What is the recommended management of diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Begin immediate aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour (approximately 1-1.5 L in an average adult), followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, and continue insulin until complete resolution of ketoacidosis regardless of glucose levels. 1, 2

Initial Diagnostic Assessment

Obtain the following laboratory studies immediately upon presentation:

• Plasma glucose, arterial or venous pH, 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, and ECG 1, 2
• Bacterial cultures (blood, urine, throat) if infection is suspected, as infection is the most common precipitating factor 1, 2

Diagnostic criteria for DKA: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, moderate-to-large ketonuria/ketonemia, and anion gap >12 mEq/L 1, 2

Fluid Resuscitation Protocol

First Hour

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (1-1.5 L in average adult) to restore intravascular volume and renal perfusion 1, 2
• This aggressive initial fluid replacement is critical for restoring tissue perfusion and improving insulin sensitivity 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, 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

When Glucose Reaches 250 mg/dL

• Change IV fluids to 5% dextrose with 0.45-0.75% NaCl while maintaining insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2
• This is a critical step—do NOT stop insulin when glucose falls; instead add dextrose 2

Alternative fluid option: Recent evidence suggests lactated Ringer's may achieve faster resolution of high anion gap metabolic acidosis compared to normal saline, with similar complication rates 3

Potassium Management

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

Critical Potassium Thresholds

• If 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 2, 4
• If K⁺ 3.3-5.5 mEq/L: 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: withhold potassium initially but monitor every 2-4 hours, as levels will fall rapidly with insulin therapy 2, 4

Target serum potassium throughout treatment: 4-5 mEq/L 2, 4

Insulin Therapy

Initiation

• Confirm serum potassium ≥3.3 mEq/L before starting insulin 2, 4
• Administer continuous IV regular insulin at 0.1 units/kg/hour (an initial bolus of 0.1-0.15 units/kg is optional but not required) 2, 4
• For critically ill and mentally obtunded patients, continuous IV insulin is the standard of care 2

Titration

• Target glucose decline of 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 hour until steady decline is achieved 1, 2

Duration

Continue insulin infusion until ALL of the following DKA resolution criteria are met, regardless of glucose level 2, 4:

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

Common pitfall: Stopping insulin when glucose reaches 250 mg/dL leads to recurrent ketoacidosis; instead add dextrose and continue insulin 2, 5

Alternative for Mild-Moderate Uncomplicated DKA

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

Monitoring During Treatment

• Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 2
• Monitor venous pH (typically 0.03 units lower than arterial pH) and anion gap to track resolution; repeated arterial blood gases are generally unnecessary 1, 2
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring ketosis resolution 2
• Avoid nitroprusside-based ketone tests, which only detect acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate) 2

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 2, 4

Rationale: 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 2, 6

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

Transition to Subcutaneous Insulin

Administer basal insulin (glargine, detemir, or NPH) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 2, 4, 5

Recent evidence: Adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 2

Once the patient can eat:

• Start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 2
• For newly diagnosed patients, start total daily insulin dose of approximately 0.5-1.0 units/kg/day 2

Identification and Treatment of Precipitating Causes

Common precipitating factors that must be identified and treated concurrently 1, 2, 4:

• Infection (most common)—obtain cultures and start appropriate antibiotics 1, 2
• Insulin omission or inadequate dosing
• New-onset diabetes
• Myocardial infarction (obtain ECG)
• Cerebrovascular accident
• Pancreatitis
• SGLT2 inhibitor use—discontinue immediately and do not restart until 3-4 days after metabolic stability 2
• Glucocorticoid therapy
• Pregnancy

Critical Complications to Monitor

Cerebral Edema

• Occurs more commonly in children and adolescents than adults and is one of the most dire complications 2, 7
• Limit change in serum osmolality to ≤3 mOsm/kg/hour to reduce risk 2
• Monitor closely for altered mental status, headache, or neurological deterioration 2

Hypokalemia

• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 2
• Check potassium every 2-4 hours during active treatment 2

Hypoglycemia

• Prevented by adding dextrose when glucose falls to 250 mg/dL while continuing insulin 2

Special Populations

Anuric End-Stage Renal Disease with Congestive Heart Failure

• Initiate urgent hemodialysis as the primary intervention while simultaneously starting insulin at reduced rates 8
• Severely restrict or eliminate fluid resuscitation entirely, as standard fluid boluses can cause life-threatening volume overload and pulmonary edema 8
• Hemodialysis becomes the primary method for correcting acidosis and electrolyte abnormalities 8

Pregnancy

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

Discharge Planning and Prevention

Before discharge, ensure:

• Identification of outpatient diabetes care providers 1, 2
• Patient education on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia 2
• Understanding of sick-day management: never stop basal insulin even when oral intake is limited 2
• Appropriate insulin regimen prescribed with attention to medication access and affordability 2
• Follow-up appointments scheduled prior to discharge 2

For patients on SGLT2 inhibitors: Educate to check urine or blood ketones during illness even if glucose is normal, avoid prolonged fasting and very-low-carbohydrate diets, and discontinue SGLT2 inhibitors during any acute illness 2