Diabetic Ketoacidosis: Definition and Comprehensive Management

What is Diabetic Ketoacidosis?

Diabetic ketoacidosis (DKA) is a life-threatening acute metabolic emergency characterized by the triad of hyperglycemia (typically >250 mg/dL), metabolic acidosis (pH <7.3, bicarbonate <15-18 mEq/L), and elevated ketone bodies (β-hydroxybutyrate), resulting from absolute or relative insulin deficiency combined with elevated counterregulatory hormones. 1

Pathophysiology

The underlying mechanism involves a reduction in effective circulating insulin coupled with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone), which leads to: 1

Increased hepatic and renal glucose production with impaired peripheral glucose utilization, causing hyperglycemia 1
Unrestrained lipolysis from adipose tissue, releasing free fatty acids 1
Hepatic fatty acid oxidation to ketone bodies (β-hydroxybutyrate and acetoacetate), resulting in ketonemia and metabolic acidosis 1
Osmotic diuresis from glycosuria, causing massive losses of water, sodium, potassium, and other electrolytes 1

Epidemiology and Risk

DKA occurs in both type 1 and type 2 diabetes, with mortality rates of approximately 5% in experienced centers 1
Recent data show concerning increases in DKA rates: up to 44.5-82.6 per 1,000 person-years in type 1 diabetes and up to 3.2 per 1,000 person-years in type 2 diabetes 1
Approximately 10% of DKA cases present as euglycemic DKA (glucose <200 mg/dL), particularly associated with SGLT2 inhibitors, pregnancy, alcohol use, reduced food intake, or liver failure 1

Diagnostic Criteria

All of the following criteria must be met to diagnose DKA: 1

Blood glucose >250 mg/dL (or prior diabetes history if euglycemic) 2
Arterial pH <7.3 2
Serum bicarbonate <15-18 mEq/L 2
Anion gap >10-12 mEq/L 2
Presence of ketonemia or ketonuria 2

Initial Laboratory Evaluation

Obtain the following tests immediately: 2, 3

Plasma glucose, blood urea nitrogen, creatinine
Serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap, osmolality
Arterial blood gases (or venous pH, which is typically 0.03 units lower than arterial) 2
Urinalysis with urine ketones
Complete blood count with differential
Electrocardiogram with continuous cardiac monitoring 3
Hemoglobin A1C 4

If infection suspected: obtain bacterial cultures (blood, urine, throat) and chest radiography 2, 4

Critical diagnostic note: β-hydroxybutyrate measurement in blood is the preferred method for diagnosis and monitoring, as nitroprusside-based tests only detect acetoacetate and acetone, not β-hydroxybutyrate (the predominant ketone in DKA) 1, 2

Management Protocol

1. Fluid Resuscitation (First Priority)

Begin immediately with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) to restore intravascular volume and tissue perfusion. 2, 5

Subsequent fluid choice depends on hydration status, serum electrolytes, and urine output 2
When glucose reaches 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 2, 3
Total fluid replacement should correct estimated deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg/hour to prevent cerebral edema 3

2. Insulin Therapy

For moderate-to-severe DKA or critically ill/mentally obtunded patients: Start continuous IV regular insulin infusion at 0.1 units/kg/hour (this is the standard of care). 2, 5, 3

If glucose does not fall by 50 mg/dL in the first hour, check hydration status; if adequate, double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour 2, 3
Target glucose decline: 50-75 mg/dL per hour 2
Continue insulin infusion until DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 2, 5
Do NOT stop insulin when glucose normalizes—this is a critical error that causes persistent ketoacidosis 2

Alternative for mild-to-moderate uncomplicated DKA in hemodynamically stable, alert patients: Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 2, 5, 3

3. Potassium Management (Critical)

Despite potentially normal or elevated initial levels, total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg body weight), and insulin therapy will unmask this by driving potassium intracellularly. 2, 3

Potassium replacement protocol: 2, 3

If K+ <3.3 mEq/L: HOLD insulin therapy and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 2, 3
If K+ 3.3-5.5 mEq/L: Add 20-40 mEq potassium per liter of IV fluid (use 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 closely every 2-4 hours, as levels will drop rapidly with insulin therapy 2, 3
Target serum potassium: 4-5 mEq/L throughout treatment 2, 3

4. Bicarbonate Therapy

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no benefit in resolution time or outcomes, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 2, 5, 3

Only consider bicarbonate if pH <6.9: Administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3
If pH 6.9-7.0: Administer 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 3

