How should I manage a patient with diabetes mellitus who presents in ketosis?

Management of Diabetes Mellitus in Ketosis

Immediately measure blood or urine ketones and blood glucose in any patient with diabetes presenting with symptoms of ketosis (nausea, abdominal pain) or unexplained hyperglycemia, then implement sick day rules or seek emergency care if ketones are elevated. 1

Initial Assessment and Diagnostic Approach

Ketone Measurement Strategy

• Measure β-hydroxybutyrate (β-OHB) in blood as the preferred test because nitroprusside-based urine dipsticks only detect acetoacetate and acetone, missing the predominant ketone body and potentially underestimating total ketone concentration by 50% or more. 1
• Urine ketone testing remains highly sensitive for ruling out significant ketosis with high negative predictive value, making it acceptable when blood ketone meters are unavailable. 1
• Normal ketone levels are <0.5 mmol/L total serum ketones; elevated levels suggest impending or established diabetic ketoacidosis (DKA). 1

Determine Severity and Type of Ketosis

For Diabetic Ketoacidosis (DKA):

• Blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, presence of ketonemia/ketonuria, and anion gap >12 mEq/L. 2, 3
• Obtain plasma glucose, electrolytes with anion gap, serum ketones (preferably β-OHB), BUN/creatinine, arterial or venous pH, osmolality, urinalysis, CBC, and ECG. 2, 3

For Euglycemic DKA:

• Blood glucose <200-250 mg/dL with pH <7.3, bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and ketonemia/ketonuria. 2
• Most commonly caused by SGLT2 inhibitors (relative risk 2.46 vs placebo), pregnancy (≈2% of pregnancies in pre-gestational diabetes), or acute illness with reduced oral intake. 2

Home Management for Mild Ketosis (Non-Emergency)

Sick Day Rules Implementation

• Increase oral hydration aggressively with water or sugar-free fluids to maintain urine output. 1
• Administer additional short- or rapid-acting insulin (typically 10-20% of total daily dose every 2-4 hours) while continuing basal insulin. 1
• Consume oral carbohydrates (15-30g every 3-4 hours) to prevent starvation ketosis while insulin is working. 1
• Monitor blood glucose and ketones every 2-4 hours to track response to treatment. 1
• Seek medical advice immediately if symptoms worsen, ketone concentrations increase, or oral hydration cannot be maintained due to vomiting or mental status changes. 1

Critical Warning: Never Stop Basal Insulin

• Continue basal insulin even when oral intake is limited or blood glucose is normal, as stopping insulin is a common precipitant of DKA. 2

Hospital Management for Moderate-to-Severe DKA

Fluid Resuscitation Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in first hour) to restore intravascular volume and renal perfusion. 2, 3
• After the first hour, calculate corrected sodium (add 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL): if corrected sodium is normal/elevated, switch to 0.45% NaCl at 4-14 mL/kg/hour; if low, continue 0.9% NaCl. 2
• When glucose reaches 250 mg/dL, change to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution. 2, 3

Potassium Management (Critical)

• If K+ <3.3 mEq/L: HOLD insulin and replace potassium aggressively until K+ ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness. 2, 3
• If K+ 3.3-5.5 mEq/L: add 20-30 mEq potassium per liter of IV fluid (2/3 KCl and 1/3 KPO₄) once adequate urine output confirmed. 2, 3
• If K+ >5.5 mEq/L: withhold potassium initially but monitor every 2-4 hours as levels will fall rapidly with insulin therapy. 2
• Target serum potassium 4-5 mEq/L throughout treatment; total body potassium depletion averages 3-5 mEq/kg despite potentially normal initial levels. 2, 3

Insulin Therapy Protocol

For Critically Ill or Mentally Obtunded Patients:

