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Are there prognostic factors which determine outcome in a patient with lactic acidosis who is ventilated and on hemodialysis? Is there a point where irreversible inhibition of oxidative phosphorylation occurs, or can supportive therapy be continued expectantly in the absence of the development of multiorgan failure?
Michael McBride, FRCP
Lactate is the end product of the cytosolic metabolism of glucose, and its accumulation in the blood signals an increase in production or a decrease in utilization, or both. The liver is a major site of removal of lactate, so abnormalities in the metabolism of lactate by mitochondria in hepatocytes and other cells may contribute to clinical conditions in which overproduction and underuse of lactate occur.
Data regarding prognosis of lactic acidosis -- as defined by arterial lactate level ≥ 5 mmol/L and blood pH ≤ 7.35 -- are largely derived from the critical care literature. To a large extent, the prognosis is dependent on the cause of the problem and the promptness of recognition. Lactic acidosis in all settings is associated with a high mortality. Treatment involves establishing and correcting its underlying cause, ensuring adequate oxygen delivery to tissues, reducing oxygen demand through sedation and mechanical ventilation, and -- most controversial -- attempting to alkalinize the blood and clear the lactate.
The most common causes of lactic acidosis in HIV-infected patients include malignancy, organ (especially liver) failure, cardiovascular disease, and diabetes mellitus. In addition, all nucleoside reverse transcriptase inhibitors have been associated with rare instances of lactic acidosis. In this case, discontinuation of all antiretroviral therapy and the institution of supportive therapy are the mainstay of treatment.
To date, evidence supporting the use of bicarbonate infusions or dichloracetic acid in improving prognosis is lacking. Data in the HIV setting regarding use of coenzyme Q10, carnitine, or riboflavin remain anecdotal at best.
The level of lactate and severity of acidosis appear to be the key issues in prognosis: the higher the lactate, the more acidotic the patient and the worse the prognosis. This does not mean that sustained support should not be considered in individuals with high lactate levels. For example, when associated with metformin use, risk of death appears to be associated with the presence of other hypoxic disease or underlying ill health rather than lactate levels. This may also be the situation in patients with HIV, where risk factors such as obesity, hepatitis coinfection, and advanced HIV infection have been suggested by reports of (mostly fatal) cases reported to the Food and Drug Administration.
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