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For further information, see CMDT Part 27-05: Lactic Acidosis

Key Features

Essentials of Diagnosis

  • Severe metabolic acidosis with compensatory hyperventilation

  • Blood pH < 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

    • Disorders that increase epinephrine levels (severe asthma with excess β-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

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

  • Diabetic ketoacidosis

  • Starvation ketoacidosis

  • Alcoholic ketoacidosis

  • Kidney failure (acute or chronic)

  • Ethylene glycol toxicity

  • Methanol toxicity

  • Salicylate toxicity

  • Other: paraldehyde, metformin, isoniazid, iron, rhabdomyolysis


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


  • 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 ...

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