What is the recommended management protocol for a patient presenting with diabetic ketoacidosis?

Management 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 potassium is ≥3.3 mEq/L, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2

Initial Diagnostic Workup

Obtain the following laboratory studies immediately upon presentation 1, 2:

• Plasma glucose, arterial or venous blood gases (pH), serum electrolytes with calculated anion gap
• Blood urea nitrogen, creatinine, serum osmolality
• β-hydroxybutyrate (β-OHB) in blood—the preferred ketone test 1, 2
• Complete blood count with differential, urinalysis with ketones, electrocardiogram
• Bacterial cultures (blood, urine, throat) if infection is suspected 1, 3

DKA diagnostic criteria require all three: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia 1, 2. Calculate the anion gap using [Na⁺] - ([Cl⁻] + [HCO₃⁻]); it should be >10-12 mEq/L in DKA 2.

Critical pitfall: Do not rely on nitroprusside-based urine or serum ketone tests for diagnosis or monitoring—they only detect acetoacetate and acetone, completely missing β-hydroxybutyrate, which is the predominant ketone body in DKA 1, 2. During treatment, β-OHB converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves 1.

Fluid Resuscitation Protocol

First Hour

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters in the average adult) to restore intravascular volume and renal perfusion 4, 1, 2. The typical total body water deficit in DKA is 6-9 liters 4, 1.

Emerging evidence: Balanced electrolyte solutions may resolve DKA faster than 0.9% saline (mean difference of 5.36 hours faster resolution) and result in lower post-resuscitation chloride and sodium levels 3, 5. However, most current guidelines still recommend starting with 0.9% saline 4, 1.

After the First Hour

Calculate corrected serum sodium: add 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 4, 1, 2.

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

When Glucose Falls to 250 mg/dL

Change IV fluids to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion 4, 1, 2. This prevents hypoglycemia and allows insulin to continue clearing ketones 1.

Critical pitfall: Stopping insulin when glucose normalizes (instead of adding dextrose and continuing insulin) leads to recurrent ketoacidosis 1, 3. Ketonemia resolves more slowly than hyperglycemia 1, 2.

Target total fluid replacement to correct estimated deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg/hour 4, 1, 2. In patients with cardiac or renal compromise, monitor closely for fluid overload 4, 1.

Potassium Management

Total body potassium depletion is universal in DKA (3-5 mEq/kg body weight), despite potentially normal or elevated initial serum levels 4, 1, 2. Insulin therapy drives potassium intracellularly, causing rapid decline 1, 2.

Potassium Replacement Algorithm

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 1, 2, 3.

If K⁺ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (approximately 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 4, 1, 2, 3.

If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor every 2-4 hours, as levels will drop rapidly with insulin therapy 1, 2.

Target serum potassium throughout treatment: 4-5 mEq/L 1, 2, 3. Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.

Insulin Therapy

Standard IV Insulin Protocol (Moderate-Severe DKA or Critically Ill Patients)

Confirm serum potassium ≥3.3 mEq/L before starting insulin 1, 2, 3.

Administer continuous IV regular insulin infusion at 0.1 units/kg/hour (an initial bolus of 0.1-0.15 units/kg may be given but is not required) 1, 2, 3.

Target glucose decline: 50-75 mg/dL per hour 1, 2. If glucose does not fall by ≥50 mg/dL in the first hour and hydration is adequate, double the insulin infusion rate every hour until steady decline is achieved 1, 2.

Continue insulin infusion until DKA resolution regardless of glucose level 1, 2:

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

Alternative Approach 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 1, 3. This requires adequate fluid replacement, frequent point-of-care glucose monitoring, treatment of concurrent infections, and appropriate follow-up 1.

Continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients 1, 3.

Bicarbonate Therapy

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 1, 2, 3. 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 1, 3.

Only consider bicarbonate for pH <6.9:

• pH <6.9: 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3
• pH 6.9-7.0: 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 3

Monitoring During Treatment

Draw blood every 2-4 hours for 1, 2, 3:

• Serum electrolytes, glucose, BUN, creatinine, osmolality
• Venous pH (typically 0.03 units lower than arterial pH—arterial gases are generally unnecessary after initial diagnosis) 1, 2
• β-hydroxybutyrate levels (preferred method for monitoring ketosis resolution) 1, 2

Follow venous pH and anion gap to monitor resolution of acidosis 1, 2. Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early 3.

Identification and Treatment of Precipitating Causes

Common precipitants that must be sought and treated concurrently 1, 3:

• Infection (most common trigger—obtain cultures and start appropriate antibiotics) 1, 3
• Myocardial infarction, cerebrovascular accident, pancreatitis
• Insulin omission or inadequacy
• SGLT2 inhibitor use (can cause euglycemic DKA—discontinue immediately and do not restart until 3-4 days after metabolic stability) 1, 3
• Glucocorticoid therapy, trauma, pregnancy

Transition to Subcutaneous Insulin

Administer basal insulin (intermediate or long-acting such as glargine, detemir, or NPH) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3. This overlap period is essential 1.

Critical pitfall: Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1.

Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 4, 1. For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day 1, 3.

Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1, 3.

Special Considerations

Euglycemic DKA

SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA (blood glucose <200-250 mg/dL with acidosis and ketonemia) 1. Incidence is 0.6-4.9 events per 1,000 patient-years with a relative risk of 2.46 versus placebo 1. Pregnant women with pre-gestational diabetes also have increased risk (≈2% develop DKA, frequently euglycemic) 1.

Management is identical to hyperglycemic DKA, but add dextrose earlier when glucose falls to 200-250 mg/dL 1. Check urine or blood ketones during illness even if glucose is normal in patients on SGLT2 inhibitors 1.

Cerebral Edema

Cerebral edema is a rare but frequently fatal complication, occurring in 0.7-1.0% of children with DKA 3. It occurs more commonly in children and adolescents than adults 1. Risk factors include higher BUN at presentation and overly aggressive fluid resuscitation 1, 3.

Prevention: Limit osmolality changes to ≤3 mOsm/kg/hour and monitor mental status continuously 1, 2, 3. Consider endotracheal intubation for Glasgow Coma Scale <8, pH <7.15 with respiratory acidosis, or severe respiratory distress 2.

Discharge Planning

Prior to discharge 1, 3:

• Identify outpatient diabetes care providers and schedule follow-up appointments
• Provide education on recognition, prevention, and management of DKA
• Educate on glucose monitoring, insulin administration, and recognition/treatment of hyperglycemia and hypoglycemia
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability
• Verify all prescriptions are filled and reviewed with patient and family
• Transmit comprehensive discharge summary to primary care clinician

Patient education should include: never stop basal insulin even when oral intake is limited, measure ketones when glucose exceeds 200 mg/dL or during illness, seek immediate medical attention if unable to tolerate oral hydration or symptoms worsen 1.