What are the key investigations and management for diabetic ketoacidosis (DKA), including medications and non-medical management?

Management of Diabetic Ketoacidosis (DKA)

For DKA management, begin with aggressive isotonic fluid resuscitation at 15-20 mL/kg/hour in the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L throughout treatment. 1, 2

Key Investigations

Initial Laboratory Workup

• Plasma glucose, blood urea nitrogen, creatinine, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, osmolality, arterial blood gases, complete blood count with differential, and electrocardiogram 1, 2, 3
• Urinalysis and urine ketones 1, 2
• Direct measurement of β-hydroxybutyrate in blood is preferred over nitroprusside method, as nitroprusside only measures acetoacetic acid and acetone, not β-hydroxybutyrate 2, 3

Diagnostic Criteria

• Plasma glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <18 mEq/L (some guidelines use <15 mEq/L), and positive serum/urine ketones 1, 2
• Note that euglycemic DKA is increasingly recognized, particularly with SGLT2 inhibitor use, so hyperglycemia should not be overemphasized 4

Identify Precipitating Causes

• Obtain bacterial cultures (urine, blood, throat) if infection is suspected and administer appropriate antibiotics 1, 2
• Search for myocardial infarction, stroke, pancreatitis, trauma, or medication non-compliance as triggers 2, 3
• Consider troponin, creatine kinase, amylase, lipase, hepatic transaminases, blood and urine cultures, and chest radiography based on clinical presentation 4

Fluid Therapy

Initial Resuscitation

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg body weight/hour during the first hour (approximately 1-1.5 L in average adults) 1, 2, 3
• Some guidelines now recommend balanced electrolyte solutions rather than 0.9% saline to avoid hyperchloremic acidosis 3

Subsequent Fluid Management

• Continue fluid replacement based on hydration status, serum electrolyte levels, and urine output 1, 2
• Total fluid replacement should correct estimated deficits within 24 hours, with induced change in serum osmolality not exceeding 3 mOsm/kg/hour to prevent cerebral edema 3
• When serum glucose reaches 250 mg/dL, change fluid to 5% dextrose with 0.45-0.75% NaCl 2

Insulin Therapy

Initial Insulin Administration

• Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour without an initial bolus for moderate to severe DKA 1, 2, 3
• Some protocols include an initial IV bolus of 0.15 units/kg, though this is not universally recommended 3

Insulin Dose Adjustment

• If plasma glucose does not fall by 50 mg/dL in the first hour, check hydration status; if acceptable, double the insulin infusion rate hourly until steady glucose decline of 50-75 mg/hour is achieved 1, 2, 3
• When serum glucose reaches 250 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 1
• Continue insulin infusion until DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 2, 3

Alternative Approach for Mild DKA

• For uncomplicated mild DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective, safer, and more cost-effective than IV insulin 5, 2, 3
• This approach requires adequate fluid replacement, frequent bedside glucose monitoring, treatment of concurrent infections, and appropriate follow-up 5

Electrolyte Management

Potassium Replacement (Critical)

• If serum potassium <3.3 mEq/L, DELAY insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 2
• Once renal function is assured and serum potassium is <5.3 mEq/L (some guidelines use <5.5 mEq/L), add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) 1, 2, 3
• Maintain serum potassium between 4-5 mEq/L throughout treatment 1, 2
• Monitor potassium levels closely as insulin therapy and correction of acidosis cause rapid shifts into cells, leading to hypokalemia 1, 3

Bicarbonate Administration

• Bicarbonate is generally NOT recommended for DKA patients with pH >6.9-7.0, as studies show no difference in resolution of acidosis or time to discharge 5, 1, 2, 3
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 2
• For adult patients with pH <6.9, consider 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3

Phosphate Replacement

• Routine phosphate replacement has not shown beneficial effects on clinical outcomes in DKA 3
• Consider phosphate replacement only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 3

Monitoring During Treatment

Glucose Monitoring

• Check blood glucose every 1-2 hours 1
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 2

Laboratory Monitoring

• Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2, 3
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1, 2, 3

Cardiac Monitoring

• Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early, particularly related to potassium disturbances 3

Fluid Balance

• Monitor fluid input/output, hemodynamic parameters, and clinical examination to assess progress with fluid replacement 3

Resolution Criteria

DKA is resolved when ALL of the following are met: 1, 2, 3

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

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 5, 1, 2, 3
• Recent evidence suggests adding low-dose subcutaneous basal insulin analog (e.g., glargine) alongside IV insulin may prevent rebound hyperglycemia and shorten hospital stays 3

Insulin Regimen After Resolution

• When patient can eat, transition to multiple-dose regimen using combination of short/rapid-acting and intermediate/long-acting insulin 2, 3
• For newly diagnosed patients, initiate multidose regimen at approximately 0.5-1.0 units/kg/day 3

Non-Medical Management

Identify and Treat Underlying Causes

• Treat any correctable underlying cause such as sepsis, myocardial infarction, stroke, or discontinue precipitating medications 5, 2
• SGLT2 inhibitors must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 2, 3

Nutritional Support

• If patient is NPO (nothing by mouth) after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 2
• Resume oral intake as tolerated once mental status normalizes and nausea/vomiting resolves 2

Patient Education Before Discharge

• Identification of outpatient diabetes care providers 5
• Understanding of diabetes diagnosis, glucose monitoring, home glucose goals, and when to call healthcare professional 5
• Definition, recognition, treatment, and prevention of hyperglycemia and hypoglycemia 5
• Sick-day management protocols 5
• Proper insulin administration technique and disposal of diabetes supplies 5
• Referral to outpatient registered dietitian nutritionist or diabetes care and education specialist 5

Discharge Planning

• Schedule follow-up appointments prior to discharge with agreed-upon time and place to increase attendance likelihood 5
• Ensure prescriptions for new or changed medications are filled and reviewed before discharge 5
• Transmit discharge summaries to primary care clinician as soon as possible after discharge 5

Critical Pitfalls to Avoid

Insulin Management Errors

• Premature termination of insulin therapy before complete resolution of ketosis leads to recurrence of DKA 1, 2
• Interruption of insulin infusion when glucose levels fall without adding dextrose causes persistent or worsening ketoacidosis 1, 2
• Never stop IV insulin before administering basal subcutaneous insulin 2-4 hours prior 5, 1, 2

Electrolyte Management Errors

• Inadequate monitoring and replacement of potassium is a leading cause of mortality in DKA 2
• Starting insulin when potassium <3.3 mEq/L can cause cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness 3

Fluid Management Errors

• Overly rapid correction of osmolality increases risk of cerebral edema, particularly in children 2
• Higher BUN at presentation is a risk factor for cerebral edema 3

Monitoring Errors

• Relying on nitroprusside method to measure ketones is misleading as it only measures acetoacetic acid and acetone, not β-hydroxybutyrate 1, 2, 3

Special Populations

Pregnancy

• Good diabetes control is especially important; pregnancy may make diabetes management more difficult 6

Renal Disease, Heart Failure, Acute Coronary Syndrome

• These comorbidities require tailored fluid management strategies with more cautious fluid administration 7

SGLT2 Inhibitor Users

• Higher risk of euglycemic DKA; discontinue 3-4 days before surgery 2, 3