From the Guidelines
Lactic acidosis is a life-threatening medical condition characterized by the buildup of lactic acid in the bloodstream, leading to abnormally low blood pH (acidosis), which can occur due to various causes, including metformin use, especially in patients with impaired kidney function, as evidenced by a recent study 1.
Causes and Risk Factors
Lactic acidosis can be caused by various factors, including:
- Medications like metformin, especially in patients with impaired kidney function 1
- Liver disease or certain metabolic disorders
- States of decreased oxygen delivery to tissues or impaired metabolism, such as shock, severe infection, or cardiac arrest
- Impaired metformin clearance, significant renal impairment, or impaired lactic acid clearance, such as liver failure 1
Symptoms and Diagnosis
Symptoms of lactic acidosis include:
- Rapid breathing
- Confusion
- Fatigue
- Nausea
- In severe cases, hypotension and organ failure The condition is diagnosed through arterial blood gas analysis showing metabolic acidosis with elevated lactate levels (typically above 4 mmol/L) 1.
Treatment and Management
Treatment focuses on addressing the underlying cause, which might involve:
- Fluid resuscitation
- Oxygen therapy
- Discontinuation of offending medications, such as metformin
- In critical cases, bicarbonate administration or dialysis Prompt recognition and treatment are essential, as severe lactic acidosis can be life-threatening with mortality rates increasing significantly when lactate levels exceed 10 mmol/L, highlighting the importance of careful monitoring and management of patients at risk, particularly those with impaired kidney function or taking metformin 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. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis 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;
Lactic acidosis is a condition characterized by:
- Elevated blood lactate concentrations (>5 mmol/L)
- Anion gap acidosis (without evidence of ketonuria or ketonemia)
- Increased lactate: pyruvate ratio It may be caused by metformin and is associated with nonspecific symptoms such as:
- Malaise
- Myalgias
- Abdominal pain
- Respiratory distress
- Increased somnolence In severe cases, it can lead to hypotension and resistant bradyarrhythmias 2
From the Research
Definition of Lactic Acidosis
- Lactic acidosis is a metabolic disorder characterized by the accumulation of lactate in the body, leading to a decrease in blood pH [(3,4,5,6,7)].
- It can be caused by various factors, including metformin ingestion, acute kidney injury, and severe volume depletion [(3,4,5,6)].
Metformin-Associated Lactic Acidosis (MALA)
- MALA is a rare but potentially life-threatening condition that can occur in patients taking metformin, especially in those with pre-existing renal disease or acute kidney injury [(3,4,5,6,7)].
- The risk of MALA is increased in patients with type 2 diabetes who are taking metformin and have impaired renal function or are using renin-angiotensin system blockers 5.
Treatment of Lactic Acidosis
- Hemodialysis is a recommended treatment for severe lactic acidosis, particularly in patients with MALA [(3,4,5,6,7)].
- Prolonged hemodialysis may be necessary to improve outcomes in patients with MALA [(3,4,5)].
- Sodium bicarbonate therapy and continuous renal replacement therapy may also be effective in treating lactic acidosis [(4,7)].
Prognosis and Outcomes
- The mortality rate for MALA is high, but prompt recognition and treatment can improve outcomes [(3,4,5)].
- Patients who receive early and aggressive treatment, including hemodialysis, may recover fully from lactic acidosis [(3,4,5,7)].