From the Guidelines
Type B lactic acidosis is a rare and potentially life-threatening metabolic disorder characterized by elevated lactate levels in the absence of tissue hypoxia or hypoperfusion.
Key Characteristics
- It is often associated with certain medications, such as metformin 1, particularly at high doses and prolonged durations, as well as with conditions like diabetes, liver disease, and renal impairment.
- This condition can also be caused by other medications, including nucleoside reverse transcriptase inhibitors (NRTIs) like stavudine and zidovine, typically at therapeutic doses.
Risk Factors
- Renal impairment: Metformin should be avoided in patients with significant renal impairment, as it can increase the risk of lactic acidosis 1.
- Liver disease: Patients with liver disease are also at increased risk of lactic acidosis due to impaired lactic acid clearance 1.
- Hypoxia and sepsis: Patients with hypoxia or sepsis are at increased risk of lactic acidosis due to anaerobic metabolism 1.
Management
- Dose reduction: Metformin dose should be reduced if the estimated glomerular filtration rate (eGFR) is 30-45 mL/min per 1.73 m² 1.
- Discontinuation: Metformin should be discontinued if the eGFR is less than 30 mL/min per 1.73 m² or in clinical situations where there is an increased risk of lactic acidosis 1.
- Monitoring: Lactate concentrations should be measured in fragile patients, and metformin should be withdrawn if increased lactate concentrations are apparent 1.
From the FDA Drug Label
5 WARNINGS AND PRECAUTIONS
- 1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. ... Metformin associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio;
The FDA drug label does not answer the question about Type B lactic acidosis. The label only discusses metformin-associated lactic acidosis in general, without specifying Type B. 2
From the Research
Definition and Classification of Lactic Acidosis
- Lactic acidosis is pathophysiologically classified into type A and type B, with type B being a rare but potentially life-threatening emergency 3.
- Type B lactic acidosis is mainly described in hematological malignancies and is associated with the Warburg effect, where cancer cells switch their glucose metabolism from an oxidative pathway to a glycolytic pathway 3, 4, 5.
Causes and Associations of Type B Lactic Acidosis
- Type B lactic acidosis is often associated with hematological malignancies, such as gastric diffuse large B-cell lymphoma 3, acute lymphoblastic leukemia 4, and chronic lymphocytic leukemia 5.
- It can also be caused by other factors, including thiamine deficiency and liver disease 6.
- The Warburg effect is a key mechanism underlying type B lactic acidosis, where cancer cells exhibit altered glucose metabolism 3, 4, 5.
Clinical Presentation and Treatment of Type B Lactic Acidosis
- Type B lactic acidosis can present with severe lactic acidosis, hypoglycemia, and impaired consciousness 3, 4.
- Prompt recognition and treatment of the underlying malignancy are critical to managing this serious metabolic complication 3, 4, 5.
- Treatment may involve chemotherapy, such as a reduced-dose CHOP regimen 3, and supportive care to manage symptoms and prevent further complications.