What is the recommended drug and fluid management protocol for an adult (≥18 years) with diabetic ketoacidosis and no known contraindications?

Drug and Fluid Management for Diabetic Ketoacidosis in Adults

Immediate Initial Management

Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters) during the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour once serum potassium is confirmed ≥3.3 mEq/L. 1, 2

Critical First Steps Before Insulin

• Do NOT start insulin if serum potassium is <3.3 mEq/L – this can cause life-threatening cardiac arrhythmias and death 1, 2
• If K+ <3.3 mEq/L: continue isotonic saline, confirm adequate urine output, then aggressively replace potassium with 20-40 mEq/L in IV fluids before initiating insulin 1, 2
• Total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg), and insulin will further drive potassium intracellularly 1

Fluid Resuscitation Protocol

Hour 1: Volume Expansion

• Administer 0.9% normal saline at 15-20 mL/kg/hour to restore intravascular volume and enhance insulin sensitivity 1, 2
• This aggressive initial fluid replacement is critical for restoring tissue perfusion 1

After Hour 1: Maintenance Fluids

• Calculate corrected serum sodium: add 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
• If corrected sodium is low: continue 0.9% NaCl at 4-14 mL/kg/hour 1
• Aim to correct estimated fluid deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg H₂O per hour 3

When Glucose Falls to 250 mg/dL

• Switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion 1, 2
• This prevents hypoglycemia and ensures complete resolution of ketoacidosis 1
• A common pitfall is stopping insulin when glucose normalizes – this leads to recurrent ketoacidosis 1, 4

Insulin Therapy Protocol

Initiation (After Confirming K+ ≥3.3 mEq/L)

• Give IV bolus of regular insulin 0.15 units/kg body weight 3
• Start continuous infusion of regular insulin at 0.1 units/kg/hour 3, 1, 2
• Target glucose decline: 50-75 mg/dL per hour 3, 1

Adjusting Insulin Rate

• If glucose does not fall by 50 mg/dL in the first hour: check hydration status; if adequate, double the insulin infusion rate every hour until steady decline of 50-75 mg/dL per hour is achieved 3, 1

Continuation Until Resolution

• Continue insulin infusion until DKA resolution regardless of glucose level 1, 2
• DKA resolution criteria: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, AND anion gap ≤12 mEq/L 1, 2, 5
• Ketonemia takes longer to clear than hyperglycemia – do not stop insulin prematurely 3, 4

Potassium Management Algorithm

If K+ <3.3 mEq/L

• Hold insulin completely 1, 2
• Continue isotonic saline 1
• Aggressively replace potassium with 20-40 mEq/L in IV fluids 1, 2
• Recheck potassium before starting insulin 1

If K+ 3.3-5.5 mEq/L

• Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 3, 1
• Target serum potassium: 4-5 mEq/L throughout treatment 1

If K+ >5.5 mEq/L

• Withhold potassium initially 1
• Monitor closely every 2-4 hours as levels will drop rapidly with insulin therapy 1

Monitoring Requirements

Laboratory Monitoring Every 2-4 Hours

• Serum glucose 1, 2
• Serum electrolytes (sodium, potassium, chloride) 1, 2
• Blood urea nitrogen and creatinine 1, 2
• Venous pH (arterial gases generally unnecessary) 1
• Anion gap 1, 2
• Serum osmolality 1, 2

Preferred Ketone Monitoring

• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution 3, 1, 5
• Nitroprusside-based tests only measure acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate) 3, 1

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 1

• 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

Transition to Subcutaneous Insulin

Critical Timing to Prevent Rebound

• Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion 1, 2, 5
• This prevents recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 5
• Premature termination of IV insulin without prior subcutaneous basal insulin is a common cause of treatment failure 1, 4

Dosing Strategy

• Estimate total daily insulin requirement at 0.5-1.0 units/kg/day for newly diagnosed patients 1
• Give approximately half as basal insulin and half as prandial coverage 2
• Start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin once patient can eat 1

Alternative Approach for Mild-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-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 moderate-to-severe DKA or critically ill/mentally obtunded patients 1, 5

Identification and Treatment of Precipitating Causes

Common Precipitants to Address Concurrently

• Infection (most common): obtain bacterial cultures (urine, blood, throat) and administer appropriate antibiotics 1
• Myocardial infarction 1, 5
• Cerebrovascular accident 1, 5
• Insulin omission or inadequacy 1
• SGLT2 inhibitors: discontinue immediately and do not restart until 3-4 days after metabolic stability achieved 1, 2
• Pancreatitis, trauma, glucocorticoid therapy 1

Common Pitfalls to Avoid

• Stopping IV insulin when glucose reaches 250 mg/dL instead of adding dextrose and continuing insulin – leads to recurrent ketoacidosis 1, 4
• Starting insulin before correcting hypokalemia (K+ <3.3 mEq/L) – can cause life-threatening arrhythmias 1, 2
• Discontinuing IV insulin without prior administration of subcutaneous basal insulin – causes rebound hyperglycemia and ketoacidosis 1, 5, 4
• Using nitroprusside-based ketone tests instead of β-hydroxybutyrate measurements – misses the predominant ketone body and delays appropriate therapy 3, 1
• Inadequate potassium monitoring and replacement – a leading cause of mortality in DKA 1
• Overly rapid correction of osmolality (>3 mOsm/kg H₂O per hour) – increases risk of cerebral edema 3, 1