What are the next steps for a patient with a urinalysis showing large ketones and moderate bilirubin?

Immediate Evaluation and Management of Large Ketones with Moderate Bilirubin on Urinalysis

The first priority is to determine if this patient has diabetes or is on SGLT2 inhibitors, as large ketones in these populations signal potential diabetic ketoacidosis (DKA)—a life-threatening emergency requiring immediate blood glucose, serum beta-hydroxybutyrate, electrolytes, and arterial blood gas. 1, 2

Critical Initial Assessment

Immediate Laboratory Testing Required

• Check blood glucose immediately - if >250 mg/dL in a diabetic patient, this constitutes a medical emergency 1, 3
• Obtain serum beta-hydroxybutyrate (NOT urine ketones) - urine dipsticks only detect acetoacetate and significantly underestimate total ketone body concentration, potentially missing up to 50% of ketone bodies 1, 2, 3
• Draw electrolytes and arterial blood gas to assess for metabolic acidosis (bicarbonate <18 mEq/L suggests DKA rather than starvation ketosis) 3
• Measure serum bilirubin and liver function tests to evaluate the moderate bilirubin finding 4

Key Clinical Context to Establish Immediately

Diabetes-related questions: 1, 2

• Does the patient have type 1 diabetes, type 2 diabetes, or history of DKA?
• Is the patient taking SGLT2 inhibitors (which increase DKA risk even with normal glucose)?
• Has the patient been taking their insulin as prescribed?

Starvation/illness questions: 2, 3

• Has the patient had reduced oral intake due to illness, nausea, or vomiting?
• Is there fever or signs of infection (the most common DKA precipitant in 50% of cases)?
• Has the patient been following a ketogenic diet?

Liver-related questions: 4

• Is there jaundice, dark urine, or pale stools?
• Any history of liver disease, alcohol use, or hepatotoxic medications?

Distinguishing DKA from Starvation Ketosis

DKA Characteristics (Medical Emergency): 3

• Blood ketones >7-8 mmol/L
• Serum bicarbonate typically <18 mEq/L with low pH
• Hyperglycemia usually present (though euglycemic DKA can occur with SGLT2 inhibitors)
• Symptoms: abdominal pain, nausea, vomiting, fruity breath odor, altered mental status 1

Starvation Ketosis Characteristics (Usually Benign): 2, 3

• Blood ketones 0.3-4 mmol/L
• Serum bicarbonate usually ≥18 mEq/L with normal pH
• Blood glucose normal to mildly elevated
• History of decreased caloric intake during illness

Management Algorithm

If Patient Has Diabetes or Takes SGLT2 Inhibitors:

1. Assume DKA until proven otherwise - this is a life-threatening condition requiring immediate medical care 1
2. Hospitalize if: ketosis with vomiting, altered mental status, or marked hyperglycemia 1
3. Immediate treatment: IV fluids, insulin therapy, electrolyte replacement under physician supervision 1
4. A physician with expertise in diabetes management should direct care 1

If Patient Does NOT Have Diabetes:

1. Encourage oral hydration and carbohydrate intake to suppress ketone production 3
2. Investigate the bilirubin finding with liver function tests and imaging of biliary tree if elevated serum bilirubin confirmed 4
3. Consider alternative causes: alcoholic ketosis (especially with history of recent alcohol use and hypoglycemia), starvation from eating disorder, or metabolic disorders 5

Critical Pitfalls to Avoid

• Never rely solely on urine ketone testing for clinical decisions - blood beta-hydroxybutyrate is the gold standard and urine dipsticks miss the predominant ketone body in DKA 1, 2, 3
• Do not dismiss ketones as "just starvation" in diabetic patients - even trace ketones with fever warrant closer monitoring as infection precipitates 50% of DKA cases 3
• False-positive urine ketones can occur with sulfhydryl drugs like captopril 2
• Up to 30% of healthy individuals can have positive ketones on first morning urine, but "large" ketones are never normal and require investigation 2

Addressing the Bilirubin Finding

• Moderate bilirubin on urinalysis indicates conjugated hyperbilirubinemia (unconjugated bilirubin does not appear in urine) 4, 6
• Requires imaging assessment of the biliary tree and liver with ultrasound or CT 4
• Consider hepatobiliary causes: cholestasis, hepatitis, biliary obstruction, or drug-induced liver injury 4
• In alcoholic patients with ketosis, elevated bilirubin may indicate ketohepatitis with AST >200 IU/L being a significant association 5