From the Guidelines
To address rising lactic acid levels, focus on improving oxygen delivery to tissues and addressing the underlying cause, as recommended by the Surviving Sepsis Campaign guidelines 1. When lactic acid levels are rising, it is crucial to identify and manage the underlying cause, which could be sepsis, shock, or other conditions leading to tissue hypoperfusion.
- Improving oxygen delivery to tissues can be achieved through various means, including:
- Administering oxygen therapy to increase oxygen saturation
- Using intravenous fluids to improve circulation and blood pressure
- Implementing medications to enhance cardiac function and perfusion
- In patients with sepsis or septic shock, the Surviving Sepsis Campaign guidelines suggest guiding resuscitation to normalize lactate levels as a marker of tissue hypoperfusion 1.
- Additionally, for patients taking metformin, particularly those with diabetes, it is essential to monitor lactate levels and consider temporarily discontinuing the medication if lactic acidosis develops, as suggested by a recent study 1.
- Regular aerobic exercise and proper nutrition with adequate carbohydrates can also help improve the body's ability to clear lactate and maintain energy levels during activity.
- It is also important to note that sodium bicarbonate therapy is not recommended for the treatment of hypoperfusion-induced lactic acidemia with a pH ≥ 7.15, as stated in the Surviving Sepsis Campaign guidelines 1.
From the FDA Drug Label
Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. 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; metformin plasma levels were generally >5 mcg/mL
The lactic acid is trending up due to metformin decreasing liver uptake of lactate, increasing lactate blood levels, and potentially leading to lactic acidosis. This is especially a concern in patients with certain risk factors, such as:
- Renal impairment
- Hepatic impairment
- Age 65 or greater
- Excessive alcohol intake
- Hypoxic states
- Drug interactions
If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin. In some cases, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin 2.
From the Research
Causes of Rising Lactic Acid
- Lactic acidosis can be caused by various factors, including hypoxia, specific pathologies, use of certain drugs, presence of toxins, and trauma 3
- Metformin therapy is associated with an uncommon but potentially serious complication known as metformin-associated lactic acidosis (MALA), which is marked by severe lactic acid accumulation in the bloodstream 4, 5
- Underlying kidney disease or other risk factors can increase the risk of MALA 5
- Lactic acidosis can also be caused by overproduction of lactic acid, such as in cases of tissue hypoxia, or underutilization of lactic acid, such as in cases of liver disease or inhibition of gluconeogenesis 6
Treatment of Rising Lactic Acid
- Prompt recognition and early application of treatment, such as bicarbonate-buffered continuous venovenous hemodiafiltration (CWHDF), can produce successful results in cases of MALA 4
- Aggressive resuscitation with fluids and sodium bicarbonate, as well as antimicrobial drugs for urinary tract infections, can be effective in treating lactic acidosis 5
- High-volume venovenous hemofiltration and aggressive alkalinization therapy can also be used to treat severe lactic acidosis 7
- The ideal treatment is to stop acid production by treating the underlying disorder, rather than just removing lactate or buffering the acidosis 6
Prevention of Rising Lactic Acid
- Early identification and diagnosis of acidotic statuses can prevent poor clinical outcomes, especially in ICU patients who are more fragile compared to the general population 3
- Prevention and early treatment are the keys to controlling the negative clinical consequences of lactic acidosis 3
- Discontinuing metformin and initiating alternative treatments, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors, can be effective in preventing further episodes of MALA 5