What are the diagnostic criteria and treatment approach for an adult patient with a history of diabetes presenting with hyperglycemia, metabolic acidosis, and ketosis?

Diagnostic Criteria for Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three criteria are simultaneously present: blood glucose >250 mg/dL, arterial pH <7.3 (or venous pH <7.3), serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia. 1

Core Diagnostic Parameters

The diagnosis requires meeting all of the following thresholds simultaneously 1:

• Blood glucose >250 mg/dL (though euglycemic DKA can occur with normal or mildly elevated glucose) 1, 2
• Arterial pH <7.3 (venous pH is acceptable and typically 0.03 units lower than arterial) 1
• Serum bicarbonate <15 mEq/L 1
• Moderate ketonuria or ketonemia (direct β-hydroxybutyrate measurement preferred) 1

Severity Classification

DKA severity determines monitoring intensity and potential need for ICU admission 3:

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status 3, 1
• Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy/altered mental status 3, 1
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, stupor/coma 3, 1

Severe DKA carries higher morbidity and mortality and often requires central venous and intra-arterial pressure monitoring 1.

Essential Laboratory Evaluation

Obtain the following immediately upon presentation 3, 1:

• Plasma glucose
• Arterial or venous blood gas (venous pH suffices after initial diagnosis)
• Serum ketones (direct β-hydroxybutyrate measurement strongly preferred over nitroprusside method)
• Complete metabolic panel including electrolytes, BUN, creatinine
• Calculated anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), typically >10-12 mEq/L in DKA 1
• Serum osmolality: calculated as 2[measured Na (mEq/L)] + glucose (mg/dL)/18 3
• Urinalysis with urine ketones by dipstick
• Complete blood count with differential
• Electrocardiogram (to assess for cardiac effects of electrolyte abnormalities)

If infection is suspected, obtain bacterial cultures of urine, blood, and throat before initiating antibiotics 3. Chest X-ray should be obtained if clinically indicated 3, 4.

Critical Diagnostic Nuances

Corrected Sodium Calculation

Always correct serum sodium for hyperglycemia: add 1.6 mEq/L to the measured sodium for every 100 mg/dL glucose above 100 mg/dL 3, 1. This corrected value guides fluid selection.

Ketone Measurement Pitfall

The nitroprusside method (standard urine/serum ketone tests) only measures acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant and strongest ketoacid in DKA 1, 2. During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves 1. Direct blood β-hydroxybutyrate measurement is the gold standard for both diagnosis and monitoring 4, 1, 2.

Euglycemic DKA Recognition

Euglycemic DKA presents with pH <7.3, bicarbonate <15 mEq/L, and ketonemia but blood glucose that may be normal or only mildly elevated 2. This occurs particularly in patients on SGLT2 inhibitors, pregnant patients, or those with reduced caloric intake. The same diagnostic criteria apply except for the glucose threshold 2.

Differential Diagnosis

Not all ketoacidosis is DKA 3:

• Starvation ketosis: glucose rarely >250 mg/dL, bicarbonate usually not <18 mEq/L 3
• Alcoholic ketoacidosis: glucose ranges from mildly elevated to hypoglycemic, distinguished by clinical history 3
• Other high anion gap metabolic acidoses: lactic acidosis, salicylate ingestion, methanol, ethylene glycol, paraldehyde, chronic renal failure 3

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Treatment Approach for DKA

Begin immediate aggressive fluid resuscitation with isotonic saline at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin infusion at 0.1 units/kg/hour (with or without 0.1 units/kg bolus), while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 4, 1

Initial Fluid Resuscitation

First Hour

Infuse isotonic saline (0.9% NaCl) at 15-20 mL/kg body weight/hour (approximately 1-1.5 liters in average adults) during the first hour in the absence of cardiac compromise 3, 4, 1. This restores intravascular and extravascular volume and improves renal perfusion 3.

Subsequent Fluid Selection

After the initial hour, fluid choice depends on corrected serum sodium, hydration state, and urine output 3, 4:

• 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 4-14 mL/kg/hour 3

Total fluid replacement should correct estimated deficits within 24 hours 3, 1. Typical total body water deficit is approximately 6 liters in DKA 3.

Adding Dextrose

When blood glucose falls to 200-250 mg/dL, add 5% dextrose to IV fluids while continuing insulin infusion to clear ketosis 1, 2. In euglycemic DKA, add dextrose-containing fluids earlier to maintain adequate glucose while continuing insulin to resolve ketoacidosis 2.

