Effect Of Dexmedetomidine On Inflammatory Reaction And Cerebral Injury In Patients Undergoing Cardiac Valve Replacement

Background:The majority of open heart surgery needs the support of cardiopulmonary bypass.Due to low temperature,low flow,micro-air embolism and other factors,cardiopulmonary bypass can lead to cerebral and nervous damage,which has been confirmed by more and more studies.Dexmedetomidine is an α2 adrenergic receptor agonist that can be used for sedation in anesthetized and mechanically ventilated patients.In recent years,it is found that dexmedetomidine has neuroprotective function,which can reduce cerebral and nervous damage caused by the open heart surgery under cardiopulmonary bypass.ObjectiveTo explore the influence of dexmedetomidine on the inflammatory response and cerebral injury in patients with cardiopulmonary bypass CPB)undergoing cardiac valve replacement.MethodsSeventy cases of patients undergoing cardiac valve replacement with cardiopulmonary bypass were selected,and were randomly divided into two groups: dexmedetomidine group（group D）and control group（Group C）,35 cases in each group.In group D,after induction of anesthesia,and a bolus of dexmedetomidine 0.5μg·kg^-1 given intravenously,then,0.5 g·kg^-1 ·h^-1 of dexmedetomidine was given intravenously by micro pump.In control group,dexmedetomidine was replaced by an equal volume of normal saline.On the day preoperatively and day 3 postoperatively,cognitive function of patients in the two groups was evaluated using Mini Mental State Examination（MMSE）.Five milliliters ofblood was obtained from radial artery before operation（T₀）,immediately after cardiopulmonary bypass finished（T₁）,immediately after operation（T₂）,6 h（T₃）,24h（T₄）after operation,respectively.The serum was obtained after centrifugation and then stored in the refrigerator.The tumor necrosis factor（TNF-α）and interleukin-6（IL-6）and plasma S-100 beta,plasma neuron specific enolase（NSE）were obtained by enzyme linked immunosorbent assay（ELISA）method,and the internal jugular vein oxygen saturation（SjvO₂）,cerebral artery and internal jugular venous oxygen content difference（Ca-jvO₂）,partial pressure of arterial oxygen（PaO₂）and cerebral oxygen extraction rate（ERO₂）were also recorded to compare the difference of therapeutic effect between the two groups.ResultsThere were no significant differences of age,sex ratio,height,weight,left ventricular ejection fraction（LVEF）,cardiopulmonary bypass time,aortic cross clamping time and hospitalization time between two groups（P > 0.05）.There was no significant difference of MMSE score between D（28.34±1.29）and group C（28.06±1.18）,preoperatively（P>0.05）.At postoperative day 3,the MMSE score in group D（28.24 + 1.58）was significantly higher than that in group C（26.01 + 1.59）（P< 0.05）.There was no significant difference of MMSE score at postoperative day 3（28.24 + 1.58）compared with before operation（28.34±1.29）in group D;whereas in group C,MMSE score at postoperative day3（26.01±1.59）was significantly lower compared with that before operation（28.06±1.18）（P < 0.05）.Postoperative MMSE score less than 24 points occurred in 6 cases in group D,accounting for 17.1%;24 cases,accounting for 31.4%.The incidence of postoperative cognitive impairment in group D and C was 17.1% and 31.4%,respectively,but there was no significant difference（P > 0.05）.Serum TNF-alpha,IL-6 at each time points in the both groups after cardiopulmonary bypass were all significantly higher than those at T₀（P<0.05）.In group D,serum TNF-alpha at time points T₁-T₅ was（392±36,722±73,927±95,786±62）pg/ml,respectively,which was significantly lower than that in group C,（442±56,849±120,1024±108,863±33）pg/ml respectively,（P < 0.05）.In group D,at time pointsT₂-T₄,serum IL-6 was（91.80±9.4,139.1±15.6,100.2±7.6）pg/ml,respectively,which was significantly lower than that in group C（106.8±9.0,156.4±16.2,116.5±13.1）pg/ml,respectively（P<0.05）.After cardiopulmonary bypass,serum S-100 beta increased significantly in both groups,（P < 0.05）.In group D,serum S-100 beta at T₃（369±45）pg/ml was significantly lower than that in group C（P < 0.05）.In group D,there was no significant difference of serum NSE between T₁（13.5±2.2）ng/ml and T₂（12.2±1.8）ng/ml（P <0.05）.Serum NSE in group D at T₂-T₄ was（18.7±1.5,21.8±2.5,21.8±1.9）ng/ml significantly higher than that at T₀（12.2±1.8）ng/ml,respectively（P<0.05）.In group C,serum NSE at T₁-T₄ was（17.6±1.2,20.9±1.7 23.4±2.3 22.2±1.6）ng/ml,respectively,which was significantly higher than that at T₀（12.4±1.6）ng/ml,（P < 0.05）.In group D,serum NSE at T₁,T₂（13.5±2.2,18.7±1.5）ng/ml was significantly lower than that in group C（17.6±1.2,20.9±1.7）ng/ml,respectively（P<0.05）.There were no significant differences of SjvO₂,Ca-jvO₂,PaO₂,and ERO₂ between group D and group C at T₀,which was SjvO₂（67±7）%,Ca-jvO₂（50±8）mmol/L,PaO₂（133±66）mmHg,ERO₂（35±10）% in group D and SjvO₂（66±5）%,Ca-jvO₂（49±9）mmol/L,Pa02（135±55）mmHg,ERO₂（37±8）% in group C,respectively（P> 0.05）.SjvO₂ in group D at T₁（80±8）% was significantly higher than that in group C（73±7）%（P<0.05）;Ca-jvO₂ in group D at T₁（24±9）mmol/L was significant lower than that in group C（32±6）mmol/L（P<0.05）.PaO₂ in group D at T₁PaO₂（232±47）mm Hg was significant higher than that in group C（210±35）mmHg（P<0.05）.ERO₂ in group D at T₁（18±11）% was significantly lower than that in group C（25±9）%.At T₁,PaO₂ in both groups increased significantly,whereas,ERO₂ decreased significantly.After treatment,in group D,full recovery was 28 cases,effective 6 cases,invalid 1 case,and the total effective rate was 97.1%;in group C,full recovery was 20 cases,effective 6cases,invalid 9 cases,and the total effective rate was 74.3%.The effective rate in group D was significantly higher than that in group C（P< 0.05）.ConclusionDexmedetomidine given intravenously(0.5μg·kg^-1·h^-1)can reduce the inflammatoryresponse in patients undergoing cardiac valve replacement with cardiopulmonary bypass;Dexmedetomidine can reduce the brain metabolism in patients after cardiac valve replacement.