Syverud S A, Barsan W G, Van Ligten P F, Dronen S C, Timerding B, Zink B J
Department of Emergency Medicine, University of Cincinnati Medical Center, Ohio 45267-0769.
Ann Emerg Med. 1987 Nov;16(11):1228-30. doi: 10.1016/s0196-0644(87)80228-7.
During hemorrhagic shock, decreased perfusion and poor tissue oxygenation lead to increased lactate production. Previous animal studies have suggested that sodium dichloroacetate (DCA), an agent that decreases lactate production, can improve hemodynamics and survival when administered after severe hemorrhage. We used an unanesthetized porcine hemorrhagic shock model to assess the effect of DCA on survival time when administered during fatal hemorrhage. Immature female swine weighing 14 to 20 kg were splenectomized and instrumented with chronic indwelling aortic and right atrial catheters one week prior to hemorrhage. On the day of the experiment, the unanesthetized animals' aortic catheter was connected to a roller pump and blood was removed at a rate of 1.0 mL/kg/min until death occurred. Experimental animals (n = 8) received sodium dichloroacetate (25 mg/mL distilled water) 100 mg/kg IV bolus beginning 15 minutes after the start of hemorrhage followed by a 3 mg/kg/min constant IV infusion. Control animals (n = 8) received an equal volume of normal saline. Arterial pressure, heart rate, blood gases, serum lactate, and serum glucose were measured at baseline and every 15 minutes during hemorrhage. There were no significant differences in survival time (controls, 63 +/- 2.8 min; DCA-treated, 60 +/- 3.7 min), lactate levels, or blood pressures between the two groups. These results suggest that DCA does not decrease serum lactate or improve survival time when administered during ongoing severe hemorrhagic shock. Further study should be directed at the effects of DCA as an adjunctive treatment after hemorrhage has been controlled and tissue perfusion restored.
在失血性休克期间，灌注减少和组织氧合不良会导致乳酸生成增加。先前的动物研究表明，二氯乙酸钠（DCA）是一种可减少乳酸生成的药物，在严重出血后给药时可改善血流动力学并提高生存率。我们使用未麻醉的猪失血性休克模型来评估DCA在致命性出血期间给药对生存时间的影响。在出血前一周，对体重14至20千克的未成熟雌性猪进行脾切除术，并植入慢性留置主动脉和右心房导管。在实验当天，将未麻醉动物的主动脉导管连接到滚压泵，以1.0毫升/千克/分钟的速率抽血直至死亡。实验动物（n = 8）在出血开始后15分钟开始静脉推注100毫克/千克二氯乙酸钠（25毫克/毫升蒸馏水），随后以3毫克/千克/分钟的速率持续静脉输注。对照动物（n = 8）接受等体积的生理盐水。在出血期间，于基线及每15分钟测量动脉压、心率、血气、血清乳酸和血清葡萄糖。两组之间的生存时间（对照组，63±2.8分钟；DCA治疗组，60±3.7分钟）、乳酸水平或血压无显著差异。这些结果表明，在持续的严重失血性休克期间给予DCA不会降低血清乳酸或改善生存时间。进一步的研究应针对在出血得到控制且组织灌注恢复后，DCA作为辅助治疗的效果。
