What are the diagnostic criteria and treatment approach for a patient with suspected diabetic ketoacidosis (DKA)?

Diagnosing Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three criteria are simultaneously present: blood glucose >250 mg/dL (or prior diabetes history), arterial or venous pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia, with β-hydroxybutyrate being the preferred ketone measurement. 1, 2

Core Diagnostic Criteria

All three components must be present simultaneously for DKA diagnosis 2:

• Blood glucose >250 mg/dL - This threshold has been de-emphasized in recent guidelines due to increasing incidence of euglycemic DKA (glucose <200 mg/dL), particularly in patients on SGLT2 inhibitors, pregnant patients, those with reduced food intake, or alcohol use 3, 2, 4
• Venous pH <7.3 - Reflects severity of ketoacidosis; venous pH is acceptable and typically 0.03 units lower than arterial pH 1, 5
• Serum bicarbonate <15 mEq/L - Indicates metabolic acidosis 1, 2
• Moderate ketonuria or ketonemia - Blood β-hydroxybutyrate measurement is the gold standard, not urine ketones 1, 2

Essential Laboratory Workup

Upon presentation with suspected DKA, immediately obtain 3, 1, 2:

• Plasma glucose 3
• Venous or arterial blood gas (pH, pCO2, bicarbonate) 1, 2
• Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine) 3, 2
• Blood β-hydroxybutyrate (preferred over urine ketones) 1, 2
• Calculated anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), should be >10-12 mEq/L in DKA 2, 5
• Serum osmolality 3
• Complete blood count with differential 3
• Urinalysis with urine ketones by dipstick 3
• Electrocardiogram 3
• HbA1c to distinguish acute versus chronic poor control 3, 5

Additional tests if clinically indicated 3, 4:

• Bacterial cultures (blood, urine, throat) if infection suspected 3, 5
• Chest X-ray if respiratory symptoms present 3
• Blood lactate to distinguish lactic acidosis 5
• Amylase, lipase, hepatic transaminases, troponin, creatine kinase as clinically indicated 4

Severity Classification

DKA severity determines monitoring intensity and prognosis 1, 2:

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, anion gap >10, alert mental status 1, 2
• Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, anion gap >12, drowsy/lethargic mental status 1, 2
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, anion gap >12, stuporous or comatose mental status, associated with higher morbidity and mortality 1, 2, 5

Critical Diagnostic Pitfalls to Avoid

Never rely solely on urine ketones for diagnosis or monitoring. The nitroprusside method only measures acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant ketoacid in DKA 2, 5. During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making urine ketone tests appear worse even as the patient improves 2, 5.

Correct serum sodium for hyperglycemia using the formula: measured Na (mEq/L) + [glucose (mg/dL) - 100]/100 × 1.6 3, 5

Recognize euglycemic DKA in patients on SGLT2 inhibitors, pregnant patients, those with reduced food intake, alcohol use, or liver failure—approximately 10% of DKA cases present with glucose <200 mg/dL 3, 2

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis 3, 2:

• Starvation ketosis: Glucose rarely >250 mg/dL, bicarbonate usually not lower than 18 mEq/L 3
• Alcoholic ketoacidosis: Glucose ranges from mildly elevated to hypoglycemia, distinguished by clinical history 3
• Lactic acidosis: Measure blood lactate 2, 5
• Toxic ingestions: Salicylate, methanol, ethylene glycol, paraldehyde 3, 5
• Chronic renal failure: More typically hyperchloremic acidosis 3

Clinical Presentation

Classic symptoms include 2, 4:

• Polyuria, polydipsia, weight loss 4
• Nausea, vomiting, abdominal pain (up to 25% may have coffee-ground emesis from hemorrhagic gastritis) 2, 4
• Weakness, severe fatigue 4
• Kussmaul respirations (deep, rapid breathing) 2
• Fruity breath odor 2, 6
• Altered mental status (drowsiness, confusion, stupor, or coma depending on severity) 2, 6
• Poor skin turgor, tachycardia, hypotension 2

Monitoring During Treatment

Blood should be drawn every 2-4 hours to measure 1, 2, 5:

• Glucose (check every 1-2 hours) 1
• Electrolytes (sodium, potassium, chloride, bicarbonate) 1, 2
• Venous pH and anion gap (arterial blood gases generally unnecessary after initial diagnosis) 2, 5
• Blood β-hydroxybutyrate 2
• BUN, creatinine, serum osmolality 2, 5

Resolution Criteria

DKA is resolved when all of the following are met simultaneously 1, 2, 5:

• Glucose <200 mg/dL 1, 2
• Venous pH >7.3 1, 2
• Serum bicarbonate ≥18 mEq/L 1, 2
• Anion gap ≤12 mEq/L 1, 2

Ketonemia typically takes longer to clear than hyperglycemia, requiring continued insulin therapy even after glucose normalizes 2, 5. Continue monitoring β-hydroxybutyrate until it normalizes (<0.5 mmol/L) 2.

Initial Treatment Approach

Fluid Resuscitation

Begin immediate aggressive fluid resuscitation with isotonic (0.9%) saline at 15-20 mL/kg/hour for the first hour (1-1.5 liters in average adult) to restore circulatory volume and renal perfusion 3, 1, 5. This addresses the typical 6-9 liter total body water deficit 5.

Subsequent fluid choice depends on corrected serum sodium 3:

• If corrected sodium is normal or elevated: Use 0.45% NaCl at 4-14 mL/kg/hour 3
• If corrected sodium is low: Use 0.9% NaCl at similar rate 3
• Target total fluid replacement of approximately 1.5 times the 24-hour maintenance requirements over 24 hours 5

Insulin Therapy

Start continuous IV regular insulin infusion at 0.1 units/kg/hour without an initial bolus 1, 5. If glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until a steady decline of 50-75 mg/dL per hour is achieved 5.

When glucose falls to 200-250 mg/dL, add 5-10% dextrose to IV fluids while continuing insulin infusion to prevent hypoglycemia and allow insulin to clear ketones 1, 5. Both insulin and glucose are needed to resolve ketonuria—insulin alone cannot clear ketones without adequate carbohydrate substrate 5.

Potassium Replacement

DKA causes total body potassium depletion of 3-5 mEq/kg despite normal or elevated initial serum levels 5. Insulin therapy drives potassium intracellularly, causing rapid decline 5.

Potassium replacement algorithm 3, 1, 5:

• If K⁺ <3.3 mEq/L: Delay insulin therapy and aggressively replace potassium first to prevent fatal cardiac arrhythmias 5
• If K⁺ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) once renal function is assured 3, 1, 5
• Target serum potassium 4-5 mEq/L 1, 5

Including phosphate replacement as 1/3 of potassium replacement (KPO4) prevents severe hypophosphatemia 5.

Transition to Subcutaneous Insulin

Administer basal subcutaneous insulin 2-4 hours before stopping IV insulin infusion to prevent rebound hyperglycemia and recurrent ketoacidosis 1, 5. Continue IV insulin for 1-2 hours after administering subcutaneous insulin 1.

Never discontinue IV insulin when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia, and premature insulin cessation causes recurrence 5.

Special Considerations

Bicarbonate therapy is not recommended unless pH <6.9, as it provides no benefit in DKA resolution 5.

Monitor closely for cerebral edema during treatment, especially with overly aggressive fluid resuscitation, particularly in pediatric patients 5.

Identify and treat the underlying precipitating cause (infection, medication nonadherence, new diagnosis of diabetes, SGLT2 inhibitor use) to prevent recurrence 3, 5, 4, 7.