What are the guideline-recommended steps for managing diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Initial Assessment and Laboratory Workup

Obtain plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap, β-hydroxybutyrate (not nitroprusside-based ketone tests), BUN, creatinine, effective serum osmolality, urinalysis, complete blood count, and electrocardiogram immediately upon presentation. 1

• Confirm DKA diagnosis when all three criteria are met: glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, moderate-to-large ketonuria/ketonemia, and anion gap >12 mEq/L 2
• β-hydroxybutyrate measurement in blood is the preferred ketone test because nitroprusside-based assays detect only acetoacetate and acetone, missing the predominant ketone body and potentially delaying appropriate therapy 1, 2
• Obtain bacterial cultures (urine, blood, throat) and chest X-ray only when infection is clinically suspected 1
• Identify precipitating factors: infection (most common), myocardial infarction, stroke, pancreatitis, insulin omission, SGLT2 inhibitor use, or glucocorticoid therapy 1, 2

Fluid Resuscitation Protocol

Begin with 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. 1, 2

After the First Hour

• Calculate corrected serum sodium: add 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1, 2
• 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
• Total fluid replacement should correct the estimated 6–9 L deficit within 24 hours while limiting osmolality change to ≤3 mOsm/kg/hour to prevent cerebral edema 1, 3

When Glucose Falls to 250 mg/dL

Switch IV fluids to 5% dextrose with 0.45–0.75% NaCl while maintaining the same insulin infusion rate. 1, 2

• This prevents hypoglycemia while allowing continued insulin-mediated ketone clearance 1
• Never stop insulin when glucose falls; instead add dextrose to continue clearing ketones 1

Potassium Management (Class A Evidence)

Total body potassium depletion is universal in DKA (3–5 mEq/kg), even when initial serum levels appear normal or elevated due to acidosis and insulin deficiency. 1, 2

Critical Potassium Thresholds

• If K⁺ <3.3 mEq/L: Hold insulin completely 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 potassium per liter of IV fluid (2/3 KCl + 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K⁺ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation; monitor every 2–4 hours as levels will fall rapidly with insulin therapy 1, 2
• Target serum potassium throughout treatment: 4–5 mEq/L 1, 2

Insulin Therapy

Confirm serum potassium ≥3.3 mEq/L before initiating any insulin therapy. 1, 2

Standard IV Insulin Protocol for Moderate-to-Severe DKA

• Give an IV bolus of regular insulin 0.1 units/kg, followed immediately by continuous infusion of 0.1 units/kg/hour 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 despite adequate hydration, double the insulin infusion rate every hour until the desired decline is achieved 1, 2
• Use only regular (short-acting) insulin for IV infusion; rapid-acting analogs must not be administered intravenously 1

Preparation and Administration

• Prepare 100 units regular insulin in 100 mL normal saline (1 unit/mL concentration) 1
• Prime the infusion tubing with 20 mL of the prepared solution before patient connection to prevent insulin adsorption 1

Alternative Approach for Mild-to-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-to-moderate 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, 4

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

Monitoring During Treatment

Draw blood every 2–4 hours for serum electrolytes (especially potassium), 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; routine repeat arterial blood gases are unnecessary 1, 2
• Monitor β-hydroxybutyrate levels (when available) as the most accurate marker of ketosis resolution 1
• Check bedside glucose every 1–2 hours during initial titration, then every 2–4 hours once stable 1

DKA Resolution Criteria

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

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

Continue insulin infusion until complete resolution regardless of glucose level; ketonemia resolves more slowly than hyperglycemia. 1, 2

Transition to Subcutaneous Insulin

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

• Continue the IV insulin infusion for 1–2 hours after the basal dose to ensure adequate absorption 1
• This overlap is the single most critical step to prevent DKA recurrence; stopping IV insulin without prior basal insulin is the most common error. 1

Calculating Subcutaneous Insulin Doses

• Use approximately 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting basal insulin 1
• Divide the remaining 50% equally among three meals as rapid-acting prandial insulin 1
• For newly diagnosed patients, start with a total daily dose of approximately 0.5–1.0 units/kg/day 2, 4

Emerging Evidence

• Adding low-dose basal insulin analog (e.g., glargine) during the IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk and may shorten hospital stays 2, 4, 3

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9–7.0. 1, 2, 4

• 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
• Consider bicarbonate only if pH <6.9: administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 2, 4

Special Considerations and Common Pitfalls

Euglycemic DKA

SGLT2 inhibitors are the leading cause of euglycemic DKA (glucose <200–250 mg/dL with ketoacidosis). 1, 2

• Discontinue SGLT2 inhibitors immediately and do not restart until 3–4 days after metabolic stability is achieved 1, 2
• Start 5% dextrose with 0.45–0.75% NaCl simultaneously with insulin infusion to prevent hypoglycemia while clearing ketones 1
• Provide 150–200 g carbohydrate per day to suppress starvation ketogenesis 1

Cerebral Edema Prevention

• Cerebral edema occurs in 0.7–1.0% of children with DKA and is the most dreaded complication 4, 3
• Limit osmolality change to ≤3 mOsm/kg/hour during fluid resuscitation 1, 3
• In pediatric patients, omit the initial insulin bolus and start continuous infusion at 0.05–0.1 units/kg/hour 1
• Administer isotonic saline at 10–20 mL/kg/hour in children (not exceeding 50 mL/kg in the first 4 hours) 1

Cardiac and Renal Comorbidities

• In patients with cardiac or renal impairment, monitor closely for fluid overload 1
• Consider balanced electrolyte solutions rather than 0.9% saline, which may achieve faster DKA resolution 4, 3

Pregnancy

• Approximately 2% of pregnancies in women with pre-gestational diabetes develop DKA, frequently presenting with euglycemia 1
• Pregnant patients require prompt recognition and aggressive treatment due to high risk of fetal-maternal harm 1

Treatment of Precipitating Causes

Identify and treat the underlying precipitating factor concurrently with metabolic correction. 1, 2

• Infection is the most common precipitant; obtain appropriate cultures and start empiric antibiotics promptly when suspected 1, 2
• Consider myocardial infarction, stroke, pancreatitis, trauma, or insulin omission 1, 2
• Discontinue any precipitating medications (SGLT2 inhibitors, glucocorticoids) 1, 2

Discharge Planning

Prior to discharge, ensure the patient has identified outpatient diabetes care providers and schedule follow-up appointments. 1, 2

• Educate patients on glucose monitoring, insulin administration, recognition of hyperglycemia/hypoglycemia, and sick-day management 1, 2
• Provide detailed instructions on when to seek medical attention 1
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 1
• Include education on DKA recognition, prevention, and management to reduce readmission rates 1, 4