What is the cause of high anion gap metabolic acidosis resulting from nausea, vomiting, and diarrhea?

From the Guidelines

High anion gap metabolic acidosis typically does not result directly from nausea, vomiting, and diarrhea, but rather from complications such as dehydration leading to lactic acidosis or starvation ketoacidosis. These gastrointestinal symptoms usually cause normal anion gap metabolic acidosis due to bicarbonate loss, as seen in patients with hypokalemia, which is often the result of diuresis, administration of potassium-free intravenous fluids, potassium loss from vomiting and diarrhea, and other endocrine and renal mechanisms 1. However, severe vomiting and diarrhea can lead to dehydration, which may progress to lactic acidosis (a high anion gap condition) if tissue perfusion becomes compromised. In cases of prolonged vomiting, starvation ketoacidosis can develop as the body shifts to ketone metabolism, also causing a high anion gap. Management includes:

• Aggressive fluid resuscitation with isotonic crystalloids like normal saline at 10-20 mL/kg/hr initially,
• Followed by maintenance fluids with added potassium as needed,
• Sodium bicarbonate therapy (1-2 mEq/kg IV) may be considered for severe acidosis (pH < 7.1), though it's controversial. Addressing the underlying cause is essential -
• Antiemetics like ondansetron 4-8 mg IV/PO for vomiting and
• Antidiarrheals like loperamide 4 mg initially then 2 mg after each loose stool for diarrhea. Electrolyte replacement, particularly potassium, should be guided by laboratory values, considering the patient's potassium level, as hypokalemia has been defined as K<3.5 mEq/L 1. The distinction between high and normal anion gap acidosis is important because it directs the search for underlying causes and influences treatment approaches, and other causes of high-anion gap metabolic acidosis, such as lactic acidosis, ingestion of drugs, and chronic renal failure, should be ruled out 1.

From the Research

Causes of High Anion Gap Metabolic Acidosis

• High anion gap metabolic acidosis (HAGMA) can result from various causes, including ketoacidosis, lactic acidosis, renal failure, and certain toxic ingestions 2.
• Nausea, vomiting, and diarrhea can contribute to the development of HAGMA, as they can lead to dehydration, electrolyte imbalances, and the accumulation of organic acids 2.
• Other possible causes of HAGMA include sepsis, malnutrition, and drug toxicity, such as acetaminophen 3.

Diagnosis and Classification

• The calculation of the serum anion gap, calculated as [Na(+)] - ([HCO(3)(-)] + [Cl(-)]), aids in the diagnosis and classification of metabolic acidosis into categories of normal (hyperchloremic) anion gap or elevated anion gap 4, 5.
• The anion gap can provide vital clues that direct the clinician toward the correct diagnosis, and its calculation can be corrected for hypoalbuminemia and severe hyperglycemia 5.

Clinical Presentation and Management

• HAGMA can present with nausea, vomiting, and changes in mental status, as well as other specific hallmarks in signs, symptoms, and laboratory findings that help to differentiate among possible causes 2.
• The therapeutic approach to HAGMA should be aimed at early correction of concurrent clinical problems, such as fluids and hemodynamic optimization, mechanical ventilation, and hemodialysis, in parallel to the formulation of a diagnosis 6.
• The administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need for renal replacement therapy 6, 4.