Effect Of Dexmedetomidine On Early Exogenous Lactate Clearance In Septic Shock Dogs

Objective: To observe the effect of dexmedetomidine on exogenous lactate clearance in septic shock dogs,and to provide experimental basis for clinical application of dexmedetomidine in septic shock patients.Methods: All dogs underwent femoral artery and central venous catheteriz ation under anesthesia and mechanical ventilation and received pulse index con tinuous cardiac output monitored(Picco).After stabilization for 1 hour(point A),5 ug/kg lipopolysaccharide(LPS)was injected intravenously and then continu ed infusion for 4 ug/kg/h.One hour after LPS infusion,all dogs were given li quid resuscitation.If hypotension still existed,norepinephrine was infused to m ake their MAP reach the target value of 55-60 mmHg.Immediately after resus citation(point B),16 dogs were randomly divided into control group and dex medetomidine group(DEX group),8 in each group.In DEX group,dexmedeto midine was continuously infused at the rate of 1.0 ug/kg/h at point B.At poin t A,point B and 1 hour after resuscitation(point C)heart rate(HR),mean art erial pressure(MAP)and cardiac output(CO)were monitored and recorded,a nd blood samples were taken to detect the levels of lactate,adrenaline and tu mor necrosis factor-alpha(TNF-α),respectively.Intravenous administration of 1mmol/kg sodium L-lactate was given within 15 min after monitoring and record ing all the data of point C.Blood lactate values were measured before the ad ministration of sodium lactate(i.e.point C)and 1,3,6,9,15,and 20 min af ter the administration of sodium lactate.Finally,the area under curve for lactat e concentration against time in each dog was calculated and substituted into th e mathematical model formula to calculate the exogenous lactate clearance.Results: The values after LPS infusion of point B compared with the basic values of point A in the two groups: HR increased,blood pressure decreased,CO increased,TNF-α and blood lactate level increased at point B(P< 0.05),but there was no difference in adrenaline level in each groups(P> 0.05).Compared the values of HR,MAP,CO,NE,TNF-α,adrenaline and blood lactic acid between DEX group andcontrol group: There was no significant difference between the two groups(P > 0.05),suggesting that LPS induced the occurrence of septic shock and the increase of TNF-a and blood lactic acid,but there was no difference between the two groups.The C-point values of control group and DEX group were compared with their respective B-point values: HR,MAP and CO at C-point had no significant change(P > 0.05),NE infusion dose and blood lactic acid level increased(P < 0.05);TNF-αand adrenaline levels increased(P< 0.05)compared C-point and B-point values in control group,and TNF-alpha levels increased(P< 0.05)compared C-point and B-point in DEX group,while adrenaline levels did not differ(P>0.05).There was no significant difference in HR,MAP,CO,NE infusion and blood lactic acid between DEX group and control group at C point(P > 0.05),suggesting that DEX had no effect on hemodynamics;the lower levels of TNF-alpha and adrenaline at C point in DEX group indicated that DEX inhibited the increase of TNF-alpha and adrenaline levels.The increase of blood lactate was the most obvious in the two groups at 20 minutes after L-lactate injection(P < 0.001).Compared with the control group,the increase of blood lactate was lower in the DEX group at all time points(P < 0.05).The exogenous lactate clearance rate measured and calculated in the DEX group was significantly higher(P < 0.05).Conclusion: Dexmedetomidine can increase the clearance rate of exogenous lactate in septic shock dogs;at the same time,it may alleviate the inflammatory reaction mediated by inhibiting the elevation of serum adrenaline level and inflammatory factor TNF-alpha level;dexmedetomidine has no adverse effect on hemodynamics in septic shock dogs.