What are the updated diagnostic criteria for diabetic ketoacidosis, including glucose, pH, bicarbonate, anion‑gap, and ketone thresholds, and what is the recommended initial management?

Updated Diagnostic Criteria for Diabetic Ketoacidosis

The American Diabetes Association defines DKA by requiring all three components simultaneously: blood glucose >250 mg/dL, venous pH <7.3, and serum bicarbonate <15 mEq/L, with elevated blood ketones (preferably β-hydroxybutyrate). 1

However, the traditional glucose threshold has been de-emphasized in recent guidelines due to the increasing recognition of euglycemic DKA, particularly in patients on SGLT-2 inhibitors. 2, 3

Core Diagnostic Parameters

Glucose Threshold

• Blood glucose >250 mg/dL remains the classic criterion, though euglycemic DKA (glucose <250 mg/dL or even <200 mg/dL) is increasingly recognized, especially with SGLT-2 inhibitor use, starvation, pregnancy, chronic liver disease, or alcohol use. 1, 4, 2
• The glucose threshold should not be used as an absolute rule-out criterion; clinicians must maintain high suspicion for DKA even with normal or near-normal glucose levels. 2, 3

pH and Acid-Base Status

• Venous pH <7.3 is required for diagnosis and reflects the severity of ketoacidosis. 1, 5
• Venous pH is preferred over arterial pH for monitoring after initial diagnosis, as it adequately tracks acidosis resolution and avoids repeated arterial punctures. 5
• The venous pH is typically 0.03 units lower than arterial pH. 5

Bicarbonate Level

• Serum bicarbonate <15 mEq/L indicates metabolic acidosis and is a required diagnostic criterion. 1, 5
• For DKA resolution, bicarbonate must rise to ≥18 mEq/L. 1, 5

Anion Gap

• Calculate anion gap as [Na⁺] - ([Cl⁻] + [HCO₃⁻]), which should be >10-12 mEq/L in DKA. 1, 5
• The anion gap helps distinguish DKA from other causes of metabolic acidosis and should be monitored every 2-4 hours during treatment. 1, 5
• For DKA resolution, anion gap must normalize to ≤12 mEq/L. 1

Ketone Measurement

• Direct blood β-hydroxybutyrate measurement is the gold standard for both diagnosis and monitoring, not urine ketones or nitroprusside-based tests. 1, 5
• β-hydroxybutyrate is the predominant and strongest ketoacid in DKA; nitroprusside tests only detect acetoacetate and acetone, missing the majority of the ketone burden. 1, 5
• Normal fasting ketone levels are <0.5 mmol/L; DKA resolution requires β-hydroxybutyrate to fall below this threshold. 5
• Critical pitfall: Urine ketones lag behind serum ketone clearance and may paradoxically worsen during treatment as β-hydroxybutyrate converts to acetoacetate, falsely suggesting treatment failure. 1, 5

Severity Classification

The American Diabetes Association stratifies DKA severity to guide monitoring intensity and predict prognosis: 1, 5

Mild DKA

• Venous pH 7.25-7.30
• Bicarbonate 15-18 mEq/L
• Anion gap >10 mEq/L
• Alert mental status 1, 5

Moderate DKA

• Venous pH 7.00-7.24
• Bicarbonate 10-15 mEq/L
• Anion gap >12 mEq/L
• Drowsy or lethargic mental status 1, 5

Severe DKA

• Venous pH <7.00
• Bicarbonate <10 mEq/L
• Anion gap >12 mEq/L
• Stuporous or comatose mental status
• Associated with higher morbidity and mortality; often requires intensive monitoring including central venous and intra-arterial pressure monitoring 1, 5

Essential Laboratory Workup

Immediate Initial Tests

• Complete metabolic panel: sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose 1
• Venous blood gas: pH, pCO₂, bicarbonate 1
• Serum β-hydroxybutyrate (not urine ketones) 1, 5
• Complete blood count with differential 1, 5
• Urinalysis 1, 5
• Serum osmolality 1, 5
• Electrocardiogram to assess for cardiac effects of electrolyte abnormalities 6, 1
• HbA1c to distinguish acute versus chronic poor glycemic control 5

Corrected Sodium Calculation

• Add 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL to the measured sodium value to calculate corrected serum sodium. 6, 5
• This correction guides subsequent fluid selection during treatment. 6, 5

