What is the management approach for acute metabolic complications of diabetes, such as diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar nonketotic syndrome (HHNS)?

Management of Acute Metabolic Complications of Diabetes

Begin immediate aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous insulin infusion at 0.1 units/kg/hour for DKA, while carefully monitoring and replacing potassium to prevent life-threatening hypokalemia. 1, 2

Initial Assessment and Diagnosis

Laboratory Evaluation

Obtain the following tests immediately upon presentation 1, 2, 3:

• Plasma glucose, blood urea nitrogen/creatinine, serum ketones (preferably β-hydroxybutyrate)
• Electrolytes with calculated anion gap, osmolality
• Arterial blood gases (initial only; venous pH sufficient for monitoring)
• Complete blood count with differential, electrocardiogram
• Urinalysis with urine ketones
• HbA1c to distinguish acute versus chronic poor control
• Bacterial cultures (blood, urine, throat) if infection suspected

Diagnostic Criteria

For DKA: Blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 2, 3

For HHS: Blood glucose >600 mg/dL, arterial pH >7.3, serum bicarbonate >15 mEq/L, altered mental status or severe dehydration, and minimal ketonemia 1

Critical distinction: Up to one-third of patients present with mixed features of both DKA and HHS, requiring tailored management based on predominant clinical features 4

Fluid Resuscitation

Initial Phase (First Hour)

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters in average adults) regardless of corrected serum sodium 1, 2, 3
• This aggressive initial resuscitation is critical for restoring intravascular volume and renal perfusion 1

Subsequent Fluid Management

After the first hour, fluid choice depends on corrected serum sodium (add 1.6 mEq/L to measured sodium 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
• When glucose reaches 250 mg/dL (DKA) or 300 mg/dL (HHS): Add 5-10% dextrose to intravenous fluids while continuing insulin therapy 1, 5

Critical pitfall: In HHS, fluid replacement is the cornerstone of therapy due to more severe dehydration; however, avoid overly rapid correction of osmolality, especially in elderly patients, as this increases cerebral edema risk 4, 6

Insulin Therapy

Standard Protocol for Moderate-to-Severe DKA

• Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour without an initial bolus 1, 2, 3
• The American Diabetes Association recommends this as the preferred method for moderate-to-severe DKA 2

Monitoring and Adjustment

• If glucose does not fall by 50 mg/dL in the first hour: Verify adequate hydration, then double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/hour 1
• When glucose reaches 250 mg/dL (DKA) or 300 mg/dL (HHS): Decrease insulin infusion to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 1, 2
• Target glucose: Maintain 150-200 mg/dL until complete resolution of ketoacidosis 3

Alternative for Mild DKA

For mild, uncomplicated DKA in alert patients, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective and safer than IV insulin 3:

• Give initial dose of 0.4-0.6 units/kg (half IV bolus, half subcutaneous)
• Follow with 0.1 units/kg/hour subcutaneously 1

Critical warning: Never stop insulin infusion when glucose falls below 250 mg/dL; instead, add dextrose to prevent hypoglycemia while continuing insulin to clear ketosis 5, 7

Potassium Management

Assessment Before Insulin

Do NOT start insulin if serum potassium is <3.3 mEq/L 3:

• Delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L
• Failure to correct hypokalemia before insulin can cause life-threatening cardiac arrhythmias and respiratory muscle weakness 3, 8

Replacement Protocol

Once potassium is ≥3.3 mEq/L and urine output is adequate 1, 3:

• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to each liter of IV fluid (use 2/3 KCl and 1/3 KPO₄)
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy
• Target: Maintain serum potassium 4-5 mEq/L throughout treatment 5, 3

Critical pitfall: Despite presenting hyperkalemia, total body potassium depletion is universal in DKA; insulin therapy drives potassium intracellularly, and inadequate monitoring/replacement is a leading cause of mortality 2, 3, 8

Bicarbonate Therapy

Bicarbonate administration is NOT recommended for DKA patients with pH >6.9-7.0 3:

