DKA
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"diabetic ketoacidosis"[MeSH Terms] AND management
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Diabetic Ketoacidosis (DKA)
Overview
DKA is an acute, life-threatening complication of diabetes mellitus, defined by the triad of hyperglycemia + ketosis + metabolic acidosis. It occurs predominantly in type 1 DM but increasingly in type 2 DM (especially in African Americans, Hispanics, and patients on SGLT-2 inhibitors). In the US, there are ~140,000 hospitalizations per year. Mortality is <1% in experienced centers but higher in elderly patients and those from resource-limited settings.
- Tintinalli's Emergency Medicine, p. 1475
- Goldman-Cecil Medicine, p. 2484
Pathophysiology
The core mechanism is relative or absolute insulin deficiency + excess counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone).
| Hormone Imbalance | Metabolic Consequence |
|---|---|
| ↓ Insulin | ↑ Glycogenolysis, ↑ gluconeogenesis, ↓ glucose uptake |
| ↑ Glucagon | ↑ Hepatic glucose output, ↑ fatty acid oxidation |
| ↑ Catecholamines | ↑ Lipolysis, ↑ free fatty acids to liver |
| Net result | Hyperglycemia + ketogenesis (β-hydroxybutyrate, acetoacetate) + elevated anion gap metabolic acidosis |
Cascade:
- Lipolysis releases free fatty acids → liver converts to ketone bodies (β-hydroxybutyrate, acetoacetate, acetone)
- Hyperglycemia causes osmotic diuresis → volume depletion → worsening hyperglycemia
- Renin-angiotensin-aldosterone activation → potassium wasting (kaliuresis)
- Ketoacid excretion in urine = loss of potential bicarbonate → acidosis
- Prostaglandins I2 and E2 released from lipolysis → paradoxical vasodilation despite hypovolemia → nausea, vomiting, abdominal pain
Total body deficits (even if serum levels appear normal): K⁺ ~3-5 mEq/kg, Na ~7-10 mEq/kg, water ~6L.
- Tintinalli's Emergency Medicine, p. 1475-1476
- Goldman-Cecil Medicine, p. 2483-2484
Precipitating Causes (The "6 I's")
| Common | Other |
|---|---|
| Infection (pneumonia, UTI) | Stroke, PE, acute pancreatitis |
| Insulin non-compliance | Alcohol intoxication |
| Initial presentation (new-onset DM) | Cushing syndrome, thyrotoxicosis |
| Ischemia (ACS) | Corticosteroids, clozapine, olanzapine, cocaine |
| Unknown in ~25% | SGLT-2 inhibitors (euglycemic DKA) |
| Intercurrent illness | Severe burns, hyperthermia/hypothermia |
- Goldman-Cecil Medicine, Table 210-11
Clinical Features
Symptoms (develop over hours to days):
- Polyuria, polydipsia (early)
- Nausea, vomiting, anorexia
- Weakness, lethargy
- Diffuse abdominal pain (can mimic acute abdomen)
- Altered mental status (correlates with hyperosmolality >320 mOsm/L more than with pH)
Signs:
- Tachycardia, orthostasis, hypotension
- Dry mucous membranes, poor skin turgor
- Kussmaul respirations - deep, rapid breathing (respiratory compensation for acidosis)
- Fruity breath (acetone)
- Hypothermia possible (due to peripheral vasodilation)
- Absence of fever does NOT exclude infection
Note on abdominal pain: Pain correlates with the degree of acidosis. Elevated amylase/lipase can occur in DKA independent of pancreatitis; serum lipase is more specific for true pancreatitis.
- Tintinalli's Emergency Medicine, p. 1476
Diagnostic Criteria
Classic triad:
- Blood glucose >250 mg/dL (13.9 mmol/L) - though euglycemic DKA occurs with SGLT-2 inhibitors or pregnancy
- Serum bicarbonate <18 mEq/L (acidosis)
- Ketones in urine ≥2+ or serum ketones ≥3.0 mmol/L
- Arterial/venous pH <7.3
Severity Classification:
| Feature | Mild | Moderate | Severe |
|---|---|---|---|
| pH | 7.25-7.30 | 7.00-7.24 | <7.00 |
| Bicarbonate (mEq/L) | 15-18 | 10-14 | <10 |
| Mental status | Alert | Drowsy | Stupor/coma |
| Anion gap | >10 | >12 | >12 |
Laboratory workup:
- ABG or VBG (venous pH reliably correlates)
- BMP/CMP: glucose, BUN, creatinine, electrolytes, bicarbonate
- Serum ketones (β-hydroxybutyrate preferred over urine dipstick)
- CBC (leukocytosis common even without infection)
- Phosphate, magnesium
- Urinalysis + urine culture
- ECG (to assess ACS as precipitant + screen for hyperkalemia)
- CXR
- Blood cultures if infection suspected
- HbA1c
- Calculate corrected sodium: Na + 1.6 × [(glucose - 100)/100]
- Calculate anion gap: Na - (Cl + HCO3) - normal = 8-12 mEq/L
- Calculate effective osmolality: 2[Na] + glucose/18 (BUN does not contribute)
Note on K⁺: Serum K⁺ may appear normal or high at presentation due to acidosis-driven shift (H⁺ in, K⁺ out), but total body K⁺ is severely depleted. As insulin is given and pH corrects, K⁺ drops rapidly.