Additional Tests When Indicated

• Bacterial cultures (urine, blood, throat) if infection is suspected 6, 5
• Chest X-ray if clinically indicated 6
• Blood lactate to distinguish lactic acidosis from DKA 5
• Amylase, lipase, hepatic transaminases, troponin, creatine kinase to identify complications 2
• Toxicology screen if toxic ingestion (salicylate, methanol, ethylene glycol) is suspected 1, 5

Differential Diagnosis Considerations

DKA must be distinguished from other causes of high anion gap metabolic acidosis: 1, 5

• Lactic acidosis: measure blood lactate 1, 5
• Toxic ingestions: salicylate, methanol, ethylene glycol—obtain specific toxicology tests 1, 5
• Chronic renal failure: check BUN and creatinine 1, 5
• Alcoholic ketoacidosis: clinical history, typically lower glucose levels 5
• Starvation ketosis: clinical history, less severe acidosis, lower bicarbonate 1, 5

Monitoring During Treatment

• Check blood glucose, serum electrolytes (especially potassium), venous pH, bicarbonate, anion gap, BUN, creatinine, and osmolality every 2-4 hours until metabolically stable. 6, 1, 5
• Monitor β-hydroxybutyrate every 2-4 hours during treatment, as ketonemia typically takes longer to clear than hyperglycemia. 1, 5
• Serum potassium must be checked before initiating insulin and monitored every 2-4 hours, as insulin drives potassium intracellularly and can precipitate life-threatening hypokalemia. 6, 5

Resolution Criteria

DKA is resolved only when ALL of the following are met simultaneously: 1, 5

• Glucose <200 mg/dL
• Venous pH >7.3
• Serum bicarbonate ≥18 mEq/L
• Anion gap ≤12 mEq/L
• β-hydroxybutyrate <0.5-1.0 mmol/L 5

Critical pitfall: Do not discontinue insulin therapy prematurely before complete resolution of ketoacidosis, even if glucose normalizes, as this is the most common cause of recurrent DKA. 1, 5

Initial Management Recommendations

Fluid Resuscitation

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour (approximately 1-1.5 L in an average adult) to restore intravascular volume. 6, 5
• Total body water deficit is typically 6-9 liters; plan replacement over 24 hours. 5
• After the first hour, switch to 0.45% NaCl at 4-14 mL/kg/hour if corrected sodium is normal or elevated, or continue 0.9% NaCl if corrected sodium is low. 6, 5
• When plasma glucose falls to 250 mg/dL, change IV fluids to 5% dextrose with 0.45-0.75% NaCl while maintaining the insulin infusion rate. 6, 5

Potassium Management (Class A Evidence)

• Absolute contraindication: Do not start insulin if serum potassium is <3.3 mEq/L; aggressively replete potassium first to prevent fatal cardiac arrhythmias. 6, 5
• If potassium is 3.3-5.5 mEq/L, insulin may be started; add 20-30 mEq/L potassium to IV fluids (using 2/3 potassium chloride or acetate and 1/3 potassium phosphate) once adequate urine output is confirmed. 6, 5
• If potassium is >5.5 mEq/L, start insulin immediately but delay potassium supplementation until the level falls below 5.5 mEq/L. 6, 5
• Target serum potassium 4.0-5.0 mEq/L throughout treatment. 6, 5

Insulin Therapy

• For moderate-to-severe DKA, give an IV bolus of 0.1 units/kg regular insulin followed by continuous infusion at 0.1 units/kg/hour. 6, 5
• In pediatric patients, omit the bolus and start continuous infusion at 0.05-0.1 units/kg/hour to reduce cerebral edema risk. 6, 5
• Target glucose decline of 50-75 mg/dL per hour; if glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration and double the insulin infusion rate hourly until steady decline is achieved. 6, 5
• Never discontinue insulin when glucose normalizes; continue infusion to clear ketones and prevent recurrent DKA. 6, 5

Transition to Subcutaneous Insulin

• Administer long-acting basal insulin (glargine or detemir) 2-4 hours BEFORE stopping the IV insulin infusion to prevent rebound hyperglycemia and DKA recurrence. 6, 5
• Continue IV insulin for an additional 1-2 hours after the subcutaneous basal dose to ensure adequate absorption. 6, 5

Bicarbonate Therapy

• Routine bicarbonate administration is NOT recommended for DKA management; it provides no benefit in acidosis resolution time or hospital length of stay. 5
• Consider bicarbonate only if pH <6.9 after initial fluid resuscitation: give 100 mmol sodium bicarbonate diluted in 400 mL sterile water infused at 200 mL/hour. 6, 5