Minocycline Dcreased The Incidence Of Postoperative Delirium And Postoperative Cognitive Dysfunction In Aged Patients—A Randomised Doublie Blinded Clinical Trial

Background Postoperative delirium(POD)is an acute,reversible,widely recognized disorder of mental disorders.It is characterized by acute distraction and cognitive dysfunction,lacking of concentration,disturbance of thought,or variation in the level of consciousness.Delirium usually occurs at 1-3 days after operation and decreases with time.And delirium is associated with a variety of adverse outcomes.Delirium would increase the hospitalization time,medical expenses,cognitive dysfunction,long-term disability,reduce the quality of life of patients.And would increase morbidity and mortality of the patients after surgery,at same time postoperative readmission and reoperation rate might increase.POD may have an irreversible effect on postoperative cognitive function and accelerate the decline of cognitive function.Postoperative cognitive dysfunction is associated with anesthesia and surgery.It is characterized that attention can not be focused,memory and social behavior declined,and other cognitive function and severe personality changed.Postoperative cognitive dysfunction is also a common complication of the elderly patients after surgery,to patients with postoperative recovery caused a great impact,to the patient's family has brought great mental and economic burden.In short,the occurrence of postoperative delirium and the postoperative cognitive dysfunction,has seriously affected the recovery of postoperative patients and their quality of life.Even would affect the survival rate of patients after surgery,overload on the patient's family,result in a serious social effect.However,their pathogenesis are not completely clear,among those theories in the pathophysiological hypothesis,the central nerve inflammation hypothesis is most authorized. It is based on that surgery and anesthesia activates the macrophage system,then the blood-brain barrier damaged,and intracranial inflammatory mediators increased,pro-inflammatory and anti-inflammatory balance broken,that make patients delirium.Minocycline is a kind of tetracycline derivative,its lipophilic structure makes it easy to pass through the blood-brain barrier,and to inhibit central inflammation and produce nerve protective effect.This experiment mainly explore the preoperative application of minocycline can reduce the incidence of POD and POCD.Methods In this study,we choose 100 elderly patients that are planned to receive maj or surgery of intestinal surgery or Urology surgery.(aged>65 years),and 2 hours before the operation,they are treated with 200mg of minocycline(test group n=50)or 200mg of starch capsules(control group n=50).All of those operation and anesthesia time are supposed to be more than two hours.All patients are received general anesthesia with same types of anesthetics.Assessment:1-3 days before operation,we will complete the assessment of MMSE patients,who are chosen according to the inclusion and exclusion criteria,at the same time,we'll finish the first time of cognitive function assessment,with three kinds of neural psychology test and record the preoperative level of cognitive function score.During the operation,the vital signs of patients are recorded.And 1-3 days after operation,we use CAM and MDAS to complete the diagnosis of patients of delirium,and finish the second time of nerve psychology test before they leave hospital.This experiment also included in the same period of non operative healthy community elderly persons(community group n=50),the completion of the two nerve psychology test at 5-7 day intervals.We set this kind of group in order to exclude the affect of study caused by test with the same scale in short period of time.At the same time,the adverse events were recorded during the whole experiment.Results 100 patients were randomly divided into two groups,actually,95 patients have completed this experiment,47 of minocycline group and 48 of the control group.1 One of minocycline group occurred POD,the incidence rate was 2.1%,and 7 of control group occurred POD,the incidence rate was 14.6%,the chi square test of the incidence rate between the two groups P=0.029(P<0.05,with statistical difference).2 The MDAS score of two groups the day 1-3 post operation,score of minocycline group is significantly lower than the other's,T test showed that P(1)=0.009,P(2)=0.547,P(3)=0.272,(P<0.05,with statistical difference).35 of minocycline group occurred POCD,the incidence rate was 10.84%,and 10 of control group occurred POCD,the incidence rate was 20.33%,the chi square test of the incidence rate between the two groups P=0.173(P>0.05,without,statistical difference).4.Logistics regression analysis showed that age(P=0.030)and MMSE(P=0.038)were significantly correlated with POD.(P<0.05,with statistical difference)Conclusion Minocycline can reduce the severity of delirium in 1-3 days after operation,and may significantly reduce the incidence rate of POD.Minocycline may reduce the incidence rate of POCD,but there have not occurred statistical differences.The occurrence of delirium might be associated with certain aspects of cognitive function impairment,but there still need more evidence to support.Certainly,this experiment further verified that there is a significant correlation between POD and patients'age and pre-operation cognitive function status significant.