What are the next steps for a patient with elevated urine ketones and urine urobilinogen?

Immediate Management of Elevated Urine Ketones and Urobilinogen

Measure blood glucose immediately and assess for diabetic ketoacidosis (DKA), as urine ketones of 10 mg/dL indicate significant ketosis requiring urgent evaluation, while the elevated urobilinogen suggests concurrent hemolysis or liver dysfunction that must be investigated separately. 1, 2

Initial Urgent Assessment

Blood Glucose Measurement

• Check fingerstick or venous blood glucose immediately to differentiate between starvation ketosis (normal glucose) and DKA (glucose typically >250 mg/dL) 1, 2
• Do not delay this test—it is the single most important initial step to determine the urgency of the situation 1

If Blood Glucose >250 mg/dL or Clinical Concern for DKA

• Order blood beta-hydroxybutyrate (β-OHB), venous blood gas, and basic metabolic panel immediately 1, 2
• Calculate anion gap using [Na⁺] - ([Cl⁻] + [HCO₃⁻]) to assess metabolic acidosis severity 2
• DKA is confirmed when all three criteria are met: hyperglycemia (>250 mg/dL), venous pH <7.3, and serum bicarbonate <15 mEq/L 2, 3

Critical Pitfall to Avoid

• Never rely solely on urine ketone dipsticks for diagnosis or monitoring, as they only detect acetoacetate and completely miss β-hydroxybutyrate, which is the predominant ketone body in DKA 4, 2, 5
• Urine ketones can paradoxically increase during DKA treatment as β-hydroxybutyrate converts to acetoacetate, falsely suggesting worsening when the patient is actually improving 2, 5

If Blood Glucose is Normal (<200 mg/dL)

Starvation Ketosis

• Urine ketones in the setting of normal glucose most commonly indicate starvation ketosis from fasting, illness with poor oral intake, or very low carbohydrate intake 4, 6
• Recommend increasing oral fluid and carbohydrate intake 6
• Recheck urine ketones after adequate nutrition; they should clear within 24-48 hours 7

Special Populations at Risk

• Patients on SGLT2 inhibitors can develop euglycemic DKA (glucose <250 mg/dL with ketoacidosis), which is particularly dangerous because the lack of hyperglycemia delays recognition 4, 8, 9
• If the patient takes SGLT2 inhibitors and has nausea, vomiting, or malaise, check blood β-hydroxybutyrate and venous pH immediately 4, 9
• Pregnant women can have physiologic ketonuria (up to 30% of first morning specimens), but must be evaluated for undiagnosed diabetes 6

Addressing Elevated Urobilinogen (3 mg/dL)

Differential Diagnosis

• Elevated urobilinogen suggests hemolysis, liver disease, or increased red blood cell turnover
• Order complete blood count, comprehensive metabolic panel with liver function tests, and peripheral blood smear to evaluate for hemolytic anemia or hepatobiliary disease
• Check total and direct bilirubin, lactate dehydrogenase (LDH), and haptoglobin if hemolysis is suspected

Clinical Context

• The combination of ketones and elevated urobilinogen is unusual and suggests two separate processes occurring simultaneously
• Consider whether the patient has underlying liver disease, hemolytic anemia, or is taking medications that could cause both findings

Red Flags Requiring Emergency Department Evaluation

• Blood glucose >250 mg/dL with ketones requires immediate DKA evaluation 1
• Symptoms of DKA: abdominal pain, nausea, vomiting, altered mental status, or Kussmaul respirations 2, 6
• Patients with type 1 diabetes, history of DKA, or on SGLT2 inhibitors who have unexplained symptoms should be evaluated emergently 4

Monitoring Strategy

For Confirmed DKA

• Measure blood β-hydroxybutyrate every 2-4 hours during treatment alongside glucose, electrolytes, and venous pH 2
• DKA is resolved when glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L 2

For Starvation Ketosis

• Recheck urine ketones after nutritional intervention
• If ketones persist despite adequate carbohydrate intake, reassess for underlying diabetes or other metabolic disorders 4