Insulin Therapy

Initiation Protocol

The preferred method is continuous IV regular insulin infusion 4:

• Give IV bolus of 0.1 units/kg regular insulin (optional but recommended by American Diabetes Association) 4, 1
• Start continuous infusion at 0.1 units/kg/hour 4, 1
• Target glucose decline of 50-75 mg/dL per hour 4, 1

Critical Potassium Threshold

Do not start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication 4, 1. Insulin drives potassium intracellularly and can precipitate life-threatening cardiac arrhythmias and death 4, 5. Aggressively replace potassium first until K⁺ ≥3.3 mEq/L, then initiate insulin 4, 1.

Adjusting Insulin Infusion

If glucose does not fall by 50 mg/dL in the first hour 4, 1:

1. Verify adequate hydration status
2. Double the insulin infusion rate every hour until achieving steady decline of 50-75 mg/dL/hour

Critical Insulin Management Principle

Never stop insulin infusion when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia 1, 2. Instead, add dextrose to prevent hypoglycemia while continuing insulin to clear ketosis 1, 2. Premature insulin cessation is the most common error leading to DKA recurrence 4, 1.

Electrolyte Management

Potassium Replacement

Once renal function is assured and serum potassium is known, include 20-30 mEq/L potassium in IV fluids using 2/3 KCl (or potassium acetate) and 1/3 KPO₄ 3, 4, 1. Typical total body potassium deficit is 3-5 mEq/kg 3.

Potassium replacement algorithm 4, 1:

• K⁺ <3.3 mEq/L: Hold insulin, give 20-40 mEq/L potassium until K⁺ ≥3.3 mEq/L
• K⁺ 3.3-5.3 mEq/L: Add 20-30 mEq/L to each liter of IV fluid
• K⁺ >5.3 mEq/L: Do not add potassium; recheck every 2 hours

Maintain serum potassium between 4-5 mEq/L throughout treatment 4, 2. Monitor closely as insulin therapy and correction of acidosis lower serum potassium 4, 5.

Bicarbonate Therapy

Bicarbonate administration is generally not recommended and provides no benefit in DKA resolution 1. Consider bicarbonate only if pH <6.9 4, 1, 2.

Other Electrolytes

Typical deficits in DKA include 3:

• Sodium: 7-10 mEq/kg
• Chloride: 3-5 mEq/kg
• Phosphate: 5-7 mmol/kg
• Magnesium: 1-2 mEq/kg
• Calcium: 1-2 mEq/kg

Monitoring During Treatment

Frequency

Check blood glucose every 1-2 hours 2. Draw blood every 2-4 hours to measure electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 4, 1, 2.

What to Monitor

• Venous pH and anion gap adequately monitor acidosis resolution without requiring repeated arterial blood gases 1
• β-hydroxybutyrate levels every 2-4 hours (if available) to track ketosis resolution 1
• Serum potassium closely as levels can drop precipitously with insulin therapy 4, 5
• Hemodynamic status including blood pressure, heart rate, urine output 3
• Mental status for signs of cerebral edema (especially in children) 1

DKA Resolution Criteria

DKA is considered resolved when ALL of the following are met simultaneously 4, 1, 2:

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

Ketonemia typically takes longer to clear than hyperglycemia 1.

Transition to Subcutaneous Insulin

Timing and Protocol

When DKA resolves and the patient can tolerate oral intake, administer basal insulin (glargine or detemir) subcutaneously 2-4 hours BEFORE stopping the IV insulin infusion 4, 1, 2. This overlap prevents rebound hyperglycemia and DKA recurrence 4, 1.

Continue IV insulin for 1-2 hours after administering subcutaneous insulin to allow for absorption 4, 1.

Common Pitfall

Stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence 4, 1. This cannot be overemphasized.

Discharge Regimen

Initiate a multiple-dose insulin schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 4, 1. Provide structured education on insulin administration, glucose monitoring, and sick day management 4, 1.

Alternative Approach for Mild-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs (0.15 units/kg every 2-3 hours) combined with aggressive fluid management can be as effective and more cost-effective than IV insulin 4, 6. This approach requires frequent monitoring and is not appropriate for severe DKA or patients with altered mental status 1.

Identifying and Treating Precipitating Events

Common precipitants include 3:

• Infection (most common)—obtain cultures and initiate appropriate antibiotics
• Insulin omission or inadequate dosing
• New-onset diabetes
• Myocardial infarction
• Pancreatitis
• Medications (corticosteroids, atypical antipsychotics, SGLT2 inhibitors)

Failing to identify and treat the underlying precipitating cause leads to DKA recurrence 1.

Complications to Monitor

• Hypoglycemia from excessive insulin 5
• Hypokalemia from insulin-driven intracellular potassium shift 4, 1, 5
• Cerebral edema (rare in adults, more common in children)—monitor for headache, altered mental status, especially with overly aggressive fluid resuscitation 1
• Hyperchloremic acidosis from excessive normal saline administration 3
• Hyperosmolar shifts (should not exceed 3 mOsm/kg/hour) 3