What is the acute management for a patient presenting with a plasma glucose of 562 mg/dL suggestive of diabetic ketoacidosis or hyperosmolar hyperglycemic state?

Acute Management of Severe Hyperglycemia (Blood Glucose 562 mg/dL)

Immediately initiate aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters in the first hour) while simultaneously obtaining stat laboratory tests to differentiate between diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), as both are life-threatening emergencies requiring ICU-level monitoring. 1, 2

Immediate Diagnostic Workup

Obtain the following stat laboratory tests to establish the diagnosis and guide treatment 1:

• Plasma glucose (already known: 562 mg/dL)
• Arterial blood gases or venous pH (venous pH is adequate and 0.03 units lower than arterial) 1, 3
• Serum electrolytes with calculated anion gap 1
• Serum or blood ketones (β-hydroxybutyrate preferred over nitroprusside method) 1, 3
• Blood urea nitrogen, creatinine (assess renal function) 1
• Calculated effective serum osmolality: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 4
• Urinalysis with urine ketones 1
• Complete blood count with differential 1
• Electrocardiogram (assess for myocardial infarction as precipitant and monitor for arrhythmias from electrolyte shifts) 1
• Bacterial cultures (blood, urine, throat) if infection suspected 1, 4

Diagnostic Differentiation

DKA Criteria 1, 3:

• Blood glucose >250 mg/dL
• Arterial pH <7.3
• Serum bicarbonate <15 mEq/L
• Moderate to large ketonuria/ketonemia
• Anion gap >12 mEq/L

HHS Criteria 1, 2, 4:

• Blood glucose >600 mg/dL
• Arterial pH >7.3
• Serum bicarbonate >15 mEq/L
• Minimal ketonuria/ketonemia
• Effective serum osmolality ≥320 mOsm/kg H₂O
• Altered mental status or severe dehydration

Note: Mixed presentations can occur, with features of both DKA and HHS coexisting in the same patient 1, 5.

Fluid Resuscitation Protocol

First Hour 1, 2, 4:

• Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour to restore intravascular volume and renal perfusion
• In the average adult, this equals approximately 1-1.5 liters in the first hour
• This aggressive initial fluid replacement is critical for improving insulin sensitivity and tissue perfusion 3

Subsequent Fluid Management 1:

After the first hour, adjust based on corrected serum sodium (add 1.6 mEq to sodium value for each 100 mg/dL glucose above 100 mg/dL) 4:

• 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
• When glucose reaches 250 mg/dL (DKA) or 300 mg/dL (HHS): Change to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion 1, 3, 4

Critical Pitfall: Do not correct osmolality faster than 3 mOsm/kg/hour, as overly rapid correction increases the risk of cerebral edema, particularly in pediatric patients 4.

Potassium Management (Critical)

NEVER start insulin if serum potassium is <3.3 mEq/L 3. Despite often presenting with normal or elevated potassium due to acidosis and dehydration, total body potassium depletion is universal in both DKA and HHS (3-5 mEq/kg in DKA, 4-6 mEq/kg in HHS) 1, 3, 4.

Potassium Replacement Protocol 1, 3:

• If K⁺ <3.3 mEq/L: Hold insulin, aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness
• 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 confirmed
• If K⁺ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2-4 hours, as levels will drop rapidly with insulin therapy 3
• Target serum potassium: 4-5 mEq/L throughout treatment 3

Critical Warning: Insulin drives potassium intracellularly, and inadequate potassium monitoring/replacement is a leading cause of mortality in hyperglycemic crises 3, 6.

