Possible Mechanism And Dose-related Study Of Dexmedetomidine Inhibiting Inflammatory Response In Septic Patients

Objective:By comparing the effects of Dexmedetomidine and Propofol on inflammatory factors(TNF-?,IL-6)and nuclear transcription factor-?B in septic patients with mechanical ventilation,the possible mechanism of dexmedetomidine in reducing inflammatory response was deduced,and the dose correlation of dexmedetomidine in inhibiting inflammatory response was discussed.Sedative drugs with obvious inhibitory effect on inflammatory response were selected,providing clinical sedation reference for septic patients with mechanical ventilation in intensive care unit.Methods:According to the diagnostic criteria of sepsis 3.0 in 2016,septic patients with mechanical ventilation treated in ICU of our hospital from November 2017 to October 2018were included.Exclusion criteria:allergic to dexmedetomidine and/or propofol;pregnant women;heart failure(cardiac function class ? or ?);renal failure(Rifle classification criteria);liver failure(total plasma protein less than 30g/L,and total serum bilirubin greater than 85.5mol/L);known or suspected brain death andthose treated with Ulinastatin and XueBiJing.According to acute physiology and chronic health evaluation(APACHE?)scores,the disease severity of all patients in the group was evaluated.According to the sepsis-related organ failure assessment(SOFA)score,the organ functions of all patients at the time of admission were evaluated from respiratory,neurological,cardiovascular,liver,coagulation and kidney systems.All patients in the group were treated according to the standards of sepsis and septic shock treatment guidelines in 2014(i.e.anti-infection,fluid resuscitation,control of infection sources,prevention of complications,nutritional support,protection of organ function,mechanical ventilation and so on),patients were divided into 3 groups by random number table method,that is,group L(Dex low-dose group):after being given a loading dose of 0.5?g/kg dexmedetomidine,sedation is maintained at 0.2?g/(kg·h);Group H(Dex high-dose group):after being given a loading dose of 1.5?g/kg dexmedetomidine,sedation was maintained at 0.6?g/(kg·h);Group C(propofol group or control group):giving a loading dose of 1mg/kg propofol within 15 minutes,and then sedation was maintained at 1-3mg/(kg·h).The sedation duration of the three groups of patients exceeded 24 hours.The Ramsay scale was used to evaluate the patient's sedation depth,and the intravenous pump speed of sedative drugs was adjusted to maintain the Ramsay score at 2-3 points.If the patient has pain,1-3?g/(kg·h)remifentanil is given for appropriate analgesia,Behavior pain scale(BPS)was used to evaluate the pain of patients.Venous blood was drawn from the vacuum blood collection vessel with inert separation gel before,12 hours and 24 hours of medication respectively,supernatant is taken after centrifugation and stored at-80 DEG C,the levels of tumor necrosis factor?(TNF-?),interleukin-6(IL-6)and nuclear transcription factor?B(NF-?B)were detected by enzyme-linked immunosorbent assay(ELISA)at the same time.The mechanical ventilation time,ICU hospital stays and 28-day fatality rate were calculated among all the groups.SPSS 22.0 was used for statistical analysis.The measurement data of normal distribution are expressed by mean standard deviation(?),the measurement data of non-normal distribution are expressed by median(quartile spacing),the difference between groups is analyzed by single factor variance analysis,and the linear regression was used to analyze the correlation of variables.P<0.05 indicates that the difference has statistically significance.The design and implementation of the experiment have all passed the examination and approval of the Ethics Committee of the Second Hospital of Dalian Medical University.Results:75 patients were finally enrolled in the study,including 25 cases in Dex low dose group,25 cases in Dex high dose group and 25 cases in propofol group;There was no significant difference in age,APACHE?score and SOFA score among the three groups(P>0.05).There was no significant difference in serum TNF-?and IL-6 levels among the three groups before medication(P>0.05),the contents of TNF-?and IL-6 in serum of patients in Dex high-dose group were significantly lower than those in Dex low-dose group and propofol group at 12h and 24h after administration,and the difference was statistically significant(P<0.05),there was no significant difference between Dex low-dose group and propofol group(P>0.05).There was no significant difference in NF-?B content among the three groups before medication(P>0.05),at 12h and 24h after administration,compared with propofol group,NF-?B content of patients in Dex low-dose group and high-dose group decreased with statistical significance(P<0.05),and NF-?B content of patients in Dex high-dose group decreased more obviously than that of patients in low-dose group with statistical significance(P<0.05).Linear regression analysis showed that with the decrease of NF-?B level,the contents of TNF-?and IL-6 also decreased.The mechanical ventilation time and ICU hospital stays of patients in Dex low-dose group and high-dose group were less than those in propofol group with statistical significance(P<0.05).Conclusion:Dexmedetomidine can reduce the level of inflammatory factors in septic patients with mechanical ventilation,which may play an anti-inflammatory role by inhibiting NF-?B,a signaling molecule in cholinergic anti-inflammatory pathway,and its anti-inflammatory effect shows dose correlation.Therefore,for septic patients with mechanical ventilation,sedation with high dose of dexmedetomidine will obtain more benefits.