Effects of dichloroacetate administration during fatal hemorrhagic shock in immature swine.
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.
Syverud
S A
SA
Department of Emergency Medicine, University of Cincinnati Medical Center, Ohio 45267-0769.
Barsan
W G
WG
Van Ligten
P F
PF
Dronen
S C
SC
Timerding
B
B
Zink
B J
BJ
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005260:Female; D007773:Lactates / Q000097:blood; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D013552:Swine
D000085:Acetates; D001786:Blood Glucose; D007773:Lactates; D003999:Dichloroacetic Acid