What is the recommended management of diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Diagnostic Criteria

DKA is confirmed when blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and ketonemia or ketonuria are present. 1

• Obtain plasma glucose, BUN/creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis with ketones, arterial or venous blood gases, complete blood count with differential, and ECG 1, 2
• β-hydroxybutyrate measurement in blood is the preferred ketone test—nitroprusside-based assays only detect acetoacetate and acetone, missing the predominant ketone body β-hydroxybutyrate 1, 2
• Obtain bacterial cultures (urine, blood, throat) if infection is suspected and start appropriate antibiotics 1, 2
• Identify precipitating factors: infection (most common), myocardial infarction, stroke, pancreatitis, trauma, insulin omission, SGLT2 inhibitor use, pregnancy, or alcohol abuse 1, 2

Special Consideration: Euglycemic DKA

• Euglycemic DKA presents with glucose <200-250 mg/dL but still meets other DKA criteria (pH <7.3, bicarbonate <15 mEq/L, anion gap >12 mEq/L, ketonemia) 1
• SGLT2 inhibitors are the leading contemporary cause—discontinue immediately and do not restart until 3-4 days after metabolic stability 1, 2
• Pregnancy carries a 2% risk of euglycemic DKA in women with pre-gestational diabetes 1
• Check ketones during any acute illness even if glucose is normal in patients on SGLT2 inhibitors 1

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Initial Fluid Resuscitation

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore circulating volume and tissue perfusion. 1, 2

• Some evidence suggests balanced electrolyte solutions may be preferable to 0.9% saline, though this remains an area of practice variation 2
• Calculate corrected serum sodium: add 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1

After the First Hour:

• If corrected sodium is normal or elevated: switch to 0.45% NaCl at 4-14 mL/kg/hour 1
• If corrected sodium is low: continue 0.9% NaCl at 4-14 mL/kg/hour 1
• When glucose reaches 250 mg/dL: change to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2
• Aim to correct estimated fluid deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg/hour to reduce cerebral edema risk 1, 2

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Potassium Management

Total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg), and insulin therapy will unmask this by driving potassium intracellularly—aggressive replacement is critical. 1

Algorithm for Potassium Replacement:

• If K⁺ <3.3 mEq/L: HOLD insulin and replace potassium aggressively until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 1, 2
• If K⁺ 3.3-5.5 mEq/L: add 20-30 mEq potassium per liter of IV fluid (2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 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: 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 due to cardiac arrhythmias 1

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Insulin Therapy

For Moderate-to-Severe DKA or Critically Ill Patients:

Start continuous intravenous regular insulin at 0.1 units/kg/hour (with or without an initial 0.1-0.15 U/kg IV bolus) as standard of care. 1, 2

• Target glucose decline: 50-75 mg/dL per hour 1, 2
• If glucose does not fall by 50 mg/dL in the first hour and hydration is adequate, double the insulin infusion rate every hour until steady decline is achieved 1, 2
• Continue insulin infusion until DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose level 1, 2
• When glucose reaches 250 mg/dL, add dextrose to IV fluids while maintaining insulin infusion 1, 2

For 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 for hemodynamically stable, alert patients. 1, 2

• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1
• Continuous IV insulin remains mandatory for critically ill or mentally obtunded patients 1, 2

Critical Pitfall:

• Stopping insulin when glucose falls to 250 mg/dL (instead of adding dextrose and continuing insulin) leads to recurrent ketoacidosis—this is a common cause of treatment failure 1

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Bicarbonate Administration

Bicarbonate is NOT recommended 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, 2
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2
• For pH <6.9: consider 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 2
• For pH 6.9-7.0: consider 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 2

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Monitoring During Treatment

Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH. 1, 2

• Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring 1, 2
• Use β-hydroxybutyrate levels to monitor ketosis resolution—reduction in blood β-hydroxybutyrate is the most accurate marker of successful treatment 1, 2
• Follow anion gap to monitor resolution of acidosis 1, 2
• Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early 2
• Monitor for cerebral edema, especially in children (occurs in 0.7-1.0% of pediatric DKA cases)—higher BUN at presentation is a risk factor 1, 2

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Resolution Criteria

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

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

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Transition to Subcutaneous Insulin

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

• This overlap period is essential—stopping IV insulin without prior basal insulin administration causes rebound hyperglycemia and ketoacidosis 1, 2
• Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1, 2
• Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 2
• For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day 1, 2
• If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 1

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Special Populations and Considerations

SGLT2 Inhibitors:

• Discontinue 3-4 days before any planned surgery to prevent euglycemic DKA 1, 2
• Do not restart until 3-4 days after metabolic stability is achieved 1, 2
• Avoid prolonged fasting, very-low-carbohydrate diets, and excessive alcohol intake while taking SGLT2 inhibitors 1

Pregnancy:

• Pregnant individuals may present with euglycemic DKA and mixed acid-base disturbances, especially with hyperemesis 1
• Approximately 2% of pregnancies in women with pre-gestational diabetes develop DKA 1

Comorbidities:

• Myocardial infarction can both precipitate and be masked by DKA—obtain ECG and consider troponin 1
• Stroke can precipitate DKA—assess for focal neurological deficits 1
• Glucocorticoid use can precipitate hyperglycemia and DKA 1

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Discharge Planning

Prior to discharge, ensure: 1, 2

• Identification of outpatient diabetes care providers 1, 2
• Education on glucose monitoring, insulin administration, and recognition/treatment of hyperglycemia and hypoglycemia 1, 2
• Understanding of DKA recognition, prevention, and when to seek medical care 1, 2
• Appropriate insulin regimen prescribed with attention to medication access and affordability 1
• Follow-up appointments scheduled prior to discharge 1
• Never stop basal insulin, even when oral intake is limited—provide detailed sick-day management instructions 1

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Common Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 1
• Interruption of insulin infusion when glucose falls is a common cause of persistent or worsening ketoacidosis 1
• Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 1
• Inadequate potassium monitoring and replacement—a leading cause of mortality in DKA 1
• Using nitroprusside-based ketone tests for monitoring misses β-hydroxybutyrate and may delay appropriate therapy 1
• Overly rapid correction of osmolality increases cerebral edema risk, particularly in children 1, 2