From the Guidelines
Lactic acidosis is primarily caused by an imbalance between lactic acid production and clearance in the body, with the most common causes including tissue hypoxia and metabolic disorders, such as those associated with metformin use, as seen in a recent study 1. The most common causes of lactic acidosis include:
- Tissue hypoxia (type A), which occurs when tissues don't receive enough oxygen, leading to anaerobic metabolism and increased lactate production, as seen in shock, severe heart failure, sepsis, and cardiac arrest
- Metabolic disorders (type B), which can result from liver disease, medications like metformin 1, nucleoside reverse transcriptase inhibitors, and propofol, alcoholism, diabetes, malignancies, and certain inborn errors of metabolism Other contributing factors include:
- Seizures
- Excessive exercise
- Thiamine deficiency
- Use of certain medications, such as metformin, especially in patients with significant renal impairment or liver failure 1 Treatment focuses on addressing the underlying cause, such as:
- Improving tissue perfusion in hypoxic states
- Discontinuing offending medications, such as metformin in patients at risk for lactic acidosis 1
- Treating the primary disease In severe cases, sodium bicarbonate may be used to temporarily correct acidosis, though this remains controversial, as suggested by a study on sepsis management 1. Understanding the specific mechanism causing lactic acidosis is crucial for effective management, as treatment approaches differ significantly between hypoxic and non-hypoxic causes. It is essential to note that the use of metformin should be avoided in patients at risk for lactic acidosis, such as those with anaerobic metabolism, impaired metformin clearance, or impaired lactic acid clearance, as recommended in a recent study 1. Additionally, the use of other medications, such as SGLT-2 inhibitors, should be carefully considered in patients with COVID-19, as they may increase the risk of acute metabolic decompensation, including lactic acidosis 1.
From the FDA Drug Label
Metformin hydrochloride, the medicine in metformin hydrochloride tablets, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. You have a higher chance of getting lactic acidosis if you: have kidney problems. have liver problems. have congestive heart failure that requires treatment with medicines drink a lot of alcohol (very often or short-term "binge" drinking). get dehydrated (lose a large amount of body fluids). have certain x-ray tests with injectable dyes or contrast agents. have surgery have a heart attack, severe infection, or stroke. are 80 years of age or older and have not had your kidney function tested.
The causes of lactic acidosis include:
- Kidney problems
- Liver problems
- Congestive heart failure
- Excessive alcohol intake
- Dehydration
- Certain x-ray tests with injectable dyes or contrast agents
- Surgery
- Heart attack, severe infection, or stroke
- Advanced age (80 years or older) with unknown kidney function 2 2
From the Research
Causes of Lactic Acidosis
- Lactic acidosis can be caused by metformin, as seen in metformin-associated lactic acidosis (MALA) 3
- Shock is also a cause of lactic acidosis, with the most recent guidelines recommending against the use of bicarbonate in patients with pH at least 7.15 4
- Sepsis is another cause of lactic acidosis, with increased blood lactate concentration and lactic acidosis being common in patients with severe sepsis or septic shock 5
- Inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis can also lead to lactic acidosis 5
- Hyperchloraemic acidosis can develop as a consequence of resuscitation with 0.9% saline in patients with severe sepsis or septic shock 6
Underlying Mechanisms
- Tissue hypoxia and anaerobic glycolysis can contribute to lactate formation during sepsis 5
- Inadequate oxygen delivery and increased oxygen demand can also contribute to lactic acidosis 7
- Metabolic acidosis can be caused by the underlying pathophysiology of sepsis, such as respiratory failure, shock, and renal failure 6
Treatment Implications
- Effective therapy of lactic acidosis due to shock is to reverse the cause 4
- Continuous renal replacement therapy (CRRT) can be used to treat metformin-associated lactic acidosis (MALA) 3
- The use of sodium bicarbonate in treating lactic acidosis remains controversial, with some studies recommending against its use 4, 7