±s),conduct statistics handling on data by SPSS 14.0 software package, use one-way variance analysis inside group by comparison,comparison between groups adopts t test, enumeration data adopts chi-square test by comparison,P<0.05 indicates that difference has statistical significance.Result(1) Comparison of 3 groups of patients’age,gender,ASA grade,weight,height, education year,preoperative complication,operation time,bleeding volume etc. have all no statistical difference(P>0.05).(2) 24h non-invasive blood pressure (MAP) before operation, heart rate (HR), arterial oxygen saturation (SpO2) of 3 groups have no obvious difference; non-invasive blood pressure of group D2 at T1,T2 is lower than group D1 and C,compare-ison has obvious difference, (P＜0.05); heart rate(HR) of group D1 and D2 at T1,T2 is lower than group C, (P< 0.05)(3) Cognitive function assessment(MMSE) of patients has no statistical difference among 3 groups before operation (P>0.05); MMSE score of group C at T3,T4 is obvious lower than To (P<0.05) of this group;MMSE score of group D1 and D2 at T3,T4 has no obvious difference comparing to core of this group at T0 , (P>0.05); the MMSE score of group D1 and D2 at T2,T3,T4 are higher than group C (P<0.05), and it is faster to recover to the level before operation. POCD occurrence case of group C at T2,T3,T4 are higher than group D1 and D2, (P＜0.05)(4) The plasma S-100β protein,IL-10 and TNF-α level of patient have no sta-tistical difference 24h (T0) before operation (P>0.05); S-100β albuminand TNF-α of group C are all obvious higher than group D1 and D2 (P＜0.05); group D1 and D2 have no obvious difference, (P>0.05).IL-10 of 3 groups at T1,T2,T3,T4 are higher at T0;IL-10 of group D1 and D2 are higher than group C at T1 T2,T3,T4 (P＜0.05) IL-10 of group D2 is higher than group D1 at T1,T2, (P＜0.05)(5) Comparison of patients’ anesthesia maintenance time and spontaneous breathing recovery time has no obvious significance, (P>0.05); in group D1 and D2,the time from stopping general anesthetics infusion to eye opening and extubation time is obviously prolonged when comparing to group C,difference has obvious significance,(P＜0.05); Propofol dose of group D1 and D2 is obviously less than group C,(P< 0.05);Remifentanil dose of group D2 is obvious less than group C and group D1,(P＜0.05),in which Remifentanil dose difference of group D1 and C have no obvious difference, (P>0.05)(6) Complication occurrence situation of patient:occurrence case of bradycardia and hypotension of group D2 is more than group D1 and C, comparis-on has statistical significance,(P＜0.05); 3 patients in group C occur tachycardia,in which 2 cases before anesthesia,1 case in recovery period, comparison with group D1 and D2 has statistical significance(P<0.05); 4 patients in groups occur hypertension,in which 2 cases before anesthesia,2 cases in recovery period,comparison with group D1 and D2 has statistical significance(P<0.05); 3 patients in group D2 occur respir-atory depression, expression is slow respiratory rate and insufficient ventilation, com-parison with group D1 and C has statistical significance , (P＜0.05); other indicato-rs of various groups has no obvious difference, (P>0.05)Conclusion(1)Pre-infusion of Dexmedetomidine can improve posto-perative cognitive function of elder hip replacement surgical patient and reduce occur-ence risk of POCD,which may be related to relieving preoperative tension and anxiet-y of patient,reducing anaesthetic dose in operation, reducing production of inflamma-tory factor TNF-a and S-100β protein after operation and promoting the rising of anti-inflammatory factor IL-10 etc.(2)Intravenous infusion of 0.5μg/kg Dexmedetomidine has better effect on improving postoperative cognitive function of elder hip replacement patient after operation,less complication and more stable blood rheology, but further study is needed on whether best concentration is reached. |
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