A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. 1992

P W Stacpoole, and E C Wright, and T G Baumgartner, and R M Bersin, and S Buchalter, and S H Curry, and C A Duncan, and E M Harman, and G N Henderson, and S Jenkinson
Department of Medicine, University of Florida College of Medicine, Gainesville.

BACKGROUND 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. METHODS 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 > or = 5.0 mmol per liter and either an arterial-blood pH of < or = 7.35 or a base deficit of > or = 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. RESULTS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003999 Dichloroacetic Acid A derivative of ACETIC ACID that contains two CHLORINE atoms attached to its methyl group. Sodium Dichloroacetate,Bichloroacetic Acid,Potassium Dichloroacetate,Acid, Bichloroacetic,Acid, Dichloroacetic,Dichloroacetate, Potassium,Dichloroacetate, Sodium
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000140 Acidosis, Lactic Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE. Lactic Acidosis
D001158 Arteries The vessels carrying blood away from the heart. Artery
D015996 Survival Rate The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. Cumulative Survival Rate,Mean Survival Time,Cumulative Survival Rates,Mean Survival Times,Rate, Cumulative Survival,Rate, Survival,Rates, Cumulative Survival,Rates, Survival,Survival Rate, Cumulative,Survival Rates,Survival Rates, Cumulative,Survival Time, Mean,Survival Times, Mean,Time, Mean Survival,Times, Mean Survival

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