Insulin Therapy

For Moderate-to-Severe DKA or Critically Ill/Altered Mental Status Patients 1, 3:

1. Confirm potassium ≥3.3 mEq/L before starting insulin 3
2. IV bolus: 0.1-0.15 units/kg regular insulin 1, 3
3. Continuous IV infusion: 0.1 units/kg/hour regular insulin 1, 3
4. Target glucose decline: 50-75 mg/dL per hour 1, 3
5. If glucose does not fall by 50 mg/dL in first hour: Check hydration status; if acceptable, double insulin infusion rate every hour until steady decline achieved 1

For Mild-to-Moderate Uncomplicated DKA in Hemodynamically Stable, Alert Patients 3, 2:

• 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 3
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 3
• Continuous IV insulin remains standard for critically ill and mentally obtunded patients 3

Critical Insulin Management Points 1, 3:

• Continue insulin infusion until DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 3
• Do NOT stop insulin when glucose falls to 250 mg/dL—instead add dextrose to IV fluids while continuing insulin 1, 3
• For HHS: Continue insulin until mental status improves and hyperosmolarity resolves 4
• Premature termination of insulin before complete resolution of ketosis is a common cause of recurrent DKA 3

Monitoring During Treatment

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

• Serum electrolytes
• Glucose
• Blood urea nitrogen
• Creatinine
• Osmolality
• Venous pH (adequate for monitoring; repeat arterial blood gases generally unnecessary) 4

Monitor β-hydroxybutyrate levels (when available) as the most accurate marker of ketosis resolution 3. The nitroprusside method only measures acetoacetate and acetone, missing β-hydroxybutyrate (the predominant ketone), and should not be used for monitoring 1, 3.

Resolution Criteria

DKA Resolution 3:

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

HHS Resolution 4:

• Mental status improvement
• Effective serum osmolality <320 mOsm/kg H₂O
• Adequate hydration

Transition to Subcutaneous Insulin

Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 3, 2, 4. This overlap period is essential—stopping IV insulin without prior subcutaneous basal insulin causes rebound hyperglycemia 3.

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

Identify and Treat Precipitating Causes

Common precipitants requiring simultaneous treatment 1, 3, 2:

• Infection (most common in HHS) 2
• Myocardial infarction (can both precipitate and be masked by DKA) 3
• Cerebrovascular accident 3
• Insulin omission or inadequacy 1, 3
• Pancreatitis 3
• SGLT2 inhibitor use (discontinue immediately; do not restart until 3-4 days after metabolic stability) 3
• Glucocorticoid use 3
• Pregnancy 3

Obtain bacterial cultures and administer appropriate antibiotics if infection suspected 1, 2, 4.

Bicarbonate Administration

Bicarbonate is NOT recommended for pH >6.9-7.0 3, 4. 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 3, 4.

Special Considerations

Euglycemic DKA 3:

• Can occur with SGLT2 inhibitor use, pregnancy, or reduced oral intake
• Defined by glucose <200-250 mg/dL with pH <7.3, bicarbonate <15 mEq/L, and ketonemia
• Check ketones even when glucose is not severely elevated if patient is on SGLT2 inhibitors or pregnant
• Measure β-hydroxybutyrate (not nitroprusside-based tests) for diagnosis

Cerebral Edema Risk 3:

• More common in children and adolescents
• Monitor closely for altered mental status, headache, or neurological deterioration
• Avoid overly rapid correction of osmolality (>3 mOsm/kg/hour) 4

Common Pitfalls to Avoid

1. Starting insulin before excluding hypokalemia (K⁺ <3.3 mEq/L) can precipitate life-threatening arrhythmias 3, 4
2. Stopping insulin when glucose falls to 250 mg/dL instead of adding dextrose and continuing insulin until ketosis resolves 1, 3
3. Inadequate potassium monitoring and replacement is a leading cause of mortality 3
4. Premature discontinuation of IV insulin without prior subcutaneous basal insulin causes rebound hyperglycemia 3, 2
5. Using nitroprusside-based ketone tests instead of β-hydroxybutyrate for monitoring 1, 3
6. Overly rapid correction of osmolality increases cerebral edema risk 4
7. Administering bicarbonate for pH >7.0 provides no benefit and may cause harm 3, 4