Lactic acidosis update for critical care clinicians

Abstract

Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction. Drugs used to treat lactic acidosis can aggravate the condition. NaHCO(3) increases lactate production. Treatment of type A lactic acidosis is particularly unsatisfactory. NaHCO(3) is of little value. Carbicarb is a mixture of Na(2)CO(3) and NaHCO(3) that buffers similarly to NaHCO(3) but without net generation of CO(2). The results from animal studies are promising; however, clinical trials are sparse. Dichloroacetate stimulates pyruvate dehydrogenase and improves laboratory values, but unfortunately not survival rates, among patients with lactic acidosis. Hemofiltration has been advocated for the treatment of lactic acidosis, on the basis of anecdotal experiences. However, kinetic studies of lactate removal do not suggest that removal can counteract lactate production in any meaningful way. The ideal treatment is to stop acid production by treating the underlying disorder.