What is the appropriate management for a patient with an elevated anion gap?

Management of Elevated Anion Gap

The initial management for a patient with an elevated anion gap should focus on identifying the underlying cause while simultaneously addressing life-threatening conditions, with immediate hemodialysis recommended for anion gaps >27 mmol/L in cases of suspected ethylene glycol poisoning. 1

Diagnostic Assessment

• Calculate the anion gap using the formula: Na+ + K+ - Cl- - HCO3- to confirm elevation 1
• Determine if the elevated anion gap is associated with metabolic acidosis by checking arterial blood gases 1
• Initial laboratory evaluation should include plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes, osmolality, urinalysis, urine ketones, complete blood count, and electrocardiogram 1
• Consider calculating osmolal gap to help identify toxic alcohol ingestions (methanol, ethylene glycol) 2

Management Algorithm Based on Cause

Toxic Alcohol Ingestion

• If anion gap >27 mmol/L with suspected ethylene glycol exposure, immediately initiate hemodialysis 1
• If anion gap is 23-27 mmol/L with suspected ethylene glycol exposure, consider hemodialysis 1
• Administer fomepizole to block metabolism of ethylene glycol to toxic metabolites 1
  • Loading dose of 15 mg/kg followed by 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter 3
  • Continue until ethylene glycol or methanol concentrations are undetectable or <20 mg/dL 3
  • During hemodialysis, increase dosing frequency to every 4 hours 3

Diabetic Ketoacidosis

• Begin fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour 1
• Initiate insulin therapy to suppress ketogenesis 1
• Monitor electrolytes, particularly potassium, and replace as needed 1
• Monitor for resolution of ketoacidosis, with insulin requirements typically decreasing around 18 hours after treatment initiation 1

Lactic Acidosis

• Address the underlying cause (shock, sepsis, tissue hypoxia) to improve tissue perfusion and oxygen delivery 1
• The use of bicarbonate to increase pH is controversial and may worsen outcomes by generating CO2 4

Uremic Acidosis

• Manage the underlying renal failure 1
• Consider renal replacement therapy for severe cases 1

Special Considerations and Pitfalls

• Don't rely solely on anion gap without clinical context; it has poor predictive value if used indiscriminately 1
• Be aware that certain medications and conditions can falsely alter the anion gap (e.g., lithium, barium, hyperphosphatemia) 1
• The anion gap may overestimate (e.g., with concomitant AKI or ketoacidosis) or underestimate (e.g., with hypoalbuminemia) the severity of acidosis 1
• Remember that an elevated glycolate concentration can falsely elevate plasma lactate on some analyzers 1
• In pregnancy, consider lower thresholds for extracorporeal treatment in toxic alcohol ingestions 1
• Not all patients with ketoacidosis have DKA; starvation ketosis and alcoholic ketoacidosis are distinguished by clinical history and plasma glucose concentrations that are mildly elevated or hypoglycemic 1
• Significant elevations in anion gap (>24 mmol/L) almost always signify presence of an acidosis that can be easily identified 5
• Patients can be normothermic or even hypothermic despite infection as a precipitating factor 1

Differential Diagnosis of High Anion Gap Metabolic Acidosis

• Lactic acidosis (tissue hypoxia, decreased oxygen delivery) 4
• Ketoacidosis (diabetic, alcoholic, starvation) 4
• Toxin/drug-induced (methanol, ethylene glycol, salicylates) 4
• Uremic acidosis (chronic kidney disease) 4
• 5-oxoproline acidosis (chronic acetaminophen ingestion) 6
• Severe hyperphosphatemia 7