What is the workup for an increased anion gap and decreased bicarbonate level, indicative of metabolic acidosis?

From the Guidelines

The workup for increased anion gap and decreased bicarbonate should focus on identifying the underlying cause of metabolic acidosis, with a comprehensive history and physical examination, followed by laboratory tests including complete blood count, comprehensive metabolic panel, urinalysis, and arterial blood gas analysis, as recommended by recent studies 1. The initial step in evaluating a patient with increased anion gap and decreased bicarbonate is to calculate the anion gap (sodium minus the sum of chloride and bicarbonate) to confirm the increased gap.

• Additional targeted tests should include serum lactate, ketones (blood and urine), toxicology screening, salicylate and acetaminophen levels, and assessment of renal function with BUN and creatinine.
• For suspected diabetic ketoacidosis, check blood glucose and hemoglobin A1c.
• If alcohol-related acidosis is suspected, measure serum osmolality and calculate the osmolar gap.
• Imaging studies such as chest X-ray or abdominal CT may be indicated based on clinical presentation. This systematic approach helps identify common causes of high anion gap metabolic acidosis including diabetic ketoacidosis, lactic acidosis, toxic ingestions (methanol, ethylene glycol, salicylates), renal failure, or alcoholic ketoacidosis, as reported in recent studies 1. Prompt identification of the underlying cause is essential for appropriate management, as treatment must address both the acidosis and its primary etiology, with recent studies suggesting that an anion gap > 27 mmol/L is an indication for extracorporeal treatment in patients with ethylene glycol poisoning 1.

From the Research

Workup for Increased Anion Gap and Decreased Bicarbonate

• The serum anion gap is calculated as [Na+] - ([Cl-] + [HCO3-]) = Unmeasured anions - Unmeasured cations, with a normal range of 8-12 meq/l 2.
• An increased anion gap indicates the presence of unmeasured anions, which can be due to various causes such as lactic acidosis, ketoacidosis, or toxic ingestions 3.
• The ratio of Δ anion gap to Δ bicarbonate can help identify coexisting acid-base processes, with a ratio of 1 suggesting a simple anion gap acidosis, <1 indicating a superimposed non-gap acidosis, and >1 indicating a superimposed metabolic alkalosis 2.
• Calculating the osmolar gap can also help narrow the differential diagnosis, particularly in cases of toxic alcohol ingestions such as ethylene glycol and methanol 2, 3.
• Laboratory tests such as measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones can help differentiate between various causes of increased anion gap and decreased bicarbonate, including diabetic ketoacidosis 4.
• The serum anion gap can also be used to detect other disorders such as multiple myeloma, bromide intoxication, and lithium intoxication, and to assess quality control in the chemical laboratory 5.
• It is essential to consider additional information, such as the patient's clinical presentation and laboratory results, to obtain an accurate diagnosis 5.