Management of Diabetic Ketoacidosis
Begin with aggressive isotonic saline resuscitation at 15–20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, and continue insulin until complete resolution of ketoacidosis regardless of glucose levels. 1
Initial Assessment and Diagnosis
Obtain the following laboratory studies immediately upon presentation 1:
- Plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap
- Serum ketones (β-hydroxybutyrate preferred), BUN, creatinine, calculated effective serum osmolality
- Urinalysis with ketones, complete blood count with differential, electrocardiogram
- Blood, urine, and throat cultures if infection is suspected 1
DKA is diagnosed when all of the following criteria are met: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of moderate-to-large ketonemia or ketonuria with anion gap >12 mEq/L 1
Critical Pitfall: Euglycemic DKA
SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA, presenting with blood glucose <200–250 mg/dL but meeting all other DKA criteria 1. Discontinue SGLT2 inhibitors immediately and do not restart until 3–4 days after metabolic stability is achieved 1. Other precipitants of euglycemic DKA include pregnancy (≈2% of pregnancies in women with pre-gestational diabetes) and acute illness with reduced oral intake 1.
Fluid Resuscitation Protocol
First Hour
Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (approximately 1–1.5 L in the average adult) to restore intravascular volume and renal perfusion 1, 2. The typical total body water deficit in DKA is 6–9 L 1.
After the First Hour
Calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1, 2:
- If corrected sodium is normal or elevated: Switch to 0.45% NaCl at 4–14 mL/kg/hour 1, 2
- If corrected sodium is low: Continue 0.9% NaCl at 4–14 mL/kg/hour 1, 2
When Glucose Falls to 250 mg/dL
Change IV fluids to 5% dextrose with 0.45–0.75% NaCl while maintaining the insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2. Target glucose between 150–200 mg/dL until DKA resolution parameters are met 1.
For euglycemic DKA (initial glucose <250 mg/dL), start dextrose-containing fluids (D5W with 0.45–0.75% NaCl) simultaneously with insulin infusion from the outset 1, 2.
Fluid Correction Rate
Aim to correct the estimated fluid deficit within 24 hours while limiting the change in serum osmolality to ≤3 mOsm/kg/hour to reduce the risk of cerebral edema 1. In patients with cardiac or renal impairment, monitor closely for fluid overload 1.
Potassium Management (Class A Evidence)
Total body potassium depletion is universal in DKA (≈3–5 mEq/kg body weight), even when serum potassium appears normal or elevated initially 1, 2. Insulin therapy will unmask this depletion by driving potassium intracellularly 1.
Potassium-Based Insulin Initiation Algorithm
If serum K⁺ <3.3 mEq/L: Hold insulin and aggressively replace potassium at 20–40 mEq/hour until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 1, 2. This is a Class A recommendation based on high-quality randomized controlled trials 1.
If K⁺ 3.3–5.5 mEq/L: Start insulin and add 20–30 mEq potassium per liter of IV fluid (approximately 2/3 KCl or potassium-acetate and 1/3 KPO₄) once adequate urine output is confirmed 1, 2
If K⁺ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation initially; monitor every 2–4 hours as levels will fall rapidly with insulin therapy, then add replacement once K⁺ falls below 5.5 mEq/L 1, 2
Target serum potassium throughout treatment: 4–5 mEq/L 1, 2. Check potassium every 2–4 hours during active treatment 1.
Insulin Therapy
Standard IV Insulin Protocol for Moderate-Severe DKA
Confirm serum potassium ≥3.3 mEq/L before initiating insulin 1, 2. Administer an IV bolus of regular insulin 0.1–0.15 units/kg, then start a continuous infusion of 0.1 units/kg/hour 1, 2. Only regular (short-acting) insulin should be used for IV infusion; rapid-acting analogs must not be administered intravenously 2.
Prepare insulin by adding 100 units regular insulin to 100 mL normal saline (concentration 1 unit/mL), and prime the tubing with 20 mL of solution before connecting to the patient 2.
Insulin Titration
Target a glucose decline of 50–75 mg/dL per hour 1, 2. If plasma glucose does not fall by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each hour until a steady decline is achieved 1, 2.
