| Background: With the aging of population,the number of the elderly undergoing surgery has further increased.Several pre-operative comorbidities,such as cardiovascular,pulmonary and nervous systems,may increase the incidence of postoperative complications.These pathophysiological changes lead to poor tolerance of the elderly to the surgery and anesthesia.Peri-operative neurocognitive disorder(PND)consisting of post-operative delirium(POD)and post-operative cognitive dysfunction(POCD)is the most common postoperative complication in the elderly undergoing surgery.The complicated mechanism is not yet clearly revealed.Previous evidence shows that the neuroinflammation is associated with POD and POCD.However,the clinical evidence of whether perioperative anti-inflammatory therapy is beneficial to reduce PND in the elderly is still insufficient,which needs to be studied urgently.Objective: This study was designed to observe the effect of ulinastatin on PND in the elderly undergoing laparoscopic hepatobiliary surgery with selective intravenous combined with inhalational general anesthesia,and then to provide the evidence for clinical application.Method: This is a prospective,randomized,controlled,double-blind clinical study.Two hundred and twenty six old patients undergoing elective laparoscopic hepatobiliary surgery in our hospital from March 2018 to December 2018,aged 65 to 80,male and female,graded I to III of the American Society of Anesthesiologists(ASA),and the expected surgical time more than 2 h,were screened and included.Patients were randomly assigned to ulinastatin group(U group,n=113)or normal saline control group(C group,n=113)with block random method.Ulinastatin 10000 U/kg(diluted to 100 ml normal saline)was intravenously infused in group U.The infusion was completed within 30 min before the induction of anesthesia.Another ulinastatin 5000 U/kg was administered intravenously 24 h and 48 h after operation(diluted to 100 ml normal saline),respectively.The same volume of saline was administered at the same time points in group C.At the time of preoperation,1 day and 3 d postoperation,Serum C-reactive protein(CRP),interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-alpha(TNF-?),S100? were measured by enzyme linked immunosorbent assay(ELISA)method.Blood gas analysis was conducted at 1 and 2 h during the operation,entering PACU,as well as at 12 h,on 1 d,3 d,and 7 d after the operation to measure the serum sugar and lactate levels.At the moment of 12 h after operation,on 1 d,3 d,7 d and 10 d,the patients' condition was assessed by using the Consciousness Fuzzy Assessment Unit(CAM-ICU).The cognitive function of the two groups was tested by a simple mental state checklist(MMSE)before operation,at 12 h,on 1 d,3 d,7 d and 10 d after the operation.Result:1.There were no significant differences in age,height,weight,body mass index(BMI),ASA classification,pre-operative commodities,operation time,anesthesia time,bleeding volume,urine volume,infusion volume,sevoflurane dosage,remifentanil dosage and norepinephrine dosage between two groups(P>0.05).2.There was no significant difference in the incidence of delirium between the two groups(group C vs.group U: 11/106(10.38%)vs.7/108(6.48%),P>0.05).The results of repeated measurement variance analysis showed that there was significant difference in MMSE scores between the two groups(P<0.05).The Turkey post hoc results showed that there were significant differences in MMSE scores between the two groups on 1 d,3 d,7 d and 10 d after the operation(P<0.05).The overall incidence of post-operative cognitive impairment in group U was significantly lower than that in group C(group C vs.group U: 54/106(50.94%)vs.32/108(29.63%),P<0.05).3.The serum TNF-?,IL-6,IL-10,CRP and S100? in group U was significantly lower than that in group C(P<0.05).The Turkey post hoc results showed that there were significant differences in TNF-?,IL-6,CRP and S100? between two groups on 1 d and 3 d after the operation(P<0.05).The serum level of IL-10 was similar in two groups(P<0.05).4.The serum sugar and lactic acid in group U was significantly lower than that in group C(P<0.05).The Turkey post hoc results showed that there were significant differences in sugar between two groups at 1 and 2 h during the operation,entering PACU,as well as at 12 h,on 1 d,3 d,and 7 d after the operation(P<0.05).Besides,there were significant differences in lactic acid between the two groups at 1 and 2 h,as well as on 1 d,3 d and 7 d after the operation(P<0.05).Conclusion: The use of ulinastatin before anesthesia induction and during peri-operative period can reduce the incidence of PND in the elderly undergoing laparoscopic hepatobiliary surgery. |
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