From the Guidelines
High anion gap metabolic acidosis is primarily caused by conditions that lead to the accumulation of unmeasured anions in the blood, including methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid/iron, lactic acidosis, ethylene glycol, and salicylates, as remembered by the mnemonic MUDPILES 1.
Causes of High Anion Gap Metabolic Acidosis
The causes can be categorized into several groups:
- Toxic ingestions: Methanol and ethylene glycol poisoning can cause high anion gap metabolic acidosis due to the accumulation of toxic metabolites 1.
- Diabetic ketoacidosis: A complication of diabetes characterized by hyperglycemia, metabolic acidosis, and ketosis, which can lead to high anion gap metabolic acidosis 1.
- Lactic acidosis: Elevated lactate levels can contribute to high anion gap metabolic acidosis, often seen in conditions such as sepsis, shock, or intense physical exertion.
- Renal failure: Uremia, a buildup of waste products in the blood due to renal failure, can cause high anion gap metabolic acidosis.
- Other causes: Include propylene glycol, isoniazid/iron, and salicylate toxicity.
Diagnosis and Treatment
Diagnosis involves calculating the anion gap and identifying the underlying cause. Treatment focuses on addressing the underlying cause, providing supportive care, and correcting the acid-base imbalance. For example, in cases of diabetic ketoacidosis, insulin therapy and fluid resuscitation are essential, while in cases of toxic ingestion, fomepizole or ethanol infusion may be required to block toxic metabolite formation 1. Hemodialysis may be indicated for severe poisonings, significant renal failure, or refractory acidosis. Prompt identification and treatment of the specific cause are crucial for resolving the acidosis and preventing complications.
From the FDA Drug Label
Sodium Bicarbonate Injection, USP is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis The causes of high anion gap metabolic acidosis include:
- Severe renal disease
- Uncontrolled diabetes
- Circulatory insufficiency due to shock or severe dehydration
- Cardiac arrest
- Severe primary lactic acidosis 2
From the Research
Causes of High Anion Gap Metabolic Acidosis
The causes of high anion gap metabolic acidosis can be identified through various studies, including:
- Lactic acidosis, ketoacidosis, and renal failure are common causes of high anion gap metabolic acidosis 3, 4, 5, 6
- Intoxication with ethylene glycol, methanol, salicylate, and less commonly with pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean (gjenkolism) can also lead to high anion gap metabolic acidosis 3, 5, 6
- Severe increases in concentration of phosphorus can cause hyperphosphatemic acidosis 4
- Other causes include sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion, and paracetamol intake 6
- Chronic antibiotic treatment with fosfomycin might also play a role in the increased production of 5-oxoproline 6
Identification and Diagnosis
The diagnosis of high anion gap metabolic acidosis often involves:
- Historical and simple laboratory data to establish the cause 5
- Calculation of the anion gap to identify the presence of an increased anion gap 4, 5
- Determination of the primary causative etiology as quickly as possible 7
- Categorization of the metabolic acidosis as hyperchloremic or high-anion-gap type (or a combination of both) 7
Laboratory Findings
Laboratory findings that may indicate high anion gap metabolic acidosis include: