What are the sequelae of lactic acidosis (elevated lactate levels)?

From the Guidelines

Lactic acidosis can lead to severe and potentially life-threatening sequelae, including organ dysfunction, cardiovascular complications, neurological impairment, and death, if not promptly and effectively treated. The primary consequences of lactic acidosis include a decrease in blood pH, leading to impaired cellular function throughout the body. Cardiovascular effects include hypotension, arrhythmias, and decreased cardiac contractility, which can progress to shock and cardiovascular collapse 1. Neurologically, patients may experience altered mental status, confusion, lethargy, and in severe cases, coma. Respiratory compensation with tachypnea (rapid breathing) occurs as the body attempts to eliminate excess acid through the lungs. Kidney function may deteriorate, and patients can develop acute kidney injury. Metabolic derangements worsen as the acidosis interferes with normal enzyme function and cellular metabolism.

Some of the key factors that contribute to the development of lactic acidosis include:

• Anaerobic metabolism, such as in sepsis or hypoxia
• Impaired metformin clearance, such as in significant renal impairment
• Impaired lactic acid clearance, such as in liver failure
• Medication effects, such as with metformin use in patients with risk factors for lactic acidosis 1

Treatment of lactic acidosis must address the underlying cause, such as sepsis, tissue hypoxia, or medication effects, while supporting vital organ function. Severe cases may require:

• Intravenous bicarbonate therapy, although its use is not universally recommended and should be considered on a case-by-case basis 1
• Dialysis
• Mechanical ventilation, depending on the clinical situation and degree of physiological compromise

It is essential to note that the use of sodium bicarbonate therapy in lactic acidosis is a topic of ongoing debate, and its effectiveness in improving hemodynamics or reducing vasopressor requirements is not well established 1. Therefore, the decision to use sodium bicarbonate therapy should be made on a case-by-case basis, taking into account the individual patient's clinical situation and the potential risks and benefits of treatment.

From the FDA Drug Label

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; Hemodialysis has often resulted in reversal of symptoms and recovery

The sequelae of lactic acidosis include:

• Elevated blood lactate concentrations: Lactic acidosis is characterized by elevated blood lactate concentrations (>5 mmol/L) 2
• Anion gap acidosis: Metformin-associated lactic acidosis is also characterized by anion gap acidosis (without evidence of ketonuria or ketonemia) 2
• Increased lactate: pyruvate ratio: An increased lactate: pyruvate ratio is another characteristic of metformin-associated lactic acidosis 2
• Reversal of symptoms and recovery: Hemodialysis has often resulted in reversal of symptoms and recovery 2
• Fatal cases: There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases 2

From the Research

Sequelae of Lactic Acidosis

The sequelae of lactic acidosis can be severe and potentially life-threatening. Some of the possible outcomes include:

• High mortality rates, with an overall mortality of approximately 50% 3
• Cardiovascular collapse and acute renal failure 4
• Severe metabolic and blood gases derangements 4
• Persistent high levels of blood metformin despite treatment 4
• Cellular injury due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger 5

Treatment Outcomes

The outcomes of treatment for lactic acidosis vary depending on the severity of the condition and the effectiveness of the treatment. Some studies have reported:

• Dramatic improvement with sodium bicarbonate haemodialysis therapy 4
• Rapid correction of acid-base disorders and partial removal of metformin 4
• Improved cardiovascular function and reduced mortality with aggressive treatment strategies, including hemodialysis, peritoneal dialysis, and continuous bicarbonate infusion 3
• High mortality rates despite treatment, with 2 out of 3 patients dying in one study 6

Risk Factors

Certain risk factors can increase the likelihood of developing lactic acidosis, including:

• Diabetes, particularly type 2 diabetes 7
• Metformin use, especially in patients with end-stage renal disease (ESRD) 3, 6
• Acute cardiorespiratory illness, acute renal impairment, and sepsis 7
• Age, with older patients being at higher risk of mortality 7