From the Guidelines
Metabolic acidosis is caused by an excess of acid or a loss of bicarbonate in the body, resulting in a decreased blood pH and low bicarbonate levels, with the main causes including diabetic ketoacidosis, lactic acidosis, renal tubular acidosis, poisoning, and certain medications, as supported by the most recent evidence from 1. The main causes of metabolic acidosis include:
- Diabetic ketoacidosis, where insulin deficiency leads to fat breakdown and ketone production
- Lactic acidosis from tissue hypoxia during shock, sepsis, or severe exercise
- Renal tubular acidosis due to kidney dysfunction in excreting acid
- Poisoning from substances like methanol, ethylene glycol, or salicylates
- Severe diarrhea causing bicarbonate loss
- Certain medications such as metformin, acetazolamide, and some HIV drugs Other causes include starvation, alcoholic ketoacidosis, and rhabdomyolysis. The body attempts to compensate through increased respiratory rate to eliminate carbon dioxide. Treatment depends on identifying and addressing the underlying cause, with severe cases requiring intravenous sodium bicarbonate, as recommended by 1. Metabolic acidosis is diagnosed through arterial blood gas analysis showing low pH and bicarbonate levels, along with an elevated anion gap in certain types. It is essential to monitor treatment for metabolic acidosis to ensure it does not result in serum bicarbonate concentrations exceeding the upper limit of normal and does not adversely affect BP control, serum potassium, or fluid status, as stated in 1. In people with CKD, consider use of pharmacological treatment with or without dietary intervention to prevent development of acidosis with potential clinical implications, such as bicarbonate <18 mmol/l in adults, as recommended by 1. The goal of treatment should be to increase bicarbonate levels toward but not greater than the normal range with sodium bicarbonate or other agents, as suggested by 1.
From the FDA Drug Label
For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal impairment — The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney.
- Metformin can cause metabolic acidosis, specifically lactic acidosis, particularly in patients with significant renal impairment or other risk factors such as hepatic impairment, age 65 or greater, or hypoxic states 2.
- The risk of lactic acidosis increases with the severity of renal impairment and may be exacerbated by certain drug interactions or medical procedures.
From the Research
Causes of Metabolic Acidosis
- Metabolic acidosis can be caused by the overproduction of organic acids such as ketoacids or lactic acid, which is often seen in acute forms of the disorder 3
- Chronic metabolic acidosis can result from bicarbonate wasting and/or impaired renal acidification 3
- Diabetic ketoacidosis (DKA) is a common cause of metabolic acidosis, characterized by hyperglycemia, ketosis, and anion gap metabolic acidosis 4, 5
- Acid-base homeostasis is impaired in chronic kidney disease (CKD) and may contribute to disease progression, with diabetes exacerbating acidosis further due to differences in acid production and excretion 6
Specific Causes
- Ketoacids and lactic acid overproduction can lead to acute metabolic acidosis 3
- Bicarbonate wasting and impaired renal acidification can cause chronic metabolic acidosis 3
- Diabetic ketoacidosis (DKA) can cause metabolic acidosis, especially in patients with type 1 and type 2 diabetes 4, 5
- Impaired acid-base homeostasis in chronic kidney disease (CKD) can contribute to metabolic acidosis, especially in patients with diabetes 6