- Goldman-Cecil Medicine, p. 2484
Management
1. Fluids (most urgent)
- Normal saline (0.9% NaCl): 1-2 L over first 1-2 hours
- Then switch to 0.45% NaCl at 250-500 mL/hr based on corrected sodium and clinical status
- When glucose reaches 200 mg/dL, switch to D5W + 0.45% NaCl to prevent hypoglycemia while continuing insulin
- Target fluid replacement over 24-48 hours (average deficit ~6L)
2. Insulin
- Regular insulin IV infusion: 0.1 units/kg/hr (no bolus needed if initial fluid resuscitation is given)
- OR 0.14 units/kg/hr if no bolus
- Target glucose fall of 50-75 mg/dL per hour
- If glucose not falling in first hour → double the infusion rate
- Do NOT stop insulin until anion gap closes (even if glucose normalizes - add dextrose instead)
- Transition to subcutaneous insulin when: patient eating, anion gap closed, pH >7.3, HCO3 >18
- Give SC basal insulin 1-2 hours BEFORE stopping the IV infusion to prevent rebound ketosis
Recent evidence: A 2026 systematic review (PMID 41208563) found early subcutaneous basal insulin concurrent with IV insulin infusion reduces DKA recurrence and shortens ICU stay. A 2024 meta-analysis (PMID 39090718) showed subcutaneous insulin protocols are non-inferior to IV infusion in mild-moderate DKA.
3. Potassium - CRITICAL
- If K⁺ <3.5 mEq/L: Replace K⁺ BEFORE starting insulin (hold insulin); give 20-40 mEq/hr IV until K⁺ ≥3.5
- If K⁺ 3.5-5.0 mEq/L: Replace 20-30 mEq/L in each liter of IV fluid
- If K⁺ >5.0 mEq/L: Hold potassium; recheck every 2 hours
- Target K⁺ 4-5 mEq/L throughout treatment
- Monitor K⁺ every 2 hours for first 4-6 hours
4. Bicarbonate - Rarely indicated
- Only if pH <6.9 with hemodynamic compromise
- Routine bicarb use is NOT recommended - it can worsen hypokalemia, cause paradoxical CNS acidosis, and delay resolution
- If given: 100 mEq NaHCO3 in 400 mL sterile water + 20 mEq KCl over 2 hours
5. Phosphate - Selective replacement
- Replace if phosphate <1.0 mg/dL, or with cardiac dysfunction, hemolytic anemia, or respiratory depression
- Use potassium phosphate to simultaneously address hypokalemia
6. Identify and treat precipitating cause
- Antibiotics if infection identified
- ACS workup if chest pain, ECG changes
- Do NOT start maintenance insulin until precipitant is addressed
Monitoring During Treatment
| Parameter | Frequency |
|---|---|
| Blood glucose | Every 1 hour |
| Electrolytes, BUN/Cr, anion gap | Every 2-4 hours |
| Venous pH/HCO3 | Every 2-4 hours |
| Urine output | Continuous (Foley if altered) |
| ECG | For dysrhythmia risk (hypo/hyperkalemia) |
Resolution Criteria (all must be met)
- Blood glucose <200 mg/dL
- Serum bicarbonate ≥15 mEq/L
- Venous pH ≥7.3
- Anion gap ≤12 mEq/L
- Patient alert and able to eat
Complications
| Complication | Cause/Notes |
|---|---|
| Cerebral edema | Most feared in children; avoid rapid fluid or glucose correction; treat with mannitol/hypertonic saline |
| Hypokalemia | Most common cause of cardiac arrest during treatment |
| Hypoglycemia | Failure to add dextrose when glucose <200 |
| Hyperchloremic acidosis | From large-volume NS; non-gap acidosis persists after ketoacidosis resolves |
| Aspiration | Gastric paresis; consider NGT |
| DVT/PE | Hypercoagulable state from dehydration |
| ARDS | Rare; aggressive fluid resuscitation |
DKA vs. HHS
| Feature | DKA | HHS |
|---|---|---|
| Diabetes type | Usually T1DM | Usually T2DM |
| pH | <7.3 | >7.3 |
| Bicarbonate | <18 mEq/L | >15 mEq/L |
| Ketones | Moderate-large | Absent or trace |
| Glucose | Usually 250-600 mg/dL | Often >600 mg/dL |
| Osmolality | Mildly elevated | Very high (>320) |
| Onset | Hours | Days-weeks |
| Mental status change | Less common | Very common (10% coma) |
- Goldman-Cecil Medicine, p. 2483-2484
Special Populations
Pregnancy: DKA can occur at lower glucose levels (euglycemic DKA). Target glucose 100-140 mg/dL. Continuous fetal monitoring is required. High fetal mortality even with maternal survival.
SGLT-2 inhibitor-associated DKA (euglycemic DKA): Glucose often <200 mg/dL. High clinical suspicion required. Hold SGLT-2 inhibitor; management otherwise similar.
Children: Higher risk for cerebral edema (0.5-0.9% of pediatric DKA). Use slower fluid replacement; avoid hypotonic fluids early. Monitor neurological status closely.
Key clinical pearl: The single most dangerous electrolyte disturbance in DKA is hypokalemia. Always check K⁺ before starting insulin, and replace aggressively. Patients can arrive with a normal or even high K⁺ masking severe total body depletion - it will drop precipitously once insulin shifts K⁺ back into cells.
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