What are the symptoms and management of euglycemic acidosis?

Symptoms of Euglycemic Diabetic Ketoacidosis

Euglycemic diabetic ketoacidosis presents with nausea, vomiting, malaise, fatigue, abdominal pain, dyspnea, and altered mental status, despite blood glucose levels below 250 mg/dL, making it a diagnostic challenge that requires high clinical suspicion. 1, 2, 3

Clinical Presentation

The symptom profile of euglycemic acidosis differs from classic DKA primarily in the absence of marked hyperglycemia, which often delays recognition:

Primary Symptoms

• Gastrointestinal manifestations: Nausea and vomiting are the most common presenting complaints 2, 3
• Constitutional symptoms: Malaise, fatigue, and generalized weakness 2, 3
• Respiratory symptoms: Dyspnea and Kussmaul respirations (deep, labored breathing pattern) may occur as the body attempts to compensate for metabolic acidosis 1
• Abdominal pain: Often present and can mimic acute abdominal pathology 1
• Altered mental status: Ranging from confusion to obtundation, though typically less severe than in hyperglycemic DKA 1

Key Distinguishing Features

The hallmark of euglycemic DKA is the presence of severe metabolic acidosis with blood glucose levels less than 200-250 mg/dL, which contrasts sharply with classic DKA where glucose typically exceeds 250 mg/dL 4, 3. This relative euglycemia creates a dangerous diagnostic pitfall, as clinicians may not consider DKA in the differential diagnosis when glucose levels appear only mildly elevated or near-normal.

Laboratory Findings

When euglycemic acidosis is suspected, specific laboratory abnormalities confirm the diagnosis:

• Venous pH: Typically <7.3, often severely depressed (pH 6.95-7.30 range reported) 2
• Serum bicarbonate: Markedly reduced, often <15 mEq/L 2
• Anion gap: Elevated, typically >20 mEq/L 2, 3
• Serum beta-hydroxybutyrate: Significantly elevated (>3 mmol/L, often >9 mmol/L) 2
• Urine ketones: Strongly positive 2
• Blood glucose: 176-250 mg/dL range, distinctly lower than classic DKA 2, 4

High-Risk Populations and Precipitating Factors

SGLT2 Inhibitor Use

The FDA issued a specific warning about euglycemic DKA occurring in patients treated with SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), as these medications promote urinary glucose excretion independent of insulin, maintaining lower blood glucose while ketoacidosis develops 1. Patients should discontinue SGLT2 inhibitors 3-4 days before elective surgery to prevent this complication 1, 5.

Other Precipitating Conditions

• Reduced caloric intake or starvation states 4, 3
• Pregnancy, particularly in the second and third trimesters 4
• Heavy alcohol consumption 4, 3
• Acute infections or sepsis 4
• Pancreatitis 4
• Chronic liver disease and cirrhosis 4
• Cocaine abuse 4
• Recent insulin use prior to presentation (may lower glucose while acidosis persists) 4

Critical Clinical Pitfalls

Emergency physicians must maintain high suspicion for euglycemic DKA in any patient taking SGLT2 inhibitors who presents with unexplained anion gap metabolic acidosis, even with normal or near-normal glucose levels 2, 3. The absence of significant hyperglycemia does not exclude DKA and can lead to dangerous delays in treatment initiation.

Dehydration may be less pronounced than in classic DKA, as the osmotic diuresis from hyperglycemia is reduced, but patients still require aggressive fluid resuscitation 4, 3.

Management Principles

Immediate Treatment

• Intravenous fluid resuscitation: Begin with balanced electrolyte solutions at 15-20 mL/kg/h during the first hour 6, 5
• Insulin infusion: Start at 0.1 U/kg/h after confirming potassium >3.3 mEq/L 6, 5
• Early dextrose administration: Unlike classic DKA, patients with euglycemic acidosis require higher concentrations of dextrose (10-20%) infused concurrently with insulin to provide substrate while clearing ketones 4, 7

Monitoring Requirements

• Blood glucose every 1-2 hours until stable 6
• Electrolytes, venous pH, and anion gap every 2-4 hours 5
• Potassium replacement when levels fall below 5.5 mEq/L (20-40 mEq/L in infusion fluids) 5
• Continuous cardiac monitoring in severe cases (pH <7.0) to detect arrhythmias from electrolyte shifts 8

Refractory Acidosis Management

When acidosis proves resistant to conventional therapy despite adequate fluid resuscitation and insulin, consider high-calorie glucose infusion (10-20% dextrose) with tight glycemic control 7. In cases complicated by acute kidney injury or severe lactic acidosis (particularly with concurrent metformin use), early hemodialysis may be necessary for rapid correction of life-threatening acidemia 9.

Resolution Criteria

Treatment continues until glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 5. The median time to resolution is approximately 24 hours, though this may be prolonged in euglycemic cases 2.