What is the recommended management protocol for an adult with diabetic ketoacidosis?

Management of Diabetic Ketoacidosis in Adults

Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) while simultaneously obtaining diagnostic laboratories and confirming serum potassium ≥3.3 mEq/L before starting insulin. 1, 2, 3

Initial Diagnostic Assessment

Obtain the following stat laboratories to confirm DKA and identify precipitating factors 1, 3:

• Diagnostic criteria for DKA: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and moderate-to-large ketonemia or ketonuria with anion gap >12 mEq/L 1, 2, 3
• Essential labs: plasma glucose, arterial or venous blood gas, serum electrolytes with calculated anion gap, β-hydroxybutyrate (preferred ketone test), BUN, creatinine, calculated effective serum osmolality (2 × [Na] + glucose/18), urinalysis with ketones, complete blood count with differential, and ECG 1
• If infection suspected: obtain blood, urine, and throat cultures immediately and start appropriate antibiotics, as infection is the most common precipitating factor 1, 3
• Search for other precipitants: myocardial infarction, cerebrovascular accident, pancreatitis, insulin omission, SGLT2-inhibitor use, glucocorticoid therapy, or pregnancy 1

Critical pitfall: Use β-hydroxybutyrate measurement in blood rather than nitroprusside-based urine ketone tests, which only detect acetoacetate and acetone while missing the predominant ketone body (β-hydroxybutyrate) and may delay appropriate therapy 1

Fluid Resuscitation Protocol

First Hour

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in an average adult) to restore intravascular volume and renal perfusion 1, 2, 3
• In elderly patients or those with cardiac/renal compromise, use more cautious fluid rates with closer hemodynamic monitoring 2

After First Hour

• Calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1
• 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
• Aim to replace total fluid deficit (typically 6-9 L) within 24 hours while limiting change in serum osmolality to ≤3 mOsm/kg/hour to reduce cerebral edema risk 1

When Glucose Falls to 250 mg/dL

• Change IV fluids to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2, 3

Critical pitfall: Stopping insulin when glucose reaches 250 mg/dL without adding dextrose is a common cause of persistent or recurrent ketoacidosis 1

Potassium Management

Total body potassium depletion is universal in DKA (approximately 3-5 mEq/kg) even when serum potassium appears normal or elevated initially due to acidosis. 1, 2, 3

Potassium-Based Insulin Initiation Algorithm

• If serum K⁺ <3.3 mEq/L: HOLD INSULIN and replace potassium aggressively at 20-40 mEq/hour until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 1, 2
• If K⁺ = 3.3-5.5 mEq/L: Start insulin AND add 20-30 mEq potassium per liter of IV fluid (approximately 2/3 KCl + 1/3 KPO₄) once adequate urine output is confirmed 1, 2, 3
• If K⁺ >5.5 mEq/L: Start insulin but withhold potassium initially; monitor levels every 2-4 hours as they will fall rapidly with insulin therapy 1, 2
• Target serum potassium throughout treatment: 4-5 mEq/L 1, 2

Critical pitfall: Initiating insulin before correcting severe hypokalemia (K⁺ <3.3 mEq/L) can cause fatal cardiac arrhythmias—this is a leading cause of mortality in DKA 1, 2

Insulin Therapy

Standard IV Protocol (Moderate-to-Severe or Critically Ill DKA)

• Confirm serum potassium ≥3.3 mEq/L before starting insulin 1, 2
• Start continuous IV regular insulin infusion at 0.1 units/kg/hour (typically 5-10 units/hour); an initial bolus of 0.1-0.15 units/kg is optional 1, 2, 3
• Target glucose decline: 50-75 mg/dL per hour 1, 2
• If glucose does not fall by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each subsequent hour until steady decline is achieved 1, 2
• Continue insulin infusion until ALL resolution criteria are met (see below), regardless of glucose level 1, 2, 3

Alternative Protocol for Mild-to-Moderate Uncomplicated DKA

• For hemodynamically stable, alert patients with mild-to-moderate 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
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1
• Continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients 1, 2

Bicarbonate Administration

Do NOT administer bicarbonate for DKA patients with pH >6.9-7.0. 1, 2

• Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use 1
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2
• Consider bicarbonate only if pH <6.9: give 100 mmol sodium bicarbonate diluted in 400 mL sterile water, infused at 200 mL/hour 1

Monitoring During Treatment

• Vital signs and mental status: hourly 2
• Blood glucose: every 1-2 hours during insulin infusion 1
• Serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH: every 2-4 hours until stable 1, 2, 3
• Venous pH (typically 0.03 units lower than arterial) is adequate for ongoing monitoring after initial diagnosis 1
• β-hydroxybutyrate levels (when available) are the most accurate marker of successful treatment and ketosis resolution 1

Resolution Criteria

DKA is resolved when ALL of the following are achieved: 1, 2, 3

• Glucose <200 mg/dL
• Serum bicarbonate ≥15-18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L

Target glucose between 150-200 mg/dL until these resolution parameters are met. 1

Transition to Subcutaneous Insulin

Administer basal subcutaneous insulin (NPH, detemir, glargine, or degludec) 2-4 hours BEFORE stopping the IV insulin infusion to prevent rebound hyperglycemia and recurrent ketoacidosis. 1, 2, 3

• Once the patient can tolerate oral intake, start a multiple-dose insulin regimen using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 3
• For newly diagnosed patients, start total daily insulin dose of approximately 0.5-1.0 units/kg/day 1
• Recent evidence suggests 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

Special Considerations

SGLT2 Inhibitors

• Discontinue SGLT2 inhibitors immediately when DKA is suspected, as they are the leading contemporary cause of euglycemic DKA 1
• Do not restart until 3-4 days after metabolic stability is achieved 1
• SGLT2 inhibitors lower the renal glucose threshold, which can mask hyperglycemia that normally alerts clinicians to DKA 1

Euglycemic DKA

• 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
• Most commonly associated with SGLT2-inhibitor use, pregnancy, or acute illness with reduced oral intake 1
• Check urine or blood ketones during illness even if glucose is normal in patients on SGLT2 inhibitors 1

Pregnancy

• Approximately 2% of pregnancies in women with pre-gestational diabetes develop DKA, frequently presenting with euglycemia (glucose <200 mg/dL) 1
• Pregnant patients at risk should be counseled on DKA signs and instructed to seek prompt medical care 1

Common Pitfalls Summary

• Starting insulin before correcting hypokalemia (K⁺ <3.3 mEq/L) → fatal arrhythmias 1, 2
• Stopping insulin when glucose reaches 250 mg/dL without adding dextrose → recurrent ketoacidosis 1
• Inadequate potassium monitoring and replacement → leading cause of mortality 1, 3
• Overly rapid correction of osmolality (>3 mOsm/kg/hour) → cerebral edema 1
• Using nitroprusside-based ketone tests → misses β-hydroxybutyrate and delays therapy 1
• Stopping IV insulin without prior basal subcutaneous insulin → rebound hyperglycemia 1
• Inadequate treatment of precipitating factors (especially infection) → treatment failure 1, 3

Discharge Planning

• Identify outpatient diabetes care providers before discharge 1
• Educate patients on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and sick-day management 1
• Never stop basal insulin, even when oral intake is limited 1
• Measure ketones when glucose exceeds 200 mg/dL or during any illness with typical DKA symptoms 1
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 1