What is the recommended management of diabetic ketoacidosis, including fluid resuscitation, insulin therapy, electrolyte replacement, and treatment of the underlying cause?

Management of Diabetic Ketoacidosis

Initial Assessment and Diagnostic Criteria

Begin aggressive fluid resuscitation with isotonic saline immediately while confirming the diagnosis through laboratory evaluation. 1

Confirm DKA when all three criteria are present: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 1. Obtain plasma glucose, blood urea nitrogen/creatinine, serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap, osmolality, urinalysis, urine ketones, arterial blood gases, complete blood count with differential, and electrocardiogram 1. If infection is suspected, obtain bacterial cultures (urine, blood, throat) and administer appropriate antibiotics 1. Identify precipitating factors including infection, cerebrovascular accident, alcohol abuse, pancreatitis, myocardial infarction, trauma, drugs, or insulin discontinuation/inadequacy 1.

Fluid Resuscitation Protocol

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour for average adults) to restore intravascular volume and renal perfusion. 1, 2, 3

After the First Hour

Calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1, 2, 3:

• If corrected sodium is normal or elevated: Switch to 0.45% NaCl at 4-14 mL/kg/hour 1, 2, 3
• If corrected sodium is low: Continue 0.9% NaCl at 4-14 mL/kg/hour 1, 2, 3

When serum glucose reaches 250 mg/dL, change fluid to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy to prevent hypoglycemia and ensure complete ketoacidosis resolution. 1, 2, 3

Total fluid replacement should aim to correct estimated deficits (typically 6-9 L) within 24 hours while limiting the change in serum osmolality to ≤3 mOsm/kg/hour to prevent cerebral edema 1, 3.

Potassium Management (Class A Evidence)

Potassium management is critical because total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg), even when initial serum levels appear normal or elevated. 1, 2

Potassium-Based Insulin Initiation Algorithm

• If K⁺ <3.3 mEq/L: Hold insulin and aggressively replace potassium 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/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) once adequate urine output (≥0.5 mL/kg/hour) is confirmed 1, 2
• If K⁺ >5.5 mEq/L: Start insulin immediately without potassium supplementation; monitor every 2-4 hours and add potassium once level falls below 5.5 mEq/L 1, 2

Target serum potassium of 4-5 mEq/L throughout treatment 1, 2.

Insulin Therapy

For moderate-to-severe DKA or critically ill/mentally obtunded patients, use continuous intravenous regular insulin at 0.1 units/kg/hour (with optional initial bolus of 0.1 units/kg) after confirming serum potassium ≥3.3 mEq/L. 1, 2

Target a glucose decline of 50-75 mg/dL per hour 1, 2. If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status; if acceptable, double the insulin infusion rate every hour until a steady glucose decline is achieved 1, 2.

Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, and glucose <200 mg/dL) regardless of glucose levels. 1, 2 Never stop insulin when glucose normalizes; instead add dextrose to IV fluids while maintaining insulin infusion to clear ketones 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 (0.1-0.2 units/kg every 1-2 hours) combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2. This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1.

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. 1 Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1. For pH <6.9, consider 100 mmol sodium bicarbonate diluted in 400 mL sterile water, infused at 200 mL/hour 2.

Monitoring During Treatment

Draw blood every 2-4 hours to determine serum electrolytes (especially potassium), glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2. Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1. Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as the nitroprusside method only measures acetoacetic acid and acetone, missing the predominant ketone body. 1, 2

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 Continue the IV insulin infusion for 1-2 hours after the subcutaneous basal dose to ensure adequate absorption 1, 2. Recent evidence shows that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1.

When 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, start total daily insulin dose of approximately 0.5-1.0 units/kg/day 1.

Treatment of Underlying Cause

Identifying and treating the underlying precipitating cause is crucial for successful DKA management. 1 Common precipitants include infection (most frequent), myocardial infarction, cerebrovascular accident, pancreatitis, insulin omission or inadequacy, SGLT2-inhibitor use, glucocorticoid therapy, and pregnancy 1, 4, 5. Obtain bacterial cultures and start appropriate antibiotics when infection is suspected 1, 2.

Special Consideration: SGLT2 Inhibitors

SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA and must be discontinued immediately when DKA is suspected. 1 Do not restart until 3-4 days after metabolic stability is achieved 1. For euglycemic DKA (glucose <200-250 mg/dL), initiate dextrose-containing IV fluids simultaneously with insulin infusion to prevent hypoglycemia while allowing ketone clearance 1, 2.

Critical Pitfalls to Avoid

• Never start insulin if serum potassium is <3.3 mEq/L (Class A evidence); this can cause life-threatening cardiac arrhythmias 1, 2
• Never stop IV insulin without prior basal insulin overlap 2-4 hours earlier; this is the most common cause of recurrent DKA 1, 2
• Never hold insulin when glucose falls to 250 mg/dL; instead add dextrose to IV fluids while continuing insulin to clear ketones 1, 2
• Never allow serum osmolality to change faster than 3 mOsm/kg/hour; this causes cerebral edema, especially in children 1, 3
• Never use nitroprusside-based ketone tests for monitoring; they miss β-hydroxybutyrate and may delay appropriate therapy 1, 2
• Never administer excessive fluid in patients with renal or cardiac compromise; reduce standard rates by approximately 50% to prevent pulmonary edema 1, 3

Discharge Planning

Prior to discharge, ensure the patient has identified outpatient diabetes care providers 1, 2. Educate patients on recognition, prevention, and management of DKA, glucose monitoring, insulin administration, and when to call healthcare professionals 1. Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 1. Schedule follow-up appointments prior to discharge 1.