5. Phosphate Replacement

Routine phosphate replacement is NOT recommended, as studies show no beneficial effects on clinical outcomes 3

Consider phosphate replacement only if: 3

Cardiac dysfunction present
Anemia present
Respiratory depression present
Serum phosphate <1.0 mg/dL

Monitoring During Treatment

Draw blood every 2-4 hours to measure: 2, 3

Serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, venous pH
β-hydroxybutyrate levels (preferred over nitroprusside-based ketone tests) 1, 2

Monitor continuously: 3

Cardiac rhythm (to detect arrhythmias from electrolyte shifts)
Fluid input/output
Hemodynamic parameters
Mental status (for cerebral edema, especially in children)

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

Transition to Subcutaneous Insulin

This is a critical step where errors commonly occur:

Administer basal insulin (glargine, detemir, or intermediate-acting) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 2, 5, 3

If patient can eat: Start multiple-dose regimen using combination of short/rapid-acting and intermediate/long-acting insulin at approximately 0.5-1.0 units/kg/day 3
If patient remains NPO: Continue IV insulin and fluid replacement, supplement with subcutaneous regular insulin as needed 2
Monitor glucose every 2-4 hours during transition period 5

Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 2, 3

Treatment of Precipitating Causes

Identify and treat underlying triggers concurrently: 2, 5, 3

Infection (most common: 30-50% of cases): Obtain cultures and administer appropriate antibiotics 2, 6
Myocardial infarction, stroke, pancreatitis, trauma: Obtain troponin, ECG, imaging as indicated 2, 4
Insulin omission or inadequacy: Most common in type 1 diabetes 2
SGLT2 inhibitors: Discontinue immediately and do not restart until 3-4 days after metabolic stability; these drugs increase DKA risk 2.46-fold in type 2 diabetes 1, 3
Pregnancy, alcohol use, very-low-carbohydrate diets: Can precipitate euglycemic DKA 1

Critical Pitfalls to Avoid

Common errors that worsen outcomes: 2, 3

Stopping IV insulin when glucose normalizes before ketoacidosis resolves—this causes persistent or recurrent DKA 2
Failing to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 2
Inadequate potassium monitoring and replacement—leading cause of mortality in DKA 2
Starting insulin before correcting severe hypokalemia (K+ <3.3 mEq/L)—can cause fatal arrhythmias 2, 3
Stopping IV insulin without prior basal insulin administration—causes rebound hyperglycemia and ketoacidosis 2, 5
Overly rapid correction of osmolality—increases cerebral edema risk, especially in children 2, 3
Using nitroprusside-based ketone tests for monitoring—these do not measure β-hydroxybutyrate and may show worsening ketones as DKA improves 1, 2

Special Populations

Pregnancy

Up to 2% of pregnancies with pregestational diabetes are complicated by DKA 1
Pregnant individuals may present with euglycemic DKA (glucose <200 mg/dL) 1
Significant risk of feto-maternal harm—pregnant individuals at risk should be counseled on signs/symptoms and seek immediate medical attention 1

Type 2 Diabetes

DKA in type 2 diabetes is increasingly common, particularly with SGLT2 inhibitor use 1, 7
Type 2 diabetes patients may require longer treatment periods (36 vs 29 hours) to achieve ketone-free urine compared to type 1 diabetes 8
Infections are more common precipitants in type 2 diabetes (48% vs 22% in type 1) 8

Children and Adolescents

Cerebral edema occurs in 0.7-1.0% of pediatric DKA cases and is frequently fatal 3
Higher BUN at presentation is a risk factor for cerebral edema 3
For mild DKA in children: Use 1.5 times 24-hour maintenance fluid requirements (5 mL/kg/hour); do not exceed twice maintenance 3

Prevention and Discharge Planning

Before discharge, ensure: 2, 3

Identification of outpatient diabetes care providers with follow-up scheduled within 1-2 weeks 5, 3
Patient education on glucose monitoring, insulin administration, recognition of hyperglycemia/hypoglycemia 3
Sick day management instructions: Never stop basal insulin even if not eating; provide detailed instructions on insulin dose adjustments during illness or fasting 1
Understanding of DKA signs/symptoms and when to seek immediate medical attention 3
If on SGLT2 inhibitors: Discontinue 3-4 days before any planned surgery and during acute illness 2, 3

Patient education reduces DKA recurrence rates through early detection and improved self-management 6

What is diabetic ketoacidosis (DKA) and how is it managed in patients with type 1 and type 2 diabetes?

Help us tailor your experience