Diagnosis and Treatment of Diabetic Ketoacidosis (DKA)
Diabetic ketoacidosis is diagnosed by the triad of hyperglycemia (blood glucose >250 mg/dL), metabolic acidosis (pH <7.3, serum bicarbonate <18 mEq/L), and elevated serum or urine ketones, with varying severity based on pH levels. 1
Diagnostic Criteria for DKA
DKA is categorized by severity based on the following parameters:
| Parameter | Mild DKA | Moderate DKA | Severe DKA |
|---|---|---|---|
| Plasma glucose | >250 mg/dL | >250 mg/dL | >250 mg/dL |
| Arterial pH | 7.25-7.30 | 7.00-7.24 | <7.00 |
| Serum bicarbonate | 15-18 mEq/L | 10 to <15 mEq/L | <10 mEq/L |
| Urine ketones | Positive | Positive | Positive |
| Serum ketones | Positive | Positive | Positive |
| Anion gap | >10 mEq/L | >12 mEq/L | >12 mEq/L |
| Mental status | Alert | Alert/drowsy | Stupor/coma |
Note: Recent evidence suggests hyperglycemia has been de-emphasized due to increasing incidence of euglycemic DKA, particularly with sodium-glucose cotransporter-2 inhibitor use. 2
Essential Diagnostic Tests
- Plasma glucose
- Arterial blood gases (pH, bicarbonate)
- Serum ketones (preferred over urine ketones)
- Electrolytes with calculated anion gap
- Blood urea nitrogen/creatinine
- Complete blood count with differential
- Urinalysis
- Electrocardiogram
- A1C 2, 3
Additional Tests to Consider
- Blood and urine cultures (if infection suspected)
- Chest radiography
- Amylase, lipase
- Hepatic transaminase levels
- Troponin, creatine kinase 2
Differential Diagnosis
DKA must be distinguished from:
- Hyperosmolar hyperglycemic state (HHS)
- Other causes of high anion gap metabolic acidosis:
- Lactic acidosis
- Salicylate, methanol, ethylene glycol, or paraldehyde ingestion
- Chronic renal failure
- Alcoholic ketoacidosis
- Starvation ketosis 1, 3
Treatment Algorithm for DKA
1. Fluid Therapy
- Initial fluid: Isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (1-1.5 L in average adult) during first hour
- Subsequent fluids: Based on hydration status, electrolytes, and urine output 1
2. Insulin Therapy
For moderate to severe DKA:
- IV bolus of regular insulin at 0.15 units/kg body weight
- Followed by continuous infusion at 0.1 unit/kg/h (5-7 units/h in adults)
- If glucose doesn't fall by 50 mg/dL in first hour, double insulin infusion rate hourly until steady decline of 50-75 mg/h is achieved
For mild DKA:
- "Priming" dose of regular insulin (0.4-0.6 units/kg): half as IV bolus, half as subcutaneous/intramuscular injection
- Then 0.1 unit regular insulin subcutaneously/intramuscularly hourly 1
3. Potassium Replacement
- Begin potassium replacement when serum K+ <5.3 mEq/L and adequate urine output is established
- Withhold potassium if serum K+ >5.3 mEq/L
- If K+ <3.3 mEq/L, hold insulin and give potassium replacement first 1
4. Bicarbonate Therapy
- pH 6.9-7.0: 50 mmol sodium bicarbonate diluted in 200 mL sterile water, infused at 200 mL/h
- pH >7.0: No bicarbonate necessary 1
5. Phosphate Replacement
- Consider only for patients with:
- Cardiac dysfunction
- Anemia
- Respiratory depression
- Serum phosphate <1.0 mg/dL 1
6. Monitoring During Treatment
- Blood glucose every 1-2 hours
- Electrolytes, BUN, creatinine, venous pH every 2-4 hours
- Monitor for complications: cerebral edema, hypoglycemia, hypokalemia 1
7. Criteria for DKA Resolution
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3 1
8. Transition to Subcutaneous Insulin
- If NPO: Continue IV insulin with subcutaneous regular insulin as needed
- When eating: Start multiple-dose insulin regimen with short/rapid-acting and intermediate/long-acting insulin
- Continue IV insulin for 1-2 hours after subcutaneous regimen begins 1
Common Pitfalls and Caveats
Monitoring ketones: Nitroprusside method only measures acetoacetic acid and acetone, not β-hydroxybutyric acid (the predominant ketone in DKA). During treatment, β-hydroxybutyric acid converts to acetoacetic acid, falsely suggesting worsening ketosis. Direct measurement of β-hydroxybutyric acid is preferred. 1
Cerebral edema risk: Particularly in children, avoid too-rapid correction of glucose and osmolality. Use judicious fluid replacement. 1
Precipitating factors: Always identify and treat the underlying cause (infection, new-onset diabetes, insulin non-adherence, etc.). 4
SGLT-2 inhibitors: Be aware these medications can cause euglycemic DKA (DKA with lower-than-expected glucose levels). 2, 4
Electrolyte imbalances: Close monitoring of potassium is essential as insulin therapy drives potassium into cells, potentially causing dangerous hypokalemia. 1
Transition period: Abrupt discontinuation of IV insulin without adequate subcutaneous coverage can lead to recurrence of DKA. 1
By following this structured approach to diagnosis and management, DKA can be effectively treated with reduced risk of complications and mortality.