Critical Pitfall: Premature Insulin Discontinuation
Continue insulin infusion until complete DKA resolution regardless of glucose level 1, 3. Resolution requires all of the following criteria 1, 2:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Ketonemia resolves more slowly than hyperglycemia; stopping insulin when glucose normalizes is the most common cause of persistent or recurrent ketoacidosis 1, 3. When glucose reaches 250 mg/dL, add dextrose to IV fluids while maintaining insulin infusion 1.
Alternative Approach for Mild-Moderate Uncomplicated DKA
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 1, 2. This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1. Continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients 1.
Monitoring During Treatment
Draw blood every 2–4 hours for serum electrolytes (especially potassium), glucose, BUN, creatinine, osmolality, and venous pH 1, 2. Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring; routine repeat arterial blood gases are unnecessary 1.
Ketone Monitoring
Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution 1, 2. Nitroprusside-based ketone tests (urine or blood) detect only acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate), and should not be used for diagnosis or monitoring 1. During successful treatment, acetoacetate may rise as β-hydroxybutyrate falls, potentially giving a false impression of worsening ketosis if nitroprusside methods are employed 1.
Bicarbonate Administration
Bicarbonate is NOT recommended for DKA patients with pH >6.9–7.0, as multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 4. For pH <6.9, consider administering 100 mmol sodium bicarbonate diluted in 400 mL sterile water, infused at 200 mL per hour 1.
Transition to Subcutaneous Insulin
Administer basal insulin (glargine, detemir, or NPH) 2–4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 4. Continue the IV insulin infusion for an additional 1–2 hours after the basal dose to ensure adequate absorption 1, 2.
Subcutaneous Insulin Dosing
Use approximately 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting basal insulin 2. Divide the remaining 50% equally among three meals as rapid-acting prandial insulin 2. For newly diagnosed patients, start with a total daily insulin dose of approximately 0.5–1.0 units/kg/day 1.
Recent evidence shows that adding low-dose basal insulin analog during the IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1, 4.
Critical Pitfall: Stopping IV Insulin Without Overlap
Never stop IV insulin abruptly without prior basal insulin administration—this is the most common error leading to DKA recurrence 2, 3. The 2–4 hour overlap is essential to prevent a coverage gap that can precipitate ketoacidosis 2.
Identification and Treatment of Precipitating Causes
Infection is the most frequent precipitating factor for DKA 1. Obtain bacterial cultures (blood, urine, throat) when infection is suspected and initiate appropriate antibiotics promptly 1, 2. Other common precipitants include 1:
- Myocardial infarction (can both precipitate and be masked by DKA)
- Cerebrovascular accident
- Insulin omission or inadequacy
- Pancreatitis
- SGLT2 inhibitor use
- Glucocorticoid therapy
- Pregnancy
Treatment of the underlying cause must occur simultaneously with correction of the metabolic derangement 1.
Special Considerations
Cerebral Edema
Cerebral edema occurs more commonly in children and adolescents than adults and is one of the most dire complications of DKA 1. Monitor closely for signs of altered mental status, headache, or neurological deterioration 1. Correcting serum osmolality faster than 3 mOsm/kg/hour increases the risk of cerebral edema 1.
Pregnancy
Pregnant individuals may present with euglycemic DKA and mixed acid-base disturbances, especially in the setting of hyperemesis 1. Because of the high risk of fetal-maternal harm, pregnant patients at risk should be counseled on DKA signs and instructed to seek prompt medical care 1.
Pediatric Considerations
For pediatric patients, omit the initial insulin bolus and start a continuous infusion of 0.05–0.1 units/kg/hour 2. Administer isotonic saline at 10–20 mL/kg/hour (not exceeding 50 mL/kg in the first 4 hours) to minimize cerebral-edema risk 2.
Discharge Planning
Prior to discharge, ensure the following 1, 2:
- Identification of outpatient diabetes care providers
- Patient education on glucose monitoring, insulin administration, and recognition/treatment of hyperglycemia and hypoglycemia
- Understanding of sick day management and signs of DKA recurrence
- Appropriate insulin regimen prescribed with attention to medication access and affordability
- Follow-up appointment scheduled within 1–2 weeks if glycemic control is not optimal 4
Never stop basal insulin, even when oral intake is limited; provide detailed sick-day management instructions 1. Measure ketones when glucose exceeds 200 mg/dL or during any illness with typical DKA symptoms 1.