Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 27-05: Lactic Acidosis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Severe metabolic acidosis with compensatory hyperventilation Blood pH below 7.30 Serum bicarbonate < 15 mEq/L Anion gap > 15 mEq/L Absent serum ketones Serum lactate > 5 mmol/L +++ General Considerations ++ Characterized by accumulation of excess lactic acid in the blood Principal sources of lactic acid Erythrocytes (which lack enzymes for aerobic oxidation) Skeletal muscle Skin Brain Causes Tissue hypoxia (global or local) Disorders that increase epinephrine levels (severe asthma with excess beta-adrenergic-agonist use, cardiogenic or hemorrhagic shock, pheochromocytoma) Drugs that impair oxidative phosphorylation (antiretroviral agents and propofol) Inborn errors of metabolism The MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) Chief pathways for removal of lactic acidosis Conversion of lactic acid to glucose and its oxidation Principally by the liver Also by the kidneys Metformin-associated lactic acidosis Most cases occur when use of metformin is contraindicated, in particular kidney failure Metformin levels are usually > 5 mcg/L when the drug is implicated as the cause of lactic acidosis D-lactic acidosis can occur in patients with short bowel syndrome when unabsorbed carbohydrates are presented as substrate for fermentation by colonic bacteria + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Main clinical feature is marked hyperventilation When lactic acidosis is secondary to tissue hypoxia or vascular collapse, the clinical presentation is variable, being that of the prevailing catastrophic illness In idiopathic, or spontaneous, lactic acidosis Onset is rapid (usually over a few hours) Blood pressure is normal Peripheral circulation is good No cyanosis +++ Differential Diagnosis +++ Other causes of metabolic acidosis ++ Diabetic ketoacidosis Starvation ketoacidosis Alcoholic ketoacidosis Kidney failure (acute or chronic) Ethylene glycol toxicity Methanol toxicity Salicylate toxicity Other: paraldehyde, metformin, isoniazid, iron, rhabdomyolysis + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ High anion gap (serum sodium minus the sum of chloride and bicarbonate anions [in mEq/L] should be no > 15). A higher value indicates the existence of an abnormal compartment of anions Plasma bicarbonate and blood pH are quite low, indicating the presence of severe metabolic acidosis Ketones are usually absent from plasma and urine, or at least not prominent In the absence of azotemia, hyperphosphatemia occurs in lactic acidosis for reasons that are not clear The diagnosis is confirmed by a plasma lactic acid concentration of 5 mmol/L or higher (values as high as 30 mmol/L have been reported) Normal plasma values average 1 mmol/L, with a normal lactate–pyruvate ratio of 10:1. This ratio is greatly exceeded in lactic acidosis +++ Treatment ++ Empiric antibiotic coverage for sepsis should be given after culture samples are obtained if the cause of lactic acidosis is unknown Alkalinization with intravenous sodium bicarbonate to keep the pH above 7.2 in the emergency treatment of lactic acidosis is controversial; as much as 2000 mEq in 24 h has been used. However, there is no evidence that the mortality rate is favorably affected by administering bicarbonate +++ Therapeutic Procedures ++ Aggressive treatment of the precipitating cause is the main component of therapy, such as ensuring adequate oxygenation and vascular perfusion of tissues Hemodialysis may be useful when large sodium loads are poorly tolerated and in cases associated with metformin toxicity + Outcome Download Section PDF Listen +++ +++ Prognosis ++ Mortality rate of spontaneous lactic acidosis is high Prognosis in most cases is that of the primary disorder that produced the lactic acidosis +++ When to Admit ++ All patients because of the high mortality rate + References Download Section PDF Listen +++ + +DeFronzo R et al. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20–9. [PubMed: 26773926] + +Goergen SK et al. Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology. 2010 Jan;254(1):261–9. [PubMed: 20032157]