右美托咪定对脓毒症休克犬早期外源性乳酸清除率的影响

Effect of Dexmedetomidine on Early Exogenous Lactate Clearance in Dogs with Septic Shock

目的观察右美托咪定(DEX)对脓毒症休克犬早期外源性乳酸清除率的影响,为右美托咪啶在脓毒症休克患者中的临床应用提供实验基础。方法选取16只犬,采用脂多糖(LPS)建立脓毒症休克模型,建模成功后将其随机分为对照组和DEX组,每组8只。DEX组采用DEX 1.0μg·kg-1·h-1持续静脉泵泵注至实验结束,对照组采用等容量的0.9%氯化钠注射液持续静脉泵泵注至实验结束。实验重复3次。监测并记录2组A点(开始输注LPS前)、B点(建模成功后)、C点(DEX组输注DEX后1 h、对照组输注0.9%氯化钠注射液后1 h)时心率(HR)、平均动脉压(MAP)、心排血量(CO)及A点、B点、C点时血清TNF-α、肾上腺素和血乳酸水平、外源性乳酸清除率。结果A、B、C点时2组HR、MAP、CO水平比较差异无统计学意义(P>0.05)。2组B点、C点时HR、CO水平均高于A点,MAP水平低于A点,差异有统计学意义(均P<0.05)。2组B点时血清TNF-α和血乳酸水平均高于A点,低于C点,差异有统计学意义(均P<0.05)。2组C点时血清TNF-α和血乳酸水平均高于A点,差异有统计学意义(P<0.05)。2组C点时血清肾上腺素水平高于A点、B点,差异有统计学意义(P<0.05)。2组B点时血清肾上腺素水平与A组比较差异无统计学意义(P>0.05)。DEX组A点、B点时血清TNF-α、肾上腺素和血乳酸水平与对照组比较差异无统计学意义(P>0.05)。DEX组C点时血清TNF-α、肾上腺素水平均低于对照组,差异有统计学意义(P<0.05)。DEX组C点时血乳酸水平与对照组比较差异无统计学意义(P>0.05)。对照组的外源性乳酸清除率为(6.44±0.68)mL·kg-1·min-1,低于DEX组的(9.09±1.68)mL·kg-1·min-1,差异有统计学意义(P<0.05)。结论右美托咪定可以增加脓毒症休克犬的早期外源性乳酸清除率,其机制可能是通过抑制血清肾上腺素水平及炎症因子TNF-α水平的升高,而减轻其介导的炎症反应。右美托咪啶对脓毒症休克犬的血流动力学没有造成不良影响。

Objective To observe the effect of dexmedetomidine(DEX)on early exogenous lactate clearance in dogs with septic shock,and to provide an experimental basis for clinical application of dexmedetomidine in patients with septic shock.Methods Sixteen dogs were given lipopolysaccharide to establish the model of septic shock.After successful modeling,these dogs were randomly divided into two groups,with 8 dogs in each group.The DEX group were treated with continuous intravenous infusion of DEX 1.0μg·kg-1·h-1 our until the end of the experiment,while the control group was given an equal volume of 0.9%sodium chloride.The experiment was repeated three times.Heart rate(HR),mean arterial pressure(MAP)and cardiac output(CO)were monitored and recorded at point A(before LPS infusion),point B(after modeling),and point C(1 hour after infusion).The levels of serum tumor necrosis factorα(TNF-α),adrenaline and lactic acid and the clearance rate of exogenous lactic acid were compared between the two groups.Results There were no significant differences in HR,MAP and CO between the two groups at all time points(P>0.05).Compared with point A,HR and CO increased but MAP decreased at point B and point C in both groups(P<0.05).The levels of TNF-αand lactic acid at point B were higher than those at point A,but lower than those at point C(P<0.05).Furthermore,TNF-αand lactic acid levels at point C were higher than those at point A(P<0.05).Serum levels of adrenaline at point C were higher than those at point A and point B(P<0.05).However,the difference in serum adrenaline levels was no significant between point A and point B(P>0.05).In addition,there were no significant differences between the two groups in levels of TNF-α,adrenaline and lactic acid at point A and point B,as well as in lactic acid levels at point C(P>0.05).The levels of TNF-αand adrenaline at point C in DEX group were lower than those in control group(P<0.05).The clearance rate of exogenous lactic acid in DEX group((9.09±1.68)mL·kg-1·minute-1)was higher than that in control group((6.44±0.68)mL·kg-1·minute-1)(P<0.05).Conclusion Dexmedetomidine can increase the early exogenous lactate clearance rate in septic shock dogs through inhibiting the elevation of serum adrenaline and TNF-αand alleviating inflammatory response.Dexmedetomidine has no adverse effect on hemodynamics in septic shock dogs.