Effect Of Ulinastatin Combined With Dexmedetomidine On Postoperative Cognitive Dysfunction In Patients Who Underwent Cardiac Surgery And Evaluation Of FMRI

Part 1:Effect of ulinastatin combined with dexmedeto-midine on postoperative cognitive dysfunction in patients who underwent cardiac surgeryObjective:In this study,ulinastatin was combined with dexmedetomidine to assess whether the combination of the two drugs could reduce the incidence of POCD.Methods:One hundred and eighty patients with heart valve replacement surgery undergoing cardiopulmonary bypass from August 2017 to December 2018 were enrolled,with age 60-80 years,American Society of Anesthesiologists(ASA)grades Ⅰ-Ⅲ,education level above elementary school,and either gender.According to the random number table method,patients were grouped into ulinastatin+dexmedetomidine(U+D)group,ulinastatin(U)group,dexmedetomidine(D)group,and normal saline(N)control group.Group U was pumped 20,000 U/kg immediately after induction and the first day after surgery,group D continued to pump 0.4 μg/kg/h from induction to 2h before extubation,group U+D dexmedetomidine 0.4 μg/kg/h+ulinastatin 20,000 U/kg,and group N equal volume of physiological saline.The patients were enrolled with MiniMental State Examination(MMSE)before surgery.The cognitive function was assessed by Montreal Cognitive Assessment(MoCA)on the first day before surgery and on the seventh day after surgery.Inflammatory factors,such as S100β protein,IL-6,MMP-9,and TNF-α,were detected in peripheral blood before anesthesia(T0),immediately after surgery(T1),and immediately after extubation(T2).Results:One hundred and fifty-four patients enrolled in this study.Compared with group N,the incidence of POCD in group U+D was the lowest(P<0.05),followed by group U and group D.Group U+D had the lowest concentration of inflammatory factors at the T1 and T2 time points,followed by group U and group D.Conclusions:Both ulinastatin and dexmedetomidine can reduce the perioperative inflammatory response and the incidence of POCD in patients with heart valve surgery,and their combination can better reduce the incidence of POCD.Part 2:evaluate postoperative cognitive dysfunction in patients who underwent cardiac surgery by using rs-fMRIObjective:using rs-fMRI to look for changes in activation and functional connectivity of the default mode network,salient network,central executive network and dorsal attention network in patients undergoing cardiac valve replacement surgery.To analyze the effect of surgery on postoperative cognitive function using the method of independent component analysis(ICA).exploring the evidence of prevention and treatment for POCD.Methods:A total of 30 right-handed patients undergoing elective cardiac valve surgery were enrolled,whose age were 60-80.ASA Ⅰ-Ⅲ,no gender requirement,education background is 6 years or above in primary school.During the same period,20 volunteers who matched the age,sex and education level with the surgical patients were selected as normal controls.All patients underwent Routine cranial scans,resting state functional magnetic resonance imaging(rs-fMRI)scans and neuropsychological tests before surgery,7 days and 1 month after surgery.The volunteers underwent routine cranial scan and resting state functional nuclear magnetic resonance imaging(rs-fMRI)scan before surgery,and completed neuropsychological tests before surgery,7 days and 1 month after surgery.Results:eighteen patients and eighteen corresponding control group were enrolled.Imaging results showed that there were no significant changes in anatomical MRI after surgery,most patients with cognitive impairment recovered 3 months after surgery.rs-fMRI results showed that:There were no significant impairment in the participants’s functional networks before surgery.Changes one week after surgery:①The default mode network(DMN)function was weakened,and the activation of the posterior cingulate gyrus(PCC)in the core of the default mode network was significantly decreased.②The function of the salience network(SN)was weakened,and the activation level of bilateral anterior insula in the core brain was decreased.③ The central executive network(CEN)function was weakened,and the activation level of dorsolateral prefrontal cortex and posterior parietal cortex were decreased.④The function of the dorsal attention network(DAN)was weakened,only the lateral temporal cortex showed decreased activation level,which may be related to the small sample size of the preliminary experiment and the low attention level of the resting state.⑤ the functional connectivity between DMN and DAN was weakened,the functional connectivity between the DMN of PCC and the DAN of IPS and mPFC were reduced,the functional connectivity between PL and the DAN of IPS and FEF were reduced.Changes one month after surgery:①The default mode network(DMN)function was weakened,and brain areas included the left medial temporal lobe,the right inferior temporal gyrus and the posterior cingulate cortex(PCC).②The function of the dorsal attention network(DAN)was weakened,brain area includes bilateral occipital lobe,right parietal sulcus area.Conclusions:the functional connectivity of DMN,SN,CEN and DAN were weakened after surgery,and the functional connectivity within the default mode network and the salience network were reduced.The negative functional connectivity strength between the default mode network and the central execution network was reduced.We speculate that the effect of surgery on the four major cognitive network activities may be related to the postoperative cognitive decline of patients.