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Definition, Etiology, PathogenesisTop
Lactic acidosis is metabolic acidosis with a high anion gap and serum lactate levels >5 mmol/L (4 mEq/L). It is caused by increased anaerobic glucose metabolism and consequent lactate accumulation. Lactic acidosis is not a disease-specific complication of diabetes mellitus; it is triggered by precipitating factors and is most frequently and nonspecifically seen in patients with shock. Metformin-associated lactic acidosis is more specific to diabetes. Lactic acidosis is less frequent in patients with diabetes than other complications that may lead to coma. It develops more often in patients with type 2 diabetes, although advanced microangiopathy (especially in patients with renal failure) can be a risk factor in patients with type 1 diabetes. Mortality rates may be as high as ~50%.
Types of lactic acidosis associated with diabetes:
1) Type A lactic acidosis (anaerobic) develops in the case of tissue hypoxia or hyperperfusion (sepsis, shock, heart failure, respiratory failure).
2) Type B lactic acidosis (aerobic) is caused by factors other than hypoxia. In patients with diabetes, it accompanies severe complications of diabetes (eg, diabetic ketoacidosis [DKA]), renal failure, liver failure, and malignancy. Type B lactic acidosis is also caused by inappropriate use of metformin (contraindications: Table 5 in Diabetes Mellitus) or ingestion of high doses of salicylates, methyl alcohol, ethyl alcohol, or propylene glycol. Malignancy, intense alcohol consumption, and HIV infection have also been associated with this kind of acidosis.
Clinical Features and DiagnosisTop
Symptoms include severe weakness, nausea, vomiting, and abdominal pain. Patients may have a history of ingestion of a toxic substance, alcohol, or treatment with metformin despite contraindications.
Signs include hyperpnea (Kussmaul respiration), altered mental status with hallucinations and coma, moderate dehydration, oliguria, hypothermia, hypotension, and shock.
Diagnosis is based on lactate levels ≥5 mmol/L (4 mEq/L), even in the absence of overt acidemia. Minor hyperglycemia (or sometimes normal glucose levels), serum lactate levels usually >7 mmol/L (increasing with deteriorating renal function), low blood pH <7.35, serum bicarbonate levels <10 mmol/L, anion gap >16 mEq/L, usually hyperkalemia, and normal serum sodium levels (these may be low in patients abusing alcohol) are also typically found.
Differential diagnosis includes DKA (higher levels of glucose and ketone bodies without signs and symptoms of shock, lactate usually not as high), hyperglycemic hyperosmolar state (HHS) (significant hyperosmolality; serum lactate levels and blood pH within reference ranges), alcohol poisoning (no significant decrease in blood pH, normal blood glucose levels, no features of shock, serum lactate levels <5 mmol/L), other types of coma (hepatic, uremic), and other causes of shock.
1. Prevention and treatment of shock:
1) Use fluid resuscitation to increase intravascular volume as in DKA or HHS.
2) In patients with hypotension, intravenous administration of catecholamines may be ineffective (as in other instances of severe acidosis).
2. Improvement of blood oxygenation and treatment of hypoxia: Administer oxygen as required. When necessary, use mechanical ventilation (note that achieving levels of hyperventilation required to mimic spontaneous hyperventilation may be difficult if not impossible).
3. Reduction of hyperglycemia:
1) Administer an insulin infusion as in the treatment of HHS.
2) When blood glucose levels decrease <11.1 mmol/L (200 mg/dL), administer a 5% glucose (dextrose) infusion. Once blood glucose levels have normalized, administer a 10% glucose infusion and continue the insulin infusion.
4. Treatment of acidosis: Administer sodium bicarbonate IV (a controversial intervention, usually done with pH <7.0) (see Nonrespiratory Acidosis).
5. Hemodialysis is sometimes required to remove toxins and lactate.
6. Treatment of the underlying condition.
Observe contraindications to metformin treatment. If in doubt, measure serum lactate levels.