不同剂量右美托咪定对脓毒症大鼠血流动力学的影响

Dose-related effects of dexmedetomidine on hemodynamics and mortality in sepsis shock： experiment with rats

目的探讨不同剂量右美托咪定对脓毒症大鼠血流动力学及死亡率的影响。方法48只盲肠结扎穿孔（（malligationandpuncture，CLP）后的Wistar大鼠随机分为四组：①盲肠结扎穿孔组（CLP组）；②2．51xg／kg·h右美托咪定治疗组（DEX2．5组）；③5btg／kg·h右美托咪定治疗组（DEX5．0组）；④10μg／kg·h右美托咪定治疗组（DEX10．0组）。监测CLP术后1h、3h及5h的平均动脉压、心率，检测CLP术后3h血气及血乳酸水平，实验大鼠于24h后处死并记录24h内死亡率。结果CLP组1h、3h和5h的心率无明显变化，且随着输液时间的延长，平均动脉压不断下降。在右美托咪定治疗组（DEX2．5组，DEX5．0组，DEX10．0组）心率显著下降，平均动脉压持续输注1h后降低至最低水平随后保持稳定。与CLP组比较，有美托咪定治疗组血乳酸水平及pH明显下降（P=0．0002），BEecf及TCO2水平较CLP组明显改善（P〈0．0001），PCO2水平均显著高于CLP组（P〈0．0001）。与CLP组比较，右美托咪定治疗组的死亡率显著降低，且与剂量呈正相关，CLP组，DEX2．5组，DEX5．0组及DEX10．0组死亡率分别为91．7％，66．7％，25％，18％。结论右美托咪定能够有效改善脓毒症时的血流动力学变化，同时提高生存率。

Objective To invesyigate the effects of dexmedetomidin on the hemodynamics and mortality in septic shock. Methods 48 Wister rats underwent cecal ligation and puncture （CLP） and then were randomly allocated in 4 equal groups： CLP group transfused with normal saline for 5 hours, small-dose treatment group （group DEX 2.5）transfused with dexmedetomidin 2.5 μ g/kg· h for 5 hours, medium-dose treatment group （group DEX 5.0） transfused with dexmedetomidin 5.0 μg/kg · h for 5 hours, and large-dose treatment group （group DEX 10.0） transfused with dexmedetomidin 10.0 μg/kg, h for 5 hours. The mean arterial blood pressure （MAP）, heart rate （HR）, and temperature （T） were moniotored continuously. 3 h after the blood samples were collected by carotid catheterization to measure the arterial blood gases and lactate concentration. The rats were killed 24 hours later. The mortality rates were documented. Results In the group CLP, the heart rates in lh, 3h, and 5h did not show obvious differences, and the MAP decreased continually along with the prolongation of infusion time. In the 3 Dex groups, the HR values gradually decreased, and the MAP value 1 h later decreased to the lowest level but remained there then. In the 3 Dex groups, the lactate and pH levals were significantly lower （all P= 0.0002）, and the BEeef and TCO2 levels were all more normal than those of the group CLP （all P〈 0.0001）., and the PC02 levels were all significantly higher than that of the group CLP （P〈 0.0001）. All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively. Conclusions Dexmedetomidine effectively improves the hemodynamics in sepsis, thus improving the suvival.