What are the clinical indications of lactic acidosis?

From the Guidelines

Lactic acidosis is clinically indicated by a combination of metabolic acidosis and elevated lactate levels, typically presenting with symptoms such as tachypnea, tachycardia, hypotension, and altered mental status, as seen in patients with severe cases, particularly those associated with metformin use, as reported in a recent study from China, including more than 1200 patients with type 2 diabetes and COVID-19 1.

Clinical Indications

The clinical manifestations of lactic acidosis can be variable and nonspecific, including:

• Fatigue
• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Serum transaminase abnormalities, usually as a result of associated hepatic steatosis

Diagnosis and Treatment

Diagnosis requires arterial blood gas analysis showing metabolic acidosis with an increased anion gap, alongside elevated serum lactate levels. Treatment focuses on addressing the underlying cause while supporting vital functions. In metformin-associated lactic acidosis, hemodialysis may be necessary to remove the drug. Sodium bicarbonate administration remains controversial but may be considered in severe cases with pH below 7.1, as suggested by the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 1.

Prevention and Management

Patients starting NRTI treatment should be made aware of the symptoms of lactic acidemia and asked to report them promptly to their health care provider. A serum venous lactate level should be determined in the case of unexplained symptoms. If the level is abnormal, the measurement should be repeated, and an arterial blood gas measurement should be performed, as recommended by the primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV Medicine Association of the Infectious Diseases Society of America 1.

Key Considerations

• Lactic acidosis can be categorized as Type A, caused by tissue hypoperfusion or hypoxia, or Type B, occurring despite adequate oxygen delivery.
• Early recognition of these clinical indicators is crucial for prompt intervention and improved outcomes.
• The use of sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15 is not recommended, as stated in the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 1.

From the FDA Drug Label

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; metformin plasma levels were generally >5 mcg/mL

The clinical indications of lactic acidosis include:

• Nonspecific symptoms: malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence
• Severe symptoms: hypotension and resistant bradyarrhythmias
• Laboratory findings:
  • Elevated blood lactate concentrations (>5 mmol/L)
  • Anion gap acidosis (without evidence of ketonuria or ketonemia)
  • Increased lactate: pyruvate ratio
  • Metformin plasma levels generally >5 mcg/mL 2 2

From the Research

Clinical Indications of Lactic Acidosis

The clinical indications of lactic acidosis can be identified through various symptoms and laboratory findings. Some of the key indications include:

• High anion gap metabolic acidosis 3, 4
• Elevated serum lactate levels 3, 5, 6
• Presence of underlying conditions such as renal failure, liver disease, or diabetes mellitus 3, 5, 6
• Use of certain medications, including metformin 3, 5
• Symptoms such as malaise, respiratory distress, myalgias, disorientation, abdominal discomfort, and somnolence 3
• Laboratory findings, including leukocytosis, severe renal failure, and high anion gap metabolic acidosis 3

Underlying Causes and Risk Factors

Lactic acidosis can be caused by various underlying conditions, including:

• Metformin-associated lactic acidosis (MALA) 3, 5
• Renal failure 3, 5, 6
• Liver disease 4, 6
• Diabetes mellitus 3, 5, 6
• Sepsis or low-flow states 7
• Use of certain medications, including metformin and diclofenac sodium 3, 5

Diagnosis and Treatment

Diagnosis of lactic acidosis is based on clinical presentation, laboratory findings, and identification of underlying causes. Treatment of lactic acidosis involves:

• Prompt recognition and treatment of underlying causes 4, 6, 7
• Use of bicarbonate-buffered continuous venovenous hemodiafiltration (CWHDF) or other dialysis methods 3, 7
• Administration of intravenous fluids and bicarbonate drips 5
• Avoidance of certain medications, including metformin, in patients with underlying risk factors 3, 5