• Studies show no difference in resolution of acidosis or time to discharge with bicarbonate use
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 3

Monitoring During Treatment

Frequency

• Blood glucose: Every 1-2 hours 5
• Comprehensive metabolic panel: Every 2-4 hours (electrolytes, glucose, BUN, creatinine, osmolality, venous pH) 1, 5, 3
• Venous pH: Adequate for monitoring (typically 0.03 units lower than arterial pH); repeat arterial blood gases are unnecessary 1, 3

Ketone Monitoring

• Preferred method: Direct measurement of β-hydroxybutyrate in blood 5, 3
• Avoid relying on nitroprusside method: Only measures acetoacetic acid and acetone, not β-hydroxybutyrate (the predominant ketone body); during therapy, β-hydroxybutyrate converts to acetoacetic acid, falsely suggesting worsening ketosis 1, 5

Resolution Criteria

DKA is resolved when ALL of the following are met 2, 3:

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

For HHS: Resolution includes glucose <300 mg/dL, improved mental status, and normalized osmolality 1

Transition to Subcutaneous Insulin

Critical Timing

Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion 2, 3:

• This prevents recurrence of ketoacidosis and rebound hyperglycemia
• Most common error: Stopping IV insulin without prior basal insulin administration leads to DKA recurrence 2

Dosing for Newly Diagnosed Patients

• Start with approximately 0.5-0.8 units/kg/day as a multidose regimen combining short/rapid-acting and intermediate/long-acting insulin 1, 2
• Adjust based on subsequent glucose monitoring

Identification and Treatment of Precipitating Factors

Common precipitating causes requiring simultaneous treatment 1, 3, 9:

• Infections (most common): Obtain cultures and start appropriate antibiotics
• Insulin omission or inadequate dosing: Particularly in known diabetics
• New diagnosis of diabetes
• Myocardial infarction: Obtain ECG and cardiac biomarkers
• Medications: Corticosteroids, thiazides, sympathomimetics, SGLT2 inhibitors
• Pancreatitis, cerebrovascular accident, trauma

SGLT2 inhibitor warning: Discontinue 3-4 days before any planned surgery to prevent euglycemic DKA 3

Special Considerations

Euglycemic DKA

Increasingly recognized with SGLT2 inhibitor use 5:

• Key difference: Blood glucose may be normal or only mildly elevated (<250 mg/dL)
• Management: Add dextrose-containing fluids EARLIER in treatment while continuing insulin therapy to clear ketosis
• Never interrupt insulin infusion when glucose falls; add dextrose to prevent hypoglycemia 5

Pediatric Patients

• Use more conservative fluid replacement (1.5 times 24-hour maintenance requirements, not exceeding 2 times maintenance) to minimize cerebral edema risk 1
• Avoid overly rapid correction of hyperosmolarity 3, 4

Elderly Patients and HHS

• May require more aggressive fluid resuscitation due to severe dehydration 4, 6
• Monitor for cardiac compromise given higher prevalence of heart disease
• Mortality remains higher in this population, particularly when precipitating illness is severe 6

Common Pitfalls to Avoid

1. Premature termination of insulin therapy before complete resolution of ketoacidosis (most common cause of treatment failure) 5, 3, 7
2. Inadequate potassium monitoring and replacement leading to life-threatening hypokalemia 3, 8
3. Stopping IV insulin without prior basal insulin administration (2-4 hour overlap required) 2, 3
4. Interrupting insulin when glucose falls without adding dextrose 5, 7
5. Relying on nitroprusside method for ketone monitoring instead of β-hydroxybutyrate 1, 5
6. Overly rapid correction of osmolality increasing cerebral edema risk, especially in children 3, 4
7. Administering bicarbonate for pH >7.0 which provides no benefit and may cause harm 3

Site of Care

ICU admission is indicated for 4:

• Cardiovascular instability
• Inability to protect airway
• Severe obtundation
• Acute abdominal signs suggesting gastric dilatation
• Inadequate floor capacity for continuous insulin infusion and frequent monitoring