A Controlled Clinical Trial of Dichloroacetate for Treatment of Lactic Acidosis in Adults

Academic Article

Abstract

  • Mortality is very high in lactic acidosis, and there is no satisfactory treatment other than treatment of the underlying cause. Uncontrolled studies have suggested that dichloroacetate, which stimulates the oxidation of lactate to acetyl-coenzyme A and carbon dioxide, might reduce morbidity and improve survival among patients with this condition. We conducted a placebo-controlled, randomized trial of intravenous sodium dichloroacetate therapy in 252 patients with lactic acidosis; 126 were assigned to receive dichloroacetate and 126 to receive placebo. The entry criteria included an arterial-blood lactate concentration of ≥5.0 mmol per liter and either an arterial-blood pH of ≤7.35 or a base deficit of ≥6 mmol per liter. The mean (±SD) arterial-blood lactate concentrations before treatment were 11.6±7.0 mmol per liter in the dichloroacetate-treated patients and 10.4±5.5 mmol per liter in the placebo group, and the mean initial arterial-blood pH values were 7.24±0.12 and 7.24±0.13, respectively. Eighty-six percent of the patients required mechanical ventilation, and 74 percent required pressor agents, inotropic drugs, or both because of hypotension. The arterial-blood lactate concentration decreased 20 percent or more in 83 (66 percent) of the 126 patients who received dichloroacetate and 45 (36 percent) of the 126 patients who received placebo (P = 0.001). The arterial-blood pH also increased more in the dichloroacetate-treated patients (P = 0.005). The absolute magnitude of the differences was small, however, and they were not associated with improvement in hemodynamics or survival. Only 12 percent of the dichloroacetate-treated patients and 17 percent of the placebo patients survived to be discharged from the hospital. Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival. (N Engl J Med 1992;327:1564–9.), LACTIC acidosis is a common disorder of acid–base metabolism that occurs in patients with many life-threatening illnesses. The mortality rate among patients with lactic acidosis is high,123 but whether lactic acidosis influences the prognosis independently of the underlying disease and, if so, whether specific treatment and amelioration of lactic acidosis improve survival are not known. Several uncontrolled studies have suggested that treatment with dichloroacetate may reduce not only morbidity but also mortality in patients with lactic acidosis caused by hypotension or sepsis.456 Dichloroacetate ameliorates lactic acidosis by increasing myocardial glucose oxidation and contractility and by inhibiting glycolysis, thereby decreasing lactate… © 1992, Massachusetts Medical Society. All rights reserved.
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    Author List

  • Stacpoole PW; Wright EC; Baumgartner TG; Bersin RM; Buchalter S; Curry SH; Duncan CA; Harman EM; Henderson GN; Jenkinson S
  • Start Page

  • 1564
  • End Page

  • 1569
  • Volume

  • 327
  • Issue

  • 22