What is the recommended approach to treat diabetic ketoacidosis in an adult with type 1 or type 2 diabetes presenting with typical DKA symptoms?

Approach and Treatment of Diabetic Ketoacidosis

Immediate Initial Management

Begin aggressive isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) to restore intravascular volume and renal perfusion, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L. 1, 2

Initial Diagnostic Workup

Obtain the following laboratory studies immediately:

• Plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap, β-hydroxybutyrate (preferred ketone test), BUN, creatinine, urinalysis with ketones, complete blood count with differential, and electrocardiogram 1, 2
• Calculate corrected serum sodium by adding 1.6 mEq/L for every 100 mg/dL glucose above 100 mg/dL 1, 2
• Calculate effective serum osmolality: 2 × [measured Na (mEq/L)] + glucose (mg/dL)/18 3, 1
• Obtain bacterial cultures (urine, blood, throat) if infection is suspected and initiate appropriate antibiotics 1, 4

Diagnostic Criteria for DKA

DKA is confirmed when all of the following are present:

• Blood glucose >250 mg/dL 1, 2, 4
• Arterial pH <7.3 or venous pH <7.3 1, 2, 4
• Serum bicarbonate <15 mEq/L 1, 2, 4
• Moderate to large ketonemia or ketonuria (β-hydroxybutyrate is the preferred measurement) 1, 2, 4
• Anion gap >10-12 mEq/L 1, 4

Fluid Resuscitation Protocol

First Hour

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour for all patients 3, 1, 2. The typical total body water deficit in DKA is 6-9 liters 1, 2.

After the First Hour

• If corrected sodium is normal or elevated, switch to 0.45% NaCl at 4-14 mL/kg/hour 1, 2
• If corrected sodium is low, continue 0.9% NaCl at 4-14 mL/kg/hour 1, 2
• When plasma glucose falls to approximately 250 mg/dL, change IV fluids to 5% dextrose with 0.45-0.75% NaCl while maintaining insulin infusion 3, 1, 2
• Target total fluid replacement to correct estimated deficits within 24 hours, with osmolality change not exceeding 3 mOsm/kg/hour 3, 1

Common pitfall: In patients with renal or cardiac compromise, monitor closely for fluid overload with frequent assessment of cardiac, renal, and mental status 3, 1.

Potassium Management (Critical)

Total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg), even when initial serum levels appear normal or elevated, because insulin therapy will drive potassium intracellularly. 1, 2

Potassium Replacement Algorithm

• If serum K+ <3.3 mEq/L: HOLD insulin and aggressively replace potassium until K+ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 3, 1, 2
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (approximately 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 3, 1, 2
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor every 2-4 hours, as levels will drop rapidly with insulin therapy 1, 2
• Target serum potassium of 4-5 mEq/L throughout treatment 1, 2

Critical pitfall: Starting insulin before correcting hypokalemia (K+ <3.3 mEq/L) is a leading cause of mortality in DKA 1.

Insulin Therapy

Standard IV Insulin Protocol

After confirming serum potassium ≥3.3 mEq/L, administer continuous IV regular insulin infusion at 0.1 units/kg/hour (an initial bolus of 0.1-0.15 units/kg is optional but not required). 3, 1, 2

• Target a glucose decline of 50-75 mg/dL per hour 3, 1, 2
• If glucose does not fall by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each hour until a steady decline is achieved 3, 1, 2
• Continue insulin infusion until ALL resolution criteria are met (see below), regardless of glucose level 1, 2
• When glucose reaches approximately 250 mg/dL, add 5-10% dextrose to IV fluids while maintaining insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 3, 1, 2

Critical pitfall: Stopping insulin when glucose normalizes (instead of adding dextrose and continuing insulin) is a common cause of persistent or recurrent ketoacidosis, because ketonemia takes longer to clear than hyperglycemia 3, 1.

Alternative Approach for Mild-to-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-to-moderate uncomplicated DKA, subcutaneous rapid-acting insulin analogs at 0.15 units/kg every 2-3 hours combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1, 5, 6

However, continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients. 1, 2

Monitoring During Treatment

• Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 3, 1, 4
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis; repeat arterial blood gases are generally unnecessary after initial diagnosis 1, 4
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution 1, 2, 4

Critical pitfall: Nitroprusside-based ketone tests (urine or serum) detect only acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant ketone body in DKA. During treatment, β-hydroxybutyrate is converted to acetoacetate, which can make nitroprusside tests appear worse even as the patient improves 1, 4.

Resolution Criteria

DKA is resolved when ALL of the following criteria are met:

• Glucose <200 mg/dL 1, 2, 4
• Serum bicarbonate ≥18 mEq/L 1, 2, 4
• Venous pH >7.3 1, 2, 4
• Anion gap ≤12 mEq/L 1, 2, 4

Transition to Subcutaneous Insulin

Administer basal insulin (intermediate or long-acting such as glargine, detemir, or NPH) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 3, 1, 2

• Once the patient can tolerate oral intake, initiate a multiple-dose insulin regimen using short/rapid-acting plus intermediate/long-acting insulin 3, 1
• For newly diagnosed patients, start total daily insulin dose of approximately 0.5-1.0 units/kg/day 1
• Recent evidence shows that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1

Critical pitfall: Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1, 7.

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 2

Bicarbonate should only be considered if pH <6.9 1, 2.

Identification and Treatment of Precipitating Causes

Concurrent treatment of the underlying precipitating cause is essential for successful DKA management. 1, 5

Common precipitating factors to identify and treat:

• Infection (most common trigger)—obtain appropriate cultures and start empiric antibiotics promptly 1, 4, 5
• Insulin omission or inadequacy 3, 1
• Myocardial infarction 1
• Cerebrovascular accident 1
• Pancreatitis 1
• SGLT2 inhibitor use (can cause euglycemic DKA)—discontinue immediately and do not restart until 3-4 days after metabolic stability 1
• Glucocorticoid therapy 1
• Pregnancy 1

Special Considerations

Cerebral Edema

Cerebral edema occurs more commonly in children and adolescents than adults and is one of the most dire complications of DKA. 1

• Limit the change in serum osmolality to ≤3 mOsm/kg/hour to reduce cerebral edema risk 1, 2
• Monitor closely for signs of altered mental status, headache, or neurological deterioration 1
• Overly aggressive fluid resuscitation increases cerebral edema risk 1, 8

Euglycemic DKA

Euglycemic DKA is defined by blood glucose <200-250 mg/dL together with arterial pH <7.3, serum bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and ketonemia or ketonuria. 1

• SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA 1
• Check urine or blood ketones during illness even if glucose is normal in patients on SGLT2 inhibitors 1
• Never stop basal insulin, even when oral intake is limited 1

Discharge Planning

Prior to discharge, ensure:

• Identification of outpatient diabetes care providers 1, 4
• Education on recognition, prevention, and management of DKA, including glucose monitoring, insulin administration, and sick-day management 1, 5
• Appropriate insulin regimen is prescribed with attention to medication access and affordability 1
• Follow-up appointment scheduled prior to discharge 1
• All new or adjusted medication prescriptions are filled and reviewed with the patient and family 1