What does the presence of trace urine ketones and negative urine glucose indicate in a patient with fever?

Trace Urine Ketones with Negative Glucose in a Febrile Patient

In a patient with fever, trace urine ketones with negative urine glucose most likely indicates physiological ketosis from decreased oral intake during illness, rather than diabetic ketoacidosis, and requires clinical context to determine if intervention is needed. 1, 2

Primary Interpretation

The combination of trace ketones with negative glucose suggests:

• Starvation ketosis from reduced caloric intake during febrile illness - This is the most common scenario when patients feel unwell and eat less, causing the body to shift to fat metabolism for energy 2
• Normal physiological response to illness - Up to 30% of first morning urine specimens can show positive ketones even in healthy individuals, and this increases during fasting states 1, 2
• The negative glucose effectively rules out diabetic ketoacidosis (DKA) - DKA requires hyperglycemia (typically >250 mg/dL) as part of the diagnostic triad, though rare euglycemic DKA exists 3, 4, 5

Critical Distinction: Starvation vs. Pathological Ketosis

Starvation ketosis characteristics:

• Serum bicarbonate usually not lower than 18 mEq/L (mild acidosis only) 6, 2
• Blood glucose normal to mildly elevated, rarely >250 mg/dL 6, 2
• Ketone bodies range 0.3-4 mmol/L with normal pH 7
• Resolves with carbohydrate intake and hydration 1

Pathological ketosis (DKA) characteristics:

• Very high ketone bodies (>7-8 mmol/L) 7
• Low systemic pH with absent or severely deficient insulin 7
• Hyperglycemia typically present (though euglycemic DKA is rare) 4

Clinical Context Matters

In diabetic patients with fever:

• Infection is the most common precipitating factor for DKA, occurring in approximately 50% of cases 6, 8
• Even trace ketones warrant closer monitoring in type 1 diabetes during acute illness 1
• Check blood glucose immediately - if elevated, measure blood beta-hydroxybutyrate for accurate ketone assessment 1, 7
• Patients can be normothermic or even hypothermic in DKA despite infection; hypothermia is a poor prognostic sign 6

In non-diabetic patients with fever:

• Trace ketones are likely benign, representing decreased oral intake during illness 1, 2
• No specific intervention needed beyond treating the underlying infection and ensuring adequate hydration 2

Management Algorithm

For patients WITH diabetes:

1. Measure blood glucose immediately 1
2. If glucose >250 mg/dL: obtain blood beta-hydroxybutyrate, electrolytes, and arterial blood gas to evaluate for DKA 6, 3
3. If glucose normal but ketones present: increase oral fluid intake, monitor glucose and ketones every 3-4 hours, consider additional rapid-acting insulin if ketones increase 1
4. Consume carbohydrates along with insulin to suppress ketone production 1

For patients WITHOUT diabetes:

1. Encourage oral hydration and carbohydrate intake 2
2. Treat underlying infection causing fever 6, 8
3. No further ketone monitoring typically needed unless symptoms worsen 1

Important Caveats

Limitations of urine ketone testing:

• Urine dipsticks only detect acetoacetate, NOT beta-hydroxybutyrate (the predominant ketone in DKA) 1, 7, 9
• This can significantly underestimate total ketone body concentration 7, 2
• False-positives occur with highly colored urine or sulfhydryl drugs like captopril 1, 7
• False-negatives occur with prolonged air exposure of test strips or highly acidic urine 1, 7

Blood ketone testing is strongly preferred over urine testing for any patient where clinical decision-making depends on ketone levels, as it directly measures beta-hydroxybutyrate and provides quantitative results 1, 7, 9

Red Flags Requiring Immediate Evaluation

• Abdominal pain (could indicate DKA or be the precipitating cause) 6
• Persistent vomiting or inability to maintain hydration 5
• Dyspnea or altered mental status 5
• Any diabetic patient with ketones and symptoms of DKA regardless of glucose level (consider euglycemic DKA) 4