• Continuous IV regular insulin at 0.1 units/kg/hour is the standard of care after confirming K+ ≥3.3 mEq/L. 2, 3
• Give IV bolus of 0.1-0.15 units/kg regular insulin before starting infusion. 2
• Target glucose decline of 50-75 mg/dL per hour; if <50 mg/dL decline in first hour and hydration adequate, double infusion rate hourly until steady decline achieved. 2, 3

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. 2
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections. 2

Critical Insulin Management Principles

• Continue insulin infusion until complete DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose level. 2, 3
• Never stop insulin when glucose reaches 250 mg/dL—this is the most common cause of persistent or recurrent ketoacidosis; instead add dextrose and continue insulin. 2
• Target glucose 150-200 mg/dL until DKA resolution parameters met. 2

Bicarbonate Administration

• Bicarbonate is NOT recommended for pH >6.9-7.0 as multiple studies show no difference in resolution time or outcomes, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 2

Monitoring During Treatment

• Draw blood every 2-4 hours for electrolytes, glucose, BUN, creatinine, osmolality, and venous pH (arterial gases generally unnecessary). 2, 3
• Use serial β-hydroxybutyrate measurements to track ketosis resolution; reduction in β-OHB is the most accurate marker of successful treatment. 2
• Monitor for cerebral edema (especially in children): lethargy, behavioral changes, seizures, bradycardia, respiratory arrest. 4

Transition to Subcutaneous Insulin

• Administer basal insulin (glargine, detemir, or NPH) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 2, 3
• This overlap period is essential; stopping IV insulin without prior basal insulin administration is a common cause of treatment failure. 2
• Start multiple-dose schedule with combination of short/rapid-acting and intermediate/long-acting insulin once patient can eat. 2

Special Considerations

SGLT2 Inhibitor-Associated Ketosis

• Discontinue SGLT2 inhibitors immediately when ketosis or DKA is suspected. 2
• Do not restart until 3-4 days after metabolic stability achieved and acute illness resolved. 2
• Stop SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA. 2
• Educate patients to check ketones during illness even if glucose is normal, and avoid prolonged fasting or very-low-carbohydrate diets while on these medications. 2

Ketogenic Diet-Associated Ketosis

• Severe carbohydrate restriction can precipitate euglycemic DKA in patients with diabetes, requiring modified DKA protocol with IV dextrose-containing fluids and delayed insulin until glucose >250 mg/dL. 5

Pregnancy

• Pregnant women with pre-gestational diabetes have ≈2% risk of DKA, frequently presenting with euglycemia (glucose <200 mg/dL). 2
• Counsel high-risk pregnant patients on DKA signs and instruct to seek prompt medical care. 2

Identification and Treatment of Precipitating Causes

• Obtain bacterial cultures (urine, blood, throat) and administer appropriate antibiotics if infection suspected. 2, 3
• Consider and treat concurrently: myocardial infarction, cerebrovascular accident, pancreatitis, trauma, insulin omission/inadequacy, glucocorticoid use, or alcohol abuse. 2, 3

Common Pitfalls to Avoid

• Starting insulin before correcting hypokalemia (K+ <3.3 mEq/L) causes life-threatening arrhythmias. 2
• Stopping insulin when glucose falls to 250 mg/dL instead of adding dextrose leads to recurrent ketoacidosis. 2
• Using nitroprusside-based ketone tests for monitoring misses β-hydroxybutyrate and delays appropriate therapy. 2
• Premature termination of insulin therapy before complete resolution of ketosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L). 2
• Overly rapid correction of osmolality increases cerebral edema risk, particularly in children. 2
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 2

Patient Education Before Discharge

• Identify outpatient diabetes care provider and schedule follow-up appointment before discharge. 2
• Educate on glucose monitoring, home glucose goals, insulin administration, and recognition/treatment of hyperglycemia and hypoglycemia. 2, 3
• Teach when to check ketones: unexplained hyperglycemia >200 mg/dL, illness with nausea/vomiting, or abdominal pain. 1, 2
• Review sick day rules and when to call healthcare provider or present to emergency department. 1, 2