What are the immediate treatment steps for diabetic ketoacidosis, including fluid resuscitation, insulin therapy, potassium management, and bicarbonate administration?

Immediate Treatment of Diabetic Ketoacidosis

Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour during the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, while closely monitoring and replacing potassium to maintain levels between 4–5 mEq/L. 1

Initial Assessment and Diagnosis

Diagnostic Criteria:

• Confirm DKA with blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia 1, 2
• Calculate anion gap using [Na⁺] - ([Cl⁻] + [HCO₃⁻]); should be >10–12 mEq/L in DKA 1
• Measure β-hydroxybutyrate in blood as the preferred ketone test—nitroprusside-based urine tests miss the predominant ketone body and should not be used 1, 2

Essential Laboratory Workup:

• Obtain plasma glucose, venous blood gases, complete metabolic panel with calculated anion gap, serum β-hydroxybutyrate, BUN/creatinine, complete blood count, urinalysis, and ECG 3, 1
• Correct serum sodium for hyperglycemia by adding 1.6 mEq/L for every 100 mg/dL glucose above 100 mg/dL 1, 2
• Obtain bacterial cultures (urine, blood, throat) and start appropriate antibiotics if infection is suspected 3, 1

Fluid Resuscitation Protocol

First Hour:

• Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (approximately 1–1.5 L in average adults) to restore intravascular volume and renal perfusion 3, 1
• This addresses the typical total body water deficit of 6–9 liters in DKA 3, 1

After First Hour:

• If corrected serum sodium is normal or elevated: switch to 0.45% NaCl at 4–14 mL/kg/hour 3, 1
• If corrected serum sodium is low: continue 0.9% NaCl at 4–14 mL/kg/hour 3, 1
• Target total fluid replacement to correct estimated deficits within 24 hours 3, 1
• Critical pitfall: Monitor closely for fluid overload in patients with cardiac or renal compromise 3, 1

When Glucose Falls:

• When plasma glucose reaches 250 mg/dL, change IV fluids to 5% dextrose with 0.45–0.75% NaCl while continuing insulin infusion 1
• This prevents hypoglycemia while allowing insulin to clear ketones completely 1
• Never stop insulin when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia 1, 4

Insulin Therapy

Standard IV Insulin Protocol (for moderate-severe DKA or critically ill patients):

• Start continuous IV regular insulin infusion at 0.1 units/kg/hour without an initial bolus once serum potassium is ≥3.3 mEq/L 1, 2
• Target glucose decline of 50–75 mg/dL per hour 1
• If glucose does not fall by ≥50 mg/dL in the first hour and hydration is adequate, double the insulin infusion rate hourly until steady decline achieved 3, 1
• Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose level 1

Alternative for Mild-Moderate Uncomplicated DKA:

• For hemodynamically stable, alert patients: 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, treatment of concurrent infections, and appropriate follow-up 1
• Continuous IV insulin remains mandatory for critically ill and mentally obtunded patients 1

Potassium Management

Critical Pre-Insulin Assessment:

• If K⁺ <3.3 mEq/L: HOLD insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias 1, 2
• Total body potassium depletion is universal in DKA (3–5 mEq/kg), and insulin therapy will drive potassium intracellularly, causing rapid decline 3, 1

Potassium Replacement Protocol:

• If K⁺ 3.3–5.5 mEq/L: Add 20–30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 3, 1
• If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2–4 hours, as levels will drop rapidly with insulin therapy 1
• Target serum potassium: 4–5 mEq/L throughout treatment 1, 2
• Including phosphate as 1/3 of potassium replacement prevents severe hypophosphatemia 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 3, 1
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 3, 1
• Reserve bicarbonate only for pH <6.9 1

Monitoring During Treatment

Frequency:

• Draw blood every 2–4 hours to measure serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 3, 1
• Venous pH (typically 0.03 units lower than arterial pH) and anion gap adequately monitor acidosis resolution—repeated arterial blood gases are unnecessary 3, 1
• Monitor β-hydroxybutyrate levels to track ketosis resolution; ketonemia typically takes longer to clear than hyperglycemia 1, 2

Resolution Criteria:

• Glucose <200 mg/dL 1, 2
• Serum bicarbonate ≥18 mEq/L 1, 2
• Venous pH >7.3 1, 2
• Anion gap ≤12 mEq/L 1, 2

Transition to Subcutaneous Insulin

Critical Timing:

• Administer basal insulin (intermediate or long-acting) 2–4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 4
• This overlap period is essential—stopping IV insulin without prior basal insulin causes rebound hyperglycemia and ketoacidosis 1
• Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1

Once Patient Can Eat:

• Start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 3, 1
• Initial dose approximately 0.5–1.0 units/kg/day for newly diagnosed patients 1

Identification and Treatment of Precipitating Causes

Common Precipitants to Investigate:

• Infection (most common trigger), myocardial infarction, cerebrovascular accident, pancreatitis, trauma, insulin omission or inadequacy, SGLT2 inhibitor use, glucocorticoid therapy 3, 1
• SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA—discontinue immediately and do not restart until 3–4 days after metabolic stability 1
• Treatment of the underlying cause must occur simultaneously with correction of metabolic derangement 1

Critical Pitfalls to Avoid

• Premature insulin termination: Stopping IV insulin when glucose normalizes (instead of adding dextrose and continuing insulin) leads to recurrent ketoacidosis 1
• Inadequate potassium monitoring: Hypokalemia occurs in roughly 50% of patients during treatment and is linked to higher mortality 1
• Starting insulin with hypokalemia: Initiating insulin when K⁺ <3.3 mEq/L can cause fatal cardiac arrhythmias 1, 2
• Using nitroprusside ketone tests: These miss β-hydroxybutyrate and may falsely suggest worsening ketosis during treatment 1, 2
• Overly rapid osmolality correction: Changes in serum osmolality should not exceed 3 mOsm/kg/hour to reduce cerebral edema risk 3, 1
• Failure to identify precipitating cause: Not treating underlying infection, MI, or other triggers leads to DKA recurrence 1

Special Considerations

Cerebral Edema:

• More common in children and adolescents than adults 1
• Monitor closely for altered mental status, headache, or neurological deterioration during treatment 1
• Avoid overly aggressive fluid resuscitation 1

Euglycemic DKA:

• Defined by blood glucose <200–250 mg/dL with typical DKA criteria 1
• SGLT2 inhibitors are the leading cause—incidence 0.6–4.9 events per 1,000 patient-years with relative risk 2.46 versus placebo 1
• Check ketones during illness even if glucose is normal in patients on SGLT2 inhibitors 1